The Smooth endoplasmic reticulum (ER) is the major site at which membrane lipids are synthesized in eukaryotic cells. Because they are extremely hydrophobic, lipids are synthesized in association with already existing cellular membranes rather than in the aqueous environment of the cytosol. Although some lipids are synthesized in association with other membranes, most are synthesized in the ER. They are then transported from the ER to their ultimate destinations either in vesicles or by carrier proteins.

In many Western countries and health plans in the United States, patients have a primary care physician who acts as a formal gatekeeper for medical specialist care and thereby determines together with the patient whether or not a patient requires medical specialist care. Ideally in such systems, patients are treated in primary care if possible, and referred to medical specialist care if necessary. For the gatekeeper system to be effective, it is vital that adequate decisions are made about when and who to refer. But it is also important that referred patients comply with the referral by consulting a medical specialist. In this case, the GP should discuss with the patient the reasons why she cannot follow the treatment plan. In other words, the GP should detect why the patient is being non-compliant.

All of the aforementioned options may be important however cytogenetics, for detecting chromosomal abnormalities, is the single most important test to determine her disease prognosis.

Acute myeloid leukaemia (AML) is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly.

The disease has a poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

Acute promyelocytic leukaemia (APL) is an aggressive form of AML.

The major endocrine functions of adrenal gland are to produce catecholamines and steroids. Catecholamine, synthesized by the adrenal medulla, is responsible for blood pressure and blood flow regulation whereas steroids produced by the cortex control energy and water homeostasis and immune responses. Glucocorticoids, a major group of adrenal steroids, have a stimulatory effect on catecholamine synthesis in the medulla.

Weight gain is an extremely common (5-40%) adverse effect of atypical antipsychotics such as olanzapine (dose dependent). Olanzapine causes orthostatic hypotension ≥20% of reported cases. Parkinsonism reactions occurs in 4% of people.

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

Mumps presents with a prodromal phase of general malaise and fever. On examination there is usually painful parotid swelling which has high chances of becoming bilateral. In OM with effusion there are no signs of infection and the only symptom is usually hearing loss. Acute otitis externa produces otalgia as well as ear discharge and itching. Acute OM produces otalgia and specific findings upon otoscopy. In acute mastoiditis the patient experiences ear discharge, otalgia, headache, hearing loss and other general signs of inflammation.

The typical “rheumatoid effusion” is a sterile exudative fluid with low pH (<7.3), low glucose (<60 mg. dL−1) and elevated lactate dehydrogenase (may be >700 IU). It should initially be treated with NSAIDs. Decortication should be reserved in patients with thickened pleura who have symptomatic dyspnoea.

The main mechanism of fibrate drugs is activation of gene transcription factors known as PPARs, particularly PPAR-α, which regulate the expression of genes that control lipoprotein metabolism. There are several consequences of PPAR-α activation, which reduce circulating LDL cholesterol and triglycerides and increase HDL cholesterol.

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

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.

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.

Cystic fibrosis (CF) is a multisystemic, autosomal recessive disorder that predominantly affects infants, children, and young adults. CF is the most common life-limiting genetic disorder in whites, with an incidence of 1 case per 3200-3300 new-borns in the United States.

People with CF can have a variety of symptoms, including:
Very salty-tasting skin
Persistent coughing, at times with phlegm
Frequent lung infections including pneumonia or bronchitis
Wheezing or shortness of breath
Poor growth or weight gain in spite of a good appetite
Frequent greasy, bulky stools or difficulty with bowel movements
Male infertility

Signs of bronchiectasis include the tubular shadows; tram tracks, or horizontally oriented bronchi; and the signet-ring sign, which is a vertically oriented bronchus with a luminal airway diameter that is 1.5 times the diameter of the adjacent pulmonary arterial branch.

Bronchiectasis is characterized by parallel, thick, line markings radiating from hila (line tracks) in cylindrical bronchiectasis. Ring shadows represent dilated thick-wall bronchi seen in longitudinal section or on-end or dilated bronchi in varicose bronchiectasis.

Pseudomonas aeruginosa is the key bacterial agent of cystic fibrosis (CF) lung infections, and the most important pathogen in progressive and severe CF lung disease. This opportunistic pathogen can grow and proliferate in patients, and exposure can occur in hospitals and other healthcare settings.

Haemophilus influenzae is regularly involved in chronic lung infections and acute exacerbations of CF patients

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.

History and CXR are suggestive of tuberculosis. Acid fast bacilli should be seen on microscopy to confirm the diagnosis.

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.

NSAIDs are considered as the first line of treatment for managing pain and stiffness associated with ankylosing spondylitis. Other useful medications include TNF-alpha inhibitors. Other drugs like paracetamol, colchicine, and steroids are not routinely used. Bilateral total hip replacement might be indicated in advanced disease contrary to complicated spinal surgery.

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%)

Any antiarrhythmic drugs can potentially cause arrhythmias. Before starting amiodarone, any electrolyte imbalance including hypokalaemia, hypomagnesemia, or hypocalcaemia should be corrected to prevent any arrhythmias.

Vestibular damage is a neurological side effect of streptomycin.

Streptomycin is an aminoglycoside bactericidal antibiotic. It is used in the treatment of tularaemia and resistant mycobacterial infections.
The most common neurological side-effect is vestibular damage leading to vertigo and vomiting.
Cochlear damage is less frequent and results in deafness.
Other side-effects include rashes, angioneurotic oedema, and nephrotoxicity.

Osteomalacia is a condition due to defective mineralization of osteoid. Occurs as a result of Vitamin D deficiency secondary to poor dietary intake and sun exposure, malabsorption e.g., inflammatory bowel disease and gastrointestinal bypass surgery. Radiological findings include reduced bone mineral density (a non specific finding), inability to radiologically distinguish vertebral body trabeculae (the film appears poor quality), looser pseudo fractures, fissures, or narrow radiolucent lines (these are the characteristic findings). Osteolytic or punched out lesions may be seen with multiple myeloma and bony metastases. Areas of sclerosis may be observed with conditions like osteosclerosis and Paget disease. A Brodie abscess is a subacute osteomyelitis, which may persist for years before progressing to a chronic, frank osteomyelitis.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, comparing two independent samples from the same population.

Current guidelines recommend the use of ambrisentan, Bosentan (recommendation I, level of evidence A) and macitentan (I, B) in patients with PAH and WHO functional class II and III. In WHO functional class IV, the first-line drug is Epoprostenol and the recommendation for Endothelin receptor antagonists is weaker (IIb, C).

β-blockers are the class of drug most often chosen to treat glaucoma, although other medical therapies are available. Systemic absorption of timolol eye drops can cause unsuspected respiratory impairment and exacerbation of asthma. Physicians should be alert to the possibility of respiratory side-effects of topical therapy with β-blockers. Leukotriene antagonists and salbutamol are used in asthma treatment. HRT and ferrous sulphate do not lead to the exacerbation of asthma.

Temporal arteritis is a chronic large- and medium-sized vessel vasculitis that typically involves the temporal arteries. Classical symptoms include temporal headaches, jaw claudication, amaurosis fugax. Physical exam shows scalp tenderness, palpation of the temporal area may demonstrate an absent pulse, knot-like swelling, and vision loss. Lab results reveal an increased erythematous sedimentation rate and C-reactive protein. Temporal artery biopsy confirms the diagnosis. Management approach: high-dose systemic corticosteroids should be promptly administered even before the diagnosis is established. Temporal artery biopsy confirms the diagnosis. Inability to manage this or administer glucocorticoids might lead to development of blindness.

The most likely cause for acute breathlessness is due to papillary muscle rupture which causes mitral regurgitation.

Rasburicase should be given prior to chemotherapy in order to reduce the risk of tumour lysis syndrome (TLS). Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is 5–10 times more soluble than uric acid, hence, renal excretion is more effective.

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.

Burkitt lymphoma is a high-grade B-cell neoplasm. There are two major forms:
1. Endemic (African) form: typically involves maxilla or mandible.
2. Sporadic form: abdominal (e.g. ileocaecal) tumours are the most common form. More common in patients with HIV.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14). The Epstein-Barr virus (EBV) is strongly implicated in development of the African form of Burkitt lymphoma and to a lesser extent, the sporadic form.

Management of the lymphoma is with chemotherapy. This tends to produce a rapid response which may cause TLS.

In patients with polycystic ovarian syndrome (PCOS), FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated for Tanner stage, sex, and age. The LH-to-FSH ratio is usually greater than 3.

Women with PCOS have abnormalities in the metabolism of androgens and oestrogen and in the control of androgen production. PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis.
The major features of PCOS include menstrual dysfunction, anovulation, and signs of hyperandrogenism. Other signs and symptoms of PCOS may include the following:
– Hirsutism
– Infertility
– Obesity and metabolic syndrome
– Diabetes
– Obstructive sleep apnoea

Androgen excess can be tested by measuring total and free testosterone levels or a free androgen index. An elevated free testosterone level is a sensitive indicator of androgen excess. Other androgens, such as dehydroepiandrosterone sulphate (DHEA-S), may be normal or slightly above the normal range in patients with polycystic ovarian syndrome (PCOS). Levels of sex hormone-binding globulin (SHBG) are usually low in patients with PCOS.

Some women with PCOS have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one-third of women with PCOS who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by 30 years of age.

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.