Early clinical pathologists. 4: John Hunter (1728-1793).
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Biomedical subjects
Publications and source records attributed to S Lakhani.
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In a retrospective review of 73 patients with in situ breast carcinoma seen in the Combined Breast Clinic at the Royal Marsden and St. George's Hospitals between 1969 and 1988, 20 (27%) were found to have in situ lobular and 53 (73%) in situ intraduct carcinoma. Of 19 patients with in situ lobular carcinoma treated by breast conserving surgery alone there were three (16%) recurrences of in situ lobular carcinoma and one (5%) of infiltrating carcinoma after a mean follow-up period of 65.8 months. Of 53 patients with in situ intraduct carcinoma, 37 were treated by breast conserving surgery alone and in this group there were 14 (38%) recurrences, of which seven (19%) were in situ intraduct and seven (19%) were infiltrating carcinoma, after a mean follow-up of 96.5 months. Following successful salvage there were no breast cancer related deaths in either group.
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The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation.
In a consecutive series of studies, 164 patients with symptomatic and/or visceral metastatic malignant melanoma were treated with single agent vindesine, high dose melphalan with autologous bone marrow transplantation (AMBT), high dose BCNU with ABMT or the BOLD (bleomycin, vincristine, CCNU and DTIC) combination. The high dose treatments and the combination chemotherapy resulted in significantly higher response rates but no prolongation of survival. Factors associated with longer survival included the absence of visceral metastases, the absence of bulky disease and good performance status. For all treatments, life table estimates of survival at 1 and 2 years were only 10% and 4% respectively.
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Forty-five patients with relapsed or refractory multiple myeloma received continuous infusions of vincristine (0.4 mg total dose daily for 4 days) and adriamycin (9 mg m-2 daily for 4 days) with a high dose of methylprednisolone (1 g m-2 i.v. or p.o. daily by 1 h infusion), the VAMP regimen. Sixteen (36%) responded, with a median duration of remission of 11 months and median survival of 20 months. Major toxicities encountered were infective and cardiovascular. Two smaller groups of myeloma patients were treated with high dose methylprednisolone (HDMP) alone, or VAMP plus weekly low dose cyclophosphamide (Cyclo-VAMP). HDMP produced short responses in 25% of patients with less toxicity than VAMP. Cyclo-VAMP was used in a highly selected group of patients who had previously responded to high dose melphalan. It was well tolerated and produced responses in 61% of this group.
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The effect of a surgical day unit (SDU) on the waiting lists of a busy district general hospital is reported over a 4-year period. During this time, 18 (15%) of the general surgical beds were closed for financial reasons. A real saving rather than an apparent one is reported due to the work expansion in the SDU.
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