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Biomedical subjects

B Roche

Publications and source records attributed to B Roche.

At least 19 recordsLinked to original sources

Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.

BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.

Antiviral Agents↗

[Primary hypothyroidism in the adult older than 60 years. Characteristics and follow-up after initiation of replacement treatment in hospital].

OBJECTIVE: Primary hypothyroidism is common in the elderly. Yet its care remains unclear. PATIENTS AND METHODS: Clinical, biological characteristics and outcome of 45 patients aged over 60 years admitted for in-hospital initiation of treatment for primary hypothyroidism were recorded. Causes and tolerance of treatment (clinical and ECG monitoring in hospital) were seek for. RESULTS: Initial symptoms, predominantly fatigue (84.4%), were moderate, contrasting with severe biological hormonal deficiency. The most common routine biological change was hypercholesterolemia (57.6%). Female predominance was obvious (77.8%) and the most usual aetiology autoimmune chronic thyroiditis. Despite variability of symptoms, long term follow-up demonstrates a positive response to treatment, including an improvement in fatigue, eye-lid swelling, bradycardia and overweight. This clinical improvement was achieved on an average dose of 1.22 +/- 0.47 mg/kg/day L-T4 in order to maintain normal TSH (3.76 +/- 2.93 mUI/l). Cardiovascular incidents while starting treatment require experienced care and low dose initial treatment. CONCLUSION: Primary hypothyroidism is still lately discovered in the elderly. Yet, since treatment is efficacious and simple, the disease should be searched for and cared after whenever a related symptom occurs.

Aged↗

Derived stimulus--response and stimulus--stimulus relations in children and adults: assessing training order effects.

Preschool children and adults received training on three sets of successive discriminations: (1) A1-R1,A2-R2, (2) B1-R1,B2-R2, and (3) A1-R3,A2-R4. Then they received tests assessing derived stimulus-response relations (B1-R3, B2-R4) and stimulus-stimulus relations (e.g., A1-B1, A2-B2). Four training protocols were used. The protocols differed with regard to the order in which the sets were trained: Many-To-One (1-2-3), One-To-Many-1 (1-3-2), One-To-Many-2 (3-1-2), and One-To-One (3-2-1 or 2-3-1). The adults displayed class-consistent B-R and A-B performances over all conditions. The children displayed class consistent B-R performances more often in Many-To-One and One-To-Many than in One-To-One. Their A-B performances were highly consistent with the trained A-R and tested B-R performances. Present findings are consistent with the stimulus equivalence account rather than with the mediated response account.

Child Development↗

Comparison of transanal and external perineal ultrasonography.

Anal endosonography with rotating endoprobes provides state-of-the-art imaging of sphincter integrity; however, the technique is not widely available and requires expensive equipment. Since pelvic anatomy permits the use of standard external ultrasound probes, we tested the feasibility, tolerance and reproducibility of uniplanar perineal sonography, with respect to visualisation of the anal sphincter, using both convex and linear 3.5- to 7.5-MHz and 360 degree rotating 7-MHz probes. Twenty healthy nulliparus female volunteers were investigated. Two operators performed endosonography and perineal sonography in duplicate, each blinded to the findings of the other. We then used this technique to examine 20 postpartum primiparus patients. The examination was well tolerated by all subjects. The internal anal sphincter appeared in perineal sonography as a hypoechogenic ring surrounded by an echogenic ring representing the external anal sphincter. Endosonography revealed six sphincter tears, four external and internal sphincter tears, one isolated external tear and one isolated internal tear. Perineal sonography recognised in all cases external sphincter tears. In one case the internal sphincter defect was missed. Perineal sonography appears to be a feasible alternative to anal endosonography in female patients and provides good information on external sphincter defects suggesting that this procedure might be particularly useful in incontinence screening. Perineal sonography gives a good image of internal sphincter. The lack of an isolated internal defect cannot be considered as relevant to our study.

Adult↗

Does a second delivery increase the risk of anal incontinence?

OBJECTIVE: To evaluate the prevalence of anal incontinence and anal sphincter defects after a first vaginal delivery and assess the effect of a second delivery. DESIGN: Prospective cohort study using postal questionnaires assessing incontinence to flatus and stools at three and thirty months postnatally and anal endosonography at three months following delivery. SETTING: Recruitment was from the antenatal clinic at the University Hospitals of Geneva, Switzerland. POPULATION: One hundred women with a vaginal delivery of their first child. MAIN OUTCOME MEASURES: Prevalence of anal incontinence and anal sphincter defects. RESULTS: Anal incontinence was reported by 16/92 (17%) of women at three months after delivery and by 11/77 (14%) at 30 months. At that time, 5/54 (9%) with no further delivery reported incontinence, compared with 6/ 23 (26%) of those who had had another delivery (RR 2.8, 95% CI 1.0-8.3). Anal sphincter defects were diagnosed by endosonography in 46/87 (53%) women and were associated with reported incontinence at both three months (RR 1.9; 95% CI 1.4-2.6) and 30 months (RR 1.9: 95% CI 1.3-2.8) after delivery. The prevalence of anal incontinence at 30 months was highest (5/13, 39%) among those in whom a sphincter defect was diagnosed by endosonography after their first delivery and with a second delivery. CONCLUSION: Anal incontinence after childbirth is associated with defects of the anal sphincter diagnosed by endosonography. Subsequent deliveries increase the risk of incontinence, particularly among women with a sphincter defect diagnosed after the first delivery.

Adult↗

Assessing the New York City involuntary outpatient commitment pilot program.

OBJECTIVE: The study evaluated the effectiveness of a three-year outpatient commitment pilot program established in 1994 at Bellevue Hospital in New York City. METHODS: A total of 142 participants were randomly assigned; 78 received court-ordered treatment, which included enhanced services, and 64 received the enhanced-service package only. Between 57 and 68 percent of the subjects completed interviews at one, five, and 11 months after hospital discharge. Outcome measures included rehospitalization, arrest, quality of life, symptomatology, treatment noncompliance, and perceived level of coercion. RESULTS: On all major outcome measures, no statistically significant differences were found between the two groups. No subject was arrested for a violent crime. Eighteen percent of the court-ordered group and 16 percent of the control group were arrested at least once. The percentage rehospitalized during follow-up was about the same for both groups-51 percent and 42 percent, respectively. The groups did not differ significantly in the total number of days hospitalized during the follow-up period. Participants' perceptions of their quality of life and level of coercion were about the same. From the community service providers' perspective, patients in the two groups were similarly adherent to their required treatments. CONCLUSIONS: All results must be qualified by the fact that no pick-up order procedures for noncompliant subjects in the court-ordered group were implemented during the study, which compromised the differences between the conditions for the two groups, and that persons with a history of violence were excluded from the program.

Adult↗

Residual hepatitis B virus particles in liver transplant recipients receiving lamivudine: PCR quantitation of HBV DNA and ELISA of preS1 antigen.

Lamivudine, an antiviral agent, has a potential role in the treatment of recurrent or acquired de novo hepatitis B virus (HBV) infection after liver transplantation. During lamivudine therapy, residual HBV particles in serum, PBMC, and liver were quantified in 7 patients in whom hepatitis B occurred de novo (n = 4) or recurred (n = 3). HBV DNA and preS1 antigen were measured using a sensitive PCR technique and an in-house ELISA method, respectively. The genetic and antigenic properties of HBV variants that emerged during lamivudine treatment were also examined. One month after the outset of lamivudine treatment, all 7 patients remained positive for both HBV DNA and preS1 antigen in serum, reflecting residual HBV replication. At the end of therapy, four patients were considered to be lamivudine responders, including one who seroconverted to anti-HBs but remained HBV DNA positive in the liver (> 10(3) copies/microg of DNA). Among the three patients who did not respond to lamivudine, one had pol mutations (L450P and S550C) that had not been described previously, in addition to the common mutations within the YMDD locus and B domain. Defective core and preS viral proteins and atypical sedimentation profiles of HBV DNA-positive particles were observed in all three lamivudine-resistant patients. These findings confirm the persistence of HBV in liver transplant recipients despite strong inhibition of replication by lamivudine, and show abnormal viral transcription and/or morphogenesis in lamivudine-resistant patients.

Adult↗

Analysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma.

BACKGROUND: Uterine sarcomas (US) are rare and carry a poor prognosis characterized by high rates of local recurrence and metastasis. The aim of this study was to test, for what the authors believe was the first time with US, the prognostic impact of the histologic grade validated by the French Federation of Anticancer Centers (FNCLCC) for soft tissue sarcomas (STS). The grade is the sum of the scores allocated for three major histologic criteria: tumor differentiation, mitotic count, and tumor necrosis. Other histologic and clinical factors were tested as well. METHODS: The study included 157 patients in whom 78 leiomyosarcomas (LMS), 52 malignant mixed müllerian tumors (MMMT), and 27 endometrial stroma sarcomas (ESS) were documented. RESULTS: The median follow-up was 54 months (range, 6-230 months). The median OS and EFS were 33 and 13 months, respectively. The FNCLCC grade validated in soft tissue sarcomas was not a prognostic factor for survival or relapse for any of the US histologic subtypes. For LMS, stage and mitotic count were the only factors that had an influence on survival and relapse. For MMMT, stage and age were the only prognostic factors, and none of the histologic criteria impacted on the outcome. For ESS, the grade defined by Norris and Taylor was an important prognostic factor, particularly for survival. CONCLUSIONS: The FNCLCC grading score could not be used as a prognostic indicator for uterine sarcomas. The diagnosis of US is in itself an unfavorable prognostic factor, except when the diagnosis is low grade ESS.

Adult↗

Distinction between coeliac disease and refractory sprue: a simple immunohistochemical method.

AIMS: We recently showed that refractory sprue is distinct from coeliac disease, the former being characterized by abnormal intraepithelial T-lymphocytes expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface expression, and showing TCRgamma gene rearrangements. To take advantage of the abnormal phenotype of CD3c + CD8 - intraepithelial lymphocytes (IEL) in refractory sprue we developed a simple method to distinguish coeliac disease from refractory sprue. METHODS AND RESULTS: Comparative immunohistochemical studies using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and frozen biopsy specimens in refractory sprue (n = 6), coeliac disease (n = 10), healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable results were obtained on fixed and frozen biopsy specimens. In four of the six patients with suspected refractory sprue, abnormal CD3c + CD8 - IEL and TCRgamma gene rearrangements were found, as in refractory sprue; the remaining two patients had normal (CD3 + CD8 +) IEL and no TCRgamma gene rearrangements. Both patients had coeliac disease, as one failed to comply with a gluten-free diet, while the other was a slow responder. CONCLUSION: This simplified immunostaining method using anti-CD3 and anti-CD8 antibodies on paraffin sections can distinguish active coeliac disease from refractory sprue and should prove useful in clinical practice.

Adult↗

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↗

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↗

Long-term ganciclovir therapy for hepatitis B virus infection after liver transplantation.

BACKGROUND/AIMS: Hepatitis B virus (HBV) disease on a liver graft is associated with florid viral replication and graft failure. The aim of this study performed between 1992 and 1995 was to investigate the safety and efficacy of long-term intravenous ganciclovir for HBV infection in liver transplant recipients. METHODS: Twelve patients with HBV re-infection and four with de novo HBV infection were studied. HBV DNA was positive in all (median titer: 437.5 pg/ml) and HBeAg was positive in seven. Intravenous ganciclovir was started after a median of 14.5 months from HBsAg positivation and continued for a median of 10 months. RESULTS: A complete response with HBV DNA negativation was seen in ten cases, a partial response with a decrease of more than 50% of initial HBV DNA levels in four and no response in two. Overall tolerance was good. Among the ten complete responders, two seroconverted for both HBsAg and HBeAg and one for HBsAg alone. Among these ten patients, three were re-transplanted for liver failure: two of them are alive; three had a viral breakthrough during treatment; and four remained HBV DNA negative: two are alive and two died. Partial responders and nonresponders were treated with other antiviral agents and three were re-transplanted, two of them are alive. Overall 12 out of 16 patients (75%) survived with a median follow up of 46 months. CONCLUSIONS: Long-term intravenous ganciclovir can persistently inhibit HBV DNA replication in liver transplant recipients and is well tolerated. Further evaluation should be encouraged, especially for HBV recurrence after first-line treatments.

Adult↗

[Primary surgical care of pelvic fractures associated with perineal laceration].

Unstable fractures of the pelvic ring, associated to perineal lacerations are severe injuries occurring during high-energy trauma. High rates of septic complications and mortality have been reported with these injuries. Current treatment guidelines, while dealing with open pelvic fractures or dislocations are discussed, based on a current review of the literature and on our local experience. At our institution, 55 unstable type B or C fractures of the pelvic ring were treated by osteosynthesis between 1991 and 1997. Of these, 11 patients presented with an associated perineal laceration (20%). Simultaneously to the immediate pelvic ring fixation, a diversion colostomy was performed in all these patients. Repeated wound debridements and wide spectrum antibioprophylaxis were associated. Of these 11 patients presenting an open pelvic fracture, only one died of pelvic sepsis at three weeks. 10 patients survived (91%) and went on to bony union, without any local infectious complications. Aggressive multidisciplinary initial surgical management is a rule when dealing with this type of injuries, immediate colostomy and careful wound debridement must be associated to the initial osteosynthesis.

Adult↗

Rubber band ligation of hemorrhoids: relapse as a function of time.

Rubber band ligation is a well established treatment of internal second-degree hemorrhoids. Up to now, the long-term results (> 5 years) of this method have not been assessed. The aim of this study was to determine the long-term success rate of rubber band ligation in patients with a first episode of second-degree hemorrhoids not responding to medical treatment (local cream with laxative). A total of 92 patients who were treated between 1979 and 1997 for second-degree hemorrhoids responded to a questionnaire. The need for complementary conservative (sclerotherapy, cryotherapy or rubber band ligation) or surgical treatment was considered indicative of relapse. The collected data were analyzed according to the Kaplan-Meier method. The average follow-up time was 5.6 years. There were 21 patients who suffered a relapse. The probability of successful treatment was 0.77 (range: 0.67-0.88) after 5 years and 0.68 (range: 0.5-0.86) after 10.6 years. We conclude that rubber band ligation represent an efficient long-term treatment for second-degree hemorrhoids. Approximately two thirds of the patients are cured after 5 years and more than a half after 10 years.

Female↗