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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 73 records · Page 4Linked to original sources
PubMed2004

Retrospective study of feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases.

A retrospective study of 155 cats and 40 dogs diagnosed with cryptococcosis between 1981 and 2001 was undertaken. Age, sex, breed, clinical findings, feline immunodeficiency virus and feline leukaemia virus status (in cats), species of Cryptococcus causing disease and region of domicile were recorded. Associations between variables were tested. Male and female cats were affected equally. Age ranged from 1 to 16 years, with a preponderance of cats aged between 2 and 3 years. Siamese, Himalayan and Ragdoll breeds were over-represented. Rural cats were more frequently infected with Cryptococcus gattii. Retroviral infection was not identified as a predisposing condition and was not correlated with either species of Cryptococcus or physical findings. Most cats had signs of nasal cavity infection, which was typically localised for a substantial period before invasion of adjacent structures or dissemination. Male and female dogs were affected equally. A marked preponderance of young, large breed dogs was noted. Border Collies, Boxers, Dalmatians, Dobermann Pinschers, Great Danes and German Shepherds were over-represented. Cryptococcus species involved was not affected by place of domicile. Although nasal cavity involvement was important, the canine cohort had a greater propensity to develop secondary central nervous system involvement and disseminated disease than feline cases. There were no clinical findings in either cats or dogs which could be reliably used to distinguish disease caused by Cryptococcus neoformans variety grubii from disease caused by Cryptococcus gattii. Both Cryptococcus species appear to be primary pathogens of cats and dogs, with the upper respiratory tract presumed to be the predominant primary site of inoculation in most but not all cases.

Animals↗
PubMed2004

Meta-analysis: Effect of hepatitis C virus infection on mortality in dialysis.

BACKGROUND: The natural history of hepatitis C virus infection among patients on long-term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life-expectancy is substantially diminished by end-stage renal disease. AIM: To conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus infection on the survival of patients receiving chronic dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. METHODS: We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality with hepatitis C virus across the published studies. RESULTS: We identified four clinical trials (2341 unique patients); three (75%) of them were prospective, cohort studies; the fourth was a case-control study. Pooling of study results demonstrated that presence of antihepatitis C virus antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for relative risk was 1.57 with a 95% confidence interval (CI) of 1.33-1.86. A test for homogeneity of the relative risks across the four studies gave a P-value of 0.77. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among antihepatitis C virus-positive than -negative dialysis patients. CONCLUSIONS: This meta-analysis demonstrates that antihepatitis C virus-positive patients on dialysis have an increased risk of mortality compared with hepatitis C virus-negative patients. The excess risk of death in hepatitis C virus-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. Clinical trials with extended follow-up are currently under way to assess the effect of hepatitis C virus treatment on the excess risk of mortality in this population.

Case-Control Studies↗
PubMed2004

Fetal blood group genotyping from DNA from maternal plasma: an important advance in the management and prevention of haemolytic disease of the fetus and newborn.

The cloning of blood group genes and subsequent identification of the molecular bases of blood group polymorphisms has made it possible to predict blood group phenotypes from DNA with a reasonable degree of accuracy. The major application of this technology, which has now become the standard of care, is the determination of a fetal RHD genotype in women with anti-D, to assess whether the fetus is at risk of haemolytic disease of the fetus and newborn (HDFN). Initially, the procurement of fetal DNA required the invasive procedures of amniocentesis or chorionic villus sampling. Since the discovery of fetal DNA in maternal plasma in 1997, the technology of detecting an RHD gene in this very small quantity of fetal DNA has developed rapidly, so that non-invasive fetal D typing can now be provided as a diagnostic service for D-negative pregnant women with anti-D. Within a few years, it is probable that fetuses of all D-negative pregnant women will be tested for RHD, to establish whether the mother requires antenatal anti-D immunoglobulin prophylaxis.

Blood Group Antigens↗
PubMed2004

Infections of the subcutis and skin of dogs caused by rapidly growing mycobacteria.

Nine dogs with panniculitis due to rapidly growing mycobacteria (RGM) were examined over 17 years. Dogs were two to 15 years; five were male, four were female. All were obese or in good condition. Antecedent injury, typically a dog bite or vehicular trauma, could be identified in some patients, while one bitch had hyperadrenocorticism. Infections involved different locations, although the cervicothoracic region, dorsum or flank were most often affected. Patients were systemically well, apart from one dog with pyrexia and two with pain or lameness. Cytology demonstrated pyogranulomatous inflammation, but in only one case was it possible to see acid-fast bacilli (AFB) in smears. Histology demonstrated chronic active pyogranulomatous panniculitis and dermatitis; AFB could be detected in only four specimens. Culture of aspirates or resected tissues demonstrated RGM in all cases, comprising six Mycobacterium smegmatis group and three Mycobacterium fortuitum group isolates. Resection of infected tissues, perioperative injectable antimicrobials and long courses of oral antimicrobials chosen according to susceptibility data generally effected a cure, although some cases recurred.

Animals↗
PubMed2004

Epidemiology and clinical significance of hepatotropic infections in dialysis patients. Recent evidence.

Hepatitis C virus (HCV) infection is frequent among patients receiving long-term dialysis in developed and developing countries. It is difficult to assess the natural history of HCV in the dialysis population; however, recent studies have demonstrated that positive anti-HCV status is a significant and independent risk factor for mortality among dialysis patients. Recent meta-analyses have shown that interferon (IFN) initial monotherapy is effective in the treatment of chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy was rather poor. Large, multicenter and prospective trials based on pegylated IFN for the treatment of chronic hepatitis C are planned. The frequency of HBV infection in patients undergoing maintenance dialysis in the industrialized world is low but not negligible; persistent HBsAg seropositivity is much higher in less-developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA status in serum is an independent and significant predictive factor for hepatocellular dysfunction in dialysis patients. No significant difference in morbidity and mortality between dialysis patients according to hepatitis B surface antigen status has been consistently shown. Preliminary reports suggest that lamivudine appears to be safe and effective in patients receiving long-term dialysis.

Hepatitis B↗
PubMed2003

ARX mutations in X-linked lissencephaly with abnormal genitalia.

X-linked lissencephaly with abnormal genitalia (XLAG) is a distinct form of lissencephaly associated with absent corpus callosum. Recently, forms of syndromic and nonspecific X-linked mental retardation have been found to be associated with mutations in the Aristaless-related homeobox gene ARX. The authors assessed ARX as a candidate gene for XLAG in a genetic analysis of neuronal migration disorders and found two different point mutations in two XLAG pedigrees affecting the homeodomain of the protein, confirming that ARX is a causative gene for XLAG.

Abnormalities, Multiple↗
PubMed2003

Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.

X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.

Adult↗
PubMed2003

Analysis of hepatitis C viral quasispecies in liver transplantation.

The hepatitis C virus (HCV) is an RNA virus that replicates with a high rate of mutation, especially in the hypervariable region 1 (HVR-1). Continuous viral mutations lead to a mixed and changing populations of mutants, called quasispecies. The nature of the HCV quasispecies may have implications for viral persistence and pathogenies. Studies with liver transplant patients suggest a relationship between the degree of immunosuppression and the complexity of the quasispecies. This study evaluated whether immunosuppressive therapy modifies the evolution of HCV quasispecies among liver transplant recipients compared with immunocompetent HCV patients. Two groups were studied: 11 patients who underwent OLT for HCV-related cirrhosis and 10 control group patients. Two serum samples from each patient were obtained to analyze the HCV HVR1 region by RT-PCR. SSCP analysis failed to show statistically significant differences in the number of quasispecies at basal and final time points or at pretransplant versus posttransplant (7.3+/-2 vs 6.7+/-3 in control patients, respectively, and 4.4+/-2 vs 4.1+/-1 in transplanted patients, respectively). No significant difference was observed between missing or new variants in the control (2.8+/-2 vs 2.3+/-2, respectively) or transplanted group (2.5+/-2 vs 2.2+/-1, respectively). Upon sequence analysis, the genetic complexity was significantly lower among samples after OLT in transplanted patients (0.057+/-0.04 [pretransplant] vs 0.035+/-0.02 [posttransplant]; P=.048). However, no significant differences were found among control patients in basal versus final samples (0.04+/-0.03 vs 0.066+/-0.04, respectively). Our findings seem to demonstrate that viral quasispecies diversity is lower among patients receiving a liver transplant.

Cloning, Molecular↗
PubMed2003

Uranium and thorium series radionuclides in rainwater over several tropical storms.

The activity concentrations of uranium and thorium series radionuclides were measured in rainwater samples from 16 storms in northern Australia. For six of these storms, sequential intra-storm samples were collected. The results indicate that a substantial fraction of the measured activity concentrations of 238U, 234U, 230Th, 226Ra and, to a lesser extent, 210Po were due to below-cloud washout of dust transported from the nearby Ranger uranium mine. For the six intra-storm studies, the concentrations of these dust-related radionuclides decreased to one half or less of their initial value after the first one to two millimetres of rainfall, although in some cases they later increased when the rainfall intensity reduced. Most of the 210Pb activity appears to have been sourced from in-cloud rainout, although below-cloud washout was probably responsible for significant reductions in concentrations observed over the course of three of the six storms. 210Pb residence times based on the 210Pb-210Po couple varied significantly from storm to storm, but relatively little over the course of each of the six storms studied in detail. This implies that, apart from the initial reduction in below-cloud washout, there was no substantial change in the source air mass for the 210Pb during these storms.

Australia↗
PubMed2003

Disseminated melioidosis in two cats.

Melioidosis was diagnosed in two cats at necropsy. The first cat presented with jaundice and anaemia but died of overwhelming sepsis soon after admission, despite blood transfusion and other supportive measures. The second cat died several days after developing neurological signs; an infected digital wound may have been the primary focus of infection in this patient. The cats had presumably acquired the infection in Malaysia and northern Australia, respectively, and in both cases disease may have represented reactivation of a latent infection brought on by the stress of relocation. The epidemiology, clinical presentation, diagnosis and treatment of melioidosis are discussed from a feline perspective.

Animals↗
PubMed2003

Relationship between CsA trough blood concentration and severity of acute graft-versus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donors.

In order to determine optimal CsA trough blood concentrations (TBC) in the early post transplantation period, we analysed relationships between TBC and acute graft-versus-host disease (aGVHD) in paediatric SCT. A total of 94 children consecutively underwent allogeneic stem cell transplantation (SCT) from: matched-sibling (MSD) (n=36), mismatched-related (MMRD) (n=3) and unrelated donors (UD) (n=55). GVHD prophylaxis usually included CsA alone or with methotrexate. Antithymocyte globulin was added in UD-SCT. TBC during the first weeks of post transplantation were estimated retrospectively by a Bayesian pharmacokinetic method and statistically associated with aGVHD. In MSD-SCT, the mean TBC during the first 2 weeks post transplantation were 42+/-10 and 90+/-7 ng/ml, respectively, in patients with grade II-IV and 0-I aGVHD (P=0.001). In SCT from UD and MMRD, TBC were 73+/-4 vs 95+/-8 ng/ml (P=0.284). For TBC >85 ng/ml, no patient developed grade II-IV aGVHD, 10 developed mild aGVHD and 30 had no aGVHD. For TBC <65 ng/ml, 7/11 patients receiving an MSD-SCT and 4/18 receiving an UD- or MMRD-SCT developed grade II-IV aGVHD. The mean TBC corresponding to each grade were: no GVHD: 101+/-10 ng/ml, mild: 77+/-11 ng/ml, moderate: 61+/-13 ng/ml, severe: 56+/-15 ng/ml (P <0.001). These results reveal a strong relationship between TBC during the early post transplantation period and the severity of aGVHD in paediatric SCT.

Acute Disease↗
PubMed2003

Clinical and pharmacological risk factors for acute graft-versus-host disease after paediatric bone marrow transplantation from matched-sibling or unrelated donors.

The aim of this study was to identify the risk factors for acute graft-versus-host disease (aGVHD) in children transplanted from a matched-sibling donor (MSD) or an unrelated donor (UD). In all, 87 children consecutively underwent allogeneic bone marrow transplantation (BMT) from MSD (n=36), and UD (n=51). GVHD prophylaxis included CsA alone (n=33) or with MTX (n=51). ATG was added in UD-BMT and thalassemic recipients. CsA whole-blood concentrations were measured by EMIT and the dosing regimen was monitored by Bayesian pharmacokinetic modelling. Trough blood concentration (TBC) during the first 2 weeks post transplantation was lower in children who developed grade II-IV aGVHD than those developing no GVHD or only grade I (57+/-9 vs 94+/-8 ng/ml, P=0.007), whereas peak blood concentration and area under concentration curve vs time were similar in both groups. TBC <85 ng/ml and 'use of MTX' were associated with aGVHD in MSD-SCT (P=0.003 and 0.007, respectively) as well as in UD-SCT (P=0.006 and 0.003). Donor age >or=8 years was significant only in MSD-BMT. Our results have shown the significant decisive role of pharmacological factors such as CSA TBC or use of MTX in the occurrence of GVHD in MSD as well as in UD paediatric BMT.

Acute Disease↗
PubMed2003

Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients.

BACKGROUND: The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. METHODS AND AIMS: We evaluated the efficacy and safety of initial interferon monotherapy in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. RESULTS: We have identified 14 clinical trials (269 unique patients); two were controlled studies. The mean overall estimate for sustained virological response (SVR) and drop-out rate was 37%[95% confidence interval (CI) 28-48] and 17% (95% CI 10-28), respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms (17%), neurological (21%) and gastrointestinal (18%). The overall weighted estimate for SVR in patients with hepatitis C virus genotype 1 was 30.6% (95% CI 20.9-48). In the sub-group of clinical trials (n = 5) with standard interferon administration (3 million units [MUI] thrice weekly, subcutaneous route, 24-week treatment), the overall mean estimate of SVR was 39% (95% CI 25-56). The studies were heterogeneous with regard to SVR and drop-out rate. CONCLUSIONS: Tolerance to initial interferon monotherapy was lower in dialysis than nonuremic patients with chronic hepatitis C. However, more than one-third of haemodialysis patients with chronic hepatitis C have been successfully treated with interferon. Longer duration of interferon monotherapy does not appear to have a beneficial effect on the response rate. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in dialysis population.

Adult↗
PubMed2003

Experimentally revised repertoire of putative contingency loci in Neisseria meningitidis strain MC58: evidence for a novel mechanism of phase variation.

Analysis of the genome sequence of Neisseria meningitidis strain MC58 revealed 65 genes associated with simple sequence repeats. Experimental evidence of phase variation exists for only 14 of these 65 putatively phase variable genes. We investigated the phase variable potential of the remaining 51 genes. The repeat tract associated with 20 of these 51 genes was sequenced in 26 genetically distinct strains. This analysis provided circumstantial evidence for or against the phase variability of the candidate genes, based on the sequence and the length of the repeated motif. These predictions of phase variability were substantiated for three of these candidate genes using colony immunoblotting or beta-galactosidase as a reporter. This investigation identified a novel phase variable gene (NMB1994 or nadA) associated with a repeat tract (TAAA) not previously reported to be associated with phase variable genes in N. meningitidis. Analysis of the nadA transcript revealed that the repeat tract was located upstream of the putative -35 element of the nadA promoter. Semiquantitative RT-PCR showed that variation in the number of repeats was associated with changes in the level of expression of nadA, findings consistent with a model whereby the variable number of (TAAA) repeats modulates the promoter strength.

Antigens, Bacterial↗
PubMed2003

Man-made mineral fiber hazardous properties assessment using transgenic rodents: example of glass fiber testing.

Transgenic BigBlue rats were exposed to CM 44 glass fibers (6.3 mg/m3) by nose only, 6 h/day for 5 days. Two endpoints were examined 1, 3, 14, 28, and 90 days following exposure: fiber biopersistence and mutations in lung DNA. The half-time of the fibers >20 microm was 12.8 days, and mutant frequencies of control and exposed rats were similar across all time points. The mutation spectra of both series were similar after 28 days of fixation time. These results showed that a glass fiber with a high clearance in the lung seems to not present any significant effect on mutagenesis on lung DNA and are in marked contrast to results for asbestos, which caused a twofold mutant frequency increase as described in a previous study.

Animals↗