Fundoscopy reveals flame-shaped haemorrhages which are specific to central retinal vein occlusion (CRVO). In CRA thrombosis, fundoscopy would show a cherry-red spot. A patient with retinal detachment would give a characteristic history of seeing flashes of light and floaters. Background retinopathy is associated with diabetes.

Retinitis pigmentosa is a genetic disorder primarily affecting the peripheral retina resulting in tunnel vision. Night blindness is often the initial sign. Fundoscopy exam reveals black bone spicule-shaped pigmentation in the peripheral retina, and mottling of the retinal pigment epithelium.

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

Arthritis mutilans is a rare (occurs in only 5% of the patients) and extremely severe form psoriatic arthritis characterized by resorption of bones and the consequent collapse of soft tissue. When this affects the hands, it can cause a phenomenon sometimes referred to as ‘telescoping fingers.’ The associated nail changes are also characteristic of arthritis.

After renal transplant, asymptomatic patients can still have graft dysfunction as an early complication, with rising serum creatinine; therefore, urine and blood cultures should be ordered first. This should be followed by measuring the Tacrolimus levels, as this drug can be directly nephrotoxic. Next, a Doppler ultrasound of the transplant site should be ordered, to check for any obstructions or occlusions.

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

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

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

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

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

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

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

Chickenpox is a highly communicable viral disease caused by human (alpha) herpesvirus 3 (varicella-zoster virus, VZV). It is transmitted from person to person by direct contact (touching the rash), droplet or air born spread (coughing and sneezing).

The QT interval is the time from the start of the Q wave to the end of the T wave. It represents the time taken for ventricular depolarisation and repolarisation. The QT interval should be measured in either lead II or V5-6.

Lysosomal hydrolases are synthesized in the rough endoplasmic reticulum and specifically transported through the Golgi apparatus to the trans-Golgi network, from which transport vesicles bud to deliver them to the endosomal/lysosomal compartment. The explanation of how the lysosomal enzymes are accurately recognized and selected over many other proteins in the trans-Golgi network relies on them being tagged with a unique marker: the mannose-6-phosphate (M6P) group, which is added exclusively to the N-linked oligosaccharides of lysosomal soluble hydrolases, as they pass through the cis-Golgi network. Generation of the M6P recognition marker depends on a reaction involving two different enzymes: UDP-N-acetylglucosamine 1-phosphotransferase and α-N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase.

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

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

Botulinum toxin is a neurotoxic protein from Clostridium botulinum that causes flaccid paralysis as it acts by preventing the release of Ach at the neuromuscular joint. It is the first-line treatment for cervical dystonia (torticollis) because the condition is a neurological disorder characterised by unusual muscle contractions of the neck. With the use of Botulinum toxin, the contractions would be released.

Extra-nodal presentation is more common in non-Hodgkin lymphoma (NHL) than in Hodgkin lymphoma (HL). Bone marrow infiltration is more common in low-grade than in high-grade NHLs.

Low-grade NHL is predominantly a disease of older people. Most present with advanced disease, bone marrow infiltration being almost invariable. Anaemia, leucocytosis, and/or thrombocytopaenia in a patient are suggestive of bone marrow involvement. For definitive diagnosis, lymph node biopsy is sufficient.

The other aforementioned statements are ruled out because:
1. Renal impairment in NHL usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement.

2. Burkitt lymphoma is a high-grade NHL, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement, and ovarian tumours. It develops most often in children or young adults and is uncommon in older people.

3. High-grade lymphomas are potentially curable. They have a better prognosis and are responsive to chemotherapy unlike low-grade lymphomas, which are incurable with conventional therapy.

Anorexia nervosa is an eating disorder characterized by an abnormally low body weight, an intense fear of gaining weight and a distorted perception of weight. People with anorexia place a high value on controlling their weight and shape, using extreme efforts that tend to significantly interfere with their lives.

The minimum level of severity is based, for adults, on current body mass index (BMI) (see below) or for
children and adolescents, on BMI percentile. The ranges below are derived from World Health
Organization categories for thinness in adults; for children and adolescents, corresponding BMI percentiles
should be used. The level of severity may be increased to reflect clinical symptoms, the degree of
functional disability, and the need for supervision.
Mild: BMI > 17 kg/m2
Moderate: BMI 16-16.99 kg/m2
Severe: BMI 15-15.99 kg/m2
Extreme: BMI < 15 kg/m2 Anorexia nervosa is more common in women than in men, with a female-to-male ratio of 10-20:1 in developed countries. The prognosis of anorexia nervosa is guarded. Morbidity rates range from 10-20%, with only 50% of patients making a complete recovery. Of the remaining 50%, 20% remain emaciated and 25% remain thin. The main change in the diagnosis of Anorexia Nervosa was to remove the criterion of amenorrhea (loss of menstrual cycle). Removing this criterion means that boys and men with Anorexia will finally be able to receive an appropriate diagnosis.
Similarly, girls and women who continue to have their period despite other symptoms associated with Anorexia, such as weight loss and food restriction, will now be eligible for a diagnosis of Anorexia.

Zinc deficiency can present with alopecia, dermatitis, poor growth, increased susceptibility to infection, and cognitive deficiency. Magnesium deficiency can cause fatigue, cramping and an irregular EKG. Copper deficiency can present with fatigue and weakness. Chromium deficiency can present with hyperglycaemia.

This patient presents with a combination of akinetic rigid syndrome, cerebellar signs and the suggestion of autonomic features. This is most indicative of a diagnosis of multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia.

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.

5-ASA is not an acute treatment; it is for maintenance therapy for ulcerative colitis and/or Crohn’s. The most benefit is seen in patients with ulcerative colitis.

Varicose eczema is a common problem, particularly in elderly patients due to stasis or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins. It is often mistaken for cellulitis, but cellulitis is rarely bilateral and is painful rather than itchy.

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

Central retinal artery occlusion (CRAO) is a disease of the eye where the flow of blood through the central retinal artery is blocked (occluded). There are several different causes of this occlusion; the most common is carotid artery atherosclerosis. It causes sudden vision loss in one eye. Fundoscopic exam will show a red lesion, called a cherry red spot, with surrounding pale retina (the pale colour is caused by ischemia of the retina)

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

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.

The somatostatin-secreting D-cells comprise ,5% of the cells of the pancreatic islets. The D-cells have a complex morphology and may, via cellular process, interact with many more islet cells than suggested by their low number. D-cells are equipped with ATP-sensitive potassium channels (KATP channels).

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

This patient is most likely suffering from hand, foot mouth disease which is caused by coxsackie virus A16. Its incubation period ranges from 5-7 days and only symptomatic treatment is required.

Patients with active cancer are at a continuous risk of having venous thromboembolism (VTE), such as DVT. Therefore, a six-month course of an anticoagulant such as LMWH is recommended. LMWH is the drug of choice since its side effects can be reversed and it can be stopped easily in case of a cancer-related bleed, for example, massive haemoptysis in a patient with lung cancer.

Among the options provided, hypothermia is not a symptom of opioid withdrawal.

Symptoms of opioid withdrawal include dysphoric mood, yawning, insomnia, muscle aches, lacrimation/rhinorrhoea, papillary dilatation, piloerection, fever, sweating, nausea/vomiting, diarrhoea.
If the patient is having an opioid withdrawal reaction, then give 10 mg of methadone syrup and wait about 60 min to determine its effect.

COWS (Clinical Opioid Withdrawal Scale) assessment for opioid withdrawal is commonly used to determine the severity of opioid withdrawal.

Most new moms experience postpartum baby blues after childbirth, which commonly include mood swings, crying spells, anxiety and difficulty sleeping. Baby blues typically begin within the first two to three days after delivery, and may last for up to two weeks.

Postpartum depression may be mistaken for baby blues at first — but the signs and symptoms are more intense and last longer, and may eventually interfere with your ability to care for your baby and handle other daily tasks. Symptoms usually develop within the first few weeks after giving birth, but may begin earlier, during pregnancy or later, up to a year after birth.

The period prevalence of postpartum depression among women is a striking 21.9% the first year after birth, which makes it one of the most common medical complications of childbearing. Sertraline has been identified as an antidepressant of choice for breastfeeding women because infants are unlikely to develop quantifiable serum sertraline levels and very few adverse events associated with sertraline have been reported.

Women with a prior episode of postpartum psychosis have about a 30% risk of having another episode in the next pregnancy.

Indications for surgery for the treatment of primary hyperparathyroidism:
1. Symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation
2. End-organ disease (renal stones, fragility fractures or osteoporosis)
3. An albumin-adjusted serum calcium level of 2.85 mmol/litre or above.

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.

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

The patient’s history points to absence seizures. Carbamazepine has been shown to aggravate generalized seizure types, especially absence seizures, because it acts directly on the ventrobasal complex of the thalamus which is critical to the neurophysiology of absence seizures.

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

Treatment with ARB or ACE-I may slow further deterioration in renal function in this patient, as studies have shown that blocking of the RAS in type 2 diabetic patients improve renal function.

Bilateral median nerve dysfunction is suggestive of degenerative cervical myelopathy (DCM) rather than bilateral carpal tunnel syndrome. DCM should be suspected in elderly patients presenting with limb neurology. This patient’s twitches are probably fibrillations, a sign of lower motor neuron dysfunction.
Degenerative cervical myelopathy is associated with a delay in diagnosis. It is most commonly misdiagnosed as carpal tunnel syndrome. In one study, 43% of patients who underwent surgery for degenerative cervical myelopathy had been initially diagnosed with carpal tunnel syndrome.
Management of these patients should be by specialist spinal services (neurosurgery or orthopaedic spinal surgery). Decompressive surgery is the mainstay of treatment and has been shown to stop disease progression. Physiotherapy and analgesia do not replace surgical opinion, though they may be used alongside. Nerve root injections do not have a role in management.

Furosemide is a loop diuretic that is known to have significant ototoxicity side-effects although the mechanism is not fully known.

The level of haemoglobin A1c (HbA1c), also known as glycated haemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8–12 weeks. Recent studies have been made to correlate between HbA1c and average glucose level.
Using the following formula: Average blood glucose (mmol/l) = (1.98 x 1 HbA1c) – 4.29

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

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

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

This patient has polycystic ovarian syndrome (PCOS). Medical management of PCOS is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.
First-line medical therapy usually consists of an oral contraceptive to induce regular menses. The contraceptive not only inhibits ovarian androgen production but also increases sex hormone-binding globulin (SHBG) production. The American College of Obstetricians and Gynaecologists (ACOG) recommends the use of combination low-dose hormonal contraceptive agents for long-term management of menstrual dysfunction.
If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. Pregnancy should be excluded before therapy with oral contraceptives or androgen-blocking agents are started.
First-line treatment for ovulation induction when fertility is desired is clomiphene citrate. Second-line strategies may be equally effective in infertile women with clomiphene citrate–resistant PCOS.

Uric acid stones will most likely be found in this case because of the patient’s long history of gout. Additionally, studies have shown that ileostomy patients have an increased risk for the development of uric acid stones.

You may treat chickenpox with acyclovir if it is commenced within the first 24 hours of the rash’s appearance. Erythromycin, doxycycline, and ampicillin would not help because it’s a viral infection (Varicella) not a bacterial infection.

The history is suggestive of hypertrophic obstructive cardiac myopathy. The degree of left ventricular hypertrophy is strongly associated with sudden cardiac death.

CMV infection is usually asymptomatic in adults. However, if the mother is infected for the first time during pregnancy then there is high chances of this infection passing on to the foetus. CMV infection can cause blindness, deafness, learning difficulties, restricted growth etc. Hepatitis B, herpes simplex, syphilis and HIV do not present with these classical signs of CMV infection in new-borns. It is estimated that 10 stillbirths occur in England and Wales every year due to CMV infection. The foetus is most at risk in early pregnancy. There is no effective prevention.

Lofgren’s syndrome is an acute form of sarcoidosis characterized by erythema nodosum, bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. Other symptoms include anterior uveitis, fever, ankle periarthritis, and pulmonary involvement.

Löfgren syndrome is usually an acute disease with an excellent prognosis, typically resolving spontaneously from 6-8 weeks to up to 2 years after onset. Pulmonologists, ophthalmologists, and rheumatologists often define this syndrome differently, describing varying combinations of arthritis, arthralgia, uveitis, erythema nodosum, hilar adenopathy, and/or other clinical findings.

Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.

Contraindications:
– Patients taking nitrates and related drugs such as nicorandil
– Hypotension
– Recent stroke or myocardial infarction (NICE recommend waiting 6 months)

Side-effects:
Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic Neuropathy
Nasal congestion
Flushing
Gastrointestinal side-effects
Headache

Sun burn reactions usually occur after individuals with a light skin tone have prolonged exposure to the sun. The usual symptoms are redness and itching of the skin. The best treatment plan would be further avoidance of sun exposure and the topical application of emollients. These are Ist degree burns and aggressive therapy is not required in such cases.

Age-related macular degeneration is the most common cause of blindness in the UK. Degeneration of the central retina (macula) is the key feature with changes usually bilateral. Smoking and genetic factors are risk factors for macular degeneration. The severity is divided into early, intermediate, and late types. The late type is additionally divided into dry and wet forms with the dry form making up 90% of cases.

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.

Carbon monoxide (CO) poisoning:
It is considered as the great imitator of other diseases as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Clinical features of carbon monoxide toxicity:
Headache: 90% of cases (most common clinical feature)
Nausea and vomiting: 50%
Vertigo: 50%
Confusion: 30%
Subjective weakness: 20%
Severe toxicity: ‘pink’ skin and mucosa, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
Cherry red skin is a sign of severe toxicity and is usually a post-mortem finding.
Management
• 100% oxygen
• Hyperbaric oxygen therapy (HBOT)

The use of Hyperbaric oxygen therapy (HBOT) for treatment mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)

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.

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.

If 3mg of adenosine has no effect, then adenosine 6 mg can be given by rapid IV push. If patient does not convert to a normal rhythm, give another dose of adenosine 12 mg via rapid IV push. This can be repeated if there is no response. If no response, diltiazem or beta-blockers can be given as alternatives.

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.

Burkholderia cepacia is an aerobic gram-negative bacillus found in various aquatic environments. B cepacia is an organism of low virulence and is a frequent colonizer of fluids used in the hospital (e.g., irrigation solutions, intravenous fluids).
B cepacia, as a non-aeruginosa pseudomonad, is usually resistant to aminoglycosides, antipseudomonal penicillin, and antipseudomonal third-generation cephalosporins and polymyxin B.
B cepacia is often susceptible to trimethoprim plus sulfamethoxazole (TMP-SMX), cefepime, meropenem, minocycline, and tigecycline and has varying susceptibility to fluoroquinolones.
Based on the options available, ceftazidime and aminoglycoside would be the best option.

Group AB donors are the universal donors of FFP. This is because they produce neither anti-A nor anti-B antigens in their plasma and are, therefore, compatible with all ABO groups.

The aforementioned patient’s blood group is B meaning, thereby, she naturally produces anti-A antigens in her plasma and would need to receive plasma that does not have anti-B antigens in it. Hence, she can only receive FFP from donors of group B or AB. Moreover, as she is of childbearing age, she must receive RhD negative blood in order to avoid problems with future pregnancies if her foetus would be RhD positive.

In general, the aim is to keep the homocysteine (Hcy) concentration as close to normal as possible. In patients who are fully-responsive to pyridoxine, standard doses can lead to tHcy levels below 50 μmol/L (and sometimes within the normal range). Some patients who are partially-responsive to pyridoxine may be able to achieve a tHcy level below 50 μmol/L if they are also on a low-Met diet; for others it is not a realistic goal.

The patients high morning blood sugar levels are suggestive to Somogyi Phenomenon which suggests that hypoglycaemia during the late evening induced by insulin could cause a counter regulatory hormone response that produces hyperglycaemia in the early morning.
Substitution of regular insulin with an immediate-acting insulin analogue, such as Humulin lispro, may be of some help.

Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signalling pathways that activate innate and adaptive immune responses.

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.

Anti ds-DNA antibodies are very specific for SLE and their presence most often indicates systemic spread of the disease. These antibodies are present in about 30 percent of the total cases of SLE.

The most likely diagnosis is idiopathic Parkinson’s disease because of the unilateral presentation. In addition, cogwheel rigidity is a classic presenting symptom. Neuroleptic-induced parkinsonism is usually bilateral and symmetrical. Essential tremors do not cause rest tremors.

According to NICE guidelines (2013) all people who have had an acute MI, treatment should be offered with ACE inhibitor, dual antiplatelet therapy (aspirin plus a second antiplatelet agent), beta-blocker and a statin.

A very common complication after ERCP is post-ERCP pancreatitis, which based on the clinical scenario , this man has. The treatment for this is pain control, lots of intravenous fluids, and traditionally bowel rest, although more recent evidence suggests early feeding is better.

The diagnosis is Refsum’s disease. This is an autosomal recessive disorder that causes a sensorimotor peripheral neuropathy. It is caused by defective alpha oxidation of phytanic acid leading to its accumulation in tissues. Cardiac conduction abnormalities and cardiomyopathies may also occur.
Epiphyseal dysplasia causes a characteristic shortening of the fourth toe. Serum phytanic acid levels are elevated. Treatment is by dietary restriction of foods containing phytanic acid (dairy products, fish, beef and lamb).

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.

This case is most likely tumour lysis syndrome, often occurring immediately after starting chemotherapy because the tumour cells are killed and their contents are released into the bloodstream. After treating lymphomas or leukaemia, there is a sudden hypocalcaemia, hyperphosphatemia, and hyperkalaemia

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

People with Systemic Juvenile Idiopathic Arthritis (also known as Stills disease) can have recurrent fevers, a macular rash, joint pain, joint deformities, an enlarged liver and/or spleen, and can occasionally have polyserositis, lung involvement or pericardial effusions. Rheumatoid factor and antinuclear antibodies are usually negative. Treatment is with non-steroidal anti-inflammatory drugs (NSAIDs) and the prognosis is better than for adult rheumatoid arthritis.
In pauciarticular Still’s disease, antinuclear antibodies are present. Large joints are affected and most patients develop classic features of seronegative spondylarthritis.

NICE guidelines on hypercalcemia recommend that maintaining good hydration equals drinking 3-4 L of fluid/day, provided there are no contraindications. A low calcium diet is not necessary because intestinal absorption of calcium is reduced. The patient should avoid any other drugs or vitamins that could worsen the hypercalcemia. Mobilization is encouraged and any symptoms of hypercalcemia should be reported.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. In this example, the ARR is 8 per cent (20 per cent – 12 per cent = 8 per cent). This means that, if 100 children were treated, 8 would be prevented from developing bad outcomes. Another way of expressing this is the number needed to treat (NNT). If 8 children out of 100 benefit from treatment, the NNT for one child to benefit is about 13 (100 ÷ 8 = 12.5). CER = 20 / 400 = 1 / 20 = 0.05, EER = 10 / 400 = 0.025, ARR =CER – EER = 0.025

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

This question describes Charcot’s triad– fever, RUQ pain, and jaundice, which is seen in ascending cholangitis. Reynold’s pentad is a worsened version of this, where you have RUQ pain, fever, jaundice, hypotension, and altered mental status. Risk factors for gallstones are the 4F’s- female, fat, forty, and fertile. You would not have the elevated bilirubin, ALP, transaminases with a kidney stone or in peptic ulcer disease. Hepatitis would not cause elevation of bilirubin.

One of the options of Psoriasis treatment is vitamin D analogues i.e. calcipotriol. Acne is exacerbated by steroids. Erythema nodosum can be caused by various diseases and the treatment of the primary condition resolves the symptoms. Lipomas require surgery, whereas Steven-Johnson syndrome requires use of steroids and eliminating the culprit drug, which is one of the most common causes.

Nitric oxide, known as an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes and is a signaling molecule in many physiological and pathological processes in humans.
One of the main enzymatic targets of nitric oxide is guanylyl cyclase. The binding of nitric oxide to the haem region of the enzyme leads to activation, in the presence of iron.

Acute angle closure glaucoma can manifests itself with severe headache, nausea or vomiting, very blurry or hazy vision, seeing rainbows or halos around lights and redness in the white part of the affected eye. It is caused by a rapid or sudden increase in pressure inside the eye – intraocular pressure (IOP). In order to establish the diagnosis and start treatment immediately, IOP should first be measured.

Euthyroid sick syndrome (also known as nonthyroidal illness syndrome) can be described as abnormal findings on thyroid function tests that occurs in the setting of a nonthyroidal illness (NTI), without pre-existing hypothalamic-pituitary and thyroid gland dysfunction. After recovery from an NTI, these thyroid function test result abnormalities should be completely reversible.
Multiple alterations in serum thyroid function test findings have been recognized in patients with a wide variety of NTIs without evidence of pre-existing thyroid or hypothalamic-pituitary disease. The most prominent alterations are low serum triiodothyronine (T3) and elevated reverse T3 (rT3), leading to the general term low T3 syndrome. Thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 (FT4), and free T4 index (FTI) also are affected in variable degrees based on the severity and duration of the NTI. As the severity of the NTI increases, both serum T3 and T4 levels drop, but they gradually normalize as the patient recovers.
Reverse T3 is used to differentiate between this condition and secondary thyroid failure.

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.

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.

Prostacyclin (PGI2) generated by the vascular wall is a potent vasodilator, and the most potent endogenous inhibitor of platelet aggregation so far discovered. Prostacyclin inhibits platelet aggregation by increasing cyclic AMP levels. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation. Circulating platelets are, therefore, subjected constantly to prostacyclin stimulation and it is via this mechanism that platelet aggregability in vivo is controlled.

From the given history and physical examination findings, this patient has Bell’s palsy. There is no evidence to suggest involvement of any other cranial nerves, which might raise suspicion of a cerebello-pontine angle space-occupying lesion. With her history of possible optic neuritis, there is a possibility that the lesion is in fact a manifestation of multiple sclerosis, although this should be differentiated by examination of an upper motor neuron lesion (with sparing of the forehead facial muscles because of bilateral innervation). In light of her diabetes and the limited evidence of benefit from corticosteroid use, the most sensible first management step for her would be meticulous eye care to avoid corneal ulceration, as a result of the difficulty she is having closing her left eye.

Pneumonitis is a serious and unpredictable side-effect of treatment with methotrexate (MTX) that may become life-threatening. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxaemia and tachypnoea are always present and crackles are frequently audible. Chest radiography reveals a diffuse interstitial or mixed interstitial and alveolar infiltrate, with a predilection for the lower lung fields. Pulmonary function tests show a restrictive pattern with diminished diffusion capacity. Lung biopsy reveals cellular interstitial infiltrates, granulomas or a diffuse alveolar damage pattern accompanied by perivascular inflammation. Most patients present in the first few months of starting methotrexate. It is important that all patients receiving methotrexate be educated concerning this potential adverse reaction and instructed to contact their physicians should significant new pulmonary symptoms develop while undergoing therapy. If methotrexate pneumonitis is suspected, methotrexate should be discontinued, supportive measures instituted and careful examination for different causes of respiratory distress conducted. This may be treated with corticosteroids once underlying infection has been excluded.

The patient has primary Hypogonadism.
Since he already had two children, Klinefelter syndrome is excluded and the patient does not need karyotyping.
His lab results are normal indicating normal pituitary gland functions.
So the next step is testicular ultrasound as testicular tumour, infiltration or idiopathic failure is suspected.

The most appropriate intervention in this patient is intravenous hydroxocobalamin.
The clinical scenario provided is suggestive of acute cyanide toxicity secondary to burning plastics in the house fire.
Cyanide ions inhibit mitochondrial cytochrome oxidase, preventing aerobic respiration. This manifests in normal oxygen saturations, a high pO2 and flushing (or ‘brick red’ skin) brought on by the excess oxygenation of venous blood. In the question above it is important to note that the blood gas sample given is venous rather than arterial. His blood gas also demonstrates an increased anion gap, consistent with his high lactate (generated by anaerobic respiration due to the inability to use available oxygen).

The recommended treatment for moderate cyanide toxicity in the UK is one of three options: sodium thiosulfate, hydroxocobalamin or dicobalt edetate.

Among the options given is hydroxocobalamin and this is, therefore, the correct answer. Hydroxocobalamin additionally has the best side-effect profile and speed of onset compared with other treatments for cyanide poisoning.

Other options:
– Intubation would be appropriate treatment in the context of airway burns but this patient has no evidence of these, although close monitoring would be advised.
– High-flow oxygen is the treatment for carbon monoxide poisoning – a sensible differential, but this man’s very high lactate and high venous pO2 fit better with cyanide toxicity. Intravenous dexamethasone would be another treatment for airway oedema once an endotracheal tube had been placed.
– Intravenous sodium nitroprusside is a treatment for high blood pressure that can cause cyanide poisoning, and would, therefore, be inappropriate.

Note:

Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidizing enzymes
Clinical presentation:
Classical features: brick-red skin, the smell of bitter almonds
Acute: hypoxia, hypotension, headache, confusion
Chronic: ataxia, peripheral neuropathy, dermatitis

Management:
Supportive measures: 100% oxygen
Definitive: hydroxocobalamin (intravenously), also a combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously).

Temazepam is an orally available benzodiazepine used in the therapy of insomnia.
The soporific activity of the benzodiazepines is mediated by their ability to enhance gamma-aminobutyric acid (GABA) mediated inhibition of synaptic transmission through binding to the GABA-A receptor.
The recommended initial dose for insomnia is 7.5 mg before bedtime, increasing as needed to a maximum dose of 30 mg.

The most common side effects of temazepam are dose-related and include daytime drowsiness, lethargy, ataxia, dysarthria, and dizziness.
Tolerance develops to these side effects, but tolerance may also develop to the effects on insomnia.

As the patient has early menopause, hormone replacement therapy (HT) is considered to be the first line of choice for prevention of bone loss and fracture in the early postmenopausal period for 5 years.

Diabetic peripheral neuropathy usually goes in parallel with retinopathy and nephropathy. It is also slowly progressive and affects mainly the spinothalamic pathway.
Alcohol induced peripheral neuropathy is also slowly progressive and affects mainly the spinothalamic pathway.
Vitamin B 12 deficiency usually causes a more rapidly progressive neuropathy with dorsal column involvement (joint position and vibration involvement with sensory ataxia and pseudoathetosis of upper limbs).

One of the questions the therapist poses himself while informing a patient is: whom shall I inform about the diagnosis, treatment and prognosis? If we unconditionally accepted the view that information belongs to the patient from an ethical and legal standpoint, we would automatically exclude the partner and the family. Therefore, the therapist should raise another question: what is the benefit to the patient? To answer the question and the resulting dilemma, we have to leverage the long experience of family therapy and tailor it to the cases we are dealing with. It should be taken into consideration that patient and family are a dynamic system which was balanced before the onset of the disease, but is now disrupted, entering into crisis. Therefore, the denial mechanisms and personality characteristics we have previously elaborated on, and communication among members play a crucial role in determining the information strategy and the way family should be approached. In this particular case, the most appropriate person to inform the patient is the consultant, meaning the one currently responsible for the patient’s care. The patient most probably has already developed some form of close and trustful relationship with his consultant.

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

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

Flow-volume loop is an easy, non-invasive diagnostic tool that can be used even in severely-ill patients. It can provide information about the location of the obstruction and can differentiate between obstructive pulmonary disease and upper-airway obstruction. Therefore, it is recommended to obtain a flow-volume loop during the assessment of patients with upper airway obstruction.

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)

Senile cataract is an age-related, vision-impairing disease characterized by gradual progressive clouding and thickening of the lens of the eye. Patients with senile cataracts often present with a history of gradual progressive visual deterioration and disturbance in night and near vision.

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

Initiation of allopurinol treatment during an attack can exacerbate and prolong the episode. Thus treatment should be delayed until the attack resolves.

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

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

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

Yellow nails are present in pulmonary and renal disease.

The most probable diagnosis in this patient is post-traumatic stress disorder (PTSD). The first-line treatment for this patient would be cognitive behavioural therapy or eye movement desensitization and reprocessing therapy.

Post-traumatic stress disorder (PTSD) can develop in people of any age following a traumatic event, for example, a major disaster or childhood sexual abuse. It encompasses what became known as ‘shell shock’ following the first world war. One of the DSM-IV diagnostic criteria is that symptoms have been present for more than one month.

Clinical features:
Re-experiencing: flashbacks, nightmares, repetitive and distressing intrusive images
Avoidance: avoiding people, situations or circumstances resembling or associated with the event
Hyperarousal: hypervigilance for threat, exaggerated startle response, sleep problems, irritability and difficulty concentrating
Emotional numbing – lack of ability to experience feelings, feeling detached from other people
Depression
Drug or alcohol misuse
Anger

Management:
Following a traumatic event single-session interventions (often referred to as debriefing) are not recommended
Watchful waiting may be used for mild symptoms lasting less than 4 weeks
Trauma-focused cognitive-behavioural therapy (CBT) or eye movement desensitization and reprocessing (EMDR) therapy may be used in more severe cases
Drug treatments for PTSD should not be used as a routine first-line treatment for adults.
If drug treatment is used then paroxetine or mirtazapine are recommended.

The Stages of COPD:
Mild COPD or Stage 1—Mild COPD with a FEV1 about 80 percent or more of normal.
Moderate COPD or Stage 2—Moderate COPD with a FEV1 between 50 and 80 percent of normal.
Severe COPD or Stage 3—Severe emphysema with a FEV1 between 30 and 50 percent of normal.
Very Severe COPD or Stage 4—Very severe or End-Stage COPD with a lower FEV1 than Stage 3, or people with low blood oxygen levels and a Stage 3 FEV1.

This patient has a FEV1 percent of 40 which falls within the stage 2 or moderate COP

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

The first line treatment for ascites that is symptomatic is paracentesis. If it is not symptomatic, treatment could be with salt and fluid restriction as well as spironolactone. If spironolactone maximum dosage is reached, you can use furosemide additionally. Amiloride is not a diuretic that is recommended in this case.

There are two types of Non-alcoholic fatty liver disease (NAFLD); simple fatty liver and non-alcoholic steatohepatitis (NASH). Simple fatty liver and NASH are two separate conditions.
Simple fatty liver, also called non-alcoholic fatty liver (NAFL), is a form of NAFLD in which you have fat in your liver but little or no inflammation or liver cell damage. Simple fatty liver typically does not progress to cause liver damage or complications.
Non-alcoholic steatohepatitis (NASH)
NASH is a form of NAFLD in which you have hepatitis and liver cell damage, in addition to fat in your liver. Inflammation and liver cell damage can cause fibrosis, or scarring, of the liver. NASH may lead to cirrhosis or liver cancer. Type I diabetes is not associated with NASH (non-alcoholic steatohepatitis), but type II diabetes is. Hyperlipidaemia, obesity, sudden weight loss/starvation and jejunoileal bypass are all associated with NASH. This is the most common cause of liver disease in the developed world.

Rifampicin specifically inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription, by forming a stable drug-enzyme complex with a binding constant of 10(-9) M at 37 C.

According to different guidelines for patients above 80 years, the targeted systolic blood pressure varies from 140-150 mmHg. As this patient’s BP is within that range, he can be kept under observation.

Confusion in the patient refers to neurological symptoms that are more associated with thrombotic thrombocytopenic purpura than with haemolytic uremic syndrome. All the other symptoms present in both conditions similarly.

The history is consistent with carpal tunnel syndrome (CTS) arising as a result of pressure on the median nerve in the carpal tunnel. The median nerve supplies the muscles of the thenar eminence: the abductor pollicis (C7, C8), flexor pollicis brevis and opponens pollicis, and the lateral two lumbricals. The nerve conduction studies confirm marked denervation and absent sensory potentials within the median nerve territory.

Nice guidelines for lung reduction surgery:

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

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

Methadone and cocaine can cause QT prolongation through the direct effects on the resting membrane potential. Methadone can increase QT dispersion in addition to QT interval. Methadone inhibits the Human Ether-a-go-go Related Gene (hERG) and causes QTc prolongation and development of Torsades de point. Brugada-like syndrome is another condition found in methadone users which predisposes the users to life-threatening ventricular tachycardia and sudden cardiac death.

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before age 40 and various patterns of disease are recognised, including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy.
Non-invasive ventilation (usually BIPAP) is used at night, with studies having shown a survival benefit of around 7 months. Riluzole prevents stimulation of glutamate receptors, used mainly in amyotrophic lateral sclerosis and has been shown to prolong life by about 3 months.

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.

Obsessive-Compulsive Disorder (OCD) is a common, chronic and long-lasting disorder in which a person has uncontrollable, reoccurring thoughts (obsessions) and behaviours (compulsions) that he or she feels the urge to repeat over and over.
People with OCD may have symptoms of obsessions, compulsions, or both. These symptoms can interfere with all aspects of life, such as work, school, and personal relationships.

Obsessions are repeated thoughts, urges, or mental images that cause anxiety. Common symptoms include:
Fear of germs or contamination
Unwanted forbidden or taboo thoughts involving sex, religion, and harm
Aggressive thoughts towards others or self
Having things symmetrical or in a perfect order

Compulsions are repetitive behaviours that a person with OCD feels the urge to do in response to an obsessive thought. Common compulsions include:
-Excessive cleaning and/or handwashing
-Ordering and arranging things in a particular, precise way
-Repeatedly checking on things, such as repeatedly checking to see if the door is locked or that the oven is off
-Compulsive counting

Research also shows that a type of CBT called Exposure and Response Prevention (ERP) is effective in reducing compulsive behaviours in OCD, even in people who did not respond well to SRI medication. ERP has become the first-line psychotherapeutic treatment for OCD

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

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

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

Acute breathlessness in SLE can be due to a pericardial effusion or a pulmonary embolism. Normal peripheral oxygen saturation and normal ECG, make the diagnosis of pulmonary embolism less likely. To exclude pericardial effusion, an urgent transthoracic echocardiogram is needed.

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.

The prompt is suggestive of acute appendicitis. The Alvarado score is a clinical scoring system used to determine the likelihood of appendicitis, so this is the correct answer. A score greater than 6 is generally considered at risk for having acute appendicitis. It has 8 different criteria included (symptoms, signs, and lab results) and divides patients into appendicitis unlikely, possible, probable, and definite. The Center Score is a score to access the likelihood that pharyngitis is due to Strep. The Child-Pugh score predicts prognosis in liver cirrhosis. The Glasgow score is two different scores– the Glasgow coma score in trauma, which estimates level of consciousness, essentially, and The Glasgow Imrie Criteria which determines the severity of acute pancreatitis based on 8 lab values. The MELD score predicts the severity of end-stage liver disease.

Lesions in the optic radiation can cause a homonymous hemianopia with macular sparing, as a result of collateral circulation offered to macular tracts by the middle cerebral artery.
Lesions in the optic tract also cause a homonymous hemianopia, but without macular sparing.
Lesions in the optic chiasm, optic nerve, and temporal lobe cause bitemporal hemianopia, ipsilateral complete blindness, and superior homonymous quadrantanopia respectively.

Dapagliflozin works by inhibiting sodium glucose cotransporter 2 (SGLT2) and blocking resorption of glucose in the kidney, leading to an increase in urinary glucose excretion and lowering of both plasma glucose levels and body weight.
All studies with SGLT2 inhibitors have found significant reductions in BP, with greater reductions seen in systolic (1.66 to 6.9mmHg) than diastolic (0.88 to 3.5mmHg) BP.
While some trials have shown no change in lipid parameters, others have shown a modest but statistically significant increase in both HDL and LDL cholesterol with no effect on triglycerides or the LDL/HDL ratio.

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.

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

Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless oedema, but oedema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule.

In central and nephrogenic diabetes insipidus (DI), urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI.

In primary polydipsia, water deprivation results in an increase in urine osmolality, anywhere between 300 – 800 mOsm/Kg (usually up to 600 – 700 mOsm/Kg), without a substantial increase in plasma osmolality, but the increase in urine osmolality is not as substantial as in a normal response.

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

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

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

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.

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.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group). The relative risk is mistaken by some, with the odds ratio and absolute risk. Relative risk is the ratio of the probability of an event occurring with an exposure versus the probability of the event occurring without the exposure. Thus to calculate the relative risk, we must know the exposure status of all individuals (either exposed or not exposed). This implies that relative risk is only appropriate for cases where the exposure status and incidence of disease can be accurately determined such as prospective cohort studies.

Hereditary C1 inhibitor deficiency leads to recurrent angioedema without urticaria or pruritus. Physical triggers include dental work, surgery or intubation. Medical triggers include angiotensin-converting enzyme (ACE) inhibitor, tamoxifen, oestrogen-containing medications (e.g., hormone replacement therapy and oral contraceptives). It is diagnosed on the basis of low levels of C1 esterase inhibitor or elevated levels of dysfunctional C1 esterase inhibitor. C4 levels are low between attacks. IgE levels, eosinophils, skin prick tests and RASTs are helpful in other allergic conditions and asthma but not of use in this case.

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

Diagnosis of RA is mainly based on clinical features (e.g., morning stiffness, symmetrical joint swelling) and laboratory tests (e.g., anti-CCP). Rheumatoid factor is not very specific for this disease and hence has low reliability. X-ray findings (e.g., soft tissue swelling or joint space narrowing) occur late in the disease and are therefore not typically used for diagnosis.

The fact that he has recently stopped taking his valganciclovir, anti-viral, is key to the answer to this question. This makes the answer quite plainly donor-acquired CMV infection over all of the other answer choices. He needs to stay on prophylaxis against this, particularly in the first 3 months after transplant. Symptoms and presentations of CMV infection can include fever, abdominal pain, diarrhoea, pneumonitis, hepatitis, hematologic abnormalities, retinitis, and esophagitis.

Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism.

Xeroderma pigmentosum is an X-linked recessive condition, which is caused by mutations in DNA gyrase which further encodes the XP gene. The defect may lead to skin cancer at an early stage of life, especially at photo exposed sites.

Macular disease can affect central vision at any stage of diabetic retinopathy and may be seen in type 2 diabetic patients. Diabetic retinopathy affects up to 80 percent of those who have had diabetes for 20 years or more. Macular oedema occurs when damaged blood vessels leak fluid and lipids onto the macula, the part of the retina that lets us see detail. The fluid makes the macula swell, which blurs vision.

Once thyrotoxicosis has been identified by laboratory values, the thyroid radio-iodine uptake and scan may be used to help distinguish the underlying aetiology. Thyroid radioiodine uptake is raised in Graves’ disease. It may be normal or raised in patients with a toxic multinodular goitre. It is very low or undetectable in thyrotoxicosis resulting from exogenous administration of thyroid hormone or the thyrotoxic phase of thyroiditis.

Polycythaemia vera (PV) is associated with a low ESR.

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. PV is associated with a low ESR.

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 acute myeloid leukaemia (AML). The risk of having AML is increased with chemotherapy treatment.

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

Lithium acts by:
– I inhibiting postsynaptic D2 receptor super sensitivity
– Altering cation transport in nerve and muscle cells and influencing reuptake of serotonin or norepinephrine
– Inhibiting phosphatidylinositol cycle second messenger systems

The NICE guidelines for depression and bipolar disorder both recommend Lithium as an effective treatment; patients who take lithium should have regular blood tests to monitor the amount of lithium in their blood (every 3 months), and to make sure the lithium has not caused any problems with their kidneys or thyroid (every 6 months).

Lithium adverse effects include:
– Leucocytosis (most patients) which is when the white cells are above the normal range in the blood.
– Polyuria/polydipsia (30-50%)
– Dry mouth (20-50%)
– Hand tremor (45% initially, 10% after 1 year of treatment)
– Confusion (40%)
– Decreased memory (40%)
– Headache (40%)
– Muscle weakness (30% initially, 1% after 1 year of treatment)
– Electrocardiographic (ECG) changes (20-30%)
– Nausea, vomiting, diarrhoea (10-30% initially, 1-10% after 1-2 years of treatment)
– Hyperreflexia (15%)
– Muscle twitch (15%)
– Vertigo (15%)

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)

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

Ethylene glycol poisoning is the only poison listed that will cause dilation of the pupils whereas all the other listed conditions and poisons will present with small pupils other than in the case of Myotonic dystrophy wherein the patient will present with a cortical cataract.

The Koebner phenomenon refers to skin lesions appearing on lines of trauma, exposure to a causative agents including: molluscum contagiosum, warts and toxicodendron dermatitis or secondary to scratching rather than an infective or chemical cause include vitiligo, psoriasis, lichen planus, lichen nitidus, pityriasis rubra pilaris, and keratosis follicularis (Darier disease).

Myotonic dystrophy is the most likely diagnosis here.
It is a multisystem disorder causing cognitive impairment, cataracts, cardiac problems and testicular atrophy, as well as affecting the muscles. Patients have muscle weakness, normally worse distally, and/or myotonia (which is worse in cold weather).
On examination, patients may also have frontal balding, a myopathic facies, bilateral ptosis, an ophthalmoplegia and wasting of facial muscles and other limb muscles. Myotonic dystrophy is associated with diabetes mellitus and pituitary dysfunction.
Diagnosis is normally based on clinical features with a characteristic electromyogram (EMG) of myotonic discharges. Creatine kinase is generally normal and muscle biopsy is non-specific.

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.

N-acetylcysteine depletes glutathione reserves by providing cysteine, which is an essential precursor in glutathione production.

Glutathione within the liver can normally detoxify these minuscule quantities of NAPQI and prevent tissue damage.
N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity.

Paracetamol overdose:
The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose, the conjugation system becomes saturated leading to oxidation by cytochrome P450 (predominately CYP2E1) mixed-function oxidases. This produces a toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).

Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death.

Other uses: In COPD, cystic fibrosis, and other lung conditions, nebulized NAC has mucolytic, anti-inflammatory, and antioxidant properties.

MDMA commonly known as ecstasy or molly, is a psychoactive drug primarily used as a recreational drug. The desired effects include altered sensations, increased energy, empathy, and pleasure. Features of MDMA abuse include hyponatraemia, tachycardia, hyperventilation, and hyperthermia.

The rationale behind the use of sodium bicarbonate is that it increases the alkalinity of the urine promoting lithium excretion. The preferred treatment in severe cases would be haemodialysis.

Lithium is a mood-stabilizing drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.

Toxicity may be precipitated by dehydration, renal failure, diuretics (especially Bendroflumethiazide), ACE inhibitors, NSAIDs and metronidazole.

Features of toxicity
Coarse tremor (a fine tremor is seen in therapeutic levels)
Hyperreflexia
Acute confusion
Seizure
Coma

Management
Mild-moderate toxicity may respond to volume resuscitation with normal saline
Haemodialysis may be needed in severe toxicity
Sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion.

Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin.

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

Patients at high risk of TLS should be given IV rasburicase or IV allopurinol immediately prior to and during the first few days of chemotherapy. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower-risk groups should be given oral allopurinol during cycles of chemotherapy in an attempt to avoid the condition.

TLS is graded according to the Cairo-Bishop scoring system as:
1. Laboratory tumour lysis syndrome
2. Clinical tumour lysis syndrome

Myasthenia gravis (MG) is an organ-specific autoimmune disease caused by an antibody-mediated assault on the muscle nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Binding of antibodies to the AChR leads to loss of functional AChRs and impairs the neuromuscular signal transmission, resulting in muscular weakness.

The patient has hyperinsulinemia and hypoglycaemia, but her C-peptide levels are normal. This is strongly suggestive of the fact that she is self-administering insulin.
In Insulinoma, common diagnostic criteria include:
– blood glucose level < 50 mg/dl with hypoglycaemic symptoms,
– relief of symptoms after eating
– absence of sulfonylurea on plasma assays.
The classic diagnostic criteria include the demonstration of the following during a supervised fast:
Increased plasma insulin level
Increased C peptide level
Increased proinsulin level
However, the patient has normal C-peptide levels.
In type-1 diabetes mellitus, insulin and C-peptide levels are low.

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Where

a = Number of exposed cases

b = Number of exposed non-cases

c = Number of unexposed cases

d = Number of unexposed non-cases

OR=(a/c) / (b/d) = ad/bc

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

Poor prognostic factors for breast cancer include:
1. Young age (<40 years)
2. Premenopausal at the time of diagnosis
3. Increased tumour size
4. High-grade tumour
5. Oestrogen and progesterone receptor-negative tumour
6. Positive lymph node status

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

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

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

The correct course of action after giving terlipressin and resuscitating with IV fluids is to perform an EGD with endoscopic variceal band ligation. According to NICE: ‘Offer endoscopic variceal band ligation for the primary prevention of bleeding for people with cirrhosis who have medium to large oesophageal varices. There are serious complications of a TIPS procedure and it is not the first line treatment.

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

L4 dermatome distribution includes the kneecaps.

Othello syndrome (OS) is a type of paranoid delusional jealousy, characterized by the false absolute certainty of the infidelity of a partner, leading to preoccupation with a partner’s sexual unfaithfulness based on unfounded evidence. OS has been associated with psychiatric and neurological disorders including stroke, brain trauma, brain tumours, neurodegenerative disorders, encephalitis, multiple sclerosis, normal pressure hydrocephalus, endocrine disorders, and drugs.

The patient most likely suffers from Paget’s disease of the bone as his radiological examination shows both osteolytic and osteosclerotic lesions. Any bone or bones can be affected, but Paget’s disease occurs most frequently in the pelvis > lumbar spine > femur > thoracic spine > sacrum > skull > tibia.

Triptans are specific 5-HT1 agonists used in the acute treatment of migraine. They are generally used as first-line therapy in combination with an NSAID or paracetamol.

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

Polymerase chain reaction (PCR) is a method widely used in molecular biology to make several copies of a specific DNA segment. Using PCR, copies of DNA sequences are exponentially amplified to generate thousands to millions of more copies of that particular DNA segment.The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections. PCR is also extensively used in forensics.

Bivalirudin is a competitive, direct thrombin inhibitor. It inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade. So inhibition of fibrinogen conversion to fibrin inhibits thrombus development.

This patient’s symptoms of anaemia, leukopenia, and elevated non-albumin protein concentration with fatigue and weight loss, point to myeloma. Thus plasma protein electrophoresis or Serum Protein Electrophoresis (SPE) is indicated when there is suspicion of myeloma.

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.

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.

Metabolic acidosis is associated with cocaine overdose.
In overdose, cocaine leads to agitation, tachycardia, hypertension, sweating, hallucinations, and finally convulsions.
Metabolic acidosis, hyperthermia, rhabdomyolysis, and ventricular arrhythmias also occur.
Chronic use may be associated with premature coronary artery disease, dilated cardiomyopathy, and increased risk of cerebral haemorrhage.
There are 3 stages for acute cocaine toxicity:
Stage I: CNS symptoms of headache, vertigo, pseudo hallucinations, hyperthermia, hypertension.
Stage II: increased deep tendon reflexes, tachypnoea, irregular breathing, hypertension.
Stage III: Areflexia, coma, fixed and dilated pupils, hypotension, ventricular fibrillation, apnoea, and respiratory failure.

Treatment:
– Airway, breathing, and circulation to be secured. The patient’s fever should be managed, and one should rule out hypoglycaemia as a cause of the neuropsychiatric symptoms.
– Cardiovascular toxicity and agitation are best-treated first-line with benzodiazepines to decrease CNS sympathetic outflow.
– The mixed beta/alpha blocker labetalol is safe and effective for treating concomitant cocaine-induced hypertension and tachycardia.
– Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil have been shown to reduce hypertension reliably, but not tachycardia.
– Dihydropyridine agents such as nifedipine should be avoided, as reflex tachycardia may occur.
– The alpha-blocker phentolamine has been recommended but only treats alpha-mediated hypertension and not tachycardia.

Throughout pregnancy the tubular reabsorption of glucose is less effective than in the non-pregnant state, this leads to glycosuria.

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.

The CD15 antigen, also known as Lewis (hapten)X, serves as an immuno-phenotypic marker for Reed-Sternberg cells and its expression has diagnostic, but also prognostic significance in Hodgkin Lymphoma.

Northern blotting’s purpose is to measure the size and amount of RNA transcribed from a specific gene of interest.

In boys, the first manifestation of puberty is testicular enlargement; the normal age for initial signs of puberty is 9 to 14 years in males. Pubic hair in boys generally appears 18 to 24 months after the onset of testicular growth and is often conceived as the initial marker of sexual maturation by male adolescents.

The patient is asymptomatic but matches the diagnostic criteria for multiple myeloma (MM). Therefore, the underlying diagnosis of this condition is smouldering multiple myeloma (SMM). SMM is an early precursor to MM. Its treatment is typically to watch and wait.

MM is a neoplasm of the bone marrow plasma cells. Peak incidence is in patients aged 60–70 years.

Clinical features of MM include:
1. Ostealgia, osteoporosis, pathological fractures (typically vertebral), and osteolytic lesions
2. Lethargy
3. Infections
4. Hypercalcaemia
5. Renal failure
6. Other features: amyloidosis e.g. macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

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

The delusion of grandeur is more indicative of mania than hypomania.
While criteria (e.g. ICD-10, DSM-5) vary regarding the diagnosis between hypomania and mania, the consistent difference between mania and hypomania is the presence of psychotic symptoms.

Hypomania vs. mania:
The presence of psychotic symptoms such as delusions of grandeur
auditory hallucinations point towards mania rather than hypomania/

The following symptoms are common to both hypomania and mania
Mood:
Predominately elevated
Irritable

Speech and thought:
Pressured
Flight of ideas
Poor attention

Behaviour
Insomnia
Loss of inhibitions: sexual promiscuity, overspending, risk-taking
increased appetite

A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment.

Consider giving a single dose of intravenous magnesium sulphate to patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy. Magnesium sulphate (1.2–2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

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

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.

Cryoglobulinemia may be caused by paraprotein bands such as those seen in Waldenström’s macroglobulinemia and multiple myeloma (MM). Meltzer’s triad of arthralgia, weakness, and palpable purpura are common to all types of cryoglobulinemia—as are membranoproliferative glomerulonephritis and low C4 levels. Raynaud’s phenomenon, however, occurs only in type 1 cryoglobulinemia, and its presence can be helpful in ascertaining the underlying cause.

Cryoglobulinemia is a condition in which the blood contains large amounts of pathological cold-sensitive antibodies called cryoglobulins—proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. One-third of the cases are idiopathic.

There are three types of cryoglobulinemia:
1. Type I (25%):
Monoclonal—IgG or IgM
Associated with multiple myeloma (MM), Waldenström’s macroglobulinemia

2. Type II (25%):
Mixed monoclonal and polyclonal—usually with rheumatoid factor (RF)
Associated with hepatitis C, rheumatoid arthritis (RA), Sjogren’s syndrome

3. Type III (50%):
Polyclonal—usually with RF
Associated with rheumatoid arthritis, Sjogren’s syndrome

Investigation results for cryoglobulinemia show low complement (especially C4) and high ESR. Treatment options include immunosuppression and plasmapheresis.

The patient’s history of a blood transfusion and lab results showing a markedly low C4 (with normal C3), elevated rheumatoid factor, and elevated serum IgM is highly suggestive of hepatitis C-associated cryoglobulinaemic vasculitis. Testing for Cryoglobulins will confirm this suspicion.

The principal mechanism by which strontium inhibits osteoclast activity is by enhancing the secretion of osteoprotegerin (OPG) and by reducing the expression of the receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts.

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.

Management:
Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
Alendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.
Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Riboflavin, vitamin B2, is a water-soluble and heat-stable vitamin that the body uses to metabolize fats, protein, and carbohydrates into glucose for energy. Riboflavin deficiency can cause fatigue, swollen throat, blurred vision, and depression. It can affect the skin by causing skin cracks, itching, and dermatitis around the mouth. Hyperaemia and oedema around throat, liver degeneration, and hair loss can also occur along with reproductive issues. Usually, people with riboflavin deficiency also have deficiencies of other nutrients. In most cases, riboflavin deficiency can be reversed unless it has caused anatomical changes such as cataracts.

Thalassaemias are a group of genetic disorders characterised by decreased production of either alpha or beta chains of haemoglobin (Hb). Beta thalassaemia trait is an autosomal recessive condition in which a disproportionate hypochromic, microcytic anaemia occurs—microcytosis is disproportionate to the Hb level. It is usually asymptomatic.

Microcytic anaemia in a female should raise the possibility of either gastrointestinal blood loss or menorrhagia. However, there is no history to suggest this in the aforementioned patient. This, combined with characteristic disproportionate microcytosis and raised HbA2 levels ( >3.5%), point towards beta thalassaemia trait.

Basophilic stippling is also seen in lead poisoning but the raised HbA2 levels cannot be explained in such a case.

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.

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

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

Primary gout is related more often to underexcretion of uric acid or overproduction.

Supravalvular aortic stenosis, is associated with a condition called William’s syndrome.
William’s syndrome is an inherited neurodevelopmental disorder caused by a microdeletion on chromosome 7. The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. Individuals with Williams syndrome tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.
Most individuals with Williams syndrome are highly verbal relative to their IQ, and are overly sociable, having what has been described as a cocktail party type personality.

Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index
– Assays for thyrotropin-receptor antibodies (particularly TSIs) almost always are positive.
– Detection of TSIs is diagnostic for Graves disease.
– Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroid peroxidase antibodies, are usually present.
– Other autoantibodies that may be present include thyrotropin receptor-blocking antibodies and anti–sodium-iodide symporter antibody.
The presence of these antibodies supports the diagnosis of autoimmune thyroid disease.
– The radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland.