Cisplatin is a cytotoxic agent that acts by causing cross-linking in DNA. Its adverse effects include ototoxicity, peripheral neuropathy, hypomagnesaemia, etc.

The causative cytotoxic agents acting through the other aforementioned MOAs are as follows:

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

2. Hydroxyurea (hydroxycarbamide): Inhibits ribonucleotide reductase, decreasing DNA synthesis.

3. Mercaptopurine (6-MP): Purine analogue that is activated by HGPRTase, decreasing purine synthesis.

4. Vincristine, vinblastine: Inhibits formation of microtubules.

Scabies is due to an infestation of Sarcoptes scabiei and most commonly presents with these symptoms. The organism resides in burrows in a pattern specifically affecting the interdigital spaces and the skin folds of the arms and legs. The infection spreads from one person to another, especially in populated communities, through close contact.
Henoch-Schönlein purpura is a type of vascular inflammation.
Psoriasis rash is characterised by scaly plaques affecting the extensor surfaces of the body. Pemphigus vulgaris and bullous pemphigoid both are bullous disorders of the skin. They may present as crusted, weeping, diffuse lesions and there may be involvement in other sites; erosions in the mouth are typically involved in pemphigus vulgaris. Bullous pemphigoid involves the flexural areas and may be associated with a new medication.

The woman seems to have a chancroid, which may or may not drain to the lymph nodes of the groin. These nodes are the superficial inguinal lymph nodes.

The patient most likely has reactive arthritis which is usually diagnosed on history and clinical examination. The classic triad of symptoms include conjunctivitis, urethritis and arthritis. Arthritis and conjunctivitis may occur 4-6 weeks after a gastrointestinal or genitourinary infection. Arthritis usually occurs acutely, mostly involving the lower limb and is asymmetrical. Blood culture, urine culture and arthrocentesis (joint aspiration) will not yield positive results.

Cefalexin should be avoided in this patient.
This patient is known to have a severe penicillin allergy. None of the above antibiotics are penicillin based. However, 0.5 – 6.5% of patients who are proven to have an IgE mediated penicillin allergy will also be allergic to cephalosporins, including cefalexin.

Penicillin, cephalosporins, and carbapenems are all members of the beta-lactam group of antibiotics and share a common beta-lactam ring. There is, therefore, a small risk of allergy cross-over between all these antibiotics. The rates of allergy cross-over are lower with second and third-generation cephalosporins than first-generation cephalosporins such as cefalexin.

It is important to question the patient carefully to ascertain what symptoms they had on exposure to penicillin. Symptoms such as an urticarial rash or itching make it more likely that they have an IgE mediated allergy.

Cabergoline, an ergot derivative, is a long-acting dopamine agonist. It is usually better tolerated than Bromocriptine (BEC), and its efficacy profiles are somewhat superior to those of BEC. It offers the convenience of twice-a-week administration, with a usual starting dose of 0.25 mg biweekly to a maximum dose of 1 mg biweekly. Some studies have shown efficacy even with once-a-week dosing. Cabergoline appears to be more effective in lowering prolactin levels and restoring ovulation. Up to 70% of patients who do not respond to BEC respond to cabergoline.

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.

Thrombolytic therapy is indicated in patients with evidence of ST-segment elevation MI (STEMI) or presumably new left bundle-branch block (LBBB) presenting within 12 hours of the onset of symptoms if there are no contraindications to fibrinolysis. STEMI is defined as new ST elevation at the J point in at least two contiguous leads of 2 mm (0.2 mV) or more in men or 1.5 mm (0.15 mV) in women in leads V2-V3 and/or 1 mm (0.1 mV) or more in other contiguous limb leads.

Both long-acting calcium channel blockers and beta blockers improve symptoms of patients with SVT. Verapamil does not have adverse maternal or fetal side effects which would suggest that the use of verapamil in the treatment of supraventricular arrhythmias in pregnancy is safe and effective. Beta blockers are associated with intrauterine fetal growth restriction.

Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals. This would be the most likely option as it is the only disease that can affect both liver and lung functions.
People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema. Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs.
About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and sclera (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1 antitrypsin deficiency are also at risk of developing hepatocellular carcinoma.

Patients with compressive neuropathy of the ulnar nerve typically describe numbness and tingling of the ulnar-sided digits of the hand, classically in the small finger and ulnar aspect of the ring finger. Among the general population, symptoms usually begin intermittently and are often worse at night, particularly if the elbow is flexed while sleeping. As the disease progresses, paraesthesia may occur more frequently and during the daytime.

When you have a patient with HIV and diarrhoea on the exam, think Cryptosporidium. In those who are immunocompetent this organism doesn’t usually cause symptoms, but in immunocompromised people like those with HIV, it causes infection and diarrhoea. Typically those with CD4 counts of <100 cells/µL1 have the greatest risk for prolonged, severe, or extraintestinal cryptosporidiosis.

This patient has a combination of right cerebellar dysfunction with right-sided cranial nerve palsies (VI, VII, and VIII). The magnetic resonance imaging (MRI) shows a calcified meningioma within the right cerebellar pontine area, which would account for these findings. The cerebrospinal fluid (CSF) analysis shows oligoclonal bands, however, these are matched in the serum, which reflects a systemic inflammatory response from his rheumatoid arthritis.

The MRI scan and CSF analysis would not be consistent with progressive multiple sclerosis. The progressive nature of her symptoms would be against a diagnosis of brainstem infarct, and one would expect more pyramidal signs in the peripheral nervous system.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect nearly any organ system: the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin. The histopathological features are similar across organs, regardless of the site. IgG4-RD is analogous to sarcoidosis, in which diverse organ manifestations are linked by similar histopathological characteristics. Raised concentrations of IgG4 in tissue and serum can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.

Some IgG4-RDs are:
1. Autoimmune pancreatitis
2. Riedel’s Thyroiditis
3. Mediastinal and Retroperitoneal Fibrosis
4. Periaortitis/periarteritis/Inflammatory aortic aneurysm
5. Kuttner Tumour (submandibular glands)
6. IgG4-related Mikulicz disease (lacrimal, parotid, and submandibular glands)

Although this patient’s left ventricular function is normal at the time of examination, there is chance of deterioration of it due to aortic regurgitation. It is found that ACE inhibitors slow the development of left ventricular dysfunction. So this patient should be started on an ACE inhibitor.

A study conducted showed that the average post smoking cessation weight gain was about 2 kg.
Withdrawal symptoms usually peak after 1–3 days and then decrease over a period of 3–4 weeks. After this time, the body has expelled most of the nicotine, and the withdrawal effects are mainly psychological.

In asthma, a reversible increase in residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) may occur. There is a fall in FEV1, FVC and gas transfer.

Catatonia is a state of apparent unresponsiveness to external stimuli and apparent inability to move normally in a person who is apparently awake. Catatonia can be acute and occur in severely ill patients with underlying psychiatric or other medical disorders.

A history of behavioural responses to others usually includes the presence of the following:
– Mutism (absence of speech)
– Negativism (performing actions contrary to the commands of the examiner)
– Echopraxia (repeating the movements of others)
– Echolalia (repeating the words of others)
– Waxy flexibility (slight, even resistance to positioning by examiner)
– Withdrawal (absence of responses to the environment).

In the presence of a catatonic state, both first and second generation antipsychotics (SGA) may contribute to maintaining or worsening the catatonic state and increase the risk of developing NMS (neuroleptic malignant syndrome).

Electroconvulsive therapy (ECT) is effective in all forms of catatonia, even after pharmacotherapy with benzodiazepines has failed. Response rate ranges from 80% to 100% and results superior to those of any other therapy in psychiatry. ECT should be considered first-line treatment in patients with malignant catatonia, neuroleptic malignant syndrome, delirious mania or severe catatonic excitement, and in general in all catatonic patients that are refractory or partially responsive to benzodiazepines. Early intervention with ECT is encouraged to avoid undue deterioration of the patient’s medical condition.

Electroconvulsive therapy (ECT) is a procedure, done under general anaesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental health conditions.

Generalized Anxiety Disorder (GAD) is characterized by persistent and excessive worry about a number of different things. People with GAD may anticipate disaster and may be overly concerned about money, health, family, work, or other issues. Individuals with GAD find it difficult to control their worry. They may worry more than seems warranted about actual events or may expect the worst even when there is no apparent reason for concern.

GAD is diagnosed when a person finds it difficult to control worry on more days than not for at least six months and has three or more symptoms.

Treatment usually consists of a combination of pharmacotherapy and/or psychotherapy. Antidepressant agents are the drugs of choice in the treatment of anxiety disorders, particularly the newer agents, which have a safer adverse effect profile and higher ease of use than the older tricyclic antidepressants (TCAs), such as selective serotonin reuptake inhibitors (SSRIs).

Seasonal affective disorder (SAD) is a type of depression that’s related to changes in seasons. SAD begins and ends at about the same time every year. For most people with SAD, the symptoms start in the fall and continue into the winter months, sapping the person’s energy and making him feel moody. Less often, SAD causes depression in the spring or early summer.

Treatment for SAD may include light therapy (phototherapy), medications and psychotherapy.

Signs and symptoms of SAD may include:
Feeling depressed most of the day, nearly every day
Losing interest in activities you once enjoyed
Having low energy
Having problems with sleeping
Experiencing changes in your appetite or weight
Feeling sluggish or agitated
Having difficulty concentrating
Feeling hopeless, worthless or guilty
Having frequent thoughts of death or suicide.

Seasonal affective disorder is diagnosed more often in women than in men. And SAD occurs more frequently in younger adults than in older adults.

Factors that may increase your risk of seasonal affective disorder include:
Family history. People with SAD may be more likely to have blood relatives with SAD or another form of depression.
Having major depression or bipolar disorder. Symptoms of depression may worsen seasonally if you have one of these conditions.
Living far from the equator. SAD appears to be more common among people who live far north or south of the equator. This may be due to decreased sunlight during the winter and longer days during the summer months.

Giant Cell Arteritis (Temporal Arteritis) is the most probable diagnosis. GCA should always be considered in the differential diagnosis of a new-onset headache in patients 50 years of age or older with an elevated erythrocyte sedimentation rate. Temporal artery biopsy remains the criterion standard for diagnosis of this granulomatous vasculitis. High-dose corticosteroid therapy is the universally accepted treatment.

Carboxylation of factor II, VII, IX, X and protein C is affected by warfarin. Factor XII is not affected.

The NICE 2019 guidelines states that in patients who are uncontrolled with a SABA (Salbutamol) and ICS (Beclomethasone), LTRA should be added.
If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS as maintenance therapy, offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review the response to treatment in 4 to 8 weeks.

Glioblastoma multiforme, also considered as grade IV astrocytoma, is the most malignant form of the tumour and accounts for about 20% of all cerebral tumours. These often remain clinically silent until they have reached a large enough size. In adults, glioblastoma multiforme usually occurs in the cerebral hemispheres, especially the frontal and temporal lobes of the brain. About half occupy more than one hemisphere at presentation, and some are multicentric. Biopsy shows high cellularity with mitoses, pleomorphism, and vascular hyperplasia. Prognosis is extremely poor, with only 20% surviving beyond 1 year and 10% beyond 2 years.

The prompt is suggestive of celiac disease as an aetiology. The antibody that is used primarily to suggest this diagnosis is anti-tissue transglutaminase antibody. You can also check anti-gliadin and anti-endomyseal antibodies, although anti-TTG antibodies are now the preferred test. To get an official diagnosis you must have a tissue diagnosis (biopsy). Anti-smooth muscle antibodies would be seen in autoimmune hepatitis. Anti-thyroid antibodies are not at all related to this, and are associated with thyroid. Anti-nuclear antibodies are non-specific.

The most common cause of cervical radiculopathy is degenerative disease in the cervical spine. In 80–90% of patients with cervical radiculopathy, the C5/C6 or C6/C7 motion segments are affected by degenerative disease and the nearby C6 and/or C7 nerve roots are producing the symptoms. Patients with cervical radiculopathy complain of neck pain and radiating pain in the arm sometimes combined with sensory and motor disturbances in the arm and/or hand. These symptoms are accepted as being caused by the nerve root compression. Middle finger and palm of the hand are mostly rising the suspicion for C7 nerve root and median nerve involvement.

Hashimoto thyroiditis is the most common cause of hypothyroidism in developed countries. In contrast, worldwide, the most common cause of hypothyroidism is an inadequate dietary intake of iodine. This disease is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis.

West Nile virus is an RNA virus transmitted by the Culex species of mosquitoes. It is mostly prevalent in South America, Africa and some parts of Europe. Clinically it presents with high grade fever, headache, abdominal pain, anorexia and a morbilliform rash over the body. It can also lead to meningitis, encephalitis and flaccid paralysis by affecting the anterior horn cells, a process suggesting similarity to poliomyelitis. It can be fatal if not treated abruptly. Studies suggest that it can be transferred from mother to offspring. New-borns may present with encephalitis, chorioretinitis and wide spread brain damage. Patients suffering from West Nile virus can be effectively treated with interferon, IV immunoglobulin and Ribavirin.

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.

B-type natriuretic peptide (BNP) is secreted mainly from the left ventricle and it is secreted as a response to stretching caused by increased ventricular blood volume.

The next step in managing this patient is to give 10 mg and continue administering in 10 mg increments each hour until symptoms are under control.

Methadone alleviates opioid withdrawal symptoms and reduces cravings. Methadone is useful for detoxification from longer-acting opioids such as morphine or methadone itself.
Methadone should be used with caution if the patient has:
Respiratory deficiency
Acute alcohol dependence
Head injury
Treatment with monoamine oxidase inhibitors (MAOIs)
Ulcerating colitis or Crohn’s disease
Severe hepatic impairment
The dose must be reviewed on a daily basis and adjusted based upon how well the symptoms are controlled and the presence of side effects. The greater the dose of opioids used by the patient, the greater the dose of methadone required to control withdrawal symptoms.

To avoid the risk of overdose in the first days of treatment The recommended dosing of methadone is 30mg in two doses of 15mg morning and evening.

It is important to note that a methadone dose equivalent to what the patient reports they are taking should never be given.
It is rare to need more than 40 mg per 24 hours: beware of overdosing which can lead to respiratory arrest.

This case has hypercalcaemia most likely associated with the bony metastases from her pre-existing breast carcinoma. The most appropriate next step is to give Pamidronate 60mg intravenously, a bisphosphonate, to immediately inhibit bone resorption and formation.

Distal renal tubular acidosis is due to defective proton secretion from the alpha intercalated cells of the distal tubule caused by dysfunction of the H+/K+ antiporter on the apical membrane. This leads to failure of H+ excretion thereby causing systemic acidosis and potassium depletion. Inability to lower the urine pH below 5.3 in the presence of systemic acidosis is the diagnostic hallmark of type I or distal renal tubular acidosis. Hypercalciuria, hypocitraturia and elevated urinary pH observed in distal renal tubular acidosis can lead to nephrocalcinosis and may cause renal calculi, obstructive uropathy and renal failure necessitating surgical or endoscopic stone extraction.

Squamous-cell skin cancer usually presents as a hard lump with a scaly top but can also form an ulcer. Onset is often over months and it is more likely to spread to distant areas than basal cell cancer vie the lymphatics. The greatest risk factor is high total exposure to ultraviolet radiation from the Sun. Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowen’s disease, arsenic exposure, radiation therapy, poor immune system function, previous basal cell carcinoma, and HPV infection. While prognosis is usually good, if distant spread occurs five-year survival is ,34%

Of all the listed options, gastric cancer is least likely to be inherited.

The above mentioned tumours are ruled out as explained below:
1. Breast and Ovarian cancers: Between 5%–10% of all breast cancers are thought to be hereditary. Mutation in the BRCA1 and BRCA2 genes also increase the risk of ovarian cancer.

2. Colorectal and Endometrial cancers: About 5% of cases of colorectal cancer are caused by hereditary non-polyposis colorectal carcinoma (HNPCC) and 1% are due to familial adenomatous polyposis. Women who have HNPCC also have a markedly increased risk of developing endometrial cancer—around 5% of endometrial cancers occur in women with this risk factor.

The immunological changes in HIV include depletion in CD4+ T cell, cytokine dysregulation and immune dysfunction. The dominant immunologic feature of HIV infection is progressive depletion of the helper T cell (CD4+ T cell), which reverses the normal CD4:CD8 ratio and subsequently lead to immunodeficiency. Other imuunological changes include:
increased B2-microglobulin
decreased IL-2 production
polyclonal B-cell activation
decreased NK cell function
reduced delayed hypersensitivity responses

The patient has bloody diarrhoea that sounds like a food poisoning in the clinical scenario. Campylobacter is the most common cause of this in the United Kingdom. This is then followed by Salmonella and Shigella. The symptoms are usually self limiting. This is more likely to be bacterial from the food than a viral gastroenteritis.

Statins are a selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which is the enzyme responsible for the conversion of HMG-CoA to mevalonate in the cholesterol synthesis pathway.
Statins are usually well tolerated with myopathy, rhabdomyolysis, hepatotoxicity, and diabetes mellitus being the most common adverse reactions.
This is the rate-limiting step in cholesterol synthesis, that leads to increased hepatic low-density lipoprotein (LDL) receptors and reduced hepatic VLDL synthesis coupled with increased very-low-density lipoprotein (VLDL) clearance.

Cervical radiculopathy is usually due to compression or injury to a nerve root by a herniated disc or degenerative changes. Levels C5 to T1 are the most commonly affected. It is usually, but not always, accompanied by cervical radicular pain, a sharp and shooting pain that travels from the neck and down the upper limb and may be severe. This needs to be differentiated from pain referred from the musculoskeletal (somatic) structures in the neck, which may be aching rather than sharp, and is more severe in the neck than in the upper limb. The neurological signs of cervical radiculopathy depend on the site of the lesion. The patient may have motor dysfunction, sensory deficits or alteration in tendon reflexes. While pain is a common presenting symptom, not all radiculopathies are painful (i.e. only motor deficits may be obvious). CT scanning cannot accurately demonstrate the commonest cause for cervical radiculopathy (disc herniation) without myelography, which requires hospital admission, lumbar puncture and the use of contrast. In patients with cervical radiculopathy, MRI is the imaging technique of choice for the detection of root compression by disc herniation and osteophytes. MRI allows the nerve roots to be directly visualised. Nerve conduction studies are also useful in determining the nerve roots that are involved.

Gastrin is released from G cells in the antrum of the stomach after a meal. It stimulates parietal cells to release HCl. Gastrin is stimulated by a number of things: antrum distention, vagal stimulation, peptides (especially amino acids) in the stomach, hypercalcemia. Gastrin release is inhibited by acid, SST, GIP, VIP, secretin, glucagon, and calcitonin.

Normal distribution describes the spread of many biological and clinical measurements. Usually, 68.3% lies within 1 standard deviation (SD) of the mean, 95.4% lies within 2 SD of the mean and 99.7% lies within 3 SD of the mean.

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)

L4 dermatome distribution includes the kneecaps.

IgA nephropathy’s characteristic presentation is haematuria following a non-specific upper respiratory infection as was evident in this case. IgA nephropathy also usually occurs in children and young males, like this patient.

COPD is commonly associated with progressive hypoxemia. Oxygen administration reduces mortality rates in patients with advanced COPD because of the favourable effects on pulmonary hemodynamics.

Long-term oxygen therapy improves survival 2-fold or more in hypoxemic patients with COPD, according to 2 landmark trials, the British Medical Research Council (MRC) study and the US National Heart, Lung and Blood Institute’s Nocturnal Oxygen Therapy Trial (NOTT). Hypoxemia is defined as PaO2 (partial pressure of oxygen in arterial blood) of less than 55 mm Hg or oxygen saturation of less than 90%. Oxygen was used for 15-19 hours per day.

Therefore, specialists recommend long-term oxygen therapy for patients with a PaO2 of less than 55 mm Hg, a PaO2 of less than 59 mm Hg with evidence of polycythaemia, or cor pulmonale. Patients should be evaluated after 1-3 months after initiating therapy, because some patients may not require long-term oxygen.

Primary hyperparathyroidism (PHPT) is diagnosed based upon levels of blood calcium and parathyroid hormone (PTH). In most people with PHPT, both levels are higher than normal. Occasionally, a person may have an elevated calcium level and a normal or minimally elevated PTH level. Since PTH should normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates PHPT.

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

Community-acquired pneumonia (CAP) is one of the most common infectious diseases and is an important cause of mortality and morbidity worldwide. Typical bacterial pathogens that cause CAP include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
The CURB-65 is used as a means of deciding the action that is needed to be taken for that patient.
Score 3-5: Requires hospitalization with consideration as to whether they need to be in the intensive care unit

Recent studies have suggested that the use of a beta-lactam alone may be noninferior to a beta-lactam/macrolide combination or fluoroquinolone therapy in hospitalized patients.

Therapy in ICU patients includes the following:
– Beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) plus either a macrolide or respiratory fluoroquinolone
– For patients with penicillin allergy, a respiratory fluoroquinolone and aztreonam

Therefore the appropriate treatment would be Cefotaxime and erythromycin.

Infection of chickenpox in the first half of pregnancy can result in congenital varicella syndrome. It presents as cerebral, cortical and cerebellar hypoplasia with convulsions and rudimentary digits. Prevention is by administering varicella vaccine, even before pregnancy. Varicella immunoglobulin is administered to pregnant women who are exposed to infection. Infection during pregnancy is treated with acyclovir.

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)

The upper motor neurone signs in this patient point towards a diagnosis of spinal cord compression above the level of L1 and rules out cauda equina syndrome.

Spinal cord compression is an oncological emergency and affects up to 5% of cancer patients. Extradural compression accounts for the majority of cases, usually due to vertebral body metastases. One of the most common causes of spinal cord compression is osteoarthritis. It is also more commonly seen in patients with lung, breast, or prostate cancer.

Clinical features include:
1. Back pain: the earliest and most common symptom, may worsen on lying down or coughing
2. Lower limb weakness
3. Sensory changes: sensory loss and numbness
4. Neurological signs: depending on the level of the lesion.
Lesions above L1 usually result in upper motor neurone signs in the legs. Lesions below L1 usually cause lower motor neurone signs in the legs and perianal numbness. Tendon reflexes are increased below the level of the lesion and absent at the level of the lesion.

Management options are:
1. High-dose oral dexamethasone
2. Urgent MRI for consideration of radiotherapy or surgery

Alpha1-antitrypsin (AAT) deficiency, first described in 1963, is one of the most common inherited disorders amongst white Caucasians. Its primary manifestation is early-onset of pan acinar emphysema. In adults, alpha1-antitrypsin deficiency leads to chronic liver disease in the fifth decade. As a cause of emphysema, it is seen in non-smokers in the fifth decade of life and during the fourth decade of life in smokers.

Symptoms of alpha1-antitrypsin (AAT) deficiency emphysema are limited to the respiratory system. Dyspnoea is the symptom that eventually dominates alpha1-antitrypsin deficiency. Similar to other forms of emphysema, the dyspnoea of alpha1-antitrypsin deficiency is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities.
The serum levels of some of the common genotypes are:
•PiMM: 100% (normal)
•PiMS: 80% of normal serum level of A1AT
•PiSS: 60% of normal serum level of A1AT
•PiMZ: 60% of normal serum level of A1AT, mild deficiency
•PiSZ: 40% of normal serum level of A1AT, moderate deficiency
•PiZZ: 10–15% (severe alpha 1-antitrypsin deficiency)

Squamous cell carcinoma like other skin cancers mostly arise on photo exposed sites. A patient usually presents with a history of a non healing lesion or wound. Confirmatory diagnosis requires a skin biopsy and histopathological screening. It is rarely metastatic and treatment of choice is surgical excision.

Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols.

Ocular manifestations of rheumatoid arthritis are common, with 25% of patients having eye problems. These manifestations include keratoconjunctivitis sicca (most common), episcleritis (erythema), scleritis (erythema and pain), corneal ulceration, and keratitis.

When statistically comparing data sets, researchers estimate the population of each sample and examine them to see whether they are identical. The standard error of the mean (SEM) – not the standard deviation (SD), which represents the variation in the sample – is used to estimate the population mean. Via this process, researchers conclude that the sample used in their studies appropriately represents the population within the error range specified by the pre-set significance level.
The SEM is smaller than the SD, as the SEM is estimated usually with the SD divided by the square root of the sample size. For this reason, researchers are tempted to use the SEM when describing their samples. It is acceptable to use either the SEM or SD to compare two different groups if the sample sizes of the two groups are equal; however, the sample size must be stated in order to deliver accurate information. For example, when a population has a large amount of variation, the SD of an extracted sample from this population must be large. However, the SEM will be small if the sample size is deliberately increased.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. Symmetric lower limb arthropathy and a sterile joint aspirate points towards reactive arthropathy.

One of the most important complications in patients with PKD is being affected by berry aneurysms that may burst, causing a subarachnoid haemorrhage, which seems to be the case in this patient.

Herpes zoster is a viral disorder in which painful vesicular lesions are present in a specific dermatome area. High-grade fever may present as well due to infection. Varicella zoster, measles, herpes simplex and HIV do not present with tender lesions of a limited area.

Favus is a fungal infection of the scalp, resulting in the formation of a yellowish crusted plaque over the scalp and leads to scar formation with alopecia. Tinea capitus is a fungal infection of the scalp resulting in scaling and non scarring hair loss. Folliculitis presents with multiple perifollicular papules which can be caused by both bacteria and fungi. Cradle cap usually affects infants where the whole scalp is involved. It can lead to hair loss and responds to topical antifungals and keratolytics.

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.

Pseudomembranous colitis is caused by a C. difficile infection that causes membranes to form on the colon wall. It is caused most commonly by broad-spectrum antibiotics. This would include cephalosporins, broad-spectrum penicillin, and clindamycin. Macrolides and quinolones have also been reported as potential aetiologies, but much less commonly.

Classically, pheochromocytoma manifests with the following 4 characteristics:
– Headaches
– Palpitations
– Sweating
– Severe hypertension

The Endocrine Society, the American Association for Clinical Chemistry, and the European Society of Endocrinology have released clinical practice guidelines for the diagnosis and management of pheochromocytoma.
Biochemical testing via measurement of plasma free metanephrines or urinary fractionated metanephrines should be performed in patients suspected of having pheochromocytoma.

Catecholamines produced by pheochromocytomas are metabolized within chromaffin cells. Norepinephrine is metabolized to normetanephrine and epinephrine is metabolized to metanephrine. Because this process occurs within the tumour, independently of catecholamine release, pheochromocytomas are best diagnosed by measurement of these metabolites rather than by measurement of the parent catecholamines.

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.

Patients with varicella zoster infection present with general fatigue and fever along with multiple lesions which do not appear to be identical.

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

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.

Criteria for the diagnosis of diabetes

1. A1C ≥6.5%. The test should be performed in a laboratory using a method that is certified and standardized.*
OR
2. Fasting glucose ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*
OR
3. 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycaemia or hyperglycaemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycaemia, criteria 1–3 should be confirmed by repeat testing.

Secretin stimulates bicarbonate secretion from the pancreas and liver. VIP induces relaxation of the stomach and gallbladder, secretion of water into pancreatic juice/ bile, and inhibits gastric acid secretion/absorption. CCK classically stimulates gallbladder contraction and relaxation of the sphincter of Oddi. Gastrin stimulates the secretion of HCl by parietal cells in the stomach. Motilin, as the name suggests, increases motility.

Perinatal transmission is the most common cause of Hepatitis B infection worldwide. Post-exposure prophylaxis should be provided, which consists of hepatitis B immune globulin and hepatitis B vaccine within 12 hours of birth. Without this, about 40% will develop chronic infection.

Peroneal nerve injury is also known as foot drop. The common peroneal nerve supplies the ankle and toe extensor muscle groups as well as sensation over the dorsum of the foot; thus, there is also loss of sensation in these cases.

The use of hormone replacement therapy (HRT) based on unopposed oestrogen increases the risk of endometrial cancer, and uterine hyperplasia or cancer.
Evidence from randomized controlled studies showed a definite association between HRT and uterine hyperplasia and cancer. HRT based on unopposed oestrogen is associated with this observed risk, which is unlike the increased risk of breast cancer linked with combined rather than unopposed HRT.

Speaking to your consultant is the most appropriate first action to take in this scenario. They are best placed to be able to take action to try and amend the situation. The consultant is also ultimately responsible for patient care and hterefore have a right to know if you are struggling, as this may affect patient care.
Arriving early and taking time off sick do not address the problem.

Uhthoff’s phenomenon is worsening of vision following a rise in body temperature.
Lhermitte’s sign describes paraesthesia in the limbs on neck flexion.
Oppenheim’s sign is seen when scratching of the inner side of leg leads to extension of the toes. It is a sign of cerebral irritation and is not related to multiple sclerosis.
Werdnig-Hoffman’s disease is also known as spinal muscular atrophy.

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.

Features that affect prognosis are tumour thickness in millimetres (Breslow’s depth – the deeper the Breslow thickness the poorer the prognosis.), depth related to skin structures (Clark level – the level of invasion through the dermis), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, presence of tumour-infiltrating lymphocytes (if present, prognosis is better), location of lesion, presence of satellite lesions, and presence of regional or distant metastasis. Malignant melanoma tends to grow radially before entering a vertical growth phase. The diameter it reaches has not been found to be a prognostic factor.

Allergic bronchopulmonary aspergillosis (ABPA) is a form of lung disease that occurs in some people who are allergic to Aspergillus. With ABPA, this allergic reaction causes the immune system to overreact to Aspergillus leading to lung inflammation. ABPA causes bronchospasm (tightening of airway muscles) and mucus build-up resulting in coughing, breathing difficulty and airway obstruction.

Treatment of ABPA aims to control inflammation and prevent further injury to your lungs. ABPA is a hypersensitivity reaction that requires treatment with oral corticosteroids. Inhaled steroids are not effective. ABPA is usually treated with a combination of oral corticosteroids and anti-fungal medications. The corticosteroid is used to treat inflammation and blocks the allergic reaction. Examples
of corticosteroids include: prednisone, prednisolone or methylprednisolone. Inhaled corticosteroids alone – such as used for asthma treatment – are not effective in treating ABPA. Usually treatment with an oral corticosteroid is needed for months.

The second type of therapy used is an anti-fungal medication, like itraconazole and voriconazole. These medicines help kill Aspergillus so that it no longer colonizes the airway. Usually one of these drugs is given for at least 3 to 6 months. However, even this treatment is not curative and can have side effects.

Primary hyperaldosteronism, also known as Conn’s Syndrome, is one of the most common causes of secondary hypertension (HTN).
The common clinical scenarios in which the possibility of primary hyperaldosteronism should be considered include the following:
– Patients with spontaneous or unprovoked hypokalaemia, especially if the patient is also hypertensive
– Patients who develop severe and/or persistent hypokalaemia in the setting of low to moderate doses of potassium-wasting diuretics
– Patients with treatment-refractory/-resistant hypertension (HTN)
Patients with severe hypokalaemia report fatigue, muscle weakness, cramping, headaches, and palpitations. They can also have polydipsia and polyuria from hypokalaemia-induced nephrogenic diabetes insipidus. Long-standing HTN may lead to cardiac, retinal, renal, and neurologic problems, with all the associated symptoms and signs.

Characteristic findings on patients suffering from diphtheria are the grey membrane on the uvula and tonsils together with the low grade fever and dyspnoea. It’s of great importance that the patient has recently been to India where there is a know prevalence.

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.

Anticholinergic syndrome occurs following overdose with drugs that have prominent anticholinergic activity including tricyclic antidepressants, antihistamines and atropine. Features include dry, warm, flushed skin, urinary retention, tachycardia, mydriasis (dilated pupils) and agitation.

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.

Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus.

Some patients return spontaneously to a euthyroid state within a few months, but most patients experience a phase of hypothyroidism that takes 2 to 6 months to resolve; of this group, some develop permanent hypothyroidism. About 50% of patients, however, will develop permanent hypothyroidism within 5 years of the diagnosis of postpartum thyroiditis.

High titres of anti-TPO antibodies during pregnancy have been reported to have high sensitivity and specificity for postpartum autoimmune thyroid disease.

The wedged hepatic venous pressure is a reflection of the portal venous pressure in the hepatic sinusoids. This is a fact to remember. Here is a great but concise explanation as to why: https://www.ncbi.nlm.nih.gov/pubmed/18695309

Tiotropium is a specific long-acting antimuscarinic agent indicated as maintenance therapy for patients with COPD (chronic obstructive pulmonary disease).
It should be used cautiously in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction.
The most frequently encountered adverse effects of tiotropium include pharyngitis, bronchitis, sinusitis, dry mouth, cough, and headaches. Paradoxical bronchospasm may also occur as a rare side-effect.
Dry mouth occurs in up to 14% of patients taking tiotropium, in keeping with its anticholinergic profile.
Rarer side-effects include tachycardia, blurred vision, urinary retention, and constipation.

Idiopathic hypercalciuria presents with excess calcium in the urine without an apparent cause. Dietary modification is the first step in addressing this condition, however, because hypercalciuria increases the risk of developing renal stones and bone demineralisation, thiazide diuretics should be prescribed to increase calcium reabsorption when these symptoms are also present.

Insulinoma is associated with LOW fasting glucose, HIGH insulin level, and HIGH C peptide. Insulin-abuse or overdose will cause HGH insulin levels and a LOW C peptide. If the C peptide is low, be suspicious.

Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelin, and sympathetic stimulation (beta-adrenoceptor mediated). ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. The main physiological actions of natriuretic peptides is to reduce arterial pressure by decreasing blood volume and systemic vascular resistance. It causes a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion.

Beef liver is one of the best sources of folic acid, amongst others like green vegetables and nuts.

The diagnosis for the aforementioned case is thrombotic thrombocytopenic purpura (TTP). TTP is classically characterised as a pentad of thrombocytopaenia, microvascular haemolysis, fluctuating neurological signs, renal impairment, and fever.

The differential diagnosis for severe thrombocytopaenia is immune thrombocytopenic purpura (ITP). ITP is more common than TTP. However, a patient of ITP would not present with the range of symptoms seen in this scenario.

In TTP, there is deficiency of a protease which breaks down large multimers of von Willebrand factor. This leads to abnormally large and sticky multimers of von Willebrand factor which cause platelets to clump within the vessels.

Untreated TTP has a mortality rate of up to 90%. Therefore, rapid plasma exchange (PEX) may be a life-saving intervention. Platelet transfusion in TTP is only indicated if there is an ongoing life-threatening bleed. Intravenous methylprednisolone is indicated after treatment with PEX has been completed. There is no current role of intravenous immunoglobulin in the routine management of TTP. However, there have been reports of its successful use in PEX- and steroid-refractory cases. Intravenous argatroban is indicated in heparin-induced thrombocytopaenia (HIT), but there is no history of recent heparin administration or hospitalisation in this patient nor are the clinical signs consistent with HIT.

Management options for TTP include PEX as the treatment of choice. Steroids and immunosuppressants are also given. Antibiotics are not recommended as they may worsen the outcome of the disease. For cases resistant to PEX and pharmacologic therapy, vincristine is given.

Philadelphia translocation, t(9;22), is a marker of poor prognosis in acute lymphoblastic leukaemia (ALL).

ALL is the malignancy of lymphoid progenitor cells affecting B or T cell lineage. This results in the arrest of lymphoid cell maturation and proliferation of immature blast cells (lymphoblasts), leading to bone marrow and tissue infiltration.

ALL is the most common type of childhood cancers. Its peak incidence is between two to three years of age.

Acute B lymphoblastic leukaemia (B-ALL) is the most common type of ALL, involving overproduction of B-cell lymphoblasts. It is manifested by low initial WCC and is associated with a good prognosis.

Poor prognostic factors for ALL include:
1. Pre-B cell or T-cell ALL (T-ALL)
2. Philadelphia translocation, t(9;22)
3. Age <2 years or >10 years
4. Male sex
5. CNS involvement
6. High initial WBC (e.g. >100 x 10^9/L)
7. non-Caucasian

CD8+ T cells recognize antigens in the form of short peptide fragments bound to major histocompatibility complex class I (MHCI) molecules on the target cell surface.1 Specific engagement of peptide-MHCI (pMHCI) complexes via the clonotypically expressed αβ T-cell receptor (TCR) triggers a range of effector functions that play a critical role in protective immunity against intracellular infections and various malignancies.

Tumour marker CA 125 is mostly associated with primary peritoneal cancer and ovarian cancer. It can be used to monitor response to chemotherapy, alongside regular CT scans.

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)

Insulin remains the standard of care for the treatment of uncontrolled gestational diabetes. Tight control maintained in the first trimester and throughout pregnancy plays a vital role in decreasing poor fetal outcomes, including structural anomalies, macrosomia, hypoglycaemia of the new-born, adolescent and adult obesity, and diabetes.
The baby is already large for dates so nutritional therapy can not be used alone.

Delivery of ubiquitinated substrates to the proteasome.
Ubiquitinated proteins are delivered to the proteasome by various routes and the complete picture of how these pathways fit together has yet to emerge, reviewed in. Some substrates bind directly to the proteasome by interacting with the 19S regulatory particle subunits Rpn1028 or Rpn1329, and probably Rpt530. Alternatively, ubiquitinated substrates can be brought to the proteasome by adaptors that bind both the proteasome and the ubiquitin chain on the substrate to deliver it for degradation.

The type of significance test used depends on whether the data is parametric (can be measured, usually normally distributed) or non-parametric.
Parametric tests:
Student’s t-test – paired or unpaired*
Pearson’s product-moment coefficient – correlation

Non-parametric tests:
Mann-Whitney U test – unpaired data
Wilcoxon signed-rank test – compares two sets of observations on a single sample
chi-squared test – used to compare proportions or percentages
Spearman, Kendall rank – correlation.

The outcome measured is not normally distributed, i.e. it is non-parametric. This excludes the Student’s t-tests. We are not comparing percentages/proportions so the chi-squared test is excluded. The Mann–Whitney U test is a nonparametric test of the null hypothesis that it is equally likely that a randomly selected value from one sample will be less than or greater than a randomly selected value from a second sample.
This test can be used to investigate whether two independent samples were selected from populations having the same distribution.

Vestibular damage is a neurological side effect of streptomycin.

Streptomycin is an aminoglycoside bactericidal antibiotic. It is used in the treatment of tularaemia and resistant mycobacterial infections.
The most common neurological side-effect is vestibular damage leading to vertigo and vomiting.
Cochlear damage is less frequent and results in deafness.
Other side-effects include rashes, angioneurotic oedema, and nephrotoxicity.

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.

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.

Loss of vision after consumption of antifreeze is a characteristic presentation of methanol poisoning.

Pathophysiology of methanol toxicity:
When ingested, methanol is absorbed rapidly via the gastrointestinal tract in less than 10 minutes. Methanol is not protein-bound and is absorbed directly into the total body water compartment.
Metabolism occurs mainly in the liver through serial oxidation via alcohol dehydrogenase and aldehyde dehydrogenase but begins with alcohol dehydrogenase present in the gastric mucosa.
Alcohol dehydrogenase oxidizes methanol to formaldehyde, and aldehyde dehydrogenase subsequently oxidizes formaldehyde to formic acid.
Formic acid is the primary toxic metabolite that accounts for the associated anion gap metabolic acidosis and end-organ damage.

Clinical presentation:
Patients who present within the first 12 to 24 hours following ingestion may appear normal, and this is described as the latent period.
Nausea, vomiting, and abdominal pain subsequently ensue, followed by CNS depression and hyperventilation due to metabolic acidosis.
Ocular symptoms associated with retinal toxicity are often evident in the form of blurry vision, decreased visual acuity, photophobia, and “halo vision.”

Treatment:
Treatment options for methanol toxicity include supportive care, fomepizole (Antizole, 4-Methylpyrazole or 4MP), ethanol, dialysis, and folate.

Angioid retinal streaks are seen on fundoscopy as irregular dark red streaks radiating from the optic nerve head. They are caused by degeneration, calcification and breaks in Bruch’s membrane. They are typically associated with Paget’s disease.

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.

This patient has a poorly controlled T2DM with an underlying diabetic nephropathy. The histological findings are Kimmelstiel-Wilson lesions (nodular glomerulosclerosis) and hyaline arteriosclerosis. This is due to nonenzymatic glycosylation.

Diabetic nephropathy is the chronic loss of kidney function occurring in those with diabetes mellitus. Protein loss in the urine due to damage to the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) and result in the nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD). It usually is slowly progressive over years.

Methotrexate lung disease (pneumonitis and fibrosis) is the specific etiological type of drug-induced lung disease. It can occur due to the administration of methotrexate which is an antimetabolite, which is given as disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxemia and tachypnoea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy. Methotrexate withdrawal is indicated in such cases.

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.

Peak Expiratory Flow (PEF), also called Peak Expiratory Flow Rate (PEFR) is a person’s maximum speed of expiration, as measured with a peak flow meter. Measurement of PEFR requires some practise to correctly use a meter and the normal expected value depends on a patient’s gender, age and height.
It is classically reduced in obstructive lung disorders, such as Asthma, COPD or Cystic Fibrosis.

Left ventricular hypertrophy due to long standing hypertension is the most probable cause. The irregularly irregular pulse was suggestive of atrial fibrillation, which is due to diastolic dysfunction. Poor ventricular filling causes pulmonary congestion which manifests as bibasal crepitations.

β-blockers are the class of drug most often chosen to treat glaucoma, although other medical therapies are available. Systemic absorption of timolol eye drops can cause unsuspected respiratory impairment and exacerbation of asthma. Physicians should be alert to the possibility of respiratory side-effects of topical therapy with β-blockers. Leukotriene antagonists and salbutamol are used in asthma treatment. HRT and ferrous sulphate do not lead to the exacerbation of asthma.

The most probable diagnosis in the given scenario would be body dysmorphic disorder or dysmorphophobia

It is a mental disorder where patients have a significantly distorted body image.

Diagnostic and Statistical Manual (DSM) IV criteria:
Preoccupation with an imagined defect in appearance. If a slight physical anomaly is present, the person’s concern is markedly excessive.
The preoccupation causes clinically significant distress or impairment in social, occupational, or other important areas of functioning
The preoccupation is not better accounted for by another mental disorder (e.g., dissatisfaction with body shape and size in Anorexia Nervosa).

Treatment:
Cognitive-behavioural therapy (CBT) is the most commonly used and most empirically supported intervention to improve body image.
Several drugs have been targets of study in anorexia nervosa treatment, including selective serotonin reuptake inhibitors, antidepressants, antipsychotics, nutritional supplementation, and hormonal medications.

The Hyperlipidaemia Effect: Pseudohyponatremia in Pancreatic Cancer; Patients who have disorders of cholestasis commonly present with volume depletion due to vomiting and poor oral intake, which, in turn, often leads to hypovolemic hyponatremia. It is less well known that disorders of cholestasis, including tumours of the hepatobiliary system, can be accompanied by hyperlipidaemia.

Renal biopsy in this patient will most likely show thickened glomerular basement membrane with deposits of IgG and C3 as a result of membranous glomerulonephritis that has caused the nephrotic syndrome in this patient. Membranous glomerulonephritis in this case is most likely associated with an underlying bronchial carcinoma, consistent with the patient’s smoking history and physical presentation.

With a clinical history of weight loss, smoking, drinking alcohol, and hematemesis, the most likely answer is gastric carcinoma (also a mass). Based on symptomatology alone this is more likely than gastric lymphoma, as she has many risk factors for adenocarcinoma and/or squamous cell carcinoma. Helicobacter gastritis would not likely present with the severity of symptoms, neither would benign gastric ulcers.

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).

According to the latest research, beta blockers are associated with higher incidence of fatal and non-fatal strokes, all cardiovascular events, and cardiovascular mortality. New-onset diabetes also associates with beta blockers.

The best next step is to try a dairy-free diet, many patients may develop this in their lifetime. IBS is a diagnosis of exclusion, and one would need to rule lactose intolerance out as a potential aetiology first. She is only 28, and without overt bleeding or signs/sxs/labs suggestive of obstruction or inflammation; colonoscopy, flex sig and a barium enema are not indicated.

The diagnosis of polycystic ovarian syndrome (PCOS) is based on hyperandrogenism or chronic anovulation in the absence of specific pituitary and/or adrenal disease.
Pelvic ultrasonography may be very helpful in the evaluation as well, but polycystic ovaries are not specific for PCOS with over 20% of “normal” women having this finding. The number of follicles and ovary volume are both important in the ultrasound evaluation. The criteria for PCOS put forth by Adams et al. are the most often cited: the presence of ≥10 cysts measuring 2–8 mm around a dense core of stroma or scattered within an increased amount of stroma.
A recent proposal to modify these criteria has been put forth by Jonard et al.: “increased ovarian area (>5.5cm2) or volume (>11 mL) and/or presence of ≥12 follicles measuring 2 to 9 mm in diameter (mean of both ovaries)”.
These criteria have a specificity of 99% and a sensitivity of 75% for the diagnosis of PCOS.

The vas deferens is a long tube that connects the epididymis to the ejaculatory ducts. It acts as a canal through which mature sperm may pass through the penis during ejaculation.

Most men with CF (97-98 percent) are infertile because of a blockage or absence of the vas deferens, known as congenital bilateral absence of the vas deferens (CBAVD). The sperm never makes it into the semen, making it impossible for them to reach and fertilize an egg through intercourse. The absence of sperm in the semen can also contribute to men with CF having thinner ejaculate and lower semen volume.

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.

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.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14).

Burkitt lymphoma is a rare high-grade non-Hodgkin lymphoma endemic to west Africa and the mosquito belt. It has a close association with the contraction of Epstein-Barr virus (EBV). Burkitt lymphoma often presents with symmetrical painless lymphadenopathy, systemic B symptoms (fever, sweats, and weight loss), central nervous system involvement, and bone marrow infiltration. Classically in the textbooks, the patient also develops a large jaw tumour.

Other aforementioned options are ruled out because:
1. t(9;22)—Chronic myeloid leukaemia
2. t(15;17)—Acute promyelocytic leukaemia
3. t(14;18)—Follicular Lymphoma
4. t(11;14)—Mantle Cell Lymphoma

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.

Again, remember the Hepatitis B serologies: 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. IN THIS CASE, the person is HBsAg+ for 6 months and everything else is negative, normal transaminase. They do not need antiviral therapy, but their serology should be monitored serially. There would be no reason to do a liver biopsy.

Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. It is secreted mainly by macrophages and monocytes and acts as a costimulator of T cell and B cell proliferation.

Silicosis is a common occupational lung disease that is caused by the inhalation of crystalline silica dust. Silica is the most abundant mineral on earth. Workers that are involved for example in construction, mining, or glass production are among the individuals with the highest risk of developing the condition. Acute silicosis causes severe symptoms (e.g., exertional dyspnoea, cough with sputum) and has a very poor prognosis.
Chronic silicosis has a very variable prognosis and affected individuals may remain asymptomatic for several decades. However, radiographic signs are usually seen early on. Typical radiographic findings are calcifications of perihilar lymph nodes, diffuse ground glass opacities, large numbers of rounded, solitary nodules or bigger, confluent opacities. Avoiding further exposure to silica is crucial, especially since the only treatment available is symptomatic (e.g., bronchodilators). Silicosis is associated with an increased risk of tuberculosis and lung cancer. Berylliosis typically affects individuals who are exposed to aerospace industry. Histoplasmosis and tuberculosis do not form eggshell calcifications.

Pregnancies affected by T1DM are at increased risk for preterm delivery, preeclampsia, macrosomia, shoulder dystocia, intrauterine fetal demise, fetal growth restriction, cardiac and renal malformations, in addition to rare neural conditions such as sacral agenesis.
Successful management of pregnancy in a T1DM patient begins before conception. Research indicates that the implementation of preconception counselling, emphasizing strict glycaemic control before and throughout pregnancy, reduces the rate of perinatal mortality and malformations.
The 2008 bulletin from the National Institute for Health and Clinical Excellence recommends that preconception counselling be offered to all patients with diabetes. Physicians are advised to guide patients on achieving personalized glycaemic control goals, increasing the frequency of glucose monitoring, reducing their HbA1C levels, and recommend avoiding pregnancy if the said level is > 10%.
Other sources suggest deferring pregnancy until HbA1C levels are > 8%, as this margin is associated with better outcomes.

Contact dermatitis is a red, itchy rash caused by direct contact with a substance or an allergic reaction to it. The entry of allergen into the epidermis or dermis causes a localized allergic reaction. Local mast-cell activation in the skin leads immediately to a local increase in vascular permeability, which causes extravasation of fluid and swelling. Histamine released by mast cells activated by allergen in the skin causes large, itchy, red swellings of the skin.

The patient presents with worsened renal condition from the last consultation when he was started on enalapril (an ACE inhibitor) so this medication should be stopped. Because there is also no fluid overload; furosemide, a diuretic, should also be stopped.

5–15% of the cases of polycythaemia vera progress to myelofibrosis or acute myeloid leukaemia (AML).

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. The other factors that are mentioned do not play a key prognostic role.

St John’s wort interferes with warfarin by increasing its breakdown and decreasing its effectiveness. This leads to the need for adjustment in the dose of warfarin and careful attention to monitoring if the patient decides to continue with the drug. Ideally, an alternative antidepressant should also be considered.

Cystic fibrosis (CF) is a multisystemic, autosomal recessive disorder that predominantly affects infants, children, and young adults. CF is the most common life-limiting genetic disorder in whites, with an incidence of 1 case per 3200-3300 new-borns in the United States.

People with CF can have a variety of symptoms, including:
Very salty-tasting skin
Persistent coughing, at times with phlegm
Frequent lung infections including pneumonia or bronchitis
Wheezing or shortness of breath
Poor growth or weight gain in spite of a good appetite
Frequent greasy, bulky stools or difficulty with bowel movements
Male infertility

Signs of bronchiectasis include the tubular shadows; tram tracks, or horizontally oriented bronchi; and the signet-ring sign, which is a vertically oriented bronchus with a luminal airway diameter that is 1.5 times the diameter of the adjacent pulmonary arterial branch.

Bronchiectasis is characterized by parallel, thick, line markings radiating from hila (line tracks) in cylindrical bronchiectasis. Ring shadows represent dilated thick-wall bronchi seen in longitudinal section or on-end or dilated bronchi in varicose bronchiectasis.

Pseudomonas aeruginosa is the key bacterial agent of cystic fibrosis (CF) lung infections, and the most important pathogen in progressive and severe CF lung disease. This opportunistic pathogen can grow and proliferate in patients, and exposure can occur in hospitals and other healthcare settings.

Haemophilus influenzae is regularly involved in chronic lung infections and acute exacerbations of CF patients

The incubation periods of disorders is extremely important to diagnose, treat, prevent or attenuate a disease.

• Chickenpox: 7-21 days.
• Whooping cough: 10-14 days.
• Hand, foot and mouth disease: 2-6 days.
• German measles: 14-21 days.
• Mumps: 14-18 days.

The given clinical scenario warrants urgent admission and psychiatric evaluation as the mother seems to be suffering from puerperal psychosis.

Post-partum mental health problems can range from the ‘baby-blues’ to puerperal psychosis.

The Edinburgh Postnatal Depression Scale may be used to screen for depression:
A 10-item questionnaire, with a maximum score of 30
indicates how the mother has felt over the previous week
score > 13 indicates a ‘depressive illness of varying severity’
sensitivity and specificity > 90%. It includes a question about self-harm

Postpartum psychosis has a complex multifactorial origin. Risk factors include a history of bipolar disorder, history of postpartum psychosis in a previous pregnancy, a family history of psychosis or bipolar disorder, a history of schizoaffective disorder or schizophrenia and discontinuation of psychiatric medications during pregnancy.
Incidence rate: 2.6 per 1000 births.
Onset usually within the first 2-3 weeks following birth
Symptoms of puerperal psychosis include confusion, lack of touch with reality, disorganized thought pattern and behaviour, odd effect, sleep disturbances, delusions, paranoia, appetite disturbances, a noticeable change in the level of functioning from baseline, hallucinations and suicidal or homicidal ideation.
The safety of the patient and new-born is of utmost importance, and thus, immediate hospitalization is warranted if there is a risk of harm to either one.
Cognitive-behavioural therapy may be beneficial. Certain SSRIs such as sertraline and paroxetine may be used if symptoms are severe – whilst they are secreted in breast milk it is not thought to be harmful to the infant
There is around a 20% risk of recurrence following future pregnancies

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
– Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
– Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney
This patient has the central type from metastases.
In patients with central DI, desmopressin is the drug of choice. It is a synthetic analogue of antidiuretic hormone (ADH). It is available in subcutaneous, IV, intranasal, and oral preparations. Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended during the initial phase of treatment.

Porphyria cutanea tarda (PCT) is the most common of the porphyries. It is characterised by fragility and blistering of exposed skin. Typically, patients who are ultimately diagnosed with PCT first seek treatment following the development photosensitivities in the form of blisters and erosions on commonly exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. It heals slowly and with scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations like hyperpigmentation (as if they are getting a tan) and hypertrichosis (mainly on top of the cheeks) also occur. Risk factors for the development of PCT include alcohol and sun.

The C8 nerve forms part of the radial and ulnar nerves via the brachial plexus, and therefore has motor and sensory function in the upper limb. It originates from the spinal column from below the cervical vertebra 7 (C7).
The C8 nerve receives sensory afferents from the C8 dermatome. This consists of all the skin on the little finger, and continuing up slightly past the wrist on the palmar and dorsal aspects of the hand and forearm.
The other options available correspond to the C6 or C7 roots and these are unaffected as evidenced by normal elbow flexion and thumb sensation (C6) and normal sensation over the middle finger (C7). Elbow extension is weak as it has roots from both C7 and C8 and so cannot be used alone to decide between the two levels clinically.
The C8 nerve contributes to the motor innervation of many of the muscles in the trunk and upper limb. Its primary function is the flexion of the fingers, and this is used as the clinical test for C8 integrity, in conjunction with the finger jerk reflex.

Trunk:
– Pectoralis major – Medial and lateral pectoral nerves (C5, C6, C7, C8, T1)
– Pectoralis minor – Medial pectoral nerve (C5, C6, C7,C8, T1)
– Latissimus dorsi – Thoracodorsal nerve (C6, C7, C8)
Upper arm:
– Triceps brachii – Radial nerve (C6, C7,C8)
Forearm
– Flexor carpi ulnaris – Ulnar nerve (C7, C8, T1)
– Palmaris longus – Median nerve (C7,C8)
– Flexor digitorum superficialis – Median nerve (C8, T1)
– Flexor digitorum profundus – Median and Ulnar nerves (C8, T1)
– Flexor pollicis longus – Median nerve (C7,C8)
– Pronator quadratus – Median nerve (C7,C8)
– Extensor carpi radialis brevis – Deep branch of the radial nerve (C7,C8)
– Extensor digitorum – Posterior interosseous nerve (C7,C8)
– Extensor digiti minimi – Posterior interosseous nerve (C7,C8)
– Extensor carpi ulnaris – Posterior interosseous nerve (C7,C8)
– Anconeus – Radial nerve (C6, C7,C8)
– Abductor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor pollicis brevis – Posterior interosseous nerve (C7,C8)
– Extensor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor indicis – Posterior interosseous nerve (C7,C8)
Hand
– Palmaris brevis – Superficial branch of ulnar nerve (C8, T1)
– Dorsal interossei – Deep branch of ulnar nerve (C8, T1)
– Palmar interossei – Deep branch of ulnar nerve (C8, T1)
– Adductor pollicis – Deep branch of ulnar nerve (C8, T1)
– Lumbricals – Deep branch of ulnar, Digital branches of median nerve
– Opponens pollicis – Recurrent branch of median nerve (C8, T1)
– Abductor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Flexor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Opponens digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Abductor digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Flexor digiti minimi brevis – Deep branch of ulnar nerve (C8, T1)

Funnel plots are graphical tools to assess and compare clinical performance of a group of care professionals or care institutions on a quality indicator against a benchmark. Incorrect construction of funnel plots may lead to erroneous assessment and incorrect decisions potentially with severe consequences.

This patient presentation is unlikely to be an L5 nerve root lesion given the results of the MRI scan. Therefore, the most likely diagnosis is a mononeuritis affecting the left common peroneal nerve. This would lead to sensory loss over the dorsum of the foot and anterolateral leg on the left.

Acute dystonic reactions (extrapyramidal symptoms) such as spasmodic torticollis, trismus, and oculogyric crises can occur following the administration of metoclopramide or stemetil and thus, neither is recommended for the treatment of nausea in young women.

Such reactions respond well to treatment with benztropine or procyclidine.
– Benztropine: It is an anticholinergic medication with significant CNS penetration.
A single dose of benztropine 1 to 2 mg IV followed by 1 to 2 mg p.o twice a day for up to 7 days to prevent a recurrence. Subsequently, both the offending agent and those from the same group should be avoided.
– Alternatively, diphenhydramine can be used intravenously (up to a dose of 50mg) or intramuscularly followed by p.o therapy every 6 hours for 1 to 2 to prevent a recurrence.
– Second-line therapy with IV benzodiazepines is reserved for those patients who do not respond to anticholinergics.

The best option would be the combination of ampicillin and gentamycin. Changing to IV amoxicillin+gentamycin is however the best among the given choices here.

Because the patient has chronic kidney disease, we need to consider the associated adverse effects of trying to maintain normal haemoglobin levels (14-18g/dl in this patient) and instead only instigate therapy when the level falls below 11 g/dl. Thus, in this case we should just monitor the haemoglobin levels and not initiate therapy just yet.

This patient is a case of chronic myeloid leukaemia (CML) and should be started on imatinib as the first-line drug of choice.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

This patient is having a myasthenic crisis. Opinions vary as to whether plasmapheresis or intravenous immunoglobulins should be given first-line. Plasmapheresis usually works much faster, but is more costly due to equipment.
Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases. Myasthenia gravis is more common in women (2:1).

DGI presents as two syndromes: 1) a bacteremic form that includes a triad of tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis and 2) a septic arthritis form characterized as a purulent arthritis without associated skin lesions. Many patients will have overlapping features of both syndromes. Time from infection to clinical manifestations may range from 1 day to 3 months. There is no travel history and the rash of Lyme disease is not purulent. Reactive arthritis presents with conjunctivitis, urethritis and arthritis usually with a red hot tender and swollen joint.

Hypothermia is defined as a core body temperature of < 35 °C.
Hypothermia may produce the following ECG changes:
-Bradyarrhythmia
-Osborne Waves (= J waves)
-Prolonged PR, QRS and QT intervals
-Shivering artefact
-Ventricular ectopics
-Cardiac arrest due to VT, VF or asystole

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.

Glomerulosclerosis is the scarring and hardening of the glomeruli known as diabetic glomerulosclerosis occurring in long-standing diabetes.

To differentiate VT from SVT with aberrant conduction the following electrocardiographic features should be looked for:

Evidence of preceding atrial activity for SVT. Oesophageal leads are helpful if P waves are hidden in the QRS complex.
QRS duration more than 140 ms for VT.
QRS morphology: Features of QRS morphology that favour SVT are RBBB or triphasic patterns like rSR in V1 and qRS in V6. Monophasic pattern like R or qR in V1 and rS or QS in V6 or multiple morphology QRS complexes favour VT.
AV dissociation for VT.

Gilles de la Tourette syndrome is the most severe and rare of the tic syndromes, consisting of multiple tics involving both motor actions and vocalisation. Onset is usually in childhood. Symptoms include utterance of obscenities (coprolalia); echolalia (repetition of another person’s spoken words) and palilalia (involuntary repetition of words, phrases, or sentences).
The underlying cause is unknown, with no particular imaging or standard histopathological abnormalities having been identified. The EEG shows non-specific abnormalities in about half of patients. However, more recent immunocytochemical studies have suggested altered dopamine uptake in the striatal system.
Risperidone is an effective therapeutic option without the effects associated with chlorpromazine and haloperidol.

The SEM is an indicator of how close the sample mean is to the population mean. In reality, however, only one sample is extracted from the population. Therefore, the SEM is estimated using the standard deviation (SD) and a sample size (Estimated SEM). The SEM computed by a statistical program is an estimated value calculated via this process.

Estimated Standard Error of the Mean (SEM)=SDn√

Felty syndrome is a severe subtype of seropositive Rheumatoid arthritis. Clinical triad consists of arthritis, splenomegaly, and neutropenia (leads to an increased risk of recurrent bacterial infections). Other symptoms include skin ulcers of the lower limbs (indicating vasculitis), hepatomegaly, fever, and chest pain (indicating pleuritis or pericarditis). It is associated with increased risk of developing non-Hodgkin lymphoma.

Normal cerebrospinal fluid (CSF) glucose together with lymphocytosis, an increased opening pressure and raised CSF protein are typical of a viral meningitis.

Pregnant patient in a third world country with hepatitis: The answer is most likely Hepatitis E. The mortality for Hepatitis E in pregnant women is very high. It is transmitted faecal-orally. There is no hepatitis G. Hepatitis C, B, A are less likely to be the correct answer than E given it’s classic association with pregnancy and poor living conditions.

The patient has paroxysmal nocturnal haemoglobinuria (PNH). The classic sign of the disease is red discolouration of the urine due to the presence of haemoglobin and hemosiderin from the breakdown of red blood cells. As the urine is more concentrated in the morning, this is when the colour is most pronounced.

PNH is an acquired clonal disorder of haematopoietic stem cells, characterised by variable combinations of intravascular haemolysis, thrombosis, and bone marrow failure. Diagnosis is made by flow cytometric evaluation of blood, which confirms the CD55 and CD59 deficiencies and deficiency of expression of other GPI-linked proteins. This test is replacing older complement-based assays such as the Ham test and sucrose lysis test.

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.

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Chiari Type I malformation usually presents with symptoms due to brain stem and lower cranial nerve dysfunction, which includes DBN.

Café-au-lait spots is hyperpigmented lesions that vary in colour from light brown to dark brown, with borders that may be smooth or irregular. Causes include:
Neurofibromatosis type I
McCune–Albright syndrome
Legius syndrome
Tuberous sclerosis
Fanconi anaemia
Idiopathic
Ataxia-telangiectasia
Basal cell nevus syndrome
Benign congenital skin lesion
Bloom syndrome
Chediak-Higashi syndrome
Congenital nevus
Gaucher disease
Hunter syndrome
Maffucci syndrome
Multiple mucosal neuroma syndrome
Noonan syndrome
Pulmonary Stenosis
Silver–Russell syndrome
Watson syndrome
Wiskott–Aldrich syndrome

Although microscopic analysis of joint fluid aspirate and culture is the basis of septic arthritis diagnosis and should usually be collected before the administration of antibiotics, the patient is showing signs of septic shock. A delay in antibiotics might lead to worsening of symptoms so they are administered first.

Vincristine is part of the antimitotic agents, cell cycle specific (M phase). It binds to microtubules in the spindle apparatus and prevents their proper function, finally arresting mitosis.

Baclofen is used to treat spastic movement symptoms such as those seen in cerebral palsy and multiple sclerosis. It is known to be associated with a withdrawal syndrome similar to alcohol withdrawal; thus, gradual withdrawal is necessary to avoid this.

With biliary obstructive symptoms in a patient with ulcerative colitis, one should immediately think of primary sclerosing cholangitis (PSC). PSC is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic ducts. The best diagnostic test for PSC is ERCP. ANCA antibiotics may be positive, but not the best test to DIAGNOSE THE CONDITION. The same can be said of serum transaminase levels– they will be abnormal but nonspecific. While a liver ultrasound may be helpful, it is not the best test. Liver biopsy would be used to stage the PSC later.

Corticosteroids are well known for their ocular complications such as glaucoma and cataracts.

Henoch-Schönlein purpura (HSP) rashes are commonly found on the legs, feet, and buttocks while Immune thrombocytopenia (ITP) rashes manifest predominantly on the lower legs. HSP happens following a sore throat while ITP usually happens following an URTI or Flu. HSP is an inflammation of a blood vessel (vasculitis) while ITP is immune mediated insufficiency of platelets.

Blood pressure should be routinely measured as leflunomide may cause hypertension and thus an increase in BP. It doesn’t cause changes in blood sugar levels, peak expiratory flow rate or haematuria.

From the given answers, complete heart block with a narrow complex QRS complex is associated with the least risk of asystole. Transvenous pacing is indicated by the other given responses.

Pulsus paradoxus is defined as the exaggerated fall in systolic blood pressure during inspiration by greater than 10 mmHg. Cardiac tamponade is the classic cause of pulsus paradoxus. Kussmaul’s sign (a rise in the jugular venous pressure on inspiration) is mostly seen in constrictive pericarditis. Hypotension, muffled heart sounds and raised JVP can be seen in both conditions.

For medical management of carcinoid syndrome, there are two somatostatin analogues available, Octreotide and Lanreotide. Somatostatin is an amino acid peptide which is an inhibitory hormone, which is synthesized by paracrine cells located ubiquitously throughout the gastrointestinal tract. Both somatostatin analogues provide symptom relief in 50% to 70% of patients and biochemical response in 40% to 60% patients. Many studies have shown that Octreotide and Lanreotide also inhibit the proliferation of tumour cells.

Bronchopneumonia presents as a patchy consolidation involving one or more lobes, usually the dependent lung zones, a pattern attributable to aspiration of oropharyngeal contents.

Symptoms of bronchopneumonia may be like other types of pneumonia. This condition often begins with flu-like symptoms that can become more severe over a few days. The symptoms include:
– fever
– a cough that brings up mucus
– shortness of breath
– chest pain
– rapid breathing
– sweating
– chills
– headaches
– muscle aches
– pleurisy, or chest pain that results from inflammation due to excessive coughing
– fatigue
– confusion or delirium, especially in older people

There are several factors that can increase your risk of developing bronchopneumonia. These include:
– Age: People who are 65 years of age or older, and children who are 2 years or younger, have a higher risk for developing bronchopneumonia and complications from the condition.
– Environmental: People who work in, or often visit, hospital or nursing home facilities have a higher risk for developing bronchopneumonia.
– Lifestyle: Smoking, poor nutrition, and a history of heavy alcohol use can increase your risk for bronchopneumonia.
– Medical conditions: Having certain medical conditions can increase your risk for developing this type of pneumonia. These include: chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), HIV/AIDS, having a weakened immune system due to chemotherapy or the use of immunosuppressive drugs.

Bulimia nervosa is a serious, potentially life-threatening eating disorder characterized by a cycle of bingeing and compensatory behaviours such as self-induced vomiting designed to undo or compensate for the effects of binge eating.

According to the DSM-5, the official diagnostic criteria for bulimia nervosa are:
Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
Eating, in a discrete period of time (e.g. within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances.
A sense of lack of control over eating during the episode (e.g. a feeling that one cannot stop eating or control what or how much one is eating).
Recurrent inappropriate compensatory behaviour in order to prevent weight gain, such as self-induced vomiting, misuse of laxatives, diuretics, or other medications, fasting, or excessive exercise.
The binge eating and inappropriate compensatory behaviours both occur, on average, at least once a week for three months.
Self-evaluation is unduly influenced by body shape and weight.
The disturbance does not occur exclusively during episodes of anorexia nervosa.

Antidepressants as a group – particularly selective serotonin reuptake inhibitors (SSRIs) – are the mainstay of pharmacotherapy for bulimia nervosa. These may be helpful for patients with substantial concurrent symptoms of depression, anxiety, obsessions, or certain impulse disorder symptoms. They may be particularly good for patients who have not benefited from or had suboptimal response to suitable psychosocial therapy or who have a chronic, difficult course in combination with other treatments.

Food and Drug Administration (FDA) approved treatments
Fluoxetine (Prozac): Initial dose 20 mg/d with advance over 1–2 weeks to 60 mg/d in the morning as tolerated. Some patients may need to begin at a lower dose if side effects are intolerable. A maximum dose of 80 mg/d may be used in some cases.

All of the aforementioned listed tumours, except brain tumours, can metastasise to lungs and produce the typical CXR picture consisting of hilar lymphadenopathy with either diffuse multinodular shadows resembling miliary disease or multiple large well-defined masses (canon balls). Occasionally, cavitation or calcification may also be seen.

Most brain tumours, however, do not metastasise. Some, derived form neural elements, do so but in these cases, intraparenchymal metastases generally precede distant haematogenous spread.

The history is suggestive of acute gingivostomatitis, which is a manifestation of primary HSV-1 infection. Patients present with gingivitis and vesicular lesions which develop on the oral mucosa, tongue, and lips and later rupture and coalesce, leaving ulcerated plaques.

The correct answer based on the clinical scenario is Crohn’s disease. Associated with this disease are abscesses and fistulas in the anorectal region, skip lesions, cobble stoning, stricturing, granulomas, and crypt distortion. The other answer choices are not correct. How to rule out ulcerative colitis: it only involves ileocolorectal regions, and this is above that level. You will not see crypt distortion and cobble stoning; it is a more superficial process.

Generally, underlying causes of confusion need to be looked for and treated as appropriate, for example, hypercalcaemia, infection, urinary retention, and medication. If specific treatments fail, the following may be tried:

1. First choice: haloperidol
2. Other options: chlorpromazine, levomepromazine

In the terminal phase of the illness, agitation or restlessness is best treated with midazolam.

Historically, high rates of maternal and fetal death have been reported for pregnant women with pulmonary hypertension (30–56% and 11–28%, respectively). The causes of poor maternal outcomes are varied and include risk of death from right heart failure and stroke from intracardiac shunting. Furthermore, there is a high peri-/post-partum risk due to haemodynamic stress, bleeding complications and the use of general anaesthesia, which can all lead to right heart failure.
The most common risk to the foetus is death, with premature birth and growth retardation being reported in successfully delivered children.
CXR is not contraindicated in pregnancy. D-dimers are not used as a diagnostic aid as they are almost always elevated in pregnancy. Nifedipine, although contraindicated in pregnant women may be used judiciously if the need arises.

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.

Carcinoembryonic antigen (CEA) is a known tumour marker for colorectal cancer. It is not used diagnostically, but in patients with a known diagnosis of colorectal cancer associated with raised CEA levels, it can be used to monitor disease activity and help with the early identification of disease recurrence.

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 most likely diagnosis with anaemia, raised erythrocyte sedimentation rate (ESR), hypercalcaemia, renal impairment, and raised total protein with low albumin is multiple myeloma (MM). Protein electrophoresis will confirm the presence of monoclonal band of paraprotein. Of note, a radioisotope bone scan is not a good test for picking up the lytic lesions of MM.

Diagnosis of MM is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). It significantly helps in reducing pulmonary hypertension associated with COPD and treating underlying pathology of future heart failure. There is little to no benefit of oxygen therapy for less than 15 hours.

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.