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Biomedical subjects

J Halkett

Publications and source records attributed to J Halkett.

9 recordsLinked to original sources
PubMed2004

The use of a cyclosporin-ketoconazole combination: making renal transplantation affordable in developing countries.

OBJECTIVES: The costs of immunosuppressive drugs in renal transplant recipients remains prohibitively high. Ketoconazole (KZ) has, in limited studies, been shown to significantly reduce the dose of cyclosporin (CyA) after renal transplantation. We report our long-term experience with the use of KZ in a large group of renal transplant recipients. Although this study was not a formal health economic assessment, we undertook a cost-saving analysis of the CyA-KZ combination usage. METHODS: The 170 patients (174 transplants) undergoing renal transplantation between 1991 and 1997 included in the study received CyA (10 mg/kg/day), prednisone (30 mg/day) and azathioprine (100 mg/day) in the immediate perioperative period. At 1 month post-transplantation, KZ (100 mg twice daily) was added and the CyA dose reduced to 25% and the prednisone dose to 50%. The CyA dose was adjusted to maintain trough levels of 150-200 ng/ml. RESULTS: There was an 85% reduction in the dose of CyA. The average costs were 10.61 pounds sterling for CyA alone compared with pound 2.26 (pounds sterling) for the CyA-KZ combination, which represents an average savings of 8.35 pounds sterling (79%) per patient per day. The estimated savings during the study period was 999,930 pounds sterling. The patient and graft survival for patients receiving KZ was similar to patients on the South African Dialysis and Transplant Registry. Graft survival was significantly worse in black patients. CONCLUSION: The use of KZ with CyA in renal transplant recipients with stable allograft function results in a significant reduction in the dose of CyA and a significant cost savings, without compromising patient or graft survival. The regimen may be useful in countries with limited resources.

Adolescent↗
PubMed2000

Withdrawal of cyclosporine in renal transplant recipients with acute tubular necrosis improves renal function.

In this study, patients with acute tubular necrosis (ATN) after renal transplantation were prospectively randomized to either conventional immunosuppression or withdrawal of cyclosporine and replacement with anti-thymocyte globulin (ATG). The patients treated with cyclosporine withdrawal and ATG had a significantly shorter duration of ATN (8.9 +/- 1.5 vs 10.8 +/- 1.4 days; P < 0.05) and better renal function (mean serum creatinine on day 5 postoperatively: 740 +/- 49 vs 918 +/- 73 micromol/l; P < 0.05). The incidence of acute rejection was lower in the patients with cyclosporine withdrawal and ATG. In conclusion, cyclosporine is toxic to the renal allograft with ATN, and withdrawal of cyclosporine shortens the duration of ATN and improves renal function.

Adult↗
PubMed1997

Acute intermittent porphyria: the in vitro expression of mutant hydroxymethylbilane synthase.

Acute intermittent porphyria (AIP) is an inborn error of haem biosynthesis caused by a variety of mutations in the gene coding for hydroxymethylbilane synthase (HMB-S). The entire coding sequence of this gene, from each of three South African AIP patients, was therefore screened for mutations using chemical cleavage mismatch (CCM) analysis and any changes detected characterized by DNA sequencing. Three single base changes were identified; a G77 to A in exon 3, a C346 to T in exon 8 and a G518 to A in exon 10. These missense mutations, previously reported to be present in other populations, are known to be responsible for the structurally deleterious amino acid replacements R26H, R116W and R173Q, respectively. The in vitro expression of the enzymes containing these mutations and the subsequent measurement of their specific activities revealed a reduction to approximately 4% of normal activity.

Escherichia coli↗
PubMed1996

Detection of four mutations in six unrelated South African patients with acute intermittent porphyria.

We have screened the hydroxymethylbilane synthase cDNA from six South African patients with acute intermittent porphyria, using a combination of chemical cleavage mismatch analysis and direct sequencing of asymmetrically amplified PCR products. Four mutations were detected, a novel T insertion (771insT) and three missense mutations (R26H, R116W and R173Q). The 771insT mutation produces a stop codon, thirty-three codons downstream and a loss of approximately 20% of the protein is predicted. The R116W mutation, which was found to have a high prevalence in the Dutch population, was detected in three unrelated South African patients.

DNA Mutational Analysis↗
PubMed1993

Abdominal tuberculosis: still a potentially lethal disease.

The findings in a 4-yr survey of 82 patients with abdominal tuberculosis are described and compared with those encountered in previous surveys. Fourteen cases of intestinal, 11 of mesenteric-lymphnodal, and 57 of peritoneal tuberculosis were identified. The disease occurred essentially in patients living under worsening socioeconomic conditions, and 51 of them had associated pulmonary tuberculosis. Symptoms and clinical findings were again nonspecific, but newer imaging, endoscopic, and other invasive procedures were helpful in establishing a definite diagnosis. In addition, adenosine deaminase determination showed great promise as a noninvasive diagnostic procedure in patients with tuberculous ascites. The six hospital deaths in the series highlight the hazard of potentially lethal delays in early diagnosis and treatment, even in centers with a high awareness of the disease.

AIDS Serodiagnosis↗
PubMedDate not supplied

Identification of two novel mutations in the hydroxymethylbilane synthase gene in three patients from two unrelated families with acute intermittent porphyria.

We have screened the hydroxymethylbilane synthase cDNAs of 3 patients from 2 families suffering from acute intermittent porphyria (AIP) from Scotland and South Africa using heteroduplex and chemical cleavage of mismatch analyses. Direct sequencing was used to characterise the mutations. The two novel mutations identified were a missense mutation at nucleotide position 64 in exon 3 (R22C) and a single base-pair deletion in exon 15. These mutations are predicted to affect the normal function of the enzyme and, therefore, are expected to be the primary cause of disease in these patients.

Female↗