Alternative postmeniscectomy regimen.

Eighty patients who had undergone routine meniscectomy were divided into two groups for postoperative management. The first 40 patients were treated by the traditional method of a compression bandage with a backsplint, followed by a 10-day stay in hospital. In the other 40 patients a compression bandage was applied, reinforced by a plaster cylinder. Weight-bearing was allowed with the aid of crutches, and patients were discharged after four days in hospital. Adequate splintage and early ambulation was more convenient and comfortable for postoperative management, and no complications ensued. Less time was needed for physiotherapy, and earlier return to work and resumption of normal activities were made easier.     

The light-dark regimen and cancer development

The role of the modulation of the pineal gland function in development of cancer is discussed in the review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen.     

Long-acting intramuscular anesthetic regimen for swine

A two-stage, long-acting, injectable anesthetic regimen which provided pain-free restraint for swine was developed using nine mixed-breed domestic pigs. Each animal was administered a first-stage drug combination consisting of meperidine hydrochloride and azaperone in the caudal thigh muscles, followed after 20 minutes by a second-stage group of injections consisting of ketamine hydrochloride combined with morphine sulfate in the same muscles of the opposite leg. A mean surgical anesthetic time of 60.6 +/- 18.6 minutes was achieved with this regime and it was found that total anesthetic time could be doubled by a second injection of the ketamine and morphine components alone. All animals had a rapid, uneventful recovery. This combination regime not only provided reliable, long-acting anesthesia but was administered easily, required no tracheal intubation and produced no significant changes in the animals' heart rate or body temperature during the anesthetic period.     

Optimization of hydroxythiamine administration regimen in vitaminological research

A correlation between the different doses and inhibitory effect of hydroxythiamine relative to the activity of main thiamine pyrophosphate-dependent enzymes is studied in experiments on animals. It is established that the maximal inhibitory effect on the transketolase and oxoglutarate dehydrogenase activities is at a dose of antivitamin of 0.35 mmol/kg and that of pyruvate dehydrogenase of 0.55 mmol/kg. At lower doses of hydroxythiamine the inhibition of enzyme activities occurred in a dose-dependent manner.     

MVPP chemotherapy regimen for advanced Hodgkin's disease

During January 1968 to December 1972, 133 patients with advanced Hodgkin''s disease (HD) were admitted to hospital for combination chemotherapy with mustine, vinblastine, procarbazine, and prednisolone (MVPP regimen). Remission rates were 76% among 49 untreated patients and 90% among 42 patients who had relapsed after radiotherapy. The corresponding five-year survival rates were 65% and 86% respectively. Provided the observed yearly mortality (6%) remains unchanged 75% of patients who had previously received no treatment or irradiation and achieved remission are expected to continue in first remission after five years. Forty-two patients had received prior chemotherapy. They had lower remission and five-year survival rates (40% and 33% respectively), and fewer than half of those achieving remission were still in first remission after five years. There were several reasons for the poor prognosis in this group, including advanced-stage disease (stage IVB), age over 40, and achievement of remission.Chemotherapy was administered on an outpatient basis. Haematological toxicity and immediate drug-related side effects were similar to those of other regimens but there was no appreciable neurotoxicity. Most deaths were due to either HD itself or complications of advanced disease. Five malignancies other than HD occurred in patients who had received both single-agent chemotherapy and radiotherapy before MVPP chemotherapy. Two patients developed osteonecrosis of the femoral heads.Combination chemotherapy has a profound effect on the prognosis of advanced HD. The MVPP regimen yields results comparable to those of other regimens but with perhaps less toxicity.     

Evaluation of a proposed breast cancer screening regimen.

The Forrest working group on breast cancer screening recommended routine mammography for women in the United Kingdom at ages 50, 53, 56, 59, 62, and 65. Benefits were costed at about 3000 pounds for each life year recovered, but there was no estimate of the cost of each life saved, and the consequent reduction in mortality from breast cancer in the general population of the United Kingdom was not estimated. The present study addressed both of these issues using an interactive computer modelling process. Long term savings were calculated at 900 deaths a year in England and Wales--that is, about 8% of the total deaths from breast cancer--and 9% of life years currently lost. The cost of each death saved from breast cancer was estimated at 39,000 pounds.     

Prevention of prostate cancer through custom tailoring of chemopreventive regimen

One practical way to control cancer is through chemoprevention, which refers to the administration of synthetic or naturally occurring agents to block, reverse or delay the process of carcinogenesis. For a variety of reasons, the most important of which is human acceptance, for chemopreventive intervention naturally occurring diet-based agents are preferred over synthetic agents. For a long time, the prevailing mantra of cancer chemoprevention has been: "Find effective agents with acceptable or no toxicity and use them in preventing cancer in relatively healthy people or individuals at high risk for developing cancer". In pursuing this goal many naturally occurring phytochemicals capable of affording protection against carcinogenesis in preclinical settings in experimental animals have been described. However, clinical trials of single agents have yielded disappointing results. Since carcinogenesis is a multistage phenomenon in which many normal cellular pathways become aberrant, it is unlikely that one agent could prove effective in preventing cancer. This review underscores the need to build an armamentarium of naturally occurring chemopreventive substances that could prevent or slow down the development and progression of prostate cancer. Thus, the new effective approach for cancer prevention "building a customized mechanism-based chemoprevention cocktail of naturally occurring substances" is advocated.     

Retinoid teratogenicity in the macaque: verification of dosing regimen

To further define teratogenicity associated with 13-cis-retinoic acid (13-cis-RA) in the cynomolgus monkey, the drug was orally administered on three different treatment regimens. Experiment (Exp.) 1 (2.5 mg/kg/day, gestational day [GD] 12-27, n = 11) investigated the teratogenicity of a single daily dose of 13-cis-RA administered shortly after embryo implantation. Pharmacokinetic sampling was done to determine retinoid profiles on the first (GD12) and last (GD27) days of treatment. Exposure to 13-cis-RA during early organogenesis in Exp. 2 (2.5 mg/kg/day, GD20-27, and 2 x 2.5 mg/kg/day, GD28-30, n = 5) investigated the potential adverse effects of 13-cis-RA on the developing limb. The use of multiple doses of 13-cis-RA in Exp. 3 (2 x 2.5 mg/kg/day, GD26-27, n = 5) investigated the necessity of double dosing on the induction of retinoid embryopathy in the macaque. Malformations of retinoid target organs as well as embryolethality were most prevalent when single daily doses of 13-cis-RA were administered during pre- and early organogenesis in Exp. 1. Moreover, multiple doses on GD26-27 failed to induce any manifestation of abnormal development in Exp. 3. These results confirm that the lowest observed adverse effect level (LOAEL) in macaques is 2.5 rather than 5.0 times greater than that observed in human pregnancies. Exposure during forelimb development (GD20-30) in Exp. 2 was unsuccessful in inducing defects of this skeletal region, although defects in several retinoid target organs (i.e., cerebellum and internal ear) were present, indicating that a teratogenic threshold was achieved. Pharmacokinetic analysis of 13-cis-RA and its metabolites on GD12 and 27 in Exp. 1 showed considerable exposure to the administered drug and its 4-oxo-metabolite. In contrast, the exposure to all-trans-RA was negligible. The results support the use of a specific treatment schedule in early gestation in the macaque as the most appropriate model for characterizing the teratogenic potential of retinoids in humans.     

Divided dose intramuscular regimen and single dose subcutaneous regimen for chloroquine: plasma concentrations and toxicity in patients with malaria.

Adults with malaria in Sri Lanka were treated with parenteral chloroquine diphosphate, either 2.5 mg base/kg intramuscularly at 0, 1, 12, 13, 24, and 25 hours or 5 mg base/kg subcutaneously at 0, 12, and 24 hours. Both regimens were completed with oral chloroquine phosphate, 5 mg base/kg, at 36 and 48 hours. Mean peak chloroquine concentrations in the first 12 hours, which were 0.5 (range 0.3-0.6) mg/l (1.4 (0.9-1.7) mu mol/l) [corrected] with the intramuscular regimen and 0.3 (0.2-0.4) mg/l (1.0 (0.7-1.3) mu mol/l) [corrected] with the subcutaneous regimen (p less than 0.05), were reached in median times of 90 (65-90) minutes and 30 (30-60) minutes respectively (p less than 0.05) after the start of treatment. The mean area under the plasma concentration curve for the first 12 hours was 1.4 (0.9-2.1) mg/l.h (4.5 (2.8-6.4) mu mol/l.h) [corrected] after intramuscular administration and 1.8 (0.8-2.3) mg/l.h (5.7 (2.7-7.2) mu mol/l.h) [corrected] after subcutaneous administration (p greater than 0.1). Mean maximum plasma concentrations were higher after intramuscular administration (0.6 (0.4-0.8) mg/l (1.7 (1.3-2.5) mu mol/l)) [corrected] than after subcutaneous administration (0.4 (0.4-0.5) mg/l (1.3 (1.3-1.5) mu mol/l)) [corrected] (p less than 0.05), but both regimens produced satisfactory plasma profiles. Chloroquine resistance was found in the only case of Plasmodium falciparum malaria. Chloroquine is absorbed rapidly after divided dose intramuscular injection and single dose subcutaneous injection and does not cause hypotension or neurotoxicity in adults. Similar regimens should be evaluated in children before the parenteral use of this drug is abandoned.