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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 253 records · Page 14Linked to original sources
PubMed1993

Pharmacodynamic and hemodynamic effects of mivacurium in infants anesthetized with halothane and nitrous oxide.

BACKGROUND: The newly developed neuromuscular blocking agent, mivacurium, has been evaluated in adults and children, but there are no data on its effects in infants. This study was designed to evaluate the neuromuscular effects of mivacurium by dose-response analysis, and its cardiovascular effects in 90 infants 2-11 months of age anesthetized with 1% halothane and nitrous oxide:oxygen. METHODS: The neuromuscular response was measured by recording the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The infants were divided according to age into two equal groups of 45; group A infants were 2-6 months of age, and group B infants were 7-11 months of age. Each group was further subdivided into five subgroups of nine. Infants in group A received mivacurium at sequential doses of 40, 50, 55, 75, and 150 micrograms/kg, while those in group B received mivacurium at doses 40, 50, 60, 75, and 150 micrograms/kg. The first four doses in each group were used to determine dose-response relationships. The last two doses of 75 and 150 micrograms/kg were based on the observed preceding dose-response data to approximate the ED95 and 2XED95. Heart rate and blood pressure were determined every minute for a minimum of 3 min after mivacurium. RESULTS: The effective doses for 50% depression of the first twitch response of the train-of-four (ED50) were 44-50 micrograms/kg (confidence limits 29-74 micrograms/kg), without any significant difference between groups A and B. In both groups, a larger dose of mivacurium, 150 micrograms/kg, caused complete ablation of the twitch response in 1.3 +/- 0.2 min (mean +/- SE) with recovery to 5, 25, and 95% of control in 7.6 +/- 0.5, 9.4 +/- 0.6, and 16.2 +/- 0.9 min, respectively. In infants, the 25-75% recovery index was 3.8 +/- 0.4 min, and the 5-95% recovery index was 8.5 +/- 0.8 min. In 28 infants, in whom surgical relaxation was required for more than 20 min, the infusion requirements to maintain 90-99% neuromuscular block in infants 2-6 and 7-11 months of age were 12.1 +/- 1 and 9.9 +/- 1 micrograms.kg-1.min-1, respectively (NS). No significant changes of heart rate of blood pressure occurred in infants, except in the subgroup of infants 7-11 months of age who received 150 micrograms/kg mivacurium. In this group, a 13-mmHg increase in mean systolic blood pressure was seen without any significant change in diastolic pressure or heart rate. In addition, in 7 of 36 patients receiving 75-150 micrograms/kg mivacurium, a greater than 29% change in systolic or diastolic pressure occurred. One infant with cholinesterase deficiency had a prolonged neuromuscular block from mivacurium. CONCLUSIONS: The ED50 duration of action and infusion requirements of mivacurium in infants 2-6 months of age are comparable with those of infants 7-11 months of age.

Anesthesia, Inhalation↗
PubMed1993

Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel beta subunit from normal human heart.

We have cloned and sequenced cDNAs for three isoforms of the L-type voltage-dependent calcium channel beta subunit isolated from a normal human heart cDNA library. One of these subunits, designated beta a, hybridized with a 3.4-kb message, and the other two, designated beta b and beta c, hybridized with a message of approximately 1.9 kb. The presence of both of these latter two messages in human heart was confirmed by polymerase chain reaction methodology. Considering the differences between beta a and beta b/beta c, we find it likely that these messages may be encoded by two different gene sequences, beta a and beta b/beta c, and that the beta b/beta c sequence can be alternatively spliced in the 209-260 region. The data suggest that the human heart presents a different pattern of beta subunit expression from that found in the rat and rabbit heart.

Amino Acid Sequence↗
PubMed1993

Evidence for embolization from a posterior cerebral artery thrombus by transcranial Doppler monitoring.

BACKGROUND: Transcranial Doppler monitoring enables the detection of emboli passing through intracranial arteries. Comparison of the different intracranial vessels with respect to emboli detection can be of use in identifying the source of embolism. CASE DESCRIPTION: We report the case of a patient with an acute posterior cerebral artery (PCA) infarct on the right side, with evidence for high-degree ipsilateral PCA narrowing on admission. During transcranial Doppler monitoring 3 days later, we found frequent emboli-like signals in the power spectrum of the right PCA distal to the stenosis but not in any other intracranial vessels. Four days later, angiography and transcranial Doppler failed to show PCA narrowing, and transcranial Doppler monitoring of the right PCA showed no further emboli-like signals. A stenosis of the right vertebral artery was regarded as the possible source of thromboembolic narrowing of the PCA. CONCLUSIONS: We assume that in our patient a thrombotic clot in the PCA was resolved autolytically through detachment of small emboli into the distal part of the PCA. We speculate that in the early course of autolysis a larger fragment of the clot had occluded one of the distal branches, thus leading to the small PCA territory infarct.

Blood Flow Velocity↗
PubMed1993

Magnetic resonance angiography in vertebrobasilar ischemia.

BACKGROUND AND PURPOSE: Magnetic resonance angiography is a new, noninvasive technique whose diagnostic value in vertebrobasilar artery disease has not yet been determined. METHODS: Forty-one patients with acute cerebellar and/or brain-stem ischemia were examined by routine magnetic resonance imaging, extracranial and transcranial Doppler ultrasound, and selective intra-arterial arteriography. Results were correlated with magnetic resonance angiography. Magnetic resonance angiography was accomplished using a three-dimensional time-of-flight gradient-echo technique. RESULTS: Magnetic resonance angiography correctly identified all occlusions, stenoses, and an aneurysm within the distal vertebrobasilar system as revealed by conventional intra-arterial arteriography but missed the diagnosis of vertebral artery dissection in one case. This results in a sensitivity of magnetic resonance angiography of 97% and a specificity of 98.9%. However, the degree of stenoses was difficult to evaluate by magnetic resonance angiography. At least for severe obstructive lesions, this drawback can be eliminated by application of presaturation pulses, which allow the analysis of flow direction and collateral blood flow. Doppler ultrasound studies add useful hemodynamic information for less severe degrees of stenoses. CONCLUSIONS: The combined use of magnetic resonance angiography and Doppler ultrasound findings may replace the invasive intra-arterial arteriography examination in many patients with suspected macroangiopathy of the vertebrobasilar arteries.

Adult↗
PubMed1993

Safety of heparin-coated circuits in primates during deep hypothermic cardiopulmonary bypass.

The purpose of this study is to evaluate the biologic impact of heparin-coated circuits without systemic heparinization during deep hypothermia. Baboons (n=6) were placed on a heparin-coated pediatric closed-circuit cardiopulmonary bypass (CPB) system and cooled to 18 degrees C. A control group (n=7) underwent similar protocol with a non heparin-coated circuit and received systemic heparin. Either low flow at 0.5 L/min/m 2 (n=8; 4 in each group) or circulatory arrest (n=5; 2 in experimental group and 3 in control group) was used during deep hypothermia. Samples for complete blood count (CBC), hepatic and renal function tests, activated clotting time (ACT) and thrombelastogram (TEG) were obtained before, during, and after bypass. Cerebral blood flow was measured using Xenon-133 and autopsies were performed to assess end-organ damage. The ACT returned to baseline in both groups, and renal and hepatic function were within normal limits. There was no significant difference between the TEG values between the groups post bypass. Fibrin split products were absent and fibrinogen levels were normal in both groups following bypass. Cerebral blood flows were equivalent in both groups before and after bypass, although in the heparin-coated group cerebral blood flows were significantly higher during CPB. There were no brain histologic changes in the heparin-coated group and one focal cortical infarct in the control group. This study suggests that hypothermia induced a state of anticoagulation that did not result in thrombus formation or end organ dysfunction during CPB with a heparin-coated circuit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Adult dental health in the Keewatin.

In 1990, as part of a major health status assessment, a dental survey was carried out on a 20 per cent random sample of the adult population in the Keewatin region of the Northwest Territories. A 73 per cent response rate was obtained. Of the 397 people examined, 334 (88 per cent) identified themselves as Inuit. More than 20 per cent of the respondents were edentulous, including 10 per cent of those 18 to 34 years old. The median DMFT was 24 for all respondents and 21 for dentulous respondents. There was a significant difference between Inuit and non-Inuit respondents, which was most marked in the 18 to 34 year old age group (mean DMFT 22.1 versus 15.6, p < .001). The proportion of filled to decayed and filled surfaces (F/DF) was 50 per cent. Periodontal disease was common and increased with age. More than 73 per cent of the dentate individuals had gingival bleeding at one or more sites. Very few were free of calculus. Mean pocket depth increased with age (1.3 mm at 18-34 years of age, rising to 2.3 at 55 plus, p < .001). Sixty per cent of adults needed at least one restorative procedure, 68 per cent needed prophylaxis, and 45 per cent needed periodontal treatment. Men required more treatment of all types than women. The results of this study confirm the clinical impression that dental disease is rampant among the Inuit population. There are major needs for both preventive and treatment services.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Molecular and cellular aspects of calcium channel antagonism.

Calcium fluxes play a key role in controlling many physiologic processes and responses in the body. The past few years have witnessed major advances in understanding of L-type calcium channels and their blockade with calcium channel antagonists. The L-type calcium channels comprise 5 subunits termed alpha 1, alpha 2, beta, gamma, and delta. Elucidation of the mechanisms of action of the calcium channel antagonists has been advanced by cloning and genetic manipulation of these subunits. The alpha 1 subunit appears to be responsible for channel opening and voltage dependency, and it contains receptors for calcium channel antagonists; these geographically distinct receptors correspond to each of the 3 different chemical classes of antagonists, exemplified by diltiazem, nifedipine, and verapamil. Diltiazem appears to have an inhibitory effect on mitochondrial sodium-calcium exchange that is unique among calcium channel antagonists. Preliminary data suggest that a diltiazem-specific receptor also exists in the endothelium. It appears, therefore, that despite advances in the understanding of L-type calcium channels, much remains to be learned about other possible receptors for the calcium channel antagonists.

Calcium Channel Blockers↗
PubMed1992

Evidence for the existence of RNA of Ca(2+)-channel alpha 2/delta subunit in Xenopus oocytes.

Ba(2+)-currents (IBa) through voltage-dependent Ca(2+)-channels were studied in Xenopus oocytes injected with RNA from several excitable tissues, using the two-electrode voltage-clamp technique. Previous studies have shown that the expression of cardiac Ca(2+)-channels can be suppressed by an hybrid-arrest procedure that includes co-injection of the tissue-derived RNA with an 'antisense' oligonucleotide complementary to a part of RNA coding for the Ca(2+)-channel alpha 1 subunit. In this study, this method was used to investigate the role of the alpha 2/delta subunit. Co-injection of RNA extracted from either rabbit heart, rat brain or rat skeletal muscle (SkM) with 'antisense' oligonucleotides complementary to the alpha 2/delta subunit RNA did not substantially affect the expression of IBa in the oocytes. Using the Northern blot hybridization method, it was shown that native oocytes contain large amounts of alpha 2/delta subunit RNA of Ca(2+)-channel. It is proposed that te oligonucleotide treatment fails to eliminate the alpha 2/delta RNA because of the vast excess of endogenous alpha 2/delta RNA. These results impose a limit on the use of the hybrid-arrest method.

Animals↗
PubMed1992

Distortions induced in DNA by cis-platinum interstrand adducts.

A 22 base pair double-stranded oligonucleotide containing a unique interstrand adduct resulting from chelation of the two guanine residues within the central sequence d(TGCT/AGCA) by a cis-platinum residue has been studied by means of gel electrophoresis, chemical probes, and molecular mechanics. The anomalously slow electrophoretic mobility of the multimers of the platinated and ligated oligomers suggests that the platinated oligonucleotide is bent. The two cytosine residues (complementary to the platinated guanines) are hyperreactive to hydroxylamine, indicating a large exposure of the two bases to the solvent. The adduct does not induce a local denaturation within the flanking sequences since the adenine residues are not reactive with diethyl pyrocarbonate. This is confirmed by the nonreactivity of the complementary T residues with osmium tetraoxide. These results and the molecular mechanics modeling suggest that the interstrand adduct bends the double helix by approximately 55 degrees toward the major groove, that the double helix conserves its average twist angle, and that the distortion induced by the adduct is localized at the platinated sequence d(GC/CG).

Base Sequence↗
PubMed1992

Mutually exclusive exon splicing of the cardiac calcium channel alpha 1 subunit gene generates developmentally regulated isoforms in the rat heart.

Several clones were isolated from a rat genomic library in order to further characterize a region of variability within the third membrane-spanning region of the fourth motif (IVS3) of the L-type voltage-dependent calcium channel. We report here that this diversity arises from alternative splicing of a primary transcript containing a single pair of adjacent exons each encoding a unique sequence for the IVS3 region. Definitive proof of a mutually exclusive splicing mechanism was obtained by genomic mapping of flanking upstream and downstream exons and by extensive sequence analysis of the relevant exon/intron boundaries. S1 nuclease protection experiments revealed that both variant forms of the IVS3 were equally expressed in newborn and fetal rat heart, whereas only a single isoform predominated in adult rat heart. The results demonstrate the existence of an important developmentally regulated switch mediated by alternatively spliced exons in cardiac tissue at a time when major changes in excitation occur.

Amino Acid Sequence↗
PubMed1992

Native-type DHP-sensitive calcium channel currents are produced by cloned rat aortic smooth muscle and cardiac alpha 1 subunits expressed in Xenopus laevis oocytes and are regulated by alpha 2- and beta-subunits.

Native tissue-like L-type voltage-dependent calcium channels (L-VDCC's) were expressed by in vitro transcribed cRNA injection of rat aorta or rabbit cardiac alpha 1 subunit into Xenopus laevis oocytes. Co-injection of VSM-alpha 1 with the cloned skeletal muscle beta-subunit (SK-beta) of the L-type VDCC significantly increased the expressed peak current amplitude without significant changes in kinetics. Similar results were obtained by co-injection of cardiac alpha 1 (DSHT-alpha 1) the cloned skeletal alpha 2-subunit (SK-alpha 2) or with SK-beta. The oocytes co-expressing cRNA's retained L-type VDCC pharmacology.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Beta-subunit expression is required for cAMP-dependent increase of cloned cardiac and vascular calcium channel currents.

In contrast to vascular smooth muscle (VSM), cAMP-dependent phosphorylation increases L-type voltage dependent Ca(2+)-channel (L-VDCC) activity in heart. To investigate whether this difference depends on the tissue-specific alpha 1-subunit of the L-VDCC or its regulation by other subunits, we used a Xenopus laevis oocyte expression system. Injection of cAMP into oocytes expressing cardiac alpha 1 or VSM alpha 1 alone had no effect on L-VDCC activity. However, cAMP increased L-VDCC activity 2-fold in oocytes co-expressing cardiac alpha 1 or VSM alpha 1 with the skeletal muscle beta-subunit. These results suggest that the presence of the beta-subunit is required for cAMP-mediated increase of L-VDCC activity and that the characteristics of tissue-specific beta-subunits may explain differential regulation of L-VDCC activity.

Animals↗
PubMed1992

Magnetic resonance imaging follow-up in Creutzfeldt-Jakob disease.

The history of a 67-year-old woman with histologically proven Creutzfeldt-Jakob disease (CJD) is presented. Before typical clinical and neurophysiological signs of CJD developed, magnetic resonance imaging (MRI) showed slightly enhanced signal intensity of the caudate nuclei and putamina in T2-weighted and proton density images, corresponding to spongiform degeneration in neuropathological examination. Five weeks later characteristical progressive cortical atrophy was demonstrated by follow-up MRI.

Aged↗
PubMed1992

Racial differences in cancer of the male breast--15 year experience in the Detroit metropolitan area.

Characteristics of cancer of the male breast were evaluated in a population based review of 244 cases identified retrospectively through the Metropolitan Detroit Cancer Surveillance System (MDCSS) between 1973 and 1987. The mean age at diagnosis was 65 years and median survival time, 44 months. There were no apparent time trends in incidence for either white or black men from 1973 through 1987. Modified radical mastectomy was the most common surgical procedure, while simple and radical mastectomy declined in popularity over time. Cox's proportional hazards regression model was used to test the simultaneous effects of age, race, stage, and treatment on survival. Men older than 65 at diagnosis had a greater risk of dying than men under 65 (RR 1.52, 95% confidence interval, 1.01-2.28). Survival was significantly worse for men who presented at a more advanced stage; regional versus localized (RR 2.19, 95% confidence interval, 1.39-3.45) and remote versus localized (RR 4.31, 95% confidence interval 2.26-8.23). Race had no significant effect on survival in men with breast cancer in the Detroit Metropolitan Area.

Adult↗