Search PubMed⌕ Search

Biomedical subjects

J A Khan

Publications and source records attributed to J A Khan.

At least 19 recordsLinked to original sources
PubMed2005

Trends in hospital-based management of acute asthma from a teaching hospital in South Asia.

The aim of this study is to evaluate the hospital-based management of acute asthma in south Asia and to compare practices over a 10-year period. Adult patients (n = 102) admitted at a teaching hospital with acute asthma were studied. Documentation of precipitating factors, family history and physical signs were inadequate in more than half of patients. Pulse oximetry was documented in 95 (93%) patients, but peak flow monitoring was performed only in 50 (49%) patients. Ten-year trend showed deterioration in history and physical examination skills, under use of peak flow readings, and poor pre-discharge instructions. Some aspects of improved care included frequent use of pulse oximeter, preference of inhaled over systemic bronchodilators and increased use of systemic steroids. Significant deficiencies were identified in hospital-based management of acute asthma. Most aspects of asthma care continued to fall short of asthma guidelines.

Acute Disease↗
PubMed2005

Medical interns knowledge of TB in Pakistan.

Of 460 interns from five Pakistani teaching hospitals surveyed, only 22% correctly identified the estimated number of new TB cases in Pakistan. The majority (96%) knew that droplet infection was the usual mode of transmission. Only 38% considered sputum smears for acid-fast bacilli as the best test for diagnosis of pulmonary TB and 43.5% for follow-up during TB treatment. The recommended four-drug anti-TB regimen was prescribed by 56.5% in the initiation phase and the recommended two-drug combination in the continuation phase by 52%. Most interns (82%) were unable to identify a single component of directly observed treatment short course (DOTS) strategy. Our study reflects poor awareness of and low compliance to the World Health Organization/National Tuberculosis Programme guidelines among interns. For effective control of TB, immediate action to improve undergraduate and continuing medical education is essential, with special emphasis on national guidelines.

Clinical Competence↗
PubMed2004

Invasive aspergillosis with polyarthritis.

We report a case of septic arthritis of multiple joints in an 18-year-old male caused by Aspergillus fumigatus. His initial presentation was of low-grade fever followed by involvement of both knee and ankle joints. Later, there was also involvement of metacarpophalangeal joints. Diagnosis was based on biopsy and culture of the skin and joint lesions. The symptoms resolved readily under administration of itraconazole. We recommend that clinicians should be alerted of potential fungal etiology in cases of fever and chronic arthritis, which is unresponsive to conventional medical therapy.

Adolescent↗
PubMed2004

Asthma management by general practitioners in Pakistan.

SETTING: Teaching university hospital in Karachi, Pakistan. OBJECTIVES: Asthma management guidelines have been developed to assist practising physicians in treating asthma patients. The objective of this study was to evaluate if the prescribing habits of practitioners in Karachi were consistent with the published asthma guidelines. DESIGN: A questionnaire survey was conducted among practitioners attending a pulmonary continuing medical education (CME) programme. Three case scenarios of asthma were given, and the doctors were asked to write a prescription for each case. Doctors were asked about their views on inhaler therapy and dietary restrictions in asthma. RESULTS: Of 120 doctors, 100 (83%) responded. Thirty different regimens of short acting beta2-agonist and 16 regimens of steroid therapy were prescribed by the practitioners. Only 35% of the doctors prescribed corticosteroids for persistent asthma symptoms. The great majority of doctors were not aware of treatment options for persistent symptoms despite the use of preventive therapy (8% prescribed long-acting beta2-agonists, 6% high-dose inhaled corticosteroids and 13% theophyllines). Misconceptions about inhaler therapy and diet were found in 20 and 50 doctors, respectively. CONCLUSION: General practitioners in Pakistan did not follow asthma management guidelines. There was serious lack of knowledge about asthma medications coupled with misconceptions about inhaler therapy and dietary factors.

Administration, Inhalation↗
PubMed2004

Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country.

SETTING: A university teaching hospital in Karachi, Pakistan. OBJECTIVE: To define the clinical characteristics and outcome of miliary tuberculosis (TB) patients from a low human immunodeficiency virus (HIV) prevalence country. DESIGN: Review of adult miliary TB patients admitted between 1994 and 2001. Clinical characteristics of those dying from miliary TB were compared with those of the survivors. RESULTS: Most of the 110 cases reviewed were middle aged or elderly, with a female preponderance. An underlying medical condition was present in 47%. Presenting symptoms were of several weeks' duration, and mostly constitutional (fever and weight loss). Common laboratory findings included anaemia (62%), lymphopaenia (71%), hyponatraemia (74%), elevated serum alkaline phosphatase (57%) and hypoalbuminaemia (92%). Typical miliary pattern was observed in 77% of radiographs. Sputum smear and culture were positive in respectively 36% and 52% of those tested. Biopsy was performed in selected patients. Mean hospital stay was 8.8 days, and mortality was 30%. Those who died were significantly older than survivors and had a more fulminant course. Presence of altered mental status, lung crackles, leucocytosis, thrombocytopaenia and the need for ventilation were associated with increased mortality. CONCLUSION: Miliary TB carries a high mortality. It should be considered in patients who present with prolonged systemic symptoms. A positive TB culture or biopsy is needed to establish a diagnosis.

Adolescent↗
PubMed2003

An uncommon case of neck fistula.

Congenital fistulae of the neck are branchial in origin and of these 2nd arch fistula is by far the most common, 3rd and 4th arch fistulae being very rare. Here, a case of fistula present since birth and extending from the neck, near the midline to the alveololingual sulcus, considered very rare, is presented. The patient was a 32-year-old male having sticky discharge through an opening in the upper part of the neck. Examination revealed an opening of approximately 1 mm diameter about 1 cm to the left of the midline just above the hyoid bone. A sinogram revealed a fistulous linear tract communicating with the oral cavity. Surgery was undertaken and the fistulous tract was excised.

Adult↗
PubMed2002

The current naming of plant viruses: a critical appraisal.

The revised International Code of Virus Classification and Nomenclature [7] followed by the Seventh Report of the International Committee on Taxonomy of Viruses (ICTV) [9] have generated a lot of criticism [2,4-6]. The main causes of criticism are (i) use of monomials instead of non-latinized binomials, as has been practice for some time in the past, e.g., tobacco mosaic tobamovirus, tobacco ringspot nepovirus etc. (ii) in toto italicization of official virus names. Following the expression of different views among virologists on this issue, it is being debated and an opportunity has been provided for reconsideration of the revised ICTV code [1,8,10]. This note attempts to analyse the existing criticisms being raised and justifies the continuation of the present ICTV code.

Plant Viruses↗
PubMed2002

Cancer patterns in Quetta (1998-1999).

INTRODUCTION: Quetta, the capital of Baluchistan, is located at latitude 30.25; longitude 67.00. It has a population of 759,245; 425,474 males (56%) and 333,771 females (44%); Census 1998. The majority of residents are Persian or Baluchi speaking Baluchs. METHODOLOGY: The cancer cases from Quetta reported to the Karachi Cancer Registry were reviewed. The data included cases from the Aga Khan University Hospital (AKUH), Pathology Department (Quetta collection point) and health care facilities in Karachi. The residents of Baluchistan were ascertained and cancer cases residents of Quetta identified with the help of recorded addresses and retraceable telephone numbers. RESULTS: During a 2-year period, 1st January 1998 to 31st December 1999 the Karachi Cancer Registry received 1077 cancer notifications from Quetta. Approximately half the cases were registered from the AKUH Quetta collection point. Others were the referral patterns in Karachi. The age-standardized incidence rate (ASR) of cancer, all sites (1998-99) was 137.0 for males and 92.8/100,000 for females. The commonest cancer in the males and females was cancer of the esophagus (ICD-10 categories C15; males- ASR 25.5, 17.2%; females-ASR 23.4,23.1%). One ofthe highest in the world, for both genders. Incidence of cancer breast in the females (ICD-10 categories C50; ASR 11.8, 13.3%) was low. CONCLUSION: The cancer data from Quetta is quite distinct from the cancer pattern of Karachi. It represents only a part of the cancer burden of Quetta; nonetheless it gives a glimpse into the cancer profile of Baluchistan. The high incidence of esophageal cancer indicates an extension of the geographical limits of the esophageal cancer belt.

Female↗
PubMed2001

Identification of novel polyphenol oxidase inhibitors by enzymatic one-pot synthesis and deconvolution of combinatorial libraries.

The feasibility of enzymatic synthesis of combinatorial libraries using multifunctional starting materials [i.e., 2,4-dihydroxy-N-(2-hydroxyethyl)benzamide, 1; 4-hydroxyphenethyl alcohol, 2; 3,5-dihydroxybenzyl alcohol, 3; and 4-hydroxybenzyl alcohol, 4] with six vinyl esters, in a one-pot reaction, was investigated. Candida antarctica lipase was employed as a biocatalyst. The resulting 24-compound library contained all the expected species with no significant bias toward particular combinations of substrates. As expected, the library contained a substance(s) that showed significant inhibition of polyphenol oxidase, which was used as a model target. The deconvolution was accomplished via resynthesis of ten partial libraries, which were prepared with either an equimolar mixture of the four alcohols and a single vinyl ester, or a single alcohol and equimolar mixture of the activated esters. Analysis of the inhibition pattern observed with these partial libraries suggested that 4-hydroxybenzyl benzoate (4e) should be the most potent inhibitor. This conclusion was confirmed by the preparation and comparison of all 24 components of the initial library. Finally, it was shown that 4e was a competitive inhibitor of polyphenol oxidase, with a K(i) of 40 microM. This value compared favorably with a K(i) of 400 microM, which was determined for parent phenol 4.

Catalysis↗
PubMed2001

Protein intermediate trapped by the simultaneous crystallization process. Crystal structure of an iron-saturated intermediate in the Fe3+ binding pathway of camel lactoferrin at 2.7 a resolution.

This is the first protein intermediate obtained in the crystalline state by the simultaneous process of Fe(3+) binding and crystal nucleation and is also the first structure of an intermediate of lactoferrin in the Fe(3+) binding pathway. Lactoferrin is an iron-binding 80-kDa glycoprotein. It binds Fe(3+) very tightly in a closed interdomain cleft in both lobes. The iron-free structure of lactoferrin, on the other hand, adopts an open conformation with domains moving widely apart. These studies imply that initial Fe(3+) binding must be in the open form. The protein intermediate was crystallized by the microdialysis method. The protein solution, with a concentration of 100 mg/ml in 10 mm Tris-HCl, pH 8.0, was loaded in a capillary and dialyzed against the same buffer containing 26% (v/v) ethanol placed in a reservoir. FeCl(3) and CO(3)(2-) in excess molar ratios to that of protein in its solution were added to the reservoir buffer. The crystals appeared after some hours and grew to the optimum size within 36 h. The structure was determined by molecular replacement method and refined to final R- and R-free factors of 0.187 and 0.255, respectively. The present structure showed that the protein molecule adopts an open conformation similar to that of camel apolactoferrin. The electron density map clearly indicated the presence of two iron atoms, one in each lobe with 4-fold coordinations: two by the protein ligands of Tyr-92(433) OH and Tyr-192(526) OH and two other coordination sites occupied by oxygen atoms of bidentate CO(3)(2-) ions leading to a tetrahedral intermediate. The CO(3)(2-) anion is stabilized through hydrogen bonds with the synergistic anion-binding site Arg-121(463) and with Ser-122 Ogamma in the N-lobe and Thr-464 Ogamma in C-lobe. The third oxygen atom of CO(3)(2-) interacts with a water molecule in both lobes.

Animals↗
PubMed2001

Camel lactoferrin, a transferrin-cum-lactoferrin: crystal structure of camel apolactoferrin at 2.6 A resolution and structural basis of its dual role.

Camel lactoferrin is the first protein from the transferrin superfamily that has been found to display the characteristic functions of iron binding and release of lactoferrin as well as transferrin simultaneously. It was remarkable to observe a wide pH demarcation in the release of iron from two lobes. It loses 50 % iron at pH 6.5 and the remaining 50 % iron is released only at pH values between 4.0 and 2.0. Furthermore, proteolytically generated N and C-lobes of camel lactoferrin showed that the C-lobe lost iron at pH 6.5, while the N-lobe lost it only at pH less than 4.0. In order to establish the structural basis of this striking observation, the purified camel apolactoferrin was crystallized. The crystals belong to monoclinic space group C2 with unit cell dimensions a=175.8 A, b=80.9 A, c=56.4 A, beta=92.4 degrees and Z=4. The structure has been determined by the molecular replacement method and refined to an R-factor of 0.198 (R-free=0.268) using all the data in the resolution range of 20.0-2.6 A. The overall structure of camel apolactoferrin folds into two lobes which contain four distinct domains. Both lobes adopt open conformations indicating wide distances between the iron binding residues in the native iron-free form of lactoferrin. The dispositions of various residues of the iron binding pocket of the N-lobe of camel apolactoferrin are similar to those of the N-lobe in human apolactoferrin, while the corresponding residues in the C-lobe show a striking similarity with those in the C-lobes of duck and hen apo-ovotransferrins. These observations indicate that the N-lobe of camel apolactoferrin is structurally very similar to the N-lobe of human apolactoferrin and the structure of the C-lobe of camel apolactoferrin matches closely with those of the hen and duck apo-ovotransferrins. These observations suggest that the iron binding and releasing behaviour of the N-lobe of camel lactoferrin is similar to that of the N-lobe of human lactoferrin, whereas that of the C-lobe resembles those of the C-lobes of duck and hen apo-ovotransferrins. Hence, it correlates with the observation of the N-lobe of camel lactoferrin losing iron at a low pH (4.0-2.0) as in other lactoferrins. On the other hand, the C-lobe of camel lactoferrin loses iron at higher pH (7.0-6.0) like transferrins suggesting its functional similarity to that of transferrins. Thus, camel lactoferrin can be termed as half lactoferrin and half transferrin.

Animals↗
PubMed2001

Analysis of conformational states of Candida rugosa lipase in solution: implications for mechanism of interfacial activation and separation of open and closed forms.

In this study, an analysis of the transition between the inactive ("closed") and active ("open") conformations of Candida rugosa lipase in solution is performed using irreversible enzyme inhibitors, cyclic saligenin phosphates. It is shown that >90% inhibition of the enzyme activity toward water-soluble substrates (esterolytic activity) can be achieved with as little as 0.3 mol of the inhibitor per mole of enzyme, whereas activity toward emulsified substrates decreases by approximately 20% under the same conditions. It is also shown that short-term exposure of this inhibited enzyme preparation to an interface leads to a significant increase in esterolytic activity, which even exceeds that of the untreated control. These experimental observations suggest that the inhibitors interact predominantly, if not exclusively, with the open form of the enzyme and that any transitions occurring between the two conformers of the enzyme in solution, in the absence of an interface, are extremely slow. This conclusion is verified by separating the open and closed forms of the enzyme by hydrophobic interaction column chromatography on phenyl-sepharose. Fractions enriched with the respective conformations of the enzyme are further purified using gel-permeation chromatography. On the basis of the elution pattern from this step, and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the open (active in the absence of interface) form of the lipase is found to be present in solution as a dimer, whereas the closed form appears to be a monomer. The latter form of the enzyme may be activated by up to 60-fold when exposed to triolein.

Benzyl Alcohols↗
PubMed2000

Detection of tomato leaf curl geminivirus in its vector Bemisia tabaci.

Geminiviruses are single-stranded DNA plant infecting viruses that cause major losses in important crops in tropical and subtropical countries. Tomato leaf curl virus (TLCV) belonging to the genera Begomovirus, is a whitefly-transmitted geminivirus that causes a severe leaf curl disease in tomato (Lycopersicon esculentum). The importance of this disease has prompted a great need for a rapid identification of TLCV in its hosts and vector. Polymerase chain reaction (PCR) is the most sensitive approach to detect a minute amount of viral nucleic acid. It is the most ideal method to amplify geminiviruses as they replicate via a double-stranded, circular DNA form. In this study, geminivirus specific degenerated primers were employed to detect TLCV occurring in its vector whitefly Bemisia tabaci by PCR based approach. One primer pair, amplified TLCV DNA fragment of about 1.1 Kb representing partly replicase gene, intergenic region and partly coat protein gene was used. When a set of primer targeted to the core region of the coat protein gene of geminivirus was used, a PCR amplified fragment of about 0.5 Kb was obtained. This approach is highly useful for an early detection of TLCV occurring in very small amount in the vector B. tabaci. Its implications in geminivirus management strategies and their differentiation and being discussed.

Animals↗
PubMed1999

Kinetic analysis of cyclic CMP-specific and multifunctional phosphodiesterases by quantitative positive-ion fast-atom bombardment mass spectrometry.

Two enzymes, cyclic CMP-specific phosphodiesterase and multifunctional phosphodiesterase, are responsible for the hydrolysis of cytidine 3',5'-cyclic monophosphate in living cells. Quantitation of both enzymes has been carried out by positive-ion fast-atom bombardment mass spectrometric analysis of the enzyme incubates after termination of the reaction. The kinetic data obtained are in close agreement with parallel data obtained by the conventional radiometric assay. The extra facility of the mass spectrometry based assay to monitor several incubation components simultaneously has been exploited to study the concurrent hydrolysis of alternate cyclic nucleotide substrates and provides kinetic parameters of significance in interpreting substrate-enzyme interactions. This is extended by the use of collisionally-induced dissociation of the protonated molecules of the liberated products to identify the mononucleotide isomers resulting from the cyclic nucleotide hydrolysis.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗