Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

The patient is most likely suffering from Waldenström’s macroglobulinemia in which IgM paraproteinemia is found. Hyperviscosity syndrome can occur in the patients accounting for 10-15% of the cases.

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.

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

Warfarin is contraindicated during pregnancy due to its teratogenic effects. She should be given heparin throughout her pregnancy. It can be converted to warfarin if necessary after the delivery.

Jaundice in a new-born on the day of delivery is most likely due to Rh incompatibility. This occurs when the mother is Rh-negative and the baby is Rh-positive. Antibodies in the mother against the Rh factor in the baby will destroy the red blood cells in the baby, increasing the bilirubin in the blood. Breast milk jaundice and Galactosemia do not occur immediately after birth, and congenital rubella syndrome and formula feeding does not cause jaundice in babies.

Hypertension along with haematuria give an indication of cystic kidneys which can be diagnosed with an ultrasound.

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

The most likely complaint of this patient would be hot flushes.

Alopecia and cataracts are listed in the BNF as possible side-effects. They are however not as prevalent as hot flushes, which are very common in pre-menopausal women.

Tamoxifen is a Selective Oestrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer

Adverse effects:
Menstrual disturbance: vaginal bleeding, amenorrhoea
Hot flushes – 3% of patients stop taking tamoxifen due to climacteric side-effects.
Venous thromboembolism.
Endometrial cancer
Tamoxifen is typically used for 5 years following the removal of the tumour.

Raloxifene is a pure oestrogen receptor antagonist and carries a lower risk of endometrial cancer.

Although antagonistic with respects to breast tissue tamoxifen may serve as an agonist at other sites. Therefore the risk of endometrial cancer is increased cancer.

The patient’s symptoms along with his age indicates a diagnosis of colorectal cancer. Blood test marker CA-19-9 is a prognostic index for colorectal cancer which confirms the suspicion. Celiac disease is not usually associated with bleeding per rectum and it is associated with a reaction to products containing gliadin. Crohn’s disease and UC are inflammatory bowel diseases and on endoscopy, show many other features of inflammation and not just a single ulcer. A patient with IBS will also have bloating and intermittent diarrhoea with constipation.

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.

Painful haematuria suggests trauma, infection or calculi, whereas painless haematuria suggests a possible occult malignancy. This man is apyrexial with normal WCC and CRP which should effectively exclude infection as a cause for his symptoms. There is no history of trauma in this scenario (often catheter-associated) which makes this cause unlikely. It is worth noting that haematuria associated with injury tends to be macroscopic. Therefore, bladder calculi are the most likely source of his symptoms. Imaging will help to determine the presence of calculi.

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH).
GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

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

Unconjugated bilirubin is conjugated to glucuronic acid in the hepatocyte. Conjugated bilirubin passes into the enterohepatic circulation and the bilirubin which evades this system is metabolised by bacteria, primarily in the large intestine, to urobilinogen, then stercobilinogen and eventually oxidised to stercobilin. Stercobilin gives faeces its brown colour.

Ankylosing spondylitis (spondylarthritis) is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell’s sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease.
The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumour necrosis factor-? inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life. The spine adopts a bamboo shape, not lordosis. The pain usually improves as the day progresses. leg raise test causes pain in cases of meningitis etc not in this case.

The features mentioned in this case indicate an internal haemorrhage. This should be managed initially by passing an IV line and IV fluids.

Fat necrosis is often a result of a trauma or surgery. In fat necrosis the enzyme lipase releases fatty acids from triglycerides. The fatty acids combine with calcium to form soaps. These soaps appear as white chalky deposits which are firm lumps with no associated discharge. The given case has a bruise which indicates prior trauma.

The localisation of intracranial lesions (based on both history and examination) is crucial. Meningiomas are slow in growth, and its subtle effects are very different from the more aggressive, intrinsic lesions. Olfactory groove lesions affect the sense of smell and may produce ipsilateral optic atrophy. Sphenoid ridge lesions will produce exophthalmos. Chiasmal lesions usually produce bitemporal hemianopia.

This patient shows classic symptoms of autosomal-dominant polycystic kidney disease (ADPKD). The abdominal pain and early satiety is caused by the enlarged kidneys that were apparent from the physical examination. Additionally, hypertension is a common symptom along with the systolic murmur that was heard, suggesting mitral valve involvement. In ADPKD cases, the most common extra-renal manifestation is the development of liver cysts which are associated with hepatomegaly.

An aspergilloma is a fungus ball (mycetoma) that develops in a pre-existing cavity in the lung parenchyma. Underlying causes of the cavitary disease may include treated tuberculosis or other necrotizing infection, sarcoidosis, cystic fibrosis, and emphysematous bullae. The ball of fungus may move within the cavity but does not invade the cavity wall. Aspergilloma may manifest as an asymptomatic radiographic abnormality in a patient with pre-existing cavitary lung disease due to sarcoidosis, tuberculosis, or other necrotizing pulmonary processes. In patients with HIV disease, aspergilloma may occur in cystic areas resulting from prior Pneumocystis jiroveci pneumonia. Of patients with aspergilloma, 40-60% experience haemoptysis, which may be massive and life threatening. Less commonly, aspergilloma may cause cough and fever.

The most common type of Hodgkin’s lymphoma (HL) is nodular sclerosing.

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

According to the histological classification, there are four types of HL:

1. Nodular sclerosing: most common (around 70%), more common in women, associated with lacunar cells, good prognosis

2. Mixed cellularity: Around 20%, associated with a large number of Reed-Sternberg cells, good prognosis

3. Lymphocyte-predominant: Around 5%, Reed-Sternberg cells with nuclei surrounded by a clear space found, best prognosis

4. Lymphocyte-depleted: rare, worst prognosis

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.

The patient is experiencing an acute myocardial infarction and percutaneous angiography is the next most appropriate step in management. Percutaneous coronary intervention (PCI), also known as coronary angioplasty, is a nonsurgical technique for treating obstructive coronary artery disease, including unstable angina, acute myocardial infarction (MI), and multivessel coronary artery disease (CAD).

Domperidone is a D2 dopaminergic receptor antagonist which works as an anti emetic by increasing the tone of the lower oesophageal sphincter and increasing the gut motility.

The history is suggestive of a post-traumatic seizure which frequently occurs after moderate or severe traumatic brain injury. Although upgoing plantars can be identified in a post-ictal status, an intracranial bleed has to be excluded. A single seizure cannot be considered epilepsy

Scabies is a parasitic skin infestation caused by Sarcoptes scabiei mite, which is primarily transmitted via direct human-to-human contact. The female scabies mite burrows into the superficial skin layer, causing severe pruritus, particularly at night. Primary lesions commonly include erythematous papules, vesicles, or burrows. Treatment involves topical medical therapy (e.g. permethrin) and decontamination of all clothing and textiles.

A diabetic patient is a patient with depressed immunity. It is not uncommon to develop abscesses. Diabetic patients have a defected cellular innate immunity. On the other hand, bacteria become much more virulent in a high glucose environment in the interstitium.

This patient meets the diagnostic criteria for neutropenic sepsis, which is a relatively common complication of cancer therapy – usually chemotherapy occurring 7-14 days after. It is defined as a neutrophil count of <0.5 x 10^9/L in a patient undergoing anticancer treatment and who has either a temperature higher than 38°C or has other features consistent with clinically significant sepsis. Management approach is the same as mentioned in this case. However, if the patient still remains unwell, then an antifungal such as amphotericin B is started after risk-stratifying the patient and carrying out investigations (e.g. HRCT and Aspergillus PCR) to determine the likelihood of systemic fungal infection.

Amiodarone is a class III antiarrhythmic agent, and prolongs phase 3 of the cardiac action potential.
Digoxin increases the force of contraction of the heart muscle by inhibiting the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium.
Sotalol blocks beta-adrenoreceptors (Vaughan Williams Class II) and prolongs the cardiac action potential duration (Vaughan Williams Class III).
Streptokinase creates an active complex which promotes the cleavage of the Arg/Val bond in plasminogen to form the proteolytic enzyme plasmin. Plasmin degrades the fibrin matrix of the thrombus.

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.