[Small hospitals--future tasks and functions].
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Biomedical subjects
Publications and source records attributed to J Lotsberg.
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In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.
A Phase I study was carried out with ricin, a plant toxin acting by inhibiting protein synthesis, on 54 cancer patients with advanced disease. Ricin was given as i.v. bolus injections every two weeks at dose levels ranging from 4.5 to 23 micrograms/sq m of estimated body surface area. Ricin was well tolerated at doses up to 18 to 20 micrograms/sq m. At these levels and at higher levels, flu-like symptoms with fatigue and muscular pain appeared and, in some patients, nausea and vomiting occurred also. No myelo-suppression was seen. Antibodies to ricin were detected in serum after two to three ricin injections. Ricin was eliminated from blood according to first order kinetics. At each dose level, the plasma concentrations, as well as the side effects, showed only minor differences between patients. The highest dose given, 23 micrograms/sq m, gave plasma concentrations twice those found previously to be therapeutically effective in tumor-bearing mice. Of 38 evaluable patients, one patient with lymphoma had a partial response. Stable disease was observed in four patients with renal cancers, in two with soft tissue sarcomas, and in one patient each with mesothelioma, thyroid, and rectal cancer. A dose of 23 micrograms/sq m is recommended for Phase II trials of ricin.
In a double-blind controlled study, oral acyclovir was compared with placebo in 39 consecutive patients undergoing bone-marrow transplantation. Acyclovir was given at a dose of 200 mg every 6 h from 8 days before to 35 days after bone-marrow transplantation. Pharmacokinetic studies showed good absorption of the drug, despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease. There was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group compared with the placebo group even in patients with high anti-HSV antibody titres before transplantation. The same protection was observed against cytomegalovirus (CMV) infection. The frequencies of HSV and CMV infections were the same in both groups after the cessation of treatment.
In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.
To study the usefulness of an in vitro colony-forming assay in predicting individual clinical responses to chemotherapy, tumor cells obtained from 150 melanoma metastases (119 patients) were grown in soft agar according to the method of Courtenay and Mills (1978), and tested for sensitivity to DTIC, CCNU, vinblastine, procarbazine, abrin and ricin. In 83% of the cases colony formation was observed (plating efficiency, PE, greater than 0.01%). Twenty-seven per cent of the tumors gave PEs greater than 1%, 45% gave PEs in the range 0.1-0.9%, whereas 11% of the tumors gave 0.01-0.09%. The PEs were not correlated with the degree of pigmentation or with the clinical course. Evaluable chemosensitivity data were obtained on 104 metastases from 83 patients. Large differences in sensitivity were seen. In cases which were evaluable both in vivo and in vitro a clear correlation was found between the in vitro chemosensitivity, expressed as the expected growth delay, and the clinical response to chemotherapy. Tumors from patients with partial response, mixed response or stable disease after prior progression, all had rather high in vitro sensitivity to the drug used (expected growth delay greater than 2.0), whereas patients with progression had lower sensitivity. The results confirm that the soft agar method used here provides good culture conditions for human melanoma cells and show that chemosensitivity data can be obtained in a high percentage of melanoma patients. The approach used seems promising in aiding clinicians to adjust chemotherapy to individual patients.
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