Acute exacerbations of chronic obstructive pulmonary disease (COPD) are immediately treated with inhaled beta2 agonists and inhaled anticholinergics, followed by antibiotics (if indicated) and systemic corticosteroids. Methylxanthine therapy may be considered in patients who do not respond to other bronchodilators.
High flow oxygen would worsen his symptoms. Usually titrated oxygen (88 to 92 %) is given in such patients to avoid the risk of hyperoxic hypercarbia in which increasing oxygen saturation in a chronic carbon dioxide retainer can inadvertently lead to respiratory acidosis and death.

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

Pre-eclampsia is excluded from negative proteinuria. White coat hypertension is excluded with ambulatory blood pressure monitoring. Pregnancy induced hypertension develops after 20 weeks of gestation. So the most likely answer is pre-existing hypertension. She should be investigated for a secondary cause for hypertension.

The patient is 74 years old. She has had a recent gastroscopy and colonoscopy. She has a history of angina and a right CEA. She is having colicky abdominal pain after meals and weight loss, which points to a possible diagnosis of chronic mesenteric ischemia. Thus, you would want to do a contrast-enhanced CT scan of the abdomen to look for this. A 24 hour cardiac monitor would also be helpful to look for any abnormal rhythm that could be a potential aetiology of her disease.

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

The combination of frequent infections, eczema, and thrombocytopaenia are characteristic of Wiskott-Aldrich syndrome, which is due to an abnormality in the WASP gene. It is an X-linked recessive disorder that causes primary immunodeficiency owing to a combined B- and T-cell dysfunction.

The other listed options are:
1. PKD1: polycystic kidney disease
2. CFTR: cystic fibrosis
3. HFE1: haemochromatosis
4. RET: multiple endocrine neoplasia, Hirschsprung’s disease

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

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.

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.

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.

Diagnosis of multiple myeloma (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

Primary aldosteronism now is considered one of the more common causes of secondary hypertension (HTN).
Individuals with primary aldosteronism may present with hypokalaemia metabolic alkalosis; however, as many as 38% of patients with primary aldosteronism may be normokalaemia at presentation.
Routine laboratory studies can show hypernatremia, hypokalaemia, and metabolic alkalosis resulting from the action of aldosterone on the renal distal convoluted tubule (DCT) (i.e., enhancing sodium reabsorption and potassium and hydrogen ion excretion).
Plasma aldosterone/plasma renin activity ratio is used for screening because it is fairly constant over many physiologic conditions.

The patient is clinically free, so Cushing diseases can be exclude.

Androgen deprivation therapy (ADT) for prostate cancer:

Goserelin (Zoladex) is a synthetic gonadotropin-releasing hormone (GnRH) analogue; chronic stimulation of goserelin results in suppression of LH, FSH serum levels thereby preventing a rise in testosterone.

Dosage form: 3.6 mg/10.8mg implants.

Adverse effects include flushing, sweating, diarrhoea, erectile dysfunction, less commonly, rash, depression, hypersensitivity, etc.

Venesection should be done (essentially blood-letting) to decrease the too-high ferratin level. IV Desterrioxamine would have the opposite effect. ASA does not have to do with ferritin. You do not just watch this and recheck. And you do not want to make the patient anaemic.

The power of a test is defined as 1 − the probability of Type II error. The Type II error is concluding at no difference (the null is not rejected) when in fact there is a difference, and its probability is named β. Therefore, the power of a study reflects the probability of detecting a difference when this difference exists. It is also very important to medical research that studies are planned with an adequate power so that meaningful conclusions can be issued if no statistical difference has been shown between the treatments compared. More power means less risk for Type II errors and more chances to detect a difference when it exists.

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.

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

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

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

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

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

This is a classic clinical presentation, with alcohol intake and nausea/vomiting that leads to hematemesis, of a Mallory-Weiss tear. 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.

The patient has small cell lung cancer presented by paraneoplastic syndrome; Ectopic ACTH secretion.

Small cell lung cancer (SCLC), previously known as oat cell carcinoma is a neuroendocrine carcinoma that exhibits aggressive behaviour, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and a frequent association with distinct paraneoplastic syndromes.
Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:
– Shortness of breath
– Cough
– Bone pain
– Weight loss
– Fatigue
– Neurologic dysfunction
Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
SIADH is present in 15% of the patients and Ectopic secretion of ACTH is present in 2-5% of the patients leading to ectopic Cushing’s syndrome.

The history is suggestive of leptospirosis. This is a zoonotic infection caused by a spirochete. As the patient is in shock, resuscitation with IV fluids is the first step in the management. IV antibiotics should be started (Doxycycline or Penicillin) as soon as possible. Other investigations mentioned are important during the management to rule out other possible diagnoses.

The patient is displaying signs and symptoms of hyperviscosity syndrome, secondary to the Waldenström’s macroglobulinemia. Treatment of choice is plasmapheresis.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; weight loss and lethargy; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

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.

Osteoblastic (or sclerotic) bone metastases, characterized by deposition of new bone, present in prostate cancer, carcinoid, small cell lung cancer, Hodgkin lymphoma or medulloblastoma.

Post-concussion syndrome is a complex disorder in which various symptoms, such as headaches and dizziness, last for weeks and sometimes months after the injury that caused the concussion.

Concussion is a mild traumatic brain injury that usually happens after a blow to the head. It can also occur with violent shaking and movement of the head or body. You don’t have to lose consciousness to get a concussion or post-concussion syndrome. In fact, the risk of post-concussion syndrome doesn’t appear to be associated with the severity of the initial injury.

Post-concussion symptoms include:
Headaches
Dizziness
Fatigue
Irritability
Anxiety
Insomnia
Loss of concentration and memory
Ringing in the ears
Blurry vision
Noise and light sensitivity
Rarely, decreases in taste and smell

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

The given history suggests a small fibre painful peripheral sensory neuropathy, the most common cause of which is diabetes. Joint position sense and vibratory sensation are carried through large fibres, and therefore are not currently affected. Sensory nerves are affected more often than motor, so reflexes usually remain in tact.

Vitamin B12 deficiency causes impairment of joint position and vibratory sensation.

Chronic inflammatory demyelinating polyneuropathy (CIPD) causes a large fibre peripheral neuropathy with areflexia.

In syringomyelia there is impaired pain and temperature noted in the upper limbs.

Finally, with alcoholic polyneuropathy, all fibre types are affected (sensory and motor loss). It is usually gradual with long term alcohol abuse and may be accompanied by a nutritional deficiency. In addition, pain is a more dominant feature.

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

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.

In a patient with chronic alcoholism, one can expect confabulations, which point towards a diagnosis of Korsakoff’s syndrome.

Korsakoff’s is characterized by confabulation and amnesia, typically occurring in alcoholics secondary to chronic vitamin B1 (thiamine) deficiency.

Other options:
Dysthymia refers to mild depression.
Hydrophobia is a feature of rabies
Lilliputians may be observed in delirium tremens.
Perseveration is repetitive speech patterns, commonly seen after traumatic brain injury.

According to the Caine criteria, the presence of any two among the four following criteria can be used to clinically diagnose Wernicke’s Encephalopathy:
Dietary deficiency
Oculomotor abnormalities
Cerebellar dysfunction
Either altered mental status or mild memory impairment
Korsakoff psychosis:
Altered mental status – disorientation, confabulations
Oculomotor findings – most often horizontal nystagmus, ophthalmoplegia, cranial nerve IV palsy, conjugate gaze
Ataxia – wide-based gait

Treatment:
The mainstay of treatment in an acute presentation is thiamine replacement.
Electrolyte abnormalities should be corrected and fluids replaced.
In particular, magnesium requires replacement, as thiamine-dependent enzymes cannot operate in a magnesium-deficient state.
After the acute phase of vitamin and electrolyte replacement, memory rehabilitation is beneficial in Korsakoff syndrome.

Traditionally two forms of macular degeneration are seen:
– Dry (geographic atrophy) macular degeneration is characterized by drusen – yellow round spots in Bruch’s membrane.
– Wet (exudative, neovascular) macular degeneration is characterized by choroidal neovascularization. Leakage of serous fluid and blood can subsequently result in a rapid loss of vision. This carries the worst prognosis.