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Biomedical subjects

J R Lake

Publications and source records attributed to J R Lake.

At least 91 records · Page 5Linked to original sources
PubMed1995

Liver transplantation for hepatocellular carcinoma: results with preoperative chemoembolization.

At the University of California, San Francisco, 17 patients who met the following criteria-hepatic tumor unresectable because of location or inadequate liver reserve, no metastases, HBsAg negative, no tumor larger than 5 cm in diameter, and no more than three tumors--were enrolled prospectively in a protocol employing preoperative chemoembolization to assess whether orthotopic liver transplantation (OLT) could cure a majority of highly selected patients with hepatocellular carcinoma (HCC). Thirteen patients had biopsy-proven HCC, 2 had the fibrolamellar variant, and 2 had radiological findings of HCC but no biopsy confirmation. Fourteen had underlying liver disease. All arteriographically apparent lesions were chemoembolized using a mixture including Gelfoam powder, doxorubicin, mitomycin-c, and cisplatin. Eight patients with poor hepatic reserve were chemoembolized when a donor organ became available, whereas 9 patients were chemoembolized and then placed on the waiting list. The only complication of chemoembolization was a gangrenous gallbladder in 1 patient. Thirteen patients underwent liver transplantation (2 patients without prior histological confirmation of carcinoma had no identifiable tumor at OLT); 3 patients developed metastases between the time of enrollment and donor organ availability and subsequently died; and 1 patient underwent a trisegmentectomy. Ten of the 11 patients with biopsy-proven HCC who underwent transplantation remain free of recurrent cancer at a median of 40 months; 1 patient died at 6 months of lymphoproliferative disease with no cancer found at autopsy. Although the role of chemoembolization is uncertain, these data show that the majority of carefully selected patients with HCC may achieve long-term survival with OLT.

Angiography↗
PubMed1995

Should liver transplantation be performed for patients with chronic hepatitis B? Yes!

The use of passive immunoprophylaxis to prevent HBV reinfection of the allograft following liver transplantation has led to a dramatic improvement in the outcome of patients who undergo transplantation for chronic hepatitis B. Hepatitis B previously was not one of our favorite diseases for which to perform liver transplantation. However, we now regard patients with this disease as good candidates for liver transplantation. I hope I have presented a compelling argument that no patient with hepatitis B, regardless of serological status, should be a priori denied liver transplantation. Studies from both the U.S. and Europe have shown that HBV reinfection can be prevented in almost all patients at a cost not out of line with other accepted indications for liver transplantation. Thus, I once again, ask the question, "Should patients with chronic hepatitis B undergo liver transplantation?" At our institution, the answer is an emphatic Yes!

Cost-Benefit Analysis↗
PubMed1995

Two-year outcome following transjugular intrahepatic portosystemic shunt for variceal bleeding: results in 90 patients.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a new therapy for variceal bleeding. Immediate technical and short-term clinical results have been reported. This study was undertaken to evaluate mid-term outcome after TIPS in patients who successfully underwent the procedure for variceal bleeding. METHODS: Ninety patients were followed up prospectively by clinical examination and radiological shunt evaluation including Doppler sonography and transjugular portal venography. RESULTS: The average follow-up in surviving patients was 2.2 years. The cumulative survival rate was 60% at 1 year and 51% at 2 years. The rate of cumulative rebleeding was 26% at 1 year and 32% at 2 years. A shunt abnormality was noted in all rebleeding patients. Rebleeding was successfully controlled in all but 1 of the patients who underwent shunt revision. Cumulative detection of stenosis or occlusion was 31% at 1 year and 47% at 2 years. Thirty-eight percent of shunt abnormalities were detected by routine surveillance. Percutaneous shunt revision was attempted in 22 patients and was successful in 21 (95%). CONCLUSIONS: Although mid-term primary patency is limited in many patients by the development of a shunt stenosis or occlusion, shunt function can be maintained in most patients by careful surveillance and periodic percutaneous intervention.

Adolescent↗
PubMed1995

Subcutaneous injection of an analog of neuropeptide FF prevents naloxone-precipitated morphine abstinence syndrome.

There is evidence that neuropeptide FF (NPFF) has antiopiate activity and may play a role in opiate dependence and subsequent abstinence syndrome. A fragment of NPFF was modified at the C-terminal in an effort to convert it to an NPFF antagonist. It was also dansylated at the N-terminal in an effort to render it more lipophilic and increase its penetration of the blood-brain barrier. Third ventricle administration of the resulting compound, dansyl-PQRamide (0.75 microgram and 1 microgram), dose-dependently antagonized the quasi-morphine abstinence activity of NPFF (10 micrograms) in opiate-naive rats. Subcutaneous injection of dansyl-PQRamide (13 mg/kg) in chronically morphine-infused rats attenuated opiate dependence as indicated by prevention of naloxone-precipitated abstinence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPFF receptors in a concentration-dependent manner with a Ki of 13 microM, and had a half-life over 300 times longer than NPFF under aminopeptidase digestion.

Animals↗
PubMed1995

Detection of hepatitis C after liver transplantation. Four serologic tests compared.

To determine the best method for detecting HCV infection in immunosuppressed patients, stored frozen serum from 101 liver transplant recipients was tested for hepatitis C virus. Each sample was tested by four assays. HCV RNA was detected by both polymerase chain reaction (PCR) and branched DNA signal amplification. Antibody to HCV was determined using second-generation enzyme-linked immunoassay (EIA) and recombinant immunoblot assay. Forty one transplant recipients met the working definition for true positives of HCV infection. Of these "true positives," 98% were positive by HCV RNA PCR assay, 88% by b-DNA signal amplification assay, 88% by anti-HCV EIA, and 63% demonstrated two or more reactive bands on recombinant immunoblot. Five of 57 (9%) HCV-antibody negative recipients had HCV RNA detected by both methods. Of 44 HCV enzyme-linked immunoassay (EIA) repeatedly reactive samples, the recombinant immunoblot was negative in 2 and indeterminate in 13. HCV RNA was present in 9 of 13 recombinant immunoblot indeterminate sera. Nine EIA repeatedly reactive sera were negative by both tests for HCV RNA. In liver transplant recipients, HCV infection is best determined by measurement of HCV RNA. Antibody formation may be delayed or suppressed in a minority of patients despite > 10(9) equivalents/L (> 10(6)/mL) of HCV RNA in serum. Recombinant immunoblots with a single reactive band pattern often indicate HCV infection in immunosuppressed patients.

Hepacivirus↗
PubMed1995

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunts: incidence and risk factors.

OBJECTIVES: The aim of this study was to determine the incidence of new or worsened hepatic encephalopathy after transjugular intrahepatic portosystemic shunts (TIPS) and to ascertain which clinical characteristics are associated with this complication. METHODS: At the University of California, San Francisco, over 22 months, TIPS were placed successfully in 108 adults. Seventy-seven patients in whom it was possible to assess the development of encephalopathy comprised the study population. Clinically significant encephalopathy was assessed at protocol clinic follow-up and, in some cases, by phone contact with the patient and the referring physician. Post-TIPS encephalopathy was defined as new onset of clinical encephalopathy requiring treatment or worsening of preexisting encephalopathy within 1 yr of TIPS. RESULTS: The overall incidence of new or worsened encephalopathy was 23% (18/77). Post-TIPS encephalopathy was well controlled with lactulose in 78% of cases and was progressive in 22%. Multivariate analysis showed that an increased risk of encephalopathy was associated with an etiology of liver disease other than alcohol [relative risk (RR) 9.2, p = 0.0052], female gender (RR 3.0, p = 0.029), and hypoalbuminemia (RR 2.2 for each 1 g/dl decrease, p = 0.044). CONCLUSIONS: Hepatic encephalopathy is a common complication of TIPS that can be controlled medically in most patients. The identification of clinical variables associated with an increased risk of encephalopathy may be useful in the selection of appropriate candidates for this procedure.

Adult↗
PubMed1995

Transjugular intrahepatic portosystemic shunts for refractory ascites: assessment of clinical and hormonal response and renal function.

Cirrhosis is frequently complicated by ascites that may become resistant to diuretic therapy. Transjugular intrahepatic portosystemic shunts (TIPS) represent a new treatment for this debilitating condition. The aim of this study was to ascertain the clinical efficacy of TIPS, as well as its impact on renal function and on hormonal parameters. Five inpatients with refractory ascites were studied prospectively before TIPS, and 3 and 14 days after TIPS. After TIPS, ascites completely resolved or was minimal in all patients. Diuretics were discontinued in three subjects and decreased by at least 50% in two. One patient developed liver failure after TIPS and required liver transplantation; the others remained stable after a mean follow-up of 14 months. Mean urinary sodium excretion increased from 2.1 +/- 0.6 mEq/24 hr before TIPS to 13.0 +/- 4.3 mEq/24 hr 14 days after TIPS. Mean serum creatinine and glomerular filtration rate also tended to improve during the study period. With the exception of the patient who developed liver failure, plasma aldosterone concentration decreased from a mean of 126.0 +/- 29.9 ng/dL to 22.8 +/- 6.8 ng/dL (P = .04), and plasma renin activity decreased from a mean of 9.0 +/- 3.0 micrograms/L/h to 0.9 +/- 0.1 microgram/L/h (P = .08). Additionally, 19 patients who underwent TIPS for refractory ascites outside of this protocol were followed prospectively for a mean of 282 days. Clinical improvement in ascites control was noted in 74%, and the mean dose of diuretics was decreased by more than 50%. Nonresponders more often had underlying renal disease. In conclusion, TIPS is an effective therapy for refractory ascites in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Long-term management of biliary tract complications.

Biliary tract complications represent an important problem after transplantation. They are not only important in the immediate posttransplantation period, but perhaps of even greater importance in the long-term management of transplant recipients. One of the major changes that has occurred over the past several years is an increasing use of nonoperative therapy, either via endoscopic or percutaneous routes. In many cases of biliary leak, stones, and T-tube malposition, nonoperative management may be curative. The exact role they play in the management of strictures, particularly diffuse stricturing and isolated hepatic duct strictures, remains to be determined. At the least, it provides temporary drainage before initiating surgical therapy. In addition to being efficacious, nonsurgical management is quite safe. In 64 cases of biliary complications managed nonoperatively, complications occurred at UCSF in only four patients. One patient developed bleeding along the percutaneous catheter tract and required replacement with a larger diameter catheter to tamponade the bleeding. Two patients developed hemobilia secondary to intrahepatic pseudoaneurysms caused by the percutaneous drainage catheter. One patient developed an osteomyelitis of a rib related to an indwelling percutaneous biliary catheter that responded to antibiotics and rib resection. Finally, understanding several of the biliary complications that occur after transplantation (ie, sphincter of Oddi dysfunction) will require additional research and hopefully will determine the pathophysiology of these complications. This should lead to more rational therapy.

Biliary Tract Diseases↗
PubMed1994

The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat.

Recently, a rodent model of nicotine abstinence syndrome has been developed based on observing the frequency of spontaneous behavioral signs following termination of continuous subcutaneous infusion of nicotine tartrate. In the present study, the nicotinic antagonist mecamylamine precipitated an abstinence syndrome in nicotine-dependent rats. Twelve rats were each infused for 7 days with 9 mg/kg per day nicotine tartrate in saline via Alzet osmotic minipumps; another 12 rats were sham-operated and remained nicotine-naive. Six rats from each group received 1 mg/kg mecamylamine in saline SC immediately before a 30-min observation, while the remaining six rats from each group received saline alone. Nicotine-infused rats receiving mecamylamine exhibited significantly more (P < 0.01), overall abstinence signs than all other groups. In terms of categories of signs, they displayed significantly more gasps/writhes, teeth chatter/chews, shakes/tremors and ptosis. In a second experiment utilizing only nicotine-naive rats, a far higher dose of mecamylamine (5 mg/kg sc) induced a quasi-nicotine abstinence syndrome. The results provide further validation for this rodent model of nicotine abstinence syndrome.

Animals↗
PubMed1994

Predicting recidivism after orthotopic liver transplantation for alcoholic liver disease.

With appropriate selection criteria, patients with end-stage alcoholic liver disease who undergo orthotopic liver transplantation have similar graft and patient survivals as patients undergoing transplantation for other causes. However, because of the possibility of recidivism after orthotopic liver transplantation there is still reluctance to transplant alcoholic patients. This study examined the association between pretransplant psychosocial variables and the risk of recidivism after orthotopic liver transplantation. At our institution, 43 patients received orthotopic liver transplantation for the referral diagnosis of alcoholic liver disease from February 1, 1988 to May 1, 1991. This represented 17% of all first transplants (43 of 257) performed during this period. Patients were interviewed before orthotopic liver transplantation by a single psychiatrist and responses to a defined set of questions were entered into a clinical database. All 43 patients diagnosed with alcoholic liver disease and a comparison group of patients transplanted for diagnoses other than alcoholic liver disease received a postoperative questionnaire regarding past and present alcohol use. Patients enrolled in the study all had at least 7 mo of follow-up, with the median follow-up being 21 mo. Eighty-six percent of alcoholic liver disease patients (37 of 43) and 86% of patients in the comparison group (37 of 43) of ALD patients agreed to participate in the study. Nineteen percent of alcoholic liver disease patients (7 of 37) and 24% of patients in the comparison group (9 of 37) admitted to having used alcohol after orthotopic liver transplantation, wtih 8% (3 of 37) and 11% (4 of 37) currently using alcohol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Liver transplantation for hepatitis C virus-related cirrhosis.

Since the introduction of techniques to reliably identify antibody to the hepatitis C virus and quantitation of hepatitis C virus, there has been an increasing interest in the behavior of chronic hepatitis C infection with liver transplantation. Ninety-seven patients with chronic active hepatitis C and fifty-nine patients with cryptogenic cirrhosis underwent 100 and 62 liver transplantation procedures, respectively, at a single institution. This represents 35% of the total liver transplantations performed during this time period. Twenty-three percent of transplants were performed in patients with evidence of chronic active hepatitis C. Patients and graft survival were excellent in both groups. One-, 2- and 3-yr patient survival rates for chronic active hepatitis C and cryptogenic cirrhosis were 94%, 89% and 87% and 84%, 84% and 73%, respectively. Hepatitis C can frequently be identified after transplantation. More than 95% of patients show persistence of antibody to the hepatitis C virus. Forty-one of 95 patients (surviving > 1 mo) showed recurrent hepatitis (initially seen 3 to 20 mo after transplantation), and 12 progressed to chronic active hepatitis. In 16 patients of the cryptogenic group in whom hepatitis developed, 11 were associated with de novo hepatitis C infection. Seven of these 11 cases went on to a chronic state. Of 11 deaths after transplant in the hepatitis C group, 2 were directly related to recurrent disease. There were 15 deaths in the cryptogenic group, 2 related to de novo hepatitis C. Patients were not serotyped. Interferon therapy was attempted in a small number of patients with disease, with inconclusive results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Tyr-MIF-1 precipitates abstinence syndrome in morphine-dependent rats.

The endogenous neuropeptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) has been shown to counteract various opiate actions. In the current study, third ventricular injection of 35 micrograms Tyr-MIF-1 protected by the enzyme inhibitor bestatin precipitated an abstinence syndrome in morphine-dependent rats, but not in opiate-naive rats. The results raise the possibility that Tyr-MIF-1 might participate in opiate dependence and opiate abstinence syndrome.

Animals↗
PubMed1993

Liver transplantation for fulminant hepatic failure.

OBJECTIVE: The purpose of this study was to assess outcome after liver transplantation for fulminant (FHF) and subfulminant (SHF) hepatic failure and to determine the factors responsible for outcome. PATIENTS AND SETTING: Thirty-five patients who underwent 42 liver transplantations for FHF and eight patients who underwent eight liver transplantations for SHF at a large university medical center were followed up for 1 month to 5 years. OUTCOME MEASURES: Actuarial patient and graft survival for FHF and SHF were assessed and compared with the outcome for all patients who underwent liver transplantation at the same center over the same period (445 transplants in 420 patients). Patients were treated with intracranial pressure monitoring, aggressive measures to decrease intracranial pressure, and rapid transplantation. Functional status and recurrent disease were additional end points. RESULTS: One-year actuarial patient survival rates for FHF and SHF were 92% and 100%, respectively. Minor neurological sequelae were noted in two patients. Functional status was excellent. Posttransplant hepatitis was present in two patients with an original diagnosis of FHF and acute hepatitis B and in three patients with an original diagnosis of FHF and non-A, non-B, non-C hepatitis. CONCLUSION: Patients with FHF and SHF can achieve excellent results after liver transplantation. Rapid assessment of candidacy with monitoring of intracranial pressure and aggressive treatment for intracranial hypertension are thought to be essential in the outcome of these patients.

Actuarial Analysis↗
PubMed1993

Naloxone precipitates nicotine abstinence syndrome in the rat.

Recently, a rodent model of nicotine abstinence syndrome has been developed based on continuous subcutaneous infusion of nicotine tartrate and observing the frequency of spontaneous behavioral signs following termination of infusion. The observed signs closely resemble those commonly seen in rat opiate abstinence syndrome, raising the possibility that there is an endogenous opioid component in nicotine dependence. The present study demonstrates that the opiate antagonist naloxone can precipitate an abstinence syndrome in nicotine-dependent rats. Fourteen rats were infused for 7 days with 9 mg/kg/day nicotine tartrate in saline via an Alzet osmotic minipump. Fourteen rats were sham-operated and remained nicotine-naive. Half of each group received 4.5 mg/kg naloxone SC immediately before a "blind" 15-min observation, while the other half received saline alone. ANOVA revealed significant nicotine infusion, naloxone injection and interaction effects. Post-hoc analysis showed that the nicotine-infused rats injected with naloxone had significantly more signs than all other groups (P < 0.01). In a second experiment, 2 mg/kg morphine sulfate SC produced a significant (P < 0.01) 91.2% reduction of spontaneous abstinence signs observed 21 h after termination of nicotine infusion. These results are consistent with the hypothesized endogenous opioid component in nicotine dependence and abstinence syndrome.

Animals↗
PubMed1993

Subcutaneous injection of an analog of neuropeptide FF precipitates morphine abstinence syndrome.

Neuropeptide FF (NPFF) has been shown to exert various antiopiate actions, including precipitation of opiate abstinence syndrome by third ventricle injection in morphine dependent rats. In the present study, dansyl-Pro-Gln-Arg-Phe-amide, a lipophilic analog of NPFF, was injected into morphine dependent rats and appropriate sham controls at a dose of 9 mg/kg s.c. Comparison groups were injected with ethanol/water vehicle alone. The NPFF analog precipitated a vigorous opiate abstinence syndrome in morphine dependent rats, but not in sham controls.

Amino Acid Sequence↗
PubMed1993

Fulminant hepatic failure.

FHF is an uncommon but devastating condition affecting otherwise healthy persons which causes significant morbidity and mortality. The etiologic factor is most commonly viral infection, with drugs and metabolic disorders being relatively less common causes. Hopefully, newer diagnostic techniques such as PCR will increase our understanding of the causes and pathogenesis of this disorder. Medical management at the present time must focus on anticipating, preventing, and rapidly identifying and treating complications that may affect every major organ system. Encouraging research continues on the clinical application of hepatotrophic drugs and artificial liver support systems, both as potentially definitive therapies and as maintenance for patients awaiting transplantation. Consultation with physicians at a transplant center should be sought early in the course of the patient's hospitalization when OLT is being considered. Liver transplantation has dramatically changed the outlook for patients with FHF, with current survival rates in the 55% to 75% range. The continuing challenge for the transplant team is to allocate available donor organs to those patients who would not otherwise survive, but also to provide OLT in a timely fashion to ensure the best chance of post-transplantation recovery. Newer techniques such as heterotopic liver transplantation, reduced-size organ transplantation, and the utilization of living related donors may further improve the survival of these patients.

Artificial Organs↗