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Biomedical subjects

John Horvath

Publications and source records attributed to John Horvath.

6 recordsLinked to original sources
PubMed2004

Potential clinical implications of substitution of generic cyclosporine formulations for cyclosporine microemulsion (Neoral) in transplant recipients.

Cyclosporine (CsA) is a critical-dose drug for which a minor change in absorption can have important clinical implications. Generic formulations of CsA are becoming more widely available, but standard criteria for bioequivalence require only that a single study in healthy volunteers demonstrate that mean pharmacokinetic parameters fall within 80-125% of the mean values for Neoral, the reference formulation of CsA. However, CsA absorption is known to differ between healthy volunteers and transplant patients and between different types of transplant patients, such that standard bioequivalence testing may be inadequate to ensure interchangeability of CsA formulations in all patients. The limited available clinical evidence has shown that stable renal transplant patients receiving Neoral have a significant reduction in mean CsA trough level after transfer to the Cicloral formulation. Mean pharmacokinetic values have been reported as equivalent following transfer to Gengraft in one study, but mean CsA trough fell and mean serum creatinine rose significantly in a separate trial. The only clinical outcomes data available are from a retrospective study of de novo renal transplant patients, which reported a significantly higher incidence of biopsy-proven acute rejection in patents receiving Gengraf versus Neoral (39% versus 25%, P<0.05). Until robust clinical data demonstrate that different formulations of CsA are interchangeable, it is advisable to prescribe CsA by brand, and any transfer to a different CsA formulation should be undertaken with close supervision and only at the direction of the transplant physician.

Animals↗
PubMed2003

Preeclampsia is associated with a reduced interleukin-10 production from peripheral blood mononuclear cells.

PROBLEM: This study aims to investigate and compare in vitro, immune cell production of the immunosuppresor cytokine interleukin-10 (IL-10) and the proinflammatory cytokine tumor necrosis factor (TNF-alpha) between normal pregnancy (NP) and preeclampsia. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from age-matched patients with preeclampsia and women with a NP (n=3/group) and cultured for 48 hr in the absence and presence of the mitogen phytohaemagluttanin (PHA, 1/100). The concentration of IL-10 and TNF-alpha in the culture medium (CM) was measured by ELISA. RESULTS: Stimulated PBMCs associated with preeclampsia had significantly less IL-10 in the CM compared to NP (347+/-39, preeclampsia vs. 689+/-128, NP; p<0.05) but no difference in TNF-alpha. There was no significant difference in IL-10 or TNF-alpha concentration in the CM of unstimulated PBMCs between preeclampsia and NP. CONCLUSIONS: These findings suggest that under in vitro stimulated conditions preeclampsia is associated with an abnormality characterized by a diminished ability of peripheral immune cells to produce the immunosupressor cytokine interleukin-10.

Adult↗
PubMed2002

Karyomegalic nephropathy: an uncommon cause of progressive renal failure.

BACKGROUND: Karyomegalic nephropathy, first identified in 1974, represents an increasingly recognized, but perhaps underdiagnosed condition associated with interstitial nephritis. It undoubtedly leads to end-stage renal disease requiring renal support. METHODS AND RESULTS: We present a series of six cases of karyomegalic nephropathy. The age at diagnosis was 9-51 years, median 33 years. Impaired renal function, proteinuria, and haematuria were present in the majority of cases. Non-specific elevated liver enzymes were present in three cases. Two patients died soon after transplantation from overwhelming respiratory sepsis. The classical histological features of large, abnormal hyperchromatic nuclei with irregular outlines within epithelial cells were present in renal epithelial cells. Abnormality of DNA ploidy distributions compared with age- and sex-matched controls, and characterized by the presence of significant numbers of cells with high ploidy values was present in cases but not in controls. Mitotic figures were absent. Proliferation markers, Ki-67 and proliferating cell nuclear antigen/cyclin were not significantly elevated in those cases examined. Human leukocyte antigen analysis did not support the clustering of A9 or B35, in the cases or their families. CONCLUSIONS: The presence of significant renal impairment, positive urine sediment, abnormal liver enzymes, and early age of onset should alert one to the presence of karyomegalic nephropathy. It represents an underdiagnosed disorder with a high degree of ploidy indicative of karyotypic abnormality.

Adult↗
PubMed2002

Women in medicine: a four-nation comparison.

OBJECTIVES: to determine the impact of increasing numbers of women in medicine on the physician work force in Australia, Canada, England, and the United States. METHODS: We collected data on physician work force issues from professional organizations and government agencies in each of the 4 nations. RESULTS: Women now make up nearly half of all medical students in all 4 countries and 20% to 30% of all practicing physicians. Most are concentrated in primary care specialties and obstetrics/gynecology and are underrepresented in surgical training programs. Women physicians practice largely in urban settings and work 7 to 11 fewer hours per week than men do, for lower pay. Twenty percent to 50% of women primary care physicians are in part-time practice. CONCLUSIONS: Work force planners should anticipate larger decreases in physician full-time equivalencies than previously expected because of the increased number of women in practice and their tendency to work fewer hours and to be in part-time practice, especially in primary care. Responses to these changes vary among the 4 countries. Canada has developed a detailed database of work/family issues; England has pioneered flexible training schemes and reentry training programs; and Australia has joined consumers, physicians, and educators in improving training opportunities and the work climate for women. Improved access to surgical and subspecialty fields, training and practice settings that provide balance for work/family issues, and improved recruitment and retention of women physicians in rural areas will increase the contributions of women physicians.

Australia↗
PubMedDate not supplied

Commonwealth pandemic preparedness plans.

This paper describes the work being done by the Australian Government Department of Health and Ageing to prepare for a possible influenza pandemic. It provides an overview of Australian Government initiatives and explains both the purpose and the content of the Australian Health Management Plan for Pandemic Influenza. It summarises efforts to improve regional detection and response capabilities and it explains the role of simulation exercises in Australian pandemic planning.

Animals↗