Epirubicin for pretreated advanced ovarian cancer.
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Adult↗
Biomedical subjects
P Harper
Publications and source records attributed to P Harper.
Do we pay too dearly for our sport and leisure activities? An investigation into fatalities as a result of sporting and leisure activities in England and Wales, 1982-1988.
Analysis of deaths from sports and leisure activities in England and Wales during 1982-88 found that horse riding (98 deaths), air sports (92 deaths), motor sports (86 deaths) and mountaineering (74 deaths) were the most hazardous activities. The most hazardous activity for children was horse riding (19 deaths). The commonest activities resulting in drowning in adults were swimming (128 deaths) and fishing (82 deaths). The main drowning deaths in children followed swimming (24 deaths). When exposure was taken into account, mountaineering, motor sports and horseriding were found to be the most hazardous activities. Mountaineering was one hundred times more dangerous than ball games or water sports. We can expect an increase in sport and leisure accidents in the next few years. Strict control, sensible safety precautions and adequate training are paramount if we are to see any improvement.
Adolescent↗
Breakup of the projectile at 35 MeV/nucleon.
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Journal Article↗
Congenital biliary atresia and jaundice in lambs and calves.
An outbreak of congenital biliary atresia and jaundice is described, in which approximately 300 crossbred lambs and 9 crossbred calves died. The affected animals failed to thrive, developed jaundice and white scours and died within 4 weeks of birth. A common feature of this outbreak and a similar occurrence 24 years previously was the grazing of plants growing on the exposed silt foreshores of Burrinjuck Dam by ewes and cows in the early stages of pregnancy. Epidemiological and pathological findings suggested that a toxic insult to the foetus in early gestation caused choledysgenesis and biliary atresia, leading to diffuse, subacute to chronic cholangiohepatopathy and cirrhosis.
Animals↗
Veno-occlusive disease of the liver complicating ABMT successfully treated with recombinant tissue plasminogen activator (rt-PA).
A 45-year-old man underwent autologous bone marrow transplantation for relapsed myeloma. The procedure was complicated by the development of veno-occlusive disease (VOD) of the liver. Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) resulted in rapid resolution of hepatic encephalopathy and ascites with improvement in liver function. The use of rt-PA in the management of VOD appears effective and should be evaluated in further patients.
Bone Marrow Transplantation↗
Distinction of Becker from limb-girdle muscular dystrophy by means of dystrophin cDNA probes.
The similarity in clinical features of X-linked Becker muscular dystrophy (BMD) and the autosomal recessive limb-girdle (LGD) type of adult muscular dystrophy makes differential diagnosis of the isolated male case difficult. DNA probes complementary (cDNA) to the Duchenne/Becker muscular dystrophy gene product, dystrophin, can detect molecular deletions in 60-70% of affected subjects. Thirty-three patients with BMD or LGD (thirty isolated and three with an affected brother) were screened with a panel of cDNA probes for the whole dystrophin gene. Deletions were found in thirteen of eighteen (72%) patients with a diagnosis of BMD. Deletions were also found in four of the fifteen (27%) patients previously thought to have LGD, who were therefore reclassified as having BMD. All male patients with progressive muscular dystrophy of limb-girdle pattern should be routinely screened with these cDNA probes as a useful adjunct to their clinical diagnosis since the results have important implications for genetic counselling of affected families.
Adult↗
A phase II study of mitozantrone in advanced carcinoma of the ovary.
A total of 37 patients with advanced epithelial ovarian cancer were treated with single-agent mitozantrone at a dose of 12-16 mg/m2. All patients had received previous chemotherapy, including a platinum compound in 36. In all, 35 patients were evaluable for response. One patient (3%) achieved a partial response lasting 4 months. Treatment was well tolerated, and at the doses used in this study significant bone marrow suppression was uncommon. Our results suggest that mitozantrone has only minimal activity in previously treated ovarian cancer. However, the possibility of its useful activity in first-line treatment or at higher doses has not been excluded.
Adult↗
Haematological recovery following high-dose cyclophosphamide with autologous bone marrow transplantation.
A total of 31 patients with previously untreated small-cell carcinoma of the lung were treated with very-high-dose cyclophosphamide, using autologous bone marrow transplantation (ABMT) to assist haematological recovery. The period of neutropenia was shorter with 40 mg/kg cyclophosphamide x 4 (7 patients) than when the dose of cyclophosphamide was increased to 50 mg/kg x 4 (11 patients), despite ABMT 2 days after chemotherapy in each group. In all, 13 patients were treated with 50 mg/kg cyclophosphamide x 4, with infusion of bone marrow delayed to day 4, 6 or 8 after chemotherapy to determine the contribution of ABMT to haematological recovery. The period of neutropaenia was increased when marrow was returned 6 days following chemotherapy, confirming that ABMT contributed to haematological recovery after this schedule of treatment. A total of 11 patients had a second cycle of 50 mg/kg cyclophosphamide x 4 after recovery from the first cycle of high-dose chemotherapy. The period of myelosuppression was greater with the second cycle of chemotherapy, although ABMT was carried out during both cycles. The results show that ABMT contributes to haematological recovery when the dose of cyclophosphamide is high enough to produce prolonged hypoplasia. The increased myelosuppression observed after a second high-dose treatment in spite of ABMT suggests either that both transplanted and endogenous marrow activity contribute to recovery of myelopoiesis or that there is residual damage to marrow stroma after the first cycle of treatment. The data indicate the necessity of carefully assessing the role of ABMT in haematological recovery with high-dose chemotherapy regimens.
Blood↗
A survey of manifesting carriers of Duchenne and Becker muscular dystrophy in Wales.
Manifesting carriers of Duchenne and Becker muscular dystrophy are uncommon but well described. Such patients are of particular importance with regard to the differential diagnosis from autosomal recessive limb-girdle muscular dystrophy. All mothers of affected males known to the Genetic Register of Muscular Dystrophy Families in Wales were contacted, and 167 out of a possible 190 were examined. It was estimated from pedigree and creatine kinase analysis that 119 out of the 167 were carriers of the Duchenne/Becker gene. Three manifesting carriers were identified, giving the proportion affected as 3/119 = 2.5%. We estimate the prevalence of manifesting carriers to be 1 in 100,000 of the female population, a figure comparable to the prevalence of autosomal recessive limb-girdle muscular dystrophy. During the period of the survey, several other women with similar clinical findings but without an appropriate family history were seen. We strongly suspect that some of these are also manifesting carriers of the Duchenne/Becker gene.
Adolescent↗
Enzyme linked immunosorbent assay for measuring antithrombin III.
A competitive ELISA for the measurement of antithrombin III antigen was developed using a pure preparation of antithrombin. This two step immunoassay requires only one antibody binding step and avoids the binding of anti-antithrombin antibody to the solid phase. Plasma samples measured by this ELISA correlated well with measurements taken with immune electrophoresis measurements (r = 0.933); the ELISA was also shown to be both sensitive and precise.
Antithrombin III↗
Cyclosporine induced alterations in vasopressin signalling in the glomerular mesangial cell.
Nephrotoxicity is the major limiting factor in the clinical use of cyclosporine A (CyA), which in its acute form results in a decrease in renal blood flow and glomerular filtration rate. Contractile mesangial cells regulate glomerular capillary patency in response to vasoactive stimuli including vasopressin. Hence the effects of CyA on the cellular signalling mechanism of vasopressin in cultured glomerular mesangial cells were investigated. Vasopressin induced a transient rise in intracellular calcium which was enhanced in the presence of CyA. In addition, CyA decreased both basal and vasopressin stimulated PGE2 production. This inhibition was mediated at least in part at the level of arachidonate release and may involve inhibition of phospholipase A2. We conclude that the increased renal and systemic vasoconstriction that occurs with CyA treatment may be the result of an exaggerated rise in intracellular calcium combined with diminished production of vasorelaxant prostaglandins in response to vasoconstrictor hormones.
Animals↗
Phase II trial of idarubicin in patients with advanced lymphoma.
A phase II trial of idarubicin was performed in 24 patients with advanced lymphoma. The drug was administered in a dose of 10-15 mg/m2 i.v. or 15-70 mg/m2 p.o. (single dose) every 3 weeks. There were four partial responses and four minor responses. All but one of the responders had received prior doxorubicin therapy. The toxicities were myelosuppression, nausea and vomiting, and alopecia. Two patients with compromised cardiac function were observed to have further deterioration in the ejection fraction as measured by gated cardiac scan after idarubicin therapy. Further assessment of the activity of idarubicin against lymphoma is recommended in less heavily pretreated patients. The cardiac toxicity should be carefully monitored in future studies.
Antibiotics, Antineoplastic↗
Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.
The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t1/2 beta of the elimination phase (beta) was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h-1 and the plasma carnitine clearance was 5.4 vs 6.11.h-1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.
Administration, Oral↗
Pharmacokinetics of intravenous and oral bolus doses of L-carnitine in healthy subjects.
The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet. Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t1/2 beta of the elimination phase (beta) was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h-1 and the plasma carnitine clearance was 5.4 vs 6.1 1 x h-1 (p less than 0.025), thus showing dose-related elimination. Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively. Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.
Administration, Oral↗
Translocation 5;21 and interstitial deletion of chromosome 7 in a case of chronic myelomonocytic leukemia.
We report a case of chronic myelomonocytic leukemia with a translocation involving chromosome 5 and 21, namely, t(5;21)(q35.3;q22.1), and an interstitial deletion of the long arm of chromosome 7. High-resolution analysis at the 900-band stage has shown that the lesion in chromosome 7 is an interstitial deletion involving loss of the segments q22-q35 of the long arm of chromosome 7 and retaining the telomere.
Aged↗
Bradykinin stimulates a rise in cytosolic calcium in renal glomerular mesangial cells via a pertussis toxin insensitive pathway.
Bradykinin elicits a complex response in the renal glomerulus which includes a reduction in the glomerular capillary ultrafiltration coefficient. To elucidate the biochemical mechanism of this response, we investigated calcium signalling in rat renal glomerular mesangial cells in culture using the calcium-sensitive fluorescent dye, Indo-1. Bradykinin was found to cause a concentration-dependent transient rise in cytosolic free calcium followed by a sustained slower secondary rise. The bradykinin response persisted with acute removal of extracellular calcium using EGTA, indicating that calcium entry from outside the cell did not mediate this primary response. Prolonged exposure to EGTA, which reduced intracellular stores, eliminated the calcium response to bradykinin but not to vasopressin, indicating differential sensitivity to intracellular calcium stores of these two hormonal responses. In agreement, prior stimulation with vasopressin significantly attenuated the response to bradykinin, but the converse did not occur. Aluminum fluoride and pertussis toxin were used to investigate the possible involvement of a guanyl nucleotide regulatory protein in signal transduction. Aluminum fluoride induced a transient rise in cytosolic calcium that was abrogated by prior exposure of the cells to pertussis toxin. This demonstrates the effectiveness of pertussis toxin and the presence of a calcium-signalling pathway susceptible to pertussis toxin in these cells. In contrast, the responses to bradykinin and vasopressin were unaffected by pertussis toxin. We conclude that bradykinin stimulates release of calcium from intracellular stores in glomerular mesangial cells via a pertussis toxin insensitive pathway. This mesangial response provides a direct biochemical basis for the bradykinin-induced fall in glomerular capillary ultrafiltration coefficient which has been observed in vivo.
Animals↗
Report of the committee on clinical disorders and chromosomal deletion syndromes.
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Chromosome Deletion↗