Quantifying leukocyte and thrombocyte suppression-recovery after Re-186 HEDP for bone metastases.

Using a standard quantity of Re-186 HEDP, for therapy of osseous metastases from carcinoma of the breast, Palmedo and associates reported leukocyte and thrombocyte responses at 4 and 8 weeks. These were analyzed by dividing results into categories, based on the numeric initial values. Thrombocytes at 8 weeks exceeded pretreatment values in 10 of 18 cases. This "over-rebound" was also found in 7 of 19 leukocyte responses. The ability to predict thrombocyte-leukocyte response, in most cases, was linked to the initial hematologic values. If coupled with data on the status of bone marrow, this may allow the quantity of therapeutic radiopharmaceutical used to be increased or decreased without irreversibly compromising hematopoietic responses.

Niacin deficiency in rats increases the severity of ethylnitrosourea-induced anemia and leukopenia.

Many chemotherapeutic agents function by damaging the DNA of rapidly dividing cells, leading to side effects in the bone marrow, including anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We have created an animal model of alkylation-based chemotherapy, in nontumor-bearing rats, to investigate the effect of niacin deficiency on the side effects of chemotherapy [2 x 2 design, niacin-deficient (ND) vs. pair-fed (PF) control, and ethylnitrosourea (ENU) vs. vehicle control (C)]. Weanling Long-Evans rats were fed ND diet or PF niacin replete diet for 4 wk. ENU or C treatment started after 1 wk of feeding and consisted of 12 doses delivered by gavage, every other day. At 4 wk postweaning, niacin deficiency and ENU treatment ended, the rats were fed a high-quality control diet (AIN-93M) and the recovery of blood variables was monitored. ND alone decreased growth rate and caused anemia and neutrophilia. ENU treatment alone caused anemia, lymphopenia, neutropenia and an increase in circulating reticulocytes. In combination, ND and ENU treatment synergistically decreased hematocrit. ND prevented the ENU-induced increase in reticulocyte numbers observed in control rats. ND also increased the severity of ENU-induced lymphopenia. A combination of ND and ENU abolished the neutrophilia caused by ND alone. In summary, ND significantly increased the susceptibility of young Long-Evans rats to ENU-induced bone marrow suppression, suggesting that niacin-deficient cancer patients may benefit from supplementation.

[Prevention of wasting and opportunistic infections in HIV-infected patients in West Africa: a realistic and necessary strategy before antiretroviral treatment]. / Prévention de la dénutrition et des infections opportunistes chez lespatients infectés par le VIH en Afrique de l'Ouest: une démarche réaliste, nécessaire, préalabe aux antirétroviraux.

The medical inequalities between countries of the North and South (infrastructure, drug availability, medical techniques) are particularly marked in terms of the challenge posed by HIV infection. We propose a strategy for monitoring adult patients in West Africa that is appropriate to the situation in the field and to economic constraints. The aim of this strategy is to increase the quality of life and the life expectancy of HIV-infected adults and to prevent the overcrowding of hospital departments with patients in the terminal phase of AIDS. We analyzed the biological and clinical spectrum of HIV infection before the onset of the diseases that define AIDS (excluding pulmonary tuberculosis). We found that it was particularly important to diagnose B-stage diseases early, especially atypical chronic cutaneous and mucous diseases. Careful analysis of data from a routine hemogram (total lymphocyte count 2500/ml; paradoxical eosinopenia), even in the absence of a CD4 lymphocyte count, should also enable clinicians from a wide variety of health structures to identify the HIV-infected patients most likely to benefit from more detailed clinical follow up, prophylaxis of opportunistic infections using cotrimoxazole, nutritional checkups and prevention of wasting. Cachexia is the most common AIDS-associated disease in West African patients. It involves an overall decrease in calorific intake, diarrhea, immune system activation, an increase in TNFalpha production and greater energy expenditure when resting. Recent nutritional studies have shown that it is vital to optimize the calorific intake of HIV-infected patients presenting with chronic diarrhea, before the onset of severe immune deficiency, to prevent wasting. So, spontaneous calorific intake should de routinely determined in HIV-infected patients and an optimal diet provided. Specific training in nutrition is required for doctors and nurses, as is consideration of the logistic organization required to provide nutritional support to HIV-infected adults. Despite the large number of individuals infected and the lack of sophisticated paraclinical facilities, we feel that it is possible to establish rational management "a minima" of HIV infection in West Africa, whilst waiting for antiretroviral drugs to become more widely available. This strategy could be of direct benefit to patients without swallowing up the financial resources of the health system in expensive biological follow up. Such basic management is also required before the new antiretroviral drugs become widely available. Research should be carried out in parallel in several reference centers in West Africa to determine the most effective associations of antiretroviral drugs and the optimal timing of treatment during the course of infection and to assess the potential side effects of these drugs in HIV patients exposed to recurrent antigenic stimulation by a wide diversity of pathogens.

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

Standardization of definitions and criteria for causality assessment of adverse drug reactions. Drug-induced blood cytopenias: report of an international consensus meeting.

International reporting of adverse drug reactions to pharmaceutical companies or drug regulatory authorities requires internationally accepted standard definitions of reactions and criteria for assessment of causality. Under CIOMS (Council for International Organizations of Medical Sciences) auspices, the Roussel Uclaf pharmaceutical company organized an international meeting concerning drug-induced blood cytopenias. The meeting resulted in proposed standard designations of blood cytopenias and criteria for causality assessment of neutropenia, thrombocytopenia and aplastic anemia.

[Taxonomic analysis of the distribution of peripheral blood indicators in workers in chemical plants and automobile transport]. / Taksonomicheskii analiz raspredeleniia pokazatelei perifericheskoi krovi rabotnikov predpriiatii khimicheskogo profilia i avtotransporta.

Certain occupational groups demonstrate some deviations in the peripheral blood parameters which can be regarded as a multi-component hematological trait for selection of the group to be placed under observation.