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J Marsh

Publications and source records attributed to J Marsh.

At least 37 records · Page 2Linked to original sources
PubMed2000

An analysis of the effect of chronic GvHD on relapse and survival following allogeneic PBSC transplantation.

BACKGROUND: PBSC are increasingly being used as the source of stem cells in allogeneic transplantation. An increased incidence of chronic GvHD has been suggested following unmanipulated allogeneic PBSC transplantation (PBSCT), however, how this affects overall survival is not yet clear. Our aim was to study the impact of chronic GvHD on survival and relapse following allogeneic PBSCT. METHODS: We have analyzed data from 73 patients undergoing HLA-matched allogeneic PBSCT. GvHD prophylaxis was with CYA and MTX in 97% of patients. We have studied the incidence of chronic GvHD and its affect on relapse and survival in these patients. All patients were at least 100 days post-transplant at the time of analysis. RESULTS: Seventy-three patients were evaluable for analysis of chronic GvHD. The overall incidence of chronic GvHD was 55% (limited in 18% and extensive in 37%). Overall median survival was 991 days, with a 4 year survival rate of 48%. Twelve patients relapsed. Patients with chronic GvHD had a significantly lower incidence of disease relapse (p = 0.005) with a relapse probability of 8% at 3 years, compared with 40% in patients with no chronic GvHD. In addition, the extent of chronic GvHD had a marked effect on survival, patients with limited chronic GvHD had a 4 year survival rate of 83%, compared with 45% in patients with extensive chronic GvHD and 38% in patients with no chronic GvHD. This difference was primarily due to the low incidence of relapse and low mortality seen in patients with limited chronic GvHD. DISCUSSION: The presence and extent of chronic GvHD is an important predictor of outcome following allogeneic PBSCT, in that patients who developed either limited or extensive chronic GvHD had a low risk of disease relapse.

Adolescent↗
PubMed2000

Evaluation of the Applied Biosystems automated Taqman polymerase chain reaction system for the detection of meningococcal DNA.

In a period where the proportion of culture confirmed cases in the UK has been steadily declining, diagnosis by PCR has been used to increase the number of confirmed cases and provide additional epidemiological data. This report presents a comparative evaluation of the fluorogenic probe-based 5' exonuclease assay (Taqman) using the Perkin-Elmer Applied Biosystems automated sequence detection system 7700 with previously reported polymerase chain reaction enzyme-linked immunosorbent (PCR ELISA) assays for the detection of meningococcal DNA in CSF, plasma and serum samples. Taqman assays developed were based on the detection of a meningococcal capsular transfer gene (ctrA), the insertion sequence IS1106 and the sialytransferase gene (siaD) for serogroup B and C determination and compared with similar assays in a PCR ELISA format. The Taqman ctrA assay was specific for Neisseria meningitidis, however the IS1106 assay gave false positive reactions with a number of non-meningococcal isolates. Sensitivity of the Taqman ctrA, IS1106 and siaD assays testing samples from culture-confirmed cases were 64, 69 and 50%, respectively, compared with 26, 67 and 43% for the corresponding PCR ELISA assays. Improvements to the DNA extraction procedure has increased the sensitivity to 93 and 91% for the TaqMan ctrA and siaD assays, respectively, compared to culture confirmed cases. Since the introduction of Taqman PCR a 56% increase in laboratory confirmed cases of meningococcal disease has been observed compared to culture only confirmed cases. The developed Taqman assays for the diagnosis of meningococcal disease enables a high throughput, rapid turnaround of samples with considerable reduced risk of contamination.

Bacterial Proteins↗
PubMed2000

Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation.

We have analyzed 2,002 patients grafted in Europe between 1976 and 1998 from an identical twin (n = 34), from an HLA-identical sibling (n = 1,699) or from an alternative donor (n = 269), which included unrelated and family mismatched donors. The proportions of patients surviving in these three groups are, respectively, 91, 66 and 37%: major causes of failure were acute graft-versus host disease (GvHD) (11%), infection (12%), pneumonitis (4%), rejection (4%). In multivariate Cox analysis, factors predicting outcome were patient's age (p < 0.0001), donor type (p < 0.0001), interval between diagnosis and bone marrow transplantation (BMT) (p < 0.0005), year of BMT (p = 0.0005) and female donor for a male recipient (p = 0.02). Patients were then divided in two groups according to the year of BMT: up to or after 1990. The overall death rate dropped from 43 to 24% (p < 0.00001). Improvements were seen mostly for grafts from identical siblings (from 54 to 75%, p < 0.0001), and less so for alternative-donor grafts (from 28 to 35%; p = 0.07). Major changes have occurred in the BMT protocol: decreasing use of radiotherapy in the conditioning regimen (from 35 to 24%; p < 0.0001) and increasing use of cyclosporin (with or without methotrexate) for GvHD prophylaxis (from 70 to 98%; p < 0.0001). In conclusion, the outcome of allogeneic BMT for patients with severe aplastic anemia has considerably improved over the past two decades: young patients, grafted early after diagnosis from an identical sibling, have currently an over 80% chance of long-term survival. Transplants from twins are very successful as well. The risk of complications with alternative donor transplants is still high.

Acute Disease↗
PubMed2000

Intravenous cereport (RMP-7) modifies topographic uptake profile of carboplatin within rat glioma and brain surrounding tumor, elevates platinum levels, and enhances survival.

Several experiments studied the effects of i.v. infusions of the bradykinin agonist, Cereport (RMP-7), on permeability of the blood-brain tumor barrier in rat gliomas. First, the ability of Cereport to increase uptake of two poorly blood-brain barrier-penetrating drugs (lypophilic paclitaxel and hydrophilic carboplatin) was directly compared to provide new information regarding the scope of delivery effects achieved with Cereport. Next, the increased uptake of platinum into tumor and brain surrounding tumor was shown to closely parallel that of radiolabeled carboplatin, confirming that delivery of a biologically active moiety is increased with Cereport. This study also demonstrated that the elevated tumor levels of platinum persisted for at least 2 h. The enhanced carboplatin uptake was then examined using a novel, high spatial resolution analysis of autoradiography. This revealed that the effects of Cereport were not uniform throughout the tumor, because it especially modified those areas normally impermeable to carboplatin. Finally, a range of i.v. Cereport doses (3.0 and 9.0 microg/kg) was tested in combination with carboplatin to determine whether increased survival might be achieved and to define the relationship between Cereport dose, plasma levels, uptake of carboplatin, and enhanced survival. Survival was enhanced only by the high dose of Cereport; the high dose also produced robust increases in carboplatin uptake and plasma concentrations of Cereport estimated to achieve the K(i), whereas the low dose did not. These data offer fundamental information regarding the effects of Cereport on delivery of chemotherapeutic agents to brain tumors and provide new insight into receptor-mediated permeability of the blood-brain tumor barrier.

Animals↗
PubMed2000

Consensus Conference on the Treatment of Aplastic Anemia.

This article presents guidelines for the diagnosis and treatment of aplastic anemia (AA) established by a consensus panel of investigators from various countries. The panel used the scientific evidence presented during the Consensus Conference forum and found in the scientific literature to prepare guidelines categorized as immunosuppressive therapy, unrelated bone marrow transplantation in patients with AA, and myelodysplasia/acute myeloid leukemia after immunosuppressive therapy.

Anemia, Aplastic↗
PubMed1999

Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party.

We report the results of the first prospective randomized multicenter study of immunosuppressive treatment in patients with previously untreated nonsevere aplastic anemia (AA) as defined by a neutrophil count of at least 0.5 x 10(9)/L and transfusion dependence. Patients were randomized to receive cyclosporin (CSA) alone or the combination of horse antithymocyte globulin ([ATG] Lymphoglobuline; Merieux, Lyon, France) and CSA. The endpoint of the study was the hematologic response at 6 months. One hundred fifteen patients were randomized and assessable with a median follow-up period of 36 months; 61 received CSA and 54 ATG and CSA. In the CSA group, the percentage of complete and partial responders was 23% and 23%, respectively, for an overall response rate of 46%. A significantly higher overall response rate of 74% was found in the ATG and CSA group, with 57% complete and 17% partial responders (P =. 02). Compared with CSA alone, the combination of ATG and CSA resulted in a significantly higher median hemoglobin level and platelet count at 6 months. Fewer patients required a second course of treatment before 6 months due to a nonresponse. In the CSA group, 15 of 61 (25%) patients required a course of ATG before 6 months because of disease progression, compared with only 3 of 54 (6%) in the ATG and CSA group. The survival probabilities for the two groups were comparable, 93% (CSA group) and 91% (ATG and CSA group), but at 180 days, the prevalence of patients surviving free of transfusions, which excluded patients requiring second treatment because of nonresponse, death, disease progression, or relapse, was 67% in the CSA group and 90% in the ATG and CSA group (P =.001). We conclude that the combination of ATG and CSA is superior to CSA alone in terms of the hematologic response, the quality of response, and early mortality, and a second course of immunosuppression is less frequently required.

Adolescent↗
PubMed1999

Effectiveness of immunosuppressive therapy in older patients with aplastic anemia. European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party.

BACKGROUND: Immunosuppressive therapy has been used for successful treatment of severe aplastic anemia, but little information is available on outcome in older patients. OBJECTIVE: To evaluate outcome in patients older than 50 years of age who received immunosuppressive therapy for aplastic anemia. DESIGN: Retrospective cohort study. SETTING: 56 centers of the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS: 810 patients with aplastic anemia reported between 1974 and 1997. Patients were evaluated according to age group: 60 years of age or older (n = 127), 50 to 59 years of age (n = 115), and 20 to 49 years of age (n = 568; reference group). INTERVENTION: Antilymphocyte globulin, cyclosporine, or both. MEASUREMENTS: Survival, cause of death, response to treatment, relapse rate, and risk for late complications were analyzed in all patients and by age group. RESULTS: The 5-year survival rate was 57% (95% CI, 46% to 66%) in patients 50 to 59 years of age and 50% (CI, 39% to 60%) in patients 60 years of age or older compared with 72% (CI, 68% to 76%) in patients younger than 50 years of age (P < 0.001). Response to therapy, relapse rate, and risk for clonal complications were similar in all three age groups (P > 0.2). Age was significantly associated with an increased risk for death (relative risk compared with patients 20 to 49 years of age, 1.80 [CI, 1.29 to 2.52] for patients 50 to 59 years of age and 2.57 [CI, 1.87 to 3.53] for patients > or = 60 years of age), mainly because of bleeding or infection (P = 0.02). Response to immunosuppressive therapy in all patients at 12 months was 62% (CI, 58% to 66%); no difference was seen among the age groups in multivariate analysis (P > 0.2). Sixty-six of the 379 responding patients (17%) subsequently had relapse. The risk for clonal disorders at 10 years was 20% (CI, 15% to 27%). CONCLUSIONS: Response to immunosuppression in aplastic anemia is independent of age, but treatment is associated with increased mortality in older patients.

Adult↗
PubMed1999

CD44 expression in cervical intraepithelial neoplasia (CIN) and carcinoma.

BACKGROUND: The expression of the CD44 gene is markedly changed in many neoplastic tissues. The identification of tumor-specific CD44 expression patterns may aid tumor diagnosis. METHODS AND RESULTS: The transcription and translation of the CD44 gene were analyzed by reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and by immunohistochemistry. Samples were obtained from 24 normal and 24 neoplastic or malignant human cervical tissues. Southern blot hybridization analysis of RT-PCR products revealed an increase in the size and number of CD44 standard and variant transcripts in malignant cervical tissues compared with corresponding normal tissues. Misprocessing of mRNA was indicated in cervical carcinoma cells by the retention of intronic sequences. Multiple CD44 mRNA and protein isoforms were present throughout carcinoma tissues, whereas localization was restricted to the basal epithelium in normal cervical tissue. Analysis of desquamated cervical cells from cases of cervical intraepithelial neoplasia stages I-III showed progressively deranged patterns of CD44 expression, with more alterations being detected in the more advanced stages. CONCLUSIONS: Marked alterations in CD44 expression occur in cervical tissues during progression to malignancy. CD44 expression analysis could aid the early diagnosis of cervical malignancy using minimally invasive methods.

Antigens, Neoplasm↗
PubMed1999

Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene.

Fanconi anaemia (FA) is a genetically heterogeneous autosomal recessive disorder associated with chromosomal fragility, bone-marrow failure, congenital abnormalities and cancer. The gene for complementation group A (FAA), which accounts for 60-65% of all cases, has been cloned, and is composed of an open reading frame of 4.3 kb, which is distributed among 43 exons. We have investigated the molecular pathology of FA by screening the FAA gene for mutations in a panel of 90 patients identified by the European FA research group, EUFAR. A highly heterogeneous spectrum of mutations was identified, with 31 different mutations being detected in 34 patients. The mutations were scattered throughout the gene, and most are likely to result in the absence of the FAA protein. A surprisingly high frequency of intragenic deletions was detected, which removed between 1 and 30 exons from the gene. Most microdeletions and insertions occurred at homopolymeric tracts or direct repeats within the coding sequence. These features have not been observed in the other FA gene which has been cloned to date (FAC) and may be indicative of a higher mutation rate in FAA. This would explain why FA group A is much more common than the other complementation groups. The heterogeneity of the mutation spectrum and the frequency of intragenic deletions present a considerable challenge for the molecular diagnosis of FA. A scan of the entire coding sequence of the FAA gene may be required to detect the causative mutations, and scanning protocols will have to include methods which will detect the deletions in compound heterozygotes.

Base Sequence↗
PubMed1999

Bone marrow transplants for paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare clonal haematological disorder characterized by intravascular haemolysis and increased risk of thrombosis. PNH is associated with bone marrow failure syndromes including aplastic anaemia, myelodysplasia and leukaemia. Bone marrow transplants are sometimes used to treat PNH, but small series and reporting biases make assessment of transplant outcome difficult. The outcome of 57 consecutive allogeneic bone marrow transplants for PNH reported to the International Bone Marrow Transplant Registry (IBMTR) between 1978 and 1995 was analysed. The 2-year probability of survival in 48 recipients of HLA-identical sibling transplants was 56% (95% confidence interval 49-63%). Two recipients of identical twin transplants remain alive 8 and 12 years after treatment. One of seven recipients of alternative donor allogeneic transplants is alive 5 years after transplant. The most common causes of treatment failure were graft failure and infections. Our results indicate that bone marrow transplantation can restore normal bone marrow function in about 50% of PNH patients.

Adolescent↗
PubMed1999

Sphincter pharyngoplasty for the surgical management of speech dysfunction associated with velocardiofacial syndrome.

There are no reports in the literature that document the effectiveness of sphincter pharyngoplasty as a surgical alternative to pharyngeal flap for management of velopharyngeal dysfunction in patients with velocardiofacial syndrome. A retrospective review of patients with velocardiofacial syndrome was undertaken at our tertiary cleft care centre. All patients were managed between 1984 and 1996 at the Cleft Palate and Craniofacial Deformities Institute, St Louis Children's Hospital. Subjects (n = 19) underwent velopharyngeal surgical management on the basis of perceptual speech evaluations and instrumental assessments of inadequate velopharyngeal closure. All patients had a molecular diagnosis of velocardiofacial syndrome based on fluorescent in situ hybridisation analysis of peripheral blood lymphocytes and independent evaluation by a medical geneticist. Surgical outcome was classified as successful if perceptual speech assessment indicated elimination of hypernasality, nasal emission and turbulence, and instrumental assessment indicated 100% velopharyngeal closure. Results showed that 18 of 19 patients were managed successfully with sphincter pharyngoplasty. Our data corroborate that sphincter pharyngoplasty is a reasonable alternative to pharyngeal flap in patients with velopharyngeal dysfunction secondary to velocardiofacial syndrome.

Adolescent↗
PubMed1999

Effect of renal impairment on the pharmacokinetics of intravenous zanamivir.

OBJECTIVE: Zanamivir is eliminated almost exclusively by renal excretion. This study evaluated the effect of renal impairment on the pharmacokinetics of intravenous zanamivir. DESIGN: This open-label study compared individuals with mild/moderate or severe renal impairment, as defined by creatinine clearance (CLCR), with healthy participants. STUDY PARTICIPANTS: There were 17 participants (9 men and 8 women), of whom 7 had normal renal function (CLCR > 70 ml/min), 5 had mild/moderate renal impairment (CLCR 25 to 70 ml/min) and 5 had severe renal impairment (CLCR < 25 ml/min). INTERVENTIONS: Single 4 mg doses of zanamivir were administered intravenously to healthy participants and those with mild/moderate renal impairment; participants with severe renal impairment received 2 mg. Zanamivir concentrations were determined in blood and urine. Safety was evaluated by monitoring adverse events, vital signs and laboratory parameters. RESULTS: Zanamivir was well tolerated both in participants with renal impairment and in healthy volunteers. There were no clinically significant changes attributable to zanamivir treatment. Renal dysfunction had marked effects on the pharmacokinetics of zanamivir. Although no statistically significant differences were detected between either renal impairment group and the normal renal function group for the maximum serum concentration (Cmax) or the time this occurred (tmax), a strong relationship was detected between CLCR and total body clearance (CL), renal clearance (CLR) and the terminal phase elimination rate constant (lambda z). Each 2-fold increase in CLCR produced average increases of 100, 121 and 85% in CL, CLR and lambda z, respectively. The area under the serum concentration-time curve from zero to infinity (AUC infinity) was on average increased 2-fold in individuals with mild/moderate renal impairment (4 mg dose) and 3.5-fold in those with severe impairment (2 mg dose) compared with healthy individuals (4 mg dose). CONCLUSIONS: The proposed total daily dosage of zanamivir by oral inhalation is 20 mg. Given the tolerability (observed in a separate study to be reported in this supplement) after daily intravenous dosages of 1200 mg, and the limited systemic absorption after oral inhalation, the increased drug exposure in patients with severe renal failure is not considered clinically significant. Furthermore, the local concentrations in the lung following oral inhaled delivery are essential for efficacy. Therefore, for orally inhaled zanamivir, no dosage adjustment is required in patients with renal impairment.

Adult↗
PubMed1999

Multicenter clinical and analytical evaluation of the AxSYM troponin-I immunoassay to assist in the diagnosis of myocardial infarction.

We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the detection of acute myocardial infarction (AMI). At four sites, the total imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI) - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39-3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy individuals was </=0.5 microgram/L, whereas the ROC curve-determined cutoff for AMI was 2.0 microgram/L. This gave a diagnostic sensitivity of 91.8% and specificity of 92.4% when tested in serial samples collected within 24 h of admission in 633 patients presenting with chest pain, of which 122 had an AMI. The concordances of the AxSYM cTnI with the Stratus cTnI, OPUS cTnI, and Access cTnI were 95.3%, 95.1%, and 94.3%, respectively, from patients with suspected AMI. The AxSYM cTnI demonstrated excellent clinical specificity, >/=96%, in skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery patients.

Evaluation Studies as Topic↗
PubMed1998

Differential sensitivities to risperidone and olanzapine in a human immunodeficiency virus patient.

BACKGROUND: Neuroleptic sensitivity presents a considerable problem for the treatment of psychosis in the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive patient population. As yet, there are few data on the response of these patients to newer atypical antipsychotic medications. METHODS: We present the detailed medication history of a 33-year-old man with AIDS, who had a prior history of extrapyramidal symptoms (EPS) with both typical antipsychotics and risperidone, and was treated with olanzapine for major depression with psychotic features. RESULTS: The patient developed akathisia in a dose-dependent manner at dosages between 10 and 15 mg daily of olanzapine, but no EPS. Akathisia responded to dose reduction and use of beta-adrenergic blockade. CONCLUSIONS: The AIDS patient may exhibit sensitivity even to newer atypical antipsychotics. The lack of EPS and response to a beta-blocker underscore the different mechanisms causing akathisia and EPS.

Adult↗
PubMed1998

T-cell lymphoma associated with natural killer-like T-cell reaction.

We report a case of T-cell lymphoma showing in the peripheral blood (PB) exclusively T-lymphocytes with suppresser T-cell preponderance and a high percentage of natural killer (NK) marker positive cells by flow cytometry. A T-cell receptor (TCR) gene analysis of the PB leukocytes demonstrated rearrangements of TCRalpha, TCRbeta, and TCRgamma genes. Therefore, the phenotype and genotype appeared to be consistent with an NK-like T-cell leukemia/lymphoma. However, when the PB lymphocytes were separated by size, it was found that 80% of NK marker positive cells were in the smaller cell population, while the neoplastic cells were in the large cell gate. A diagnosis of T-cell lymphoma with reactive NK-like T-cells was finally confirmed by demonstrating the presence of both large atypical lymphoid cells and large granular lymphocytes (LGL) on PB smears. Although immunoperoxidase stain of bone marrow and colon showed positive T-cell markers in the tumor cell population, cytoplasmic granules could not be identified in tissue sections and, thus, a distinction between T-cell lymphoma and NK-like T-cell lymphoma could not be made by light microscopy until NK markers were studied. CD57 was demonstrated immunohistochemically in small lymphocytes but not in the large tumor cells in the colon. Electron microscopy, however, demonstrated LGL reaction to the lymphoma cells in the colonic biopsy. NK-like T-cell lymphoma usually carries a poorer prognosis than peripheral T-cell lymphoma, thus the distinction of these neoplasms is important. This study emphasizes that T-cell lymphoma may cause an LGL reaction or proliferation. If the lymphoma cells were of the same size as LGL, flow cytometric studies may have misled the diagnosis to NK-like T-cell-lymphoma.

Aged↗
PubMed1998

Can patients predict which consultations can be dealt with by telephone?

The use of telephone consultations to reduce the workload of general practitioners is well established both in this country and abroad. The principal aim of this study was to discover the proportion of consultations currently carried out in the surgery that would be suitable, for both doctor and patient, to be managed over the telephone. The second aim was to establish what proportion of such consultations could be predicted.

England↗