Reverse transcription polymerase chain reaction is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is primarily used to measure the amount of a specific RNA. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections.

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. There is poor genotype:phenotype correlation. Within a tissue or cell there can be different mitochondrial populations (this is known as heteroplasmy).
Examples of mitochondrial diseases include:
– Leber’s optic atrophy
– MELAS syndrome (mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes)
– MERRF syndrome (myoclonus epilepsy with ragged-red fibres)
– Kearns-Sayre syndrome (more severe syndromic variant of chronic progressive external ophthalmoplegia, onset in patients < 20 years old)

Ataxic telangiectasia is an inherited combined immunodeficiency disorder that is characterised by cerebellar ataxia and telangiectasia as seen in this child, as well as frequent infections as noted in this child’s history. The other differentials would not present with this clinical picture:

Friedreich’s ataxia and Infantile-onset spinocerebellar ataxia do not present with immune problems, whereas Cerebral palsy and Di-George Syndrome do not present with ataxia.

This man has gingivostomatitis, a characteristic feature of primary herpes simplex virus infection. Herpetic gingivostomatitis is often the initial presentation during the first (primary) herpes simplex infection. It is of greater severity than herpes labialis (cold sores) which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.
Primary herpetic gingivostomatitis (PHGS) is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings.

Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses.

The wedged hepatic venous pressure is a reflection of the portal venous pressure in the hepatic sinusoids. This is a fact to remember. Here is a great but concise explanation as to why: https://www.ncbi.nlm.nih.gov/pubmed/18695309

The patient has Acromegaly.
Acromegaly is a chronic disorder characterised by growth hormone (GH) hypersecretion, predominantly caused by a pituitary adenoma.

Random GH level testing is not recommended for diagnosis given the pulsatile nature of secretion. Stress, physical exercise, acute critical illness and fasting state can cause a physiological higher peak in GH secretion.

Pegvisomant is a US Food and Drug Administration-approved treatment for use after surgery. In a global non-interventional safety surveillance study, pegvisomant normalised IGF-1 in 67.5% of patients after 5 years (most likely due to lack of dose-up titration), and also improved clinical symptoms. Pegvisomant improves insulin sensitivity, and long-term follow-up showed significantly decreased fasting glucose over time, while the first-generation SRL only have a marginal clinical impact on glucose homeostasis in acromegaly. Pegvisomant does not have any direct anti-proliferative effects on pituitary tumour cells, but tumour growth is rare overall.

Giant Cell Arteritis (Temporal Arteritis) is the most probable diagnosis. GCA should always be considered in the differential diagnosis of a new-onset headache in patients 50 years of age or older with an elevated erythrocyte sedimentation rate. Temporal artery biopsy remains the criterion standard for diagnosis of this granulomatous vasculitis. High-dose corticosteroid therapy is the universally accepted treatment.

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.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect nearly any organ system: the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin. The histopathological features are similar across organs, regardless of the site. IgG4-RD is analogous to sarcoidosis, in which diverse organ manifestations are linked by similar histopathological characteristics. Raised concentrations of IgG4 in tissue and serum can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.

Some IgG4-RDs are:
1. Autoimmune pancreatitis
2. Riedel’s Thyroiditis
3. Mediastinal and Retroperitoneal Fibrosis
4. Periaortitis/periarteritis/Inflammatory aortic aneurysm
5. Kuttner Tumour (submandibular glands)
6. IgG4-related Mikulicz disease (lacrimal, parotid, and submandibular glands)