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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 487 records · Page 27Linked to original sources
PubMed1995

Hepatocellular carcinoma during pregnancy and its comparison with other pregnancy-associated malignancies.

BACKGROUND: Cancer in pregnancy is rare and hepatocellular carcinoma (HCC) in pregnancy even rarer. The impact of pregnancy on the prognosis of patients with different types of cancer remains controversial. Reported cases of HCC in pregnancy are largely isolated and highly scattered. Thus, the effect of pregnancy on the prognosis of patients with HCC and the risk factors of developing HCC in pregnancy are not well documented. METHODS: A series of five patients with HCC in pregnancy seen at two different centers is reported. A Medlar search for articles between 1957 and 1993 with the key words "Hepatocellular Carcinoma" and "Pregnancy" was conducted. All reported cases were combined and analyzed in terms of race, age, parity, hepatitis B surface antigen status, cirrhosis, serum alpha-fetoprotein (AFP) levels at presentation, history of taking oral contraceptive pills and fetal and maternal outcome. The impact of pregnancy on 12 other malignancies as reported in the medical literature also was reviewed. RESULTS: To the authors' knowledge, The five cases reported here constitute the largest series of HCC in pregnancy. A literature search revealed 23 additional cases. Analysis of the 28 cases suggests that the rarity of HCC in pregnancy results from a combination of three factors: the male predominance of HCC, the late age at which the tumor usually presents in women, and decreased fertility in women with advanced cirrhosis (hepatitis is a predisposing factor for HCC development). Long term use of oral contraceptives and high parity enhance the risk. Elevated AFP level is useful for diagnosis. The median survival is shorter than for patients who are not pregnant. There is no significant difference in survival between pregnant and not pregnant women matched by tumor stage, age, and other clinical parameters in most malignancies except in some tumors like lymphoma, thyroid cancer, and nasopharyngeal carcinoma. CONCLUSION: Pregnancy has an adverse effect on the prognosis of patients with HCC, lymphoma, thyroid cancer, and nasopharyngeal carcinoma but not of most other malignancies. Measurement of AFP level is recommended for screening HCC in pregnant women at high risk.

Adult↗
PubMed1995

Structural organization of the Ni and (4Fe-4S) centers in the active form of Desulfovibrio gigas hydrogenase. Analysis of the magnetic interactions by electron paramagnetic resonance spectroscopy.

The Desulfovibrio gigas hydrogenase is a typical (NiFe) hydrogenase containing a Ni center and three FeS centers, one [3Fe-4S] and two [4Fe-4S] clusters. When the enzyme is activated under hydrogen gas, the Ni center becomes paramagnetic, giving a characteristic electron paramagnetic resonance (EPR) signal with g values at 2.19, 2.14 and 2.01, the Ni-C signal. Two redox states of the enzyme can be prepared, in which the [4Fe-4S] clusters are either diamagnetic or paramagnetic. In this latter state, the magnetic coupling between metal centers induces both the appearance at low temperature of a complex EPR spectrum, the split Ni-C signal, and a significant enhancement of the relaxation rates of the Ni center. Good simulations of the split Ni-C signal recorded at three different microwave frequencies (X-band, Q-band, and S-band) are obtained by using a model based on a point dipole approximation of the dipolar and exchange interactions between paramagnets. The spectral analysis demonstrates that only one [4Fe-4S]1+ cluster is significantly coupled to the Ni site and provides a detailed description of the relative arrangement of the two centers. In addition, the magnetic characteristics of this [4Fe-4S]1+ cluster can be deduced from the simulations. Moreover, the spin-spin and spin-lattice relaxation times of the interacting centers were measured in the two redox states of the enzyme, either by power saturation and pulsed EPR experiments at low temperature or from the broadening of the EPR lines at higher temperature. The relaxation behavior of the Ni center is well explained by using in the theoretical analysis, the set of structural and magnetic parameters deduced from the spectral simulations. Our structural conclusions on the active D. gigas hydrogenase are compared to the preliminary data of a low-resolution crystal structure of the oxidized enzyme [Volbeda, A., Piras, C., Charon, M. H., Hatchikian, E. C., Frey, M., & Fontecilla-Camps, J. C. (1993) News Lett. Protein Crystallogr. 28, 30-33].

Desulfovibrio↗
PubMed1995

Anti-tuberculous therapy and acute liver failure.

The incidence of tuberculosis has been increasing since 1987, exposing a greater number of patients to the risks of three potentially hepatotoxic drugs, isoniazid, rifampicin, and pyrazinamide. Awareness of potentially severe drug hepatotoxic reactions is vital because fulminant hepatic failure is a devastating and often fatal condition without liver transplantation. We report four cases of fulminant hepatic failure caused by rifampicin, isoniazid, or both. These cases highlight the need for stricter adherence to and review of current guidelines on liver function tests after starting anti-tuberculous therapies.

Adult↗
PubMed1995

Importance of concomitant viral infection during late acute liver allograft rejection.

We have determined accompanying events and reviewed the management and outcome of late acute cellular rejection episodes in 384 consecutive liver recipients. A significant proportion of patients experienced concomitant viral infection (group 1, n = 15 [41%]), with CMV infection comprising the largest group and smaller contributions from other viruses (CMV, 30%; HSV, 5%; EBV, 3%; varicella zoster virus, 3%). Thirteen (35%) patients (group 2) developed late rejection associated with low maintenance immunosuppression, and in a further 10 patients (group 3), no accompanying factor could be identified. Refractory rejection was higher in late compared with early rejection episodes in our series (29% vs. 9.2%, P < 0.05). Antiviral chemotherapy administered in rejection episodes with concomitant viral infection, either as sole treatment in cases with accompanying hepatitis or as adjunctive therapy to further supplemental immunosuppression in episodes of steroid-resistant rejection, controlled the rejection process in all treated patients.

Adolescent↗
PubMed1995

Developmentally regulated expression of mRNA for neurotrophin high-affinity (trk) receptors within chick trigeminal sensory neurons.

To investigate the distribution of neurons within the developing trigeminal sensory system which express mRNA for each of the three known high-affinity neurotrophin receptors (trk, trkB and trkC), we have performed in situ hybridization histochemistry on serial sections through the trigeminal ganglion and trigeminal mesencephalic nucleus at various ages of development using specific antisense oligonucleotide probes. We show that trkC mRNA is first expressed in the chicken embryo at stage 13, in presumptive neurons prior to the formation of the ganglion, that trkB mRNA labelling is initially observed within peripheral neurons slightly later, at stage 19, and that trk mRNA expression is not detectable until around embryonic day 3.5 (stage 21/22). The neurons which exhibit mRNA labelling for each of the high-affinity receptors occupy discrete regions within the ganglion, indicating that the ganglion comprises distinct neuronal subpopulations, each of which has a different capacity to respond to the different neurotrophins. Neurons which express trk mRNA are confined to the proximal region of the ganglion, whereas those which express trkB mRNA and trkC mRNA are located in two distinct regions within the distal aspect and also within the trigeminal mesencephalic nucleus. From the estimation of the number of neurons which exhibit labelling between embryonic days 9 and 18, we determined that the expression of mRNA for the high-affinity receptors changes during embryonic development of the ganglion. This is consistent with the observed differences in the response to neurotrophins in vitro.

Age Factors↗
PubMed1995

Experience of orthotopic liver transplantation and hepatic resection for hepatocellular carcinoma of less than 8 cm in patients with cirrhosis.

Fifteen patients with cirrhosis underwent orthotopic liver transplantation for small hepatocellular carcinoma (HCC) and 12 patients with cirrhosis underwent hepatic resection for similar HCC. All tumours were of the non-fibrolamellar variant. The majority of the patients in the transplant group had Child's grade B or C cirrhosis. Median follow-up was 37 months with a minimum of 18 months. Eleven of 12 patients in the resection group had Child's grade A cirrhosis. Median follow-up was 29 months with a minimum of 16 months. Actuarial survival rates at 1 and 3 years for the transplanted patients were 80 and 63 per cent and all were tumour free. Tumour recurrence rate was 15 per cent. The overall 1- and 3-year tumour-free survival rates for patients in the resection group were 61 and 33 per cent. Tumour recurrence rate was 45 per cent. The results show orthotopic liver transplantation to be an important surgical option in cirrhotic patients with small HCC, particularly in those with moderate to severe hepatic decompensation.

Adult↗
PubMed1995

Bacterial and fungal infections after liver transplantation: an analysis of 284 patients.

A prospective study of bacterial and fungal infections after liver transplantation in 284 adults was undertaken. One hundred seventy-five (62%) became infected; bacterial or fungal infections occurred in 159 (56%) and 36 (13%) patients, respectively. Gram-positive cocci, in particular Staphylococcus aureus and Enterococcus faecium, were the commonest bacterial pathogens, and bacteremia and wound infection were the most frequent bacterial infections. Acute rejection and prolonged admission were independent risk factors for bacterial infection; pretransplantation antibacterials had a protective effect. Fungal infection most frequently involved the urinary tract and chest; Candida albicans was the most common pathogen. Four independent variables predicted fungal infection: low pretransplantation hemoglobin, high pretransplantation bilirubin, return to surgery, and prolonged therapy with ciprofloxacin. Patients with acute liver failure were more prone to bacterial, but not fungal, infection. No associations were found between infections and duration of surgery. Bacterial, and to a lesser extent, fungal infections are important complications of liver transplantation. However, liver transplantation surgery per se may not be the major determinant of infection.

Abscess↗
PubMed1995

Effects of ribavirin on intrahepatic and extrahepatic expression of hepatitis C virus in interferon nonresponsive patients.

Response to ribavirin therapy (1,000-1,200 mg/day for 6 months) was evaluated in nine patients with chronic hepatitis C virus (HCV) infections who had previously failed to respond to a 6-month course of alpha-interferon. All had chronic active hepatitis with elevated serum aminotransferase activities (mean +/- SD = 138 +/- 66IU/I). During ribavirin therapy, three showed a complete response (normalized serum aminotransferase), although in one patient this returned to the pretreatment level 2 months after treatment was stopped. Three others showed a partial response (serum aminotransferase reduction by > or = 50%) and the remainder showed no response. There were no consistent changes in HCV-RNA (positive strand) in serum, liver, or peripheral blood mononuclear cells during therapy, but two patients lost HCV-RNA from serum and three of five patients with negative strand HCV-RNA in their livers lost this putative replicative form of the virus. The findings suggest that ribavirin may exert its effects by suppressing viral replication rather than by eradicating the virus, at least in this group of patients, and that the drug may have some benefit in selected cases of chronic hepatitis C that are resistant to interferon. However, peripheral blood mononuclear cells represent a major extrahepatic reservoir of HCV and the present regimen of ribavirin therapy did not significantly affect this situation. More prolonged therapy may be required to eradicate the virus from this large pool of cells with the potential to continually reinfect the liver.

Adult↗
PubMed1995

Clinical recurrence of hepatitis A following liver transplantation for acute liver failure.

This paper documents clinically significant recurrence of hepatitis A virus (HAV) infection in a 63-year-old man transplanted for HAV-related acute liver failure. HAV RNA was documented in the explant and, following early clearance from the blood and graft, was again detected in post-operative biopsies at the time of an acute hepatic illness. Although the clinical and biochemical abnormalities resolved completely, the patient had a second episode of graft dysfunction 6 months later and investigations revealed hepatitis C virus (HCV)-related chronic active hepatitis consistent with acquired HCV infection at the time of transplantation. The possible interaction with hepatitis A may have delayed the appearance of hepatitis C. Administration of HAV immunoglobulin at the time of transplantation should be considered in all cases of HAV-related fulminant hepatic failure.

Base Sequence↗
PubMed1995

Hepatitis C virus infection in Schistosomiasis mansoni in Brazil.

The involvement of the hepatitis C virus (HCV) in the severity of liver disease in chronic schistosomiasis was investigated in 215 Brazilian patients with S. mansoni infections, but without evidence of hepatitis B surface antigen (HBsAg). Forty-three had hepatointestinal (HIS) and 172 had hepatosplenic schistosomiasis (HSS), and 135 had compensated (HSSC), and 37 had decompensated (HSSD) liver disease. Fifty-two (24%) were found to have evidence of HCV infection (seropositive for anti-HCV antibodies and/or HCV-RNA). These comprised 35 (95%) of the 37 with HSSD, 16 (12%) of the 135 with HSSC, and 1 (2.4%) of the 43 with HIS, compared with only 1 (2%) of 50 control patients without S. mansoni. Testing of matched liver tissue and peripheral blood mononuclear cells (PBMCs) from 25 patients (6 HSSC and 19 HSSD) with HCV infections showed that 17 (68%) had "active" viral infections, in that negative strand HCV-RNA (the presumed replicative intermediate of the virus) could be detected in liver and/or PBMCs. Among these 25, negative strand HCV-RNA was found in 16 (84%) of the 19 with chronic active hepatitis, but in only 1 (17%) of the 6 with mild or inactive disease (P < 0.01). HCV-RNA was detected in matched spleen specimens from 9 of 10 patients (all of whom were also positive in PBMCs), suggesting that the spleen is an important extrahepatic reservoir of the virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Overview: the management of metastatic carcinoid tumors.

Chemotherapy, IFN, octreotide, and hepatic artery embolization can be useful for palliation, both of local symptoms and of the carcinoid syndrome, but they have little effect on tumor progression, MIBG therapy is still experimental but may have a future role. OLT should be considered as a palliative procedure in those patients with severe symptoms and no evidence of extrahepatic disease.

Antineoplastic Agents↗
PubMed1995

Orthotopic liver transplantation in the treatment of metastatic neuroendocrine tumors of the liver.

The place of orthotopic liver transplantation (OLT) in the management of metastatic hepatic neuroendocrine tumors has not been adequately defined. The present report is concerned with patient survival, disease recurrence, and symptom relief in 11 such patients in a single center who, at the time of transplantation, had no extrahepatic tumor. All patients obtained complete symptom relief initially but tumor recurrence was observed in 6 of the 11 cases (5 carcinoid and 1 apudoma) at a median of 11 months (range 3.5-26). Five patients have died, 4 in the carcinoid group with recurrence and one from chronic rejection in the other apudoma group. Of the 6 patients currently alive one of 2 carcinoids and one of 4 other apudomas have tumor recurrence. Recurrent deposits were found predominantly in bone and in the transplanted liver. Actuarial survival post transplant was 82% and 57% at 1 and 5 years respectively. It is concluded that OLT is effective at controlling symptoms from secreting carcinoid deposits in the liver. Although the tumor will recur in most cases, this is not necessarily associated with early return of symptoms. Prolonged disease free survival is more likely in the non carcinoid apudoma group.

Adult↗
PubMed1995

Evaluation of extracorporeal bioartificial liver devices.

The initial clinical studies on artificial liver support were performed at King's College Hospital, London during the late 1970s. Initially using charcoal haemoperfusion, and subsequently resin haemoperfusion, and these studies culminated in a controlled clinical trial of charcoal haemoperfusion in which overall survival was high, but no statistically significant benefit was found. From this study, much information was also obtained about the clinical importance of the various complications of acute liver failure, and the experience of King's over the last 2 decades exceeds 1,000 patients. The aim of this article is to review the potential of the exciting new developments in this field of bioartificial liver support incorporating hepatocytes. It focuses on the published findings of early clinical use of these systems and attempts to identify what is needed in further studies. It is of paramount importance that future trials are designed to give the greatest information on the effects of bioartificial liver support. For these, the biocompatibility of the systems should to be confirmed with detailed assessment and sensitive tests need to be developed to determine the metabolic functional efficacy of these devices. The possible relationship of treatment to liver regeneration has been considered, because without this these systems will in many cases be limited to use as a bridge to liver transplantation. Finally, some of the possible future modifications of the cell-based liver support systems are discussed.

Animals↗
PubMed1995

Centrilobular necrosis after orthotopic liver transplantation: a longitudinal clinicopathologic study in 71 patients.

Centrilobular necrosis (CLN) is a histological finding often encountered after orthotopic liver transplantation, but its pathogenesis is still unknown. In this study, the significance of CLN was assessed in a series of 227 consecutive liver transplantations performed between January 1989, and December 1991. Seventy-one patients (30.9%) showed CLN on at least one biopsy result, which were obtained because of an increase of aspartate aminotransferase activity. Their liver specimens were reviewed, and 19 histological features were recorded with particular attention given to lobular changes in acinar zone 3, to features commonly attributed to cellular and ductopenic rejection, and to changes suggestive of ischemia. CLN could first be observed either soon (within 4 days) or late (up to 3 years) after transplantation. Only 23 (32.4%) specimens had centrilobular necrosis affecting more than 75% of acinar zones 3. In 60 cases (84.5%) the lesion was limited to acinar zone 3. An important associated feature was sinusoidal congestion in 73.2% of cases. Fifty-one of 71 patients (71.8%) had histological features of cellular rejection before or at the time of CLN, and 13 of these progressed to ductopenic rejection versus 3 of the 156 patients without CLN (P < .0001). Nine patients had a recurrence of CLN, of whom 2 progressed to ductopenic rejection, a recurrence rate of 16.7% in this series. The survival of patients with CLN is worsened by associated ductopenic portal tracts compared with those without ductopenia (P = .0189-Mantel-Cox). This histological combination, irrespective of the serum bilirubin level, may warrant an early conversion to FK506-based immunosuppression.

Adult↗
PubMed1995

Contribution of true cold and rewarming ischemia times to factors determining outcome after orthotopic liver transplantation.

The role of true cold ischemia times (CIT) and rewarming ischemia times (WIT) in determining outcome after liver transplantation was investigated in 230 adult recipients. Using multivariate analysis, WIT (time from the start of implantation until restoration of arterial and portal blood supply) and donor intensive care stay (P = .04 and .0004, respectively) but not CIT (the time from donor portal vein flushing until the graft was removed from University of Wisconsin solution; P > .30) emerged as independent determinants of graft survival. In the small number of patients with a WIT of greater than 180 minutes, there were reductions in graft survival (58% v 80% for WIT greater than 180 minutes) but these just failed to reach significance (P = .055). CIT had no influence on graft survival using cut-offs of 12 or 18 hours. A WIT of greater than 180 minutes was associated with an increased median area under the curve of day 1 through 7 serum bilirubin (1,370 v 915 mumol/L.day; P = .048) and trends towards an increased incidence of primary graft nonfunction or dysfunction (22.2% v 6.2% for WIT of less than 180 minutes; P = .065) and the day 1 through 7 area under the curve of serum aspartate aminotransferase (3,310 v 1,440 IU/L.day; P = .092). A prolonged CIT (greater than 18 hours) led to a prolonged hospital stay (69 v 31 days; P = .03), an increased area under the curve of day 8 through 14 serum bilirubin (2,500 v 995 mumol/L.day; P = .003), and a trend towards an increased incidence of initial poor graft function (33.3% v 6.3% for less than 18 hours; P = .092). The incidence of acute rejection increased (to 64.3% from 53.4%; P = .04) in patients with preservation injury (serum aspartate aminotransferase greater than 1,500 IU/L during the first 2 postoperative days). True CIT and WIT are important determinants of outcome after liver transplantation.

Adenosine↗
PubMed1995

FK506 in liver transplantation for chronic hepatitis B: in vitro studies on lymphocyte activation and virus replication.

Recurrence of hepatitis B virus (HBV) in the graft is the major problem for patients with chronic HBV infection undergoing liver transplantation, which could be potentiated by the immunosuppression. In the present study, we used lymphocytes and hepatocytes isolated from patients with chronic HBV infection to investigate in vitro the effects of FK506 with and without methylprednisolone (25 ng/mL) on mitogen-induced lymphocyte proliferation, T-cell activation marker expression, and HBV replication in human hepatocytes. Increasing concentrations of FK506 (0.1, 0.5, and 5 ng/mL) resulted in a dose-dependent inhibition of lymphocyte proliferation with a reduction of the stimulation index by 9.2%, 39.0%, and 55.1%, respectively, with no difference between 25 chronic HBV carriers and normal controls. Methylprednisolone alone had no effect but potentiated the inhibitory effect of all three FK506 concentrations, such that the stimulation index was decreased by 20%, 56.2%, and 65.7%, respectively. FK506 (0.5 ng/ mL) reduced both the percentage of interleukin-2 receptor expressing T cells and the cell surface density of this receptor by 7.1% and 8.7% (P < .01), whereas it only reduced the proportion of HLA-DR expressing T cells by 6.8%. FK506 did not change significantly the intracellular HBV DNA or the hepatic expression of hepatitis B surface antigen (HBsAg) in short-term culture of human hepatocytes, whereas methylprednisolone increased the percentage of HBsAg-positive hepatocytes in all 5 patients with active viral replication. These results indicate that the effects of FK506 on T-cell activation in chronic HBV carriers are identical to normal subjects, resulting in marked suppression of T-lymphocyte function but only modest reduction in the expression of cell surface activation markers. The drug showed no direct stimulatory effect on viral replication, suggesting that FK506 can be a useful, steroid-sparing immunosuppressive agent for liver graft recipients with chronic HBV infection.

Adult↗