Chloride channels are involved in a diverse set of functions in normal physiology and acquired diseases. Additionally, there are genetic diseases caused by mutations in chloride channels (channelopathies) — the most common being cystic fibrosis, which has a prevalence of 1 in 2,000 Caucasians.

Among the following hypertensives, lisinopril (an ACE inhibitor) is contraindicated in patients who are planning for pregnancy.

Per the NICE guidelines, when treating the woman in question, she should be treated as if she were pregnant given the absence of effective contraception.
ACE inhibitors such as lisinopril are known teratogens and most be avoided.

Drugs contraindicated in pregnancy:
Antibiotics
Tetracyclines
Aminoglycosides
Sulphonamides and trimethoprim
Quinolones

Other drugs:
ACE inhibitors, angiotensin II receptor antagonists
Statins
Warfarin
Sulfonylureas
Retinoids (including topical)
Cytotoxic agents
The majority of antiepileptics including valproate, carbamazepine, and phenytoin are known to be potentially harmful.

Hepatorenal syndrome is renal vasoconstriction that cannot overcome the effects of splanchnic vasodilation. Vasoactive mediators cause this splanchnic vasodilation, reducing SVR, which is sensed by the juxtaglomerular apparatus, activating the RAAS system, leading to renal vasoconstriction. However, the overall splanchnic vasodilation effect is greater than this renal vasoconstriction effect.

The incidence rate is the number of new cases per population at risk in a given time period. For example, if a population initially contains 1,000 non-diseased persons and 28 develop a condition over two years of observation, the incidence proportion is 28 cases per 1,000 persons per two years, i.e. 2.8% per two years.
Prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is usually expressed as a fraction, as a percentage, or as the number of cases per 10,000 or 100,000 people.
Incidence should not be confused with prevalence, which is the proportion of cases in the population at a given time rather than rate of occurrence of new cases. Thus, incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is.

There is a high risk of bleeding due to recent surgery and heparin. So thrombolysis is not an option. The most appropriate management is percutaneous coronary intervention.

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

Triamterene is a potassium-sparing diuretic that can cause hyperkalaemia, therefore, it was stopped in this patient. With all other lab results returning normal values and a normal ECG, management will simply require repeating the U & E after one week since the Triamterene has already be stopped.

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.

Serum vitamin D levels are influenced by sun exposure and diet. Cod liver oil is an important dietary vitamin D source in high-latitude countries like Norway where there is no sun-induced vitamin D production during the winter. 14 Norwegian Health Authorities have recommended 5 ml of cod liver oil daily (400 IU of vitamin D) for more than 60 years to prevent diseases like rickets, formerly more prevalent in areas with little access to vitamin D-rich fatty fish.

Pseudogout is a paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate). Aetiology includes mostly idiopathic (primary form) and secondary form occurring as a result of joint trauma, familial chondrocalcinosis, hyperparathyroidism, hemochromatosis, gout, hypophosphatemia. Clinical presentation: Often asymptomatic.
Acute (pseudogout attack): monoarthritis (rarely oligoarthritis), mostly affecting the knees and other large joints (e.g., hips, wrists, and ankles). It may become chronic (can affect multiple joints). Osteoarthritis with CPPD (most common form of symptomatic CPPD): progressive joint degeneration with episodes of acute inflammatory arthritis typical of pseudogout attacks. Arthrocentesis should be performed, especially in acute cases. Polarized light microscopy: detection of rhomboid-shaped, positively birefringent CPPD crystals. Synovial fluid findings: 10,000-50,000 WBCs/μL with > 90% neutrophils. X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis). Fibrocartilage (meniscus, annulus fibrosus of intervertebral disc) and hyaline cartilage (joint cartilage) may be affected.

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

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.

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

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

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

Molluscum contagiosum (MC), is a viral infection of the skin that results in small, raised, pink lesions with a dimple in the center with little to no surrounding erythema. They may occasionally be itchy or sore. They may occur singularly or in groups. Any area of the skin may be affected, with abdomen, legs, arms, neck, genital area, and face being most common. Onset of the lesions is around 7 weeks after infection. It usually goes away within a year without scarring.
Chickenpox lesions in the early stages may be mistaken for molluscum. However, the presence of associated macules and later vesicles and pustules help to differentiate them.

Transposition of the great arteries results in a significant hypoxemic status that is observed clinically by central cyanosis. The bluish discoloration of the skin and mucous membranes is therefore the basic pattern of clinical presentation in transposition. Its onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulations. Limited intercirculatory mixing, usually present if the ventricular septum is intact or the atrial septal defect is restrictive, is related to progressive and profound central cyanosis evident within the first hours of life. Tachypnoea, tachycardia, diaphoresis, poor weight gain, a gallop rhythm, and eventually hepatomegaly can be then detected later on during infancy. Heart murmurs associated with left outflow tract obstruction, due to a persistent arterial duct or a septal defect may be heard, but they are not a constant finding.

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

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

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

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

Only cystine stones are semi-opaque because they contain sulphur. All the other stones will appear either radio-lucent or radio-opaque.

Friedreich’s ataxia is an autosomal recessive disorder that usually begins before the end of the teens. It has an estimated prevalence in Europe of 1 in 50,000 and life expectancy is around 40–50 years. Neurological features include a progressive ataxia, cerebellar dysarthria, lower limb areflexia, decreased vibratory sensation and proprioception, and pyramidal weakness. Pes cavus and scoliosis are also both seen. Cardiomyopathy occurs in over 70% of cases. Less common features include optic atrophic, diabetes mellitus, and deafness.

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

Bilateral occipital cortex infarction will produce varying degrees of cortical blindness, wherein the patient has no vision but fundoscopy findings are normal. When there are extensive lesions, patients my present with denial of their condition, known as Anton’s Syndrome, and begin to describe objects that they have never seen before.

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon. GLP-1 is released in response to meal intake.
The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the ileal brake mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake.
Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycaemia.

The clinical picture points to Lambert– Eaton myasthenic syndrome (LEMS) which often presents with weakness of the arms and legs. In LEMS, antibodies against voltage-gated calcium channels (VGCC) decrease the amount of calcium that can enter the nerve ending, causing autonomic symptoms like dry mouth and slurring of speech, as seen in this patient.

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.

Exposure to excessive androgens is usually accompanied by premature epiphyseal maturation and closure, resulting in a final adult height that is typically significantly below that expected from parental heights.

congenital adrenal hyperplasia (CAH) is associated with precocious puberty caused by long term exposure to androgens, which activate the hypothalamic-pituitary-gonadal axis. Similarly, CAH is associated with hyperpigmentation and hyperreninemia due to sodium loss and hypovolaemia.

The most likely diagnosis is Wernicke’s encephalopathy. This presents in a long time alcoholic from vitamin BI deficiency. Symptoms include confusion and confabulation, oculomotor symptoms/signs, and ataxia.

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

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

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

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

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

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

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

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

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

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

Management

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

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

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

The patient’s symptoms are suggestive of ankylosing spondylitis which is often accompanied by iritis, the cause of this patient’s red eye.