CADASIL is the most common form of hereditary stroke disorder. This case has a strong history of migraine with aura with stroke-like episodes, characteristic of CADASIL. Additionally, there is positive family history of migraine and early dementia but no other vascular risk factors like hypertension, diabetes, or hypercholesterolaemia, which all confirm the suspicion of CADASIL, an arteriopathy where there is thickening of the smooth muscle cells in the blood vessels.

CMV is a common viral infection that can be transmitted from a pregnant woman to her unborn child, leading to congenital CMV infection. Congenital CMV infection can result in a range of symptoms and complications in newborns, including deafness. In fact, CMV is one of the leading causes of non-genetic sensorineural hearing loss in children.

Given the mother’s history of symptoms during pregnancy and the concern for deafness in the infant, CMV should also be considered as a potential cause.

Meningiomas are the most common benign tumours of the brain. Their name is derived from the fact that they arise from the dura mater which together with the pia matter and arachnoid mater form the meninges. The chances that a meningioma is benign are almost 98%. They are non-invasive and well delineated, causing sign and symptoms of brain compression.

This is a low protein level, indicating the fluid is transudative. The only answer choice that is a transudative fluid is in hepatic cirrhosis. Exudative fluid would be seen in tuberculous peritonitis, peritoneal lymphoma, with liver mets, and with intra-abdominal malignancy.

Tumour lysis syndrome (TLS) occurs most notably in patients with haematological malignancies including, Non-Hodgkin’s Lymphoma (NHL) and Acute Lymphocytic Leukaemia (ALL).
Risk factors for TLS include:
• Large tumour burden
• Sensitivity of the tumour to chemotherapy
• Rapid tumour growth rate
TLS is characterized by:
• Hyperuricemia
• Hyperkalaemia
• Hyperphosphatemia
• Hypocalcaemia
Treatment of TLS:
• Allopurinol: It is a xanthine oxidase inhibitor, it reduces the conversion of nucleic acid by-products to uric acid. Thus, it prevents urate nephropathy and subsequent oliguric renal failure. Note: dose reduction is essential in renal failure or if given along with mercaptopurine or azathioprine.
Alternatives to Allopurinol: Febuxostat; Rasburicase are useful in patients with hyperuricemia.
• Hydration
• Diuresis: Should be considered in well hydrated patients with insufficient urine output. Furosemide to be considered in normo-volemic patients with hyperkalaemia. Urine alkalization can be considered for promoting alkaline diuresis.
• Treatment of electrolyte imbalances including hyperkalaemia, hyperphosphatemia, and hypocalcaemia.
• Dialysis can be considered in refractory cases.

J waves in an ECG is associated with hypothermia, hypercalcemia, the Brugada syndrome, and idiopathic ventricular fibrillation. The other responses are all associated with atrial myxoma

Whilst asthma and COPD are different diseases they cause similar symptoms, which can present a challenge in identifying which of the two diseases a patient is suffering from. COPD causes chronic symptoms and narrowed airways which do not respond to treatment to open them up. In the case of asthma the constriction of the airways through inflammation tends to come and go and treatment to reduce inflammation and to open up the airways usually works well.

COPD is more likely than asthma to cause a chronic cough with phlegm and is rare before the age of 35 whilst asthma is common in under-35s. Disturbed sleep caused by breathlessness and wheeze is more likely in cases of asthma, as is a history of allergies, eczema and hay fever. Differentiating between COPD and asthma requires a history of both symptoms and spirometry. The spirometry history should include post bronchodilator measurements, the degree of reversibility and, ideally, home monitoring which gives a history of diurnal variation.

Airflow Obstruction: Both asthma and COPD are characterised by airflow obstruction. Airflow obstruction is defined as a reduced FEV1 and a reduced FEV1/FVC ratio, such that FEV1 is less than 80% of that predicted, and FEV1/FVC is less than 0.7.

These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

COPD: COPD is a chronic, slowly progressive disorder characterised by airflow obstruction (reduced FEV1 and FEV1/VC ratio) that does not change markedly over several months. The airflow obstruction is not fully reversible.

Spirometry COPD Asthma
VC Reduced Nearly normal
FEV1 Reduced Reduced in attack
FVC (or FEV6) Reduced Nearly normal
FEV1 Ratio
(of VC/FVC/FEV6) Reduced in attack

This man has a low FEV1 and FVC. His diffusions capacity is also low despite having a normal total lung capacity. These values confirm a diagnosis of COPD.

Monoclonal gammopathy of undetermined significance (MGUS)—also known as benign paraproteinemia and monoclonal gammopathy—is a pre-malignant condition not necessarily leading to its malignant form—multiple myeloma. MGUS causes increase of a serum monoclonal protein (M protein). It is not associated with ostealgia or increased risk of infections. It is often mistaken for multiple myeloma, differing from the latter in, no immunosuppression, anaemia, hypercalcaemia, lytic bone lesions, or renal failure; normal levels of beta-2 microglobulin; and stable lower levels of paraproteinemia.

It is a metabolic bone disease caused by defective osteoclastic resorption of immature bone. Osteopetrosis is also known as marble bone disease. Osteoclasts are unable to adequately acidify bone matrix. Impaired bone resorption leads to overly dense bone that is more likely to fracture. It is usually treated with bone marrow transplant and high dose calcitriol.

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, and they belong to the same patients, so a paired t test should be used.

The principal mechanism of action of taxanes (e.g. docetaxel) is the prevention of microtubule disassembly.

Other aforementioned options are ruled out because:

1. Doxorubicin: stabilizes DNA topoisomerase II complex and inhibits DNA and RNA synthesis.

2. Vincristine, vinblastine: inhibits formation of microtubules.

3. Cisplatin: causes cross-linking in DNA.

The clinical picture is characteristic of retinal detachment, which should be treated immediately to prevent permanent loss of vision. Scleral buckling is a surgical procedure used to repair a retinal detachment, where the surgeon attaches a piece of silicone or a sponge onto the white of the eye at the spot of a retinal tear pushing the sclera toward the retinal tear or break, promoting repair. Signs of detachment include an increase in the number of eye floaters, flashes of light in the field of vision, and reduced peripheral vision.

Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.
The most recent update to the NICE guidelines for management of neuropathic pain occurred in 2013: first-line treatment* includes amitriptyline. If the first-line drug treatment does not work then move on to one of the other 3 drugs: duloxetine, gabapentin or pregabalin. Tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain. Topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia). Pain management clinics may be useful in patients with resistant problems.

*please note that for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia.

A history of ischaemic heart disease in a contraindication for prescribing triptans because they act by constricting cerebral and also coronary vessels, increasing the risk of stroke.

Palmar xanthomas and tuberoeruptive xanthomas are found in type III hyperlipoproteinemia (dysbetalipoproteinemia,broad-beta disease, remnant removal disease)

Drug metabolism can be broadly classified into:
Phase I (functionalization) reactions: also termed non-synthetic reactions, they include oxidation, reduction, hydrolysis, cyclization and de-cyclization. The most common and vital reactions are oxidation reactions. (Of the given enzymes only Alcohol dehydrogenase is involved in phase I drug metabolism. Succinate dehydrogenase, is a vital enzyme involved in the Kreb’s cycle and the mitochondrial electron transport chain). They are mainly catalysed by Cytochrome P-450 enzyme.

Phase II (conjugation) reactions: occur following phase I reactions, they include reactions: glucuronidation and sulphate conjugation, etc. They are mostly catalysed by UDP-glucuronosyltransferase enzyme. Other phase II enzymes include: sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases.

The dose is calculated, using the conversion factor, as follows:

(Conversion factor used to convert oral morphine to subcutaneous diamorphine = Divide the total daily dose of oral morphine by 3)
Hence,
60mg*2 = 120mg
120mg/3 = 40mg

The side effects of opioids can be transient or persistent, and these include constipation, nausea, and drowsiness. Therefore, all patients taking opioids should also be prescribed a laxative and an anti-emetic (if the nausea is persistent). Dose-adjustment may be necessary in cases of persistent drowsiness. Moreover, strong opioids can also provide quick relief from metastatic bone pain, as compared to NSAIDs, bisphosphonates, and radiotherapy.

Achondroplasia is the most common type of short-limb disproportionate dwarfism. A single gene mapped to the short arm of chromosome 4 (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait. All people with achondroplasia have a short stature.
Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Examination of the infant after birth shows increased front-to-back head size. There may be signs of hydrocephalus. It may be diagnosed radiographically at birth, or becomes obvious within the first year with disparity between a large skull, normal trunk length and short limbs.

Paget disease is a localized disorder of bone remodelling that typically begins with excessive bone resorption followed by an increase in bone formation. This osteoclastic over activity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.
Approximately 70-90% of persons with Paget disease are asymptomatic; however, a minority of affected individuals experience various symptoms, including the following:
– Bone pain (the most common symptom)
– Secondary osteoarthritis (when Paget disease occurs around a joint)
– Bony deformity (most commonly bowing of an extremity)
– Excessive warmth (due to hypervascularity)
– Neurologic complications (caused by the compression of neural tissues)
Measurement of serum alkaline phosphatase—in some cases, bone-specific alkaline phosphatase (BSAP)—can be useful in the diagnosis of Paget disease. Elevated levels of urinary markers, including hydroxyproline, deoxypyridinoline, C-telopeptide, and N -telopeptide, may help identify patients with Paget disease.
Serum calcium and phosphate levels should be within the reference range in patients with Paget disease.

There are five prognostic factors which indicate poor prognosis in HOCM:
-family history of HOCM-related sudden cardiac death
-unexplained recent syncope
-large left ventricular wall thickness (MLVWT ≥ 30 mm)
-multiple bursts of nsVT on ambulatory electrocardiography
-hypotensive or attenuated blood pressure response to exercise

The symptoms of ataxia, slurred speech and blurred vision are all suggestive of phenytoin toxicity. Cimetidine increases the efficacy of phenytoin by reducing its hepatic metabolism.

Phenytoin has a narrow therapeutic index (10-20 mg/L) and its levels are monitored by measuring the total phenytoin concentration.
Cimetidine is an H2 receptor antagonist used in the treatment of peptic ulcers. It acts by decreasing gastric acid secretion.
Cimetidine also has an inhibitory effect on several isoforms of the cytochrome enzyme system including the CYP450 enzymatic pathway. Phenytoin is metabolized by the same cytochrome P450 enzyme system in the liver.
Thus, the simultaneous administration of both these medications leads to an inhibition of phenytoin metabolism and thus increases its circulating levels leading to phenytoin toxicity.

West Nile virus (WNV) is a single-stranded RNA flavivirus transmitted via the culex mosquito. This previously ‘tropical’ disease has became topical in recent years following a large scale outbreak in the New York area. Incidence of neurological involvement is around 1%, although some suggest that the incidence of meningoencephalitis in America is higher than in other parts of the world. Risk factors for neurological involvement include increasing age, and immunosuppression. The usual picture is of sudden onset fever and myalgia with nausea and vomiting and a non-specific rash. Transient meningitis is occasionally seen. Frank meningoencephalitis is seen in two-thirds of cases with neurological involvement; 15% progress to coma. A flaccid paralysis similar to acute Guillain–Barré is increasingly recognised.
Diagnosis is initially clinical with subsequent serological confirmation. Treatment is supportive; results from trials of antivirals have yielded disappointing results.

The most probable diagnosis of this patient is Cotard syndrome.

Cotard syndrome is a rare mental disorder where the affected patient believes that they (or in some cases just a part of their body) is either dead or non-existent. This delusion is often difficult to treat and can result in significant problems due to patients stopping eating or drinking as they deem it not necessary. Cotard syndrome is often associated with severe depression and psychotic disorders.

Other delusional syndromes:
– Othello syndrome is a delusional belief that a patients partner is committing infidelity despite no evidence of this. It can often result in violence and controlling behaviour.
– De Clerambault syndrome (otherwise known as erotomania), is where a patient believes that a person of higher social or professional standing is in love with them. Often this presents with people who believe celebrities are in love with them.
– Capgras syndrome is characterised by a person believing their friend or relative had been replaced by an exact double.
– Couvade syndrome is also known as ‘sympathetic pregnancy’. It affects fathers, particularly during the first and third trimesters of pregnancy, who suffer the somatic features of pregnancy.
– Ekbom syndrome is also known as delusional parasitosis and is the belief that they are infected with parasites or have ‘bugs’ under their skin. This can vary from the classic psychosis symptoms in narcotic use where the user can ‘see’ bugs crawling under their skin or can be a patient who believes that they are infested with snakes.

T. gondii infection in immunocompetent people is usually asymptomatic. It can present as fits in patients with AIDs, who are immunosuppressed. Additionally, infection in the first trimester of pregnancy is very harmful. Congenital toxoplasmosis presents with intracranial calcifications, classically. It can also present with hydrocephalus, microcephaly, blindness, petechiae. Siramycin is the drug of choice to try to prevent vertical transmission from mother to baby. It is typically gotten from cat faeces or raw/undercooked meat, not raw eggs (raw eggs: think salmonella).

Sodium cromoglycate principally acts by inhibiting the degranulation of mast cells triggered by the interaction of antigen and IgE.
The inhibitory effect on mast cells appears to be cell-type specific since cromoglycate has little inhibitory effect on mediator release from human basophils.
Thus, it inhibits the release of histamine, leukotrienes, and slow-reacting substance of anaphylaxis from mast cells by inhibiting degranulation following exposure to reactive antigens.

Adverse effects include cough, flushing, palpitation, chest pain, nasal congestion, nausea, fatigue, migraine, etc.

Pneumonia is the predominant clinical manifestation of Legionnaires disease (LD). After an incubation period of 2-10 days, patients typically develop the following nonspecific symptoms:
Fever
Weakness
Fatigue
Malaise
Myalgia
Chills

Respiratory symptoms may not be present initially but develop as the disease progresses. Almost all patients develop a cough, which is initially dry and non-productive, but may become productive, with purulent sputum and, (in rare cases) haemoptysis. Patients may experience chest pain.
Common GI symptoms include diarrhoea (watery and non bloody), nausea, vomiting, and abdominal pain.

Fever is typically present (98%). Temperatures exceeding 40°C occur in 20-60% of patients. Lung examination reveals rales and signs of consolidation late in the disease course.

Males are more than twice as likely as females to develop Legionnaires disease.

Age
Middle-aged and older adults have a high risk of developing Legionnaires disease while it is rare in young adults and children. Among children, more than one third of reported cases have occurred in infants younger than 1 year.

Situations suggesting Legionella disease:
-Gram stains of respiratory samples revealing many polymorphonuclear leukocytes with few or no organisms

-Hyponatremia

-Pneumonia with prominent extrapulmonary manifestations (e.g., diarrhoea, confusion, other neurologic symptoms)

Specific therapy includes antibiotics capable of achieving high intracellular concentrations (e.g., macrolides, quinolones, ketolides, tetracyclines, rifampicin).
Clarithromycin, a new macrolide antibiotic, is at least four times more active in vitro than erythromycin against Legionella pneumophila. In this study the safety and efficacy of orally administered clarithromycin (500 to 1,000 mg bid) in the treatment of Legionella pneumonia were evaluated.
Clarithromycin is a safe effective treatment for patients with severe chest infections due to Legionella pneumophila.

Memantine is an antagonist of the NMDA (N-Methyl-D-Aspartate)-receptor subtype of glutamate receptor. It is used to slow the neurotoxicity thought to be involved in Alzheimer’s disease and other neurodegenerative diseases.

Drug interactions:
When given concomitantly with other NMDA-receptor antagonists (e.g., ketamine, amantadine) increase the risk of psychosis.
Dopamine agonists, L-dopa, and anticholinergics enhance effects of memantine.
Antispasmodics (e.g., baclofen)  enhance effects, as memantine has some antispasmodic effects.
Drugs excreted by cationic transporters in the kidney (e.g. quinine, cimetidine, ranitidine) reduce excretion.

Common adverse effects include dizziness, headache, confusion, diarrhoea, and constipation.

The tumour has only invaded the visceral pleura and measures 3cm in the greatest dimension. Hence it is designated at T2. Ipsilateral peribronchial and/or hilar lymph node involvement would make it N1. There is no distal metastasis so M would be 0.

Inclusion body myositis (IBM) is a progressive muscle disorder characterized by muscle inflammation, weakness, and atrophy (wasting). It is a type of inflammatory myopathy. IBM develops in adulthood, usually after age 50. The symptoms and rate of progression vary from person to person. The most common symptoms include progressive weakness of the legs, arms, fingers, and wrists. Some people also have weakness of the facial muscles (especially muscles controlling eye closure), or difficulty swallowing (dysphagia). Muscle cramping and pain are uncommon, but have been reported in some people. The underlying cause of IBM is poorly understood and likely involves the interaction of genetic, immune-related, and environmental factors. Some people may have a genetic predisposition to developing IBM, but the condition itself typically is not inherited. Elevated creatine kinase (CK) levels in the blood (at most ,10 times normal) are typical in IBM. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins.

History and CXR are suggestive of tuberculosis. Acid fast bacilli should be seen on microscopy to confirm the diagnosis.

Posterior vitreous detachment is thought to occur in up to 50-75% of the population over 65 years and is the most likely diagnosis here. Patients should be reviewed by an ophthalmologist to assess the risk of progressing to retinal detachment. Flashes of light (photopsia) occur in the peripheral field of vision while floaters often occur on the temporal side of the central vision.

Melanocytic nevi are benign neoplasms or hamartomas composed of melanocytes. Melanocytes are derived from the neural crest and migrate during embryogenesis to selected ectodermal sites (primarily the skin and the CNS), but also to the eyes and the ears.
They tend to appear during early childhood and during the first 30 years of life. They may change slowly, becoming raised, changing color or gradually fading.. Pregnancy can increase the number of naevi as well as the degree of hyperpigmentation.
They may become malignant and this should be suspected if the naevus increases in size, develops an irregular surface or becomes darker, itches or bleeds.

The patient is most likely complaining of the effects of hyperkalaemia, due to missing his dialysis sessions. Additionally, because the patient presents with a risk of cardiac arrest (based on pulmonary oedema and ECG findings), the best intervention is to give calcium gluconate that will address the hyperkalaemia as well as improve the cardiac condition.

Tinea manum is a superficial fungal infection of the hands characterised by dry scaly rash and also involves the interdigital spaces of the hands.

Tinea pedis is a fungal infection of feet, whereas onychomycosis represents a fungal infection of the nails, characterised by nail dystrophy, hyperkeratosis.

Kerion is the name given to secondarily infected tinea capitis leading to a soft boggy swelling over the scalp.

Psoriasis presents as silvery scales over the extensors of the body and it may involve the nails, scalp and joints.

The classes refer to the WHO classification of glomerulonephritis in SLE patients.
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis

Class IV: diffuse proliferative glomerulonephritis is the most common and the most severe form, where more than 50% of the glomeruli are involved.

Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 is considered mild or subclinical hypothyroidism.
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be asymptomatic. Symptoms and signs are often subtle and neither sensitive nor specific.
The following are symptoms of hypothyroidism:
– Fatigue, loss of energy, lethargy
– Weight gain
– Decreased appetite
– Cold intolerance
– Dry skin
– Hair loss
– Sleepiness
– Muscle pain, joint pain, weakness in the extremities
– Depression
– Emotional lability, mental impairment
– Forgetfulness, impaired memory, inability to concentrate
– Constipation
– Menstrual disturbances, impaired fertility
– Decreased perspiration
– Paraesthesia and nerve entrapment syndromes
– Blurred vision
– Decreased hearing
– Fullness in the throat, hoarseness
Physical signs of hypothyroidism include the following:
– Weight gain
– Slowed speech and movements
– Dry skin
– Jaundice
– Pallor
– Coarse, brittle, straw-like hair
– Loss of scalp hair, axillary hair, pubic hair, or a combination
– Dull facial expression
– Coarse facial features
– Periorbital puffiness
– Macroglossia
– Goitre (simple or nodular)
– Hoarseness
– Decreased systolic blood pressure and increased diastolic blood pressure
– Bradycardia
– Pericardial effusion
– Abdominal distention, ascites (uncommon)
– Hypothermia (only in severe hypothyroid states)
– Nonpitting oedema (myxoedema)
– Pitting oedema of lower extremities
– Hyporeflexia with delayed relaxation, ataxia, or both.

Hyperacute rejection appears in the first minutes following transplantation and occurs only in vascularized grafts. This very fast rejection is characterized by vessel thrombosis leading to graft necrosis. Hyperacute rejection is caused by the presence of antidonor antibodies existing in the recipient before transplantation. These antibodies induce both complement activation and stimulation of endothelial cells to secrete Von Willebrand procoagulant factor, resulting in platelet adhesion and aggregation. The result of these series of reactions is the generation of intravascular thrombosis leading to lesion formation and ultimately to graft loss. Today, this type of rejection is avoided in most cases by checking for ABO compatibility and by excluding the presence of antidonor human leukocyte antigen (HLA) antibodies by cross-match techniques between donor graft cells and recipient sera. This type of rejection is also observed in models of xenotransplantation of vascularized organs between phylogenetically distant species when no immunosuppressive treatment is given to the recipients.

Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes’ pubertal development.
Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and treatment.
Since she is still 14, adequate diet and observation are enough.

Nice guidelines for lung reduction surgery:

FEV1 > 20% predicted
PaCO2 < 7.3 kPa
TLco > 20% predicted
Upper lobe predominant emphysema

This patient has pCO2 of 7.4 so she is unsuitable for referral for lung reduction surgery.

A high level of anti-dsDNA in the blood is strongly associated with lupus and is often significantly increased during or just prior to a flare-up. When the anti-dsDNA is positive and the person tested has other clinical signs and symptoms associated with lupus, it means that the person tested likely has lupus. This is especially true if an anti-Sm test is also positive.

In the evaluation of someone with lupus nephritis, a high level (titre) of anti-dsDNA is generally associated with ongoing inflammation and damage to the kidneys.

A very low level of anti-dsDNA is considered negative but does not exclude a diagnosis of lupus. Only about 65-85% of those with lupus will have anti-dsDNA.

Low to moderate levels of the autoantibody may be seen with other autoimmune disorders, such as Sjögren syndrome and mixed connective tissue disease (MCTD).

This girl most probably has Turner’s syndrome, which is caused by the absence of one set of genes from the short arm of one X chromosome.
Turner syndrome is a lifelong condition and needs lifelong oestrogen replacement therapy. Oestrogen is usually started at age 12-15 years. Treatment can be started with continuous low-dose oestrogens. These can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months; progestin can be added later.

In childhood, growth hormone therapy is standard to prevent short stature as an adult.

Fetal ovarian development seems to be normal in Turner syndrome, with degeneration occurring in most cases around the time of birth so pulsatile GnRH and luteinising hormone would be of no use.

Nephrotic syndrome usually presents with the symptoms in this patient: low albumin, abnormal cholesterol, increased urinary albumin excretion, oedema, and as a consequence, hypertension as well.

The a wave indicates atrial contraction. The c wave indicates ventricular contraction and resulting bulging of the tricuspid valve into the right atrium during isovolumetric systole. The v wave indicates venous filling. The x descent indicates the atrium relaxation and the movement of tricuspid valve downward. The y descent indicates the filling of the ventricle after the opening of the tricuspid valve.

The cause of Vitiligo is typically unknown. It is believed to be due to genetic susceptibility that is triggered by an environmental factor such that an autoimmune disease occurs. This results in the destruction of skin pigment cells. Risk factors include a family history of the condition or other autoimmune diseases, such as hyperthyroidism, alopecia areata, and pernicious anaemia. Vitiligo is classified into two main types: segmental and non-segmental. Most cases are non-segmental meaning they affect both sides and typically get worse with time. The prevalence of vitiligo is 0.5-1% of populations worldwide. Typical sites include backs of hands, wrists, knees, neck and around body orifices. The Koebner phenomenon refers to skin lesions appearing on lines of trauma. This occurs in vitiligo secondary to scratching.

A translocation between chromosome 15 and 17 is seen in acute promyelocytic leukaemia (APL), which is known to carry a good prognosis.

Acute myeloid leukaemia (AML) is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly. The disease has poor prognosis if:

The disease has poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

APL is an aggressive form of AML. It is associated with t(15;17) and has a good prognosis. The general age of presentation is less than that in other types of AML (average age is 25 years old). On blood film, abundant Auer rods are seen with myeloperoxidase staining. Thrombocytopaenia or DIC is seen in patients presenting with this disease.

European guidelines for the treatment of syndrome of inappropriate antidiuresis include the following recommendations for the management of moderate or profound hyponatremia:
– Restrict fluid intake as first-line treatment.
– Second-line treatments include increasing solute intake with 0.25–0.50 g/kg per day or a combination of low-dose loop diuretics and oral sodium chloride.
– Use of lithium, demeclocycline, or vasopressin receptor antagonists is not recommended.
Recommendations on the treatment of SIADH from an American Expert Panel included the following:
– If chronic, limit the rate of correction.
– Fluid restriction should generally be first-line therapy.
– Consider pharmacologic therapies if serum Na + is not corrected after 24-48 hr of fluid restriction or if the patient has a low urinary electrolyte free water excretion.
– Patients being treated with vaptans should not be on a fluid restriction initially.
– Water, 5% dextrose or desmopressin can be used to slow the rate of correction if the water diuresis is profound.

The question describes a patient who has had an ileal resection. Bile acids are reabsorbed in the distal ileum. Since this has been resected in this patient, one would expect her to have malabsorption of bile acids, causing her diarrhoea. This is a more likely correct answer than a Crohn’s flare, bacterial overgrowth, gastroenteritis, or tropical sprue, given the details included in the question prompt.

Koplik’s spots are pathopneumonic for MEASLES. They are blue/white spots, small, occurring on the buccal mucosa. They typically occur next to premolars, not opposite to the incisors. They are not related to fever height. They are not on the hands. They usually occur BEFORE the rash.

1B: Individual Randomised Control Trial (with narrow confidence intervals)

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles, thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which results in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

Warfarin inhibits the vitamin K-dependent procoagulants II, VII, IX, and X as well as anticoagulant protein C and S. It is highly protein-bound and can be displaced by a wide variety of drugs. It has a half-life of 36–48 hours.

Bleeding is the major side effect. Easy bruising, as seen in this case, is commonly seen in patients of warfarin overdose. Grossly prolonged PT and lesser increase in APTT may be seen in such cases.

Acute angle closure glaucoma is associated with hypermetropia, whereas primary open-angle glaucoma is associated with myopia. Glaucoma is a group of eye disorders characterised by optic neuropathy due, in the majority of patients, to raised intraocular pressure (IOP). It is now recognised that a minority of patients with raised IOP do not have glaucoma and vice versa.

Retinitis pigmentosa is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreased peripheral vision. Onset of symptoms is generally gradual.
– In keratitis, there will be pain, redness and photophobia but vision is not affected
– In macular degeneration, near blindness does not occur rather the inability to identify faces or read small print
– Cataracts are more common in elderly
– It is not angle closure glaucoma as angle closure glaucoma occurs usually after the age of 50; In open angle glaucoma visual loss is not gradual but rather occurs suddenly following progression

The diagnosis is acute inferior ST elevation myocardial infarction so the most appropriate management is primary angioplasty.

Among the above statements, gastric lavage and normal saline IV infusion are the two appropriate interventions for a patient of acute lithium toxicity.

Activated charcoal is not effective after lithium overdose, although gastric lavage should be considered if patients present within 6–8 h.
Where levels are above 3 mmol/l, the use of normal saline to induce diuresis should be considered, although careful monitoring of fluid balance is necessary.
Where levels of lithium are above 4 mmol/l, dialysis is often required. Haemodialysis is preferred, but in a facility where haemodialysis is not possible, peritoneal dialysis may be considered.
Patients should not be discharged until they are asymptomatic and have a serum lithium level less than 1.5 mEq/L.

Bombesin is a tumour marker elevated in small cell lung carcinomas, as well as in gastric carcinomas and retinoblastomas.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

Bronchial carcinoids are uncommon, slow growing, low-grade, malignant neoplasms, comprising 1-2% of all primary lung cancers.
It is believed to be derived from surface of bronchial glandular epithelium. Mostly located centrally, they produce symptoms and signs of bronchial obstruction such as localized wheeze, non resolving recurrent pneumonitis, cough, chest pain, and fever. Haemoptysis is present in approximately 50% of the cases due to their central origin and hypervascularity.
Central bronchial carcinoids are more common than the peripheral type and are seen as endobronchial nodules or hilar/perihilar mass closely related to the adjacent bronchus. Chest X-ray may not show the central lesion depending on how small it is.

Hypopyon can be seen in anterior uveitis, however the combination of a normal pupillary reaction and contact lens use make a diagnosis of keratitis more likely. Keratitis describes inflammation of the cornea, and features include red eye with pain and erythema, photophobia, and foreign body/gritty sensation.

Stricturing is associated with Crohn’s disease, and elevated CRP supports this diagnosis in this patient, as well. Infliximab should not yet be started. Acute treatment is steroids (of a flare) however this man needs surgery. Although surgery should be avoided if at all possible in Crohn’s disease, and minimal surgery should occur (resecting as little as possible, given possible need for future resections), including possible stricturoplasty instead of resection. Chronic pancreatitis is unlikely given it would not cause stricture. Patients undergoing surgery should always have informed consent, which always includes risk of a stoma for any bowel surgery. Given the amount of weight he has lost he is at significant risk for refeeding syndrome, which can cause hypokalaemia, hypophosphatemia and hypomagnesemia.

Rheumatoid Scleritis is a painful inflammatory condition of the sclera in patients with rheumatoid arthritis. It might be diffuse, nodular, or necrotizing in nature. This occurs mostly in the sixth decade of life and mostly when the rheumatoid disease is in remission. Sclera is the first ocular manifestation in a patient of rheumatoid arthritis. This inflammation might later spread to the adjacent ocular structures like the cornea, causing keratitis, the uveal tract causing uveitis and the lens causing cataracts.

Risk factors specific to depression:
-Family history of mental disorder.
-History of previous suicide attempts (this includes self-harm).
-Severe depression.
-Anxiety.
-Feelings of hopelessness.
-Personality disorder.
-Alcohol abuse and/or drug abuse.
-Male gender.

Protective Factors for Suicide.
Protective factors buffer individuals from suicidal thoughts and behaviour. To date, protective factors have not been studied as extensively or rigorously as risk factors. Identifying and understanding protective factors are, however, equally as important as researching risk factors.

Protective Factors:
-Effective clinical care for mental, physical, and substance abuse disorders
-Easy access to a variety of clinical interventions and support for help seeking
-Family and community support (connectedness)
-Support from ongoing medical and mental health care relationships
-Skills in problem solving, conflict resolution, and nonviolent ways of handling disputes
-Cultural and religious beliefs that discourage suicide and support instincts for self-preservation

Oxycodone is a safer opioid to use in patients with moderate to end-stage renal failure.
Active metabolites of morphine accumulate in renal failure which means that long-term use is contraindicated in patients with moderate/severe renal failure.
These toxic metabolites can accumulate causing toxicity and risk overdose.
Oxycodone is mainly metabolised in the liver and thus safer to use in patients with moderate to end-stage renal failure with dose reductions.
Adverse effects:
Constipation is the most common overall side effect. Others include: asthenia, dizziness, dry mouth, headache, nausea, pruritus, etc.

Medications in renal failure:
Drugs to be avoided in patients with renal failure
Antibiotics: tetracycline, nitrofurantoin
NSAIDs
Lithium
Metformin
Drugs that require dose adjustment:
Most antibiotics including penicillin, cephalosporins, vancomycin, gentamicin, streptomycin
Digoxin, atenolol
Methotrexate
Sulphonylureas
Furosemide
Opioids
Relatively safe drugs:
Antibiotics: erythromycin, rifampicin
Diazepam
Warfarin

The most probable cause for diarrhoea is pseudomembranous colitis which is caused by Clostridium difficile. Pseudomembranous colitis is an inflammatory disease of the colon where the antibiotic-induced change in the balance of normal gut flora allows overgrowth of C difficile. Any antibiotic can cause this but the chances are higher with ampicillin, clindamycin, fluoroquinolones, and cephalosporins.

The most common location for a duodenal ulcer bleed is the posterior duodenum (remember: posterior bleeds, anterior perforates). The perfusion to this area is most specifically from the posterior superior pancreaticoduodenal artery.

The anterior superior pancreaticoduodenal artery supplies the anterior region. The gastroepiploic artery supplies mostly the stomach. The splenic artery goes, obviously, toward the spleen, in the other direction. The gastroduodenal artery is a branch of the celiac artery, and it’s branches are the anterior superior pancreaticoduodenal artery and posterior superior pancreaticoduodenal artery.

This patient is having vaso-occlusive event/crisis (thrombotic crisis) which is a type of sickle cell crisis. It may be associated with ostealgia.

There is no evidence of an aplastic crisis in this case as the haemoglobin level is reasonable with a good reticulocyte count. Conversely, the haemoglobin is not low enough and reticulocyte count and bilirubin are not high enough for a haemolytic crisis.

Sickle cell anaemia is characterised by periods of good health with intervening crises. The four main types of sickle cell crises are thrombotic crisis (painful or vaso-occlusive crisis), sequestration crisis, aplastic crisis, and haemolytic crisis.

Thrombotic crisis is precipitated by infection, dehydration, alcohol, change in temperature, and deoxygenation. Sequestration crisis is characterised by acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates). Aplastic crisis is characterised by a sudden fall in haemoglobin without marked reticulocytosis. It usually occurs secondary to parvovirus infection. In haemolytic crisis, a fall in haemoglobin occurs secondary to haemolysis. It is a rare type of sickle cell crisis.

Though a common community pathogen, Staphylococcus Aureas is found twice as frequently in pneumonias in hospitalized patients. It often attacks the elderly and patients with CF and arises as a co-infection with influenza viral pneumonia. The clinical course is characterized by high fevers, chills, a cough with purulent bloody sputum, and rapidly progressing dyspnoea. The gross pathology commonly reveals an acute bronchopneumonia pattern that may evolve into a necrotizing cavity with congested lungs and airways that contain a bloody fluid and thick mucoid secretions.

The most common causes of a sudden painless loss of vision are:
– ischaemic optic neuropathy
– occlusion of central retinal vein or artery
– vitreous haemorrhage
– retinal detachment.
Central retinal artery occlusion is due to thromboembolism (from atherosclerosis) or arteritis (e.g. temporal arteritis). Features include afferent pupillary defects, and a ‘cherry red’ spot on a pale retina.

Sunlight, especially its ultraviolet radiation component, can cause increased or additional types of damage in predisposed individuals, such as those taking certain phototoxic drugs, or those with certain conditions associated with photosensitivity, including:
– Psoriasis
– Atopic eczema
– Erythema multiforme
– Seborrheic dermatitis
– Autoimmune bullous diseases (immunobullous diseases)
– Mycosis fungoides
– Smith–Lemli–Opitz syndrome
– Porphyria cutanea tarda
Also, many conditions are aggravated by strong light, including:
– Systemic lupus erythematosus
– Sjögren’s syndrome
– Sinear Usher syndrome
– Rosacea
– Dermatomyositis
– Darier’s disease
– Kindler-Weary syndrome
Acute intermittent porphyria (AIP) belongs to the group inborn errors of metabolism and most patients with AIP are not light sensitive.

Vitamin B12 is mostly used in the body for the development of red blood cells and maintenance of the nervous system. It is actively absorbed in the terminal ileum after binding to the intrinsic factor (IF) which is secreted from the parietal cells of stomach. Moreover, a small amount is also passively absorbed without being bound to IF.

Vitamin B12 deficiency is characterised by sore tongue and mouth, mood disturbances, ataxia, and macrocytic anaemia. Its causes include poor diet, impaired absorption (due to disorders of terminal ileum), pernicious anaemia, and post-gastrectomy. While managing this condition, if the person is also deficient in folic acid, then it is important to treat the B12 deficiency first in order to avoid precipitating subacute combined degeneration of the cord.

A case-control study is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest). In theory, the case-control study can be described simply. Case-control studies have specific advantages compared to other study designs. They are comparatively quick, inexpensive, and easy. They are particularly appropriate for (1) investigating outbreaks, and (2) studying rare diseases or outcomes. Sudden infant death syndrome is a rare medical event, thus case-control study is the most suitable option.

Based on the provided cardiac catheterization results, the following abnormalities are present in this patient:

1. Central Cyanosis: The presence of central cyanosis indicates decreased oxygenation of the blood. This is likely due to an intracardiac shunt, causing unoxygenated blood to mix with oxygenated blood.
2. Right-to-Left Shunt: The saturation readings in the right atrium (60%), right ventricle (55%), and pulmonary artery (55%) are all lower than the expected systemic saturation of 98%. This suggests a right-to-left shunt, allowing deoxygenated blood from the right side of the heart to enter the systemic circulation without passing through the lungs.
3. Pulmonary Hypertension: The pulmonary artery pressure of 20/5 mmHg is elevated compared to normal values, indicating pulmonary hypertension. This could be secondary to increased pulmonary blood flow or resistance, often seen in the presence of a right-to-left shunt.
4. Left-to-Right Shunt: Although not explicitly stated in the results, the elevated left atrial pressure (9 mmHg) suggests increased left-sided filling pressures. This could be due to increased blood flow from a left-to-right shunt, which commonly occurs in congenital heart defects.
5. Normal Left Ventricular Pressure: The left ventricular pressure (110/80 mmHg) falls within normal limits, indicating that the left ventricle is not significantly affected by the shunting.

Based on these findings, a likely diagnosis would be a congenital heart defect causing a right-to-left shunt, such as Tetralogy of Fallot or Eisenmenger syndrome, resulting in central cyanosis and pulmonary hypertension.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, comparing two independent samples from the same population.

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

Supraspinatus tendinopathy is a common and disabling condition that becomes more prevalent after middle age and is a common cause of pain in the shoulder. A predisposing factor is resistive overuse. This patient has the classic painful arc that is a sign of shoulder impingement characteristic of supraspinatus tendonitis.

Mitochondrial DNA (mtDNA) is a double-stranded molecule of 16.6 kb (Figure 1, lower panel). The two strands of mtDNA differ in their base composition, with one being rich in guanines, making it possible to separate a heavy (H) and a light (L) strand by density centrifugation in alkaline CsCl2 gradients.

This is most likely describing irritable bowel syndrome (IBS). Symptoms are either diarrhoea, constipation, or both, abdominal pain, bloating, with various durations. It is a functional, not organic, problem, as far as research shows at this point. It is essentially a diagnosis of exclusion. Treatment is a high fibre diet with fluids. Caffeine should be avoided as this can worsen symptoms. Full colonoscopy is not warranted at this time, neither is a barium enema. A wheat-free diet is not likely to help as there is no evidence they have an allergy to this.

According to latest NICE guidelines, patients with isolated atrial septal defects do not require prophylactic antibiotics originally used in prevention of infective endocarditis in dental procedures.

Pulmonary alveolar proteinosis (PAP) is a lung condition that is caused by a build-up of proteins and other substances in the alveoli. The alveoli are the part of the lungs that contain air. PAP has the following symptoms:
Shortness of breath, also called dyspnoea
Chest pain or tightness
Fever
Weight loss
Cough (sometimes, but not always)
Low levels of oxygen in the blood
Nail clubbing (abnormal growth of toenails or fingernails)

Serologic studies are generally not useful for PAP. Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard. Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful. Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF. Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.

High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as crazy paving.

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material.

Absolute contraindications for fibrinolytic use in STEMI

Prior intracranial haemorrhage (ICH)
Known structural cerebral vascular lesion
Known malignant intracranial neoplasm
Ischemic stroke within 3 months
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed head trauma or facial trauma within 3 months
Intracranial or intraspinal surgery within 2 months
Severe uncontrolled hypertension (unresponsive to emergency therapy)
For streptokinase, prior treatment within the previous 6 months

Alpha-1-antitrypsin (AAT) is a member of the serine proteinase inhibitor (serpin) family of proteins with a broad spectrum of biological functions including inhibition of proteases, immune modulatory functions, and the transport of hormones.

This patient present with the classical symptoms of Amyotrophic neuralgia, characterised by sudden onset of pain in the shoulders that radiate down to the forearms and later resolve spontaneously but is followed by muscle wasting.

Chronic hepatitis B patients have an increased risk of hepatocellular carcinoma. In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have+HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, +anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. It is important to remember these serologies, it will get you a lot of points on the test.

The oxygen saturation in the pulmonary artery is higher than that of the right ventricle. The pressure of the pulmonary artery and of the PCWP are also high. So patent ductus arteriosus is highly suggestive.

A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing a cross-section at intervals through time.
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Relative risk is used in the statistical analysis of the data of experimental, cohort and cross-sectional studies, to estimate the strength of the association between treatments or risk factors, and outcomes.

Oesophageal stricture is a complication of systemic sclerosis, think of the oesophagus as sclerosing (fibrosing) leading to stricture and you never forget. Based on the clinical presentation of systemic sclerosis this is more likely than pancreatic dysfunction, PSC, lymphoma, or diverticulitis. Additionally, CREST syndrome stands for: calcinosis cutis, Raynaud’s phenomenon (which the patient has), oesophageal dysmotility, sclerodactyly, and telangiectasias), this is a form of systemic sclerosis you should be familiar with.

Secretin is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Secretin helps regulate the pH of the duodenum by
1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and
(2) stimulating the production of bicarbonate from the ductal cells of the pancreas.
G cells in the antrum of the stomach release gastrin
I cells in upper small intestine release CCK
D cells in the pancreas & stomach secrete somatostatin
K cells secrete gastric inhibitory peptide, an incretin, which also promotes triglyceride storage.

In rheumatoid arthritis (RA), clinical symptoms of joint stiffness, pain, and functional disability are commonly most severe in the early morning. These symptoms closely follow the circadian rhythm of the pro-inflammatory cytokine, interleukin (IL)-6. In RA, the increase in nocturnal anti-inflammatory cortisol secretion is insufficient to suppress ongoing inflammation, resulting in the morning symptoms characteristic of RA. Established diagnostic criteria for RA include prolonged morning stiffness that could last up to an hour. Loss of joint mobility, pain, malaise and swelling of finger joints are features that are not specific to rheumatoid arthritis, and are found in many other conditions.

People with polyarteritis nodosa often exhibit anaemia of chronic disease. Leucocytosis and eosinophilia may also be present. ANCA is only rarely positive. As polyarteritis nodosa affects the kidneys as well, the creatinine is elevated in most cases.

HIV can cause strictures in the biliary tract (see source for details of the disease). This makes the diagnosis of primary sclerosing cholangitis most likely given the clinical presentation and lab values. Due to its association with HIV this is more likely than all of the other answer choices. Know this association.

Haemoptysis is a symptom which indicates the worsening of mitral stenosis. It occurs due to the rupture of pulmonary veins or the capillary system due to pulmonary venous hypertension. Elevated serum creatinine is seen in worsening aortic stenosis. Worsening of tricuspid regurgitation causes ascites and a pulsatile liver.

The following drugs should be used as normal during pregnancy:
short acting β2 -agonists
long acting β2- agonists
inhaled corticosteroids
oral and intravenous theophyllines

Use steroid tablets as normal when indicated during pregnancy for severe asthma. Steroid tablets should never be withheld because of pregnancy.
If leukotriene receptor antagonists are required to achieve adequate control of asthma then they should not be withheld during pregnancy.

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.

Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.

In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.

Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.

Management:
– Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.
– Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline).
– On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.
– Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

After renal transplantation, cytomegalovirus has been identified to affect 1/4 of the post-op patients. It is the most common viral infection causing morbidity and mortality in post-op patients in the first 3 months.

Central chemoreception refers to the detection of changes in CO2/H+ within the brain and the associated effects on breathing. In the conscious animal the response of ventilation to changes in the brain’s interstitial fluid (ISF) pH is very sensitive. Note that a small change in cerebrospinal fluid (CSF) pH from 7.30 to 7.25 is associated with a doubling of alveolar ventilation; it is a very sensitive reflex response. Note also that the relationship of alveolar ventilation to ISF pH is essentially the same for both types of stimulation, metabolic acid-base disorders and primary CO2 stimulation.

Tumour lysis syndrome (TLS), triggered by the introduction of chemotherapy, has resulted in the aforementioned symptoms in this patient.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Rasburicase should be given prior to chemotherapy in order to reduce the risk of tumour lysis syndrome (TLS). Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is 5–10 times more soluble than uric acid, hence, renal excretion is more effective.

Burkitt lymphoma is a high-grade B-cell neoplasm. There are two major forms:
1. Endemic (African) form: typically involves maxilla or mandible.
2. Sporadic form: abdominal (e.g. ileocaecal) tumours are the most common form. More common in patients with HIV.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14). The Epstein-Barr virus (EBV) is strongly implicated in development of the African form of Burkitt lymphoma and to a lesser extent, the sporadic form.

Management of the lymphoma is with chemotherapy. This tends to produce a rapid response which may cause TLS.

The presentation of the patient is typical of chronic lithium toxicity (due to the presence of mainly neurological manifestations). Additional to the blood investigations mentioned, urine analysis, electrolyte levels, and renal function should also be performed. A low urine Anion gap and a low urine specific gravity are highly suggestive of lithium toxicity.
ECG obtained in this patient is likely to show: nonspecific, diffuse ST segment depression with T wave inversion.
Acute lithium toxicity presents with more GI manifestations while, the clinical features of chronic lithium toxicity are mainly neurological and can include:
Coarse tremors (fine tremors are seen in therapeutic levels), hyperreflexia, acute confusion, seizures, and coma.
The management of lithium toxicity is as follows:
Immediate GI decontamination with gastric lavage (in case of acute intoxication)
Saline Administrations: the goal of saline administration is to restore GFR, normalize urine output and enhance lithium clearance.
Haemodialysis remains the mainstay treatment for lithium toxicity as lithium is readily dialyzed because of water solubility, low volume of distribution, and lack of protein binding.
The Extracorporeal Treatments in Poisoning Workgroup (EXTRIP Workgroup) recommendations for dialysis (extracorporeal treatment) in lithium toxicity include:
• Impaired kidney function and lithium levels > 4.0 mEq/L
• Decreased consciousness, seizures, or life-threatening dysrhythmias, regardless of lithium levels
• Levels are > 5.0 mEq/L, significant confusion is noted, or the expected time to reduce levels to < 1.0 mEq/L is more than 36 hours
As post-dialysis rebound elevations in lithium levels have been documented, continuous veno-venous hemofiltration (CVVH) has been advocated.

Carcinoid tumours are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. They can be seen in other organs, including the lungs, mediastinum, thymus, liver, bile ducts, pancreas, bronchus, ovaries, prostate, and kidneys. While carcinoid tumours tend to grow slowly, they have the potential to metastasise.
Signs and symptoms seen in larger tumours may include the following:
– Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome.
– Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck.
– Diarrhoea and malabsorption (84%): Watery, frothy, or bulky stools, gastrointestinal (GI) bleed or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps.
– Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure with tachycardia and hypertension.
– Wheezing or asthma-like syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnoea.
– Pellagra with scale-like skin lesions, diarrhoea and mental disturbances.
– Carcinoid crisis can be the most serious symptom of the carcinoid tumours and life-threatening. It can occur suddenly or after stress, including chemotherapy and anaesthesia.

PPI will affect the accuracy of the test. In general, most recommend discontinuing PPI therapy for 2 weeks prior to a urea breath test. PPI’s have an anti-H. pylori effect.

First and foremost, the patient should be put on ECG monitoring to identify the cardiac state, and because of the markedly raised serum potassium, a calcium gluconate bolus will have the immediate effect of moderating the nerve and muscle performance.

The normal partial pressure reference values are:
– PaO2 more than 80 mmHg (11 kPa)
– PaCO2 less than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 (7.4kPa)
Hypoxemia (PaO2 <8kPa) with hypercapnia (PaCO2 >6.0kPa).
The pH is also lower than 7.35 at 7.3

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the build-up of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated. The underlying causes include:
– Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)
– Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)
– A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)
– Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)
– Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

The SEM is dependent on the variation in the population and the number of the extracted samples. A large variation in the population causes a large difference in the sample means, ultimately resulting in a larger SEM. However, as more samples are extracted from the population, the sample means move closer to the population mean, which results in a smaller SEM. In short, the SEM is an indicator of how close the sample mean is to the population mean. Standard error of the mean = standard deviation / square root (number of patients)
The standard error of the mean is calculated by the standard deviation / square root (number of patients)

= 12 / square root (64) = 12 / 8 = 1.5

Extrinsic allergic alveolitis (EAA) refers to a group of lung diseases that can develop after exposure to certain substances. The name describes the origin and the nature of these diseases:

‘extrinsic’ – caused by something originating outside the body
‘allergic’ – an abnormally increased (hypersensitive) body reaction to a common substance
‘alveolitis’ – inflammation in the small air sacs of the lungs (alveoli)

Symptoms can include: fever, cough, worsening breathlessness and weight loss. The diagnosis of the disease is based on a history of symptoms after exposure to the allergen and a range of clinical tests which usually includes: X-rays or CT scans, lung function and blood tests.

EAA is not a ‘new’ occupational respiratory disease and occupational causes include bacteria, fungi, animal proteins, plants and chemicals.

Examples of EAA include:

Farmer’s lung
This is probably the most common occupational form of EAA and is the outcome of an allergic response to a group of microbes, which form mould on vegetable matter in storage. During the handling of mouldy straw, hay or grain, particularly in a confined space such as a poorly ventilated building, inhalation of spores and other antigenic material is very likely.

There also appears to be a clear relationship between water content of crops, heating (through mould production) and microbial growth, and this would apply to various crops and vegetable matter, with the spores produced likely to cause EAA.

Farmer’s lung can be prevented by drying crops adequately before storage and by ensuring good ventilation during storage. Respiratory protection should also be worn by farm workers when handling stored crops, particularly if they have been stored damp or are likely to be mouldy.

Streptococcus pneumonia is the chief causative organism for lobar pneumonia in this age group patients. Typically patients present with rusty coloured sputum and a cough. Pneumocystis jiroveci is responsible for causing pneumocystis pneumonia among immunocompromised patients.

The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. Mitochondrial inheritance therefore has the following characteristics:
– Inheritance is only via the maternal line
– All children of affected males will not inherit the disease
– All children of affected females will inherit it

There are many possible causes of a red eye. It is important to be able to recognise the causes which require urgent referral to an ophthalmologist. Acute angle closure glaucoma presents with severe pain, decreased visual acuity, patient seeing haloes, semi-dilated pupils, and hazy cornea. Anterior uveitis presents with acute onset pain, blurred vision and photophobia, with small, fixed oval pupils and ciliary flush.

The foramen rotundum is one of the several circular apertures (the foramina) located in the base of the skull, in the anterior and medial part of the sphenoid bone. The maxillary branch (V2) of the trigeminal nerve (CN V) passes through and exits the skull via the pterygopalatine fossa and the foramen rotundum.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumours: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumours, adrenocortical carcinoma (ACC), and leukaemia. LFS is diagnosed in individuals meeting established clinical criteria or in those who have a germline pathogenic variant in TP53 regardless of family cancer history.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Normal distribution, also known as the Gaussian distribution, is a probability distribution that is symmetric about the mean. The normal distribution has the following properties:
– It is symmetric around the mode, the median and the mean of the distribution.
– It is unimodal
– The area under the curve and over the x-axis is unity (i.e. equal to one).
– Its density has two inflection points.
– Its density is log-concave.
The standard deviation (SD) is a measure of how much dispersion exists from the mean. SD = square root (variance)

Relative risk reduction (RRR) tells you by how much the treatment reduced the risk of bad outcomes relative to the control group who did not have the treatment. In the previous example, the relative risk reduction of fever and rash in the group of the children on the intervention was 40 per cent (1 – 0.6 = 0.4 or 40 per cent). RRR = (EER -CER) / CER = (0.1 – 0.4) / 0.4 = -0.75 or 75% reduction.

There is a strong suspicion of Thrombotic Thrombocytopenic Purpura (TTP) in this patient as he presents with neurological changes (from confusion to convulsions and coma), fever, haemolysis, thrombocytopenia, and renal failure. Additionally, TTP cases may present with jaundice, splenomegaly, and hypertension as seen in this patient. With a diagnosis of TTP, recent studies have shown that platelet transfusion is not recommended in this case because it has been shown to increase the risk for arterial thrombosis and mortality possibly due to increased aggregations.

It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines. Prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients. NICE advises either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives.

Old age, persistent backache, weight loss, and osteosclerotic lesions make prostatic adenocarcinoma the most likely diagnosis. The sequelae include severe pain, pathological fractures, hypercalcemia and cord compression. Prostatic adenocarcinoma is detected by elevated levels of prostate specific antigen. Positive serology for borrelia burgdorferi would hint at Lyme disease which does not cause osteosclerotic bone lesions, neither would Neisseria gonorrhoeae have such a presentation.

Both fibrates and nicotinic acid have been associated with myositis, especially when combined with a statin. However, the Committee on Safety of Medicines has produced guidance which specifically warns about the concomitant prescription of fibrates with statins concerning muscle toxicity.

Bezafibrate: It is a fibric acid derivative (fibrate) that has been used as a class of agents known to decrease triglyceride levels while substantially increasing HDL-C levels.
Pharmacological effects:
– Increases VLDL catabolism by increasing lipoprotein and hepatic triglyceride lipase.
– Decreases triglyceride synthesis by inhibiting acetyl-CoA reductase.
– Decreases cholesterol synthesis by inhibiting HMG-CoA reductase.

Side effects:
– Hypersensitivity
– Primary biliary cirrhosis
– Pre-existing gallbladder disease
– Concurrent use with HMG-CoA inhibitors (statins) can produce myopathy
– Hepatic/renal impairment in a patient warrants dose adjustment as this drug is primarily excreted via the renal mechanism.

Contraindications: Concurrent use of MAO inhibitors, hypersensitivity, pre-existing cholestasis, and pregnancy.

Use: It can be used to treat Barth syndrome (characterized by dilated cardiomyopathy, neutropenia (presenting with recurrent infections), skeletal myopathy and short stature)

There are number of diseases that have to be notified to relevant authorities to prevent or reduce their spread. Those conditions include Cholera, Diphtheria, Food poisoning, Infectious bloody diarrhoea, Malaria, Measles, Meningococcal septicaemia, Mumps, Plague, Rabies and Rubella.

Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.
Thus, ethanol’s inhibitory effect helps to explain the increased diuresis experienced during intoxicated states as well as increased free water loss; without appropriate ADH secretion, more water is excreted by the kidneys.

Nausea associated with hangovers is mainly due to vagal stimulation to the vomiting centre.
Following a particularly severe episode of alcohol excess, people may experience tremors due to increased glutamate production by neurons to compensate for the previous inhibition by ethanol.

Management of alcoholism:
Nutritional support:
– Alcoholic patients should receive oral thiamine if their ‘diet may be deficient’.
Pharmacological management:
– Benzodiazepines for acute withdrawal
– Disulfiram promotes abstinence – alcohol intake causes a severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis.
– Acamprosate reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo-controlled trials.

The patient is most likely a case of haemophilia A which is the genetic deficiency of clotting factor VIII in blood.

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is more common than haemophilia B and accounts for 90% of the cases. In haemophilia B (Christmas disease), there is a deficiency of clotting factor IX.

Characteristic features of haemophilia include hemarthrosis, haematomas, and prolonged bleeding following trauma or surgery. Coagulation profile of a haemophiliac person shows prolonged bleeding time, activated partial thromboplastin time (APTT), thrombin time (TT), but a normal prothrombin time (PT).

Adverse effects due to IFN-alpha have been described in almost every organ system. Many side-effects are clearly dose-dependent. Taken together, occurrence of flu-like symptoms, haematological toxicity, elevated transaminases, nausea, fatigue, and psychiatric sequelae are the most frequently encountered side effects.

Attacks or exacerbations of multiple sclerosis (MS) are characterized by symptoms that reflect central nervous system (CNS) involvement, hence upper motor neuron symptoms are seen.

The case presents with an underlying ovarian tumour, associated with psychiatric symptoms; thus, an organic illness must first be ruled out before considering the other conditions listed which often present with psychiatric features without an underlying organic disease. Among the listed conditions Anti-NMDA receptor encephalitis is the only condition that presents with psychiatric features including agitation, hallucinations, delusions and disordered thinking that is associated with tumours 50% of the time.

The most probable diagnosis in the given scenario would be Charles-Bonnet syndrome.

Charles-Bonnet syndrome (CBS) is characterized by persistent or recurrent complex hallucinations (usually visual or auditory), occurring in clear consciousness. This is generally against a background of visual impairment (although visual impairment is not mandatory for a diagnosis). Insight is usually preserved. This must occur in the absence of any other significant neuropsychiatric disturbance.

Risk factors include:
Advanced age
Peripheral visual impairment
Social isolation
Sensory deprivation
Early cognitive impairment

CBS is equally distributed between sexes and does not show any familial predisposition. The most common ophthalmological conditions associated with this syndrome are age-related macular degeneration, followed by glaucoma and cataract.

Well-formed complex visual hallucinations are thought to occur in 10-30 percent of individuals with severe visual impairment. The prevalence of CBS in visually impaired people is thought to be between 11 and 15 percent.

This is a classic clinical presentation, with alcohol intake and nausea/vomiting that leads to hematemesis, of a Mallory-Weiss tear. In Mallory-Weiss tear, they typically present as a hemodynamically stable patient after a night of binge drinking and excessive resultant vomiting. Given his EGD did not show any other pathology and he is now stable, he can be discharged home.

Extended-spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Extended spectrum beta-lactamase (ESBL) production is the main reason for multi-drug resistance among E.coli. Commonly used medications to treat ESBL-involved infections include carbapenems (imipenem, meropenem, and doripenem), cephamycins (cefoxitin and cefotetan), Fosfomycin, nitrofurantoin, beta-lactamase inhibitors (clavulanic acid, tazobactam, or sulbactam), non-beta-lactamases and colistin (if all other medications have failed.)

The size of the kidneys on ultrasound would differentiate chronic from acute renal failures. Chronic renal failure is more associated with small-sized kidneys.

Fundoscopy findings of cotton wool spots and retinal tears, accompanied by a history of blurred vision, are characteristic of retinitis. Cytomegalovirus is known to cause retinitis.

Any antiarrhythmic drugs can potentially cause arrhythmias. Before starting amiodarone, any electrolyte imbalance including hypokalaemia, hypomagnesemia, or hypocalcaemia should be corrected to prevent any arrhythmias.

In hyperkalaemia the ECG will show tall, tented T waves as well as small P waves and widened QRS complexes. 

Proton pump inhibitors can reduce gastric acid secretion by up to 99%. Acid production resumes following the normal renewal of gastric parietal cells.

In patients with acute renal tubular necrosis, infection in the form of gram-negative septicaemia is the most common cause of death, especially while the patient is awaiting spontaneous recovery of their renal function.

Lead can be absorbed through the skin and by inhalation. It is associated with iron deficiency and a microcytic anaemia. The most common gastrointestinal symptoms are abdominal colic and constipation.

Sarcoidosis is an inflammatory disease that affects one or more organs but most commonly affects the lungs and lymph glands. The inflammation may change the normal structure and possibly the function of the affected organ(s).
The presentation in sarcoidosis varies with the extent and severity of organ involvement, as follows:
Asymptomatic (incidentally detected on chest imaging): Approximately 5% of cases.
Systemic complaints (fever, anorexia): 45% of cases
Pulmonary complaints (dyspnoea on exertion, cough, chest pain, and haemoptysis [rare]): 50% of cases

Löfgren syndrome (fever, bilateral hilar lymphadenopathy, and polyarthralgias): Common in Scandinavian patients, but uncommon in African-American and Japanese patients.

Dermatologic manifestations may include the following:
– Erythema nodosum
– A lower-extremity panniculitis with painful, erythematous nodules (often with Löfgren syndrome)
– Lupus pernio (the most specific associated cutaneous lesion)
– Violaceous rash on the cheeks or nose (common)
– Maculopapular plaques (uncommon)

Staging of sarcoidosis is as follows:
Stage 0: Normal chest radiographic findings
Stage I: Bilateral hilar lymphadenopathy
Stage II: Bilateral hilar lymphadenopathy and infiltrates
Stage III: Infiltrates alone
Stage IV: Fibrosis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for the treatment of arthralgias and other rheumatic complaints. Patients with stage I sarcoidosis often require only occasional treatment with NSAIDs.

Treatment in patients with pulmonary involvement is as follows:
Asymptomatic patients may not require treatment
In patients with minimal symptoms, serial re-evaluation is prudent
Treatment is indicated for patients with significant respiratory symptoms
Corticosteroids can produce small improvements in the functional vital capacity and in the radiographic appearance in patients with more severe stage II and III disease.

This patient has Stage 1 Sarcoidosis so observation is the most appropriate action.

Hypogammaglobulinemia is a complication of chronic lymphocytic leukaemia (CLL) that leads to recurrent infections.

CLL is a type of cancer caused by monoclonal proliferation of well-differentiated lymphocytes, typically B cells (99%). Onset of the disease is usually asymptomatic and later constitutes anorexia, weight loss, bleeding, and recurrent infections. Lymphadenopathy is more marked in CLL than in chronic myelogenous leukaemia (CML).

Investigations to diagnose CLL include blood film and immunophenotyping. Smudge cells (also known as smear cells) seen on the blood film point towards CLL. Complications of the disease include hypogammaglobulinemia leading to recurrent infections, autoimmune haemolytic anaemia in 10–15% of the patients, and transformation to high-grade lymphoma (Richter’s transformation).

Clubbing of the fingers can be present in many clinical conditions like CLD, bronchiectasis, lung abscess, Ulcerative colitis and Crohn’s Disease.

Koilonychia or spoon shaped nails are a typical finding in iron deficiency anaemia.

Splinter haemorrhages are pin point haemorrhages found in infective endocarditis and secondary to trauma.

Yellow nails are present in pulmonary and renal disease.

Urinary porphobilinogen is increased between attacks of acute intermittent porphyria (AIP) and even more so, between acute attacks.

AIP is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. This results in the toxic accumulation of delta-aminolaevulinic acid and porphobilinogen.

Abdominal and neuropsychiatric symptoms are characteristic of AIP especially in people between the ages of 20–40 years. The disease is more common in females than in males (5:1). Major signs and symptoms of AIP include abdominal pain, vomiting, motor neuropathy, hypertension, tachycardia, and depression.

Diagnosis:
1. Urine turns deep red on standing (classical picture of AIP)
2. Raised urinary porphobilinogen (elevated between attacks and to a greater extent, between acute attacks)
3. Raised serum levels of delta-aminolaevulinic acid and porphobilinogen
4. Assay of red blood cells for porphobilinogen deaminase

Colonoscopy screening should begin 10 years after the first diagnosis in ulcerative colitis, given the increased risk for colon cancer. Given that she has developed primary sclerosing cholangitis, her risk of colon cancer is even higher. Colonoscopy screening should occur at 3 year intervals in the second decade, 2 year intervals in the third decade, and 1 year intervals by the first decade, making A the correct answer choice.

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.
Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess.
Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.
Normal Ultrasound rules out Turner’s syndrome.

Cerebral venous sinus thrombosis (CVST) is associated with headache (>90% of cases), seizures, focal weakness (40%) and papilledema (40%), all seen in this patient.
Risk factors for CVST include genetic or acquired prothrombotic disorders, pregnancy, the oral contraceptive pill, vasculitis, malignancy, dehydration and infection. However, there are multiple other associated factors.
Diagnosis is normally confirmed with magnetic resonance venography (MRV). Treatment is with anticoagulation, initially with heparin and subsequently with warfarin.

Depressive disorders require long-term treatment with antidepressants, psychotherapy, or both. The goal of antidepressant therapy is complete remission of symptoms and return to normal daily functioning. Studies have shown that achieving remission and continuing antidepressant therapy long after the acute symptoms remit can protect against the relapse or recurrence of the psychiatric episode. Many patients, however, inadvertently or intentionally skip doses of their antidepressant, and even discontinue it, if their symptoms improve or if they experience side effects. Antidepressant discontinuation may increase the risk of relapse or precipitate certain distressing symptoms such as gastrointestinal complaints, dizziness, flu-like symptoms, equilibrium disturbances, and sleep disorders.

Pharmacologic therapy should be continued long enough to sustain remission and avoid relapses and recurrences. Recurrence refers to a return of depression at a time beyond the expected duration of the index episode (> 9 months after remission). This means that physicians and patients alike should not be too eager to discontinue medication prematurely. An interval of 6 months has been thought to be the usual duration of antidepressant therapy. New recommendations, however, suggest that treatment should continue for up to 9 months after symptoms have resolved (continuation phase) to prevent relapse and for longer to help prevent recurrence (maintenance phase).

SSRI discontinuation symptoms are similar to those of the TCAs, with dizziness, gastrointestinal symptoms, and sleep disorders common. Anecdotal reports have included complaints of “electric shock–like” sensations, flashes, and “withdrawal buzz.” The type and severity of the symptoms correlate with the relative affinities of the agents for the serotonin reuptake sites and with secondary effects on other neurotransmitters; with SRIs that also affect cholinergic systems, the symptoms possibly correlate with cholinergic rebound.

Among the given anti-epileptics the best drug that can be given in this patient is lamotrigine.
Topiramate, carbamazepine, phenytoin, and phenobarbital are all hepatic enzyme inducers and are associated with decreased effectiveness of the oral contraceptive (OCP) due to acceleration of the metabolism of oestrogens and progestogens.
If she is planning on pregnancy then registry studies suggest that lamotrigine would also be the best choice.
Other hepatic enzyme inducers include rifampicin, spironolactone, griseofulvin, etc.

Paget’s accelerates the remodelling process with old bone breaking down more quickly which disrupts the normal growth process. New bone development eventually adjusts to the faster pace and speeds up on its own. The pace is too fast for healthy bone growth, and the regrowth ends up softer and weaker than normal. The effect of this accelerated process causes bone pain, fractures, and deformities. Since osteosarcoma is a type of bone cancer linked to abnormal bone growth, this makes it a rare but possible complication of Paget’s disease although the chances of developing osteosarcoma are minimal. Fractures are painful and restrict movement whereas this patients pain is gradually developing. Pain associated with osteoarthritis is usually mild to moderate and worsens as the day progresses.

Central retinal vein occlusion includes features such as sudden painless loss of vision, but is distinguished from central retinal artery occlusion by the presence of severe retinal haemorrhages on fundoscopy examination.

Carbon monoxide has high affinity for haemoglobin and myoglobin resulting in a left-shift of the oxygen dissociation curve and tissue hypoxia. There are approximately 50 deaths per year from accidental carbon monoxide poisoning in the UK. In these circumstances, antidotal therapy to block alcohol dehydrogenase with ethanol or 4-MP alone is insufficient to treat the poisoning. Data suggest that a severe lactic acidosis needs initial correction and in this patient the most appropriate treatment would be IV fluids with bicarbonate to correct the metabolic acidosis. Haemodialysis may be required thereafter.

Exposure to aniline dyes is a risk factor for transitional cell carcinoma. Aniline dyes are used in dyestuffs and pigment manufacturing.

The other aforementioned options are ruled out because:
1. Feed production may expose to aflatoxin (hepatocellular carcinoma).

2. Being a military personnel may expose to mustard gas (lung cancer).

3. Rubber industry may expose to nitrosamines (oesophageal and gastric cancer).

4. Refrigerant production before 1974 may expose to vinyl chloride (hepatic angiosarcoma).

The peak incidence of seizures is expected 36 hours following the onset of alcohol withdrawal.

Pathophysiology:
Chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors. Alcohol withdrawal is thought to lead to the opposite (decreased inhibitory GABA and increased NMDA glutamate transmission).

Clinical course in alcohol withdrawal:
Symptoms begin 6-12 hours following the onset of alcohol withdrawal
Seizures occur 36 hours following the onset of withdrawal
Delirium tremens (coarse tremor, confusion, delusions, auditory and visual hallucinations, fever, tachycardia) occurs approximately 72 hours after the onset of alcohol withdrawal.

Management
First-line: benzodiazepines e.g. lorazepam, chlordiazepoxide.
Carbamazepine is also effective in the treatment of alcohol withdrawal.
Phenytoin is said not to be as effective in the treatment of alcohol withdrawal seizures.

This is most likely describing irritable bowel syndrome (IBS). Symptoms are either diarrhoea, constipation, or both, abdominal pain, bloating, of varying duration. It is a functional, not an organic problem, as far as research shows at this point. It is essentially a diagnosis of exclusion. Treatment is a high fibre diet with fluids. Caffeine should be avoided as this can worsen symptoms.

In Wilson’s disease, serum caeruloplasmin is decreased. Skin pigmentation is not increased, but may become jaundiced. 24 hour urine copper excretion is increased. Hepatic copper concentration is increased. Serum copper level is also increased. Key point: high copper. Remember Kayser-Fleisher rings for the eyes in Wilson’s disease.

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.
Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:
Short stature
Stocky habitus
Obesity
Developmental delay
Round face
Dental hypoplasia
Brachymetacarpals
Brachymetatarsals
Soft tissue calcification/ossification
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.
The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

A retrospective cohort study of the primary care records of 247 lung cancer patients diagnosed between 1998–2002 showed that 10% of the X-rays were reported as normal.
Other tests may include:
– Imaging tests: A CT scan can reveal small lesions in your lungs that might not be detected on an X-ray.
– Sputum cytology: sputum may reveal the presence of lung cancer cells.
– Tissue sample (biopsy): A sample of abnormal cells may be removed for histological analysis. A biopsy may be performed in a number of ways, including bronchoscopy, mediastinoscopy and needle biopsy. A biopsy sample may also be taken from adjacent lymph nodes.

Haemophilia is a X-linked recessive disorder. In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner’s syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters.

NSAIDs are considered as the first line of treatment for managing pain and stiffness associated with ankylosing spondylitis. Other useful medications include TNF-alpha inhibitors. Other drugs like paracetamol, colchicine, and steroids are not routinely used. Bilateral total hip replacement might be indicated in advanced disease contrary to complicated spinal surgery.

The true statement among the given options is that she will still be protected against pregnancy if she takes amoxicillin for a lower respiratory tract infection while on the combined pill.

Other than enzyme-inducing antibiotics such as rifampicin, antibiotics do not reduce the efficacy of the combined oral contraceptive pill.

It was previously advised that barrier methods of contraception should be used if taking an antibiotic while using the contraceptive pill, due to concerns that antibiotics might reduce the absorption of the pill. This is now known to be untrue. However, if the absorptive ability of the gut is compromised for another reason, such as severe diarrhoea or vomiting, or bowel disease, this may affect the efficacy of the pill.

The exception to the antibiotic rule is that hepatic enzyme-inducing antibiotics such as rifampicin and rifaximin do reduce the efficacy of the pill. Other enzyme-inducing drugs, such as phenytoin, phenobarbital, carbamazepine or St John’s Wort can also reduce the effectiveness of the pill.

Other options:
The combined pill is often prescribed for women with heavy periods as it can make them lighter and less painful.
There is no evidence that women on the combined pill put on any significant weight, although they may experience bloating at certain times in the course.
Women on the pill require monitoring of their blood pressure.
There are multiple different types of combined pills.

The duration of these cell cycle phases varies considerably in different kinds of cells. For a typical rapidly proliferating human cell with a total cycle time of 24 hours, the G1 phase might last about 11 hours, S phase about 8 hours, G2 about 4 hours, and M about 1 hour. The proliferation of most animal cells is similarly regulated in the G1 phase of the cell cycle. In particular, a decision point in late G1, called the restriction point in animal cells, is the point at which the cell becomes committed to the cell cycle and after which extracellular proliferation stimulants are no longer required.. Although the proliferation of most cells is regulated primarily in G1, some cell cycles are instead controlled principally in G2.

The pattern of muscle involvement seen with quadriceps and long-finger flexors is characteristic of inclusion body myositis, an inflammatory myopathy. Polymyositis is likely to cause a predominantly proximal weakness, associated with muscle pain. The signs and symptoms are not consistent with upper cord compression, as there would likely be sensory signs, reflex changes, and possible urinary symptoms. Motor neuron disease cannot be ruled out, but there are no findings of upper motor neuron or bulbar features.

Hypertrophic cardiomyopathy is an autosomal dominant condition. Patients present with sudden cardiac death, dyspnoea, syncope and presyncope, angina, palpitations, orthopnoea and paroxysmal nocturnal dyspnoea, Congestive heart failure and dizziness. Physical findings include double or triple apical impulse, prominent a wave in the JVP, an ejection systolic crescendo-decrescendo murmur and a holosystolic murmur at the apex and axilla of mitral regurgitation.
ECG shows ST-T wave abnormalities and LVH, axis deviation (right or left), conduction abnormalities (P-R prolongation, bundle-branch block), sinus bradycardia with ectopic atrial rhythm, atrial enlargement, abnormal and prominent Q wave in the anterior precordial and lateral limb leads.
2D echocardiography shows abnormal systolic anterior leaflet motion of the mitral valve, LVH, left atrial enlargement, small ventricular chamber size, septal hypertrophy with septal-to-free wall ratio greater than 1.4:1, mitral valve prolapse and mitral regurgitation, decreased midaortic flow, partial systolic closure of the aortic valve in midsystole

Acquired asplenia or hyposlenia can occur following splenectomy. Hyposplenism is used to describe reduced (‘hypo-‘) splenic functioning and is associated with increased risk of sepsis from polysaccharide encapsulated bacteria. In particular, patients are at risk from Streptococcus pneumoniae, Haemophilus influenzae, and meningococcus. The risk is elevated as much as 350–fold.

Classic Kallmann syndrome (KS) is due to isolated hypogonadotropic hypogonadism. Most patients have gonadotropin-releasing hormone (GnRH) deficiency, as suggested by their response to pulsatile GnRH therapy. The hypothalamic-pituitary function is otherwise normal in most patients, and hypothalamic-pituitary imaging reveals no space-occupying lesions. By definition, either anosmia or severe hyposmia is present in patients with Kallmann syndrome.

Weight gain is an extremely common (5-40%) adverse effect of atypical antipsychotics such as olanzapine (dose dependent). Olanzapine causes orthostatic hypotension ≥20% of reported cases. Parkinsonism reactions occurs in 4% of people.

In any patient with asthma, a decreasing PaO2 and an increasing PaCO2, even into the normal range, indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.

Chest tightness and cough, which are the most common symptoms of asthma, are probably the result of inflammation, mucus plugs, oedema, or smooth muscle constriction in the small peripheral airways. Because major obstruction of the peripheral airways can occur without recognizable increases of airway resistance or FEV1, the physiologic alterations in acute exacerbations are generally subtle in the early stages. Poorly ventilated alveoli subtending obstructed bronchioles continue to be perfused, and as a consequence, the P(A-a)O2 increases and the PaO2 decreases. At this stage, ventilation is generally increased, with excessive elimination of carbon dioxide and respiratory alkalemia.

The main cardiovascular manifestations associated with Marfan’s syndrome are aortic dilatation and mitral valve prolapse.

CURB Pneumonia Severity Score:
– Confusion (abbreviated Mental Test Score <=8) (1 point)
– Urea (BUN > 19 mg/dL or 7 mmol/L) (1 point)
– Respiratory Rate > 30 per minute (1 point)
– Blood Pressure: diastolic < 60 or systolic < 90 mmHg (1 point) Based on the CURB Pneumonia Severity Score, the patient has severe pneumonia. According to the 2009 Centres for Medicare and Medicaid Services (CMS) and Joint Commission consensus guidelines, inpatient treatment of pneumonia should be given within four hours of hospital admission (or in the emergency department if this is where the patient initially presented) and should consist of the following antibiotic regimens, which are also in accordance with IDSA/ATS guidelines. For non-intensive care unit (ICU) patients:
Beta-lactam (intravenous [IV] or intramuscular [IM] administration) plus macrolide (IV or oral [PO])
Beta-lactam (IV or IM) plus doxycycline (IV or PO)
Antipneumococcal quinolone monotherapy (IV or IM)

If the patient is younger than 65 years with no risk factors for drug-resistant organisms, administer macrolide monotherapy (IV or PO)

For ICU patients:
IV beta-lactam plus IV macrolide
IV beta-lactam plus IV antipneumococcal quinolone

If the patient has a documented beta-lactam allergy, administer IV antipneumococcal quinolone plus IV aztreonam.

The most suitable antibiotic therapy for this patient is therefore Intravenous co-amoxiclav + clarithromycin.

Tumour marker CA 15-3 is mostly associated with breast cancer.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

The a wave indicates atrial contraction. The c wave indicates ventricular contraction and the resulting bulging of tricuspid valve into the right atrium during isovolumetric systole. The v wave indicates venous filling. The x descent indicates the atrium relaxation and the movement of the tricuspid valve downward. The y descent indicates the filling of the ventricle after tricuspid opening.

To confirm the diagnosis, especially in patients with negative anti-Ro or anti-La antibodies, labial gland biopsy is done. In performing a labial biopsy, the surgeon typically makes a shallow 1/2 inch wide incision on either side of the inner lip after numbing the area with a local anaesthetic. Schirmer’s test determines whether the eye produces enough tears to keep it moist. This test can be done for ocular symptoms of Sjogren syndrome but is of no diagnostic importance as it can be positive with many other diseases.

The patient should be prescribed IV iron and subcutaneous erythropoietin to enhance erythropoiesis to address the dropped haemoglobin.

Agitation, hypomania and suicidal intent within a few days after initiating corticosteroid therapy is highly suggestive of a diagnosis of corticosteroid-induced psychosis.

In some patients corticosteroid related psychosis has been diagnosed up to 12 weeks or more after commencing therapy.

Euphoria and hypomania are considered to be the most common psychiatric symptoms reported during short courses of steroids.
During long-term treatment, depressive symptoms were the most common.
Higher steroid doses appear to carry an increased risk for such adverse effects; however, there is no significant relationship between dose and time to onset, duration, and severity of symptoms.

Management: Reduction or cessation of corticosteroids is the mainstay of treatment for steroid psychosis. For those patients who cannot tolerate this reduction/cessation of steroids, mood stabilizers may be of some benefit.

Churg-Strauss disease (CSD) is one of three important fibrinoid, necrotizing, inflammatory leukocytoclastic systemic small-vessel vasculitides that are associated with antineutrophil cytoplasm antibodies (ANCAs).
The first (prodromal) phase of Churg-Strauss disease (CSD) consists of asthma usually in association with other typical allergic features, which may include eosinophilia. During the second phase, the eosinophilia is characteristic (see below) and ANCAs with perinuclear staining pattern (pANCAs) are detected. The treatment would therefore be different from asthma. For most patients, especially those patients with evidence of active vasculitis, treatment with corticosteroids and immunosuppressive agents (cyclophosphamide) is considered first-line therapy

The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8(+) T-cell lymphocytosis associated with a CD8(+) T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also manifest itself independently of CD4(+) T-cell counts. The syndrome may present as a Sjögren-like disease that generally associates sicca signs with bilateral parotiditis, lymphadenopathy, and extra glandular organ involvement. The latter may affect the lungs, nervous system, liver, kidneys, and digestive tract. Anomalies of the respiratory system are often identified as lymphocytic interstitial pneumonia. Facial nerve palsy, aseptic meningitis or polyneuropathy are among the more frequent neurological features. Hepatic lymphocytic infiltration, lymphocytic interstitial nephropathy and digestive tract lymphocytic infiltration account for more rarely noted complications. Sicca syndrome, organomegaly and/or organ dysfunction associated with polyclonal CD8(+) T-cell organ-infiltration are greatly suggestive of DILS in people living with HIV.

Over consumption of fluids, prolonged race duration and inadequate training all can predispose to acute hyponatraemia.
Mild symptoms include a decreased ability to think, headaches, nausea, and an increased risk of falls. Severe symptoms include confusion, seizures, and coma. Normal serum sodium levels are 135 – 145 mEq/liter (135 – 145 mmol/L). Hyponatremia is generally defined as a serum sodium level of less than 135 mEq/L and is considered severe when the level is below 120 mEq/L.
The correct treatment to give is hypertonic saline. Decompressive craniotomy would help alleviate raised intracranial pressure due to cerebral oedema however is not an appropriate first line treatment. Demeclocycline is used for SIADH and mannitol is more likely to be used in the context of traumatic brain injury.
Hyponatremia is corrected slowly, to lessen the risk of the development of central pontine myelinolysis (CPM), a severe neurological disease involving a breakdown of the myelin sheaths covering parts of nerve cells. During treatment of hyponatremia, the serum sodium (salt level in the blood) should not rise by more than 8 mmol/L over 24 hours.

Subcutaneous low molecular weight heparin (LMWH) is the preferred treatment for most patients with acute DVT, including in pregnancy. A large meta-analyses comparing LMWH to unfractionated heparin (UFH) showed that LMWH decreased the risk of mortality, recurrent veno-thrombo embolism (VTE), and haemorrhage compared with heparin. Other advantages of LMWH may include more predictable therapeutic response, ease of administration and monitoring, and less heparin-induced thrombocytopenia. Disadvantages of LMWH include cost and longer half-life compared with heparin.

Warfarin, which is administered orally, is used if long-term anticoagulation is needed. The international normalized ratio (INR) is followed, with a target range of 2-3. Warfarin crosses the placenta and is teratogenic, causing a constellation of anomalies known as warfarin embryopathy, with greatest risk between the sixth and twelfth week of gestation.
Other options are not indicated for use.

Erythromycin is a bacteriostatic antibiotic. This means it stops the further growth of bacteria rather than directly destroying it. This is achieved by inhibiting protein synthesis. Erythromycin binds to the 23S ribosomal RNA molecule in the 50S subunit of the bacterial ribosome. This causes a blockage in the exiting of the peptide chain that is growing. Given that humans have 40S and 60S subunits, and do not have 50S subunits, erythromycin does not affect protein synthesis in human tissues.

Spironolactone is an aldosterone antagonist which acts in the distal convoluted tubule. It is a potassium-sparing diuretic that prevents the body from absorbing too much salt and keeps the potassium levels from getting too low. Spironolactone is used to treat heart failure, high blood pressure (hypertension), or hypokalaemia (low potassium levels in the blood).

The patient is most likely to have Postpartum thyroiditis which goes through 2 phases; hypothyroid and a hyperthyroid phase.
The hyperthyroid phase of postpartum thyroiditis occurs between 2 and 10 months postpartum. Most commonly, it presents at 3 months. Symptoms more common in women with hyperthyroid postpartum thyroiditis include palpitations, fatigue, heat intolerance, and irritability/nervousness. The frequency of asymptomatic hyperthyroidism is 33%.
Untreated, the hyperthyroidism resolves spontaneously within 2–3 months. This phase is diagnosed by the combination of a low serum TSH concentration in the presence of thyroid peroxidase antibodies, in women who are TSH receptor antibody-negative. Free T4 levels are typically elevated but may be normal.
Treatment of hyperthyroidism, when necessary, is based on symptom severity and should be a joint decision of patient and physician. Beta-blockers such as propranolol are given to alleviate palpitations, irritability, and nervousness. The morbidity associated with treatment is the side effects of beta-blockade. The downside of withholding treatment is allowing the woman to remain symptomatic. Antithyroid medicines (thioureas) are not a potential treatment alternative, because the hyperthyroidism is caused by destructive thyroiditis resulting in the release of preformed thyroid hormone.

The walls of the ascending limb of the loop of Henle are not permeable to water. The tubular fluid thus becomes increasingly dilute as it ascends toward the cortex, whereas the interstitial fluid around the loops of Henle in the medulla becomes increasingly more concentrated.

The ascending limb actively reabsorbs NaCl but has an extremely low transepithelial osmotic water permeability, even in the presence of vasopressin. This combination of NaCl reabsorption without water reabsorption serves two vital functions: it provides NaCl to increase the osmolality of the medullary interstitium, tubules, vasculature, and collecting ducts; and it dilutes the luminal fluid within the thick ascending limb.

This case describes Zollinger-Ellison syndrome. It is characterized by refractory peptic ulcer disease, often multiple ulcers. This is typically caused by secretion of gastrin from a gastrinoma, a neuroendocrine tumour. The most common site of ulceration is the duodenum. A symptom of a pancreatic gastrinoma may be steatorrhea from hypersecretion of gastrin. Serum gastrin levels > 1000 and a pH < 2 are diagnostic of pancreatic gastrinoma. The secretin test is a test that can differentiate gastrinoma from other causes of high gastrin levels. Gastrin will rise after secretin injection if the patient has a gastrinoma.

1mg Prednisolone = 4mg hydrocortisone, so the actual equivalent daily dose is 7mg.

Herpes zoster oticus is a viral infection of the inner, middle, and external ear. It manifests as severe otalgia with associated cutaneous vesicular eruption, usually of the external canal and pinna. When associated with facial paralysis, the infection is called Ramsay Hunt syndrome.

A fasting blood glucose level from 110 to 126 mg/dL (5.5 to 6.9 mmol/L) is considered prediabetes. This result is sometimes called impaired fasting glucose.
Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by plasma glucose. If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.