Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

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.

Scleritis, or inflammation of the sclera, is usually painful whereas episcleritis is not painful.

Keratoconjunctivitis sicca is usually bilateral and associated more with dryness, burning and itching.

In such a clinical scenario, NICE guidelines support initiating treatment with bisphosphonates without waiting for a DEXA scan.

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.

Management:
Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
Alendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.
Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.
Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

From the given history the patient has NYHA grade III heart failure. He can be safely started on an ACE inhibitor as his serum potassium was towards the lower limit. As there an impairment of renal function, his urea, creatinine and serum electrolytes should be closely monitored after commencing an ACE inhibitor. Adding atenolol will not have any clinical benefit. Increasing the digoxin dose is not needed as the patient is in sinus rhythm. Increasing furosemide will only have symptomatic relief.

With biliary obstructive symptoms in a patient with ulcerative colitis, one should immediately think of primary sclerosing cholangitis (PSC). PSC is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic ducts. The best diagnostic test for PSC is ERCP. ANCA antibiotics may be positive, but not the best test to DIAGNOSE THE CONDITION. The same can be said of serum transaminase levels– they will be abnormal but nonspecific. While a liver ultrasound may be helpful, it is not the best test. Liver biopsy would be used to stage the PSC later.

Hemiballismus or hemiballism in its unilateral form is a very rare movement disorder. It is a type of chorea caused in most cases by a decrease in activity of the subthalamic nucleus of the basal ganglia, resulting in the appearance of flailing, ballistic, undesired movements of the limbs. Symptoms may decrease while the patient is asleep. Antidopaminergic agents (e.g. Haloperidol) are the mainstay of treatment.

Again, remember the Hepatitis B serologies: In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have +HBsAg, + anti-HBc, + IgM anti-HBc, and negative anti-HBs. In immunity due to natural infection, you have negative HBsAg, + anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. IN THIS CASE, the person is HBsAg+ for 6 months and everything else is negative, normal transaminase. They do not need antiviral therapy, but their serology should be monitored serially. There would be no reason to do a liver biopsy.

Blue tinge of vision/cyanopsia is caused due to the intake of sildenafil citrate.

Sildenafil citrate (Viagra) is the first oral drug to be widely approved for the treatment of erectile dysfunction.
It is a potent and selective inhibitor of type-V phosphodiesterase, the primary form of the enzyme found in human penile erectile tissue, thereby preventing the breakdown of cyclic guanosine monophosphate (cGMP), the intracellular second messenger of nitric oxide.

Uses:
It is used for the treatment of erectile dysfunction, idiopathic pulmonary hypertension, premature ejaculation, high altitude illness, penile rehabilitation after radical prostatectomy, angina pectoris, and lower urinary tract symptoms.

Adverse effects:
Mild headache, flushing, dyspepsia, cyanopsia, back pain, and myalgias – due to a high concentration of PDE11 enzyme in skeletal muscle, which shows significant cross-reactivity with the use of tadalafil.
It can also cause hypotension, dizziness, and rhinitis.

Note: Xanthopsia (yellow-green vision) may occur secondary to treatment with digoxin.

Prostate cancer is the most common primary tumour that metastasises to the bone.

Most common tumours causing bone metastasis (in descending order):
1. Prostate (32%)
2. Breast (22%)
3. Kidneys (16%)
4. Lungs
5. Thyroid

Most common sites of bone metastasis (in descending order):
1. Spine
2. Pelvis
3. Ribs
4. Skull
5. Long bones

Prednisolone although has many undesirable side effects it may be considered relatively safe compared to the drugs that are provided here. Prolonged treatment with sulphasalazine may depress semen quality and cause irreversible infertility. Methotrexate and leflunomide both inhibit purine/pyrimidine synthesis (the former by inhibiting folate metabolism) and are contraindicated in pregnancy or while trying to conceive. In males, a temporary or permanent decrease in sperm count may occur with cyclophosphamide. Because the recovery of fertility after cyclophosphamide therapy is variable, sperm banking should be considered before treatment is begun.

Post-primary pulmonary tuberculosis is a chronic disease commonly caused by either endogenous reactivation of a latent infection or exogenous re-infection by Mycobacterium tuberculosis.
Post-primary pulmonary tuberculosis (also called reactivation tuberculosis) develops in 5%–20% of patients infected with M. tuberculosis.

Found mainly in adults, this form of tuberculosis arises from the reactivation of bacilli that lay dormant within a fibrotic area of the lung. In adults, reinfection with a strain of mycobacterium that differs from that which caused the primary infection is also possible. Predisposing factors include immunosuppression, diabetes, malnutrition and alcoholism.

Infliximab is a monoclonal antibody against tumour necrosis factor α (TNF-α). It is FDA approved for many autoimmune conditions, including rheumatoid arthritis and Crohn’s disease. One of the many known side effects of infliximab therapy is reactivation of latent tuberculosis (TB). Because of the resemblances in clinical and radiological features, tubercular lesions in the lung may mimic malignancy. TB accounts for 27% of all infections initially presumed to be lung cancer on imaging studies.

Cavitating pneumonia is a complication that can occur with a severe necrotizing pneumonia and in some publications it is used synonymously with the latter term. It is a rare complication in both children and adults. Albeit rare, cavitation is most commonly caused by Streptococcus pneumoniae, and less frequently Aspergillus spp., Legionella spp. and Staphylococcus aureus.

In children, cavitation is associated with severe illness, although cases usually resolve without surgical intervention, and long-term follow-up radiography shows clear lungs without pulmonary sequelae
Although the absolute cavitary rate may not be known, according to one series, necrotizing changes were seen in up to 6.6% of adults with pneumococcal pneumonia. Klebsiella pneumoniae is another organism that is known to cause cavitation.

Causative agents:
Mycobacterium tuberculosis
Klebsiella pneumoniae
Streptococcus pneumoniae
Staphylococcus aureus

Enterococcus faecalis was not found to be a causative agent.

Once thyrotoxicosis has been identified by laboratory values, the thyroid radio-iodine uptake and scan may be used to help distinguish the underlying aetiology. Thyroid radioiodine uptake is raised in Graves’ disease. It may be normal or raised in patients with a toxic multinodular goitre. It is very low or undetectable in thyrotoxicosis resulting from exogenous administration of thyroid hormone or the thyrotoxic phase of thyroiditis.

This patient presents with a combination of akinetic rigid syndrome, cerebellar signs and the suggestion of autonomic features. This is most indicative of a diagnosis of multiple system atrophy.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia.

Permanent pacing is not indicated as the bradycardia is reversible. Temporary pacing is the definite treatment. Isoprenaline can be used until temporary pacing is available.

DIAGNOSIS:
A consensus definition for hemodynamically significant PDA is lacking. The diagnosis is often suspected clinically, when an infant demonstrates signs of excessive shunting from the arterial to pulmonary circulation. Continuous or a systolic murmur; note, a “silent” PDA may also occur when the ductus shunt is large enough that nonturbulent flow fails to generate a detectible murmur.
A low diastolic blood pressure (due to runoff into the ductus during diastole, more frequent in the most premature infants).
A wide pulse pressure (due to ductus runoff or steal)Hypotension (especially in the most premature infants)
Bounding pulses
Increased serum creatinine concentration or oliguria
Hepatomegaly

Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index
– Assays for thyrotropin-receptor antibodies (particularly TSIs) almost always are positive.
– Detection of TSIs is diagnostic for Graves disease.
– Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroid peroxidase antibodies, are usually present.
– Other autoantibodies that may be present include thyrotropin receptor-blocking antibodies and anti–sodium-iodide symporter antibody.
The presence of these antibodies supports the diagnosis of autoimmune thyroid disease.
– The radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland.

According to the updated GMC guidelines, patient safety is more important than anything else, thus the correct thing to do is inform your colleague’s employing body.

Allergic bronchopulmonary aspergillosis (ABPA) is a form of lung disease that occurs in some people who are allergic to Aspergillus. With ABPA, this allergic reaction causes the immune system to overreact to Aspergillus leading to lung inflammation. ABPA causes bronchospasm (tightening of airway muscles) and mucus build-up resulting in coughing, breathing difficulty and airway obstruction.

Blood tests are used to look for signs of an allergic reaction. This includes evaluating your immunoglobulin E (IgE) level. This level is increased with any type of allergy. Many people with asthma have higher than normal IgE levels. In ABPA however, the IgE level is extremely high (more than 1000 ng/ml or 417 IU/ml). In addition to total IgE, all patients with ABPA have high levels of IgE that is specific to Aspergillus. A blood test can be done to measure specific IgE to Aspergillus. A blood or skin test for IgE antibodies to Aspergillus can be done to see if a person is sensitized (allergic) to this fungus. If these skin tests are negative (i.e. does not show a skin reaction) to Aspergillus fumigatus, the person usually does not have ABPA.
Therefore, there should be no change in medication since this patient does not have ABPA.

After renal transplant, asymptomatic patients can still have graft dysfunction as an early complication, with rising serum creatinine; therefore, urine and blood cultures should be ordered first. This should be followed by measuring the Tacrolimus levels, as this drug can be directly nephrotoxic. Next, a Doppler ultrasound of the transplant site should be ordered, to check for any obstructions or occlusions.

Hypogammaglobulinemia is a complication of chronic lymphocytic leukaemia (CLL) that leads to recurrent infections.

CLL is a type of cancer caused by monoclonal proliferation of well-differentiated lymphocytes, typically B cells (99%). Onset of the disease is usually asymptomatic and later constitutes anorexia, weight loss, bleeding, and recurrent infections. Lymphadenopathy is more marked in CLL than in chronic myelogenous leukaemia (CML).

Investigations to diagnose CLL include blood film and immunophenotyping. Smudge cells (also known as smear cells) seen on the blood film point towards CLL. Complications of the disease include hypogammaglobulinemia leading to recurrent infections, autoimmune haemolytic anaemia in 10–15% of the patients, and transformation to high-grade lymphoma (Richter’s transformation).

The principal mechanism of action of taxanes (e.g. docetaxel) is the prevention of microtubule disassembly.

Other aforementioned options are ruled out because:

1. Doxorubicin: stabilizes DNA topoisomerase II complex and inhibits DNA and RNA synthesis.

2. Vincristine, vinblastine: inhibits formation of microtubules.

3. Cisplatin: causes cross-linking in DNA.

The key to this question is anti-smooth muscle antibodies. This is a finding of autoimmune hepatitis, which can be seen in type I diabetics. This also fits with her clinical picture. If you know these two facts, you should get every question correct regarding autoimmune hepatitis. Liver function testing is the best answer, then and should be elevated to indicate inflammation of the liver. Hepatic US, CK, thyroid function testing, short synacthen test are not helpful in the diagnosis of autoimmune hepatitis.

Osteoarthritis (OA) is a disabling joint disease characterized by a noninflammatory degeneration of the joint complex (articular cartilage, subchondral bone, and synovium) that occurs with old age or from overuse. It mainly affects the weight-bearing and high-use joints, such as the hip, knee, hands, and vertebrae. Despite the widespread view that OA is a condition caused exclusively by degenerative “wear and tear” of the joints, newer research indicates a significant heterogeneity of causation, including pre-existing peculiarities of joint anatomy, genetics, local inflammation, mechanical forces, and biochemical processes that are affected by proinflammatory mediators and proteases. Major risk factors include advanced age, obesity, previous injuries, and asymmetrically stressed joints. In early-stage osteoarthritis, patients may complain of reduced range of motion, joint-stiffness, and pain that is aggravated with heavy use. As the disease advances, nagging pain may also occur during the night or at rest. Diagnosis is predominantly based on clinical and radiological findings. Classic radiographic features of OA do not necessarily correlate with clinical symptoms and appearance. RA involves proximal interphalangeal joints not distal. Gout occurs as a result of overproduction or underexcretion of uric acid and frequently involves first toe. Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory and mood issues.

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors.

A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. Tumor suppressor genes can be grouped into categories including caretaker genes, gatekeeper genes, and landscaper genes; the classification schemes are continually evolving.
Examples include:
Gene Associated cancers
p53 Common to many cancers, Li-Fraumeni syndrome
APC Colorectal cancer
BRCA1 Breast and ovarian cancer
BRCA2 Breast and ovarian cancer
NF1 Neurofibromatosis
Rb Retinoblastoma
WT1 Wilm’s tumour

Infection with Klebsiella organisms occurs in the lungs, where they cause destructive changes. Necrosis, inflammation, and haemorrhage occur within lung tissue, sometimes producing a thick, bloody, mucoid sputum described as currant jelly sputum.
The illness typically affects middle-aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease. An increased tendency exists toward abscess formation, cavitation, empyema, and pleural adhesions.

This case presents with sensorimotor neuropathy secondary to his DM. The progression of the neuropathy, known dying-back neuropathy, is a distal axonopathy or axonal degeneration as where the sensorimotor loss begins distally and travels proximally.

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.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group). The relative risk is mistaken by some, with the odds ratio and absolute risk. Relative risk is the ratio of the probability of an event occurring with an exposure versus the probability of the event occurring without the exposure. Thus to calculate the relative risk, we must know the exposure status of all individuals (either exposed or not exposed). This implies that relative risk is only appropriate for cases where the exposure status and incidence of disease can be accurately determined such as prospective cohort studies.