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Biomedical subjects

J Curtis

Publications and source records attributed to J Curtis.

At least 19 recordsLinked to original sources
PubMed2006

Long-term safety and efficacy after conversion of maintenance renal transplant recipients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPA, myfortic).

AIM: A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium (EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population. METHODS: All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented. RESULTS: Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups. CONCLUSIONS: These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.

Adult↗
PubMed2005

Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study.

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.

Adult↗
PubMed2005

Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course.

Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant.

Bacteremia↗
PubMed2005

Dendritic cells in autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma: graft content and post transplant recovery predict survival.

Allograft dendritic cell (DC) content has been identified as a predictor of relapse and event-free survival after allogeneic bone marrow transplantation. However, the prognostic importance of DCs has not been evaluated in the setting of autologous hematopoietic stem cell transplantation (HSCT). We prospectively determined pre-transplant and post transplant DC levels, including DC1 and DC2 subset levels, in 53 patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBC NHL) undergoing autologous HSCT. Pre-transplant DCs were measured in the collected stem cell products and were therefore indicative of cell numbers infused directly into patients; post transplant analysis of DCs was performed on the peripheral blood of patients 6 weeks after the infusion of autologous stem cells. Higher pre-transplant levels of DC1 cells and total DCs were significantly associated with improved survival. Similarly, greater post transplant levels of total DCs and both subsets were significantly associated with survival. These findings suggest a relationship between DC reconstitution and survival following autologous HSCT for DLBC NHL. Strategies to increase autograft DC content or accelerate DC recovery after autologous HSCT might improve outcomes in this setting.

Adult↗
PubMed2005

Nurse case manager effectiveness and case load in a large clinical practice: implications for workforce development.

AIMS: Description of nurse case management experiences across different settings and patient populations is needed to define critical elements of the intervention and to help develop a workforce capable of responding to the growing diabetic population. METHODS: In a clinic providing services to American Indian and Alaska Native people, a retrospective cohort design was used to assess outcomes of patients who did and did not receive case management services and to quantify the case load of a team of four nurse case managers. RESULTS: Patients with nurse case managers were more likely to have an eye examination [OR 2.9, 95% CI (2.1, 3.8)], diet and exercise instruction by a registered dietitian [OR 2.8, 95% CI (1.9, 4.1)], self monitor blood glucose [OR 2.1, 95% CI (1.5, 3.1)], dental examination [OR 1.7, 95% CI (1.3, 2.3)], foot examination [OR 1.6, 95% CI (1.2, 2.1)], and nephropathy screening [OR 1.6, 95% CI (1.2, 2.1)]. After adjustment for type of treatment, initial HbA(1c), and diet instruction by a registered dietitian, the change in HbA(1c) remained significantly greater among those patients with a case manager than in those without (-0.52 units with vs. -0.17 units without, P < 0.006). The case load used to achieve this outcome averaged one nurse case manager per 365 patients. CONCLUSIONS: In this setting, a case management team comprised of four nurses with varying degrees of clinical experience was effective in improving adherence with diabetes services and had a favourable effect on short-term glucose control trends.

Adult↗
PubMed2004

A comparison of microsatellite polymorphism and heterozygosity among field and laboratory populations of Schistosoma mansoni.

The genetic diversity of a field population (recently collected in Melquiades, Brazil) and two laboratory strains (LE and NMRI) of a human blood fluke, Schistosoma mansoni, were analysed using microsatellite markers. Data from the three groups showed an extreme and consistent discrepancy in the level of polymorphism at all microsatellite loci between the field population and laboratory populations. The numbers of alleles detected in LE and NMRI populations averaged only 14 and 10% of those found in the field population, respectively. Especially apparent was the abundance of rare alleles in the Melquiades population when compared with the laboratory strains. The reduction in allelic diversity in the laboratory strains is most likely due to the founder effect and potential bottlenecks that may have occurred during decades of laboratory maintenance. Surprisingly, a much less drastic difference was found when comparing the average heterozygosity of the field population with the laboratory strains. This apparent anomaly may be explained by observed population substructuring (and a potential resultant Wahlund effect) in the natural population. Our comparison of genetic diversity between laboratory and field populations of S. mansoni emphasizes the need for studies of representative populations in schistosome vaccine development.

Alleles↗
PubMed2004

Cutaneous leishmaniasis in red kangaroos: isolation and characterisation of the causative organisms.

This is the first report of cutaneous leishmaniasis in kangaroos where infection was acquired within Australia. The diagnosis is based on the clinical criteria used for humans, the lesion histopathology, the detection and isolation of parasites from the lesions, and the analysis of the small subunit ribosomal RNA genes using the polymerase chain reaction. Despite a clear indication that the parasites belong to the genus Leishmania, no assignation to a known Leishmania species could be made using these or other less conserved genetic loci such as the non-transcribed spacer of the mini-exon repeat. As is the case in humans, some but not all animals harbouring lesions had antibodies to the isolated parasites or to several other Leishmania species. The isolated parasites displayed two well characterised Leishmania glycoconjugates, the lipophosphoglycan and proteophosphoglycan. They were infectious for mouse macrophages in vitro and established long-term infection at 33 degrees C but not at 37 degrees C. Our findings raise the possibility of transmission to humans, which may be unrecognised and suggest the possibility that imported species of Leishmania could become endemic in Australia.

Animals↗
PubMed2004

Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined.

Bone Marrow Transplantation↗
PubMed2002

Mutations in dhfr in Plasmodium falciparum infections selected by chlorproguanil-dapsone treatment.

Treatment with the novel antifolate drug combination chlorproguanil-dapsone effectively cleared asymptomatic Plasmodium falciparum infections in 246 (93.5%) of 263 children in the Usambara Mountains of Tanzania during the course of a 2-week follow-up. Samples from 71 recurrent infections, collected over a 9-week follow-up, showed selection for parasites with the triple mutant Ile(51)-Arg(59)-Asn(108) in dihydrofolate reductase. There was no selection for mutations in dihydropteroate synthetase, the target enzyme of dapsone. Search for complete identity in the highly polymorphic genes coding for merozoite surface proteins 1 and 2 in parasite samples collected before and after treatment indicated that the majority of recurrent parasitemias were new infections. These observations on selection in Tanzania and the lack of selection reported from a less endemic area suggest that the active metabolite of chlorproguanil, which has a short half-life in the blood, may persist in the liver, where it exerts selective pressure on growing preerythrocytic stages.

Animals↗
PubMed2002

Schistosome genetic diversity: the implications of population structure as detected with microsatellite markers.

Blood flukes in the genus Schistosoma are important human parasites in tropical regions. A substantial amount of genetic diversity has been described in populations of these parasites using molecular markers. We first consider the extent of genetic variation found in Schistosoma mansoni and some factors that may be contributing to this variation. Recently, though, attempts have been made to analyze not only the genetic diversity but how that diversity is partitioned within natural populations of schistosomes. Studies with non-allelic molecular markers (e.g. RAPDs and mtVNTRs) have indicated that schistosome populations exhibit varying levels of gene flow among component subpopulations. The recent characterization of microsatellite markers for S. mansoni provided an opportunity to study schistosome population structure within a population of schistosomes from a single Brazilian village using allelic markers. Whereas the detection of population structure depends strongly on the type of analysis with a mitochondrial marker, analyses with a set of seven microsatellite loci consistently revealed moderate genetic differentiation when village boroughs were used to define parasite subpopulations and greater subdivision when human hosts defined subpopulations. Finally, we discuss the implications that such strong population structure might have on schistosome epidemiology.

Animals↗
PubMed2002

Pulmonary arteriovenous malformations: effect of embolization on right-to-left shunt, hypoxemia, and exercise tolerance in 66 patients.

OBJECTIVE: This study assessed the effect and safety of percutaneous transcatheter coil embolization of pulmonary arteriovenous malformations. MATERIALS AND METHODS: In 58 (88%) of 66 patients, all malformations with feeding vessels greater than or equal to 3 mm in diameter were embolized with steel coils. Arterial oxygen saturation at rest and exercise, intrapulmonary right-to-left anatomic shunt fraction ((99m)Tc-macroaggregate injection), maximum exercise capacity (incremental work rate test), and pulmonary function were measured before and after embolization. Complications were analyzed. RESULTS: Three categories of patients were identified. Patients in group 1 (27%) had complete occlusion of all angiographically visible pulmonary arteriovenous malformations; patients in group 2 (61%) had complete occlusion of all malformations with feeding vessels greater than or equal to 3 mm in diameter, but with smaller lesions persisting; and patients in group 3 (12%) had incomplete embolization, with feeding vessels greater than or equal to 3 mm in diameter remaining. The mean right-to-left shunt after embolization was least in group 1 (7%), intermediate in group 2 (10%), and greatest in group 3 (19%). Arterial oxygen saturation and right-to-left shunt fraction returned to normal levels (>96% and <3.5%, respectively) in 33% of patients. A significant improvement occurred after embolization in carbon monoxide diffusing capacity per unit of alveolar volume and in exercise capacity in 16 and 10 patients, respectively. In 93 procedures, 12 complications (13%) occurred. CONCLUSION: Coil embolization of pulmonary arteriovenous malformations is effective in reducing right-to-left anatomic shunt fraction and in improving arterial oxygenation. Coil embolization of pulmonary arteriovenous malformations is well tolerated and has a low complication rate.

Adolescent↗
PubMed2001

Molecular and immunological characterisation of the glucose regulated protein 78 of Leishmania donovani(1).

To identify novel potential Leishmania vaccine antigens, antibodies from patients with visceral leishmaniasis (VL) were used to isolate clones from a cDNA expression library of L. donovani amastigotes. Glucose Regulated Protein (GRP78), a member of the 70 kDa heat-shock protein family was identified and characterised. The GRP78 gene was localised to chromosome 15 in L. donovani, L. major, and L. mexicana by pulse-field gel electrophoresis. The Leishmania GRP78 protein contain a carboxy-terminal endoplasmic reticulum retention signal sequence (MDDL) as does the Trypanosoma cruzi GRP78. Immunofluorescence using antibodies to the recombinant DNA-derived GRP78 protein showed staining localised to reticular material throughout the cytoplasm and in the perinuclear region of promastigotes, suggesting that the protein is localised in the endoplasmic reticulum. The protective efficacy of GRP78 was assessed in mice vaccine experiments. A GRP78 DNA vaccine primed for an immune response that protected C57Bl/6 and C3H/He mice against infection with L. major. Similarly vaccination with a recombinant form of GRP78 purified from Escherichia coli and administered with Freund's as adjuvant induced protective immunity in C57Bl/6 mice.

Amino Acid Sequence↗
PubMed2001

Impact of problem-based learning on residents' self-directed learning.

OBJECTIVE: To examine the effect of a problem-based learning (PBL) curriculum on self-directed learning behaviors among a group of pediatric residents. METHODS: A controlled comparison study was conducted with 80 pediatric residents at a large urban academic medical center. Residents were observed over 3 distinct but consecutive periods. First, all residents participated in a 3-month-long daily lecture series (pre-exposure phase). Then, for another 3 months, 39 residents (PBL group) were exposed to twice-weekly PBL sessions while 41 residents continued with the daily lectures (lecture-based group) and served as controls. Problem-based learning was withdrawn after 3 months and all residents returned to the lecture series (follow-up phase). Residents' self-directed learning behaviors were assessed through self-administered questionnaires during the pre-exposure, exposure, and follow-up phases. RESULTS: There were no significant preexposure differences in self-directed learning behaviors between the groups. During the exposure phase, the PBL group had significantly higher self-directed learning: 5 or more hours of independent study (26% vs 7%) [corrected] (P=.001); 5 or more hours of medical discussions (28% vs 4%) (P=.008); 2 or more computer literature searches (51% vs 30%) (P=.005); and total hours of self-study per week (6 vs 4 hours) (P<.05). At the 3-month follow-up, the PBL group had returned to baseline levels of self-directed learning and there were no significant differences between the groups. CONCLUSION: Residents exposed to PBL engaged in significantly higher levels of self-directed learning than their counterparts.

Adult↗
PubMed2001

The influence of drug treatment on the maintenance of schistosome genetic diversity.

Drug treatment of patients with schistosomiasis may select for drug-resistant parasites. In this article, we formulate a deterministic model with multiple strains of schistosomes (helminth parasites with a two-host life cycles) in order to explore the role of drug treatment in the maintenance of a polymorphism of parasite strains that differ in their resistance levels. The basic reproductive numbers for all strains are computed, and are shown to determine the stabilities of equilibria of the model and consequently the distribution of parasite phenotypes with different levels of drug tolerance. Analysis of our model shows that the likelihood that resistant strains will increase in frequency depends on the interplay between their relative fitness, the cost of resistance, and the degree of selection pressure exerted by the drug treatments.

Animals↗
PubMed2001

Beneath the surface: collaboration in alcohol and other drug treatment. An analysis using Foucault's three modes of objectification.

AIM OF STUDY: This study investigated the perceptions of alcohol and other drug (AOD) clinicians and consumers regarding the concepts of collaboration and empowerment. BACKGROUND/RATIONALE: Working collaboratively is seen as a cornerstone of empowerment, a concept used extensively over the last decade in an attempt to isolate power and control issues. It is generally assumed that health professionals strive to achieve collaboration, but little research has been undertaken. DESIGN/METHODS: The study was carried out in a variety of AOD treatment facilities in a large regional city in Australia. Facilities included an inpatient detoxification unit, an outpatients' clinic, a methadone maintenance clinic, a residential detoxification and rehabilitation unit using a 12-step treatment model and a residential unit using cognitive behavioural therapy (CBT). The nonprobability sample consisted of 57 staff and consumers who were interviewed using a semi-structured format. Data were analysed thematically using a Foucauldian analysis of discourse. RESEARCH FINDINGS: Findings suggest that clinicians may be unwittingly imposing their beliefs and prejudices on consumers and in fact disempowering the very people they want to empower. Collaboration is not happening. Foucault's theory of objectification illuminates the processes involved. CONCLUSIONS: There is much more happening than originally thought between consumers and staff when Foucault's three modes of objectification are used to examine this practice area. Analysing discourse enables us to see how health workers interact with consumers and the effect this may have on treatment objectives, outcomes and self-esteem. It also illuminates the work environment where the therapeutic encounter takes place. The need for further effort in empowering both consumers and staff and working collaboratively becomes evident.

Adult↗