Increased risk of salivary gland tumors after low-dose irradiation

Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation.     

The anti-leukaemic activity of novel synthetic naphthoquinones against acute myeloid leukaemia: induction of cell death via the triggering of multiple signalling pathways

Naphthoquinones, such as menadione, display lower toxicity than anthracyclins used in cancer chemotherapy. Novel anti-leukaemic compounds comprised of chloro-amino-phenyl naphthoquinones with substitutions on the benzoic ring were developed. Structure–activity relationship studies indicated that the analogue with both methyl and amine substitutions (named TW-92) was the most efficient in killing leukaemic cells. Treatment of U-937 promonocytic cells with TW-92 induced apoptotic or necrotic cell death, dependent on incubation and dose conditions. TW-92 induced rapid phosphorylation of p38 mitogen-activated protein kinase (p38^MAPK) and of extracellular signal-regulated protein kinases (ERK1/2). The generation of apoptosis was preceded by intracellular H₂O₂ accumulation accompanied by glutathione depletion, the former inhibited by di-phenyl-iodonium (DPI), an inhibitor of NADPH oxidase. TW-92 induced swelling of isolated rat liver mitochondria, indicative of a direct effect on mitochondria. Apoptosis in intact cells was accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase activation. In addition, the level of Mcl-1, an anti-apoptotic regulatory protein, was down-regulated, whereas the expression of the pro-apoptotic BAX was elevated. Finally, TW-92 exerted strong pro-apoptotic and necrotic effects in primary acute myeloid leukaemia samples when given in submicromolar concentrations. Together, these findings demonstrate that TW-92 may provide an effective anti-leukaemic strategy.     

Measles epidemic in Israel-successful containment in the military

BACKGROUND: Measles vaccination at ages 12-15 months is a routine part of standard health care in developed countries. Nonetheless, the prevention and control of measles outbreaks remain a challenge, owing to incomplete or variable compliance with immunization programs and primary vaccine failure (approximately 5%). In Israel, vaccination coverage against measles is high, yet sero-epidemiological studies conducted in the early 1990s showed that 15% of 18-year-olds were unprotected. METHODS: 1994 there was a countrywide epidemic of measles, which spread to the military. The Israel Defense Forces Medical Corps immediately launched a wide-scale vaccination campaign, targeting primarily field units and training bases, where crowded living conditions are the rule. RESULTS: The immunization campaign led to an abrupt cessation of morbidity in the military. In the civilian sector, where no intervention was undertaken, the epidemic continued for another 4 months. CONCLUSIONS: Institutional measles outbreaks, especially in the presence of crowded conditions or high contact rates, may be effectively controlled by mass vaccination.     

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% Cl 11.2–23.1 months) and a 2 year survival of 34.3 ± 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% Cl, lower limit 29.8 months) and a 2 year survival of 71.6 ± 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 ± 6.6% in the IDAC group and 67.3 ± 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 ± 10.8% versus 23.5 ± 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 ± 15.78 versus 44.4 ± 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.     

Non-Hodgkin's lymphoma and residential proximity to toxic industrial waste in southern Israel

Environmental exposure has been linked to non-Hodgkin's lymphoma (NHL). Toxic volatile compounds were found in groundwater downstream of an industrial site in southern Israel. The risk of NHL and clinical characteristics of NHL patients were analyzed in relation to their proximity to the site.     

Debulking surgery for patients with diffuse large B-cell non-Hodgkin's lymphoma

Chemotherapy and radiotherapy have been the principal modalities of treatment for diffuse large B-cell non-Hodgkin's lymphoma (B-NHL) for over 30 years. Various treatment regimens have been designed over the years to try to increase response and cure rates. The role of surgery has been generally restricted to defined and limited situations including diagnostic tissue biopsies and treating abdominal emergencies such as organ rupture or perforation. We present two cases of refractory B-NHL, where surgery was used as a part of stepwise and multi-modal treatment with curative intent. In both cases, the treatment approach included standard dose chemotherapy, eradication of residual mass by surgery, high dose chemotherapy (HDC) with stem cell support and posttransplantant immunotherapy. Currently, 2 years after completing the therapy, both patients are well with no evidence of active disease. Based on our experience with 2 patients we believe that in specific cases of residual chemo-resistant lymphomatous mass, surgery should be considered as a part of a multimodal approach.     

Conventional dose fludarabine-based regimens are effective but have excessive toxicity in elderly patients with refractory chronic lymphocytic leukemia

The best approach to elderly patients with relapsing chronic lymphocytic leukemia (CLL) or disease refractory to conventional therapy with alkylating agents has not yet been established. Fludarabine and its combination with mitoxantrone and/or cyclophosphamide, which is the most effective treatment in younger patients, has not been extensively utilized in the elderly CLL. Here we report our results with fludarabine-based chemotherapy in 32 previously treated patients over the age of 65 years. The overall response rate was 59% with no complete remission, 3 nodular partial remissions and 16 partial remissions. The median time to progression of disease was 7 months. Only 10 patients completed the entire treatment program, because of poor compliance due to toxicity. Eight patients developed neutropenic fever, 14 severe bacterial infections and 2 patients showed progressive encephalopathy. For comparison, in a younger group of patients with refractory CLL (< 65 years), 38 of 50 patients completed the treatment plan, and the ORR was 80% (10 CR, 11 PR-nodular, 19 PR) with a median response of 12 months. Neutropenic fever was diagnosed in 10 and severe bacterial infection in 4 patients. In conclusion, fludarabine-based chemotherapy is effective for refractory CLL, however, excessive toxicity such as severe infections and neurological complications, do not allow completion of treatment in the majority of the elderly patients. Because maintenance of a good quality of life should be the main goal in the elderly CLL population, dose reduction of fludarabine and the appropriate use of myeloid growth factors and prophylactic antibiotics appear mandatory in this group of patients.     

Does immune serum globulin confer protection against skin diseases?

BACKGROUND: Following a case of serologically proven hepatitis A in a food-handling worker serving several military bases in the same vicinity, the entire military population was vaccinated with immune serum globulin (ISG). OBJECTIVE: To evaluate the effectiveness of ISG in preventing skin disease. METHODS: The data for this study were drawn from the military archives of the Medical Corps. The population of the bases was followed for a period of 3 months after immunization. Rates of selected skin diseases were compared with those of a nearby base during the same period, and with those in the population of the same bases a year earlier. RESULTS: The rates of several skin diseases (bacterial skin infections, dermatitis and eczema, fungal infections, acne, warts, nail disorders, and nonspecific skin diseases) among the vaccinated population were significantly lower when compared to the historical control group and to the contemporary control group of the nearby base. CONCLUSIONS: ISG provides a protecting effect for skin diseases, especially those of infectious origin.     

Salvage therapy of refractory and relapsed acute leukemia with high dose mitoxantrone and high dose cytarabine.

We have assessed the outcome of 66 refractory and relapsed acute leukemia patients treated with high dose mitoxantrone and cytarabine. Therapy consisted of a total dose of 40-60 mg/m2 mitoxantrone and 3 g/m2 of cytarabine daily on 5 consecutive days. A total of 28 patients were treated for primary resistant and 38 patients for early or late relapsed leukemia. A total of 35 patients achieved CR. Four patients died during the induction course. Toxicity was acceptable and comparable to other salvage regimens. The median disease-free and overall survivals were 4 and 6 months, respectively. Although this regimen is effective in achieving remission in refractory leukemia, its duration is short.