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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 343 records · Page 19Linked to original sources
PubMed1998

Effect of HLA matching on outcome of related and unrelated donor transplantation therapy for chronic myelogenous leukemia.

This article examines the diversity and biologic role of human lymphocyte antigen (HLA) genes as related to marrow transplantation for chronic myelogenous leukemia (CML). A better understanding of the nature and function of HLA variation is necessary as unrelated marrow transplantation evolves into a safe and effective treatment for CML. HLA matching is an important aspect of donor selection criteria and has a role in engraftment as well as the development of graft-versus-host disease and tolerance after transplant.

Bone Marrow Transplantation↗
PubMed1998

Adult liver transplantation for metabolic liver disease.

Liver replacement provides an effective method of replacing a failing liver, and corrects the underlying defect in many metabolic conditions. Results of liver transplantation for metabolic diseases have been encouraging, with the exception of hereditary hemochromatosis, in which infectious and for which cardiac complications appear to increase posttransplant mortality. An improved understanding of the underlying genetic and molecular defect will lead to advances in medical therapy and perhaps will decrease the need for liver replacement. The prospects of gene therapy are being pursued for many metabolic disorders, however until this research leads to direct clinical application, liver transplantation remains the only effective option for many patients with metabolic liver disease.

Amyloidosis↗
PubMed1998

Interferon-alpha2b therapy is efficacious in Asian-Americans with chronic hepatitis B infection: a prospective controlled trial.

Chronic hepatitis B virus infection is endemic in Asian communities in the United States. The purpose of the current study was to compare the antiviral efficacy of interferon-alpha2b in a group of adult Asian patients chronically infected with hepatitis B with active replication compared to a control group of Caucasian patients treated with the same regimen. Patients with entry aminotransferase (ALT) levels greater than three times the upper limit of normal received interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients with pretreatment ALT levels 1.5-3 times the upper limit of normal received prednisone for a total of six weeks prior to interferon starting at 60 mg daily with reduction in dosage by 20 mg every two weeks with a two-week period between finishing prednisone and starting interferon-alpha2b. Eight (62%) of the 13 Asians and six (60%) of the 10 Caucasians cleared HBeAg and HBV DNA from serum (NS). By the end of one year of follow-up after therapy, four (67%) of six Caucasian responders but none of the Asian responders had cleared hepatitis B surface antigen from serum (P < 0.05). Loss of serum markers of active replication appeared less durable in the Asian responders compared to the Caucasians with reappearance of serum HBeAg in two (25%) of eight of the former but only one (17%) of the latter group. Three other Asian patients subsequently redeveloped HBeAg in serum. It is concluded that adult Asian-Americans have an identical initial response rate to antiviral therapy with interferon-alpha2b; however, the response may be less durable and does not usually lead to loss of HBsAg.

Adult↗
PubMed1998

Reproducibility in retrospective grading of acute graft-versus-host disease after allogeneic marrow transplantation.

We have undertaken a formal study to evaluate the reproducibility of retrospective assessments for grading the severity of acute GVHD. Using criteria previously established by the Seattle group, three reviewers independently assigned GVHD severity grades for a set of 100 marrow transplant patients. Significant differences were found in the distribution of GVHD grades assigned by one of the reviewers as compared to the other two reviewers. In only 40% of cases did all three reviewers assign the same GVHD grade, and in only 68-71% of cases did all three reviewers assign the same grade within 0-I vs II-IV or 0-II vs III-IV categories. Despite the high rate of disagreement between any two reviewers, at least two reviewers assigned the same overall GVHD grade in 93% of cases. These results suggest that current criteria for assessing the severity of GVHD by a single reviewer are not sufficiently reliable for rigorous clinical studies. As an alternative to the original criteria, we have developed and tested simplified criteria that summarize the clinical course of GVHD as reflected by the progression of disease and the amount of immunosuppressive treatment used to control the disease. Our results suggest that the revised criteria might yield more reproducible retrospective grading than the original criteria. Although the original criteria and the revised criteria might produce different results for individual patients, the overall distributions of grades with the two systems were similar. The proposed revised criteria could be implemented without disrupting the continuity and consistency with previous grading assigned by the original criteria.

Bone Marrow Transplantation↗
PubMed1998

Oxidative activity of the type 2 isozyme of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) predominates in human sebaceous glands.

Sebum production is regulated by the opposing effects of androgens and estrogens. The intracrine activity of steroid metabolizing enzymes is important in regulating sebum production because these enzymes can convert weak steroids from the serum into potent androgens and estrogens within the sebaceous gland (SG). 17Beta-hydroxysteroid dehydrogenase (17beta-HSD) interconverts weak and potent sex steroids via redox reactions. In this regard, it may function as a gatekeeping enzyme regulating the hormonal milieu of the SG. Six isozymes of 17beta-HSD have been identified that differ in their substrate preference and their preference to produce weak or potent sex steroids via oxidation or reduction, respectively. The goals of this study are: (i) to identify which isozyme (s) of 17beta-HSD is active in SG; (ii) to determine if its activity differs in facial skin compared with nonacne-prone skin that may account for the regional differences in sebum production; (iii) to compare the activity of 17beta-HSD in intact glands and in SG homogenates; and (iv) to determine if 13-cis retinoic acid inhibits 17beta-HSD activity. Human SG were assayed for 17beta-HSD activity using estrogens, androgens, and progestins as substrates. Oxidative activity of the type 2 isozyme predominated in all samples tested. Although transcripts for the types 1, 2, 3, and 4 isozymes were detected using reverse transcriptase-polymerase chain reaction, only mRNA for the predominant type 2 isozyme and the type 4 isozyme were detected in northern analysis. Greater reductive activity of 17beta-HSD was noted in SG from facial areas compared with nonacne-prone areas, suggesting an increased net production of potent androgens in facial areas. Oxidation was more predominant over reduction in intact SG compared with homogenized SG, thus supporting the hypothesis that 17beta-HSD protects against the effects of potent androgens in vivo. Activity of the type 2 17beta-HSD was not inhibited by 13-cis retinoic acid. In conclusion, SG possess the cellular machinery needed to transcribe the genes for the type 1-4 isozymes of 17beta-HSD. At the protein level, however, oxidative activity of the type 2 isozyme predominates, suggesting that 17beta-HSD isozyme activity may be translationally regulated.

17-Hydroxysteroid Dehydrogenases↗
PubMed1998

Acquisition of hepatitis C virus in hemodialysis patients: a prospective study by branched DNA signal amplification assay.

Serological data indicate that hepatitis C virus (HCV) infection is very common among chronic hemodialysis (HD) patients. Circumstantial evidence suggests that hemodialysis per se is an important risk factor for this infection. We used a novel methodology, the branched DNA (bDNA) signal amplification assay, which is capable of detecting HCV RNA and of quantifying HCV viral load in serum, to prospectively determine the rate of acquisition of HCV infection in 274 anti-HCV-negative patients undergoing HD treatment in four hemodialysis units. Moreover, we used bDNA testing to analyze the dynamics of HCV acquisition among HD patients, a high-risk group for HCV infection with immune compromise conferred from uremia. Two patients were identified with de novo acquisition during 1 year of prospective bDNA testing. Thus, the HCV incidence was 0.73% per year. De novo acquisition of HCV infection was observed in the absence of identifiable parenteral risk factors. Both patients showed the same pattern of HCV acquisition: they underwent an initial viremic phase that was associated with an increase in alanine transaminase (ALT) activity and that preceded the anti-HCV seroconversion. This was followed by HCV RNA clearance and normalization of ALT activity. Anti-HCV positivity occurred 1 and 2 months after the ALT increase in the first and second patients, respectively. Although HCV incidence was low (0.73%), further research is warranted to set the optimal policy for eliminating the risk of nosocomial transmission of HCV in the HD setting. Our findings show the pattern of HCV acquisition in chronic HD patients and emphasize the need to screen the HD population for ALT measurement combined with anti-HCV testing for detecting hepatitis C. HCV RNA testing can identify HCV before seroconversion in individuals with deranged liver function tests. The acquisition of HCV in HD patients without identifiable risk is confirmed.

Aged↗
PubMed1998

Resolution of recurrent hepatitis B in two liver transplant recipients treated with famciclovir.

Recurrent hepatitis B infection after orthotopic liver transplantation remains problematic despite prophylaxis with hepatitis B immune globulin (anti-HBs IgG). Recently, famciclovir (an oral nucleoside analog) has been shown to have potent antiviral activity against hepatitis B in vitro as well as in patients with chronic hepatitis B. We present two patients who developed recurrent hepatitis B after orthotopic liver transplantation and were treated with famciclovir, 500 mg t.i.d. Both patients subsequently responded with marked improvement in biochemical liver tests and histology, with subsequent loss of hepatitis B surface antigen. Famciclovir is a useful agent in the treatment of hepatitis B in the liver transplant recipient.

2-Aminopurine↗
PubMed1998

A novel complication of peritoneovenous shunt: cardiac tamponade.

For the last two decades, peritoneovenous shunts (PVS) have commonly been used in the management of refractory ascites. However, these devices are associated with a wide variety of complications. We report a case of cardiac tamponade due to ventricular perforation by a PVS. Given the substantial morbidity associated with PVS, other therapeutic options should be considered before proceeding with PVS placement.

Ascites↗
PubMed1998

Animal models sensitive to anti-anxiety agents.

Animal models of anxiety serve two primary purposes in psychopharmacological research. (i) The pharmacological profile observed in the model provides a basis which, depending on its predictive validity, permits an estimation of clinical activity. (ii) Insofar as the 'anxiety' occurring in the animal model is homologous to human anxiety disorders, it is possible to investigate the underlying cellular and molecular mechanisms. The most commonly used laboratory procedures for the identification of anxiolytic effects of drugs are described in this paper.

Animals↗
PubMed1998

Pneumonia associated with Mycoplasma spp in three cats.

Mycoplasma spp were isolated in pure culture from bronchoalveolar lavage specimens from three cats with clinical, cytological and radiographic signs of bronchopneumonia or suppurative bronchitis. Predisposing factors were not identified in the first case, the second cat had oesophageal hypomotility, while the third cat had been exposed to cigarette smoke and had advanced periodontal disease. Respiratory signs resolved promptly and completely in all cases following antimicrobial therapy directed against mycoplasmas. Mycoplasma spp are possible causes of lower respiratory tract disease in cats and this should be considered when selecting empirical therapy for feline airway disease and pneumonia. In some situations mycoplasmas may behave as primary lower respiratory tract pathogens in cats.

Animals↗
PubMed1998

Subcutaneous granuloma caused by Mycobacterium avium complex infection in a cat.

A localised subcutaneous swelling developed on the nasal bridge of a cat receiving chemotherapy for alimentary tract lymphosarcoma. Cytological and histological examination of representative samples of the lesion demonstrated pyogranulomatous inflammation and abundant acid-fast bacilli. A Mycobacterium sp was cultured from tissue excised from the lesion. Extensive testing at three reference laboratories indicated the strain was a member of the Mycobacterium avium complex. The infection was treated successfully by cytoreductive surgery and a 6 weeks course of orally administered clofazimine.

Animals↗
PubMed1998

Mycobacterial nodular granulomas affecting the subcutis and skin of dogs (canine leproid granuloma syndrome).

OBJECTIVE: To obtain a better understanding of a disease affecting dogs in which nodular mycobacterial granulomas are present in the subcutis or skin. DESIGN: Retrospective survey PROCEDURE: A diagnosis of an unidentified mycobacterial infection was made in 45 dogs following detection of acid-fast bacilli surrounded by granulomatous or pyogranulomatous inflammation in tissue sections. Eight cases were identified from the records of our diagnostic laboratory. In all cases culture for mycobacteria was unsuccessful. Another 37 cases were identified by practitioners and veterinary pathologists in response to a survey mailed to veterinary clinics throughout Australia. Data from these 45 cases were entered into a data base. The data set was incomplete, as some respondents did not answer all questions. RESULTS: Over 90% of affected dogs had short coats and about half were Boxers or Boxer-cross dogs. A weak seasonal trend for the development of primary lesions in autumn and winter was identified. Cases were recorded from New South Wales (35 dogs), Western Australia (4), Queensland (4), Tasmania (1) and New Zealand (1). The subcutis and skin of the ears and head (including the ears) were involved in 64% and 85% of cases, respectively, for which lesion site was recorded. Culture was attempted but was unsuccessful in 19 cases, including 11 cases where material was submitted to our laboratory and/or a Mycobacteria Reference Laboratory. Lymph node enlargement, internal organ involvement or constitutional signs were not a feature of the syndrome, and most lesions did not worry the dogs. Although many practitioners recorded a favourable response to therapy with doxycycline (response rate 57%) or amoxycillin-clavulanate (63%), spontaneous resolution of infection was thought to have occurred in six of seven dogs (86%) not given systemic antimicrobials, and three dogs where antimicrobials had failed previously. A minority of cases failed to respond to antimicrobial therapy and continued to have chronic lesions. There was no discernible trend for dogs of a particular age or sex to be affected. CONCLUSION: This syndrome is caused by saprophytic mycobacteria of limited pathogenicity that give rise to lesions restricted principally but not exclusively to the subcutis and skin of body extremities. Fastidious growth requirements have prevented their isolation on synthetic media used for culture of mycobacteria. Organisms presumably enter the subcutis following a breach in integrity of the epidermal barrier and produce self-limiting disease in immunocompetent dogs. Lesions tend to resolve spontaneously. The possibility of a public health threat from affected dogs is highly unlikely.

Animals↗
PubMed1998

Automated RIBA hepatitis C virus (HCV) strip immunoblot assay for reproducible HCV diagnosis.

A comparison between the CHIRON RIBA hepatitis C virus (HCV) processor and manual systems was performed by using 88 specimens repeatedly reactive by the second-generation HCV enzyme-linked immunosorbent assay (ELISA) (HCV 2.0 ELISA) and 111 random specimens from volunteer donors. For the second-generation RIBA HCV strip immunoblot assay (SIA) (RIBA HCV 2.0 SIA), test results correlated strongly between the manual and the automated runs (kappa value, 0.937). For the RIBA HCV 3.0 SIA, the correlation of the test results was also high (kappa value, 0.899). Among the specimens with positive results by RIBA HCV 2.0 and 3.0 SIAs, there was a very strong concordance of the test results between the manual and the automated runs with regard to the reactive bands. Nine samples had discordant results between the manual and the automated runs; this was probably attributable to increased variability in antigen scores close to the cutoff values for both tests. Run-to-run and within-run testing by the CHIRON RIBA HCV Processor System showed a very low rate of conflicting values. In conclusion, the CHIRON RIBA HCV Processor System is capable of performing RIBA HCV 2.0 and 3.0 SIAs accurately with minimal operator involvement. In addition, the CHIRON RIBA HCV Processor System shows excellent reproducibility, with the potential for operator-to-operator and site-to-site variability being greatly reduced. Our data indicate that this novel methodology may be very useful for supplemental anti-HCV testing of specimens repeatedly reactive by ELISA in routine clinical assessments and epidemiologic evaluations.

DNA, Viral↗
PubMed1998

Quantitative assessment of HCV load in chronic hemodialysis patients: a cross-sectional survey.

UNLABELLED: Recent evidence has been accumulated showing that chronic hemodialysis (HD) patients have a very high prevalence of antibodies to hepatitis C virus (HCV). In contrast, there is little information addressing the virological characteristics of HCV infection in this population. AIM: To measure HCV viral load and to correlate this with demographic, biochemical, and clinical features of a large cohort of HCV-infected patients on chronic HD. METHODS: 394 chronic HD patients were tested by branched-DNA signal amplification assay, anti-HCV enzyme-linked immunosorbent assay 2.0, and on the basis of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) activity. Multivariate analysis by ordinal logistic regression model was performed: age, gender, race, time on HD, allocation of the patients among the HD units, etiology of end-stage renal disease, HBsAg status, anti-HCV positivity, HCV genotype, and AST/ALT levels were independent factors, and viremic levels of HCV in serum were assumed as dependent variables. RESULTS: 88 (22.3%) patients showed serological and/or virological signs of HCV infection. 59 (15%) out of 394 had detectable HCV RNA in serum, the mean HCV load was 19.4 x 10(5) (95% CI, 6.06 x 10(7) to 6.2 x 10(4)) Eq/ml. According to the criteria suggested by others [J Infect Dis 1994;169:1219-1225], there were 8 (13.5%) individuals with high-titer viremia (>1 x 10(7) Eq/ml) in the subset of viremic patients. A small subset (8/394 or 2%) of individuals was seronegative, but viremic; 29 (7%) out of 394 were seropositive without detectable HCV RNA in serum. Univariate analysis showed that the frequency of anti-HCV positivity was significantly higher in viremic patients as compared with individuals with no detectable HCV viremia: 51/59 (86%) vs. 29/335 (8.6%), p = 0.0001. Serum AST and ALT levels were significantly higher in viremic patients than in individuals with no detectable HCV RNA in serum: 23.8 (95% CI 60.8-9.3) vs. 17.1 (95% CI 50.4-5.8) U/l (p = 0.009) and 14.4 (95% CI 48.9-4.3) vs. 9.8 (95% CI, 37.3- 2. 5) U/l (p = 0.008). Logistic regression analysis showed an association between HCV viremia and anti-HCV positivity (p = 0. 00001) and ALT activity (p = 0.01). CONCLUSIONS: Hepatitis C virus infection is highly prevalent in the HD population; the viral load is relatively low, and it was associated with elevated hepatic enzyme levels and anti-HCV positivity. No other clinical characteristics were associated with HCV RNA levels. Seronegative but viremic patients were also found. Longitudinal studies with long follow-up periods are necessary to evaluate the course of HCV load over time in this population.

Aged↗
PubMed1998

Antenatal HIV prevalence in Yaounde, Cameroon.

From June 1994 to July 1996, 4100 pregnant women living in Yaounde, Cameroon, were tested for human immunodeficiency virus type 1 (HIV-1) and syphilis. The HIV seroprevalence was 4.2% (95% confidence interval (CI): 3.6%-4.8%), and that of antibodies to Treponema pallidum was 17.4% (95% CI: 16.3%-18.6%) (HIV infection was twice as common in women with positive syphilis serology) (7.2% vs 3.6%). Over the study period, the antenatal seroprevalence of syphilis remained stable, while there was an increase in the HIV seroprevalence rate. There was an increase in HIV seropositivity in women uninfected with syphilis between 1994/1995 and 1995/1996 from 2.9% to 4.3%. By the end of the study, HIV infection was no commoner in women with negative compared with positive syphilis serology. It is therefore postulated that HIV infection in Yaounde has entered the general, sexually active female population. We suggest that management of pregnant women in Cameroon should include routine screening for both HIV infection and other sexually transmitted diseases (STDs).

Cameroon↗
PubMed1998

High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.

Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.

Amino Acid Substitution↗