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Biomedical subjects

K L Cox

Publications and source records attributed to K L Cox.

At least 55 records · Page 3Linked to original sources

Hepatocellular carcinoma and liver cell dysplasia in children with chronic liver disease.

The histology of 72 livers from 72 children who underwent liver transplantation was reviewed. Nine children (12.5%) had hepatocellular carcinoma (HCC) and/or liver cell dysplasia (LCD) in their native livers. Ages at the time of transplantation ranged from 2 months to 11 years. Primary liver diseases included tyrosinemia (3), biliary atresia (2), chronic active hepatitis B (1), chronic active non-A non-B non-C hepatitis (1), idiopathic neonatal hepatitis (1), and neonatal iron storage disease (1). Explanted livers showed large multifocal HCC in two cases, incidental HCC in three, and dysplastic nodules in four. LCD also was present in three cases in conjunction with HCC. All patients had cirrhosis. Alpha-fetoprotein was measured in six children and was elevated in all six (range, 300 to 1,770,000 ng/mL; normal, 0 to 15 ng/mL). Abdominal computed tomography, ultrasonography, and/or magnetic resonance imaging showed large masses in two cases, but did not detect the tumors of less than 2 cm or the dysplastic nodules in the other seven children. After a follow-up period of 2 months to 3 years (mean, 19.8 +/- 12.1 months), eight children are alive and have no evidence of recurrence. The patient with neonatal iron storage disease died 2 months after transplantation, without evidence of tumor recurrence. The authors conclude that children with end-stage liver disease of diverse causes referred for liver transplantation may have LCD and/or HCC. Serial determination of alpha-fetoprotein and images studies may detect early lesions curable by liver transplantation.

Carcinoma, Hepatocellular↗

Liver transplantation at California Pacific Medical Center, San Francisco, California.

A number of modifications in patient selection, operative technique, and immunosuppressive management have greatly contributed to the success of the liver transplant program at CPMC. Graft rejection and the timely detection of EBV infection are ongoing problems in hepatic transplantation that are foci of active research in our field. To address these issues, our group is investigating the activity of cytokines and adhesion molecules using sophisticated molecular techniques, and we are developing a sensitive assay for EBV markers in blood. These and other projects currently in progress will continue when we move our liver transplant program to Stanford University Medical Center in January 1995.

Actuarial Analysis↗

The influence of portoenterostomy with stoma on morbidity in pediatric patients with biliary atresia undergoing orthotopic liver transplantation.

A portoenterostomy (PE) procedure for extrahepatic biliary atresia (EHBA) is sometimes performed with a stoma in an attempt to reduce the incidence of acute cholangitis. The purpose of this study was to determine if the presence of a stoma increased the complication rate of patients undergoing orthotopic liver transplantation (OLT) for EHBA. The medical records of 42 consecutive patients with EHBA who underwent primary OLT between October 1988 and October 1991 were retrospectively reviewed. Three patients were excluded, since their grafts were lost within 3 days of OLT. The remaining 39 patients were divided into three groups: no PE (n = 7), PE without stoma (n = 23), and PE with stoma (n = 9). The mean age of the whole group was 19.62 +/- 24.37 months, with a range of 5 to 132 months. Mean weight was 9.62 kg, with a range of 4.2 to 41 kg. Survival at 3 and 12 months as well as number of retransplantations were similar among the three groups. However, at the time of OLT increased morbidity was observed, consisting of increased operative time and number of reoperations, whether or not the stoma had been closed prior to OLT.

Biliary Atresia↗

Revascularization technique for reduced-size liver transplantation for infants weighing less than 10 kg.

Reduced-size liver transplantation has been recognized as a powerful modality in alleviating the global donor shortage in pediatric liver transplantation. We describe, for the first time, a technique for revascularizing reduced-size grafts which has not been patterned after adult revascularization techniques. This revascularization method for reduced-size liver transplantation is particularly suitable for infants weighing < 10 kg. This technique differs from adult revascularization techniques in that the supraceliac aorta is always used as the origin for graft arterialization, and that the anastomoses are always performed in the following order: end-to-side donor celiac artery to supraceliac aorta anastomoses first, followed by the suprahepatic vena caval anastomoses, infrahepatic vena caval anastomoses, and then portal vein anastomoses. Hepatic artery thrombosis in infants weighing < 10 kg has occurred in 4 of 32 nonreduced versus 0 of 21 reduced transplantations (P = .05616, Z test, one tail). Adult revascularization was primarily used in the nonreduced group, whereas our proposed revascularization method was primarily used in the reduced group. We conclude that, for infants weighing < 10 kg receiving reduced grafts, this proposed technique should be used to decrease hepatic artery thrombosis.

Adult↗

The combined effects of aerobic exercise and alcohol restriction on blood pressure and serum lipids: a two-way factorial study in sedentary men.

OBJECTIVES: To determine whether vigorous exercise and alcohol restriction have additive and independent effects in reducing blood pressure in sedentary male alcohol drinkers. Also to assess whether 4 weeks of vigorous exercise could offset the fall in high-density lipoprotein cholesterol (HDL-cholesterol) usually observed after alcohol restriction. DESIGN: Seventy-five sedentary men were randomly assigned to drink low-alcohol beer or continue their normal drinking habits. Within these two groups subjects were further assigned either to a vigorous exercise programme of three 30-min sessions a week of cycling at 60-70% of maximum workload or to a control light-exercise programme. RESULTS: Seventy-two subjects completed the trial. Alcohol consumption fell by 85% in the low-alcohol group. Fitness increased by 10% following vigorous exercise, with a significant improvement in maximum oxygen uptake. After adjustment for weight loss, a significant effect of alcohol restriction in reducing both systolic and diastolic blood pressure was demonstrated. There was no effect of vigorous exercise on blood pressure. Serum total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B were not influenced by alcohol restriction or vigorous exercise. However, alcohol restriction significantly reduced triglyceride, HDL-cholesterol, its subfractions HDL2-cholesterol and HDL3-cholesterol, and its major apolipoproteins apo A-I and apo A-II. These reductions were unaffected by moderate exercise. CONCLUSIONS: This study provides further evidence that alcohol restriction results in reductions in blood pressure in men who are regular alcohol drinkers. However, a simultaneous increase in fitness did not lead to lower blood pressures than those achieved with alcohol restriction alone, and was unable to offset alcohol-related falls in HDL-cholesterol, its subfractions and its major apolipoproteins.

Adult↗

Characterization of cholecystokinin receptors on the human gallbladder.

BACKGROUND: Several studies examined in vivo and in vitro biologic activity of the human gallbladder in response to cholecystokinin (CCK). However, few studies have demonstrated directly the interaction of CCK with receptors on the human gallbladder, which is responsible for this biologic activity. METHODS: To characterize CCK receptors on human gallbladder tissue, gallbladders were removed from human donor grafts that were being used for liver transplantation. The gallbladders were rapidly frozen and sectioned for measurement of binding of 125I-Bolton-Hunter-labeled-CCK-8 and were cut into strips for in vitro bioassay. RESULTS: Binding of 125I-BH-CCK-8 to human gallbladder was saturable, specific, and dependent on time, pH, and temperature. The binding was inhibited only by cholecystokinin-related peptides including CCK-8 (IC50 10 +/- 1.0 nmol/L) (mean +/- SD), des(SO3) CCK-8 (IC50 0.9 +/- 0.2 mumol/L), and gastrin-17-I (IC50 9.0 +/- 2.0 mumol/L) or specific CCK receptor antagonist L-364,718. Computer analysis of binding of 125I-BH-CCK-8 to gallbladder tissue showed a single class of binding sites with high affinity for CCK-8. Autoradiography localized binding of 125I-BH-CCK-8 only to the smooth muscle layer of the gallbladder. In the bioassay des(SO3) CCK-8 (EC50 1.2 +/- 0.7 mumol/L) and gastrin-17-I (EC50 4.5 +/- 2.4 mumol/L) were 150- and 563-fold less potent than CCK-8 (EC50 8.0 +/- 2.2 nmol/L). The relative potencies of CCK agonists for inhibiting binding of 125I-BH-CCK-8 agreed closely with their relative potencies for causing gallbladder contraction. The dose-response curve for CCK-8 alone to induce gallbladder contraction was not significantly different from those caused by CCK-8 plus 1 mumol/L tetrodotoxin or 1 mumol/L atropine. CONCLUSIONS: These results characterized the CCK receptors on smooth muscle of human gallbladder as sulfate dependent and causing gallbladder contraction.

Autoradiography↗

Characterization of cholecystokinin receptors on the human sphincter of Oddi.

BACKGROUND: The present in vitro study investigated the interaction between cholecystokinin (CCK) and receptors on human sphincter of Oddi tissue obtained from donated human livers that were being transplanted. METHODS: Radiolabeled ligands with cholecystokinin receptor specificity, autoradiography, and crystal scintillation counting were used to directly characterize cholecystokinin receptors on tissue sections. RESULTS: The binding of 125I-BH-CCK-8 to the tissue was saturable, specific, and dependent on time, pH, and temperature. Saturable binding of 125I-BH-CCK-8 was localized on the smooth muscle layer, and binding was inhibited only by cholecystokinin-related peptides. Computer analysis of 125I-BH-CCK-8 binding indicated the presence of two classes of binding sites, one with a high affinity and the other with a low affinity for CCK-8. CCK-8 caused relaxation (half-maximal concentration, 6 nmol/L) and carbachol caused contraction (half-maximal concentration, 10 nmol/L) of circular, cross-sectional strips of the tissue. Longitudinal strips were less responsive. The relative 125I-BH-CCK-8 binding inhibition potency of CCK-8 agreed closely with its relative ability to cause sphincter relaxation. Tetrodotoxin (1 mumol/L) and atropine (1 mumol/L) caused a rightward shift of the dose-response curve for CCK-8-stimulated sphincter relaxation. CONCLUSIONS: The present results indicate that cholecystokinin receptors on the human sphincter of Oddi are sulfate dependent and mediate sphincter relaxation.

Atropine↗

Recent advances in pediatric liver transplantation.

The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in pediatrics. Each item, in the judgement of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in pediatrics that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Pediatrics of the California Medical Association, and the summaries were prepared under its direction.

Child↗

Graft involvement by Legionella in a liver transplant recipient.

Legionella pneumophila, serogroup 1, was identified by direct immunofluorescence in the lung and liver graft from a 2 1/2-month-old infant who underwent orthotopic liver transplantation because of fulminant hepatic failure secondary to neonatal hepatitis. The patient died of respiratory failure owing to this infection 22 days after transplantation despite treatment with erythromycin lactobionate. To our knowledge, this represents the first reported case of hepatic infection with Legionella in liver transplant recipients.

Fluorescent Antibody Technique↗

Effects of alcohol intake on plasma fatty acids assessed independently of diet and smoking habits.

1. This study was designed to determine prospectively whether changing alcohol consumption influenced the proportion of plasma linoleic acid independently of diet or smoking habits, and to evaluate changes in the plasma linoleic acid concentration as a potential marker of changes in alcohol consumption. 2. Fasting plasma fatty acid profiles were investigated in 72 male drinkers who were randomly assigned to drink low-alcohol beer or to maintain their usual drinking habits for a period of 4 weeks. 3. At entry to the study, a higher alcohol intake was associated with lower proportions of plasma linoleic acid, arachidonic acid and dihomolinolenic acid and higher proportions of plasma palmitoleic acid, independently of changes in body mass index. Smoking habits were unchanged and there were no major changes in diet during the period of the intervention. 4. Because the plasma palmitoleic acid concentration has been suggested as a possible marker of 'at risk' drinking, we investigated plasma fatty acid concentrations as indicators of alcohol intake. The plasma palmitoleic acid concentration was not a useful discriminator. Indices determined using logistic regression and combining plasma apolipoprotein A-II and linoleic acid concentrations gave better discrimination than either variable alone.

Adult↗

Liver transplantation in Langerhans' cell histiocytosis (histiocytosis X).

Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious osteolytic lesions at the time of transplantation. The histologic examination of the excised liver showed features consistent with primary sclerosing cholangitis. The two patients had an excellent recovery with no evidence of progression of LCH or recurrence of the underlying disease in the hepatic allograft at 1 and 3 years after organ transplantation.

Adolescent↗

Mediastinal pancreatic pseudocysts in children.

Mediastinal pseudocyst is an unusual complication of pancreatitis, with only four cases previously reported in children. The extent of the pseudocyst can be defined by computed tomography or magnetic resonance imaging scan and preoperative aspiration of cyst fluid for amylase level can establish the diagnosis. Endoscopic retrograde cholangiopancreatography to define ductal anatomy can help plan the appropriate drainage procedure. Although exceedingly rare, the diagnosis of pseudocyst should be considered for any cystic mass in the abdomen or thorax, even in the absence of elevated amylase or history suggesting pancreatitis.

Amylases↗

Controlled comparison of effects of exercise and alcohol on blood pressure and serum high density lipoprotein cholesterol in sedentary males.

1. Seventy-two sedentary male drinkers, aged 20-45 years, and with mean blood pressure (BP) at entry of 132 +/- 1.2/73 +/- 0.9 mmHg, completed a 4 week study during which they were assigned randomly to either drink a low alcohol beer (effectively reducing their weekly alcohol intake from 481 +/- 47 mL to 52 +/- 5 mL) or to continue their normal drinking habits. 2. Within these two groups subjects were further assigned to either a moderate exercise programme of three 30 min sessions per week of stationary cycling at 60-70% maximum workload or to a control light exercise programme where they pedalled against zero or minimal resistance. 3. Both alcohol restriction and moderate exercise were associated with mean falls in bodyweight of 0.5 kg. After adjustment for bodyweight a significant main effect of alcohol restriction on systolic BP (-4.1 +/- 1.7 mmHg, P less than 0.05) and diastolic BP (-1.6 +/- 0.8 mmHg, P = 0.05) was demonstrated. There was no significant main effect of moderate exercise on systolic or diastolic blood pressure despite a significant improvement in physical fitness (maximal oxygen uptake increasing from 33.2 +/- 0.8 mL/kg per min to 35.5 +/- 0.1 mL/kg per min). 4. Significant falls in high density lipoprotein cholesterol (HDLC) and triglyceride levels seen with alcohol restriction were unaffected by the increase in fitness, the magnitude of the fall being similar in both the moderate and light exercise groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗