Cyclophosphamide is a cytotoxic alkylating agent that acts by causing cross-linking of DNA strands. Its major adverse effects include haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma.

Cardiomyopathy is caused by doxorubicin and ototoxicity is caused by cisplatin. Alopecia and weight gain are associated with a variety of chemotherapeutic agents especially those that treat breast cancers (e.g. paclitaxel).

Posterior vitreous detachment is thought to occur in up to 50-75% of the population over 65 years and is the most likely diagnosis here. Patients should be reviewed by an ophthalmologist to assess the risk of progressing to retinal detachment. Flashes of light (photopsia) occur in the peripheral field of vision while floaters often occur on the temporal side of the central vision.

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. Dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum)

Scabies is due to an infestation of Sarcoptes scabiei and most commonly presents with these symptoms. The organism resides in burrows in a pattern specifically affecting the interdigital spaces and the skin folds of the arms and legs. The infection spreads from one person to another, especially in populated communities, through close contact.
Henoch-Schönlein purpura is a type of vascular inflammation.
Psoriasis rash is characterised by scaly plaques affecting the extensor surfaces of the body. Pemphigus vulgaris and bullous pemphigoid both are bullous disorders of the skin. They may present as crusted, weeping, diffuse lesions and there may be involvement in other sites; erosions in the mouth are typically involved in pemphigus vulgaris. Bullous pemphigoid involves the flexural areas and may be associated with a new medication.

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

Good prognosis of chronic lymphocytic leukaemia (CLL) is associated with deletion of the long arm of chromosome 13 (del 13q). This is the most common abnormality, seen in around 50% of all CLL patients. Poor prognosis of the disease is related to deletion of part of the short arm of chromosome 17 (del 17p). This is seen in around 5-10% of the patients suffering from CLL.

Poor prognostic factors of CLL include:
1. Male sex
2. Age >70 years
3. Lymphocyte count >50
4. Prolymphocytes comprising more than 10% of blood lymphocytes
5. Lymphocyte doubling time <12 months
6. Raised LDH
7. CD38 expression positive

The most probable cause for diarrhoea is pseudomembranous colitis which is caused by Clostridium difficile. Pseudomembranous colitis is an inflammatory disease of the colon where the antibiotic-induced change in the balance of normal gut flora allows overgrowth of C difficile. Any antibiotic can cause this but the chances are higher with ampicillin, clindamycin, fluoroquinolones, and cephalosporins.

Osteopenia is an early sign of bone weakening that is less severe than osteoporosis.
The numerical result of the bone density test is quantified as a T score. The lower the T score, the lower the bone density. T scores greater than -1.0 are considered normal and indicate healthy bone. T scores between -1.0 and -2.5 indicate osteopenia. T scores lower than -2.5 indicate osteoporosis.
DEXA also provides the patient’s Z-score, which reflects a value compared with that of person matched for age and sex.
Z-score values of –2.0 SD or lower are defined as below the expected range for age and those above –2.0 SD as within the expected range for age.

Erythropoietin (EPO) is used to distinguish between primary and secondary polycythaemia. Secondary polycythaemia can be caused by tumours in the kidney that may secrete EPO or EPO-like proteins.

Vasopressin, also called antidiuretic hormone (ADH), regulates the tonicity of body fluids. It is released from the posterior pituitary in response to hypertonicity and promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels.. An incidental consequence of this renal reabsorption of water is concentrated urine and reduced urine volume. In high concentrations may also raise blood pressure by inducing moderate vasoconstriction.

The question describes an alcohol abusing man with chronic epigastric discomfort, radiating into his back, worse with meals, and foul-smelling stools, weight loss, as well as chronic nausea. This is likely, thus chronic pancreatitis due to alcohol abuse. Hepatomegaly and peripheral neuropathy secondary to anaemia support the diagnosis of long term alcohol abuse. Bacterial overgrowth may present with diarrhoea and is a less likely diagnosis than pancreatitis. Celiac disease is a less likely diagnosis than pancreatitis, and you would also expect mention of diarrhoea. VIPoma would also likely present with diarrhoea. Cecal carcinoma would more than likely present with blood in the stool.

The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.
DiGeorge’s syndrome (DGS) is a developmental abnormality affecting the thymus. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia).

Loss of vision after consumption of antifreeze is a characteristic presentation of methanol poisoning.

Pathophysiology of methanol toxicity:
When ingested, methanol is absorbed rapidly via the gastrointestinal tract in less than 10 minutes. Methanol is not protein-bound and is absorbed directly into the total body water compartment.
Metabolism occurs mainly in the liver through serial oxidation via alcohol dehydrogenase and aldehyde dehydrogenase but begins with alcohol dehydrogenase present in the gastric mucosa.
Alcohol dehydrogenase oxidizes methanol to formaldehyde, and aldehyde dehydrogenase subsequently oxidizes formaldehyde to formic acid.
Formic acid is the primary toxic metabolite that accounts for the associated anion gap metabolic acidosis and end-organ damage.

Clinical presentation:
Patients who present within the first 12 to 24 hours following ingestion may appear normal, and this is described as the latent period.
Nausea, vomiting, and abdominal pain subsequently ensue, followed by CNS depression and hyperventilation due to metabolic acidosis.
Ocular symptoms associated with retinal toxicity are often evident in the form of blurry vision, decreased visual acuity, photophobia, and “halo vision.”

Treatment:
Treatment options for methanol toxicity include supportive care, fomepizole (Antizole, 4-Methylpyrazole or 4MP), ethanol, dialysis, and folate.

The C8 nerve forms part of the radial and ulnar nerves via the brachial plexus, and therefore has motor and sensory function in the upper limb. It originates from the spinal column from below the cervical vertebra 7 (C7).
The C8 nerve receives sensory afferents from the C8 dermatome. This consists of all the skin on the little finger, and continuing up slightly past the wrist on the palmar and dorsal aspects of the hand and forearm.
The other options available correspond to the C6 or C7 roots and these are unaffected as evidenced by normal elbow flexion and thumb sensation (C6) and normal sensation over the middle finger (C7). Elbow extension is weak as it has roots from both C7 and C8 and so cannot be used alone to decide between the two levels clinically.
The C8 nerve contributes to the motor innervation of many of the muscles in the trunk and upper limb. Its primary function is the flexion of the fingers, and this is used as the clinical test for C8 integrity, in conjunction with the finger jerk reflex.

Trunk:
– Pectoralis major – Medial and lateral pectoral nerves (C5, C6, C7, C8, T1)
– Pectoralis minor – Medial pectoral nerve (C5, C6, C7,C8, T1)
– Latissimus dorsi – Thoracodorsal nerve (C6, C7, C8)
Upper arm:
– Triceps brachii – Radial nerve (C6, C7,C8)
Forearm
– Flexor carpi ulnaris – Ulnar nerve (C7, C8, T1)
– Palmaris longus – Median nerve (C7,C8)
– Flexor digitorum superficialis – Median nerve (C8, T1)
– Flexor digitorum profundus – Median and Ulnar nerves (C8, T1)
– Flexor pollicis longus – Median nerve (C7,C8)
– Pronator quadratus – Median nerve (C7,C8)
– Extensor carpi radialis brevis – Deep branch of the radial nerve (C7,C8)
– Extensor digitorum – Posterior interosseous nerve (C7,C8)
– Extensor digiti minimi – Posterior interosseous nerve (C7,C8)
– Extensor carpi ulnaris – Posterior interosseous nerve (C7,C8)
– Anconeus – Radial nerve (C6, C7,C8)
– Abductor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor pollicis brevis – Posterior interosseous nerve (C7,C8)
– Extensor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor indicis – Posterior interosseous nerve (C7,C8)
Hand
– Palmaris brevis – Superficial branch of ulnar nerve (C8, T1)
– Dorsal interossei – Deep branch of ulnar nerve (C8, T1)
– Palmar interossei – Deep branch of ulnar nerve (C8, T1)
– Adductor pollicis – Deep branch of ulnar nerve (C8, T1)
– Lumbricals – Deep branch of ulnar, Digital branches of median nerve
– Opponens pollicis – Recurrent branch of median nerve (C8, T1)
– Abductor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Flexor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Opponens digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Abductor digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Flexor digiti minimi brevis – Deep branch of ulnar nerve (C8, T1)

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.

Delivery of ubiquitinated substrates to the proteasome.
Ubiquitinated proteins are delivered to the proteasome by various routes and the complete picture of how these pathways fit together has yet to emerge, reviewed in. Some substrates bind directly to the proteasome by interacting with the 19S regulatory particle subunits Rpn1028 or Rpn1329, and probably Rpt530. Alternatively, ubiquitinated substrates can be brought to the proteasome by adaptors that bind both the proteasome and the ubiquitin chain on the substrate to deliver it for degradation.

The patient presents with worsened renal condition from the last consultation when he was started on enalapril (an ACE inhibitor) so this medication should be stopped. Because there is also no fluid overload; furosemide, a diuretic, should also be stopped.

B-type natriuretic peptide (BNP) is secreted mainly from the left ventricle and it is secreted as a response to stretching caused by increased ventricular blood volume.

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.

Cryoglobulinemia may be caused by paraprotein bands such as those seen in Waldenström’s macroglobulinemia and multiple myeloma (MM). Meltzer’s triad of arthralgia, weakness, and palpable purpura are common to all types of cryoglobulinemia—as are membranoproliferative glomerulonephritis and low C4 levels. Raynaud’s phenomenon, however, occurs only in type 1 cryoglobulinemia, and its presence can be helpful in ascertaining the underlying cause.

Cryoglobulinemia is a condition in which the blood contains large amounts of pathological cold-sensitive antibodies called cryoglobulins—proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. One-third of the cases are idiopathic.

There are three types of cryoglobulinemia:
1. Type I (25%):
Monoclonal—IgG or IgM
Associated with multiple myeloma (MM), Waldenström’s macroglobulinemia

2. Type II (25%):
Mixed monoclonal and polyclonal—usually with rheumatoid factor (RF)
Associated with hepatitis C, rheumatoid arthritis (RA), Sjogren’s syndrome

3. Type III (50%):
Polyclonal—usually with RF
Associated with rheumatoid arthritis, Sjogren’s syndrome

Investigation results for cryoglobulinemia show low complement (especially C4) and high ESR. Treatment options include immunosuppression and plasmapheresis.