Guillain-Barre syndrome is an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni). Characteristic features include progressive weakness of all four limbs, and it is classically ascending, affecting the lower extremities first. Sensory symptoms tend to be mild.

Functional neurological syndrome can be discounted due to presence of hard neurological signs. Multiple sclerosis can be excluded because of the presence of lower motor neuron signs and absence of upper motor neuron signs. Chronic inflammatory demyelinating polyneuropathy is the chronic form of Guillain-Barre syndrome.

Mitochondrial DNA (mtDNA) is a double-stranded molecule of 16.6 kb (Figure 1, lower panel). The two strands of mtDNA differ in their base composition, with one being rich in guanines, making it possible to separate a heavy (H) and a light (L) strand by density centrifugation in alkaline CsCl2 gradients.

Varicose eczema is a common problem, particularly in elderly patients due to stasis or blood pooling from insufficient venous return; the alternative name of varicose eczema comes from a common cause of this being varicose veins. It is often mistaken for cellulitis, but cellulitis is rarely bilateral and is painful rather than itchy.

Normal distribution describes the spread of many biological and clinical measurements. Usually, 68.3% lies within 1 standard deviation (SD) of the mean, 95.4% lies within 2 SD of the mean and 99.7% lies within 3 SD of the mean.

Whilst asthma and COPD are different diseases they cause similar symptoms, which can present a challenge in identifying which of the two diseases a patient is suffering from. COPD causes chronic symptoms and narrowed airways which do not respond to treatment to open them up. In the case of asthma the constriction of the airways through inflammation tends to come and go and treatment to reduce inflammation and to open up the airways usually works well.

COPD is more likely than asthma to cause a chronic cough with phlegm and is rare before the age of 35 whilst asthma is common in under-35s. Disturbed sleep caused by breathlessness and wheeze is more likely in cases of asthma, as is a history of allergies, eczema and hay fever. Differentiating between COPD and asthma requires a history of both symptoms and spirometry. The spirometry history should include post bronchodilator measurements, the degree of reversibility and, ideally, home monitoring which gives a history of diurnal variation.

Airflow Obstruction: Both asthma and COPD are characterised by airflow obstruction. Airflow obstruction is defined as a reduced FEV1 and a reduced FEV1/FVC ratio, such that FEV1 is less than 80% of that predicted, and FEV1/FVC is less than 0.7.

These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

COPD: COPD is a chronic, slowly progressive disorder characterised by airflow obstruction (reduced FEV1 and FEV1/VC ratio) that does not change markedly over several months. The airflow obstruction is not fully reversible.

Spirometry COPD Asthma
VC Reduced Nearly normal
FEV1 Reduced Reduced in attack
FVC (or FEV6) Reduced Nearly normal
FEV1 Ratio
(of VC/FVC/FEV6) Reduced in attack

This man has a low FEV1 and FVC. His diffusions capacity is also low despite having a normal total lung capacity. These values confirm a diagnosis of COPD.

Spinal cord hemisection, also known as Brown-Sequard syndrome, is associated with symptoms affecting one spinothalamic and one corticospinal tract. Symptoms include ipsilateral paralysis, loss of vibration and position sense, and hyperreflexia below the level of the lesion. Contralateral loss of pain and temperature sensation is also seen, usually beginning 2-3 segments below the level of the lesion.

The chronic asymptomatic carrier state is thought to be why there is continued appearance of the bacterium in human populations. As shedding of the organism is intermittent and sometimes at low levels, methods to detect it have been limited. The Salmonella typhi may be cultured from intestinal secretions, faeces or urine in chronic carriers and is recommended to confirm the diagnosis. Vi agglutination test can also be high in normal people in areas with typhoid endemic. Full blood count or blood culture would not be helpful to determine carrier status. Widal antigen test is unable to differentiate carriers from people with a hx of prior infection.

In rheumatoid arthritis (RA), clinical symptoms of joint stiffness, pain, and functional disability are commonly most severe in the early morning. These symptoms closely follow the circadian rhythm of the pro-inflammatory cytokine, interleukin (IL)-6. In RA, the increase in nocturnal anti-inflammatory cortisol secretion is insufficient to suppress ongoing inflammation, resulting in the morning symptoms characteristic of RA. Established diagnostic criteria for RA include prolonged morning stiffness that could last up to an hour. Loss of joint mobility, pain, malaise and swelling of finger joints are features that are not specific to rheumatoid arthritis, and are found in many other conditions.

Carbon monoxide (CO) poisoning:
It is considered as the great imitator of other diseases as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Clinical features of carbon monoxide toxicity:
Headache: 90% of cases (most common clinical feature)
Nausea and vomiting: 50%
Vertigo: 50%
Confusion: 30%
Subjective weakness: 20%
Severe toxicity: ‘pink’ skin and mucosa, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
Cherry red skin is a sign of severe toxicity and is usually a post-mortem finding.
Management
• 100% oxygen
• Hyperbaric oxygen therapy (HBOT)

The use of Hyperbaric oxygen therapy (HBOT) for treatment mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

Cataract is a condition characterized by clouding of the lens of the eye. This condition most frequently occurs due to age-related degenerative processes in the lens, but can also be associated with ocular trauma, metabolic disorders, side-effects of drugs, or congenital infections. The clouding causes distortion of light, as it passes through the lens, resulting in visual impairment and glare. Initially, a cataract presents discretely and may even go unnoticed, but the visual impairment worsens as the cataract grows larger.

Diagnosis is typically established on the basis of a thorough history and direct visualization of the cataract (by means of slit-lamp microscopy). Surgery is indicated with significant visual impairment and involves lens extraction and implantation of an artificial lens. Untreated cataracts eventually lead to complete blindness.

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.

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

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

Erythromycin is a bacteriostatic antibiotic. This means it stops the further growth of bacteria rather than directly destroying it. This is achieved by inhibiting protein synthesis. Erythromycin binds to the 23S ribosomal RNA molecule in the 50S subunit of the bacterial ribosome. This causes a blockage in the exiting of the peptide chain that is growing. Given that humans have 40S and 60S subunits, and do not have 50S subunits, erythromycin does not affect protein synthesis in human tissues.

Idiopathic pulmonary fibrosis (IPF) is a condition in which the lungs become scarred and breathing becomes increasingly difficult.
The most common signs and symptoms of idiopathic pulmonary fibrosis are shortness of breath and a persistent dry, hacking cough. Many affected individuals also experience a loss of appetite and gradual weight loss.

The clinical findings of IPF are bibasilar reticular abnormalities, ground glass opacities, or diffuse nodular lesions on high-resolution computed tomography and abnormal pulmonary function studies that include evidence of restriction (reduced VC with an increase in FEV1/FVC ratio) and/or impaired gas exchange (increased P(A-a)O2 with rest or exercise or decreased diffusion capacity of the lung for carbon monoxide [DLCO]).

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.

Angioid retinal streaks are seen on fundoscopy as irregular dark red streaks radiating from the optic nerve head. They are caused by degeneration, calcification and breaks in Bruch’s membrane. They are typically associated with Paget’s disease.

Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.
Thus, ethanol’s inhibitory effect helps to explain the increased diuresis experienced during intoxicated states as well as increased free water loss; without appropriate ADH secretion, more water is excreted by the kidneys.

Nausea associated with hangovers is mainly due to vagal stimulation to the vomiting centre.
Following a particularly severe episode of alcohol excess, people may experience tremors due to increased glutamate production by neurons to compensate for the previous inhibition by ethanol.

Management of alcoholism:
Nutritional support:
– Alcoholic patients should receive oral thiamine if their ‘diet may be deficient’.
Pharmacological management:
– Benzodiazepines for acute withdrawal
– Disulfiram promotes abstinence – alcohol intake causes a severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis.
– Acamprosate reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo-controlled trials.

Beef liver is one of the best sources of folic acid, amongst others like green vegetables and nuts.

The patient has Cushing syndrome suggested by the elevated 24hr urine free cortisol. Hence, the mass is most probably a cortisol secreting adenoma.

The classic triad of symptoms in patients with aortic stenosis is chest pain, heart failure and syncope. Pulsus parvus et tardus, pulsus alternans, hyperdynamic left ventricle, reversed splitting of the S2, prominent S4 and systolic murmur are some of the common findings of aortic stenosis. A calcified aortic valve is found in almost all adults with hemodynamically significant aortic stenosis.

The clinical picture points to Lambert– Eaton myasthenic syndrome (LEMS) which often presents with weakness of the arms and legs. In LEMS, antibodies against voltage-gated calcium channels (VGCC) decrease the amount of calcium that can enter the nerve ending, causing autonomic symptoms like dry mouth and slurring of speech, as seen in this patient.

You may treat chickenpox with acyclovir if it is commenced within the first 24 hours of the rash’s appearance. Erythromycin, doxycycline, and ampicillin would not help because it’s a viral infection (Varicella) not a bacterial infection.

RET (rearranged during transfection) is a receptor tyrosine kinase involved in the development of neural crest derived cell lineages, kidney, and male germ cells. Different human cancers, including papillary and medullary thyroid carcinomas, lung adenocarcinomas, and myeloproliferative disorders display gain-of-function mutations in RET.
In over 90% of cases, MEN2 syndromes are due to germline missense mutations of the RET gene.
Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumours, and pheochromocytoma.

The power of a test is defined as 1 − the probability of Type II error. The Type II error is concluding at no difference (the null is not rejected) when in fact there is a difference, and its probability is named β. Therefore, the power of a study reflects the probability of detecting a difference when this difference exists. It is also very important to medical research that studies are planned with an adequate power so that meaningful conclusions can be issued if no statistical difference has been shown between the treatments compared. More power means less risk for Type II errors and more chances to detect a difference when it exists.

Pneumothorax is defined as air in the pleural space and may be classified as spontaneous, traumatic or iatrogenic. Primary spontaneous pneumothorax occurs in patients without clinically apparent lung disease.
Primary pneumothorax has an incidence of 18-28 per 100,000 per year for men and 1.2-6 per 100,000 per year for women. Most patients present with ipsilateral pleuritic chest pain and acute shortness of breath. Shortness of breath is largely dependent on the size of the pneumothorax and whether there is underlying chronic lung disease.

Young patients may have chest pain only. Most episodes of pneumothorax occur at rest. Symptoms may resolve within 24 hours in patients with primary spontaneous pneumothorax. The diagnosis of a pneumothorax is confirmed by finding a visceral pleural line displaced from the chest wall, without distal lung markings, on a posterior-anterior chest radiograph.

Breathless patients should not be left without intervention regardless of the size of pneumothorax. If there is a rim of air >2cm on the chest X-ray, this should be aspirated.
Aspiration is successful in approximately 70 per cent of patients; the patient may be discharged subsequently. A further attempt at aspiration is recommended if the patient remains symptomatic and a volume of less than 2.5 litres has been aspirated on the first attempt.

If unsuccessful, an intercostal drain is inserted. This may be removed after 24 hours after full re-expansion or cessation of air leak without clamping and discharge may be considered.

Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.

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.

Thyroid storm, also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis.
Patients with thyroid storm should be treated in an ICU setting for close monitoring of vital signs and for access to invasive monitoring and inotropic support, if necessary.
– Supportive measures
If needed, immediately provide supplemental oxygen, ventilatory support, and intravenous fluids. Dextrose solutions are the preferred intravenous fluids to cope with continuously high metabolic demand.
– Correct electrolyte abnormalities.
– Treat cardiac arrhythmia, if necessary.
– Aggressively control hyperthermia by applying ice packs and cooling blankets and by administering acetaminophen (15 mg/kg orally or rectally every 4 hours).
– Antiadrenergic drugs.
– Thionamides: Correct the hyperthyroid state. Administer antithyroid medications to block further synthesis of thyroid hormones (THs).
High-dose propylthiouracil (PTU) or methimazole may be used for treatment of thyroid storm.
– Administer glucocorticoids to decrease peripheral conversion of T4 to T3. This may also be useful in preventing relative adrenal insufficiency due to hyperthyroidism and improving vasomotor symptoms.
– Bile acid sequestrants prevent reabsorption of free THs in the gut (released from conjugated TH metabolites secreted into bile through the enterohepatic circulation).
– Treat the underlying condition.