Therapeutic Drug Monitoring of Imatinib in Patients of Chronic Myeloid Leukemia - Chronic Phase

Introduction: Tyrosine kinase inhibitor is recommended for the initial management of chronic phase chronic myeloid leukemia (CP CML) based on the more favorable balance of toxicity and long-term disease control. Background: Mean trough plasma Imatinib Mesylate (IM) levels are detected to be significantly higher in patients with a complete cytogenetic response or major molecular response (MMR). Methodology: The primary objective of the study was to correlate the IM drug levels with MMR on two different occasions at least 3 months apart and to study the variation in the plasma trough levels of IM during the treatment with standard dose for at least 12 months. Results: After exclusion, 30 patients of CML-CP in MMR, on standard dose over a period of 2 years were finally analyzed. The mean IM plasma levels (IPLs) of the first sample for all patients were 1722 ± 566 ng/ml (IPL-1) with a corresponding mean molecular response (MR) 0.0257 ± 0.0279 breakpoint cluster region-abelson murine leukemia (BCR-ABL) IS % (MR-1). The mean IPLs of the second sample for all patients were 1549 ± 375 ng/ml (IPL-2) with a corresponding mean MR 0.0143 ± 0.0184 BCR-ABL IS % (MR-2). Area under the receiver operating characteristic curve for IPL-1 was 0.565 and IPL-2 was 0.639. For IM level at second point of 1800 ng/ml, the specificity for predicting MMR was 81.8% and sensitivity was 31.6%. Conclusion: Monitoring of trough IM plasma concentrations may become the part of standard management of CML patients.

Study of Palmar Type of Median Artery and its Fate.

Background: The median artery is a transitory vessel that represents the arterial axis of the forearm during early embryonic life. When present, it appears mainly as two types: antebrachial and palmar. Context and purpose of the study: In the present study the objective was to investigate the occurrence and fate of palmar type of median artery. The study was conducted on 40 cadaveric upper extremities dissected in the department of Anatomy, Guru Gobind Singh Medical College, Faridkot, India. Results: In the present study, persistent median artery (palmar type) was seen in 2.5% of the limbs dissected. It was originating from the posterior aspect of the ulnar artery approximately 3.2 cm distal to the elbow joint. It pierced the median nerve (traversing from its medial to its lateral aspect) in the proximal third of the forearm. The artery then travelled lateral to the median nerve in rest of the forearm. Subsequently, it accompanied the median nerve into the palm passing deep to the flexor retinaculum. Finally, the artery terminated by completing the superficial palmar arch. In addition to the above described variant blood vessel, we also observed high division of median nerve into its medial and lateral branches. Clinical implications: When median artery is patent and reaches the hand, it forms the only arterial supply to the median nerve and damage to this artery could have serious effects. The aim of our study was to provide additional information about anomalous palmar type of median artery and its clinical implications.

Death due to ruptured ectopic pregnancy natural death or negligence.

A young adult female of low socio-economic status, and a labourer by profession, was brought dead to the Government Medical College & hospital, Chandigarh. History provided by her husband revealed that she had pain abdomen for the last five days for which she was getting treatment from a private practitioner. She had been prescribed NSAIDs and antispasmodics for the same. However, she was not investigated upon and no attempt was made by the practitioner to arrive at any diagnosis. The autopsy was conducted on the next day and at autopsy, about two-and-a-half liters of blood was present in the abdomen and pelvic cavity. Careful internal examination revealed a ruptured ectopic pregnancy as the source of bleeding. The case is discussed with regard to establishing whether the death could have been natural, due to the negligence of the treating doctor or due to contributory negligence. However, even in cases of contributory negligence, the “last chance doctrine” may not save the physician.

A Study on Treatment Outcome of Registered Tuberculosis Cases under RNTCP in Udupi Taluk, Karnataka.

Directly Observed Treatment Short Course is the internationally recommended strategy to ensure cure of tuberculosis. However, it is equally important to review the shortcomings if any of such an important strategy against tuberculosis to make it more useful. This Descriptive study carried in a Tuberculosis Unit was to find out the treatment outcome of patients registered under Revised National Tuberculosis Control Program. The data was collected from the tuberculosis register and was analyzed using SPSS 13.0 version. Study included 563 patients, 68% were males and 32.0% were females. Category I had majority of the patients 307 (54.52%); Category II had 133 (23.6%), and Category III had 116 (20.6%) patients. In Category I, 175 (57.0%) patients were cured and 13(4.2%) had treatment failure. In Category II, 61 (45.9%) were cured and 11(8.3%) had treatment failure. In Category III, 105 (90.5%) had complet treatment. Out of 236 patients who were cured, majority were under the care of government health workers 125(53%), followed by anganwadi 32(13.6%) and social workers 27(11.4%). Joint efforts of DOTS providers cured 53 (22.4%) patients. Ensuring early diagnosis and high cure rate of Tuberculosis cases is the only effective way to stop the spread of Tuberculosis.

Adequacy of two versus three sputum specimens for the diagnosis of pulmonary tuberculosis.

Background. The new guidelines issued by the Revised National Tuberculosis Control Programme for diagnosis of smear-positive tuberculosis recommend examination of only 2 sputum smears. We did a retrospective analysis of data from a designated microscopy centre to ascertain the diagnostic yield of 2 smears and the additional yield provided by the third smear. Methods. Data were obtained from the designated microscopy centre attached to our medical college. A total of 3257 patients with suspected tuberculosis had undergone sputum examination between September 2004 and March 2009. However, only 1762 of them had 3 sputum specimens examined. Data were entered and analysed using SPSS version 11.5. Results. Among the 1762 suspected patients, positivity in any 2 samples was found to be 17.7% while 19% were found to be positive in a single smear. A statistically insignificant association was found between the grading and positivity of the sputum samples using McNemar test. A positive third sample was found in 309 patients. If the first 2 samples were negative, the possibility of missing a third positive sample was 0.4%. Conclusion. Under field conditions, 2 sputum smears are as effective as 3 smears for diagnosing smear-positive tuberculosis.

Assessing the suitability of vitreous humor as a sample for toxicological analysis – A prospective study.

The incidence of poisoning and substance abuse have been steadily rising in India over the last few decades. Accurate diagnosis of poisoning is essential, both in the living as well as in the dead, for therapeutic and medicolegal purposes respectively. Poisons are generally detected in body fluids such as urine, blood, or gastric lavage during life, while they are detected in the contents of stomach, bowel and the viscera, besides urine and vomitus, after death. In a dead body, one of the better samples to complement blood is vitreous humor, because it is less likely to degrade quickly, and is fairly easy to collect at autopsy. In this study, an attempt has been made to assess the role of vitreous humor as a suitable sample for toxicological analysis in the detection of all kinds of poisoning after death. The study was done on alleged cases of poisoning subjected to medicolegal autopsy at the mortuary of Government Medical College and Hospital, Chandigarh. Attempt was also made to corelate the vitreous humor findings with that of the official report from the Chemical Examiner's Laboratory at the state or central level.

Hepatic and extra-hepatic glutathione-S-transferase activity in wild pigeons (Columba livia).

Glutathione-S-transferase (EC 2.5.1.18) activity was assayed in hepatic and extrahepatic tissues of pigeons using l-chloro-2,4-dinitrobenzene and l,2-dichloro-4-nitrobenzene as substrates. Gluthathione-S-transferase activity towards l-chloro-2,4-dinitrobenzene in pigeon was in the order: kidney >liver >testes >brain >lung>heart. The enzyme activity with 1- chloro-2,4-dinitrobenzene as substrate was 40-44 times higher in pigeon liver and kidney than that observed with l,2-dichloro-4-dinitrobenzene as substrate. Km values of hepatic and renal glutathione transferase with l-chloro-2,4-dinitrobenzene as substrate were 2.5 and 3 mM respectively. Double reciprocal plots with varying reduced gluthathione concentrations resulted in biphasic curves with two Km values (liver 0.31 mM and 4mM; kidney 0.36 mM and 1.3 mM). The enzyme activity was inhibited by oxidized gluthathione in a dose-dependent pattern. 3-Methylcholanthrene elicited about 50% induction of hepatic glutathione transferase activity whereas phenobarbital was ineffective.