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Biomedical subjects

A Iqbal

Publications and source records attributed to A Iqbal.

At least 73 records · Page 4Linked to original sources

Prognostic value of exercise radionuclide angiography in a population-based cohort of patients with known or suspected coronary artery disease.

Five hundred thirty-six residents of Olmsted County, Minnesota, who underwent supine rest and exercise radionuclide angiography because of known or suspected coronary artery disease, were followed for a median of 46 months to determine the prognostic value of exercise radionuclide angiography in a community population who generally did not undergo coronary angiography. There were 71 persons who experienced a new cardiac event (the initial events were cardiac death and nonfatal myocardial infarction in 26 and 45 persons, respectively). A proportional-hazards model identified 4 independent predictors of cardiac events: exercise ejection fraction (p < 0.001), exercise heart rate (p < 0.001), and age (p = 0.04). Four-year infarct-free survival was 98% for the 152 patients with a peak exercise heart rate at or above the median (122 beats/min) and an exercise ejection fraction at or above the median (0.58). In the 150 patients with a peak exercise heart rate < 122 beats/min and an exercise ejection fraction < 0.58, 4-year infarct-free survival was 68%. When this population-based cohort was compared with a referral case series previously reported from our institution, these population-based patients were significantly more likely to be men, to have typical angina, to have higher exercise heart rates and exercise ejection fractions, and were less likely to be receiving beta-receptor antagonist therapy. At each level of exercise ejection fraction, the population-based patients had a slightly but insignificantly greater risk than referral patients for subsequent cardiac events. These population-based data provide strong evidence of the prognostic value of exercise radionuclide angiography in community practice.

Age Factors↗

Evolution of echocardiographic modalities in detection of postmyocardial infarction ventricular septal defect and papillary muscle rupture: study of 62 patients.

Diagnostic sensitivity of various echocardiographic modalities was assessed for postinfarct ventricular septal defect (40 patients) and papillary muscle rupture (22 patients). Two-dimensional transthoracic echocardiography enabled direct visualization of ventricular septal defect in 68% and combined two-dimensional Doppler echocardiography was diagnostic in 95%. Papillary muscle rupture was directly visualized in 45%, and severe mitral regurgitation was present on Doppler color flow images in 100%. Transesophageal echocardiography was diagnostic in all nine patients (five with ventricular septal defect and four with papillary muscle rupture) in whom this modality was applied. Thus two-dimensional Doppler echocardiography (transthoracic and transesophageal if necessary) is highly sensitive in detecting postinfarct ventricular septal defect and papillary muscle rupture.

Aged↗

Protection by oestradiol against the development of cardiovascular changes associated with monocrotaline pulmonary hypertension in rats.

1. We studied the effects of oestradiol 17 beta on the development of pulmonary vascular changes and right ventricular (RV) hypertrophy in response to monocrotaline in male Sprague-Dawley rats. 2. Rats were treated with either placebo or oestradiol 17 beta (10 mg) in the form of slow release pellets implanted subcutaneously 48 h before monocrotaline administration. Rats were injected with either saline or a single dose of monocrotaline (60 mg kg-1, i.m.). Pulmonary vascular changes and RV hypertrophy were studied at 4 weeks following monocrotaline administration. 3. Monocrotaline induced a significant increase in the ratio of right ventricle (RV) to left ventricle-plus-septum (LV + S) weights. Monocrotaline-treated rats also showed significant myointimal proliferation in small pulmonary arteries, decrease of arterial numbers and increase in the number of abnormal alveolar macrophages. 4. Oestradiol 17 beta attenuated myointimal hyperplasia in pulmonary vessels, decreased the RV/(LV + S) ratio in monocrotaline-treated rats. Oestradiol 17 beta had no significant effect on control animals. 5. Oestradiol treatment prevented the increase in lung wet to dry weight ratio, observed 7 days post monocrotaline administration. 6. These results suggest that oestradiol 17 beta protects against the pulmonary vascular remodelling and RV hypertrophy associated with monocrotaline-induced pulmonary hypertension in the rat. Oestradiol also protects against microvascular leak observed in the early days of lesion.

Animals↗

Heroin addiction and sex hormones in males.

To investigate the effects of illicit heroin abuse on the endocrine system a study was carried out in North West Frontier Province (NWFP) where heroin addiction is prevalent. Sixty-eight subjects were included in this study. Thirty-three were untreated heroin addicts visiting "drug abuse treatment centres" in Peshawar and 35 age matched normal males. Urine samples of all addicts showed the presence of morphine. The serum concentrations of testosterone (T) in addicts was 228 ng/ml, leutinizing hormone (LH) 10.7 mlU/ml and folical stimulating hormone (FSH) 4.9 mlU/ml whereas the corresponding values for control males were T 630 ng/ml, LH 14.3 mlU/ml and FSH mlU/ml, respectively. Heroin exerts a depletion effect on T and FSH levels in more or less all the groups studied irrespective of age, amount of heroin intake per day and period of contact with heroin. LH levels remained affected and are within clinically accepted normal range.

Adolescent↗

Noninvasive assessment of cardiac risk in insulin-dependent diabetic patients being evaluated for pancreatic transplantation using thallium-201 myocardial perfusion scintigraphy.

We examined the value of thallium-201 myocardial perfusion scintigraphy in noninvasive assessment of cardiac risk in 36 insulin-dependent (type 1) diabetic patients being evaluated for pancreas or combined pancreas/kidney transplantation. An extensive cardiovascular evaluation including electrocardiogram was performed in all patients, and most patients were also evaluated by two-dimensional and Doppler echocardiography. Exercise thallium studies were performed in 31 patients. Five patients were unable to exercise and underwent dipyridamole-thallium study. The thallium images were abnormal in 12 patients, 10 of whom underwent coronary arteriography. Significant coronary artery disease was found in 7 of these patients. Nineteen patients underwent pancreatic (3 patients) or pancreato-renal (16) transplantation without any occurrence of cardiac death or nonfatal myocardial infarction peri-operatively or on follow-up ranging from 7 months to 21 months. In contrast, 3 cardiac events occurred in 12 patients not approved for transplantation, each of whom had an abnormal thallium study exhibiting significant ischemia. Resting left ventricular global and regional function was not helpful in determining perioperative risk. Thus, thallium-201 myocardial perfusion scintigraphy may be useful in identifying diabetic patients at low risk for pancreas transplantation and may obviate the need for routine coronary angiography in these patients.

Adult↗

Vascular actions of TA 3090, a novel analog of diltiazem: interaction with endothelium-dependent relaxation in canine femoral and coronary arteries.

The effects of a new 1,5-benzothiazepine calcium antagonist, TA 3090 (an analog of diltiazem), were analyzed in isolated canine femoral and coronary arteries suspended in organ chambers or studied in a bioassay system. TA 3090 (10(-9) to 10(-4) M) caused comparable relaxations in arterial rings with and without endothelium contracted by prostaglandin F2 alpha. Coronary arteries were more sensitive to the Ca++ antagonist. In both preparations, TA 3090 was more potent than diltiazem. In femoral (but not coronary) artery rings with endothelium, acetylcholine (10(-8) M) inhibited relaxations to TA 3090. Previous treatment of femoral or coronary arteries with TA 3090 (10(-6) M) had no effect on endothelium-dependent relaxations to acetylcholine. In a bioassay system, TA 3090 (2 x 10(-7) M) caused partial reversal of acetylcholine-induced relaxation in perfused femoral arteries and superfused coronary arterial rings. The dihydropyridine enantiomer (-)-202,791 did not affect acetylcholine-induced relaxations and did not prevent the reversal by TA 3090. These data indicate that, in addition to a direct action on vascular smooth muscle, this novel benzothiazepine Ca(++)-antagonist interferes with the synthesis/release of endothelium-derived relaxing factor stimulated by acetylcholine in canine femoral arteries. These findings, which are similar to those obtained with d-cis-diltiazem, support the hypothesis that a specific benzothiazepine-dependent mechanism(s) can suppress the production of endothelium-derived relaxing factor in endothelial cells.

Acetylcholine↗

Growth hormone induced stimulation of the T4 to T3 conversion in fed and fasting dwarf goats.

Fed and food deprived (7 days) adult dwarf goats were injected intravenously with 75 micrograms/kg b. w. of ovine growth hormone (o-GH). Blood samples were collected from the jugular vein -2, -1 and 0 hr prior to and 30, 60, 90 and 120 min after injection and assayed for thyroxine (T4) and triiodothyronine (T3) concentrations. The 5'-monodeiodination (5'-D) activity was consequently determined in liver and kidney samples following slaughtering. Fasting alone increased plasma concentrations of T3 and T4, whereas injection of o-GH raised T3 additionally and more profoundly in food deprived animals compared to fed ones. A small increase in plasma T4 was also observed following o-GH injection, but only in starved goats. At the same time the hepatic, but not the kidney, 5'-D activity was stimulated in food deprived and GH injected animals. It is concluded that during prolonged fasting an increased peripheral T4 to T3 conversion is occurring contrary to the known decrease in T3 production during short periods of food deprivation. This increased conversion may be under the control of GH.

Animals↗

Effect of malathion and methyl-parathion on rat liver enzymes.

The effect of sub-lethal doses of Malathion and Methyl-parathion was studied on the rat liver enzymes. Intravenous administration of both insecticides at weekly interval for four weeks resulted in increase in heart and spleen weight. Short term (24 hr.) and long term (4 weeks) treatment with insecticides resulted in increased specific activities of liver enzymes, Acid phosphatase, Alkaline phosphatase, Glutamate dehydrogenase, Glutamate oxaloacetate transaminase and Glutamate pyruvate transaminase. The increase in enzyme activity was not as profound when the insecticide administration was spread over 4 weeks. Malathion had greater effect than Methyl-parathion on the biochemical parameters studied.

Animals↗

Effect of malathion and methyl-parathion on rat liver enzymes.

The effect of sub-lethal doses of Malathion and Methyl-Parathion was studied on the rat liver enzymes. Intravenous administration of both insecticides at weekly interval for four weeks resulted in increase in weight of various tissues, i.e., heart and spleen. Short term (24 hr) and long term (4 weeks) treatment with insecticides resulted in increased specific activities of liver enzymes, Acid phosphatase, Alkaline phosphatase, Glutamate dehydrogenase, Glutamate oxaloacetate transaminase and Glutamate pyruvate transaminase. The increase in enzyme activity was not as profound when the insecticide administration was spread over 4 weeks. Malathion had greater effect than Methyl-parathion on the biochemical parameters studied.

Animals↗

Inhomogeneous deposition of radiopharmaceuticals at the cellular level: experimental evidence and dosimetric implications.

We have undertaken an experimental examination of the conventional internal dosimetry assumptions of homogeneity of radionuclide deposition in tissues. The distribution of radiolabeled Microlite has been quantitated in mouse liver at the millimeter (multicellular) and the micrometer (cellular) levels. Measurements of radioactivity in 1-mm3 tissue samples indicate homogeneous radionuclide distribution; those derived from autoradiographs of 0.5-micron tissue sections show that, relative to other cells, the colloid was concentrated 200- to 1000-fold in liver macrophages. The dosimetric implications of such inhomogeneous radionuclide distribution in human liver, where similar radionuclide distribution is expected, are discussed on the basis of a recently developed model for calculating the dose at the cellular level, and the estimates are compared to conventional internal dosimetry predictions. It is demonstrated that during routine diagnostic examinations with 99mTc-Microlite, conventional dosimetry underestimates the dose to labeled human liver cells by factors of 8-30.

Animals↗

Thyrotropic and peripheral activities of thyrotrophin and thyrotrophin-releasing hormone in the chick embryo and adult chicken.

The influence of an intravenous injection of thyrotrophin-releasing hormone (TRH) and bovine thyrotrophin (TSH) on circulating levels of thyroid hormones and the liver 5'-monodeiodination (5'-D) activity is studied in the chick embryo and the adult chicken. In the 18-day-old chick embryo, an injection of 1 microgram TRH and 0.01 I.U. TSH increase plasma concentrations of triiodothyronine (T3) and of thyroxine (T4). TRH, however, preferentially raises plasma levels of T3, resulting in an increased T3 to T4 ratio, whereas TSH preferentially increases T4, resulting in a decreased T3 to T4 ratio. The 5'-D-activity is also stimulated following TRH but not following TSH administration. The increase of reverse T3 (rT3) is much more pronounced following the administration of TSH. In adult chicken an injection of up to 20 micrograms of TRH never increased plasma concentrations of T4, but increases T3 at every dose used together with 5'-D at the 20 micrograms dose. TSH on the other hand never increased T3 or 5'-D, but elevates T4 consistently. It is concluded that TSH is mainly thyrotropic in the chick embryo or adult chicken whereas TRH is responsible for the peripheral conversion of T4 into T3 by stimulating the 5'-D-activity. The involvement of a TRH induced GH release in this peripheral activity is discussed.

Animals↗

Thyroid hormone response to thyrotropin releasing hormone after cold treatment during pre- and postnatal development in the domestic fowl.

The purpose of the present study was to compare the effect of periodic cooling during the establishment of a functional pituitary-thyroid axis at days 11-14 of incubation and at other developmental stages, on the subsequent thyroid hormone response to thyrotropin releasing hormone (TRH). In the first and second experiment chick embryos were cooled for 6 hr/day to 30 degrees C from day 11 till 14 and from day 15 till 18 respectively, whereas control groups were incubated throughout at 37.8 degrees C. In both experiments the thyroxine (T4) response upon TRH in 19 day-old embryos was higher in the previously cold treated embryos, according to the percentages of increase. However, the higher T4 response in the cold treated animals disappeared in 1 or 7 day-old chicks hatched from the 2nd experiment, but remained present in chicks of the same ages in the 1st experiment. In a third experiment the T4 response to TRH injection immediately and 3 and 8 days after a temperature treatment (25 degrees C or 12 degrees C) for one week on four weeks old broiler chickens was found to be similar in both temperature groups. In all experiments there was a concomitant triiodothyronine (T3) increase after TRH injection, but differences between experimental groups were observed at days 15 and 19 of incubation and immediately after the postnatal temperature treatment. As an overall conclusion the results indicate that cold treatment only during the establishment of the hypothalamo-hypophysial control of thyroid function can have a long lasting effect by enhancing the T4 response to TRH injection.

Animals↗

Flunarizine inhibits endothelium-dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle.

1. Hypoxia augments contractile responses to several vasoactive agents in canine isolated coronary arteries with intact endothelium. Calcium antagonists inhibit the further increases in tension caused by hypoxia. The present experiments were designed to determine whether the calcium-antagonist flunarizine would inhibit hypoxic contractions in isolated blood vessels through an action on the endothelium or on the vascular smooth muscle. 2. Rings of canine coronary arteries, with or without endothelium, were suspended at optimal length for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. 3. Hypoxia (95% N2 and 5% CO2) augmented contractile responses to prostaglandin F2 alpha (2 x 10(-6) M); removal of the endothelium abolished this hypoxic facilitation. 4. Flunarizine (5 x 10(-5)-5 x 10(-7) M) exerted a long-lasting inhibition of the hypoxic facilitation in a concentration-dependent manner. Flunarizine did not inhibit the response to prostaglandin F2 alpha. 5. To differentiate between the response of smooth muscle and the endothelium, strips of coronary arteries without endothelium were layered with strips with or without endothelium. Hypoxia augmented contractions only in layered preparations with endothelium. Flunarizine prevented the hypoxic contractions in layered preparations in which only the smooth muscle was treated with flunarizine. In contrast, when only the endothelium was treated, no or minimal inhibition of the hypoxic contraction occurred with flunarizine (10(-5) and 5 x 10(-5) M, respectively). 6. These experiments indicate that the calcium antagonist flunarizine inhibits endothelium-dependent hypoxic facilitation in canine coronary arteries primarily through its action on vascular smooth muscle.

Animals↗

The coordinate replication of the human beta-globin gene domain reflects its transcriptional activity and nuclease hypersensitivity.

The temporal order of replication of DNA sequences in the chromosomal domain containing the human beta-globin gene cluster and its flanking sequences (140 kilobases) was measured and compared in two different human cell lines. In human erythroleukemia (K562) cells, in which embryonic and fetal globin genes are transcribed, all of the sequences we examined from the beta-globin domain replicated early during S phase, while in HeLa cells, in which globin genes are transcriptionally silent, these sequences replicated late during S. Potential sites of initiation of DNA replication within this domain were identified. The beta-globin gene domain was also found to differ with respect to the nuclease sensitivity of the chromatin in these two cell lines. In K562 cells, hypersensitive sites for endogenous nucleases and DNase I were present in the chromatin near the earliest-replicating segments in the beta-globin domain.

DNA Replication↗

Inhibitors of cyclooxygenase augment serotonergic responsiveness in canine coronary arteries.

Experiments were designed to determine the role of products of cyclooxygenase in contractions of coronary smooth muscle evoked by serotonin. Rings of canine coronary artery without endothelium were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Serotonin caused concentration-dependent contractions followed by secondary relaxations at higher doses. Indomethacin and meclofenamate augmented both the contraction and the relaxation. Indomethacin did not affect contractions evoked by increasing concentrations of either phenylephrine, prostaglandin F2 alpha, or potassium chloride. Propranolol did not affect the concentration-response curve to serotonin under control conditions; it prevented the facilitated contraction to the monoamine but not the augmented secondary relaxation caused by the inhibitors of cyclooxygenase. These results suggest that endogenous prostanoids simultaneously inhibit the contractile process and brake relaxations induced by higher concentrations of serotonin. As a consequence, inhibitors of prostanoid formation facilitate the vasospastic component of the response to the monoamine in large coronary arteries. For unknown reasons, propranolol prevents this facilitation.

Animals↗