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Biomedical subjects

R E Kelly

Publications and source records attributed to R E Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1993

Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication.

We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.

Adult↗
PubMed1992

The structural organization of the hamster multifunctional protein CAD. Controlled proteolysis, domains, and linkers.

CAD is a multidomain protein that catalyzes the first three steps in mammalian de novo pyrimidine biosynthesis. The 243-kDa polypeptide consists of four functional domains; glutamine amidotransferase (GLNase), carbamyl phosphate synthetase (CPSase), aspartate transcarbamylase (ATCase), and dihydroorotase (DHOase). Controlled proteolysis of hamster CAD was found to cleave the molecule into 18 fragments which successively accumulate and disappear during the course of digestion. Each fragment was isolated and partially sequenced to determine its location in the polypeptide chain. Proteolysis was found to usually occur at the junctions between the domains and sub-domains identified by sequence homology. All proteases of low to moderate specificity cleaved the molecule in a similar fashion. The rate of proteolysis widely varied and the interdomain regions were not always accessible to proteases. Each of the major functional domains is postulated to consist of subdomains. The duplicated halves of the CPSase domain (116 kDa) have a homologous structure consisting of 11-, 25-26-, and 21-22-kDa subdomains. Prolonged digestion cleaved the DHOase domain (36.6 kDa) into two stable species suggesting that this region is comprised of 11.5- and 15.0-kDa subdomains. Similarly, proteolysis of the 21-kDa catalytic subdomain of the GLNase domain (40 kDa) indicated a bilobal structure consisting of 12.3- and 8.5-kDa chain segments. The connecting region between the two ATCase subdomains (16.4 and 18 kDa) was not cleaved. Copurification of many of the domains showed that they remain associated by noncovalent interactions even after the connecting segments have been cleaved. The chain segments, the linkers, which connect the domains and subdomains were conserved in length but not in sequence, were predicted to be relatively hydrophilic and flexible but did not show a tendency to assume a particular secondary structure. These studies provide a more detailed map of the structural organization of the CAD polypeptide.

Amino Acid Sequence↗
PubMed1992

Fertility after simulated Fowler-Stephens orchiopexy in rats.

In order to determine the effects of the Fowler-Stephens orchiopexy (FSO) on fertility, young rats underwent simulated FSO, FSO and concurrent contralateral orchiectomy (FSO/OR), unilateral orchiectomy (OR), or sham operation (controls). Twelve weeks after the operation, each male rat was mated to two proven-fertile female rats for 17 days (three ovulatory cycles). Two weeks later, both male and female rats were killed. No pregnancy resulted from the matings of the FSO/OR males. In contrast, pregnancy ensued in 13 of 16 (81%) females in the FSO group, 9 of 14 (64%) in the OR group, and 11 of 12 (92%) in the control group. There were no fertile males in the FSO/OR group. In the FSO group, eight of eight males induced pregnancy in at least one female; in the OR group, six of seven (86%) males were fertile as were all six males in the control group. No differences in litter size or fetal weight were observed between fertile females in various groups.

Animals↗
PubMed1992

Decreasing transfusion exposure risk during extracorporeal membrane oxygenation (ECMO).

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy for neonatal pulmonary hypertension but carries a significant risk for transfusion-related complications. Packed red blood cell (PRBC) and platelet exposure were quantified and reviewed in 17 ECMO survivors prior (Group I, n = 9) and subsequent to (Group II, n = 8) changes in transfusion protocols. Blood product requirements included ECMO circuit priming, maintenance of haematocrit > 0.40 or platelet count > 50 x 10(9)/l, and colloid volume expansion. Group I was exposed to 13.8 +/- 10.2 (x +/- SD) different PRBC units. In Group II, multiple transfusions from single donor units decreased exposure 71% to 3.9 +/- 0.7 units (P < 0.05). Decreases in blood withdrawn (11%) and transfusion volume (7%) were coincident with a 15% reduction in mean bypass time. Platelet volume transfusion decreased from 159 +/- 213 to 93 +/- 64 ml using volume-reduced platelet packs. Total transfusion exposure decreased 59% from 20.8 +/- 17.8 units to 8.6 +/- 2.4 donor units. No transfusion complications occurred during the aggregate 1,926 h on bypass. We conclude that neonates on ECMO have a significant transfusion exposure risk increasing with prolonged duration of ECMO therapy. In addition we noted that concentrated platelet packs decreased transfusion volume by 41%, and multiple PRBC transfusions from single donor units decreased donor exposure by 71% while both strategies decreased the overall transfusion exposure risk by 59%.

Blood Component Transfusion↗
PubMed1992

Cerebellar syndrome in myxoedema revisited: a published case with carcinomatosis and multiple system atrophy at necropsy.

One of six patients in a 1960 paper on "Cerebellar syndrome in myxoedema" was subsequently found to have adenocarcinoma. General post-mortem revealed carcinomatosis and basal pneumonia. Neuropathological examination revealed the changes of multiple system atrophy. The relationship between hypothyroidism, carcinoma, and cerebellar, pontine and striatonigral degeneration is discussed.

Adenocarcinoma↗
PubMed1992

Effects of simulated Fowler-Stephens orchiopexy on testicular structure and function in rats.

To determine the effects of the Fowler-Stephens orchiopexy (FSO) on testicular structure and function, young rats underwent simulated FSO and concurrent contralateral orchiectomy, unilateral orchiectomy, or no operation. Rats were killed at 1, 2, 4, 6, 8, and 10 weeks postoperation, and serum testosterone, as well as testicular concentrations of the enzymes LDH & SDH, protein markers of testicular germinal cell development, were measured at the time of death. Although LDH and SDH concentrations decreased by 45 per cent in testes after simulated FSO at 4 weeks, control testes showed a 5 per cent increase in these enzymes. Serum testosterone decreased to one-fourth the initial value in rats after FSO, whereas control rats showed a slight increase. Within 2 weeks after simulated FSO, spermatocytes and sperm were sparse and there was marked disruption of tubular morphology; after 4 weeks interstitial fibrosis became prominent. Only a rare testis with good collateral vessels and resultant good histologic appearance and enzyme profile survived the FSO procedure, and these testes were considerably smaller than the controls.

Animals↗
PubMed1991

Alterations in gastrointestinal motility during postoperative acute corticosteroid withdrawal.

Patients receiving exogenous corticosteroids may develop iatrogenic adrenal insufficiency, with resultant nausea, emesis, and abdominal distension if perioperative "stress steroid" dosages are inadequate. To investigate these gastrointestinal disturbances, motility measurements were obtained using perfused catheters in 10 dogs before steroid treatment (control), during administration of high-dose corticosteroids, and daily during 5 days of abrupt withdrawal. Withdrawal was characterized by a significant disruption in normal antral, duodenal, and jejunal motility with a prolongation of the migrating motor complex (MMC) and phases I and II, but not III (I = quiescence, II = irregular activity, and III = regular activity). Retrograde giant contractions (RGCs), giant migrating contractions (GMCs), and/or "intestinal fibrillation" were also observed during the first two withdrawal days. Adrenal weights and morphology did not change. We conclude: (1) high-dose corticosteroids can induce profound adrenal suppression in dogs without morphologic changes within 3 weeks; (2) high-dose steroid administration enhances gastrointestinal motility; and (3) acute withdrawal causes disappearance or shortening of MMC and the development of RGCs and GMCs with associated emesis.

Adrenal Insufficiency↗
PubMed1991

An improved model of experimental gastroschisis in fetal rabbits.

Previous animal models of gastroschisis have been associated with high mortality and variable degrees of intestinal evisceration. Using current fetal surgical techniques, an improved model of gastroschisis in fetal rabbits was developed. Twenty-eight time-mated New Zealand white rabbits underwent hysterotomies and fetal exposure on gestational day 25 (33-day gestation). Control fetuses (C) underwent fetal manipulation only. Gastroschisis fetuses (GS) had creation of right midabdominal wall defects. Twenty-five of 28 does (89%), 9 of 13 C fetuses (69%), and 18 of 22 GS fetuses (82%) survived. At the time of cesarean delivery 5 days later, GS fetuses had significantly lower body weights, intestinal lengths, and mucosa/submucosa height ratios (a measure of bowel wall edema), and significantly greater intestinal densities when compared with C fetuses (P less than .05, t test). This study demonstrates that (1) gastroschisis abdominal wall defects can be created in fetal rabbits with high survival rates; (2) experimental gastroschisis is associated with a profound decrease in fetal weight; and (3) eviscerated intestine is heavier, shorter, and thickened compared with normal control intestine, mimicking the clinical situation.

Abdominal Muscles↗
PubMed1991

Pulmonary edema and fluid mobilization as determinants of the duration of ECMO support.

The physiological variables that govern recovery of pulmonary function during neonatal extracorporeal membrane oxygenation (ECMO) remain poorly understood. We hypothesized that pulmonary hypertension (PHN) resolves soon after starting ECMO and that neonatal weight gain, pulmonary edema, and fluid mobilization are major determinants of recovery of pulmonary function and the ability to decrease ECMO support. To evaluate this, 17 consecutive neonates requiring ECMO for severe respiratory failure were reviewed. PHN was studied by daily echocardiography to assess the direction of ductal shunting. To evaluate fluid flux, pulmonary function, and edema during ECMO, we measured body weight, urine output, and ECMO flow every 12 hours. To evaluate pulmonary edema, serial chest radiographs obtained every 12 hours were randomly reviewed and scored by two radiologists with a semiquantitative chest radiograph index score (CRIS). By 25% of bypass time, PHN had resolved in all patients. However, at that time, weight had increased to 9.16% +/- 1.78% above birth weight, and the CRIS was 44% worse than the value just prior to ECMO. From 25% time on bypass, as urine output increased, patient weight and CRIS progressively decreased, allowing ECMO support to be weaned. At the time of discontinuation of ECMO support, weight had decreased to 2.0% +/- 1.3% above birth weight, and urine output remained steady at 3.0 +/- 0.3 mL/kg/h. Within 24 hours of stopping ECMO, the CRIS showed a 58% improvement compared to maximal scores during ECMO. We conclude that PHN decreases early in ECMO and that edema and its mobilization are important determinants of the improvement in pulmonary function and duration of ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Fluids↗
PubMed1990

Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD.

Glutamine-dependent carbamoyl-phosphate synthetase (EC 6.3.5.5) catalyzes the first step in de novo pyrimidine biosynthesis. The mammalian enzyme is part of a 240-kDa multifunctional protein which also has the second (aspartate carbamoyltransferase, EC 2.1.3.2), and third (dihydroorotase, EC 3.5.2.3) activities of the pathway. Shigesada et al. (Shigesada, K., Stark, G.R., Maley, J.A., and Davidson, J.N. (1985) Mol. Cell Biol. 175, 1-7) produced a truncated cDNA clone from a Syrian hamster cell line that contained most of the coding region for this protein. We have completed sequencing this clone, known as pCAD142. The cDNA insert contained all of the coding region for the glutaminase (GLN) and carbamyl phosphate synthetase (CPS) domains but lacked a short amino-terminal segment. By comparing the primary structure of the mammalian chimera to monofunctional proteins we have identified the borders of the functional domains. The GLN domain is 21 kDa, close to the size of the functionally similar polypeptide products of the Escherichia coli pabA and hisH genes. The domain has the three regions of homology common to trpG-type glutamine amidotransferases, as well as a fourth region specific to the carbamyl phosphate synthetases. The CPSase domain is similar to other reported CPSases in size (120 kDa), primary structure (37-67% amino acid identity), and homology between its amino and carboxyl halves. Analysis of the nucleotide and amino acid sequence identities among the various carbamyl phosphate synthetases suggests that the gene fusion which joined the GLN and CPS domains was an early event in the evolution of eukaryotic organisms and that the Saccharomyces cerevisiae enzyme consisting of separate subunits arose by defusion from an ancestral multifunctional protein.

Amino Acid Sequence↗
PubMed1990

Extracorporeal membrane oxygenation in the treatment of neonatal respiratory failure.

We report 18 consecutive neonates with severe respiratory failure due to pulmonary hypertension treated with extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation was begun at 52 +/- 36 hours of age with an arterial partial pressure of oxygen (PO2) of 36 +/- 14 mm Hg despite maximal pharmacologic and ventilator support (inspired fraction of oxygen [FiO2], 0.99 +/- 0.03; respiratory rate, 98 +/- 31/min; and positive inspiratory pressure, 54 +/- 11 cm of water). With initial flows of 130 +/- 17 mL/kg per minute, ventilator settings were reduced to the following: FiO2, 0.30; respiratory rates, 15/min; and positive inspiratory pressure, 24 cm of water. Support using extracorporeal membrane oxygenation was gradually reduced to 22% of initial flows and arterial blood samples showed pH 7.48 +/- .05, PO2 of 106 +/- 27 mm Hg, and PCO2 of 36 +/- 5 mm Hg just prior to decannulation. After 107 +/- 45 hours, extracorporeal membrane oxygenation was stopped and infants were extubated 61 +/- 53 hours (median, 46 hours) afterward. There was one death (94.4% survival rate); all survivors were discharged and underwent a follow-up examination at 1 to 27 months of age. Complications included two intracranial hemorrhages (one death and one asymptomatic), one patent ductus arteriosus requiring ligation on extracorporeal membrane oxygenation, and chronic lung disease in one patient. In selected neonates, extracorporeal membrane oxygenation allows for resolution of pulmonary hypertension, results in improved survival, and is associated with a low incidence of chronic lung disease. Extracorporeal membrane oxygenation should be considered in the treatment of severe respiratory failure.

Carbon Dioxide↗
PubMed1990

Early effects of colectomy and endorectal pullthrough operation on biliary lipid composition.

In order to determine the effects of total colectomy and endorectal pullthrough with ileal reservoir (ERP) on biliary lipid composition in the early postoperative period, gallbladder bile of dogs was examined after biliary cannulation alone (control); biliary cannulation and colectomy with ileorectal anastomosis (IRA); and biliary cannulation, colectomy with mucosal proctectomy, and ERP. Bile collected from 3 to 6 weeks postoperation was analyzed for total bile acids, cholesterol, phospholipids, bilirubin, and calcium concentrations. Cholesterol saturation was calculated. Serum collected over the same period was analyzed for electrolytes and liver function tests. There was no evidence of sludge or gallstones post-operatively in any animal. Significant decreases in total bile acids, phospholipids, and calcium concentrations were noted in the bile of the IRA group when compared to the bile of the controls (P less than 0.05) and in total bile acids, cholesterol, phospholipids, and calcium in ERP vs controls (P less than 0.05). Moreover, all three biliary lipids and calcium were significantly decreased in ERP animals compared to those in the IRA group (P less than 0.05). No change in cholesterol saturation was noted between any of the three groups. Other than an increase in alkaline phosphatase concentrations compared to preoperative levels (P less than 0.05) which was noted in all groups, no significant changes were noted in serum parameters. We conclude that during the early postoperative period, ERP causes a significant decrease in gallbladder bile concentrations of total bile acids, cholesterol, phospholipids, and calcium which cannot be explained by colectomy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal Canal↗
PubMed1990

Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD.

Mammalian DHOase (S-dihydroorotate amidohydrolase, EC 3.5.2.3) is part of a large multifunctional protein called CAD, which also has a carbamoyl-phosphate synthetase [carbon-dioxide: L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.5.5] and aspartate transcarbamoylase (carbamoyl-phosphate: L-aspartate carbamoyltransferase, EC 2.1.3.2) activities. We sequenced selected restriction fragments of a Syrian hamster CAD cDNA. The deduced amino acid sequence agreed with the sequence of tryptic peptides and the amino acid composition of the DHOase domain isolated by controlled proteolysis of CAD. Escherichia coli transformed with a recombinant plasmid containing the cDNA segment 5' to the aspartate transcarbamoylase coding region expressed a polypeptide recognized by DHOase domain-specific antibodies. Thus, the order of domains within the polypeptide is NH2-carbamoyl-phosphate synthetase-DHO-aspartate transcarbamoylase-COOH. The 334-residue DHOase domain has a molecular weight of 36,733 and a pI of 6.1. A fragment of CAD having DHOase activity that was isolated after trypsin digestion has extensions on both the NH2 (18 residues) and COOH (47-65 residues) termini of this core domain. Three of five conserved histidines are within short, highly conserved regions that may participate in zinc binding. Phylogenetic analysis clustered the monofunctional and fused DHOases separately. Although these families may have arisen by convergent evolution, we favor a model involving DHOase gene duplication and insertion into an ancestral bifunctional locus.

Amidohydrolases↗
PubMed1990

Surgical management of islet cell dysmaturation syndrome in young children.

Islet cell dysmaturation syndrome (ICDS) encompasses the causes of infantile hyperinsulinemic hypoglycemia histologically described as islet cell hyperplasia, pancreatic adenomatosis and nesidioblastosis. Eleven infants underwent 14 pancreatic resections for ICDS from 1965 to 1990 at the University of California at Los Angeles Medical Center for severe hypoglycemia unresponsive to medical therapy. Seizures were the presenting symptoms of hypoglycemia in eight infants. Six patients had nesidioblastosis, four had islet cell hyperplasia and one patient had an adenoma with histologically normal pancreatic islet cells. Four neonates underwent 80 per cent pancreatic resection; three with nesidioblastosis required reoperation (90 to 95 per cent resection). Four older infants underwent 80 per cent pancreatic resection but required diazoxide for less than six months postoperatively. Three infants underwent 90 to 95 per cent pancreatic resection. None have required reoperation or postoperative medications. All infants are normoglycemic without pancreatic exocrine insufficiency and none had postoperative complications. Five infants had preoperative neurologic impairment, with three having severe retardation; all showed some improvement postoperatively, but only one infant now has normal findings on neurologic examination. Early diagnosis and aggressive surgical resection should minimize neurologic complications of the ICDS.

Adenoma↗
PubMed1990

Deleterious effects of testicular venous occlusion in young rats.

To determine the differences between testicular arterial and venous obstruction, the spermatic artery or vein, or both, were occluded for varying periods of time in young rats. Two months later, at the conclusion of the study, the testes were examined. Histologic degeneration after vascular obstruction was graded by a modified Johnsen's tubular biopsy score (TBS). The testicular concentrations of enzymes (lactic dehydrogenase and sorbitol dehydrogenase), known to decrease with testicular injury, were measured. TBS and seminiferous tubule diameter (STD) were found to decrease significantly after two hours of vascular occlusion and were similar regardless of whether the obstruction was produced by occlusion of arterial inflow or venous drainage, or both. Testicular concentration of enzymes decreased significantly after permanent ligation of the spermatic artery and vein, but decreased minimally when the vascular obstruction lasted less than 120 minutes. Testicular injury produced by venous occlusion was equally severe and occurred as rapidly as injury produced by arterial or combined arteriovenous occlusion. No significant injury was noted in the contralateral testes in any group.

Animals↗
PubMed1989

Pulmonary function after extracorporeal shock wave lithotripsy--a comparison of general and regional anaesthesia.

The effect of general anaesthesia on postoperative pulmonary mechanics was studied by comparing pre- and postoperative spirometry in 30 patients undergoing extracorporal shock wave lithotripsy, 15 of whom received a unilateral intercostal nerve block, the remainder a general anaesthetic. Both groups of patients had significant postoperative changes in peak expiratory flow rate, expiratory reserve volume and vital capacity; forced expiratory volume at one second was not significantly changed in either group. There were no significant differences in the pre- or postoperative mechanics between the two groups. We conclude that general anaesthestics do not play a significant role in the generation of abnormalities in postoperative spirometry.

Adult↗
PubMed1989

Mammalian aspartate transcarbamylase (ATCase): sequence of the ATCase domain and interdomain linker in the CAD multifunctional polypeptide and properties of the isolated domain.

Mammalian aspartate transcarbamylase (ATCase; carbamoyl-phosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) is part of a 240-kDa multifunctional polypeptide called CAD, which also has carbamoyl-phosphate synthetase and dihydroorotase activities. We have sequenced selected restriction fragments of a Syrian hamster CAD cDNA that are clearly homologous to three prokaryotic ATCases. These studies, combined with previous sequence data, showed that the ATCase domain of CAD is encoded by 924 base pairs and has a mass of 34,323 Da and a pI of 9.8. While the bacterial pyrimidine biosynthetic enzymes are separate proteins, in mammals the ATCase domain is fused to the carboxyl end of the CAD chimera via a 133-amino acid (14-kDa) linker with an unusual amino acid composition, a pI of 10.2, and pronounced hydrophilic character. The fully active domain isolated from proteolytic digests was characterized by partial amino acid sequencing and amino acid analysis. Trypsin cleavage produced the ATCase domain with a 20-residue amino-terminal extension. Hydrodynamic studies showed that the isolated domain is a 110-kDa trimer with a Stokes radius of 41 A. The mammalian ATCase domain and the prokaryotic enzymes have virtually identical active-site residues and are likely to have the same tertiary fold.

Amino Acid Sequence↗