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Biomedical subjects

M M Khan

Publications and source records attributed to M M Khan.

At least 73 records · Page 4Linked to original sources
PubMed1998

Development of an indigenous screening instrument in Pakistan: the Aga Khan University Anxiety and Depression Scale.

The use of translations of instruments for detecting anxiety and depression continues to be debated. An indigenous screening instrument has been developed in Urdu for anxiety-depression syndromes at the Aga Khan University. It has been developed from the complaints of 150 anxious and depressed patients presenting to a non-speciality clinic and has been validated in 53 patients in a psychiatry clinic. The questionnaire has 25 items, 13 psychlogical and 12 somatic. At a score of 20 it has a sensitivity of 66%, a specificity of 79%, a positive predictive value of 83 and a negative predictive value of 60. In comparison with available instruments in Urdu, comprising of either psychological or somatic items, this scale includes both, which increases its reliability for use as a screening instrument by Community Health Workers in a primary health care setting, in epidemiologic work in Pakistan and in transcultural psychiatric research.

Anxiety Disorders↗
PubMed1998

Benzodiazepine self-poisoning in Pakistan: implications for prevention and harm reduction.

The pattern of all index admissions for benzodiazepine self-poisoning to a university hospital in Karachi, Pakistan are described. Of the 329 medication self-poisoning cases, 84% were benzodiazepine overdoses. Diazepam was the preferred drug in 69% of these cases, with majority ingesting between 20-30 tablets of 5 mg each, 44% bought the benzodiazepine over the counter (OTC) for the purpose of overdose. The preference for benzodiazepines over analgesics (as freely available) may be related to the motives underlying parasuicide acts and their popularity as 'sleeping pills' in Pakistan. Educating the 'chemist' and limiting the number of tablets dispensed at a time are areas to consider in reducing the incidence and harmful effects of benzodiazepine overdoses in Pakistan.

Adolescent↗
PubMed1998

Gender differences in nonfatal suicidal behavior in Pakistan: significance of sociocultural factors.

Suicidal behavior is an understudied subject in Pakistan. A variety of social, legal, and religious factors make reporting and data collection on suicide and nonfatal suicidal behavior difficult. To study the problem, a retrospective case-note analysis was carried out in which the sociodemographic and clinical characteristics of 262 female and 185 male suicidal individuals admitted to a university hospital in Karachi, Pakistan, are compared. Three quarters of the suicidal persons were under the age of 30 years. Compared to men, women were younger and more often married. Both women and men tended to use self-poisoning with benzodiazepines, but more women used organophosphate insecticides. In Pakistani society, legal, social, and economic discrimination predisposes women to psychological distress and subsequent suicidal behavior. The study highlights the need for culture-specific research on suicidal behavior in Pakistan.

Adult↗
PubMed1997

Use of bare-mounted Palmaz-Schatz stents employing the stent saddle technique on the delivery balloon: a single center experience.

The major limitations of the Palmaz-Schatz stent stem from the design of its stent delivery system (SDS). The SDS is bulky and has poor trackability in lesions with proximal tortuosity and/or vessel calcification. The use of bare-mounted Palmaz-Schatz stents on low profile balloons represents an alternate approach for lesions that are not accessible for stenting with the SDS. Thus we evaluated the indications, procedural success rate, and in-hospital complications of patients undergoing bare stenting at a single center between 1 October 1995 through 30 September 1996. A total of 363 coronary interventions were performed during this period, including coronary stenting in 194 vessels. In 18 of these 194 vessels, bare-mounted Palmaz-Schatz stents were used. The indications for bare stenting were: inability to deliver the Palmaz-Schatz stent on SDS for suboptimal angioplasty results or acute/threatened abrupt closure; use of half stents; stenting in vessels < 3.0 mm; intermediate disease in the proximal segment that would have precluded optimal visualization of stent placement; and use of guides 7 French or smaller. Bare stenting was successful in 15 of the 18 patients (vessels) in whom it was attempted. There were no deaths, myocardial infarctions, stent thrombosis, repeat interventions, or significant bleeding in patients with successful bare stent delivery. The stents were successfully retrieved in the three patients in whom the stent could not be advanced into the target coronary segment. One of these patients had a propagated spiral dissection prior to attempts at bare stenting and required emergent bypass surgery. The remaining two patients with failed deployment had suboptimal angioplasty results but had an uncomplicated hospital course. Thus bare stenting represents an alternate percutaneous approach to tackle suboptimal procedural results and/or complications in patients who have failed stent deployment with the standard sheathed stent delivery system currently available in the United States.

Angioplasty, Balloon, Coronary↗
PubMed1997

A baboon model for hematologic studies of cardiopulmonary bypass.

Objective investigation of new inhibitors of blood protein or cellular systems that are activated during cardiopulmonary bypass (CPB) is impeded by the absence of a satisfactory animal model. Because most baboon hematologic proteins immunologically cross-react with those used for human assays, we developed a robust, reusable baboon model of CPB. Blood samples were obtained from adult baboons at six time intervals before, during, and after 60 minutes of partial CPB at 37 degrees C with peripheral cannulas. Both membrane (n = 7) and bubble oxygenators (n = 7) were investigated. We measured platelet and white blood cell counts; platelet response to adenosine diphosphate and release of beta-thromboglobulin; fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, D-dimer, and plasmin-antiplasmin complex; activated complement (C3b/c and C4b/c); elastase-alpha1 proteinase inhibitor complex; and bleeding times. Adherent glycoprotein IIIa antigen in Triton X-100 washes of the perfusion circuit was also measured. Markers of baboon platelet, complement, and neutrophil activation and thrombosis significantly increased during CPB with bubble oxygenator systems but did not change appreciably in membrane oxygenator circuits. Markers of fibrinolysis, D-dimer, and plasmin-antiplasmin complex did not change with either oxygenator. The baboon model of CPB, when a bubble oxygenator is used, is a robust, reusable animal model for evaluating inhibitors of platelet, complement, and neutrophil activation and thrombosis during and after CPB.

Adenosine Diphosphate↗
PubMed1997

Zinc status of breastfed and formula-fed infants of different gestational ages.

Zinc status in 186 full term and preterm infants was determined at birth, and 3, 6, 9, and 12 months of age along with determination of zinc levels in breast or formula milk to find out if routine zinc supplements are needed during infancy. The leukocyte and plasma zinc levels in all breastfed infants were high at birth and gradually declined reaching lowest values by 4-6 months of age, and improved to normal levels by 9 months following weaning. The preterm infants however, had significantly (P < 0.05) higher leukocyte zinc (213.6 +/- 46.91 micrograms/10(10) cells) at birth compared to term infants. Colostrum of all the mothers had higher zinc concentrations which declined to significantly lower levels in breastmilk by 4-6 months of lactation, corresponding to the age when the breastfed infants had lower zinc levels. The improvement of the levels to normal after weaning suggests that the fall in zinc status during early infancy could be a transient phenomenon which could be reversed by proper weaning, thus strengthening the plea for timely food supplements rather than the need for single nutrient supplements. Formula-fed full term infants had significantly lower leukocyte zinc levels (49.3 +/- 2.59 micrograms/10(10) cells) at 3 months of age compared to breastfed infants of the same age (92.8 +/- 14.04 micrograms/10(10) cells). Even these infants improved their zinc status after weaning on par with breastfed infants. The functional significance of their transient, but low zinc values during early infancy needs to be investigated.

Analysis of Variance↗
PubMed1996

High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: angiographic, morphometric, and histopathologic analyses.

PURPOSE: We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis. METHODS AND MATERIALS: In 34 Hanford miniature swine, a segment of each coronary artery was targeted for injury and treatment. The artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion. RESULTS: The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 +/- 0.34 (mean: +/- SD) mm in the control group, compared to -0.43 +/- 0.35 mm in the 15 Gy (p = 0.04) and -0.21 +/- 0.50 mm in the 25 Gy (p = 0.01) groups; and in the balloon-injured circumflex was -0.31 +/- 0.22 mm in the control group compared to -0.03 +/- 0.18 mm in the 10 Gy (p = 0.05) and 0.00 +/- 0.33 in the 15 Gy (p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 +/- 9% in the control group compared to 18 +/- 12% in the 15 Gy (p = 0.003) and 11 +/- 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 +/- 10% in the control groups, compared to 5 +/- 5% in the 15 Gy (p = 0.02) and 2 +/- 2% in the 25 Gy (p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. Other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments. CONCLUSIONS: High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1996

Effect of factor Xa inhibitors on thrombin formation and complement and neutrophil activation during in vitro extracorporeal circulation.

BACKGROUND: Even when large doses of heparin are administered during cardiopulmonary bypass, thrombin is produced. Thrombin is a powerful protease that is associated with the thrombotic and bleeding complications of open heart surgery and is produced by cleavage of prothrombin by factor Xa. This study assessed the ability of a specific inhibitor of factor Xa, recombinant tick anticoagulant peptide (rTAP), alone or in combination with standard heparin and a low-molecular-weight heparin, enoxaparin, to suppress thrombin formation and activity during in vitro extracorporeal circulation. METHODS AND RESULTS: Fresh, anticoagulated human blood was recirculated for 2 hours in an extracorporeal membrane oxygenator perfusion circuit at 37 degrees C. Four anticoagulant protocols were evaluated; porcine heparin (3.75 U/mL); enoxaparin (17.5 U/mL); rTAP (4 mumol/L); and porcine heparin plus rTAP (2 mumol/L). Blood samples were obtained for analysis from the donor, after anticoagulation, and after 5, 30, 60, and 120 minutes of recirculation. There were no significant differences between groups in platelet count, response to adenosine diphosphate, or prothrombin fragment (F1.2) production. rTAP plus heparin reduced beta-thromboglobulin release; fibrinopeptide A concentrations were significantly higher with rTAP alone. Enoxaparin strongly and significantly inhibited complement C5b9 production and neutrophil elastase release and was associated with significantly increased concentrations of C1-C1 inhibitor and kallikrein-C1 inhibitor complexes. CONCLUSIONS: rTAP does not reduce thrombin formation or activity during in vitro extracorporeal circulation. Enoxaparin markedly inhibits formation of the complement membrane attack complex and neutrophil elastase release, possibly by accelerating C1 inhibitor activity.

Adenosine Diphosphate↗
PubMed1996

Phosphodiesterase inhibitors suppress proliferation of peripheral blood mononuclear cells and interleukin-4 and -5 secretion by human T-helper type 2 cells.

It has been suggested that interleukin-4 and -5 (IL-4 and IL-5) are instrumental in the control of allergic disease. Elevated levels of IL-4 messenger RNA (mRNA) have been detected in numerous foci of atopic activity, including bronchoalveolar lavage (BAL) fluid from atopic asthmatics and skin of atopic dermatitis patients. IL-5 is important in eosinophil activation, which is a common feature of atopic disease. IL-5 mRNA has been detected in BAL fluid from both atopic and non-atopic asthmatics, indicating that IL-5 may be a common feature of the two disease states. Production of IL-4 and IL-5 by T cells appears to be associated with a high affinity cyclic AMP (cAMP) phosphodiesterase (PDE). This study was designed to compare the effects of PDE inhibitors Ro20-1724 and theophylline on (1) the mitogenic response of peripheral blood mononuclear cells from atopic and non-atopic individuals and (2) secretion of IL-4 and IL-5 by TH(2) cells after activation with PMA and anti-CD3. Both Ro20-1724 and theophylline inhibited proliferation of PBMC in a dose-dependent manner. There was no significant difference between proliferation of PBMC from atopic versus non-atopic donors, but Ro20-1724, a specific PDE IV inhibitor, was more potent at a concentration of 10(-5)M than theophylline in suppressing lymphocyte proliferation. Similarly, both PDE inhibitors suppressed secretion of IL-4 and IL-5 from TH(2)-like cell lines in a dose-dependent manner. In conclusion, as Ro20-1724 and theophylline inhibit proliferation of PBMC and secretion of IL-4 and IL-5 from human TH(2) cell lines, the development of a selective cyclic nucleotide PDE IV inhibitor may provide a promising new approach for asthma prophylaxis.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1996

Neutrophil adhesion on surfaces preadsorbed with high molecular weight kininogen under well-defined flow conditions.

The adhesion of neutrophils and other leukocytes to biomaterial surfaces is an important phenomenon in the host response to biomaterials because the number of adherent leukocytes is often related to the inflammatory response after implantation. After adhering to biomaterial surfaces, other leukocyte reactions, such as phagocytosis, respiratory burst, and protease release, may occur and result in the deterioration of the implanted biomaterial and injury to peripheral tissue. This study of neutrophil adhesion quantitatively characterizes neutrophil adhesion under well-defined laminar flow conditions using a radial flow chamber. In this rheologically well-defined system, the fluid shear rate on the surface varies continuously with radial position. This allows the study of shear-dependent behavior of neutrophil adhesion. Exploiting the variable shear rate in the radial flow chamber, the kinetics of neutrophil adhesion was obtained using automated video microscopy and image analysis to recursively acquire cell counts from multiple fields in different radial positions, and to quantify the surface density of neutrophil as a function of time. Neutrophil adhesion was studied on glass preadsorbed with fibrinogen and high-molecular-weight kininogen (HK). At a shear rate of 20 s-1, the number of adherent cells on the preadsorbed fibrinogen surface was similar to that on bare glass, and the number of adherent cells on the HK surface was less than 10% of that on the bare glass. We conclude that surfaces preadsorbed with HK are anti-adhesive to neutrophils.

Adsorption↗
PubMed1996

Further evidence of bradykinin involvement in septic shock: reduction of kinin production in vivo and improved survival in rats by use of polymer tailored SBTI with longer t1/2.

Involvement of bradykinin in septic shock and its therapeutic endeavor using soybean trypsin inhibitor (SBTI, Kunitz type) were investigated in an in vivo model of septic shock induced by pseudomonal elastase. Pseudomonal elastase injection at 0.5 mg/kg i.v. to guinea pigs resulted in elevation level of bradykinin in the blood from < 1 ng/ml to 25 ng/ml which was accompanied by a drop of mean arterial blood pressure (MABP) (about 45 mmHg). When native soybean trypsin inhibitor (SBTI, Kunitz type, 20 kDa) was injected, into this model, induction of bradykinin generation and hypotension by the bacterial protease treatment was completely obliterated as judged by the both levels of bradykinin and MABP. Specifically, by the treatment with SBTI, bradykinin levels did not increase and the drop of the blood pressure was minimal (< 10 mmHg) in this time frame (< 30 min). We designed and prepared succinylated gelatin-conjugated SBTI (suc-gel SBTI) with enlarged molecular mass (M(r) approximately 110,000) and higher area under the curve of the plasma concentration, which exhibits about 6 times longer plasma half-life (t1/2) and about 4 times larger area under the curve of plasma concentration. Suc-gel-SBTI suppressed the pseudomonal protease-induced shock much more effectively than native SBTI, the conjugate exhibited its effect for more than 3 h, while the native SBTI showed the effect only within 2 h after i.v. injection.

Animals↗
PubMed1996

Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass.

The hypothesis that heparin-coated perfusion circuits reduce thrombin formation and activity; fibrinolysis; and platelet, complement, and neutrophil activation was tested in 20 consecutive, randomized adults who had cardiopulmonary bypass. Twenty identical perfusion systems were used; in 10, all blood-contacting surfaces were coated with partially degraded heparin (Carmeda process; Medtronic Cardiopulmonary, Anaheim, Calif.). All patients received a 300 U/kg dose of heparin. Activated clotting times were maintained longer than 400 seconds. Cardiopulmonary bypass lasted 36 to 244 minutes. Blood samples for platelet count, platelet response to adenosine diphosphate, plasma beta-thromboglobulin, inactivated complement 3b, neutrophil elastase, fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, plasmin alpha 2-antiplasmin complex, and D-dimer were obtained at these times: after heparin was given, 5 and 30 minutes after cardiopulmonary bypass was started, within 5 minutes after bypass was stopped, and 15 minutes after protamine was given. After cardiopulmonary bypass, tubing segments were analyzed for surface-adsorbed anti-thrombin, fibrinogen, factor XII, and von Willebrand factor by radioimmunoassay. Heparin-coated circuits significantly (p < 0.001) reduced platelet adhesion and maintained platelet sensitivity to adenosine diphosphate (p = 0.015), but did not reduce release of beta-thromboglobulin. There were no significant differences between groups at any time for fibrinopeptide A, prothrombin fragment F1.2, or thrombin-antithrombin complex or in the markers for fibrinolysis: D-dimer, tissue plasminogen activator, plasminogen activator inhibitor-1, and alpha 2-antiplasmin complex. In both groups, concentrations of prothrombin fragment F1.2 and thrombin-antithrombin complex increased progressively and significantly during cardiopulmonary bypass and after protamine was given. Concentrations of D-dimer, alpha 2-antiplasmin complex, and plasminogen activator inhibitor-1 also increased significantly during bypass in both groups. Fibrinopeptide A levels did not increase during bypass but in both groups increased significantly after protamine was given. No significant differences were observed between groups for levels of inactivated complement 3b or neutrophil elastase. Radioimmunoassay showed a significant increase in surface-adsorbed antithrombin on coated circuits but no significant differences between groups for other proteins. We conclude that heparin-coated circuits used with standard doses of systemic heparin reduce platelet adhesion and improve platelet function but do not produce a meaningful anticoagulant effect during clinical cardiopulmonary bypass. The data do not support the practice of reducing systemic heparin doses during cardiac operations with heparin-coated extracorporeal perfusion circuitry.

Anticoagulants↗
PubMed1996

Parasuicide in Pakistan: experience at a university hospital.

There have been few reports of parasuicide from Pakistan, where the act is considered to be a criminal offence and the Islamic religion strongly disapproves of it. In order to address the problem, a retrospective case report analysis of all index cases of parasuicide presenting over a period of 3.5 years to a university hospital in Karachi, Pakistan, was undertaken. Our results showed that most of the subjects were young adults, with married women representing the single largest group. Self-poisoning with medication was the most common method, and benzodiazepines the most frequently used drug. Interpersonal conflict with the opposite sex was the most common precipitating cause. In Pakistani culture, marriage appears to be a significant source of stress for women. Reports based on official police records do not reflect the true picture of the problem in Pakistan.

Adolescent↗
PubMed1996

Community-based health insurance in China: bending to the wind of change.

China's Cooperative Medical System, a community-based health insurance scheme, declined markedly after the economic restructuring of rural communities and the development of a private market in the health sector during the late 1970s. However, a study of the modified system in Taichang County, where it remains popular, has revealed that insurance premiums (calculated as a percentage of household income), copayments, the inclusion of non-agricultural workers, and strong political support not only favoured the system but also increased its efficiency and effectiveness.

China↗