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Biomedical subjects

C D Smith

Publications and source records attributed to C D Smith.

At least 325 records · Page 18Linked to original sources
PubMedDate not supplied

Temperature effects in cyanolysis using elemental sulfur.

As part of our studies directed at new treatments for cyanide poisoning we examined the effect of temperature on both the non-catalyzed and the albumin-catalyzed reactions of cyanide with a colloidal suspension of elemental sulfur (CSES). Using saturated sulfur solutions prepared in two solvents, pyridine (PY) and methyl cellosolve (MC), the reactions were studied at 15.0, 25.0, 30.0 and 37.5 degrees C. For all the cyanolysis reactions (non-catalyzed and albumin-catalyzed) there is an enhancement of reaction rate when the organic solvent for the sulfur is MC. Irrespective of the solvent for the CSES, the non-catalyzed reactions gave linear Arrhenius plots (PY, correlation coefficient = 0.998; MC, correlation coefficient = 0.997). In each case the entropy of activation was positive (14.1 cal K-1 mol-1 for PY and 56.4 cal K-1 mol-1 for MC). In contrast with these results the albumin-catalyzed reactions generated non-linear Arrhenius plots and negative entropies of activation. Non-linear plots were observed with the three albumins studied: human serum albumin, heat-shock bovine serum albumin and fatty acid-free bovine serum albumin. The non-linear plots are the result of a more complex reaction sequence than a simple cyanolysis reaction.

Colloids↗
PubMedDate not supplied

Completion pancreatectomy following pancreaticoduodenectomy: clinical experience.

While pancreaticoduodenectomy is today performed with an operative mortality of less than 5%, the incidence of significant operative morbidity remains at least 25%. Albeit rarely, completion pancreatectomy during the early postoperative period may be required to manage uncontrolled pancreatic anastomotic leaks. From 1964 to 1988, pancreaticoduodenectomy was performed on 479 patients at our institution, 178 (37%) of whom required re-operation in the early postoperative period. Of these, 11 (6%) patients underwent completion pancreatectomy at a mean interval of 18 days following Whipple resection. The indications prompting re-operation included a suspected pancreatic leak (n = 8), intraabdominal hemorrhage (n = 2), and pancreaticocutaneous fistula (n = 1). Operative findings necessitating completion pancreatectomy included pancreatic anastomotic dehiscence with severe surrounding inflammation/necrosis prohibiting reanastomosis or repair (n = 10) and necrotizing pancreatitis with uncontrolled hemorrhage (1). Seven (64%) of these 11 patients died postoperatively of sepsis and multiple organ failure. The mean hospital stay in the 4 surviving patients was 46 days (range, 26 to 53 days). These 4 patients survived for a mean period of 24 months following hospital dismissal.

Female↗
PubMedDate not supplied

3,4-Diaminopyridine reverses respiratory paralysis induced by a presynaptically active snake venom and its major neurotoxin.

Presynaptically active snake venom neurotoxins induce a potentially fatal neuromuscular blockade which cannot be reliably overcome by current therapy. The drug 3,4-diaminopyridine (DAP) is effective in other presynaptic paralytic conditions and was therefore tried in anaesthetized rabbits with respiratory paralysis induced by krait (Bungarus fasciatus) venom. A strain gauge pneumograph measured rabbit chest circumference during the respiratory cycle to document objectively effects of toxins and treatments. DAP counteracted the effects of both whole krait venom and its purified presynaptically active component, beta-bungarotoxin. Respiratory excursions increased within 4-8 min after DAP injection in animals paralysed with beta-bungarotoxin and 4-10 min after the injection of DAP in animals paralysed with 1 mg/kg whole krait venom. The onset of complete respiratory paralysis after a lethal dose of whole krait venom (2 mg/kg) was delayed significantly by DAP. This is the first indication that presynaptic venom paralysis can be reversed and suggests that DAP merits further evaluation as treatment for this condition.

4-Aminopyridine↗
PubMedDate not supplied

Microtubule-associated protein 2 (MAP-2): a sensitive marker of seizure-related brain damage.

We have assessed the efficacy of MAP-2 immunohistochemistry as a marker of seizure-related brain damage and its suitability for quantitation of the damage using densitometric and morphometric image analysis. Seizures were produced in rats by administration of 1.5 LD50 soman, an irreversible AChE inhibitor. Our results demonstrate that neuronal damage, assessed using hematoxylin and eosin, and cresyl violet staining, was colocalized on adjacent serial sections with clearly demarcated reductions in MAP-2 staining. The most severely damaged brain regions were devoid of MAP-2 staining. Reductions in MAP-2 immunostaining were found to be exceptionally well suited for quantitation using densitometric and morphometric image analysis. This study represents the first demonstration of seizure-induced excitotoxic alterations in MAP-2.

Animals↗
PubMedDate not supplied

31P magnetic resonance spectroscopy in Alzheimer's and Pick's disease.

Previous studies have suggested a defect in phosphorus metabolism in Alzheimer's disease (AD) gray matter. We have studied phosphorus metabolites in both gray and white matter in autopsy specimens of nine subjects with late-stage AD, three with Pick's disease and seven age-matched controls. Phosphorus metabolites sugar phosphate (SU), phosphomonoester (PME), phosphodiester (PD), and inorganic phosphate (PI) were quantified as mole percentages in regional neocortical specimens using nuclear magnetic resonance spectroscopy. Senile plaque (SP) and neurofibrillary tangle (NFT) counts were determined in adjacent cortical sections. In the inferior parietal lobule gray and white matter, mole percentage normalized PME, and PD were significantly greater than control values in both AD and Pick's disease. A significant correlation was found between PD and NFT in AD parietal gray matter. Our data indicates that phosphorus metabolite alterations are present in two cortical degenerative diseases and are not likely to be specific for AD.

Aged↗
PubMedDate not supplied

The development of beta 1-adrenoceptors in brown adipose tissue following prenatal alcohol exposure.

Prenatal alcohol exposure delays the development of thermoregulation in newborn rats. Newborns generate heat by the sympathetic nervous system's activation of nonshivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of prenatal alcohol exposure on the development of the beta-adrenergic receptor system of BAT was investigated by assessing the number and pharmacological properties of beta-adrenergic receptors in BAT in 1-, 5-, 10-, and 20-day-old offspring. Pregnant dams were given either a liquid diet with 35% of the calories derived from alcohol, a liquid diet without alcohol for any effects of the liquid diet administration, or ad lib food and water. Offspring from the alcohol prenatal treatment group had a greater number of beta 1 adrenergic receptors compared to offspring from both from the pair-fed and lab chow control groups, which did not differ from each other. The greater number of receptor sites in 5-day-old subjects suggests that the number of binding sites in alcohol-exposed BAT cells continues to rise due to the absence of sufficient neurotransmitter, and perhaps reflects a delay in the arrival of sympathetic nervous system neurons. During the second and third postnatal weeks, when NE concentrations are rising and reaching asymptotic levels, the number of beta 1 adrenergic receptors in BAT of control subjects is decreasing. This expected compensatory "downregulation" response in receptor concentration was not seen in BAT from subjects exposed to alcohol prenatally. These findings may have important implications for understanding the effects of prenatal alcohol exposure on developing plasticity in the peripheral nervous system.

Adipose Tissue, Brown↗
PubMedDate not supplied

Brain creatine kinase with aging in F-344 rats: analysis by saturation transfer magnetic resonance spectroscopy.

We measured in vivo forward flux of the creatine kinase reaction in rat forebrain in young (Y: 6 month, n = 13), mid-aged (M: 12 month, n = 7) and aged (O: 27 month, n = 10) animals using 31P magnetic resonance saturation transfer. Forward flux was reduced in the aged rats (Y: 0.42 +/- 0.08; M: 0.41 +/- 0.10; O: 0.31 +/- 0.03 s(-1) +/- SD; p = 0.008 O vs. Y). In vitro studies in a subset of the same rats showed a parallel decline in CK activity (Y: 2.16 +/- 0.40; M: 2.17 +/- 0.25; O: 1.56 +/- 0.06 IU +/- S.D.; p = 0.002 O vs. Y). The in vivo spectroscopic and in vitro biochemical measures were significantly correlated. Reduced creatine kinase activity could account for the observed decreased forward flux in aging brain. Intracellular pH, phosphocreatine/inorganic phosphate ratio, and phospocreatine/gamma-adenosine triphosphate ratio did not differ between groups. Forward flux may represent a better measure of brain energy function than relative phosphocreatine or adenosine triphosphate levels observable in vivo.

Aging↗
PubMedDate not supplied

Asthma and gastroesophageal reflux: fundoplication decreases need for systemic corticosteroids.

An association between gastroesophageal reflux (GER) and asthma has been suggested for many decades. Although antireflux therapy (medical and surgical) has been shown to be beneficial in patients with asthma, response to therapy has not been well quantified. The aim of this study was to evaluate long-term outcome in patients with asthma and associated GER undergoing fundoplication. From a database of more than 600 patients with GER treated surgically between 1991 and 1996, 39 patients with asthma as their primary indication for surgery were identified. Asthma symptom scores were determined using the National Asthma Education Program classification, and medication frequency scores were determined preoperatively and at latest follow-up (median follow-up 2.7 years). Comparisons were made using the Wilcoxon rank-sum test. Asthma symptom scores decreased significantly after antireflux surgery. More important, the medication scores for use of systemic corticosteroids decreased significantly postoperatively (2.2 preoperatively vs. 0.7 postoperatively; P = 0.0001). Of the nine patients who required daily oral corticosteroids, seven have discontinued treatment entirely (78%). In patients with asthma associated with GER, symptoms of asthma are improved following fundoplication. Especially important has been the ability to wean patients from systemic corticosteroids postoperatively. Fundoplication should be offered to those patients with GER-associated asthma, especially those who are steroid dependent.

Adolescent↗
PubMedDate not supplied

Herpes simplex virus transmission: condom studies.

The incidence of genital herpes simplex infections has risen at a rapid rate over the past 20 years. Sexually active young adults ask whether condoms will effectively block the transmission of herpes simplex virus from one individual to another. Using a laboratory plunger model to stimulate human coitus, the authors have shown that high concentrations of HSV-2 did not cross the latex or natural membrane condoms that were tested. We have also shown that high concentrations of HSV-2 left in contact with a condom for 8 hr does not penetrate the barrier. This study gives good indirect evidence that condoms block the transmission of herpes simplex virus.

Contraceptive Devices, Male↗
PubMedDate not supplied

Chronic ureteral obstruction in the rat suppresses renal tubular Bcl-2 and stimulates apoptosis.

Unilateral ureteral obstruction (UUO) results in widespread tubular apoptosis in obstructed kidneys of both adults and neonates. The oncoprotein bcl-2 inhibits many forms of apoptosis, whereas the related protein bax promotes apoptosis. To evaluate the interaction of bcl-2, bax, and apoptosis in the renal response to UUO, adult and neonatal rats were subjected to UUO or sham operation, and kidneys were harvested 14 days later. Apoptotic cells were identified by the Tunel technique, and the distribution of bcl-2 and bax was determined by immunochemistry. In both adults and neonates, tubular and interstitial apoptosis was present in the obstructed kidney, but not in intact kidneys. In both adults and neonates, there was diffuse tubular bcl-2 and bax staining of sham-operated and intact kidneys. While bcl-2 was increased in scattered nonapoptotic tubules of the obstructed kidney, there was minimal staining of dilated apoptotic tubules. These results are consistent with the premise that bcl-2 normally suppresses renal tubular apoptosis. The distribution of bax staining in tubules of the obstructed kidney overlapped that of bcl-2. We conclude that chronic UUO inhibits bcl-2 expression in selected tubules of the obstructed kidney which contributes to activation of apoptosis and progressive renal damage in either neonatal or adult kidneys. Dysregulation of apoptosis may be a response to renal injury similar to that underlying the development of cystic kidney disease or renal dysplasia.

Animals↗
PubMedDate not supplied

Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication.

We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics.

Catheterization↗
PubMedDate not supplied

Hanford miniature swine model for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is now an accepted therapy for neonatal respiratory failure due to reversible lung disease. There is a continued need to train ECMO team members using animal models. Hanford miniature swine are an appropriate model for this purpose because of the availability and size as well as anatomic and physiologic similarities to humans. This article describes training ECMO team members in venoarterial and venovenous bypass utilizing Hanford miniature swine.

Animals↗
PubMedDate not supplied

Credentialing of research surgeons: can computers help in the process?

There has been recurring debate regarding the need for a process of ensuring that individuals who propose research using live animals will be competent in the research and compassionate in their care of animals. The mechanism by which this goal can be accomplished is presently under consideration and acceptance by investigators is of concern. As a first step, the authors propose utilization of an interactive computer program that not only would evaluate cognitive knowledge but also would instruct in areas found to be deficient. Immediate feedback with educational reinforcement is possible. The authors' interest in such a program began with a pediatric surgical postgraduate course presented in 1994 at the Clinical Congress of the American College of Surgeons. The computer program utilized was IRIS (Instantaneous Response Interactive System: IRIS, Denver, CO, USA). This system was well suited to evaluation and instantaneous feedback. That program, or one like it, would be suited to initial evaluation and education of researchers. The important aspect is interaction and immediate feedback. This article also includes the results of a panel discussion at the annual meeting of the Academy of Surgical Research in Albuquerque, New Mexico.

Animal Welfare↗
PubMedDate not supplied

Behavioral correlates of soman-induced neuropathology: deficits in DRL acquisition.

Rats (N = 45) pretrained to lever press for milk reinforcement on a continuous reinforcement (CRF) schedule were injected with 100-110 micrograms/kg of the anticholinesterase soman (N = 24) or saline (N = 21) SC. Subjects exposed to soman experienced moderate to severe acute symptoms of anticholinesterase intoxication. After a 3 week recovery period, all surviving subjects were retrained on CRF, then given 45 training sessions on a differential reinforcement of low rates (DRL) 20 sec schedule, followed by 10 sessions of extinction. Brains of all subjects were then examined for evidence of neuropathology. Subjects exposed to soman showed no improvement over sessions in the number of reinforcements earned on the DRL schedule due to an inefficient patterning of responses. There were no differences between groups in the number of total DRL responses or terminal extinction responses. Neuropathology was most evident in dorsal thalamic areas, primary olfactory/piriform cortex and amygdala of subjects exposed to soman. There were significant correlations between the severity of acute intoxication scores, degree of neuropathology, and deficits in DRL performance. The results demonstrate that exposure to high doses of this anticholinesterase agent can result in neural damage and persistent decrements in performance of certain operant tasks.

Animals↗