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Biomedical subjects

M I Khan

Publications and source records attributed to M I Khan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition and remodelling during healing after transmural canine myocardial infarction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition for six weeks after myocardial infarction (MI) lowers the collagen content of infarct scars in dogs. However, temporal changes in collagen content of the infarct zone (IZ) with ACE inhibition during healing over six weeks after MI and their possible relation to IZ remodelling have not been determined. METHODS: IZ collagen (hydroxyproline) was measured over six to seven weeks in dogs treated with captopril (50 mg bid), enalapril (2.5 mg bid) or placebo, beginning on the second day following transmural anterior MI (or sham). In vivo changes in IZ and global left ventricular (LV) remodelling, mass and function (echocardiograms) and hemodynamics among six-week survivors were also measured. RESULTS: Compared with placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks. Among the six-week survivors, both inhibitors lowered IZ collagen (P < or = 0.001) and increased the collagen type I:III ratio. However, preload was lower, increase in diastolic volume and mass were less and systolic function improved. Although the doses of captopril (but no enalapril) decreased afterload, inhibition of IZ collagen was less, IZ bulging and global LV dilation were less and systolic function was better with captopril than with enalapril. In all three MI groups, deaths over the seven weeks correlated with greater infarct size, LV volume and dysfunction and lower IZ collagen. CONCLUSIONS: ACE inhibition suppresses the temporal increase in IZ collagen and attenuates IZ expansion, thinning and bulging, and LV enlargement and aneurysm formation during healing after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Changes in myocardial density during postinfarction healing: effect on estimation of in vivo left ventricular mass by echocardiographic imaging.

To determine whether changes in density (rho) of infarct and noninfarct zones during healing and remodeling after myocardial infarction influence estimates of left ventricular mass and detection of temporal changes by imaging, we measured weights (g) and volumes (mL) of infarct, noninfarct, and mixed tissue in hearts removed 1 to 42 days after anterior infarction in three groups of dogs: nonreperfused infarction treated with placebo or captopril, or infarcts reperfused after 2 h. In vivo mass was calculated from in vivo diastolic myocardial volumes (echocardiograms) and an assumed density of 1.05 g/mL or actual values derived from tissue weights and volumes. Over the 42 days, actual density deviated more from the assumed value of 1.05 in infarct than noninfarct zones, and the overall density was higher for reperfused than nonreperfused ventricles (1.09 vs. 1.06 g/mL, p < 0.01). Correction for density improved the correlation between absolute in vivo and postmortem mass slightly but not the detection of relative changes in mass in control, captopril, or reperfusion groups. These findings suggest that (i) densities of infarct and noninfarct zones differ and change during healing, especially after reperfusion, and (ii) correction for density provides more accurate estimates of volume-derived mass in reperfused hearts.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Rate of collagen deposition during healing and ventricular remodeling after myocardial infarction in rat and dog models.

BACKGROUND: We hypothesized that the rate and amount of infarct collagen deposition during healing after myocardial infarction might influence ventricular remodeling in rat and dog models. The purpose of this study was to compare rates of infarct collagen deposition and ventricular remodeling in the two models. METHODS AND RESULTS: Infarcted rat and dog hearts were removed at fixed time intervals between 1 and 50 days for measuring remodeling parameters and infarct and noninfarct collagen content (mg/g hydroxyproline). Collagen was less in sham rat (n=29) than dog (n=30) ventricles (3.32 versus 4.57 mg/g, P<.001) and markedly lower in the rat (n=48) than dog (n=59) infarcts throughout healing and by 50 days (9.98 versus 56.74 mg/g, P<.0001). Infarct collagen leveled off earlier and healing (histology) was completed sooner in the rat. Infarct scars were also thinner in the rat, with more (P<.0001) thinning and bulging (mm/g), and greater increase in ventricular volume. Although the mass to volume ratio decreased (P<.001) in both models, global remodeling was different, with greater transverse axis widening and globularity in the dog. Although infarct size, transmurality, heart rate, filling pressure, and blood pressure were greater in the rat, infarcts 10% to 30% in size in both models showed similar differences in infarct collagen and remodeling. CONCLUSIONS: Compared with dog infarcts, rat infarcts exhibited faster healing and infarct collagen deposition and markedly lower infarct collagen. In addition to larger, more transmural, and thinner infarcts, and greater hemodynamic load, the lower infarct collagen in that model might be an important factor in the greater regional remodeling.

Animals↗
PubMed1996

Effect of prolonged inotropic stimulation on ventricular remodeling during healing after myocardial infarction in the dog: mechanistic insights.

OBJECTIVES: We hypothesized that positive inotropic stimulation during healing after myocardial infarction might increase contractile pull on the infarct segment, increase expansion and promote ventricular dilation. BACKGROUND: The effect of prolonged inotropic stimulation on left ventricular remodeling during healing after myocardial infarction has not been studied. METHODS: The effects of 6 weeks of inotropic stimulation on in vivo changes in left ventricular topography, function and mass (serial two-dimensional echocardiograms), hemodynamic variables, postmortem topography (planimetry) and collagen (hydroxyproline content) were studied in 36 chronically instrumented dogs randomized, 2 days after small anterior infarction, to digoxin (0.125 mg daily) and no digoxin (control group). RESULTS: Heart rate and arterial and left atrial pressures were similar in the two groups, but the first derivative of left ventricular pressure (peak dP/dt), systolic thickening of the noninfarct wall and systolic thinning of the infarct wall were higher in the digoxin group during the 6 weeks. At 6 weeks, infarct scar size and collagen content were similar in both groups, but the digoxin group had more infarct expansion and thinning. Between 2 days and 6 weeks, the digoxin group showed more in vivo diastolic infarct expansion, thinning and bulging; more aneurysm but less global dilation and increase in mass; and no change in ejection fraction. The effects of inotropic stimulation on remodeling were more marked in infarcts with 100% than 85% transmurality. CONCLUSIONS: Prolonged inotropic stimulation with digoxin during healing after small anterior infarction increases infarct bulging without decreasing infarct collagen content and preserves global ventricular size, mass and systolic function.

Animals↗
PubMed1996

Endoscopic papillectomy: a novel approach to difficult cannulation.

BACKGROUND: Selective cannulation of the biliary and pancreatic ducts is considered to be the most difficult and rate limiting aspect of diagnostic endoscopic retrograde cholangiopancreatography (ERCP). AIMS/METHODS: A novel technique for difficult cannulation is described and its potential role in relieving malignant duodenal obstruction secondary to ampullary carcinoma. A diagnostic endoscopic papillectomy was performed in 10 patients in whom previous attempts at cannulation had failed. Five patients had exophytic ampullary carcinomas, one had carcinoma of the head of pancreas, two had an oedematous ampulla secondary to low common bile duct stones, while two had protuberant ampullae with ectopic orifices. The technique entails snaring the ampulla flush with the duodenal wall using a polypectomy snare and in a similar fashion to polypectomy removing the ensnared ampulla with diathermy using a coagulation current. The underlying exposed ducts can then be cannulated while the ensnared ampulla can be retrieved to aid histological diagnosis. RESULTS: Successful cannulation was achieved in all 10 cases with significant haemorrhage in one patient (10%). Four of the snared ampullary carcinomas (80%) were retrieved enabling a histological diagnosis to be made. CONCLUSIONS: This study demonstrates the potential role for endoscopic papillectomy as a means of cannulation in difficult circumstances, however larger comparative studies are required.

Aged↗
PubMed1995

Impact of left ventricular unloading after late reperfusion of canine anterior myocardial infarction on remodeling and function using isosorbide-5-mononitrate.

BACKGROUND: Late reperfusion during acute myocardial infarction results in delayed recovery of ventricular function and less remodeling, whereas ventricular unloading with nitrates improves function and attenuates remodeling. Whether late reperfusion combined with prolonged unloading with isosorbide-5-mononitrate (ISMN) might produce greater functional recovery and less remodeling than late reperfusion alone is not known. METHODS AND RESULTS: In vivo left ventricular function and topography (echocardiograms), postmortem topography (planimetry), and collagen (hydroxyproline) were measured in dogs that were randomized to reperfusion 2 hours after left anterior descending coronary artery ligation, and ISMN (n = 12) or placebo (n = 12) was given as 25 mg IV over 4 hours followed by 50 mg PO QID for 6 weeks. Compared with placebo, the ISMN group had similar heart rate but lower left atrial pressure, mean arterial pressure, and rate-pressure products. Although in vivo baseline remodeling and functional parameters were similar in the two groups, by 6 weeks the ISMN group had smaller (P < or = .05) infarct and noninfarct segment lengths, ventricular volumes, and mass; less (P < .001) asynergy; and greater (P < .001) ejection fraction. More important, by 2 days, ejection fraction was 18% greater (P < .025) and asynergy 26% less (P < .05) with ISMN. At 6 weeks, ISMN showed less (P < or = .05) scar size, scar collagen, cavity dilation, noninfarct wall thickness, and apical bulging than placebo. In another 4 dogs, acute ISMN produced less improvement in function and remodeling than prolonged ISMN. CONCLUSIONS: Late reperfusion of acute anterior myocardial infarction combined with prolonged ISMN unloading results in greater and earlier recovery of ventricular function and less remodeling than late reperfusion alone.

Animals↗
PubMed1995

Purification and characterization of alpha-D-mannosidase from Aspergillus sp.

alpha-D-Mannosidase from Aspergillus sp. was purified to homogeneity by preparative polyacrylamide gel electrophoresis (PAGE). The native enzyme of molecular mass 412 kDa (gel filtration) is made up of six identical subunits of molecular mass 69.2 kDa (SDS-PAGE) The enzyme is acidic (pI 4.5) and a glycoprotein with a carbohydrate content of 3.8%. The pH and temperature optima of the enzyme were in the range 6.0-6.5 and 50-55 degrees C, respectively. At pH 6.0 the enzyme was stable for 30 min at 50 degrees C. The Km and Vmax for p-nitrophenyl-alpha-D-mannopyranoside were 83 microM and 0.2 mumol/min per mg of the enzyme, respectively. The enzyme was strongly inhibited by 1 mM Hg2+ and Cu2+ and partially by 30 mM glucose and mannose. The enzyme hydrolysed Man-alpha-(1-3)Man at a very high rate followed by Man-alpha-(1-2)Man, while the rate of hydrolysis was low for Man-alpha-(1-6)Man. The rate of hydrolysis for high mannose oligosaccharide Man-6 was higher than for Man-9 and yeast mannan was not hydrolysed at all.

Aspergillus↗
PubMed1995

Effect of enalapril on ventricular remodeling and function during healing after anterior myocardial infarction in the dog.

BACKGROUND: Ventricular remodeling after myocardial infarction involves changes in ventricular size, shape, structure, and matrix that impact on function. Prolonged angiotensin-converting enzyme inhibition after infarction with captopril reduces ventricular enlargement and improves clinical outcome, but whether enalapril produces similar benefits is controversial. METHODS AND RESULTS: The effect of enalapril during healing between 1 day and 6 weeks after myocardial infarction on in vivo changes in ventricular size, shape, mass, and function (asynergy, or akinesis and dyskinesis, and ejection fraction), as determined by serial two-dimensional echocardiography, hemodynamics, postmortem topography (planimetered short- and long-axis ventricular contours), and collagen content (determined by levels of hydroxyproline, a marker for collagen), was measured in 25 instrumented dogs. The dogs were randomized 1 day after left anterior descending coronary artery ligation to a control group (no treatment) and a group receiving oral enalapril (2.5 mg BID). Compared with no treatment, enalapril produced a sustained lowering of left atrial pressure but no difference in heart rate and mean blood pressure over the 6 weeks. Also compared with no treatment, enalapril modified in vivo remodeling parameters between 1 day and 6 weeks, with less elongation of the asynergy-containing segment, a lower expansion index (ratio of endocardial lengths of infarct to non-infarct-containing segments demarcated by papillary muscle landmarks), less scar wall thinning, a lower thinning ratio (ratio of average thickness of infarcted wall to average thickness of the normal wall), smaller ventricular volume, less regional bulging and aneurysm frequency, prevention of the increase in ventricular mass, less total extent of asynergy, and higher volume ejection fraction. At postmortem examination, scar mass was similar in the two groups, but topographic maps with enalapril revealed less infarct bulging, flatter infarct scars, and less noninfarct wall thickness. In addition, postmortem collagen content was similar in noninfarct zones of the two groups but lower in infarct zones of the dogs given enalapril. CONCLUSIONS: Prolonged enalapril therapy, in a dose that did not lower blood pressure, during healing after anterior infarction produced prolonged reduction of left ventricular preload in dogs. This diastolic unloading was associated with limitation of remodeling parameters (infarct expansion and thinning, progressive ventricular dilation and hypertrophy, and regional bulging), less total asynergy, and improved left ventricular ejection fraction. Although angiotensin-converting enzyme inhibition was associated with lower collagen content in the infarct area and altered scar topography, these effects did not impact negatively on overall remodeling and function.

Aldosterone↗
PubMed1995

Combined captopril and isosorbide dinitrate during healing after myocardial infarction. Effect on ventricular remodeling, function, mass and collagen.

OBJECTIVES: We sought to compare the effects of captopril plus isosorbide dinitrate versus monotherapy on infarct collagen content and left ventricular remodeling and function during healing after myocardial infarction. BACKGROUND: Captopril or isosorbide dinitrate monotherapy can limit postinfarction dilation. Whether captopril inhibits infarct collagen content, or whether captopril plus isosorbide dinitrate might be more beneficial, is not known. METHODS: In vivo remodeling variables and function (echocardiography), hemodynamic variables, postmortem topography (planimetry) and collagen content (hydroxyproline) were measured in 48 chronically instrumented dogs that were randomized 2 days after left anterior descending coronary artery ligation to 6 weeks of therapy with captopril, isosorbide dinitrate, captopril plus isosorbide dinitrate or placebo. RESULTS: Compared with placebo, the three active therapies decreased blood pressure and left atrial pressure; limited infarct expansion, infarct thinning, noninfarct wall stretching and thickening; limited left ventricular dilation and increase in left ventricular mass; and decreased regional bulging, aneurysm frequency and left ventricular dysfunction. However, the decrease in asynergy and increase in volume ejection fraction were less with captopril or captopril plus isosorbide dinitrate than with isosorbide dinitrate. Infarct thinning and bulging at 6 weeks was also less with isosorbide dinitrate than with captopril. Although initial left ventricular asynergy, final scar sizes and noninfarct collagen content at 6 weeks were similar among the groups, collagen in the center of the infarct scar was less with captopril or captopril plus isosorbide dinitrate than with placebo or isosorbide dinitrate. CONCLUSIONS: Monotherapy with captopril or isosorbide dinitrate, or their combination, improved all remodeling variables, but isosorbide dinitrate improved function more than captopril or captopril plus isosorbide dinitrate. Inhibition of infarct collagen content by captopril suggests that benefits with captopril represent a balance between positive and negative effects, and its combination with isosorbide dinitrate might be advantageous.

Animals↗
PubMed1995

Analysis of Salmonella enteritidis isolates by arbitrarily primed PCR.

An arbitrarily primed PCR (AP-PCR) was developed to analyze the genomic DNAs of Salmonella enteritidis isolates from human outbreaks and from avian sources. The AP-PCR generated seven distinct randomly amplified DNA patterns among the S. enteritidis isolates studied. Differences in the DNA patterns among isolates of S. enteritidis phage types 13a and 8 as well as among S. enteritidis phage type 14b were observed. The AP-PCR analysis can be used to determine the differences among isolates within the same phage types and may be useful for tracing back the source of S. enteritidis outbreaks in humans more precisely.

Animals↗
PubMed1995

Hereditary proctalgia fugax and constipation: report of a second family.

A second family with hereditary proctalgia fugax and internal anal sphincter hypertrophy associated with constipation is described. Anorectal ultrasonography, manometry, and sensory tests were conducted in two symptomatic and one asymptomatic subjects within the same family and further clinical information was obtained from other family members. The inheritance would correspond to an autosomal dominant condition with incomplete penetration, presenting after the second decade of life. Physiological studies showed deep, ultraslow waves and an absence of internal anal sphincter relaxation on rectal distension in the two most severely affected family members, suggesting the possibility of a neuropathic origin. Both of these patients had an abnormally high blood pressure. After treatment with a sustained release formulation of the calcium antagonist, nifedipine, their blood pressure returned to normal, anal tone was reduced, and the frequency and intensity of anal pain was suppressed. These together improved the quality of the patients' sleep, which had previously been very troubled because of night time attacks of anal pain.

Adult↗
PubMed1995

Gastric emptying and the symptoms of vection-induced nausea.

OBJECTIVES: To examine the hypothesis that nausea during vection arises directly from an underlying alteration in gastric motility. DESIGN: The simultaneous application of vection and assessment of gastric emptying of a liquid, non-nutrient test meal allowed the examination of the interaction between changes in gastric motility and symptoms. METHODS: Studies were conducted in 14 volunteers. Vection was induced by seating the subject inside a rotating circular drum, which was painted with vertical black and white stripes. In the control study (n = 8) the drum was not rotated. Gastric emptying was measured by gamma scintigraphy of a radiolabelled isosmotic saline test meal. RESULTS: Vection induced upper abdominal sensations (epigastric awareness) in 10 subjects, eight of whom subsequently reported nausea; autonomic symptoms of sweating and pallor were experienced by 12 subjects. Two subjects remained completely asymptomatic during vection. None of the subjects experienced any sensations during the control study. Gastric emptying was significantly delayed during vection (P < 0.01). There was a highly significant correlation between gastric emptying and the intensity of nausea. However, examination of the gastric emptying profiles did not support any direct association between altered gastrointestinal motor activity and symptoms. Two subjects with slowing of gastric emptying exhibited no nausea or upper abdominal symptoms, while another two experienced nausea when the underlying rate of gastric emptying was similar to that of the control period. CONCLUSIONS: The delay in gastric emptying of a liquid test meal induced by vection appears to be a variable epiphenomenon of nausea. A cause and effect relationship between gastric emptying and nausea therefore appears unlikely.

Adult↗
PubMed1994

Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction.

BACKGROUND: Prolonged nitrate therapy during healing between 2 days and 6 weeks after anterior myocardial infarction has the potential for limiting further left ventricular remodeling (or changes in topography) and preserving function. Longterm therapy throughout healing over 6 weeks might be more beneficial than short-term therapy over the first 2 weeks after infarction. METHODS AND RESULTS: The effect of prolonged nitrate therapy between 2 days and 6 weeks during healing after infarction on serial parameters of ventricular remodeling (scar expansion, scar thinning, ventricular dilation, and hypertrophy) and function (asynergy or akinesis plus dyskinesis and ejection fraction) by serial two-dimensional echocardiography, hemodynamics, postmortem topography (computerized planimetry, geometric maps, and radiographs), and collagen content (hydroxyproline) was studied in 64 instrumented dogs randomized 2 days after left anterior descending coronary artery ligation to various nitrate regimens (n = 32) over the first 2 weeks (subgroup 1: 2% transdermal nitroglycerin at 8 AM and 4 PM, n = 6; subgroup 2: 2% transdermal nitroglycerin plus 2.6 mg of sustained-release oral nitroglycerin at 8 AM, 3 PM, and 10 PM, n = 5; subgroup 3: oral isosorbide dinitrate, 30 mg at 8 AM and 4 PM, n = 11) or 6 weeks (subgroup 4: isosorbide dinitrate, n = 10) and in matching controls (n = 32). Nitrate therapy reduced left atrial pressure, mean arterial pressure, and the rate-pressure product compared with controls over the 6 weeks. Postmortem scar mass and hydroxyproline were similar in control and nitrate groups. However, scar stretching and thinning, cavity dilation, noninfarct wall hypertrophy, and apical bulging were less with nitrates, especially in the long-term subgroup 4. In vivo remodeling parameters between 2 days and 6 weeks after ligation showed that, compared with controls, nitrate therapy prevented further stretching of the asynergic segment, decreased the expansion index, decreased further scar thinning, prevented the increase in ventricular volumes, reduced the frequency of ventricular aneurysm, prevented the increase in ventricular mass, reduced the extent of asynergy, and improved ejection fraction. Although the beneficial effect on topography and function was seen in all nitrate subgroups, the overall benefit was greater with long-term therapy over 6 weeks (subgroup 4) than short-term therapy confined to the first 2 weeks (subgroups 1, 2, and 3). CONCLUSIONS: Prolonged nitrate therapy, in various regimens during healing after infarction, effectively reduced left ventricular loading and prevented infarct thinning, further infarct expansion, progressive ventricular dilation, and the increase in mass. These effects were associated with decreased asynergy and improved ejection fraction. The beneficial effects were greater with long-term therapy over 6 weeks than short-term therapy over the first 2 weeks.

Animals↗
PubMed1994

Experimental infection of northern bobwhite quail with Borrelia burgdorferi.

Four-week-old northern bobwhite quail (Colinus virginianus) were inoculated subcutaneously with 10(6) organisms from a low passage culture of Borrelia burgdorferi. Blood was collected weekly for culture, antibody detection, and immunoblot analysis. Three weeks postinoculation, viable spirochetes were isolated from the blood of one bird, but not from kidney, spleen, liver, or heart; all infected birds from which preinfection antibody titer had been established, had antibodies by the enzyme-linked immunosorbent assay (ELISA). The inoculated birds did not show clinical signs of disease and there were no detectable gross or histopathologic lesions. Borrelia burgdorferi was detected in sections of kidneys on fluorescent antibody tests. Using a polymerase chain reaction (PCR) analysis to detect Borrelia burgdorferi DNA in tissue samples, the expected PCR product (DNA) of 246 base pairs was visible on agarose gel stained with ethidium bromide. The identity of the PCR product was confirmed by slot blot hybridization with Borrelia burgdorferi specific DNA probe. Thus, these birds sustained infections for at least 3 weeks without clinical signs and may play a role in the transmission of Borrelia burgdorferi.

Animals↗
PubMed1993

Thermodynamic and kinetic studies on the mechanism of binding of methylumbelliferyl galactosides to the basic agglutinin from winged bean (Psophocarpus tetragonolobus).

The binding of winged bean basic agglutinin (WBA I) to 4-methylumbelliferyl (MeUmb) galactosides was examined by extrinsic fluorescence titration and stopped-flow spectrofluorimetry. Upon binding to WBA I, MeUmb alpha-galactosides show quenching in fluorescence intensity, decrease in UV absorbance with a concomitant blue shift, and decrease in fluorescence excited-state lifetimes. However, their beta-analogues show enhancement in fluorescence intensity, increase in UV absorbance with a red shift, and an increase in fluorescence excited-state lifetimes. This implies that the umbelliferyl groups of alpha- and beta-galactosides experience non-polar and polar microenvironments, respectively, upon binding to WBA I. Replacement of the anomeric hydroxyl group of galactose by 4-methylumbelliferyl moiety increases the affinity of resulting saccharides. Substitution of C-2 hydroxyl of galactose by an acetamido group leads to increased affinity due to a favorable entropy change. This suggests that acetamido group of MeUmb-alpha/beta-GalNAc binds to a relatively non-polar subsite of WBA I. Most interestingly, this substitution also reduces the association rate constants dramatically. Inspection of the activation parameters reveals that the enthalpy of activation is the limiting factor for the differences in the forward rate constants for these saccharides and the entropic contribution to the activation energy is small.

Acetylgalactosamine↗
PubMed1993

Effect of varying the rate and pattern of gastric distension on its sensory perception and motor activity.

The aim of the present study was to see if varying the rate and pattern of gastric distension affected its motor and sensory responses to distension. A balloon was used to carry out distensions in male volunteers at constant rates of 20, 50, 100, and 200 ml/min. In addition rapid (75 ml/s) intermittent distensions (RID) were carried out with the use of a large hand-held syringe. Subjects were asked to indicate the first perception of the balloon, fullness, and discomfort. Increasing the rate of ramp distension caused all sensations to occur at higher volumes and higher pressures and reduced the frequency and amplitude of phasic oscillations in gastric pressure. During RID, the same sensations were experienced at much reduced volumes but were poorly sustained. These data suggest that ramp and RID are likely to induce gastric sensations by activating different populations of receptors. The responses to ramp distension are compatible with the activation of stretch receptors situated in parallel with the muscle elements, whereas RID appear to be activating a different population of rapidly adapting mechanoreceptors possibly situated in the mucosa.

Adult↗