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 the hypersecretion of gastrin. Serum gastrin levels > 1000 and a pH < 2 are diagnostic of pancreatic gastrinoma. None of the other answer choices are a better answer than this. CT abdomen may potentially show a tumour, but this is not diagnostic for type.

Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in the small intestinal endocrine I-cells and cerebral neurons.

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

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group)
Experimental event rate, EER = 10 / 200 = 0.05

Control event rate, CER = 12 / 600 = 0.02

Therefore the relative risk = EER / CER = 0.05 / 0.02 = 2.5

The patient is most likely to have Medullary Thyroid Carcinoma (MTC).
Sporadic, or isolated MTC accounts for 75% of cases and inherited MTC constitutes the rest.
Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occurs.
A 24-hour urinalysis for catecholamine metabolites (e.g., vanillylmandelic acid [VMA], metanephrine) has to be done to rule out concomitant pheochromocytoma in patients with MEN type 2A or 2B, as Pheochromocytoma must be treated before MTC.

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

The direct Coombs test will specifically confirm immune-mediated haemolysis occurring post-transfusion in the aforementioned case.

There are two types of Coombs test used in immunohematology and immunology:

1. Direct Coombs test—It confirms autoimmune haemolytic anaemia by detecting antibodies or complement proteins attached to the surface of red blood cells.

2. Indirect Coombs test—It is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. It detects antibodies floating freely in the blood, against foreign red blood cells.

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

This describes a clinical scenario of spontaneous bacterial peritonitis. The diagnosis is made when fluid removed (ascites) is found to have > 250/mm cubed of PMNs (polymorphonuclear leukocytes). Cefotaxime or another third generation cephalosporin is the treatment of choice.

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

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

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

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

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

Cataract is a condition characterized by clouding of the lens of the eye. This condition most frequently occurs due to age-related degenerative processes in the lens, but can also be associated with ocular trauma, metabolic disorders, side-effects of drugs, or congenital infections. The clouding causes distortion of light, as it passes through the lens, resulting in visual impairment and glare. Initially, a cataract presents discretely and may even go unnoticed, but the visual impairment worsens as the cataract grows larger.

Diagnosis is typically established on the basis of a thorough history and direct visualization of the cataract (by means of slit-lamp microscopy). Surgery is indicated with significant visual impairment and involves lens extraction and implantation of an artificial lens. Untreated cataracts eventually lead to complete blindness.

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).

Diabetic dermadromes constitute a group of cutaneous conditions commonly seen in people with diabetes with longstanding disease. Conditions included in this group are:
– Acral dry gangrene
– Carotenosis
– Diabetic dermopathy
– Diabetic bulla
– Diabetic cheiroarthropathy
– Malum perforans
– Necrobiosis lipoidica
– Limited joint mobility
– Scleroderma
– Waxy skin is observed in roughly 50%.

Sweet’s syndrome is also known as acute febrile neutrophilic dermatosis has a strong association with acute myeloid leukaemia. It is not associated with diabetes mellitus.

Sickle cell anaemia is characterised by periods of good health with intervening crises. One of the main types is aplastic crisis characterised by a sudden fall in haemoglobin without marked reticulocytosis (3%—in this case—is just above the normal range). It usually occurs secondary to parvovirus infection.

The other main types of sickle cell crises are thrombotic crisis (painful or vaso-occlusive crisis), sequestration crisis, and haemolytic crisis. Thrombotic crisis is precipitated by infection, dehydration, alcohol, change in temperature, and deoxygenation. Sequestration crisis is characterised by acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates). In haemolytic crisis, fall in haemoglobin occurs secondary to haemolysis. It is a rare type of sickle cell crises.

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.

Steps required in performing the Wilcoxon signed rank test:

1 State the null hypothesis and, in particular, the hypothesized value for comparison
2 Rank all observations in increasing order of magnitude, ignoring their sign. Ignore any observations that are equal to the hypothesized value. If two observations have the same magnitude, regardless of sign, then they are given an average ranking
3 Allocate a sign (+ or -) to each observation according to whether it is greater or less than the hypothesized value (as in the sign test)
4 Calculate:
R+ = sum of all positive ranks
R- = sum of all negative ranks
R = smaller of R+ and R-
5 Calculate an appropriate P value What makes this test the most appropriate for this study is that the data is non-parametric, paired and comes from the same population.

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

Achondroplasia is a common cause of dwarfism. It is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3). In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia can be born to parents that do not have the condition due to spontaneous mutation. It occurs as a sporadic mutation in approximately 80% of cases (associated with advanced paternal age) or it may be inherited as an autosomal dominant genetic disorder.
People with achondroplasia have short stature, with an average adult height of 131 centimeters (52 inches) for males and 123 centimeters (48 inches) for females.

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.

The most probable diagnosis in this patient is serotonin syndrome.

The serotonin syndrome is a cluster of symptoms and signs (range from barely perceptible tremor to life-threatening hyperthermia and shock).
It may occur when SSRIs such as citalopram, escitalopram, fluoxetine, fluoxetine, paroxetine, and sertraline that impair the reuptake of serotonin from the synaptic cleft into the presynaptic neuron are taken in combination with monoamine oxidase inhibitors or tricyclic antidepressants. It has also been reported following an overdose of selective serotonin reuptake inhibitors (SSRIs) alone.

Treatment:
Most cases of serotonin syndrome are mild and will resolve with removal of the offending drug alone.
After stopping all serotonergic drugs, management is largely supportive and aimed at preventing complications.
Patients frequently require sedation, which is best facilitated with benzodiazepines.
Antipsychotics should be avoided because of their anticholinergic properties, which may inhibit sweating and heat dissipation.

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.

Flashes and floaters are symptoms of vitreous detachment. The patient is at risk of retinal detachment and should be referred urgently to an ophthalmologist.

The most common causes of a sudden painless loss of vision are as follows:
– Ischaemic optic neuropathy (e.g. temporal arteritis or atherosclerosis)
– Occlusion of central retinal vein
– Occlusion of central retinal artery
– Vitreous haemorrhage
– Retinal detachment

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.

Tricyclic compounds can’t be cleared by haemodialysis.

Drugs that can be cleared with haemodialysis include: (BLAST)
– Barbiturate
– Lithium
– Alcohol (inc methanol, ethylene glycol)
– Salicylates
– Theophyllines (charcoal hemoperfusion is preferable)

Drugs which cannot be cleared with haemodialysis include:
– Tricyclics
– Benzodiazepines
– Dextropropoxyphene (Co-proxamol)
– Digoxin
– Beta-blockers

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.

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.

This patient has a dendritic corneal ulcer. Herpes simplex keratitis most commonly presents with a dendritic corneal ulcer. Topical acyclovir and ophthalmology review is required. Giving a topical steroid in this situation could be disastrous as it may worsen the infection.

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.

This is a classic clinical presentation, with alcohol intake and nausea/vomiting that leads to hematemesis, of a Mallory-Weiss tear. Because of the history, that makes this more likely than haemorrhagic gastritis, duodenal ulceration, or oesophagitis (also oesophagitis would not bleed a cupful). Oesophageal varices would present with copious amounts of hematemesis and most likely hemodynamic instability as a result of the amount of blood loss. In Mallory-Weiss tear they are typically presented as a hemodynamically stable patient.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. The diagnosis is based on clinical features such as patient history and physical examination; there are no specific tests for reactive arthritis. Treatment is primarily symptomatic and consists of the administration of NSAIDs, as most patients recover spontaneously. extraarticular dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum), oral ulcers. There usually is no rash and the diagnosis is unrelated to the presence of rheumatoid factor. This is a clinical diagnosis.