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Biomedical subjects

R Gordon

Publications and source records attributed to R Gordon.

At least 37 records · Page 2Linked to original sources

Hepatic artery pseudoaneurysm ligation after orthotopic liver transplantation--a report of 7 cases.

Pseudoaneurysm (PA) is a rare but life-threatening complication of liver transplantation. The authors present their experience on 7 patients treated by ligation of a post-OLT PA. Hepatic artery ligation or embolization was performed from 10 to 70 days after liver transplantation. Of the seven patients, four survived, one developed a biliary stricture, treated by percutaneous balloon dilatation, two died of a complication not related to treatment, and one died of multiple organ failure.

Adult

Ethanol-associated alterations in the kinetics of putrescine uptake and metabolism by the regenerating liver.

Biosynthesis of the polyamines, putrescine, spermidine, and spermine is required for DNA synthesis and liver regeneration after partial hepatectomy. We have previously reported that chronic ethanol consumption impairs polyamine synthesis and significantly retards liver regeneration after partial hepatectomy. In those studies, supplementation with putrescine restored hepatic DNA synthesis in ethanol-fed rats but exerted no effect in pair-fed controls. These differences in the response to putrescine treatment may have resulted from ethanol-associated differences in hepatic uptake, release, or metabolism of putrescine. To resolve these issues and define more completely how putrescine treatment affects DNA synthesis, we now assess the kinetics of putrescine uptake and metabolism after intraperitoneal or intravenous injection of radiolabeled putrescine (1.2 mmol/kg, specific activity 1 microCi/mmol) into rats fed 36% ethanol diets or isocaloric, nonethanol diets for 6 weeks prior to partial hepatectomy. After putrescine treatment, hepatic putrescine concentrations were greater in ethanol-fed rats than controls. Differences in post-treatment hepatic putrescine levels between ethanol and pair-fed groups could not be explained by differences in the rates of hepatic putrescine uptake or excretion into bile; residual de novo synthesis of putrescine from ornithine or metabolism of hepatic putrescine to its polyamine products, spermidine and spermine. Indeed, supplemental putrescine was not appreciably converted to spermidine or spermine in either ethanol or control rats. Hence, these latter polyamines are unlikely to be responsible for the treatment-associated improvement in DNA synthesis that has been noted in ethanol-fed rats. This suggests that putrescine itself acts to restore hepatic DNA synthesis in ethanol-fed rats.

Alcoholism

Changes in cognitive and language functioning of preschool children with autism.

Preschool children with autism and their normally developing peers were compared on the Stanford-Binet IV and Preschool Language Scale before and after 1 school year. Both measures showed that although the children with autism functioned at a lower level than their normally developing peers, the children with autism had narrowed this gap after treatment, making a nearly 19-point increase in IQ and an 8-point gain in language quotient. The IQ measure remained stable for the normally developing peers while their language showed a 7.73-point increase. The data support the notion that young children with autism can make very significant developmental gains.

Autistic Disorder

Interaction of felbamate and diazepam against maximal electroshock seizures and chemoconvulsants in mice.

The anticonvulsant effects of felbamate alone or in combination with diazepam were investigated against maximal electroshock-, pentylenetetrazol-, isoniazid- and bicuculline-induced seizures in mice. A single subprotective dose of felbamate, a dose which offers no protection to animals when combined with diazepam, enhanced the protective effects of diazepam against seizures induced by electroshock, pentylenetetrazol and isoniazid, as measured by significant reduction of ED50 values. However, felbamate failed to significantly affect the protective action of diazepam against bicuculline. Felbamate does not interact directly with the GABA-benzodiazepine-ionophore complex. Thus the enhancement of anticonvulsant activity of diazepam by felbamate against maximal electroshock and pentylenetetrazol may involve an indirect effect at benzodiazepine receptors. The anticonvulsant action of felbamate against isoniazid does not seem to involve benzodiazepine receptors and may be due to reversing the inhibitory effect of isoniazid on glutamate decarboxylase (GAD) activity. The interaction between felbamate and diazepam may also involve other mechanisms.

Animals

The hearing loss associated with exposure to toluene is not caused by a metabolite.

Exposure to toluene causes a marked hearing loss in rats, and this effect has been observed in some human solvent abusers. The issue of whether toluene or one of its metabolites is responsible for this effect has not been examined. To attempt to resolve this issue, we manipulated the metabolism, and thus the circulating levels, of toluene as follows. Two groups of rats were exposed to phenobarbital (PB) in their drinking water (0.1%) for seven days to induce detoxifying liver enzymes; two other groups had access to PB-free water. Then half of the rats exposed to PB or water were exposed to filtered air or a concentration of toluene expected to cause hearing loss. Levels of toluene in blood were markedly reduced by the PB and the excretion of hippuric acid was increased. All rats were tested for auditory sensitivity by brainstem auditory-evoked response (BAER) audiometry using a 16-kHz tone pip. The rats exposed to toluene alone showed a marked reduction in the integrated BAER waveform, indicative of the expected hearing deficit. None of the other treated rats showed any deviation from controls (i.e., water and air). These results provide strong evidence that toluene itself is responsible for the auditory dysfunction. Toluene also caused the rats to increase their fluid consumption and urine output; these effects were not altered by PB. Identification of toluene as the proximal ototoxicant should facilitate the search for the mechanism of this effect.

Acoustic Stimulation

Does the presence of a measurable blood alcohol level in a potential organ donor affect the outcome of liver transplantation?

The widespread application of hepatic transplantation has created a tremendous demand for donor organs. An assessment of donor parameters is thought to be important in selecting good donors; however, the criteria utilized have not been standardized. This study was performed to determine the effect of a measurable donor blood alcohol level on graft survival. Fifty-two patients who underwent orthotopic liver transplantation at the University of Pittsburgh were included in the study. Twenty-five patients received liver grafts from donors having a blood alcohol level between 0.04 and 0.4 g/l with a mean of 0.17 g/l. Twenty-seven patients received a liver graft from a donor who had no measurable blood alcohol. There were no differences between these two groups of donors regarding the time of initial hospitalization until the time of donation. Graft failure within the first 30 days was 24% for those receiving an organ from an alcohol-positive donor as compared with 22.2% in those receiving an organ from an alcohol negative donor. The recipient mortality rate was 16% and 11%, respectively. No relationships between the donor blood alcohol level and organ performance, frequency of primary graft nonfunction, or number of episodes of acute cellular rejection were evident. Based upon these data, the presence of a measurable blood alcohol level in a donor should not mitigate against organ donation.

Adult

Variability in growth of Neisseria polysaccharea on colistin-containing selective media for Neisseria spp.

In a prospective survey of 773 healthy schoolchildren in southern Alberta, Canada, Neisseria polysaccharea was isolated from the pharynxes of only 4 (0.5%) subjects, whereas Neisseria lactamica and Neisseria meningitidis were isolated from 110 (14%) and 15 (2%) children, respectively. These strains of N. polysaccharea, together with three other sporadic isolates from Alberta, Canada, were compared with the type strain from France and strains from Spain and Germany. All strains were phenotypically identical, except that the Canadian and German strains, for which the colistin MICs were 1 mg/liter, failed to grow on Thayer-Martin medium (TMM), whereas the type strain and the Spanish strains, for which the colistin MICs were greater than 7.5 mg/liter, were not inhibited. Multilocus enzyme electrophoresis indicated that six distinct electrophoretic types were present among the seven Canadian strains. Our results show that growth on gonococcal selective media which contain colistin is a variable feature of this taxon.

Adolescent

One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults.

An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration.

Adult

Diagnostic and interventional procedures for the biliary tract.

Various diagnostic imaging studies have been employed in the past year to evaluate the normal and abnormal biliary ductal system. Variations in the normal ductal drainage of the left lobe of the liver, in which the right lateral hepatic duct drained into the left hepatic duct, were studied because of the implications for the surgical resection of the left lobe. Choledochal cysts have been studied in adults using endoscopic retrograde cholangiopancreatography to evaluate the abnormal junction between the common bile duct and pancreatic duct and the long dilated common channel. An ultrasound study indicated that children with choledochal cysts also may have intrahepatic duct dilatation. An increased incidence of malignancy has been noted in adults with choledochal cysts, and their appearance on ultrasound, CT, and cholangiography were described. Cystic fibrosis produces abnormalities of the biliary tree, extrahepatic strictures, and more interestingly, intrahepatic ductal dilatation and abnormal contour without strictures. The usefulness of the preoperative ultrasonographic evaluation of the biliary tract in Oriental cholangiohepatitis was stressed. Bile duct abnormalities in fascioliasis were also noted on CT scans. Patterns of abnormality in the CT appearance of the thickened, contrast-enhanced, extrahepatic bile ducts were elucidated. Focal concentric, focal excentric, diffuse concentric, and diffuse excentric ducts were seen with various forms of pancreatic disease, choledocholithiasis, and various forms of cholangitis. An enhanced, thick-walled duct indicates disease, but is a nonspecific finding. Chronic cholecystitis was found to produce false-positive cholescintigram results in patients with suspected acute cholecystitis, but only in those with severe degrees of chronic cholecystitis. The results of multicenter trials using extracorporeal biliary lithotripsy in the United States have been published. They are somewhat disappointing and do not confirm the original excellent results reported in Germany for treatment of gallbladder stones. Much interest has been focused on the use of expandable metallic stents for the treatment of benign and malignant biliary obstruction. Preliminary data suggest good patency rates for benign lesions. Patency rates for malignant lesions are similar to those of previously available plastic stents.

Biliary Tract Diseases

Cholecystokinin cholescintigraphy: detection of abnormal gallbladder motor function in patients with chronic acalculous gallbladder disease.

CCK cholescintigrams were performed in 374 patients with recurrent postprandial right upper quadrant pain, biliary colic, and a normal gallbladder sonogram and/or cholecystogram. The results of these examinations were correlated with the patients' final medical/surgical diagnoses. Twenty-seven patients recruited as control volunteers without objective clinical evidence of biliary disease also underwent CCK cholescintigraphy to determine if the degree of gallbladder contraction post-CCK differs in symptomatic versus asymptomatic subjects. Decreased gallbladder motor function was identified (maximal gallbladder ejection fraction response to CCK less than 35%) in 94% of patients with histopathologically confirmed chronic acalculous cholecystitis or the cystic duct syndrome and in 88% of patients clinically believed to have chronic acalculous biliary disease. Decreased gallbladder motor function does not distinguish symptomatic from asymptomatic gallbladder disease.

Cholecystokinin

Liver transplantation for polycystic liver disease.

Four female patients with severe complications of polycystic liver disease were treated with liver replacement; two patients were also given kidneys from their liver donors. All four of the patients were suffering from extreme fatigue. Three of the recipients have survived for 8, 11, and 60 months with normal liver function and present good health. The fourth patient recovered from a liver-kidney transplantation, but 5 months later, fulminant hepatic failure developed in this patient due to hepatitis B virus, and she died despite emergency hepatic retransplantation.

Adult

Orthotopic liver transplantation for alcoholic liver disease.

Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 +/- 9 mo (mean +/- S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy.

Alanine Transaminase