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H Mackenzie

Publications and source records attributed to H Mackenzie.

8 recordsLinked to original sources
PubMed1996

Taxol and vinorelbine: a new active combination for disseminated malignant melanoma.

We evaluated the activity and toxicity of two sequences of taxol combined with vinorelbine in disseminated malignant melanoma, metastatic beyond regional lymph nodes. Fifteen previously untreated patients, nine males and six females (median age 56 years), were enlisted between May 1994 and February 1995. Eight patients received vinorelbine 30 mg/m2 (maximum dose 50 mg) first, follow 24 h later by taxol 120 mg/m2 (maximum dose 240 mg) infused over 3 h (the V/T sequence). Seven patients received the reverse (T/V) sequence. In 79 administered courses there were no anaphylactic episodes, the main toxicity being alopecia (WHO grade 3). Significant neutropenia, emesis or neuropathy was not observed in either schedule (WHO grades 0 or 1). Three major responses, all with the V/T sequences, were seen; one complete (CR) in nodal and cutaneous sites lasting 13 months and two partial (PR), omental, ascites in one and hepatic, splenic and nodal in the other, lasting 7 and 6 months, respectively. Clinically meaningful tumor regressions, not qualifying strictly for the criteria of major response, were observed in two additional patients in the T/V sequence. Taxol combined with vinorelbine is active against disseminated malignant melanoma. The importance of sequencing the two drugs remains to be determined with accrual of more patients into the study.

Adult↗
PubMed1994

The contribution of reduced functioning mass to chronic kidney allograft dysfunction in rats.

Chronic renal allograft dysfunction may become manifest months or years after transplantation by progressive functional deterioration associated with morphological changes that include vascular obliteration, glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Two hypotheses have evolved to explain the etiology of this process, usually described as "chronic rejection:" first, that it is primarily an antigen-dependent phenomenon influenced by continuing host alloresponsiveness; second, that nonimmunological, alloantigen-independent factors contribute to the progressive changes. Using an established model of chronic rejection of kidney transplants in rats in which the lesions progress relentlessly over time, we have determined the long-term effects of superimposing renal mass reduction on the indices of progressive allograft injury. Increasing proteinuria, a reproducible index of kidney graft dysfunction, developed after 12 weeks in all recipients of intact allografts, but was accelerated in kidneys with reduced mass, regardless of whether the organ was allogeneic or isogeneic. The coincident infiltration of macrophages and expression of cytokines and growth factors were associated with the development of glomerular sclerosis and interstitial fibrosis; such functional and morphological alterations occurred in an accelerated manner in all reduced-mass kidney allografts and isografts. Conversely, intact allografts in recipients also bearing a retained native kidney never manifested any chronic changes throughout the entire follow-up period. These findings emphasize the role of alloantigen-independent factors, particularly reduced renal mass, in the multi-factorial etiology of "chronic rejection" of kidney transplants.

Animals↗