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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 217 records · Page 12Linked to original sources
PubMed1994

Intracoronary irradiation markedly reduces restenosis after balloon angioplasty in a porcine model.

OBJECTIVES: This study examined the effects of intracoronary irradiation on neointimal proliferation after overstretch balloon angioplasty in a normolipemic swine model of restenosis. BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that ionizing radiation, delivered by means of an intracoronary source, causes focal medial fibrosis. We therefore hypothesized that intracoronary irradiation delivered at the time of balloon angioplasty might impair the restenosis process. METHODS: Nineteen juvenile swine underwent coronary angiography; a segment of the coronary artery was chosen as a target for balloon injury. In 10 swine, a ribbon of iridium-192 was positioned at the target segment, and 2,000 cGy was delivered at the vessel wall. Subsequently, overdilation balloon angioplasty was performed at the irradiated segment. In nine control swine, overdilation balloon angioplasty was performed without previous irradiation. Eighteen animals survived and were killed at 30 days. Histopathologic analysis was performed by a pathologist in blinded manner. The area of maximal lumen compromise within the target segment was analyzed by computer-assisted planimetry. RESULTS: In the control group, mean (+/- SD) neointimal area was 0.84 +/- 0.60 mm2 compared with that in the irradiated group, 0.24 +/- 0.13 mm2 (p = 0.01). In the control group, mean percent area stenosis was 47.6 +/- 20.7%, whereas that in the irradiated group was 17.6 +/- 10.5% (p = 0.001). This represents a 71.4% reduction in neointimal area and a 63.0% reduction in percent area stenosis in the irradiated group. Adjacent coronary segments and surrounding myocardium were unaffected. CONCLUSIONS: Intracoronary irradiation (2,000 cGy) delivered to a target porcine coronary segment before balloon overdilation markedly reduces neointima formation at 30 days and thus significantly impairs the restenosis process.

Angioplasty, Balloon, Coronary↗
PubMed1994

Risk factors for corneal graft failure and rejection in the collaborative corneal transplantation studies. Collaborative Corneal Transplantation Studies Research Group.

PURPOSE: To evaluate comprehensively the magnitude of suspected risk factors for corneal graft failure from any cause, failure from rejection, and immunologic reaction in patients at high risk for graft failure after corneal transplantation. METHODS: The records of the 457 participants in the Collaborative Corneal Transplantation Studies were reviewed. All participants had at least two quadrants of stromal vascularization and/or a history or previous graft rejection. Patients were followed for 2 to 5 years. Characteristics of the patient, study eye, donor, donor-recipient histocompatibility, and surgical procedure were examined for their association with the graft outcomes of failure from any cause, rejection failure, and immunologic reaction. Multivariate survival analysis techniques were used to estimate rates of graft outcome events and to estimate the magnitude of risk factors. RESULTS: Many apparent risk factors did not maintain their association with graft outcomes after adjustment for other risk factors. Young recipient age, the number of previous grafts, history of previous anterior segment surgery, preoperative glaucoma, quadrants of anterior synechiae, quadrants of stromal vessels, a primary diagnosis of chemical burn, and blood group ABO incompatibility were among the strongest risk factors identified for graft failure. Donor and corneal preservation characteristics had little influence on graft outcome. CONCLUSIONS: Risk of graft failure varies substantially, even within a high-risk population. The number of risk factors present should be considered by the patient and surgeon when contemplating transplantation and planning follow-up.

Adolescent↗
PubMed1994

Stapling instrumentation.

A number of surgical stapling instruments are on the market. The variety of instruments, stapling cartridges, and their potential veterinary uses are discussed. The basic principles of application and operation of these devices are emphasized.

Anastomosis, Surgical↗
PubMed1994

External pH effects on the depolarization-activated K channels in guard cell protoplasts of Vicia faba.

Previous studies reveal that the pH of the apoplastic solution in the guard cell walls may vary between 7.2 and 5.1 in closed and open stomata, respectively. During these aperture and pH changes, massive K+ fluxes cross the cellular plasma membrane driving the osmotic turgor and volume changes of guard cells. Therefore, we examined the effect of extracellular pH on the depolarization-activated K channels (KD channels), which constitute the K+ efflux pathway, in the plasma membrane of Vicia faba guard cell protoplasts. We used patch clamp, both in whole cells as well as in excised outside-out membrane patches. Approximately 500 KD channels, at least, could be activated by depolarization in one protoplast (density: approximately 0.6 micron-2). Acidification from ph 8.1 to 4.4 decreased markedly the whole-cell conductance, GK, of the KD channels, shifted its voltage dependence, GK-EM, to the right on the voltage axis, slowed the rate of activation and increased the rate of deactivation, whereas the single channel conductance was not affected significantly. Based on the GK-EM shifts, the estimated average negative surface charge spacing near the KD channel is 39 A. To quantify the effects of protons on the rates of transitions between the hypothesized conformational states of the channels, we fitted the experimental macroscopic steady state conductance-voltage relationship and the voltage dependence of time constants of activation and deactivation, simultaneously, with a sequential three-state model CCO. In terms of this model, protonation affects the voltage-dependent properties via a decrease in localized, rather than homogeneous, surface charge sensed by the gating moieties. In terms of either the CO or CCO model, the protonation of a site with a pKa of 4.8 decreases the voltage-independent number of channels, N, that are available for activation by depolarization.

Cell Membrane↗
PubMed1994

Cerebral schistosomiasis caused by Schistosoma haematobium: case report.

The CNS is an unusual site of ectopic infection in schistosomiasis. Cerebral lesions are caused primarily by Schistosoma japonicum, and spinal cord lesions are due primarily to Schistosoma mansoni and Schistosoma haematobium. S. haematobium is an unusual cause of cerebral mass lesions although schistosomal eggs can be frequently found in the brains of individuals in countries where S. haematobium is endemic. We describe a patient with a space-occupying cerebral lesion and schistosomal granulomas on pathological examination. S. haematobium was identified in urine and serologically. The cerebral lesion responded to therapy with praziquantel and corticosteroids. It has been postulated that granulomatous lesions develop following egg laying by errant worms migrating in the vicinity of the cerebral circulation or in response to eggs deposited from more distant sites by embolization. A species-specific serological diagnosis can be made by FAST (Falcon assay screening test)-ELISA with western blot confirmation.

Adult↗
PubMed1994

Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families.

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a potentially fatal hypermetabolic crisis triggered by commonly used anaesthetic agents. The demonstration of genetic heterogeneity in MHS prompted the investigation of the roles played by calcium regulatory proteins other than the ryanodine receptor (RYR1), which is known to be linked to MHS in fewer than half of the European MHS families studied to date. Previously, we have excluded the genes encoding the skeletal muscle L-type voltage-dependent calcium channel alpha 1-, beta 1- and gamma-subunits as candidates for MHS. In this report, we describe the cloning and partial DNA sequence analysis of the gene encoding the alpha 2/delta-subunits, CACNL2A, and its localization on the proximal long arm of chromosome 7q. A new dinucleotide repeat marker close to CACNL2A was identified at the D7S849 locus and tested for linkage in six MHS families. D7S849 and flanking genetic markers were found to co-segregate with the MHS locus through 11 meioses in one, three-generation family. These results suggest that mutations in or near CACNL2A may be involved in some forms of this heterogeneous disorder.

Animals↗
PubMed1994

Changes in the expression of the L-type voltage-dependent calcium channel during pregnancy and parturition in the rat.

The L-type voltage-dependent calcium channel (L-VDCC) is assumed to be a critical component of excitation-contraction coupling in smooth muscle. Using pregnant rat myometrium, we examined the hypothesis that parturition is associated with significant changes in the expression of the alpha 1 subunit of the L-VDCC at the mRNA or protein level. The binding of radiolabeled dihydropyridine, which correlates with the total number of calcium channels in the membrane, was increased by 14 days' gestation, in comparison to that in nonpregnant controls. The elevation in binding capacity persisted through labor and fell postpartum. Northern and RNA dot-blot analysis demonstrated the highest level of expression on Days 20 and 21, with a 3- to 10-fold decrease during parturition. We believe these studies are most consistent with a one-day lag time between mRNA and protein expression, and generally support a modest increase in L-VDCC expression in pregnancy and labor. Reverse transcriptase polymerase chain reaction was used to examine changes in isoform expression in Motif IV, a region of the alpha 1 subunit known to be alternatively spliced. These studies revealed the presence of multiple isoforms in rat myometrium, with a predominance of IVS3B. Interestingly, a marked increase in the ratio of S3B:S3A was noted at parturition. In summary, these data demonstrate that the number of L-type calcium channels, although increased in pregnancy, do not change prior to, or with the onset of, myometrial contraction. Intriguingly, mRNA expression was markedly decreased at parturition. The change in isoform expression during labor is of unknown, but potential, physiologic significance.

Animals↗
PubMed1994

Dihydropyridine Ca2+ channel agonists and antagonists potentiate ultraviolet light-induced relaxation through cyclic GMP formation in porcine coronary artery.

We investigated the mechanisms of dihydropyridine Ca2+ channel agonist potentiation of ultraviolet (UV) light-induced smooth muscle relaxation in porcine coronary artery rings. Rings contracted with the dihydropyridine Ca2+ channel agonist, (+)-S-202-791, were more sensitive to relaxation in response to UV light than were rings contracted with KCl or histamine. Relaxation of (+)-S-202-791-contracted rings was independent of the presence of endothelium and was associated with cyclic GMP formation. Methylene blue (MB) prevented UV light-induced relaxation and cyclic GMP formation. UV light-induced relaxation of histamine and KCl contracted rings and cyclic GMP formation were potentiated by (+)-S-202-791 or the Ca2+ channel antagonist, (-)-R-202-791. Exposure of (+)-S-202-791 to UV light decreased its contractile potency. The data suggest that UV light-induced relaxation of vascular smooth muscle (VSM) is mediated through cyclic GMP formation and that potentiation of UV light-induced relaxation by dihydropyridine Ca2+ channel agonists results from their breakdown to a compound(s) that activates guanylate cyclase.

Animals↗
PubMed1994

Intracranial vertebrobasilar system: MR angiography.

PURPOSE: To determine the reliability of magnetic resonance (MR) angiography in depicting normal vascular anatomy and its usefulness in detecting vascular disease compared with those of digital subtraction angiography (DSA). MATERIALS AND METHODS: Sixty patients with symptoms referable to disease of the vertebrobasilar system were examined with MR angiography and DSA. RESULTS: In patients with normal DSA results, all vertebral arteries (VAs) and basilar arteries (BAs) were also visualized with MR angiography. MR angiography demonstrated 117 of 120 superior cerebellar arteries and 80 of 90 posterior inferior cerebellar arteries but only 30 of 58 anterior inferior cerebellar arteries. MR angiography demonstrated disease of the VAs and BAs with 100% sensitivity. Stenoses were differentiated from occlusions in all cases. However, the degree of stenosis was overestimated in 63% of patients. In six patients with occlusive disease, collateral flow was correctly analyzed with selective saturation. CONCLUSION: Despite its limitations, MR angiography is a clinically important noninvasive technique for screening patients for macroangiopathy of the posterior arterial supply to the brain.

Adolescent↗
PubMed1994

Effects of high-dose intracoronary irradiation on vasomotor function and smooth muscle histopathology.

A significant component of restenosis after coronary angioplasty is due to medial proliferation. Targeted ablation of the proliferating cells by ionizing radiation may prevent restenosis. We delivered high-dose intracoronary gamma-irradiation in porcine coronary arteries and assessed vasomotor function acutely and at 32 days, with pathological analysis at 32 days. Changes in luminal area were assessed by intravascular ultrasound. Irradiated segments acutely displayed vasoconstriction to acetylcholine, with loss of smooth muscle response to nitroglycerin. Restudy revealed restoration of normal vasodilatory response to acetylcholine but persistent loss of response to nitroglycerin. Histopathology at 32 days revealed minor neointima formation without luminal compromise and diffuse fibrosis of the smooth muscle layer. The surrounding myocardium was normal. Focal medial fibrosis without significant endothelial or myocardial damage can be achieved via this technique; intracoronary irradiation, therefore, may be an effective way of impairing the restenosis process.

Animals↗
PubMed1994

Single amino acid substitutions within the ion permeation pathway alter single-channel conductance of the human L-type cardiac Ca2+ channel.

Voltage-dependent L-type Ca2+ channels select for Ca2+ and other divalent cations by high-affinity Ca2+ binding and ion-ion interactions in the permeation pathway. We have recently identified a series of highly conserved glutamate residues, located within the SS2 segments of each of the four repeats of the human heart Ca2+ channel alpha 1 subunit, as major determinants of ion selectivity of the channel. To further investigate the functional role of these glutamate residues in ion permeation, we have individually neutralized the glutamic acids in repeats II and IV by substitution with alanine or glutamine. Wild-type and mutant Ca2+ channels were expressed in Xenopus oocytes. Apparent affinity for external Ca2+ was assessed by measuring the block by Ca2+ of inward Li+ currents through the Ca2+ channels. Mutations reducing net negative charge at these positions resulted in a 10-fold reduction in the affinity of the channel for external Ca2+. Single-channel conductance was measured with either divalent or monovalent cations as the charge carriers. Substitution of glutamic acid at position 677 with either alanine or glutamine increased single-channel conductance, whereas the same substitutions at position 1387 resulted in a decrease in single-channel conductance with Ba2+ as the charge carrier. In contrast, the unitary current amplitude carried by Na+, in the absence of external divalent cations, was not altered by these mutations. The results suggest that these conserved glutamate residues participate in high-affinity Ca2+ binding within the pore. The different effects on Ba2+ permeation indicate an asymmetric arrangement of the glutamate residues between repeats II and IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Noninvasive monitoring of internal carotid artery dissection.

BACKGROUND AND PURPOSE: Internal carotid artery dissection has increasingly been reported as a cause of transient ischemic attack or stroke. However, scarce data exist on the natural history of the arterial lesions and the temporal profile of recanalization. METHODS: We followed 48 patients with 50 angiographically confirmed internal carotid artery dissections by sequential duplex Doppler studies in 2- to 4-day intervals during the first weeks after the onset of symptoms and after 4 weeks in 1- to 2-month intervals for up to 2 years. We assessed sonographic features as well as the frequency and time course of resolution. RESULTS: Initial Doppler findings were abnormal in all patients, most of whom (68%) presented with a characteristic bidirectional high-resistance Doppler signal in the internal carotid artery. Gradual recanalization was found in 68% of the dissections after an average interval of 51 days. Changes of Doppler flow patterns in follow-up studies and features of intra-arterial angiography correlated with the development of internal carotid artery dissection and mirrored the recanalization process. CONCLUSIONS: Our findings suggest that Doppler sonography provides early recognition of internal carotid artery dissection and monitoring of its resolution. Thus, ultrasound studies may guide clinical decisions according to the development of the dissection.

Adolescent↗
PubMed1994

Medicaid physician payment reform: using the Medicare Fee Schedule for Medicaid payments.

OBJECTIVES: The purpose of this article is to provide estimates of the costs of basing Medicaid physician payment levels on the new resource-based Medicare Fee Schedule. Two possible policy options are considered: setting all Medicaid physician fees at the Medicare Fee Schedule level and setting only office visit fees at the new Medicare levels. METHODS: Data on Medicaid physician fees, use patterns, and the Medicare Fee Schedule are used to develop state-level estimates of expenditure changes under each option. RESULTS: Setting Medicaid rates at the Medicare Fee Schedule level could increase expenditures by $3.2 to $4.1 billion nationally; the other option would result in substantially lower increases in expenditures. Because of the current variations in Medicaid physician fees and in the breadth of eligibility across states, the cost of adopting the Medicare Fee Schedule varies considerably among states. CONCLUSIONS: Adopting the new Medicare Fee Schedule for Medicaid payments, proposed by policy-makers as a way to increase access to appropriate medical care, could double physician expenditures in some states. Adoption of more limited versions of the fee schedule might achieve some access gains at lower costs.

Fee Schedules↗
PubMed1994

Distinctive functional properties of the neuronal BII (class E) calcium channel.

Functional diversity of voltage-dependent calcium channels (VDCC) is primarily due to the existence of six distinct genes of the channel-forming subunit alpha 1, which can be further classified into the L-type and neuronal non-L-type subfamilies. We have examined functional properties of the calcium channel BII expressed from the cloned cDNA, in Xenopus oocytes, and compared the results with the other members of the non-L-type subfamily, the BI and BIII channels. The BII channel is a high voltage-activated calcium channel pharmacologically features by its unique sensitivity to the inorganic blocker Ni2. The decaying component of the BII current shows high sensitivity to Ni2+ similar to that of the low voltage-activated channels and the R-type channel in cerebellar granule cells, whereas the sustained component is relatively resistant to Ni2+ as are the other high voltage-activated calcium channels. Dihydropyridines, omega-CgTx-GVIA, and omega-Aga-IVA, which have been used to discriminate L-, N-, and P-types, do not affect the BII current. The mode of modulation of the BII channel by auxiliary subunits is strikingly different from that observed in the L-type channels. Both activation and inactivation rates of the BII current are decelerated by coexpression of the beta subunit, and this effect is cancelled by further coexpression of the alpha 2 subunit. In situ tissue distribution studies indicate a higher level of BII mRNA expression in the hippocamus compared to other brain regions, revealing important difference in the relative abundance of BI, BII, and BIII channels in brain tissues. Overall, the results suggest that the BII channel forms a novel functional category of VDCC that is different from T-, L-, N-, and P-type.

Animals↗