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Biomedical subjects

M M Khan

Publications and source records attributed to M M Khan.

At least 91 records · Page 5Linked to original sources
PubMed1995

Epidemiology of smallpox in west Pakistan. III. Outbreak detection and interlocality transmission. 1971.

During one year, 121 outbreaks of variola major were detected in 99 of the 1717 localities within a rural area of West Pakistan with a total population of approximately 1.2 million. Only 19% of the outbreaks, representing 36% of the 1040 investigated cases, were officially reported, although potential strengths in the government surveillance system were also identified. Persistence of smallpox within the area depended on introductions from the outside, and more than one-half of all outbreaks of known source could be ultimately traced to cities. Within the study area, outbreaks with the largest numbers of cases and those in the larger communities were the ones from which smallpox was most frequently transported. The frequency with which variola was introduced into localities was directly related to population size and to the presence of medical care facilities. Trips between localities by infected individuals were extremely rare events. They were made most often during the late fall and winter, primarily during the incubation period of the disease, and did not differ in purpose, means or destination from journeys unassociated with smallpox. Individuals at relatively high risk of becoming introducers included the unvaccinated (primarily children under five), the unschooled and those not native to the area. Vaccination priorities based on these findings could increase the efficiency of smallpox eradication efforts.

Disease Outbreaks↗
PubMed1995

Primary corneal graft failure. A national reporting system. Medical Advisory Board of the Eye Bank Association of America.

OBJECTIVES: To describe a national eye banking registry and to assess the effects of donor age, cause of donor death, time from death to procurement, storage time, and distance between the points of recovery and transplantation on the reported occurrence of primary corneal graft failure. DESIGN: We performed a retrospective case-control study to estimate the odds ratios of five donor factors for cases of primary graft failure voluntarily reported to a national registry using controls from selected eye banks. We also performed a nested case-control cohort study to compare cases of primary graft failure that occurred in both corneas from the same donor with those of nonmated corneas in which primary graft failure was reported to assess odds ratios for the same donor factors. PATIENTS: One hundred forty-seven patients developed primary graft failure in penetrating keratoplasty transplantations performed between January 1, 1991, and December 31, 1993. These cases were reported to the Adverse Reaction Registry of the Eye Bank Association of America, Washington, DC. Controls included 7240 donor corneas distributed by nine eye banks during 1992. RESULTS: Of the 147 donor corneas that developed primary graft failure, 17 (12%) were obtained from donors who were aged 70 years and older, 39 (27%) came from donors who died of trauma, 13 (9%) had a cadaver time longer than 12 hours, 10 (7%) had a storage time longer than 7 days, and 38 (26%) were distributed outside the eye bank's region. Compared with controls, these donor corneas were more likely to have a storage time longer than 7 days (odds ratio, 2.4; 95% confidence limits, 1.2 and 4.6) and to come from donors aged 70 years and older (odds ratio, 2.4; 95% confidence limits, 1.4 and 4.0). The 22 corneas (15%) in which primary graft failure occurred in both recipients from the same donor were 8.5 times (95% confidence limits, 1.1 and 51.5) more likely to be preserved beyond 1 week than were nonmated corneas with primary failure but were not from significantly older donors. Logistic regression analysis showed that the association between prolonged storage time and primary graft failure in mated corneas remained significant even when the analysis was controlled for other donor factors. CONCLUSIONS: No clearly defined donor or eye banking factor accounted for most cases of primary graft failure, although prolonged corneal storage and advanced donor age may increase its risk. Ophthalmologists are urged to report to their eye bank all cases of primary graft failure and other adverse events that might be attributable to donor eye tissue.

Adult↗
PubMed1995

Regulation of IL-4 and IL-5 secretion by histamine and PGE2.

This study was designed to study the effects of autacoids on IL-4 and IL-5 secretion. IL-4 and IL-5 are secreted by TH2 cells. TH2 cells were generated by the culture of peripheral blood lymphocytes from atopic individuals in the presence of ragweed or dustmite antigen. The cloned TH2 lymphocytes were then stimulated with PMA (10 ng/ml) and alpha-CD3 (50 ng/ml) in the presence and absence of histamine (10(-4) - 10(-8)M) and PGE2 (10(-6) - 10(-8)M) for 48 hours. Other cAMP elevating agents were used as control. The supernatants were then assayed for the presence of IL-4 and IL-5 by ELISA. Both histamine and PGE2 suppressed the secretion of IL-4 in a dose dependent manner. Other cAMP elevating agents did not affect IL-4 secretion. In contrast, histamine upregulated the secretion of IL-5, whereas the effects of PGE2 on IL-5 secretion were not conclusive. Chloride channels have been implicated in the secretory processes. The effects of a chloride channel blocker, DIDS, were studied on histamine-induced suppression of IL-4 secretion. DIDS (10(-7) - 10(-12)M) abrogated the inhibitory effects of histamine on IL-4 secretion. The observations suggest that histamine may inhibit IL-4 secretion via activation of chloride channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Recurrent myocardial infarction with angina and normal coronary arteries.

Although it is well recognised that patients with ischemic heart disease can have normal coronary arteries on coronary angiography, most such patients have angina pectoris, whilst a minority have had a previous myocardial infarction. There are few reports of patients with recurrent myocardial infarctions and angina, but with normal coronary arteries on coronary angiography. We describe six patients who had more than one myocardial infarction, confirmed by raised cardiac enzymes and changes on the electrocardiogram. They subsequently developed classical angina and subsequent coronary angiography demonstrated no atherosclerotic coronary artery disease. Coronary artery spasm and diminished coronary reserve may have been contributory factors in these patients.

Adult↗
PubMed1995

Esophageal countershock: anthropometric determinants of impedance.

OBJECTIVE: To examine the use of a novel esophageal electrode system for countershock of atrial and ventricular tachyarrhythmias, with particular regard to the measurement of transesophageal and transthoracic impedances and their association with anthropometric variables. METHODS: Transesophageal cardioversion was attempted during 131 episodes of arrhythmia in 105 patients (including 109 episodes of atrial fibrillation). The esophageal system also used in 29 patients undergoing electrophysiologic studies for investigation of ventricular tachyarrhythmias. Transesophageal and transthoracic impedances were estimated during passage of a high-frequency, low-amplitude current between the respective electrodes. Impedance estimates were associated with anthropometric measurements using linear regression (least-squares method). RESULTS: In the group of patients undergoing attempted transesophageal cardioversion, the mean estimated transesophageal impedance of 52.6 +/- 11.7 omega was significantly lower than the mean estimated transthoracic impedance of 63.1 +/- 16.4 omega (n = 104, p < 0.01). For all the patients, transesophageal impedance was associated with weight, body mass index, and chest circumference (all r > or = 0.65, p < 0.01). Transthoracic impedance was associated with the same factors (all r > or = 0.55, p < 0.01). CONCLUSION: This esophageal electrode system results in lower impedance values for countershock between the esophagus and the cutaneous cardiac apex in comparison with standard transthoracic cutaneous electrode placement. Both techniques are dependent on anthropometric factors.

Adult↗
PubMed1995

Differential effects of histamine on T helper type 2 (TH2) lymphocytes.

Histamine inhibits IL-4 secretion from T helper type 2 cells but enhances IL-5 secretion from the same cells. Both of these effects are mediated by H2 receptors. Not all cyclic AMP-elevating agents affect IL-4 and IL-5 secretion. The observations suggest a selective effect of histamine on TH2 lymphocytes. Furthermore, Cl- channels may be involved in histamine-mediated regulation of cytokine secretion. The data suggest that histamine-induced elevation of cyclicAMP may be an important, but probably not the sole, mechanism underlying the selective effects of histamine on cytokine production.

Adolescent↗
PubMed1995

Role of alpha-2-macroglobulin and bacterial elastase in guinea-pig pseudomonal septic shock.

An essential role of alpha-2-macroglobulin (alpha 2M) was revealed in the prevention of septic shock induced in guinea-pigs by an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa. When bacterial peritonitis was induced by inoculating fibrin-thrombin clot containing viable bacteria at a dose of 10(9) c.f.u./kg body weight, the guinea-pigs (n = 6) died within 7-8 hours due to septic shock. Prior to the shock, consumption of two-thirds of the circulating alpha 2M was observed. When circulating alpha 2M was depleted 4 hours after the bacterial inoculation, the guinea-pigs immediately developed shock and died within one hour. This shock was prevented either with a specific elastase inhibitor, HONHCOCH(CH2C6H5)CO-Ala-Gly-NH2, zincov (6 microM), or with human alpha 2M. Simultaneous depletion of circulating Hageman factor also prevented shock in the alpha 2M-depleted animals. These results indicate that septic shock was induced through activation of the Hageman factor dependent system by the bacteria-produced elastase which survived alpha 2M in the circulation.

Animals↗
PubMed1995

An eye banking program for selecting donor corneas for surgical distribution.

Since fewer donated corneas have become available for surgery, we sought to chart the reasons to exclude them for surgical use over time. Those excluded from surgical use (1991-1994) were plotted using an algorithm based on the reasons for exclusion. Four general categories (universal contraindications [UC], national/local medical criteria [NLMC], serology, and morphology) yielded 13 possible areas. UC and NLMC exclusions for 1993-1994 were higher compared with 1991 and 1992 (p < 0.001). The proportion of corneas excluded for serological reasons decreased (p < 0.001) from 1991 to 1994. Exclusions due to morphology remained the same for all 4 years (p = NS). NLMC eliminate older donors but also exclude younger donors before the tissue reaches the eye bank (p > 0.001). Three of four of the youngest tissues ( < 30 years) are used for surgery, whereas one of five of the oldest ( > 70 years) is used. A quality control algorithm provides a heuristic and logical paradigm for noting changes from year to year. Heightened regulation has counteracted many gains in corneal donation fostered by favorable laws.

Adult↗
PubMed1995

Capillary perfusion--a study in two groups of radiated patients for cancer of head and neck.

Laser Doppler velocitometry is novel non-invasive technique to assess cutaneous microcirculation. Patients undergoing radiation therapy for head and neck cancer with convention and accelerated fraction action were evaluated under normal condition before and after radiation. A total of 70 sites in group A (conventional fractionation) and 35 sites in group B (accelerated fractionation were evaluated. Increase in perfusion was noted in patients undergoing radiation with accelerated fractionation.

Capillaries↗
PubMed1994

Effects of lymphokines and mitogens on a histamine derivative-induced intracellular calcium mobilization and inositol phosphate production.

Histamine trifluoromethyl-toluidine derivative (HTMT), a novel immunosuppressive agent, stimulates H1, H2 and HTMT receptors in lymphocytes. HTMT receptors are different from the classical H1, H2 or H3 receptors. Stimulation of HTMT receptors results in increased intracellular concentrations of calcium ([Ca2+]i) and inositol phosphate (IP) in human peripheral blood lymphocytes. In the present study, we investigated the effects of lymphokines [interleukin-4 (IL-4), interleukin-2 (IL-2)] and other pharmacologic agents [lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA)] on HTMT-induced Ca2+ and IP responses in non-rosetted cells. HTMT caused enhanced [Ca2+]i and IP responses when the cells were pretreated with IL-4. The effects of IL-4 were concentration dependent and became maximal after the cells were incubated with IL-4 for 48 hr. Inhibitors of protein synthesis, but not of RNA synthesis, blocked the effects of IL-4 on HTMT-induced responses. LPS was more potent than IL-4 in augmenting CA2+ mobilization induced by HTMT. However, the effects of LPS were not altered by inhibitors of either protein synthesis or RNA transcription. This indicated that LPS may act differently than IL-4 on the HTMT response. IL-2 and PMA did not affect HTMT-induced [Ca2+]i and IP responses. The effects of IL-4 and LPS were agonist specific. They did not affect the Ca2+ mobilization induced by PAF. The data indicate that the response to HTMT can be regulated by IL-4 and LPS. Although the in vivo importance of these receptors is not yet clear, the receptor is likely a contributor to immune and/or inflammatory regulation.

Calcium↗
PubMed1994

The impact of state legislation on eye banking.

Corneal transplantation, the most common transplantation procedure done in the United States, requires access to a sufficient number of donor eyes. We examined how laws governing tissue donation affect availability of corneal tissue by reviewing records of the Lions Eye Bank of Texas, Houston, from 1961 through 1990 (43,696 eyes from 21,898 donors). Relevant Texas statutes included the Uniform Anatomical Gift Act of 1970, the Justice of the Peace/Medical Examiner Law of 1977, and the Routine Inquiry Law of 1988. Before 1970, the mean (+/- SD) number of donated corneas was 72 +/- 38 per year; enactment of each statute above was associated with increased mean annual donations of 215 +/- 87, 1329 +/- 562, and 1958 +/- 33 corneas, respectively. The Justice of the Peace/Medical Examiner Law yielded significantly younger donors (who died of trauma), and the Routine Inquiry Law increased the number of hospitalized donors. Data from this eye bank were compared with current state laws nationwide. Effective legislation is a means to meet national ophthalmic surgical needs.

Adult↗
PubMed1994

Efficacy of 100 mg of double-bolus alteplase in achieving complete perfusion in the treatment of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the efficacy of 150 mg of aspirin plus 100 mg of alteplase, administered as two intravenous bolus injections of 50 mg each given 30 min apart, and followed by intravenous heparin, on infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3). BACKGROUND: Previous workers have shown in animals that reducing the duration of an infusion of recombinant tissue-type plasminogen activator increases the initial rate of thrombolysis, resulting in high early infarct-related coronary artery patency rates. The logical progression of this idea is bolus administration. METHODS: Consecutive patients presenting up to 6 h from the onset of symptoms were recruited for the study. Angiography was performed at 60 and 90 min after the first bolus and between 19 to 48 h after study entry. Patients were followed up for 1 month. RESULTS: At 60 min, angiography revealed infarct-related coronary artery patency of TIMI flow grade 3 in 55 (86%) of 64 patients (95% confidence interval [CI] 75% to 93%) and TIMI flow grade 2 or 3 in 58 (91%) of 64 patients (95% CI 81% to 97%). At 90 min, infarct-related artery patency of TIMI flow grade 3 was achieved in 74 (88%) of 84 patients (95% CI 79% to 94%) and TIMI flow grade 2 or 3 in 78 (93%) of 84 patients (95% CI 85% to 97%). Two patients (2.4%) had early angiographic reocclusion whereas 10 (11.9%) had late reinfarction. Bleeding episodes were mostly minor, and there was no cerebrovascular bleeding. Five patients (6.0%) died within 1 month of the acute myocardial infarction. CONCLUSIONS: In 84 patients with acute myocardial infarction, administration of 100 mg of double-bolus (2 x 50 mg) alteplase, aspirin and heparin is associated with remarkably high early infarct-related coronary artery patency rates (TIMI flow grade 3) of 86% and 88%, respectively, at 60 and 90 min.

Adult↗
PubMed1994

Alpha-2-macroglobulin as the major defence in acute pseudomonal septic shock in the guinea-pig model.

An intravenous injection of 1.2 mg/kg of Pseudomonas aeruginosa elastase induces immediate lethal shock in guinea-pigs. In the present study, alpha-2-macroglobulin (alpha 2M) was shown to be the major factor in guinea-pig plasma that inhibits the enzymatic activity of elastase in vitro. Depletion of circulating alpha 2M by injecting anti-guinea-pig alpha 2M rabbit IgG F(ab')2 rendered the animals sensitive to a dose of elastase of 0.05 mg/kg. When the alpha 2M-depleted guinea-pigs were reconstituted with human alpha 2M, this sensitivity was reversed. Lethal shock did not occur in alpha 2M-depleted animals even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously depleted, indicating that elastase induces shock through activation of the Hageman factor-dependent system. Similar results were obtained when the culture supernatants of an elastase-producing strain, IFO-3455, were used instead of the purified elastase, whereas no cardiovascular changes occurred, even in the alpha 2M-depleted guinea-pigs, when the culture supernatants were pretreated with an elastase specific inhibitor (zincov) or when the culture supernatants of an elastase non-producing strain, PA-103 were used.

Acute Disease↗
PubMed1993

Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs.

An intravenous injection of culture supernatants obtained from an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa exhibited immediate fall of mean arterial blood pressure from 63.8 +/- 1.62 to 35.6 +/- 2.31 mmHg (P < 0.001), increased heart rate from 249.6 +/- 3.86 to 272.6 +/- 2.18 beats/min (P < 0.05), and increased respiratory rate from 44.8 +/- 2.33 to 68.6 +/- 1.60/min (P < 0.01) within 5 min in the anesthetized guinea pigs. In contrast, culture supernatants obtained from an elastase non-producing strain (PA-103) did not cause the cardio-respiratory alterations, even though the same dose of endotoxin was contained in the supernatants. Intravenous or intracardiac injection of purified Pseudomonas aeruginosa elastase (1.2 mg/kg) but not endotoxin (up to 2.0 mg/kg) reproduced the immediate shock followed by death within 45 min in anesthetized or in conscious guinea pigs. Consistently, the shock-inducing ability of pseudomonal elastase was prevented by pretreatment with anti-pseudomonal elastase rabbit F(ab')2 antibodies or with a synthetic inhibitor of pseudomonal elastase. Furthermore, intravenous injection of a non-lethal dose of pseudomonal elastase (0.8 mg/kg) immediately decreased peripheral vascular resistance when estimated from a change of perfusion pressure at hindquarter circulation from 74.0 +/- 1.00 to 52.6 +/- 1.76 mmHg (P < 0.05) in association with fall of arterial blood pressure and of cardiac output which was estimated from a change of regional aortic flow. The same low-resistant shock was also observed in rats. We speculate, therefore, that bacterial proteinases may play an important role in human septic shock.

Animals↗
PubMed1993

Role of Hageman factor/kallikrein-kinin system in pseudomonal elastase-induced shock model.

The role of the Hageman factor dependent pathway in pseudomonal elastase-induced shock was investigated in guinea pigs. Presence of a bradykinin B2 receptor antagonist [D-Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin (200 nM) in the circulation prevented shock caused by an intrajugular injection of pseudomonal elastase (0.8 mg/kg body weight). During the lethal shock caused by elastase (1.2 mg/kg), a significant consumption of components of the Hageman factor/kallikrein-kinin system was observed such as 45.7 +/- 2.20% consumption of Hageman factor, 100 +/- 0% of prekallikrein, and 85.1 +/- 2.50 of high-molecular-weight kininogen. More striking evidence for the participation of this system was demonstrated in depletion experiments with monospecific F(ab')2 antibodies against the components of the system. After depletion of any one of the components, guinea pigs exhibited unresponsiveness to the same lethal dose of pseudomonal elastase in regard to the cardio-respiratory alterations. In vitro, pseudomonal elastase (60 micrograms/ml) possessed a capacity to generate substantial amount of bradykinin in undiluted plasmas of humans (300.0 +/- 32.16 ng/ml) as well as guinea pigs (460.2 +/- 20.67 ng/ml) at 37 degrees C but not in those deficient in Hageman factor or prekallikrein. These results strongly suggested a pathological role of elastase in pseudomonal sepsis through activation of the Hageman factor dependent pathway.

Amino Acid Sequence↗