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Biomedical subjects

M Anwar

Publications and source records attributed to M Anwar.

At least 127 records · Page 7Linked to original sources

Evaluation of human serum as a culture medium for studies of rat embryonic development in vitro.

The normal growth of rat embryos cultured in human serum supplemented with glucose and 10% rat serum is of potential use in the assessment of teratogenic risk in man. Before this technique can be widely applied, it is necessary to know whether the stages of the menstrual cycle at which a serum sample is tested materially affect the results obtained. Moreover, in order to achieve reproducible conditions we have found it necessary to add a minimal amount of rat serum to the human serum used for culture, but unnecessarily high levels of rat serum supplementation could over-compensate for any growth factor deficiency in human serum. Here we report that culture of rat conceptuses gives similar results irrespective of whether human first, second, or third trimester pregnancy serum, postnatal serum, or serum at various stages of the menstrual cycle is used. We also report that addition of 2% rat serum supplement is sufficient to achieve reproducible rat embryonic growth and differentiation in human serum.

Animals↗

Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic alpha cells.

The regulatory region of the rat preproglucagon gene targets expression of the SV40 large T oncoprotein to two cell types in transgenic mice, the pancreatic alpha cells and a set of neurons localized in the hindbrain, both of which normally produce preproglucagon. Additional neurons in the forebrain and midbrain stain for T antigen but do not express the endogenous glucagon gene. Synthesis of T antigen in endocrine alpha cells results in the heritable development of pancreatic glucagonomas. In brains of transgenic mice from three independent lineages, expression of the hybrid gene begins at embryonic day 12 in neuroblasts of the hindbrain, where it continues throughout adult life, most notably in the medulla. Remarkably, oncoprotein expression in both proliferating neuroblasts and mature neurons has no apparent consequences, either phenotypic or tumorigenic. Expression of the hybrid glucagon gene in both neurons and islet cells supports a possible interrelationship between these cell types.

Animals↗

Effect of prazosin on microvascular perfusion during middle cerebral artery ligation in the rat.

The purpose of this study was to evaluate the effects of prazosin, an alpha 1-adrenoceptor antagonist, on morphometric indexes of the total and perfused cerebral microvascular bed 1 hour after middle cerebral artery (MCA) ligation in pentobarbital-anesthetized rats. We hypothesized that this agent would prevent catecholamine-induced vasoconstriction in the ischemic brain. Cerebral blood flow (CBF) was determined with 14C-iodoantipyrine, and the perfused microvascular bed was visualized using fluorescein isothiocyanate-dextran. MCA occlusion did not alter systemic hemodynamic or blood gas parameters. CBF averaged 29 +/- 15 (mean +/- SD) ml/min/100 g in the MCA-ligated cortex and 49 +/- 18 in the other examined brain regions. Prazosin did not significantly alter these CBF values, averaging 26 +/- 14 and 48 +/- 10, respectively. There were no significant regional differences in total capillaries/mm2 in either group. The percent of the capillaries/mm2 perfused (51 +/- 6%) was similar in the two groups in all examined regions except the ischemic cortex. In the MCA-ligated cortex, 22 +/- 8% of the capillary volume was perfused in comparison with 49 +/- 8% in the prazosin-treated group. Prazosin-treated rats had an increased percentage of their microvasculature perfused despite a similarly reduced CBF. Prazosin appeared to reduce diffusion distances in the ischemic cortex. This might be due to its alpha 1-adrenoceptor blocking activity.

Animals↗

Autoradiographic determination of regional cerebral blood flow during hypoglycemia in newborn dogs.

To ascertain the regional cerebral blood flow (CBF) responses to hypoglycemia, nine newborn dogs were treated with insulin to blood glucose concentrations ranging from 1 to 35 mg/dl (mean 22 mg/dl). Systemic physiologic monitoring revealed no differences in mean arterial blood pressure, heart rate, paO2, paCO2, pHa, or blood lactate in the hypoglycemis animals and five normoglycemic controls. Significant increases in CBF occurred in 17 of 20 analyzed structures of brain in the hypoglycemic puppies, ranging from 158 to 446% of the normoglyycemic values. The percent increases in CBF were greatest in brainstem structures compared to other major regions of brain. A positive correlation existed between mean arterial blood pressure and cerebral cortical blood flow, suggesting a loss of CBF autoregulation during hypoglycemia. The pathophysiologic mechanism for the elevations in regional CBF might relate to stimulation of beta-adrenergic receptors in brain, as has been shown in adults.

Animals↗

A role of insular cortex in cardiovascular function.

We sought to determine whether the insular cortex contributes to the regulation of arterial blood pressure (AP). Responses to electrical and chemical stimulation of the cortex were studied in the anesthetized, paralyzed, and artificially ventilated Sprague-Dawley rat. The insular cortex was initially defined, anatomically, by the distributions of retrogradely labeled perikarya following injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the nucleus tractus solitarii (NTS). Injections of WGA-HRP into the insular cortex anterogradely labeled terminals in cardiopulmonary and other divisions of the NTS and confirmed projections revealed by retrograde tracing experiments. Electrical stimulation of the insular cortex elicited elevations of AP (less than or equal to 50 mm Hg) and cardioacceleration (less than or equal to 40 bpm). The locations of the most active pressor sites corresponded closely to the locations of retrogradely labeled cells in layer V of granular and posterior agranular areas of the insular cortex (areas 14 and 13) and the extreme capsule. Maximal pressor responses were obtained at a stimulus intensity of three to five times threshold current of 20-30 microA. Responses elicited mostly with higher-threshold currents were also mapped in areas 2a and 5lb and the claustrum and within the corpus callosum. Unilateral injections into the insular pressor area of the excitatory amino acid monosodium glutamate (L-Glu; 0.05 nmol to 10 nmol) or the rigid structural analogue of L-Glu, kainic acid (KA) (0.4 nmol) (which specifically excite perikarya), caused topographically specific elevations in AP and tachycardia. During the course of the anatomical transport studies, new findings were obtained on the organization and characteristics of the cortical innervation of the NTS and the nucleus reticularis parvocellularis. Topographic relationships between the cortex and the NTS were organized in a more complex manner than previously thought. Cells projecting to caudal cardiopulmonary segments of the NTS were fewer and generally located ventrally and caudally and in a more restricted area than cells projecting rostrally or to the parvicellular reticular formation. Anterograde transport data revealed new presumptive terminal fields in dorsolateral, ventral, periventricular, and commissural regions of the NTS, including an area overlapping the terminal field of the aortic baroreceptor nerve. We conclude that neurons within an area of the insular cortex projecting to multiple brainstem autonomic nuclei, including a region of the NTS innervated by baroreceptor afferents, increase arterial blood pressure and heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The course of hyperbilirubinemia in the very low birth weight infant treated with phenobarbital.

We examined the effect of early phenobarbital therapy on the course of jaundice in 57 infants with birth weight below 1,500 g. The study group of 28 infants was treated with a phenobarbital loading dose of 20 mg/kg at 4.2 (3.6) [mean (SD)] hours of age, followed by a maintenance dose of 5 mg/kg/day for one week; 29 infants served as controls. Seventeen study and 19 control infants suffered from periventricular-intraventricular hemorrhage (IVH). The two groups had comparable risk factors that can potentially affect the course of hyperbilirubinemia. Peak serum bilirubin concentration was 7.9 (1.8) mg/dl in the treated group and 8.6 (2.2) mg/dl in the control group. Three infants in the treated group and seven infants in the control group had peak serum bilirubin concentration above 10 mg/dl. These differences in the peak serum bilirubin concentration or in the number of infants with peak serum bilirubin concentrations above 10 mg/dl are not statistically significant. However, treated infants achieved peak serum bilirubin concentration earlier (mean age 90 hours as compared to 138 hours in control infants), and required phototherapy for a shorter duration of time (5.5 days in the treated group as compared to 7.5 days in the control group). While these differences in the two groups with regard to age of peak serum bilirubin concentration and duration of phototherapy are statistically significant, they do not seem to be clinically important. Thus, in our group of very low birth infants phenobarbital failed to show any clinically important effects on the course of jaundice when used in conjunction with phototherapy.

Bilirubin↗

Adrenaline-synthesizing neurons in the medulla of the cat.

In this study, the distribution of neurons containing the adrenaline-synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) was mapped in the medulla of the cat. Data from recent studies in the rat suggest that the anatomical structure responsible for cardiorespiratory changes that occur following application of neurotransmitters and drugs to Schlaefke's area on the ventral medullary surface is the nucleus reticularis rostroventrolateralis (RVL), which is distinguished from adjacent regions of the reticular formation, in part, by the presence of adrenaline-synthesizing neurons. To determine whether an equivalent adrenergic population is present in the RVL of the cat, we used antibodies raised against bovine adrenal PNMT to map the distribution of adrenaline-synthesizing neurons in the reticular formation. In the ventrolateral medulla, we found that labeled cells extended from the level of the retrofacial nucleus to the calamus scriptorius. The majority of labeled cells were seen in a nucleus designated RVL at the level of the rostral one-third of the inferior olive. In the dorsomedial medulla, cells were labeled in the caudal aspect of the nucleus tractus solitarii (NTS) and were especially dense in the subnucleus gelatinosus and commissural nucleus of the vagus. A few lightly labeled cells were also present in the rostral pole of the area postrema (AP). In contrast to the rat, few or no immunoreactive cells were found in the rostral NTS, medial longitudinal fasciculus, nucleus paragigantocellularis dorsalis, or periventricular gray. Our results are consistent with the notion that an area of the RVL containing adrenergic perikarya is the anatomical structure responsible for cardiovascular changes that occur when chemicals are applied to Schlaefke's area.

Animals↗

Cast metal arch bars.

The construction technique and the use of custom made cobalt chrome arch bar is described.

Chromium Alloys↗

Anatomical evidence for interactions between catecholamine- and adrenocorticotropin-containing neurons.

Recent studies suggest that neurons containing adrenocorticotropin and catecholamines are localized to similar areas of the brain. In this immunocytochemical study, the distributions of neurons and terminals containing adrenocorticotropin and tyrosine hydroxylase, the first enzyme in the catecholamine biosynthetic pathway, were compared using the peroxidase-antiperoxidase technique. Neurons containing adrenocorticotropin and tyrosine hydroxylase formed overlapping hyperbolic lamina in the mediobasal hypothalamus. Although adrenocorticotropin and tyrosine hydroxylase containing neurons often formed small clusters, no double labeled cells were observed. Overlap also occurred between adrenocorticotropin and tyrosine hydroxylase terminal fields in several diencephalic nuclei including the periventricular hypothalamic gray and paraventricular thalamus. In contrast, other regions displayed striking compartmentalization of terminal fields; for example, in both the paraventricular hypothalamus and central nucleus of the amygdala, adrenocorticotropin was located in ventral and tyrosine hydroxylase in more dorsal aspects of the nuclei. Adjacent sections also showed a close correspondence between adrenocorticotropin terminals and tyrosine hydroxylase cell bodies in paraventricular, periventricular, dorsomedial and ventral hypothalamic nuclei. These data provide anatomical substrates for potential functional interactions between catecholamine and adrenocorticotropin systems in forebrain.

Adrenocorticotropic Hormone↗

Management of posthemorrhagic hydrocephalus in the preterm infant.

We studied the use of a subcutaneous ventricular catheter reservoir in 19 preterm infants with birth posthemorrhagic hydrocephalus. These infants were a poor risk for insertion of ventriculoperitoneal shunt due to their small size and hemorrhagic ventricular fluid at the time of diagnosis. The age at reservoir insertion was 29 +/- 9 days and the weight was 1,217 +/- 414 g. The reservoir was kept in place for 51 +/- 29 days with the removal of 527 +/- 421 mL of fluid by 57 +/- 42 taps. All infants tolerated the procedure well. Only two infants developed infection despite multiple reservoir taps. One infant expired due to unrelated causes. Three infants did not require a permanent shunt, while 15 infants had a ventriculoperitoneal shunt inserted prior to discharge at 3 to 4 months of age. We conclude that ventricular catheter reservoir is a safe and effective palliative procedure in the management of post hemorrhagic hydrocephalus in small preterm infants.

Apgar Score↗

Phenobarbitone prophylaxis of intraventricular haemorrhage.

Thirty preterm infants (birthweight under 1500 g) were treated with phenobarbitone to examine its effectiveness in reducing the incidence of intraventricular haemorrhage (IVH), the control group comprising 28 infants. The treated group had 57% incidence of IVH and mortality of 13% compared with 68% and 14%, respectively, in controls.

Cerebral Hemorrhage↗

Effect of caffeine on pneumogram and apnoea of infancy.

We studied the efficacy of caffeine in improving pneumogram abnormalities and relieving clinically important apnoea of infancy in 23 infants. After obtaining a 12 hour pneumogram we administered caffeine citrate in a loading dose of 20 mg/kg followed by 5 mg/kg once daily. This dose achieved a trough caffeine blood concentration of 9.6 (SD 2.0) micrograms/ml. A repeat pneumogram performed seven to 10 days after the first pneumogram showed a significant reduction in the number of short and prolonged attacks of apnoea as well as in the per cent periodic breathing and apnoea density. Episodes of prolonged apnoea disappeared in all infants after administration of caffeine and in 11 infants all pneumogram abnormalities resolved. This improvement in the results of pneumograms was associated with resolution of clinically important apnoea requiring intervention. Caffeine was administered for 3.4 (SD 1.3) months and was well tolerated by all except two infants. We conclude that treatment with caffeine is helpful in preventing attacks of apnoea that require intervention, and improvement in the results of pneumograms after administration of caffeine predicts this favourable response.

Apnea↗

Distribution of neurons containing phenylethanolamine N-methyltransferase in medulla and hypothalamus of rat.

Neurons immunocytochemically labeled with the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase were mapped in the brain of rat pretreated with colchicine. In medulla, immunoreactive cells in the C1 and C2 groups were distributed in a more complex manner than described previously. C1 neurons were identified in the reticular formation of ventrolateral medulla and were organized into two populations: (1) a cell column extending throughout the ventrolateral medulla, and lying ventral to the ambiguus cell group and either dorsal to the precerebellar lateral reticular nucleus or interposed between its two subdivisions; (2) a rostral cell cluster forming medial to the column at caudal levels and enlarging close to and in parallel with the ventral surface of the rostral ventrolateral medulla. A large proportion of cells and processes of the rostral cell group were oriented medially and ventromedially. processes of C1 neurons were traced dorsally toward the nucleus tractus solitarii, dorsal motor nucleus, and principal tegmental adrenergic bundle, ventrally toward the ventral surface, laterally toward the trigeminal complex, and medially or ventromedially toward the raphe. C2 neurons were located in the dorsomedial medulla and were subdivided into four distinct populations: (1) neurons in the rostral nucleus paragigantocellularis pars dorsalis (NGCd) and medial longitudinal fasciculus (MLF) were contiguous and similar in size and shape, with their long diameters oriented horizontally or diagonally along several axes; (2) neurons of the periventricular gray were located in a cytoarchitecturally undefined area dorsal to the MLF; these cells were ovoid, smaller, and organized more compactly than those in the NGCd-MLF; (3) a cell group in the rostromedial nucleus tractus solitarii (NTS) and dorsal motor nucleus overflowed caudally into the intermediate thirds of both structures; and (4) a parvicellular group in the NTS was compactly organized in the dorsolateral NTS and was best developed at the level of the area postrema. Processes of C2 neurons were generally directed sagitally, medially, and laterally along the ventricular floor and ventrally or medially toward the raphe; other fibers arborized and terminated within the NTS and dorsal motor nucleus. In the medulla, local processes were traced from C1 and C2 neurons directly into respective ventral and dorsal parts of the medullary raphe and surrounding intraparenchymal blood vessels. Fibers from these neurons were also followed, respectively, onto the ventral subpial surface and the floor of the fourth ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Newly identified GABAergic neurons in regions of the ventrolateral medulla which regulate blood pressure.

Glutamic acid decarboxylase (GAD), the enzyme which synthesizes the inhibitory transmitter gamma-aminobutyric acid (GABA), was localized immunocytochemically within cells and processes distributed throughout the ventrolateral medulla. In caudal regions, GAD-stained cells were adjacent to the 'precerebellar' lateral reticular nucleus and partially overlapped the A1 area of norepinephrine synthesizing neurons. The largest number of labeled neurons filled the rostral ventrolateral medulla (RVL), coinciding with and extending beyond the C1 adrenergic area. GAD-positive cells also occupied the nucleus reticularis parvocellularis, raphe magnus (RM) and lateral wings of RM in the region of the pararaphe. Intrinsic GAD-containing cells in the ventrolateral medulla may tonically inhibit sympathoinhibitory neurons in the caudal ventrolateral medulla (CVL) and sympathoexcitatory neurons in the RVL.

Animals↗

Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants.

We studied 47 infants with either grade 3 or grade 4 intraventricular hemorrhage, to assess the efficacy of intermittent lumbar punctures in the prevention of post-hemorrhagic hydrocephalus in a prospective controlled trial. The control group received supportive care only, whereas the treatment group additionally underwent intermittent spinal taps. The spinal taps were started at postnatal age 11 +/- 5 days and continued for 20 +/- 16 days, with the removal of 67 +/- 101 ml cerebrospinal fluid using 16 +/- 12 taps. The two groups were comparable with regard to birth weight, gestational age, race, sex, Apgar score, and severity of hemorrhage. Three infants in the control group died, compared with two infants in the study group. Nine infants in the control group and 10 infants in the study group developed hydrocephalus requiring a ventriculoperitoneal shunt or a ventricular catheter reservoir. These differences in the outcome in the two groups are not statistically significant. We conclude that serial lumbar punctures were unsuccessful in prevention of hydrocephalus in this group of preterm infants with intraventricular hemorrhage.

Cerebral Hemorrhage↗