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D Samuel

Publications and source records attributed to D Samuel.

At least 55 records · Page 3Linked to original sources
PubMed2000

A microtitre plate method for isolation and typing of poliovirus using a blue-cell ELISA.

A simple, sensitive, specific and rapid procedure for isolating and typing polioviruses is described. Specimens are inoculated onto confluent monolayers of cell lines (Hep-2C, L20B or RD) seeded into microtitre plates. After 24-48 h, the infected cells are stained with monoclonal antibodies specific for poliovirus types 1,2,3 or a blend of the three antibodies followed by an anti-mouse IgG-horseradish peroxidase conjugate. On addition of substrate, infected cells stain an intense blue colour and are easily distinguished from uninfected cells by light microscopy. Poliovirus infection can be detected before the appearance of cytopathic effects (CPE). This Blue-Cell ELISA test was evaluated against conventional culture and seroneutralisation on a range of polio isolates and clinical specimens. The sensitivity and specificity of the Blue-Cell ELISA compared to neutralisation was 100% (87/87) on culture supernatants of poliovirus isolates sent to our reference laboratory for confirmation. All the poliovirus isolates were typed within 24 h of specimen inoculation using the new method compared to 6-10 days by conventional culture and neutralisation. The method proved to be more sensitive than conventional culture when clinical specimens were examined. Of 43 clinical specimens from which poliovirus had been previously isolated by various laboratories in the U.K., 30/43 (69.8%) were positive for poliovirus by the Blue-Cell ELISA compared to 29/43 (67.4%) by conventional culture and neutralisation. Neutralisation of specimens exhibiting CPE indicated that all of the polioviruses were correctly typed with the new method. CPE was not observed by conventional culture in any specimen that was negative in the Blue-Cell ELISA. There were no cross-reactions with a range of other enteroviruses.

Antibodies, Monoclonal↗
PubMed2000

Recurrent hepatitis C after liver transplantation: clinical and therapeutical issues.

Hepatitis C virus (HCV) reinfection after liver transplantation is almost constant, assessed by the persistence of HCV RNA in 90% of cases. Acute hepatitis appeared in 75% of patients at a median of 4 months' post-transplantation. The 5-year actuarial rate of acute and chronic hepatitis on the graft is 75% and 60%, respectively. The rate of HCV cirrhosis on the graft is variable from 8 to 25% at 5 years. After transplantation, HCV viraemia is dramatically increased and correlates with the occurrence of acute hepatitis on the graft. Intrahepatic levels of HCV are high at the time of acute hepatitis, and decrease with constitution of chronic graft hepatitis lesions, implying an immunological response to the viral infection. A relationship between genotype 1b and the prevalence of HCV hepatitis on the graft has been suggested in European but not American series. The influence of the age of the recipient, quasispecies, viral compartmentalization, immunosuppressive treatment, and of HLA matching is being evaluated. The 5-year patient survival is around 65-80%. However, the occurrence of cirrhosis with a risk of graft failure may decrease the 10 and 15-year patient survival. Attempts to give prophylactic post-transplant antiviral treatment are under evaluation. Antiviral treatment of post-transplant graft lesions with combination therapy interferon-ribavirin gave promising results but indications and duration of treatment should be evaluated. In conclusion, HCV reinfection is frequent, but medium-term survival is good. However, the long-term graft and patient survival remains unknown, and efficient prevention and treatment of HCV graft is mandatory.

Age Factors↗
PubMed2000

The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation.

Familial amyloid polyneuropathy (FAP) associated with mutations of the transthyretin (TTR) gene is the most common type of FAP, a devastating disease causing death within 10 years after the first symptoms. Because most of the amyloidogenic mutated TTR is secreted by the liver, transplantation is widely used to treat these patients, but long-term quantitative evaluation of the effects of liver transplantation on the progression of the neuropathy are not available. We have treated 45 patients with symptomatic TTR-FAP, including 43 with the Met30 TTR gene mutation, and report on the results of periodic evaluation of markers of neuropathy in 25 of them, who have been followed for more than 2 years after liver transplantation (mean follow-up 4 years). The overall survival rates at 1 and 5 years were 82 and 60%, respectively. Urinary incontinence and a low Norris score at liver transplantation were associated with poorer outcome. The motor score stabilized in seven of 11 patients (64%) with mild sensorimotor neuropathy (walking unaided) and in two of the eight patients (25%) with severe sensorimotor deficit (walking with aid) at liver transplantation. In five other patients, deterioration of motor deficit occurred only within the first year after liver transplantation, but was progressive after this interval in two patients. None of the six patients with pure sensory neuropathy developed motor loss and superficial sensory loss remained unchanged. Two years after liver transplantation, the rate of myelinated axon loss in nerve biopsy specimens was markedly lower in seven transplanted patients (0.9/mm(2) of endoneurial area/month) than in non-transplanted patients (70/mm(2) of endoneurial area/month). Symptoms of dysautonomia and quantitated cardiocirculatory autonomic tests remained unchanged. In all patients, serum mutated TTR decreased to 2.5% of pre-liver transplantation values and remained at this level during follow-up. We presently recommend liver transplantation in FAP patients at onset of first symptoms and exclusion of those with a Norris score below 55 and/or with urinary incontinence.

Action Potentials↗
PubMed2000

Proline inhibits aggregation during protein refolding.

The in vitro refolding of hen egg-white lysozyme is studied in the presence of various osmolytes. Proline is found to prevent aggregation during protein refolding. However, other osmolytes used in this study fail to exhibit a similar property. Experimental evidence suggests that proline inhibits protein aggregation by binding to folding intermediate(s) and trapping the folding intermediate(s) into enzymatically inactive, "aggregation-insensitive" state(s). However, elimination of proline from the refolded protein mixture results in significant recovery of the bacteriolytic activity. At higher concentrations (>1.5 M), proline is shown to form loose, higher-order molecular aggregate(s). The supramolecular assembly of proline is found to possess an amphipathic character. Formation of higher-order aggregates is believed to be crucial for proline to function as a protein folding aid. In addition to its role in osmoregulation under water stress conditions, the results of this study hint at the possibility of proline behaving as a protein folding chaperone.

Animals↗
PubMed2000

[Clinical trials using cell xenografts. Their place in the treatment of fulminant hepatitis].

Trials involving xenocells are mainly carried out in the context of treatment for acute liver failure. In fact, in this disease there is no accompanying chronic hepatopathy, and the liver has a significant potential for regeneration. Regarding the clinical aspect, several trials have been conducted involving patients with severe liver failure awaiting hepatic transplantation. Hepatic xenocells are the treatment of choice, as there is no normal human hepatocyte line available. Hepatic xenocells of porcine origin are used. The experimental systems adopted in man mainly consist of extracorporal systems in which the hepatocytes are present in the extracapillary space of a capillary filter. The various systems used in man have resulted in a neurological improvement. However, the risk of PERV transmission (porcine endogenous retrovirus) remains, and is a preoccupying issue. Nevertheless, no documented case of this particular risk has yet been recorded. In conclusion, clinical trials utilizing hepatic xenocells in animals and in man are ongoing, and should permit progress to be made in the field of hepatic insufficiency.

Animals↗
PubMed2000

Transplantation in the hepatitis B patient and current therapies to prevent recurrence.

Hepatitis B is the sixth most common indication for liver transplantation in the United States, accounting for about 7% of all transplants among adults. Transplantation for hepatitis B is especially problematic because the virus is not eradicated and there is great potential for reinfection that can lead to graft failure or death. This risk is higher still in patients with active viral replication and chronic liver disease. Treatment with short-term hepatitis B immune globulin (HBIG) delays reinfection of the allograft, but only long-term treatment with HBIG has led to a decline in the reinfection rate. Combination therapy using HBIG with nucleoside analogues will likely become the standard of care to maintain stable serum titers of protective anti-HBs antibody and to prevent posttransplantation reinfection.

Adult↗
PubMed2000

Paul Brousse Liver Transplantation: the first 1,500 cases.

During the past 16 years, more than 1,500 liver transplants were performed at Paul Brousse Hospital. The overall patient survival rates were 83% at one year and 65% at 10 years. Our group has pioneered a variety of new approaches to liver transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of HBV recurrence. To date more than 270 patients have received long-term treatment and the overall 10-year recurrence rate was 27%. 2. Transplantation for hepatocellular carcinoma of the cirrhotic liver in patients with uni- or binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with 18% if the liver was resected. 3. Transplantation for familial amyloidotic polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of 85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with satisfactory short-term results. 4. Reduced-size liver grafts have been used successfully to reduce pretransplant mortality and posttransplant morbidity and mortality by shortening the wait for our pediatric patients. 5. Split-liver transplantation has increased the number of transplantable livers by 28%. 6. Split-liver transplantation for 2 adults. Using optimal livers we have transplanted 34 adults with grafts prepared by ex-vivo or in-situ splitting with good survival rates. 7. Adult-to-adult living-related donor liver transplantation. In 2000, 7 adult-to-adult living donor transplants were performed with no complications from the donor surgeries. One recipient was retransplanted for arterial thrombosis, but all 7 recipients are alive at home. The Paul Brousse Hospital is committed to exploring new technologies to improve the outcome of and expand the indications for liver transplantation. We have taken a surgical approach to the organ shortage, finding new ways to serve the most patients with the limited number of livers available.

Adult↗
PubMed1999

"Silent" presentation of veno-occlusive disease after liver transplantation as part of the process of cellular rejection with endothelial predilection.

Hemorrhagic centrilobular necrosis and fibrous stenosis of hepatic venules, suggesting veno-occlusive disease (VOD) have rarely been observed after orthotopic liver transplantation (OLT). The aim of this study was to determine the prevalence of this syndrome after OLT in relation to the course with particular reference to acute rejection and to azathioprine administration. VOD was identified in 19 of 1,023 patients transplanted over a 9-year period. VOD occurred at a median of 30 days posttransplantation, without clear cut clinical evidence for hepatic vein outlet obstruction. Seventeen of the 19 patients had an episode of acute rejection before or at the time of VOD. These episodes were compared with that of patients without VOD. In patients with VOD, portal inflammation and endothelialitis were enhanced (P =.014 and P =.048) and endothelialitis was also higher than bile duct damage (P =.03). The incidence of a centrilobular endothelialitis for both groups was not different although an increased trend was observed in the study group (64% vs. 46%; P =.18). The incidence of persistent rejection was similar between both groups (47% vs. 41%). The incidence of chronic rejection was higher in the study group (29% vs. 10%; P =. 04). All patients with VOD received azathioprine as part of immunosuppressive regimen. Despite azathioprine withdrawal, zone 3 changes persisted in 57% of patients. In conclusion, the incidence of VOD was 1.9% after OLT. The association of prominent endothelial involvement and VOD with acute rejection in most cases suggests an immunological phenomenon.

Adult↗
PubMed1999

Retransplantation of the liver for recurrent hepatitis B virus infection: the Paul Brousse experience.

Recurrent hepatitis B virus (HBV) infection of the liver graft is characterized by a severe outcome and high level of HBV replication. For many investigators, retransplantation appears contraindicated because of constant recurrence and a high mortality. We report our experience in this setting. Between January 1985 and December 1995, 10 patients who underwent retransplantation for HBV graft reinfection were studied. According to the antiviral treatment administered after HBV recurrence on the first liver graft and the protocol of antiviral prophylaxis after retransplantation, two groups were defined: group 1 underwent retransplantation before January 1992 (n = 5), and group 2 underwent retransplantation after January 1992 (n = 5). At the time of reinfection, serum HBV DNA was positive in all patients, hepatitis Be antigen (HBeAg) was positive in 6 patients. Antiviral therapy was administered to 7 patients (group 1, adenine arabinoside mono phosphate [ara-Amp; n = 3]; group 2, ara-Amp [n = 5], ganciclovir [n = 4]). After retransplantation, long-term antibody to HB surface antigen (anti-HBs) immunoglobulins were administered to achieve an anti-HBs titer greater than 100 IU/L in group 1 and to achieve an anti-HBs titer greater than 500 IU/L associated with prophylactic intravenous ganciclovir administration (5 mg/kg three times weekly) for 2 years in group 2. In group 1, all patients died, either perioperatively or secondary to HBV recurrence (1 year survival, 0%). In group 2, 1 patient died 50 months after retransplantation of HBV cirrhosis on the second graft, and 4 patients remained HBsAg negative at a mean of 41 months (range, 24 to 68 months) after retransplantation. The prognosis of retransplantation for HBV recurrence was dramatically improved by the administration of antiviral therapy before retransplantation and the maintenance of a high anti-HBs level combined with antiviral therapy after retransplantation.

Antiviral Agents↗
PubMed1999

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability.

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42+/-12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36+/-0.26 versus 1.98+/-0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients.

3-Iodobenzylguanidine↗
PubMed1999

A case of disseminated histoplasmosis likely due to infection from a liver allograft.

Disseminated histoplasmosis in immunosuppressed patients rarely occurs in nonendemic areas. Reported here is a case of disseminated histoplasmosis in a patient who had undergone orthotopic liver transplantation and had never traveled outside of France. The infection was most likely transmitted via the liver allograft, since the organ donor had lived in an area highly endemic for the disease (French Guiana) 20 years earlier. Two years post-transplantation, none of the other patients who received allografts (heart, cornea, kidneys) from the same donor had developed signs of infection.

Histoplasmosis↗
PubMed1999

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Female↗
PubMed1999

Effects of PKA and PKC modulators on high affinity glutamate uptake in primary neuronal cell cultures from rat cerebral cortex.

In this study, the effects of various agents known to alter protein phosphorylation, via protein kinase C or A, on high affinity glutamate uptake were investigated in primary neuronal cell cultures of rat cerebral cortex. Incubating the culture dishes with chelerythrine or H89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), which inhibit PKC and PKA, respectively, dramatically decreased the glutamate uptake in a dose-dependent manner. Saturation kinetic analysis showed that chelerythrine and H89 decreased the Vmax (chelerythrine: -61%, P < 0.06; -59%, P < 0.05) without affecting the Km of the transport process as compared to the control values. These inhibitory effects were counteracted by the corresponding protein kinase activators, i.e. PMA (phorbol-12-myristate 13-acetate) in the case of PKC and forskolin in the case of PKA, although these protein kinase activators alone did not significantly affect the glutamate uptake. These results provide evidence that, in primary cultures of neuronal cells, the high affinity glutamate uptake may be regulated by both PKA and PKC-mediated phosphorylation processes.

Alkaloids↗