July 20, 2010

Gel to reduce risk of AIDS in women discovered

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A woman's risk of infection with the AIDS virus can be significantly cut by the use of a vaginal gel, a study has found. The research marks the first success in a 15-year search for a way women can independently protect themselves from contracting HIV infection through sex.

Short of a vaccine, an effective vaginal microbicide has been the most elusive goal in the epidemic.

The research, which was conducted in South Africa and will be presented Tuesday at the 18th International AIDS Conference in Vienna, tested a gel containing the antiretroviral drug tenofovir.

While far from perfect, it was unambiguously helpful, reducing the risk of HIV infection by 39 percent in a group of women who used it for about three-quarters of their sexual encounters. Those who used it more consistently experienced 54 percent fewer infections.

If development follows the expected course, more-potent formulations, combined with campaigns to make the product appealing (or even sexy), could result in vastly better protection.

Of the 33 million people worldwide infected with the AIDS virus, 16 million are women. In Africa, 60 percent of people with HIV infection are women, nearly all of whom acquired the virus through sex. For many, the proven methods of preventing infection, such as abstinence, being faithful and using condoms, are either not an option or out of their control. A vaginal microbicide that could be used with or without a man's knowledge is considered essential, missing until now.

News of the results of the Caprisa-004 study, which leaked out a day before they were to be presented, sent a wave of optimism through the AIDS research community.

"We have never had any kind of tool that has effectively allowed women to protect themselves," said Bruce Walker, an AIDS researcher at Harvard Medical School. "This is really a game-changer."

"It's groundbreaking," said Catherine Hankins, chief scientific officer of the United Nations' AIDS agency, UNAIDS. "This in combination with [male] circumcision in places where the epidemic is generalized could really turn the tide."

"Everyone is just delighted. There were a lot of skeptics that the concept would work at all," said Zeda Rosenberg, head of the International Partnership for Microbicides in Silver Spring.

Researchers would need to show that the microbicide is effective in at least one other group of women before it could be licensed for commercial use, several people said Monday. That effort now climbs to the top of the international research agenda, although at a minimum the work will take several years.

A larger study testing tenofovir gel and antiretroviral drugs in pill form as a way to protect women against sexual transmission of HIV is underway in four African countries but will not be finished until 2013. Several other experiments, including ones in which the drug is in a long-acting vaginal ring, are in earlier stages. A microbicide might also be useful in protecting men who acquire the virus through anal sex.

Over the past 15 years, six other microbicides were tested in 11 clinical trials, with none showing protection.
The net impact seen in the study reflects the combined effect of many variables, only one of them the action of tenofovir, which penetrates into the vaginal tissue, protecting the cells that HIV targets for infection. Other variables include the prevalence of HIV infection in the male population; the number of sexual partners a woman had; the amount of AIDS virus ("viral load") in an infected man's semen; concurrent use of condoms; and, most important, the consistency with which a woman used the gel.

For that reason, the researchers said, it's impossible to say how much protection this microbicide might afford any woman.

"We can only approximate it," said Salim Abdool Karim of the University of KwaZulu-Natal in Durban, South Africa, who helped lead the study. "What you see is a mixture of the efficacy of the product mixed with the ability to use the product. It is fundamentally dependent on human behavior."

In the study, a group of HIV-negative women (both city dwellers and rural villagers) were randomly assigned to use a gel that was either 1 percent tenofovir gel or a placebo gel.

The material came packed in syringe-like applicators. A woman was instructed to inject the gel into her vagina no more than 12 hours before intercourse and again within 12 hours afterward (but with no more than two applications in a 24-hour period). Each woman got a monthly AIDS test, and the researchers collected used and unused applicators to verify the women's reports of whether they were using them.

At the end of 2 1/2 years, there were 98 infections in the 889 women. The HIV incidence, measured as the number of new infections for every 100 "women years" in the study, was 5.6 in the volunteers using the tenofovir gel and 9.1 in those with the placebo gel.

That amounted to a prevention effectiveness of 39 percent. Among women who said they used the gel for at least 80 percent of episodes of intercourse, the effectiveness was 54 percent.

Why the drug-containing gel did not work even better perplexed some scientists and will probably be a subject of more study.

"My most likely explanation is that you have to go up on the dose," said Anthony S. Fauci, who heads the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. "You may have maxed out on 1 percent," he said, meaning a more concentrated gel might produce greater protection.

Other scientists speculated that some women who became infected despite using the tenofovir gel might have been exposed to men with very high HIV load (which occurs soon after infection). Others may have had vaginal sores or inflammation that raised their vulnerability.

The Caprisa study also looked at whether tenofovir gel decreased a woman's risk of getting genital herpes, a virus that increases her chance of acquiring HIV if she has intercourse with an HIV-infected man.

Tenofovir provides some protection. Half as many women using gel with the drug in it became infected as did those using the placebo gel.

By David Brown

July 15, 2010

MRCP 2 Question 15

No comments:
Study the slide below carefully, and answer the question beneath:


What is the most likely diagnosis?

a) Ventricular septal defect
b) Patent ductus arteriosus
c) Coarctation of aorta
d) Supravalvular aortic stenosis
e) Pulmonary valve stenosis









ANSWER
The correct answer is C

Explanation

PA chest radiograph shows bilateral rib notching (rib 5-8) with figure-3 sign and significant post-stenotic dilation of the descending aorta

July 14, 2010

MRCP 2 Question 14

No comments:
A one year old boy is brought to his pediatrician by his mother who has noted colicky adominal pain and fever.

On examination his scrotal skin is erythematous and warm and he has a urethral discharge.

Investigation reveals a leukocytosis and pyuria. Sedimentation of the urine revealed E. coli which is successfully treated with antibiotics by his pediatrician.

When next seen at the clinic the next week he is symptom-free. The most appropriate next step would be:

a) complete urologic investigation
b) no further treatment or investigation is necessary
c) radionuclide scintigraphy
d) inguinal-scrotal ultrasound
e) ceftriaxone and doxycycline







ANSWER
The correct answer is A

Explanation

The occurrence of epididymitis in infants suggests the presence of urinary infection and the likelihood of an associated structural genitourinary abnormality, requiring complete urologic investigation.

All pediatric cases of epididymitis require immediate consultation due to the high incidence of associated genitourinary anomalies.

MRCP 2 Question 13

No comments:
An immuno-competent patient develops diarrhea.


Study the slide above carefully.

From this slide, the treatment of choice would be:

a) antiretroviral therapy
b) metronidazole
c) vancomycin
d) albendazole
e) no antibiotics are necessary










ANSWER
The correct answer is E

Explanation

Look at the brush border, there are several small spores.

Once believed not to be a pathogen in humans, these little creatures live in the brush border of the gut and are an important cause of diarrhea worldwide. In people who are immunocompromised, it can be hard to shake off the infection.

The most widely used diagnostic test is the modified acid-fast or Kinyoun stain. It is used to detect Cryptosporidium in stool samples.

Several immunofluorescent assays are also available, which test for antibodies to the parasite in the blood.

Some pharmaceutical companies have produced rapid-result commercial assays, which are moderately successful (~75% detection rate). Polymerase chain reaction (PCR) techniques might also prove to be effective in diagnosing infection.

Treatment usually is not required for cryptosporidiosis in patients who are immunocompetent, and no clinical trials have convincingly demonstrated the efficacy of antimicrobics.

MRCP 2 Question 12

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Cardiac abnormalities are a known side effect of several cytotoxic drugs.

Which of the following cytotoxic drugs is most likely to lead to fatal ventricular dysrhythmia ?

a) Doxorubicin
b) 5-fluorouracil
c) taxoids
d) cyclopentenyl cytosine
e) trastuzumab








ANSWER
The correct answer is A

Explanation

Doxorubicin may cause acute effects (within hours) including supraventricular tachyarrhythmias, ECG changes, atrial and ventricular ectopy, and, rarely, fatal ventricular dysrhythmia

MRCP 2 Question 11

No comments:
A 36 yr old woman comes to the physician for evaluation of a 4 year history of infertility, severe dysmenorrhea and increasing pain with sexual intercourse.

On pelvic examination an adnexal mass is felt and nodules are palpated along the uterosacral ligaments.

Which of the following is the most likely diagnosis?
a) dermoid cyst
b) ectopic pregnancy
c) endometriosis
d) follicular cyst
e) corpus luteum cyst







ANSWER
The correct answer is C

Explanation

Endometriosis commonly occurs in the ovary; when cyclic bleeding occurs, an endometriotic cyst or endometrioma is formed. Accumulation of blood within this cavity results in the classic chocolate cyst.

The pain that is typically produced by endometriosis is similarly produced with endometriomas of the ovary.

Physical examination reveals an adnexal mass and the typical findings of endometriosis, which include uterosacral nodularity and cul-de-sac of Douglas tenderness.

July 13, 2010

Big head 'may protect against dementia' - BBC

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Most of brain growth occurs in the earliest years of life
Having a big head may help protect against the worst ravages of dementia, say researchers.

They found that people with Alzheimer's with the largest craniums had better memory and thinking skills than patients with smaller skulls.

The Munich University team believe a larger head means there are greater brain reserves to buffer against dementia-related brain cell death. Their findings, based on 270 patients, are published in the journal Neurology.

The patients were recruited through research registries or specialist memory clinics in the US, Canada, Germany and Greece.

They were given memory and cognitive skill tests and a brain scan to gauge the extent of their disease. They also had their head size measured.

A larger head was linked to better performance in the tests, even when patients had the same amount of Alzheimer's-related brain cell loss.

Specifically, for every 1% of brain cell death, an additional centimetre of head size was associated with a 6% greater score on the memory tests.

Although brain size is largely determined by genetics, the researchers say lifestyle can have an impact.

Poor nutrition or disease in early life can compromise growth, for example.

'Complex disease'

The researchers say the first few years of development are critical. By the age of six, the brain will have reached 93% of its final size.

"Improving prenatal and early life conditions could significantly increase brain reserve, which could have an impact on the risk of developing Alzheimer's disease or the severity of symptoms of the disease," lead researcher Dr Robert Perneczky said.

Dr Simon Ridley, head of research for the Alzheimer's Research Trust, said: "Alzheimer's is a very complex disease, so we should be careful not to focus too much on a single risk factor, particularly as there is little we can do about the size of our heads.

"The researchers have also posed the idea that nutrition, injury or infection in early life can have an impact on brain reserve, suggesting that we should look after our brain from day one.

"Research is the only answer to dementia. We must invest in research now to deliver the treatments needed to avert the coming dementia crisis."

MRCP 1 Question 20

No comments:
A 40 year old female presents to her physician with a goitre.

On examination, the physician finds signs suggestive of acromegaly including coarse oily skin, a large tongue, prognathism and a prominent supra-orbital ridge of the face.

Examination of the hands revealed thick, spade fingers.

Which of the following should be the initial hormonal diagnostic investigation:

a) insulin levels
b) growth hormone
c) arginine levels
d) growth hormone releasing hormone
e) insulin-like growth factor 1 (IGF-1)





ANSWER
The correct answer is E

Explanation

Since Serum GH levels vary considerably in different individuals, and in the same person at different times, measurement of random or basal GH levels are not of value in making the diagnosis of acromegaly.

IGF-1 is a growth factor produced by the action of growth hormone on the liver, kidney, muscle, pituitary and GI tract.

GH exerts its effects indirectly through IGF-1 (formerly called somatomedin-C).

Serum levels of IGF-1 may be considered a mean of the 24 hour levels of growth hormone, and is not affected by the pulsatile release of GH.

It is thus a useful screening test for acromegaly.

Suppression of GH levels by glucose is the confirmatory test for acromegaly (Suppression of GH levels to < 2 mcg/L by RIA or < 1 mcg/L by IRMA 60 - 120 minutes after a 100 gram glucose load is diagnostic).

Rare cases of acromegaly may be caused by ectopic production of GHRH, but it's measurement is not needed routinely.

As always, radiological investigation should follow biochemical diagnosis (partly because of the high prevalence of pituitary incidentalomas).

MRI is the method of choice for imaging the pituitary because of it’s excellent resolution

MRCP 1 Question 19

No comments:
A 34 year old woman has an atypical pneumonia suspected to be secondary to Mycoplasma Pneumonia.

The penicillin group of antibiotics are ineffective for the treatment of pneumonia caused by mycoplasma pneumoniae because:

a) mycoplasma produce Beta lactamase enzyme which breaks down penicillin
b) mycoplasma lack a cell wall
c) mycoplasma belong to category of viruses
d) mycoplasma are non-sporing organisms
e) the above statement is untrue









ANSWER
The correct answer is B

Explanation

Penicillin group of antibiotics bring about their bactericidal action by selective inhibition of bacterial cell wall synthesis.

Mycoplasma are a group of bacteria which are devoid of a cell wall.

Due to the absence of a cell wall these bacteria are naturally resistant to the action of penicillin group of antibiotics. Therefore penicillins are of no use for the treatment of pneumonia caused by mycoplasma pneumoniae.

Mycoplasma does not produce beta lactamase enzyme for the breakdown of penicillins. Mycoplasma are not viruses. They are classified as bacteria.

The non-sporing nature of mycoplasma has no relation to their sensitivity to penicillin. A large number of non-sporing organisms are sensitive to penicillin.

MRCP 1 Question 18

No comments:
Currently it is known that antitumor agents can arrest cell division by one or several mechanisms.

What mode of action is implicated in the use of vinblastine as an antitumor agent?
a) Microtubule Interference
b) Topoisomerase Catalytic Inhibition
c) DNA Alkylation
d) DNA Inhibition
e) Protein Synthesis Inhibition








ANSWER
The correct answer is A

Explanation

Microtubules are dynamic, polymeric structures, which (besides other biological functions) are major constituents of the mitotic spindle, the latter being essential for the separation of chromosomes during mitosis.

Chemically, they are polymers of certain heterodimers of alpha- and beta-tubuline.

A range of secondary metabolites of plants interfere with the process of assembling and disassembling of microtubules, resulting in the arrest of cells in mitosis and apoptosis.

The most significant are the Vinca alkaloids, colchicine, maytansine, and paclitaxel.

Both Vinca alkaloids (vincristine, vinblastine, and especially the second generation vinorelbine) and taxanes (paclitaxel, and especially docetaxel), largely used as antitumor agents in the conventional treatment of lung cancer, are derived by semisynthesis of natural plant compounds.

MRCP 1 Question 17

No comments:
Septic pulmonary embolism in an intravenous drug abuser is likely to be secondary to:
a) P carinii
b) Nocardia spp
c) M avium-intracellulare
d) klebsiella
e) Pseudomonas aeruginosa








ANSWER
The correct answer is E

Explanation

In pulmonary complications of intravenous drug abuse, septic pulmonary emboli are the most common complication, followed by community-acquired pneumonia and mycobacterium tuberculosis infection.

Most pulmonary infections are community acquired episodes of pneumonia caused by common respiratory pathogens.

In one series of febrile IVDUs, pneumonia was the most common cause of fever 7. In a second series, pneumonia was second only to cellulitis as a cause of fever.
  1. The usual pathogens in bacterial pneumonia include Streptococcus pneumonia, oral anaerobes, S.aureus or P. aeruginosa. Lung abscesses may arise from aspiration pneumonia, necrotizing pneumonitis or septic emboli. Pulmonary tuberculosis is a major problem even in non-HIV-1-infected drug abusers

  2. Streptococcus pyogenes appears to have become an uncommon cause of pneumonia
Catheter infection with S aureus, P aeruginosa, or Candida species can lead to septic pulmonary embolism, as can intravenous drug abuse.

MRCP 1 Question 16

No comments:
A 64 year-old woman with severe rheumatoid arthritis has severe fatigue and is found to have multiple swollen lymph nodes.

She is currently managed with infliximab.

She is found to have antinuclear antibody positivity.

What is the likely diagnosis?
a) Lymphoma
b) Generalised tuberculosis
c) SLE-type syndrome
d) Reactivation of rheumatoid disease
e) Chronic myeloid leukaemia







ANSWER
The correct answer is A

 Explanation

Early experience with antiTNF-a therapy has identified 7 types of adverse effects that seem to be of particular concern:

(a) infection including sepsis and tuberculosis

(b) malignancies such as lymphoma

(c) hematological disorders such as anemia and pancytopenia

(d) demyelinating disorders and neuropathy

(e) exacerbation of CHF

(f) production of autoantibodies and autoimmune responses (immunosuppression)

(g) infusion related problems (as hypersensitivity - pain, erythema, localized rash and hemorrhage at injection site

Use of these agents is also associated with an increased development of antinuclear antibody positivity.

Although this is insignificant in many patients, in some cases it may be associated with a systemic lupus erythematosus (SLE)-like syndrome that appears transient and resolves after drug discontinuation.

MRCP 1 Question 15

No comments:
A pet shop owner develops a febrile illness characterized by pneumonia and systemic symptoms.

Chlamydia is isolated from a clinical specimen.

The most likely diagnosis is
a) Lyme disease
b) brucellosis
c) infective endocarditis
d) listeriosis
e) psittacosis









ANSWER
The correct answer is E

Explanation

Psittacosis is primarily an infectious disease of birds caused by the bacterium Chlamydia psittaci.

Transmission from infected birds results in a relatively rare febrile illness characterized by pneumonia and systemic symptoms A flu -like illness can also occur.

Almost any bird can harbor this bacterium in their excreta, tissues, feathers, and secretions, but parrots, parakeets, and budgerigars are the most common.

Psittacosis is considered an occupational disease of pet shop owners. Psittacosis is almost always transmitted to humans by the respiratory route. Average incubation is 7-14 days.

MRCP 1 Question 14

No comments:
A patient with symptomatic WPW syndrome undergoes an intracardiac electrophysiological Study and is found to have a reciprocating tachycardia using the normal AV conduction system for the anterograde conduction and the accessory pathway for the retrograde conduction.

This is best described as:
a) Orthodromic tachycardia
b) atrial fibrillation
c) supraventricular tachycardia
d) atrial flutter
e) Ventricular tachyarrhythmias








ANSWER
The correct answer is A

Explanation

The exact nature of the preexcitation syndrome is assessed. Most of the WPW syndrome are related to a atrioventricular accessory connection or Kent bundle : the degree of prexcitation increases during premature atrial stimulation until the refractory period of accessory pathway is reached, because the conduction time does not change in accessory pathway with the shortening of atrial cycle length while it increases in the AV node.

Rarely the WPW syndrome is related to a nodoventricular accessory pathway or Mahaim bundle and the degree of preexcitation remains unchanged during premature atrial stimulation.

- The accessory pathway refractory period depends on the driven cycle length. Refractory period of the accessory pathway decreases as the driven cycle length shortens.


- Beta adrenergic stimulation results in shortening of the anterograde refractory period of the accessory pathway and an increase in ventricular rates during atrial pacing and atrial fibrillation.

Isoproterenol test was also previously used to verify the efficacy of antiarrhythmic drug before the era of catheter ablation of accessory pathway. The loss of efficacy of some antiarrhythmic drugs was demonstrated after isoproterenol administration.

- Atrial fibrillation is easily induced during intracardiac studies by salvos of rapid atrial stimulation and is not specific. The induction of an atrial fibrillation by intracardiac programmed stimulation is obtained in 45% in asymptomatic patients and in 75 % of patients with only documented reentrant tachycardia, atrial fibrillation is induced in 95 % of those with documented atrial fibrillation. The important variations of the incidence of induced atrial fibrillation depends on the technique of programmed stimulation, on the interpretation of the duration of induced arrhythmia and on the use of isoproterenol infusion or other means to reproduce the effects of adrenergic stimulation.

The induction of an atrial fibrillation during transesophageal pacing has a best clinical significance:
The incidence of induction of atrial fibrillation also depends on the presence of an associated heart disease and the age of the patient: the induction of atrial fibrillation is rarely noted in children younger than 10 years, is induced in 20 % of teenagers and adults without heart disease and becomes relatively frequent in elderly

- Ventricular tachyarrhythmias also are easily induced in asymptomatic or symptomatic patients by programmed ventricular stimulation and are not specific in patients with WPW syndrome: the induction of a ventricular fibrillation is noted in 4 % of WPW syndrome and the induction of nonsustained multiform ventricular tachycardia in 37 % of them.

- Antidromic tachycardia which is a reciprocating tachycardia using the accessory pathway for the anterograde conduction and the normal AV conduction system for retrograde conduction, is a rare finding (5%), more frequently noted in young patients with a good retrograde normal VA conduction or in patients with several accessory pathways and seems more frequent in patients at risk of rapid arrhythmias.

- Orthodromic tachycardia which is a reciprocating tachycardia using the normal AV conduction system for the anterograde conduction and the accessory pathway for the retrograde conduction, is rarely induced in asymptomatic patients (< 10%) , but represents the most frequent tachycardia of symptomatic patients complaining tachycardia and palpitations (90 %).

MRCP 1 Question 13

No comments:
What specific part of the eye is mainly responsible for acute vision ?
a) zonnule of Zinn
b) limbus
c) optic disc
d) macula
e) fovea









ANSWER
The correct answer is E


Explanation

The fovea lies slightly below and to one side of the optic disk. It is found in the centre of a shallow depression or pit (the macula).

Only cones are present at the fovea, which is an area approximately 0.2 mm in diameter: all other parts of the retina including blood vessels are pushed aside.

The cones here have individual connections with the bipolar and ganglion cells, hence the fovea gives us our most sensitive and acute vision.


MRCP 1 Question 12

No comments:
A 15 year old is concerned about the size of his penis. He says his penis is too short and is teased about this at the gym.

On examination he is noted to have delayed sexual development. He is also found to have a lack of normal smell.

Investigations reveal a gonadotropin deficiency, although the serum luteinizing hormone and testosterone levels are normal.

The most likely diagnosis is:
a) testicular dysgenesis
b) Kallmann's syndrome
c) congenital adrenal hyperplasia
d) constitutional delay
e) craniopharyngioma






ANSWER
The correct answer is B

Explanation

The basic defect leading to hypogonadism in Kallmann's syndrome is an abnormality of hypothalamic GnRH secretion secondary to failure of gonadotropin-releasing hormone(GnRH)-producing neurons to migrate from the olfactory placode to the brain, and to agenesis of the olfactory bulbs. There is therefore a hypothalamic lack of the releasing hormone for gonadotrophins (GnRH).

Patients with Kallmann's syndrome usually come to medical attention because of a delayed puberty or incomplete sexual development.

Anosmia or hyposmia is present in 80% of the patients and establishes the diagnosis of the syndrome in individuals with isolated gonadotropin deficiency. Prepuberal testes, micropenis and cryptorquidism are usually seen.

In women pubic and axillary hair are less reliable compared with absence of appearance of breast buds since adrenarche can occur independently of gonodarche.

Other manifestations include: skeletal abnormalities (syndactily, short forth metacarpals, craniofacial asymmetry), mid-line defects (cleft-lip or -palate, color blindness, renal agenesis, nerve deafness), malrotation of the gut, congenital heart disease and neurologic findings (synkinesia, impaired 'smooth pursuit' eye movements and cerebellar dysfunction).

X-linked disorder can be associated with X-linked ichthyosis, mental retardation, chondrodysplasia punctata, and short stature.

Hypogonadotropic hypogonadism is established in adults by the finding of normal or low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the presence of low concentrations of testosterone in males and estradiol in females.

MRCP 1 Question 11

No comments:
A 22 year old woman complains of increasing fatigue and double vision. She has recently has a barium swallow examination because of dysphagia, but the test was normal.

On examination her reflexes, sensation and coordination are normal. She is noted to have difficulty speaking clearly. She has breathing problems which appear to improve with edrophonium chloride injections.

Which of the following tests would be most useful?
a) HLA B27
b) anti-cholinesterase antibody
c) rheumatoid factor
d) Antinuclear antibody
e) Anti-DNA





ANSWER
The correct answer is B

Explanation

The typical features of Myasthenia Gravis are fatigability and weakness of skeletal muscles without reflex, sensory, or coordination abnormalities.

Many cases begin with involvement of ocular muscles such as diplopia and ptosis. Weakness may remain confined to ocular muscles for long periods or involve bulbar muscles, which control chewing, swallowing, or articulation.

The disorder remains confined to ocular muscles in up to 15 percent of patients, but becomes generalized in the majority.

Examination of neck extensors and flexors is often more sensitive in demonstrating generalized disease than the motor exam of other muscle groups.

Improvement of weakness after edrophonium chloride (Tensilon) injection is a useful sign, although false-negative and false-positive tests do occur. In recent years, however, the detection of anti-cholinesterase antibody in the serum, using a commercially available immunoprecipitation test, has significantly changed the evaluation of MG patients with a sensitivity of over 70%.

The usual AChR antibody test measures the binding of antibody to AChR labeled with radioactive alpha-bungarotoxin. The toxin itself is attached irreversibly to the ACh binding site of AChR. The antibody binding test result is positive in nearly all adults with moderately severe or severe MG, in 80% with mild generalized MG, and in 50% with ocular MG, but in only 25% of those in remission. The test is less reliable in juvenile than in adult MG.

In a few patients only antibodies that block the binding of ACh to AChR can be detected.

The antibody titer correlates only loosely with disease severity, but in individual patients a >50% decrease in titer for more than 12 months is nearly always associated with sustained clinical improvement.

Striated muscle antibodies also occur in MG patients. Their role remains unknown, but they often are associated with thymoma.

July 03, 2010

Life Expectancy: How to live longer and healthier

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OVERCOMING LOW LIFE EXPECTANCY IN AFRICA

When this article was first written in July 2010, official figures of life expectancy in most African countries were at record low levels, for example Nigeria was 47 years. I had gone on to point out that extreme stress almost on a daily basis, inconsiderate leaders, lack of portable water, prevalence of fake drugs and very poor healthcare delivery, amongst others, all contributed to this. I compared the African life expectancy to that of Americans which had risen to between 75-80 years, and proposed that all Africans should take responsibility for their health at a personal level, since there seemed no government interest.

Abnormal body temperatures and febrile convulsion

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Also called pyrexia, fever is abnormal rise in body temperature of a person above the normal of 37.2° C.
Body temperature normally vary between 36.4 - 37.2° C (i.e. 97.5 - 98.9° F), with the lower levels in the mornings (6 AM) and the higher levels in the evenings (4-6 PM).

Control of body temperature is regulated by the thermo-regulatory center in the brain; which sets a normal temperature point for the body. Fever results when pyrogens cause an increase of this set point such that the body sees the new set point as its 'normal' temperature.

Fever is a common symptom usually signifying infections like malaria, tuberculosis, meningitis; malignancies like leukemia, lymphoma; and many other conditions.

It can be damaging especially to children below the age of six years, in whom it may easily cause a convulsion - febrile convulsion (see what to do below).

Hyperpyrexia, hyperthermia and hypothermia

Hyperpyrexia is fever of more than 41.5° C (>106° F). It can develop in people with severe infections, but also in those with central nervous system (CNS) hemorrage, local trauma or tumor.

Hyperthermia occurs if there is an unchanged normal set point of the thermo-regulatory center in the brain, but an uncontrolled rise in body temperature that exceeds the body’s ability to lose this extra heat. Causes include working or exercising in abnormally hot environments; taking recreational drugs like cocaine; inhalational anaesthesia, thyrotoxicosis; some types of stroke; pheochromacytoma; status epilepticus; and many others.

Hypothermia is unintentional drop in the body temperature to below 35° C (95° F). It may occur in a previously healthy person who is exposed to severe cold like in the elderly, the very young, and as an occupational hazard e.g. the military; or when it complicates serious systemic disease e.g. hypothyroidism; hypoglycemia; hypopituitarism; sepsis.

The appearance of a rash with fever should prompt an immediate visit to the doctor. It could be a sign of serious disease as in measles, HIV, typhoid fever, systemic lupus erythomatosus, syphilis, drug reaction and many others.

WHAT TO DO

Especially for children between 6 months - 6 years; rapidly bring down the temperature thus: tepid-sponge (i.e. apply lukewarm water to the exposed body), give an antipyretic, and seek proper medical evaluation. Children of this age bracket are very prone to febrile convulsions, thus the need for urgent resolution of fever in them.

Hypothermic individuals must be rewarmed by covering and insulating them in a warm environment. Hot water bottles may be used. Seek expert medical help urgently.

For hyperthermia, physical cooling with sponging, fans, cooling blankets, and even ice baths should be initiated. An urgent visit to the doctor for more specific and technical measures is indicated.

Secret to long and healthy living

No comments:
WITH official figures of life expectancy in most African countries at low levels eg Nigeria is 47years, it implies that those who are above 50 in the country deserve a thanksgiving celebration.

Why not? With what we all go through in most African states, the inconsiderate leaders, the unnecessary stress, lack of potable water, prevalence of fake drugs (about 40 per cent of all the drugs in Nigeria are fake) and worst still, poor health care, how does one live long?

Comparatively, the life expectancy of Americans has risen to between 75 and 80 years. Where does that leave you and I in our Africa? It is a worthy topic to consider and dwell on because health is wealth.

Every African, and indeed Nigerian, should stand up for his or her health in the face of all this - the tyranny of the governing, death-hole roads, inadequate health services or health quackery, fake drugs and many others.

We can take simple measures right now to give time the finger and lengthen our lives.

Simple things to do

Mentally, in the course of everyday life, chances are that the average human being has some millions of brain cells ‘fried’. A simple remedy to this damage is to drink lots of water and exercise at least 20 - 30 minutes two to three times a week.

Protect your heart.

It’s easy to write off heart trouble as something that plagues only cheeseburger-grubbing big, fat and old people. Cardiovascular disease is a huge concern for both men and women and is a number one killer. It is possible to reduce the risk of heart disease by 82 per cent with simple lifestyle changes such as adding exercise into your schedule, limiting fatty foods and cutting alcohol and tobacco consumption. Prevention of Cardiovascular diseases starts from now no matter your age.

Infact the younger the age at which one starts, the better the results.

Learn to prioritise.

One famous doctor once said that Nigerians spend more on funerals and parties than on their health. Although this is not true for everyone, it is nonetheless a very important and significant point. MESSAGE: spend money to obtain appropriate health care and health information from properly qualified health care personnel for yourself and your dependents so as to improve and maintain a high quality of life.

Don’t self-medicate.

There was a woman who died from heart attack. When she had the early signs of an impending attack, she preferred to buy pain relievers not knowing the real source of her pains. Worse still, she died and N40, 000 was found in her purse! MESSAGE: Know your first aid, but be sure to consult a properly qualified medical or health care personnel immediately you have a strange unexplained symptom.

Be versatile in first aid techniques.

Accidents, whether domestic or commercial, are inevitable. Many lives have been lost because people around accident scenes are ignorant of the first thing to do with a sick patient and so by the time they rush the person to the hospital, it may be too late.

It is sad to see people moping at accident victims and when they even try to help, they are likely to worsen the situation. I have had two young men rushed in dead to a hospital casualty while i was on duty, they had had a high tension electrocution while working on an electrical unit. A simple cardio-pulmonary resuscitation (CPR) started IMMEDIATELY following their electrocution, and continued while transporting them to the hospital, may have saved their lives. Instead, they were bundled into a car and driven over several miles to my hospital's casualty unit, where they arrived dead.

A stitch in time always saves nine. First aid classes could be taken at the Red Cross or St. Johns; you never know when the knowledge will come in handy.

Aside from following all the obvious health rules (don’t smoke, keep your weight in check, don’t overindulge in alcohol, etc.), your best measure is to stay vigilant with medical checkups to reveal the possibility of any silent but ongoing health issue in time, and also to mind who you move with and where you go to and how you go to places since lifestyle and environments play a major role in maintaining good quality health.

Knowing the rules is not good enough but sticking to them and above all, valuing yourself and your health because if you do, you would do anything and everything possible to protect it.

By Dr Tony, a registrar at the University of Calabar Teaching Hospital; Calabar

July 01, 2010

MRCP 2 Question 10

No comments:
Vascular abnormalities are a known side effect of several cytotoxic drugs.

Which of the following cytotoxic drugs is most likely to lead to thrombosis and thromboembolism?

a) methotrexate
b) 5-fluorouracil
c) taxoids
d) cyclopentenyl cytosine
e) trastuzumab






ANSWER
The correct answer is A


Explanation

MRCP 2 Question 9

No comments:
An elderly woman with type 2 diabetes has poorly controlled blood glucose levels despite treatment. The physician decides to try metformin.

Which best describes the mode of action of metformin?

a) reduces insulin resistance and improves insulin sensitivity
b) suppresses basal hepatic glucose production
c) reduces fasting plasma glucose
d) activates the AMP-activated protein kinase
e) stimulates first-phase insulin secretion in the pancreatic beta cells



ANSWER
The correct answer is D

Explanation

An elevated rate of basal hepatic glucose output is the primary determinant of elevated fasting blood glucose levels in patients with type 2 diabetes.

The primary effect of metformin is the suppression of basal hepatic glucose production, thereby reducing fasting plasma glucose. Metformin does not stimulate insulin secretion; in contrast, metformin reduces fasting plasma insulin and improves whole-body insulin-stimulated glucose metabolism (insulin sensitivity).

While it is possible that the beneficial effect of metformin on insulin sensitivity is mediated directly, a more likely explanation is that it is secondary to a reduction in hyperglycemia, triglycerides, and free fatty acids.

Evidence has shown that metformin activates the AMP-activated protein kinase

MRCP 2 Question 8

No comments:
A 55 year old woman who has just gone through her menopause is concerned that she may develop vertebral fractures. She has never had any surgery before and has no relevant medical history.

What is the most effective way of preventing pathological fractures post-menopause?

a) Clonidine J Vaginal lubricant
b) Combined Oestrogen and progestogen replacement therapy
c) Oestrogen only HRT
d) Progestins
e) Mineral supplements



ANSWER
The correct answer is B

Explanation

Because established osteoporosis may not be significantly reversed, medical management should emphasize prophylaxis rather than treatment. Patients should be advised to stop smoking, reduce the intake of dietary phosphates, and exercise regularly to preserve bone mass.

Estrogens have been shown to prevent the loss of bone mass and to reduce the incidence of osteoporotic fractures. They act by decreasing bone resorption, by increasing intestinal calcium absorption, and by reducing renal calcium excretion.

The inclusion of progesterone or a progestogen in hormone replacement therapy (HRT) inhibits endometrial proliferation and minimizes the risk of endometrial hyperplasia and subsequently endometrial carcinoma caused by unopposed exogenous estrogens. Progestogens are therefore an essential part of HRT for women with an intact uterus.

There are substantial differences between the currently available progestogens both in chemical structure and in pharmacological profile. It is important to consider these differences when HRT is prescribed.

Low doses of estrogen appear to be as effective as higher doses; 0.625 mg and 1.25 mg of conjugated equine estrogen (CEE) are equally effective in preventing bone loss and in reducing the incidence of fractures. Because bone loss is irreversible, estrogen treatment initiated shortly after menopause will maximize the amount of bone preserved.

Treatment should be taken for at least 6 years to reduce substantially the lifetime risk for fracture. No method identifies all patients in whom osteoporosis will develop; hence, most postmenopausal women are potential candidates for this therapy.

A measurement of baseline bone density may help patients for whom the decision to initiate estrogen replacement is difficult. However, normal bone density does not rule out the future development of osteoporosis.

MRCP 2 Question 7

No comments:
Vascular abnormalities are a known side effect of several cytotoxic drugs.

Which of the following cytotoxic drugs is most likely to lead to hepatic veno-occlusive disease ?

a) cyclophosphomide
b) 5-fluorouracil
c) taxoids
d) cyclopentenyl cytosine
e) trastuzumab






ANSWER
The correct answer is A


Explanation

MRCP 2 Question 6

No comments:
An 8 year old boy is newly diagnosed with asthma and is initially treated with nedocromil sodium.

Eight weeks after starting treatment he is seen at the outpatient clinic.

His mother complains that her son has remained symptomatic with persistent breathing difficulties and wheezing with physical activity and occasionally complains of tightness in the chest. He has lost four days of school in this period for this reason.

Appropriate treatment at this stage should include

a) No medical treatment required
b) Nebulised ipratropium bromide
c) Single dose 1 ml 0.5% salbutamol
d) inhaled low dose corticosteroids
e) refer to an ENT specialist




ANSWER
The correct answer is D

Explanation

For children with symptomatic disease and an impaired quality of life, inhaled corticosteroids are -- and should remain -- the mainstay of asthma control

Vermiform Appendix: Useful and in fact Promising

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The body's appendix has long been thought of as nothing more than a worthless evolutionary artifact, good for nothing save a potentially lethal case of inflammation.

Now researchers suggest the appendix is a lot more than a useless remnant. Not only was it recently late last year proposed to actually possess a critical function, but scientists now find it appears in nature a lot more often than before thought. And it's possible some of this organ's ancient uses could be recruited by physicians to help the human body fight disease more effectively.

In a way, the idea that the appendix is an organ whose time has passed has itself become a concept whose time is over.

"Maybe it's time to correct the textbooks," said researcher William Parker, an immunologist at Duke University Medical Center in Durham, N.C. "Many biology texts today still refer to the appendix as a 'vestigial organ.'"

Slimy sac

The vermiform appendix is a slimy dead-end sac that hangs between the small and large intestines. No less than Charles Darwin first suggested that the appendix was a vestigial organ from an ancestor that ate leaves, theorizing that it was the evolutionary remains of a larger structure, called a cecum, which once was used by now-extinct predecessors for digesting food.

"Everybody likely knows at least one person who had to get their appendix taken out — slightly more than 1 in 20 people do — and they see there are no ill effects, and this suggests that you don't need it," Parker said.

However, Parker and his colleagues had suggested that the appendix still served as a vital safehouse where good bacteria could lie in wait until they were needed to repopulate the gut after a nasty case of diarrhea. Past studies had also found the appendix can help make, direct and train white blood cells.

Now, in the first investigation of the appendix over the ages, Parker explained they discovered that it has been around much longer than anyone had suspected, hinting that it plays a critical function.

"The appendix has been around for at least 80 million years, much longer than we would estimate if Darwin's ideas about the appendix were correct," Parker said.

Moreover, the appendix appears in nature much more often than previously acknowledged. It has evolved at least twice, once among Australian marsupials such as the wombat and another time among rats, lemmings, meadow voles, Cape dune mole-rats and other rodents, as well as humans and certain primates.

"When species are divided into groups called 'families,' we find that more than 70 percent of all primate and rodent groups contain species with an appendix," Parker said.

Several living species, including several lemurs, certain rodents and the scaly-tailed flying squirrel, still have an appendix attached to a large cecum, which is used in digestion. Darwin had thought appendices appeared in only a small handful of animals.

"We're not saying that Darwin's idea of evolution is wrong — that would be absurd, as we're using his ideas on evolution to do this work," Parker told LiveScience. "It's just that Darwin simply didn't have the information we have now."

He added, "If Darwin had been aware of the species that have an appendix attached to a large cecum, and if he had known about the widespread nature of the appendix, he probably would not have thought of the appendix as a vestige of evolution."

What causes appendicitis?

Darwin was also not aware that appendicitis, or a potentially deadly inflammation of the appendix, is not due to a faulty appendix, but rather to cultural changes associated with industrialized society and improved sanitation, Parker said.

"Those changes left our immune systems with too little work and too much time their hands — a recipe for trouble," he said. "Darwin had no way of knowing that the function of the appendix could be rendered obsolete by cultural changes that included widespread use of sewer systems and clean drinking water."

Now that scientists are uncovering the normal function of the appendix, Parker notes a critical question to ask is whether anything can be done to prevent appendicitis. He suggests it might be possible to devise ways to incite our immune systems today in much the same manner that they were challenged back in the Stone Age.

"If modern medicine could figure out a way to do that, we would see far fewer cases of allergies, autoimmune disease, and appendicitis," Parker said.

The scientists detailed their findings online August 12, 2009 in the Journal of Evolutionary Biology.

By Charles Q. Choi

MRCP 1 Question 10

No comments:
A 70 year old with chronic lung disease and with a strong family history of ischaemic heart disease presents with atypical chest pain.

An ECG is suggestive of ischemia. In view of the history of chronic lung disease a pharmacologic stress echocardiography is organised.

What is the most likely pharmacologic agent to be used in this case?

a) Dipyridamole
b) Adenosine
c) Dobutamine
d) atropine
e) Arbutamine



ANSWER
The correct answer is B

Explanation

Adenosine is by far the most commonly used pharmacologic agent in nuclear perfusion imaging.

It can be used like dipyridamole and is typically infused at a maximum rate of 140 mg/kg per minute during imaging.

The mechanism of action is probably identical to that of dipyridamole. However, adenosine has a much shorter half-life, and thus an antidote is usually not necessary in the event of an adverse reaction.

MRCP 1 Question 9

No comments:
A patient with recurrent infections with encapsulated bacteria is found to have a primary complement deficiency.

Which two primary complement deficiencies most commonly predispose to infection by encapsulated bacteria?

a) C1 and C2
b) C4 and C9
c) C3 and C5
d) C6 and C7
e) C8 and C9



ANSWER
The correct answer is C

Explanation

The complement system consists of a group of circulating proteins that have immunologic effects when they are activated.

Complement activation serves first to opsonize pathogens for phagocytosis; second, to attract inflammatory cells; and third, to kill the pathogen by creating pores in its membrane.

Because these functions are closely tied to the actions of antibodies, defects in the complement system result in recurrent infections with extracellular bacteria, including encapsulated bacteria.

Primary deficiencies of C3 or C5 predispose the host to infection by encapsulated bacteria . Deficiencies of the later complement components (ie, C5b, C6, C7, C8, and C9) cause vulnerability principally to Neisseria gonorrhoeae and Neisseria meningitidis. Secondary (ie, acquired) complement defects are seldom clinically important.

MRCP 1 Question 8

No comments:
Which of the following medications have the highest risk of producing the arrythmia known as torsades de pointes when the patient is also taking amiodarone?

a) Flecainide
b) Phenytoin
c) Propafenone
d) Amiodarone
e) Lidocaine





ANSWER
The correct answer is D

Explanation

Common clinical features in drug-induced torsade de pointes include hypokalemia and cycle-length prolongation just prior to initiation of the arrhythmia.

Among these agents sotalol, which is a class III agent, has the highest risk of producing torsades, which is a polymorphic, pause-dependent ventricular tachycardia causing syncope and sudden cardiac death.

MRCP 1 Question 7

No comments:
An obese 40 year old woman was brought to the general practitioner by her husband. The husband explained that the patient's snoring at night was disturbing him.

On questioning, the GP found that the problem was distinct from being merely annoying because the husband noted that she was also gasping for air throughout the night - and this repeatedly roused her out of her refreshing, deep sleep.

On further questioning the physician identified the telltale signs of sleep apnea: excessive daytime sleepiness and difficulty functioning.

What treatment did the physician most likely recommend?

a) adenoidectomy
b) removal of the uvula
c) night time low dose of diazepam
d) tracheostomy
e) nasal continuous positive airway pressure




ANSWER
The correct answer is E

Explanation

Sleep apnea is among the most common and most dangerous types of sleep disorder.

An estimated 18 million Americans have the condition, which is marked by repeated episodes of cessation of breathing during sleep that over time can lead to high blood pressure, cardiac disease, and disordered thinking.

The most common effective treatment for obstructive sleep apnea is nasal continuous positive airway pressure, or CPAP. The patient wears a soft plastic mask over his or her nose while sleeping.

Surgery to increase the size of the airway is another possible option for sleep apnea treatment. The removal of adenoids and tonsils, especially in children, or other growths or tissue in the airway is sometimes effective, as are other, relatively more risky surgical procedures, including uvulopalatopharyngoplasty (shaving of the excess soft tissues in the mouth and throat) and tracheotomy (creating an opening in the neck through the windpipe) for the most severe cases.

The newest device for this condition is Somnoplasty, used to treat mild cases of sleep apnea. It is a radio frequency surgical device that shrinks the soft palate in a half-hour outpatient procedure. FDA approved the Somnoplasty device in July 1997

Antiretroviral therapy for HIV/AIDS

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Standard highly active antiretroviral therapy (HAART) consists of the use of at least three antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease.

This HAART standard typically consist of two Nucleoside Reverse Transcriptase Inhibitors, NRTI and one Non-Nucleoside Reverse Transcriptase Inhibitor, NNRTI combination. Huge reductions have been seen in rates of death and suffering when use is made of a potent ARV regimen.

About 33.4 million people are now living with HIV, of whom more than 30 million live in low- and middle-income countries.

WHO estimates that at least 9.7 million of these people are in need of ART. As of the end of 2008, 4 million people had access to ART in low- and middle-income countries.

WHO is providing countries with ongoing guidance, tools and support in delivering and scaling up ART within a public health approach.

Parkinson's Disease: Frequently Asked Questions

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Parkinson's disease (PD) is a long-term degenerative disease of the central nervous system that mainly affects the motor system, and the symptoms generally come on slowly over time. With a diagnosis of such a life-changing medical condition, you may feel angry, afraid, sad, or worried about what lies ahead. MedikalNotes.com has compiled a list of possible frequently asked questions (FAQs) you may have.