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Biomedical subjects

W Moore

Publications and source records attributed to W Moore.

At least 19 recordsLinked to original sources
PubMed1991

Endotoxin and renal glutamine metabolism.

The effect of endotoxin on renal glutamine metabolism and ammoniagenesis was investigated in vivo in the rat to gain further insight into the altered glutamine flow that characterizes critical illness. Studies were done 15 hours following a single dose of Escherichia coli lipopolysaccharide (10 mg/kg). Renal blood flow and arterial glutamine concentration were similar in control and study rats, but the kidney switched from an organ of slight glutamine uptake in controls (129 +/- 52 nmol/100 g of body weight per minute) to net release in the endotoxin-treated animals (-273 +/- 170 nmol/100 g of body weight per minute). Simultaneously, the specific activity of renal glutamine synthetase increased by almost 50% (374 +/- 40 nmol/mg of protein per hour in rats given endotoxin vs 253 +/- 12 nmol/mg of protein per hour in controls), while glutaminase was unchanged. Urinary ammonia excretion was reduced by 35% in the endotoxin-treated animals (47 +/- 6 mumol/12 h in endotoxin-treated animals vs 70 +/- 8 mumol/12 h in controls) despite a 10% fall in the arterial bicarbonate value. Endotoxin alters the net flux of glutamine across the kidney which appears to be partially regulated enzymatically. This may impair the kidneys' ability to maintain acid/base homeostasis.

Ammonia↗
PubMed1991

Comparison of dipyridamole-echocardiography with dipyridamole-thallium scintigraphy for the diagnosis of myocardial ischemia.

After an intravenous infusion of dipyridamole (0.56 mg/kg), we performed both echocardiography and thallium scintigraphy in 63 patients who were referred for known or suspected coronary artery disease. Of those patients, 25 returned for coronary arteriography within 1 month after the tests, thus forming the study group for this report. Sensitivity for detection of coronary artery disease, when analyzed region-by-region, was 80% for thallium scintigraphy and 57% for echocardiography, whereas specificity was 85% and 98%, respectively. When evaluating individual patients for the presence or absence of ischemia, we found a sensitivity of 95% for scintigraphy and 58% for echocardiography; corresponding specificities were 50% and 100%. By using arteriography as the gold standard for comparison, it appears that thallium scintigraphy has a significantly higher sensitivity but lower specificity for the detection of coronary artery disease than does echocardiography. Echocardiography may, however, be a useful adjunct to thallium scintigraphy in the evaluation of patients with coronary artery disease.

Coronary Disease↗
PubMed1991

Tolbutamide stimulates proliferation of pancreatic beta cells in culture.

To investigate the beta-cell cytotrophic action of tolbutamide, pancreatic cells were dissociated from neonatal rat pancreata and then cultured for 10 days in the presence of various concentrations of tolbutamide. After counting insulin-positive beta cells, dose-response curves were plotted and analyzed. Increasing concentrations of tolbutamide cause an increase in beta-cell numbers until a maximum response is reached at a concentration of about 100 micrograms/ml. At greater concentrations, tolbutamide becomes inhibitory. At concentrations of 100 micrograms/ml of tolbutamide, beta-cell numbers are doubled. We further investigated the effect of glucose on tolbutamide-induced stimulation. Tolbutamide fails to stimulate beta cells after culture in medium containing low glucose concentrations. High concentrations of glucose are required for tolbutamide action. Preexposure for as little as 16 h to low glucose abolishes the stimulatory action of tolbutamide. The experiments indicate that adequate glucose concentrations are necessary for the preservation of tolbutamide-induced beta-cell survival and proliferation. Addition to the culture medium of the calcium channel blocker diltiazem or the calmodulin antagonist chlorpromazine affects a decrease in beta-cell numbers. This decrease depends on the concentration of the drug. Addition of tolbutamide reverses that decrease, which suggests that calcium is required for beta-cell survival and proliferation. Tolbutamide action seems to be specific, since fibroblasts are unaffected at concentrations of tolbutamide that are stimulatory for beta cells. At high concentrations, tolbutamide is cytotoxic for fibroblasts. Comparison with other sulfonylureas supports the superior activity of tolbutamide. The "second generation" sulfonylurea glyburide is cytotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Longitudinal study of cerebral spinal fluid drainage in polyethylene glycol-conjugated superoxide dismutase in paraplegia associated with thoracic aortic cross-clamping.

It has been hoped that pharmacologic prophylaxis in thoracic aortic cross-clamping may avert the unpredictable complication of spinal cord paraplegia, may avoid the mechanical difficulties associated with shunts, partial bypass, or monitoring devices, and may serve as a substitute for or as an adjunct to cerebral spinal fluid drainage. Toward this end 21 mongrel dogs were studied in four groups and underwent 60 minutes of thoracic aortic cross-clamping: group I, five with thoracic aortic cross-clamping; group II, five with thoracic aortic cross-clamping and cerebral spinal fluid drainage; group III, five with thoracic aortic cross-clamping, cerebrospinal fluid drainage and intravenous administration of a single dose (5000 units/kg) of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) given 15 to 20 minutes before thoracic aortic cross-clamping; and group IV, six with thoracic aortic cross-clamping and PEG-SOD. Paraplegia was graded by the Tarlov method at 24 hours and up to 5 days after thoracic aortic cross-clamping. The carotid and femoral artery pressures, the central venous pressure, and core temperature, taken during the experiment and at the time the dogs were killed, were found to be similar between groups. At 24 hours all dogs in group I were paraplegic; groups II and III had no paraplegic dogs (p less than 0.01), and group IV had fewer paraplegic dogs (two of six) than group I (p less than 0.05). Paraplegia was averted in all dogs treated with cerebral spinal fluid drainage, even 5 days after thoracic aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Impaired bowel motility following small intestinal transplantation.

Little information is available concerning motility following bowel transplantation and the appropriate timing of offering enteral feedings. Eight Lewis rats (300 g) underwent small bowel transplant as described by R. P. Harmel, Jr., and H. Stanley (J. Pediatr. Surg. 21:214, 1986). Silver oxide electrodes were placed in the native proximal ileum and in the distal segment of the homograft. Four control rats underwent laparotomy and placement of silver oxide electrodes in the jejunum and proximal ileum. Leads were brought out through a stab wound and the abdominal incision was closed. The electrodes were connected to a continuous recorder. Basal electrical rhythm (BER) was recorded periodically and was evaluated daily as the average of three readings per animal per day. Homograft electrical activity was not observed until at least 40 hr post-transplant and never attained the level of BER of the native intestine (P less than 0.05). Myoelectric complex potentials were not observed in the transplanted rats until post-operative day 11. These data suggest that basal electrical activity is significantly impaired following bowel transplantation. This study indicates that intestinal activity can be monitored for extended periods of time and may be a useful method of evaluating recovery of motility post bowel transplant prior to initiating enteral intake.

Animals↗
PubMed1989

Proliferation of immunocytochemically identified islet beta cells in culture: effect of growth factors, hormones, and nutrients.

Immunocytochemically identified, differentiated, single beta-cells proliferate to form colonies, which then grow into hillocks and islets. Beta-Cell proliferation is most easily quantified during the first week, when colonies are forming. The experimental objective was stimulation of beta-cell proliferation by culture medium supplementation with growth factors, hormones, or nutrients. We found that beta-cell proliferation is stimulated by iron-saturated transferrin, interleukin-1-alpha, fetal calf serum, and glucose. In response to transferrin, proliferation of beta-cells is progressively stimulated, reaching a maximum at 30 micrograms/ml. At greater concentrations the stimulatory effect is progressively lost. Interleukin-1-alpha maximally stimulates beta-cell proliferation at 10 pg/ml, regresses to control levels at 10(3) pg/ml, and inhibits proliferation progressively at greater concentrations. Fetal calf serum maximally stimulates beta-cell proliferation at concentrations of 10%, and glucose stimulates maximally at 15 mM concentrations. The proliferative response to transferrin, interleukin-1-alpha or glucose is serum dependent. Serum and transferrin synergistically stimulate glucose-induced beta-cell proliferation. Interleukin-1-beta, interleukin-2, rat growth hormone, and rat prolactin fail to stimulate beta-cell proliferation.

Animals↗
PubMed1988

Clonal growth of immunocytochemically identified islet beta and alpha cells in culture.

The proliferative capacity of individual immunocytochemically identified islet beta cells was investigated in tissue culture. The pancreatic digest was filtered through a 20-micron filter to eliminate partially digested tissue fragments and islets; it was then cultured at low density to allow assessment of single cells. The type of cell was identified immunocytochemically by reaction with antibody to insulin or glucagon, and DNA synthesis was estimated from autoradiographs after incorporation of tritiated thymidine. Single immunocytochemically reactive beta or alpha cells attached to the culture substratum and then proliferated, directly proportional to time in culture. Single beta cells did not incorporate thymidine after 1 day in culture; nonendocrine cells, presumed to be mainly fibroblasts, readily incorporated thymidine. Beyond the first day, about 10% of the beta cells incorporated thymidine. The number of radioactively labeled, immunocytochemically reactive beta cells increased for 5 days in culture and then remained at the elevated level until experiments were terminated at 12 days. DNA synthesis in beta cells occurred in two waves separated by about 3 days, suggesting a generation time of about 3 days for immunocytochemically identified beta cells. Fetal calf serum was found to be an essential culture medium ingredient to sustain thymidine incorporation; horse serum was found to be an unsuitable substitute. Mitotic figures were recorded in differentiated beta and alpha cells. These studies conclusively show that differentiated beta and alpha cells can proliferate in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparison of a totally implantable access device for chemotherapy (Port-A-Cath) and long-term percutaneous catheterization (Broviac).

Because of the difficulty in maintaining vascular access in patients receiving aggressive parenteral chemotherapy, a growing number of patients have had implantation of either percutaneous or subcutaneous devices allowing permanent intravenous access. In our study, between July 1980 and July 1985, 110 patients had placement of a Broviac catheter, while 100 patients had placement of a subcutaneous device via a subclavian venous approach. Both groups of patients were identical regarding age, primary malignancy, chemotherapy, and nutritional status. Catheter-related sepsis occurred in 15% and thrombotic occlusion in 22% of those patients with Broviac catheters, compared with 3% and 1%, respectively, in patients having subcutaneous reservoirs. Although the initial cost of the subcutaneous reservoir is greater, overall cost of maintenance of the percutaneous catheter far exceeds that of the reservoir because of the need for daily catheter care and heparin flushing of the Broviac device, which is unnecessary for the subcutaneous port. Our experience favors the use of the subcutaneous reservoir in patients receiving prolonged chemotherapy.

Antineoplastic Agents↗
PubMed1987

Inactivation of gamma-glutamylcysteine synthetase, but not of glutamine synthetase, by S-sulfocysteine and S-sulfohomocysteine.

The reactions catalyzed by gamma-glutamylcysteine synthetase and glutamine synthetase are thought to proceed via enzyme-bound gamma-glutamyl phosphate intermediates. We investigated the possibility that S-sulfocysteine and S-sulfohomocysteine might act as analogs of gamma-glutamyl phosphate or of the associated putative tetrahedral intermediates. The D- and L-enantiomers of S-sulfocysteine and S-sulfohomocysteine were found to rapidly inactivate rat kidney gamma-glutamylcysteine synthetase but to be reversible inhibitors of sheep brain glutamine synthetase. Inactivation of gamma-glutamylcysteine synthetase does not require ATP and is associated with noncovalent binding of close to 1 mol of inactivator/mol of enzyme. The findings indicate that the S-sulfo amino acids are transition-state analogs, and that binding of S-sulfo amino acid to the enzyme induces formation of a very stable enzyme-inactivator complex. The data suggest that stabilization of the enzyme-inactivator complex results from interactions involving the sulfenyl sulfur atom of the S-sulfo amino acid and the active site thiol group of the enzyme.

Animals↗
PubMed1987

Interval gangrene occurring after successful lower-extremity revascularization.

Four patients experienced a rare but devastating complication of peripheral vascular reconstructive surgery in which gangrene occurred in the presence of a functioning graft and palpable pulse. Three patients underwent bypass procedure for limb-threatening ischemia. Despite a "satisfactory" postoperative result of a well-perfused distal extremity and strongly palpable pulse, each of these patients developed progressive ischemic gangrene in an area proximal to the distal anastomosis and eventually required amputation. These patients demonstrate the importance for maintaining collaterals to perfuse bypassed segments of the lower extremities. In a patient with inadequate collateral circulation or in whom the profunda perigeniculate collateral pathway has been disrupted or is absent due to disease, it is necessary to revascularize sequential vascular beds.

Aged↗
PubMed1986

Islet neoformation in tissue culture.

We have devised a tissue culture system that permits de novo formation of islets. Neonatal rat pancreata are enzymatically dissociated into single cells. The cell suspension is filtered through polyester cloth with 20 microns pores to exclude cell aggregates as well as preformed islets and a single cell suspension is then plated into tissue culture dishes at a density precluding reaggregation. Pancreatic cells proliferate forming numerous colonies of epithelioid cells. After a confluent monolayer, cells proliferate into a third dimension, the space occupied by the culture medium. Third dimensional proliferation occurs from basal monolayers of epithelioid colonies. At about 9 days in culture, numerous hillocks are visible that are spaced at about 1 mm from one another. Islets are observed to bud from the hillock surfaces. In 1 micron-thick sections, secretion granules are detected with the light microscope in some islet cells. With the electron microscope three basic cell types are seen. One peripherally located cell type is sparsely granulated and appears to be a precursor cell. The other peripherally located cell type shows a homogeneous population of secretion granules characteristic of A-cells. The third cell type is found in the interior of islets containing granules characteristic of B-cells. Islet cells, but not hillock cells, react immunocytochemically for insulin and glucagon. The cultures secrete 2 to 10-fold the amounts of glucagon present in fresh medium. It is concluded that differentiation of A- and B-cells occurs in neoformed islets.

Animals↗
PubMed1986

Optimal proximal anastomosis/tunnel for axillofemoral grafts.

The proximal anastomosis of the axillofemoral graft may be optimally placed with standard "cobra-head" technique at an oblique angle to the axillary artery if a subpectoralis minor course of the graft into the anterior-inferior axilla is used. Theoretical advantages of such an anastomosis include improved flow characteristics, decreased tendency to pseudoaneurysm formation, and a decreased tendency to axillary artery thrombosis or brachial artery embolus.

Axillary Artery↗
PubMed1985

Is pain crisis a cause of death in sickle cell disease?

It has been a matter of controversy as to whether patients with sickle cell disease die of crisis or merely in crisis. The authors reviewed the 74 patients with sickle cell disease autopsied at The Johns Hopkins Hospital. From clinical review, there were 20 (27%) who died with pain crisis, 51 (69%) who died without pain crisis, and 3 (4%) for whom documentation was insufficient. On pathology review, death was attributable to infection in 19 (26%), uremia in 9 (12%), sequestration crisis in 9 (12%), necrotic bone marrow emboli in 7 (9%), and miscellaneous causes in 14 (19%); in 16 (22%) patients no cause of death could be identified. Death was explained in 47/51 (92%) patients without pain crisis; but only in 11/20 (55%, P less than 0.01) patients dying in pain crisis. The disproportionately large number of patients dying in pain crisis with an unexplained cause of death suggests that pain crisis may account for the death of some patients with sickle cell disease.

Adolescent↗
PubMed1985

Powassan viral encephalitis: a review and experimental studies in the horse and rabbit.

Powassan virus strain M794, a member of the Flavivirus genus known to infect man and animals in Canada, was inoculated intracerebrally into rabbits and horses. No clinical signs were observed in rabbits, but widespread encephalitis resulted, characterized by lymphoid perivascular cuffing, lymphocytic meningitis, and lymphocytic choroiditis. In horses, eight days after inoculation, prominent neurological signs occurred and lesions were those of non-suppurative encephalomyelitis, neuronal necrosis, and focal parenchymal necrosis. The virus could not be reisolated from the rabbit or horse brains. Pathologic features, useful in separating some of the common North American equine neurological diseases, are discussed.

Animals↗
PubMed1985

Iatrogenic vascular injury during peripheral revascularization.

Iatrogenic vascular injury may occur during peripheral revascularization procedures secondary to the application of vascular occlusive devices. This review summarizes the known mechanical causes of such injury, relates this to clamp design, and suggests methods to minimize such injury by appropriate selection and handling of vascular occlusive clamps.

Animals↗