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Ccp.lkCEYLON COLLEGE OF PHYSICIANS
Vol. 18 No. 1
Dr. Henry N. Rajaratnam
MD FCCP FRCP (London) (Hon) FRACP (Hon) FSLCGP FACE
1:1 What’s new in TB?.
a) Multi drug resistant TB – defined as resistance to at least Rifampicin and INAH are on
the increase and considered incurable with conventional regimes.
b) HIV increases multi drug resistance, and adverse drug events. Standard regimes are less
efficacious. Regimes that do not contain Rifampicin have a high frequency of failure and
relapse. Protease inhibitors and the non nucleoside reverse transcription inhibitors interact
with the Rifamycins and immune reconstitution can cause paradoxical clinical worsening of
c) A modified vaccinia virus expressing an M tuberculosis antigen (Antigen 85A)
substantially boosts M TB specific T cell responses when given to BCG vaccinated
d) Two new commercial assays (Quanti FERON – TB gold and T- SPOT. TB) based on the
detection of interferon Gamma (produced by T cells in response to M TB specific antigens)
are more accurate than the skin test at diagnosing latent infection.
e) The PCR amplification technique has proved more effective than a ZN stain for the rapid
diagnosis of pulmonary TB although they have performed disappointingly in pauci bacillary
extra pulmonary disease such as TB meningitis.
f) PCR is also being used for the rapid detection of drug resistance, especially Rifampicin
resistance – and overcomes the three month delay in treatment decision making, created by
conventional drug susceptibility testing.
g) Moxifloxacin – a fluroquinolone is highly active against MTB and may have a role in
shortening treatment to less than 6 months.
h) R 207910 a diarylquinoline that selectively inhibits mycobacterial ATP synthase and PA
– 824 a nitroimidazopyran that inhibits the synthesis of proteins and cell wall lipids have
demonstrated potent bactericidal activity.
Ref: Thwaites G Editorial, Clinical Medicine 2006 Nov/Dec 6(6): 523 -525.
1:2 Tyrosine Kinase (TK) inhibitors and cell surface protein antibodies.
Many oncoproteins which promote malignant transformations have increased TK activity. eg:
the p 210 oncoprotein produced by the BCR – ABL fusion gene seen in Philadelphia
Chromosome positive Chronic Myeloid Leukemia (CML). The molecule that blocks this
increased TK activity is Imatinib Mesylate (IM), which is exquisitely active in the treatment
of CML. When given in the early phase of CML it prolongs life substantially. It is also active
in the advanced phases of CML although the responses tend to be short lived. It inhibits
phosphorylation of the oncoprotein and inhibits 3 related TKs – platelet derived growth factor
receptor kinase (PDGFR), Stem cell factor receptor kinase (KIT) and Abl related gene kinase
(ARG). Relapses of the disease is due to mutations in the kinase domain of Bcr Abl. Patients
who are resistant to IM may respond to Dasatinib.
Gefitinib and Erlotinib have been found useful in advanced non small cell lung cancer.
Antibodies against cell surface proteins have also been developed against different cancers
stimulated by the targeted therapies of TK inhibitors. These are Trastuzumab for HER – 2
early and late stage breast cancer. Lapatinib for advanced breast cancer resistant to
Trastuzumab and is effective even in patients with brain metastasis. Rituximab which is
active against the CD 20 antigen expressed on many B cells, is highly active in some patients
with diffuse large cell and all small cell lymphocytic lymphomas.
Mughal T.I. and Goldman J.M. Editorial , Clinical Medicine 2006 Nov/Dec 6 (6): 526 1:3 Suspicious features of depression.
a). Feeling down, depressed or hopeless. b) Having little interest or pleasure in doing things. c) Failure to adjust to illness. d) Poorer physical functioning than due to a recent physical illness. e) Slower recovery than would be expected. f) Attempt at self harm.
Ruttley A. and Reid S. Clinical Medicine 2006 Nov/Dec 6 (6) 533 – 539.
1:4 Criteria for diagnosis of depression.
Five or more of the following with symptoms that persist over a two week period.
a) Persistent sadness or low mood. b) Loss of interest or pleasure. c) Disturbed sleep. d) Poor concentration or indecisiveness. e) Low self confidence. f) Poor or increased appetite. g) Suicidal thoughts or acts. h) Agitation or slowing of movements. i) Guilt or self blame.
Ruttley A. and Reid S. Clinical Medicine 2006 Nov/Dec 6 (6) 533 – 539.
1:5 Drugs associated with depression.
a) Anti hypertensives – Propranolol, Nifedipine. b) Anti arrhythmics - Digoxin. c) Anti Parkinsons – L Dopa. d) Hormones – Corticosteroids, Anabolic steroids, oral contraceptives. e) Anticonvulsants – Barbiturates, Carbamazepines, Vigabatrin.
Ruttley A. and Reid S. Clinical Medicine 2006 Nov/Dec 6 (6) 533 – 539. 1:6 Some aspects of antidepressant treatment.
a) SSRIs are safe in ischaemic heart disease and after recent MI. b) Venlafaxine should be avoided in cardiovascular disease and in those with electrolyte c) SSRIs are safe after stroke but Citalopram is advised if the patient is on Warfarin. d) Fluoxetine should be avoided in liver disease due to extensive hepatic metabolism e) SSRIs are safe in renal disease but used with caution in those with convulsions. Moclobemide is not proconvulsive and safe.
Ruttley A. and Reid S. Clinical Medicine 2006 Nov/Dec 6 (6) 533 – 539.
1:7 Risk factors for delirium.
a) Predisposing factors. Older age. Male. Dementia. Infections. Dehydration. Polypharmacy. Surgery. Excess alcohol. Depression. Renal failure. Hypoalbuminaemia. Hypokalaemia. b) Precipitating factors. Dehydration. Anticholinergics. Psychoactive medication. Bladder catheterization. Use of physical restraint. Hypoxia. Malnutrition. Change of environment.
Siddiqi N. and House A. Clinical Medicine 2006 Nov/Dec 6 (6) 540 – 543. Unfractionated Heparin (UH) when given subcutaneously may be as good as low
molecular weight Heparin (LMWH) in venous thromboembolism (VTE).
LMWH can be given without laboratory monitoring but is more expensive than UH. 708 adults with VTE were given sc UH without APTT monitoring in an initial dose of 333 u/Kg followed by 250 u/Kg every 12 hours or LMWH 100 iu/Kg every 12 hours. These treatments were continued for atleast 5 days and until Warfarin therapy had achieved an INR of 2.0 or higher. There was no significant difference between the two groups in rates of recurrent VTE at 3 months ( about 3.5% or in major bleeding complications at 10 days ( about 1%). 70% of both groups were treated entirely on an out patient basis. Comment: These findings indicate that weight adjusted UH sc and without APTT
monitoring – is as safe and effective as LMWH at far lower cost. Fully blinded replication of
the data are required before this approach can be recommended clinically.
Kearon C. et al JAMA 2006 Aug 23/30; 296: 935 – 42. Carson J.L. IBID 991 – 3. 1:9 ACE inhibitors (ACEI) benefit patients with coronary artery disease (CAD) and
normal LV function.
ACEI reduce rates of mortality and heart failure in patients with MI with LV systolic
dysfunction (LVSD) or heart failure. Do ACEI have similar benefits in those with CAD but
without heart failure or LVSD?. Of 3 large randomized placebo controlled trials, 2 (HOPE
and EUROPA) showed fewer cardiovascular events but a third (PEACE) did not. A meta
analysis of these 3 trials of 29,805 patients followed up for 4.5years, revealed that the
composite outcome of death, MI or stroke was less likely in patients taking ACEI ( OR 0.82).
The individual end points of death, MI, stroke, heart failure and CABG were also
significantly less likely.
Comment: The use of ACEI should be considered in all patients with CAD whether or not
they have LVSD or heart failure.
Ref: Dagenais G.R. et al Lancet 2006 Aug 12; 368: 581 – 8.
Remuzzi G and Ruggenenti P. IBID 555 -6.
1:10 Atypical antipsychotics in Alzheimers Disease.
The FDA in 2005 noted that antipsychotic drugs can increase the mortality among older
demented patients. In a 36 week DBRmulti centre trial, 421 Alzheimer patients with
psychosis, aggression or agitation received either placebo or Olanzapine, Quetiapine or
Risperidone. The primary end point was discontinuation for any reason. This did not differ
significantly among the 4 groups. 80% of subjects in each group eventually discontinued their
drug during the study ( mean 5-8 weeks). Olanzapine and Risperidone appeared to be more
effective than Quetiapine or placebo, but had more side effects.
Comment: Atypical antipsychotics were somewhat more effective but also more toxic than
placebo. Clinicians should think twice before treating such patients with antipsychotic drugs.
Ref: Schneider L.S. et al NEJ Med 2006 Oct 12; 355: 1525 – 38.
Karlawish J. NEJ Med 2006 Oct 12; 355: 1604 – 6. Which is the best EEG technique to diagnose epilepsy ?
EEG studies are normal in many individuals with epilepsy. Techniques to increase EEG
sensitivity are hyperventilation, photic stimulation, drug induced sleep and sleep deprivation.
In a study of 98 young adults with new epilepsy it was found that the EEGs were relatively
insensitive in detecting abnormalities in patients with generalized seizures (39% normal).
EEG with sleep deprivation is much more sensitive in detecting abnormalities than photic
stimulation or hyper ventilation. Sleep inducing agents gave no additional benefit.
Comment : Clinicians should consider omitting the routine EEG as a screening test and
proceed directly to the EEG with sleep deprivation.
Leach JP et al J Neurol Neuro Surg Psychiatry 2006 Sept; 77: 1040-2
1:12 What are the Cardiac morbidities from breast cancer treatments
a. Congestive heart failure may occur after trastuzumab (Herceptin), which is used in 25%
of breast caner patients whose tumours overexpress HER 2. Most of these patients recovered
cardiac function after the drug was discontinued. On rechallenge only 40% developed
recurrent cardiac toxicity and 60% could continue taking the drug.
b. Cardiac mortality over 12 years follow up following breast irradiation was the same
whether the irradiation was on the left or right side, but left sided irradiated patients were
more likely to develop coronary artery disease over 20 years (25% for left and 10% for right).
Guarneri V et al J Clin Oncol 2006 Sept. 1; 24: 4107-15 Harris EE et al J Clin Oncol 2006 Sept. 1; 24: 4100-6
1:13 Which is the colon imaging procedure which produces the least discomfort ?
Air contrast Barium enema (BE) was followed 7-14 days later by computed tomographic
colonography (CT) and then by standard colonoscopy (C). Patients experience was assessed
through validated questionnaires after each procedure. Most patients thought that BE was the
most painful procedure (54%), compared with CT (20%) and C (11%).
Comment: Most patients who undergo colonoscopy receive sedatives or analgesics. This
may explain why colonoscopy is preferred by patients over BE or CT.
Bosworth HB et al Am J Med 2006 Sep.; 119: 791-9.
1:14 Treatment of myelo proliferative diseases – some aspects
a. In polycythaemia, the haematocrit is the primary target of therapy. Treatment of
thrombocytosis is controversial.
b. In essential thrombocythaemia however, cytoreduction to mormalize the platelet count
c. The increased risk of thrombosis is not exclusively caused by erythrocytosis or
thrombocytosis but by interactions among white cells, red cells, platelets and the
d. Response to hydroxylurea but not to anagrelide may occur in thrombocythemia when
there is a mutation.
NEJ Med 2006 Dec 7, 355; 23:2462-2463 1:15 Management of Aphthous ulcers
a. Reduce inflammation and relieve pain.
b. Avoid oral trauma from hard tooth brushes or foods such as toast and acidic foods and
c. Try topical analgesics such as benzydamine or lidocaine. Protective bioadhesives such as
carmellose or cyanoacrylate can help relieve pain.
d. Topical steroids may speed the healing of ulcers and reduce pain. eg: 1% triamcinolone
dental paste (Adcortyl or Kenalog in orabase).
e. 2.5mg lozenge of hydrocortisone taken 4 times daily for 2 weeks may be useful.
f. Topical 0.05% fluocinonide in orabase upto 5 times daily for 6 weeks accelerated healing.
g. Betamethasone aerosol 4 times daily for 4 to 8 weeks reduced the duration of multiple
ulcers. The risk of oral candidiasis remains.
h. Mouth washes containing chlorhexidine gluconate (Corsodyl) or triclosan (Plax) inhibit
bacterial contamination. Listerine mouth wash and tetracycline mouth rinse (100mg
doxycycline capsule dissolved in 10ml of water and used as a rinse 4 times daily) may also be
i. 5% amlexanox paste (Apthasol, Aphtheal) bd for 3 days is a topical anti inflammatory
j. Systemic corticosteroids (30 – 60mg daily for 1 week and tapered over the 2nd week) and
thalidomide 100mg daily for 2 months are useful in severe apthous stomatitis.
NEJ Med 2006 July 13, 355;2: 168-172.
1:16 ACE inhibitors (ACEI) for claudication
ACEI improve coronary and brachial endothelial function. Can they improve claudication ?
40 adults were randomized to either ramipril 10mg/d or placebo. Patients with hypertension,
diabetes, renal failure and limiting coronary artery disease were excluded.
At 24 weeks, ramipril significantly increased the ankle brachial index at rest and after
exercise and the mean pain free walking time on a treadmill by 227 seconds compared to
Comment: Improvement in intermittent claudication could be another benefit of ACEIs but
whether this extends to patients with hypertension or diabetes remains unanswered.
Ahimastos AA et al Ann Intern Med 2006 May 2; 144: 660-4. 1:17 Capsule endoscopy(CE) for small bowel evaluation.
Current approaches for evaluating bleeding and other adverse symptoms of the small bowel
include enteroscopy (Endoscopy beyond the ligament of Treitz), enteroclysis (double contrast
study in conjunction with CT or MRI), radio nucleide scanning, angiography and capsule
endoscopy (ingestion of a capsule containing a tiny video camera).
The most common indications in 304 consecutive patients sent for CE were unexplained or
suspected GI bleeding, Crohn’s disease, polyposis, diarrhoea, malignancy and abdominal
pain. Visualization was adequate in 96% of cases, however the caecum was not reached in
20%. Conclusive diagnoses were made in 65%. The proportion of cases with positive
findings were 58% for obscure GI bleed, 31% for suspected Crohn’s disease, 25% for
diarrhoea and 17% for abdominal pain.
Comment: CE is becoming an important diagnostic tool in patients whose initial evaluations
fail to provide clinical answers.
Sturniolo GC et al Am J Med 2006 Apr; 119:341-7.
1:18 How dangerous is diastolic heart failure (preserved ejection fraction) ?
In a population based study by the Mayo clinic, 556 residents with heart failure underwent
echo studies and 501 patients had brain natriuretic peptide (BNP levels) measured. The mean
age was 76 years. 55% had preserved ejection fraction of more than 50% (diastolic heart
failure) and 45 had reduced ejection fraction (systolic heart failure). BNP levels were higher
in those with systolic heart failure (388 vs 183 pg / dl). 6 month mortality rates were 16% for
both types of heart failure.
Comment: This study, purported to be the first large community based study of heart
failure, confirmed that heart failure of diastolic type is associated with a mortality equal to
that of systolic heart failure.
Bursi F et al JAMA 2006 Nov 8; 296: 2209 – 16 Hildebrandt P JAMA 2006 Nov 8; 296: 2259-60
1:19 Prior hospital room occupants may be a source of antibiotic resistant bacteria.
In hospital transmission of MRSA and vancomycin resistant enterococcus (VRE) contributes
substantially to morbidity and mortality.
In a retrospective study of patients admitted to 8 ICUs at a tertiary medical centre over 20
months, the risk for acquiring MRSA or VRE if the room’s prior occupant was positive for
either organism was assessed. This retrospective study showed that the risk for acquiring
MRSA or VRE increases if the hospital room was previously occupied by a patient who was
positive for the organism.
Huang SS et al Arch Intern Med 2006 Oct 9; 166: 1945 – 51. 1:20 A sneeze may launch a thousand staph.
In most respiratory infections, the cough is considered the prime culprit in generating
airborne infectious particles. The sneeze should not be underestimated as a means of
launching pathogens from the pharynx into the atmosphere. During bouts of histamine
induced sneezing, the airborne spore counts increased dramatically, especially in those with
Comment: Sneezing, often dismissed as a relatively trivial reflex may have potentially
serious consequences, transmitting not only upper respiratory pathogens, but also the
pharyngeal colonizers, such as S aures and pneumococcus, that can cause severe illness.
Sneezing healthcare workers, especially those with respiratory allergies should use tissues,
masks and antihistamines to minimize the cloud of organisms they generate.
Bischoff WE et al J Inect Dis 2006 Oct 15; 194: 1119-26
Compiled by :- Dr. Henry N. Rajaratnam
MD, FCCP, FRCP (Lond), (Hon) FRACP, (Hon) FSLCGP, FACE
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