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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 199 records · Page 11Linked to original sources
PubMed2000

Acute Viral Hepatitis.

The mainstay of treatment for acute viral hepatitis is supportive care, as most cases are self-limited. General measures in all types of acute viral hepatitis include bedrest if the patient is very symptomatic, a high-calorie diet, avoidance of hepatotoxic medications, and abstinence from alcohol with the anticipation that most patients will recover uneventfully. In severe cases, hospitalization may be necessary for intravenous rehydration if the patient is unable to maintain adequate oral intake due to nausea and vomiting or if there is any alteration of mental status to suggest evolving fulminant hepatic failure. Acute hepatitis A is a self-limited disease, but can be fulminant. Lamivudine at a dosage of 100 mg/d orally may be beneficial in acute hepatitis B. Interferon-alpha therapy in acute hepatitis C may decrease the risk of developing chronic hepatitis C. Fulminant liver failure due to acute viral hepatitis is uncommon, but orthotopic liver transplantation occasionally may be life saving.

Journal Article↗
PubMed2000

Comparative effects of quinacrine and erythromycin in adult female rats: a nonsurgical sterilization study.

OBJECTIVE: To compare the efficacies of erythromycin and quinacrine for nonsurgical sterilization in rats. Quinacrine used for nonsurgical sterilization in women is mutagenic, and most clinical regimens have had a higher failure rate than surgical sterilization. DESIGN: This acute mammal study included five groups of rats assigned randomly and evaluated at two times after treatment. ANIMAL(S): Adult female Sprague-Dawley rats. INTERVENTION(S): Five groups of female Sprague-Dawley rats (20 per group) were given 70 or 280 mg/kg of erythromycin lactobionate, 350 mg/kg of quinacrine hydrochloride, or vehicle control administered transcervically. Rats were mated 21 days later. Additional groups (n = 4 per group) were treated and killed 21 days later without mating. MAIN OUTCOME MEASURE(S): Fourteen days after mating, numbers of ovarian corpora lutea, total uterine implants, and embryos were evaluated. For unmated animals, uterine sections were examined for fibrosis and lumen closure. RESULT(S): Neither drug altered numbers of corpora lutea. Erythromycin decreased pregnancy rate and number of implantations (increased preimplantation loss) in a dose-related fashion. Quinacrine increased resorptions. Uterine pathology was more extensive and frequent in erythromycin-treated animals, with extent and severity increasing from 21 to 35+ days. CONCLUSION(S): Erythromycin was more effective than quinacrine in preventing pregnancy.

Administration, Intravaginal↗
PubMed2000

HLA matching in hematopoietic cell transplantation.

Progress in hematopoietic cell transplantation has been greatly facilitated by our increasing knowledge of the HLA system, as well as by improved therapies for achieving sustained engraftment, preventing graft-versus-host disease, and protecting the patient from infection. Disparity for HLA genes can cause graft rejection and graft-versus-host disease and decrease survival in patients receiving grafts from both related and unrelated donors. The presence of patient alloantibodies against donor antigens demonstrated by a positive crossmatch is a strong risk factor for graft rejection. The availability of matched donors for patients lacking a genotypically HLA-matched sibling has been greatly improved by the establishment of international registries of HLA-typed volunteer donors. The development of accurate and reproducible high-resolution DNA-based typing methods has significantly improved the prospects for identifying unrelated donors who are well matched with the patient for HLA. The use of these methods to optimize donor selection will improve both donor identification and the success of unrelated donor transplants.

Alleles↗
PubMed2000

Serotyping strip immunoblot assay for assessing hepatitis C virus strains in dialysis patients.

Recent accumulated evidence shows that dialysis patients are a high-risk group for hepatitis C virus (HCV) infection. Assessment of HCV genotype distribution among dialysis patients may be important because specific viral genotypes are associated with different clinical manifestations, disease progression, and response to antiviral therapy. However, polymerase chain reaction-based methods are cumbersome and unsuitable for analyzing large cohorts of dialysis patients with HCV. Instead, this information can be obtained by using a novel recombinant immunoblot assay (RIBA) recently developed for determining HCV serotype. The RIBA HCV serotyping strip immunoblot assay (SIA; Chiron Corporation, Emeryville, CA), is based on an immunoblot strip with five lanes of immobilized serotype-specific HCV peptides from the nonstructural (NS4) and core regions of the genomes of HCV types 1, 2, and 3. HCV serotype is deduced by determining the greatest intensity of reactivity to the NS4 serotype-specific HCV peptide band in relation to the internal control band (human immunoglobulin G) intensity on each strip. HCV core peptide reactivity is used only in the absence of NS4 reactivity. We compared RIBA HCV serotyping SIA with genotyping using sera from a large (n = 107) cohort of HCV-infected patients undergoing chronic hemodialysis (HD). We successfully serotyped 79 of 107 patients (74%) undergoing HD. We found a remarkable concordance (65 of 70 results; 93%) between RIBA HCV serotyping SIA and genotyping (line probe assay [LiPA]) techniques (kappa = 0.786) with sera from viremic patients infected with a known genotype. Only 5 of 70 patients (7%) had apparently discordant results. In a subset of patients (28 of 107 patients; 26%) not typed by RIBA HCV serotyping SIA, most (24 of 28 patients; 86%) were successfully genotyped by LiPA technology. It was possible to assess serotype reactivity in some patients (9 of 107 patients; 7%) who could not be genotyped. The distribution of HCV serotypes was associated with the antibody response against HCV proteins and the patterns of reactivity by RIBA HCV 2.0 SIA. In conclusion, (1) we found good agreement between serotyping and genotyping methods in our large cohort of dialysis patients infected with HCV; (2) the impaired immunocompetence conferred by uremia may limit serotyping analysis in some HCV-infected patients undergoing HD; (3) RIBA HCV serotyping SIA may be useful in tracking transmission routes for HD patients who cleared the virus and have only anti-HCV antibody; and (4) the distribution of HCV serotypes was associated with the antibody response against HCV proteins and the patterns of reactivity by RIBA HCV 2.0 SIA. Assessment of HCV strains appears to be very useful in the routine clinical activity of nephrologists within HD units because consistent biological differences among HCV strains exist. RIBA serotyping SIA is a simple, inexpensive, and highly reproducible assay to obtain information about HCV types in the HD setting.

Female↗
PubMed2000

Biological dynamics of viral load in hemodialysis patients with hepatitis C virus.

The biological dynamics of hepatitis C virus (HCV) viremia in uremic patients with chronic infection have not been fully characterized. We prospectively studied fluctuations of HCV-RNA in sera from 52 patients with end-stage renal disease who were undergoing maintenance hemodialysis (HD) and had chronic HCV infection. We measured HCV viremia monthly over the course of 13 months with the branched-chain DNA (bDNA) signal amplification assay and prospectively analyzed liver function, expressed by monthly serum aspartate (AST) and alanine aminotransferase (ALT) determinations. We observed three different patterns of HCV viremia: (1) patients persistently positive by bDNA assay (persistent viremia; 23 of 52 patients; 44%), (2) individuals with alternatively positive and negative results (intermittent viremia; 17 of 52 patients; 33%), and (3) patients persistently negative by bDNA assay (12 of 52 patients; 23%). The HCV viral load over the follow-up was greater among patients with persistent compared with intermittent viremia (persistent, 31.7 x 10(5) Eq/mL; range, 6.3 x 10(5) to 16.03 x 10(6) Eq/mL versus intermittent, 10.4 x 10(5) Eq/mL; range, 1.1 x 10(5) to 9.4 x 10(6) Eq/mL; P = 0.0001). In addition, patients with persistent viremia had over time greater AST and/or ALT activities than the intermittent group (AST: persistent, 26.5 IU/L; range, 9.6 to 73.7 IU/L versus intermittent, 21.3 IU/L; range, 8 to 56.8 IU/L; P = 0.001 and ALT: persistent, 14.7 IU/L; range, 3.7 to 57.9 IU/L versus intermittent, 10.9 IU/L; range, 2.3 to 52.1 IU/L; P = 0.001). In the group with persistent viremia, the mean difference between maximum and minimum values of HCV-RNA observed in each individual patient was 2.09 +/- 0.7 natural logarithm (Log(n)) and in intermittent viremic patients, 1.55 +/- 1 Log(n) (P = 0.045). The HCV load at study entry (19.4 x 10(5) Eq/mL) was rather low and did not change versus the end of follow-up in all patients (P = not significant [NS]). In the entire group, the fluctuations in HCV-RNA levels over time between and within individuals were not significant (P = NS). No difference in variability of HCV-RNA values over time between patients infected with different HCV genotypes was seen. In conclusion, three different patterns of HCV viremia in HD over time were assessed; one third of viremic patients had intermittent viremia, and those patients had less HCV-RNA, enzyme-linked immunosorbent assay, and aminotransferase activity than did patients with persistent HCV load. Larger fluctuations in HCV RNA levels occurred in patients with persistent than with intermittent HCV viremia. However, the viremic HCV load was low and relatively stable over a 13-month follow-up in our population. Studies with longer observation periods are warranted to understand fully the natural history of HCV in these immunosuppressed individuals.

Adult↗
PubMed2000

DNA rearrangements at the extremities of the Streptomyces ambofaciens linear chromosome: evidence for developmental control.

In Streptomyces, a genomic instability results from frequent recombination events which occur at the ends of the linear chromosomal DNA. These events are believed to be responsible for the variability observed in these regions among Streptomyces species and strains. In order to identify functions able to control this type of genome plasticity, mutators as well as mutants produced at different stages of development have been characterized in S. ambofaciens. Their characterization suggests the existence of a relationship between genomic instability and colony development.

Chromosomes, Bacterial↗
PubMed2000

Viral hepatitis in the liver transplant recipient.

Understanding and management of HBV and HCV infection in the OLT recipient has evolved rapidly in the last decade. The spontaneous risk for viral recurrence after transplantation is high, but has been decreased effectively in hepatitis B-positive recipients with the use of HBIG and lamivudine. HCV recurrence as defined by histologic injury is almost universal, although graft or patient outcomes for the first 8 years after OLT do not appear to be limited by HCV serostatus. However, effective prophylactic regimens that alter the natural history of HCV reinfection do not currently exist, and with longer follow-up into the second decade, the prevalence of HCV-related graft failure is likely to increase.

Antiviral Agents↗
PubMed2000

Identification and typing of Streptomyces strains: evaluation of interspecific, intraspecific and intraclonal differences by RAPD fingerprinting.

The suitability of random amplified polymorphic DNA PCR for the detection of differences between Streptomyces species and strains was evaluated. For this purpose, a protocol of RAPD specific for Streptomyces DNA, i.e. suitable for DNA presenting a high G+C content, was developed using S. ambofaciens ATCC23877. Among the 30 primers tested, all containing 80% G+C, 17 gave a pattern with this strain. Six oligonucleotides were chosen to compare 12 strains belonging to six species of Streptomyces. These oligonucleotides were then used to determine whether these strains could be differentiated at the DNA level with this method. All fingerprints obtained with six primers differed from one species to another. We showed that the RAPD method could be used to reveal intraspecific and intraclonal polymorphisms. Thus, RAPD allows for the rapid, sensitive and specific detection of genetic diversity among species and strains of Streptomyces.

Base Composition↗
PubMed2000

Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is the principal cause of transplantation-related morbidity and nonrelapse mortality late after allogeneic hematopoietic stem cell transplantation. The safety and potential efficacy of tacrolimus for the salvage treatment of chronic GVHD was evaluated in a single-arm, open-label phase 2 study. A total of 39 evaluable patients with chronic GVHD who failed previous immunosuppressive therapy with cyclosporine and prednisone were treated with tacrolimus starting at a median of 20 months (range, 3-68 months) after transplantation. At 3 years after the start of treatment, 5 patients (13%) had discontinued tacrolimus and were in complete remission, and 3 were considered clinically stable but not able to discontinue tacrolimus. A total of 31 patients (79%) experienced treatment failure; 22 (56%) who failed therapy had a change in immunosuppressive regimen because of progression (n = 18) or toxicity (n = 4). Nine patients (23%) died during continued treatment with tacrolimus. Two patients were lost to follow-up, at 11 and 19 months. The median duration of treatment with tacrolimus was 9 months (range, 1-29 months). Infections (144 episodes) were the most frequent adverse event. Nephrotoxicity occurred in 16 patients (41%); tacrolimus was discontinued in only 2 patients because of progressive deterioration in renal function. The Kaplan-Meier estimate of survival was 64% (95% confidence interval, 49%-79%) at 3 years posttransplantation. Seven patients had discontinued all immunosuppression at last contact, leading to an estimated 29% probability of stopping all immunosuppression by 3 years posttransplantation. Four patients died after relapse of malignancy. The response rate is consistent with previous reports of salvage treatment for chronic GVHD, indicating that a small group of patients failing cyclosporine may respond or stabilize with tacrolimus.

Adolescent↗
PubMed2000

Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation.

We conducted 2 sequential studies of donor leukocyte infusion (DLI) in 26 patients with chronic myeloid leukemia in hematologic relapse after unmodified allogeneic bone marrow transplantation. In the first study, cells for DLI were collected from 13 donors who were not treated with granulocyte colony-stimulating factor (G-CSF) (group 1). In the second study, cells were collected from 13 donors who received G-CSF before apheresis (group 2) in an attempt to avoid aplasia after DLI. Patients in group 2 received 550-fold more CD34+ cells than those in group 1. We found no significant difference in the incidence (31% versus 22%), onset time (41 vs. 48 days), or duration (15 vs. 14 days) of cytopenia after DLI in the 2 groups. G-CSF given to donors before collection of cells did not prevent aplasia. These findings support the hypothesis that the pathogenesis of aplasia after DLI is not restricted to the destruction of recipient hematopoietic cells but also involves failure of donor hematopoiesis by undefined mechanisms.

Adolescent↗
PubMed2000

Liver transplantation. Selection, listing criteria, and preoperative management.

Although only the expansion of the donor pool will have a major impact on the survival of patients with decompensated cirrhosis awaiting OLT, anticipation of complications such as SBP may improve the likelihood of a patient surviving until OLT, and may ameliorate some of the major causes of morbidity of cirrhosis, such as osteoporosis. Close communication between the treating physicians and the transplant center is crucial to ensure that the patients' UNOS status can be appropriately adjusted if additional complications of cirrhosis, such as intractable ascites, have occurred.

Adult↗
PubMed2000

Quantitative ultrasound and dual X-ray absorptiometry measurements of the calcaneus in patients on maintenance hemodialysis.

It has been suggested that quantitative ultrasound measurements (QUS), which reflect mainly bone density, could be influenced by bone micro-architecture. The aim of the study was to assess whether the relationship of QUS to dual X-ray absorptiometry (DXA) would reflect abnormalities of bone structure observed in renal osteodystrophy. QUS and bone mineral density of the calcaneus (BMDc) were measured by DXA in 30 patients on maintenance hemodialysis and 34 age- and gender-matched controls. QUS parameters and BMDc were significantly lower in hemodialysis patients than in controls (speed of sound [SOS] and broadband ultrasound attenuation [BUA], p = 0. 030; stiffness, p = 0.003; BMDc, p = 0.006). Bone measurements were not correlated with serum parathyroid hormone (PTH). The regression lines of SOS, BUA, and stiffness to BMDc were not significantly different from that of the controls. When dividing the patients into two subgroups according to their median PTH (203 pg/mL), the slopes of the regression lines of BUA to BMDc were significantly different between these two subgroups (p = 0.052). The slope of the subgroup with PTH </= 203 pg/mL was significantly different from that of the controls (p = 0.030). In conclusion, QUS of the calcaneus can be used for bone assessment in patients on maintenance hemodialysis. The differences in the slopes of patients with a less pronounced degree of hyperparathyroidism compared with patients with a higher degree of hyperparathyroidism and to controls suggest that BUA of the calcaneus contains information on bone complementary to DXA measured at the same site. The clinical relevance of this finding is presently unclear.

Absorptiometry, Photon↗
PubMed2000

SIVcpz from a naturally infected Cameroonian chimpanzee: biological and genetic comparison with HIV-1 N.

Thus far, simian immunodeficiency virus from chimpanzees (SIVcpz) genomes have been characterized as Pan troglodytes troglodytes and show a strong relation with human immunodeficiency virus (HIV)-1 N in their env genes. We fully characterized another SIVcpz from P. t. troglodytes. This chimpanzee (Cam5) was, as was also the host of SIVcpz-cam3, wild born in Cameroon, a region where all three groups of HIV-1 (M, N and O) co-occur. In contrast to other SIVcpz, SIVcpz-cam5 was isolated immediately after the rescue of the animal. Our data demonstrate that SIVcpz-cam5, like SIVcpz-cam3, grows easily on human peripheral blood mononuclear cells (PBMCs) and uses CCR5 as a co-receptor similar to HIV-1 N YBF30. Phylogenetic analysis based on the entire env gene shows that SIVcpz-cam5 falls into the same unique subcluster as HIV-1 N YBF30, SIVcpz-cam3 and SIVcpz-US. A phylogenetic relationship was also found with the vif gene of HIV-1 N. This study provides proof that HIV-1 N related viruses circulate in wild P. t. troglodytes.

Amino Acid Sequence↗
PubMed2000

Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities.

This retrospective study describes the outcome in 53 patients who had immunosuppressive treatment changed from cyclosporine (CSP) to tacrolimus for resistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CSP-associated neurotoxicity (n = 17). Tacrolimus was administered at doses of 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, as tolerated. Median time of conversion to tacrolimus after transplant was day 47. Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades III or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution of GVHD after changing treatment to tacrolimus, with 18 showing no improvement. Eleven evaluable patients had therapy changed to tacrolimus for CSP-associated neurotoxicity at a median of 36 days after transplant. Eight patients had resolution of neurotoxicity and three had partial improvement. Eleven evaluable patients had therapy changed to tacrolimus for HUS at a median of 46 days after transplant. One patient had complete resolution of HUS and 10 showed no response. Side-effects related to tacrolimus included renal toxicity (34%), neurotoxicity (15%) and HUS (9%). Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CSP-associated neurotoxicity. While often successful for dealing with neurotoxicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD.

Acute Disease↗
PubMed2000

Severe factor V deficiency and neonatal intracranial haemorrhage: a case report.

We report a case of severe factor V (FV) deficiency (<1%) associated with multiple episodes of intracranial bleeding which presented at birth. The clinical course was further complicated by the development of an inhibitor, episodes of sepsis and cardiac failure. The management using virally inactivated FFP and platelets is discussed.

Bacterial Infections↗
PubMed2000

Successful orthotopic liver transplantation for lamivudine-associated YMDD mutant hepatitis B virus.

YMDD hepatitis B virus (HBV) mutants emerge in more than one third of patients treated with lamivudine. The development of escape mutants potentially limits the efficacy of this new therapy for chronic HBV infection. Transplant centers may be hesitant to perform orthotopic liver transplantation (OLT) in patients with progressive liver disease who develop the YMDD mutant because of concerns of graft reinfection. We describe a 56-year-old man with chronic liver disease caused by HBV who successfully underwent OLT after the emergence of a YMDD mutant and progressive liver disease. Perioperatively, he received high-dose intravenous hepatitis B immune globulin (HBIG) treatment with continued lamivudine treatment. Thirty-two months after OLT, there was no evidence of HBV reinfection with the use of lamivudine and high-dose HBIG. Our experience suggests that the emergence of a YMDD HBV mutant is not a contraindication to OLT. The combination of lamivudine and high-dose HBIG can protect against reinfection of the hepatic allograft with the YMDD HBV escape mutant.

Hepatitis B virus↗