Irradiation with or without misonidazole for patients with stages IIIB and IVA carcinoma of the cervix: final results of RTOG 80-05. Radiation Therapy Oncology Group.

PURPOSE: The purpose of this study was to evaluate tumor response, progression-free survival, local tumor control, patterns of relapse, and toxicity in patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix treated with irradiation or irradiation and misonidazole. This is a report of the final results of the study. METHODS: This study was a prospective randomized Phase III trial performed by the Radiation Therapy Oncology Group (RTOG). Between August 1980 and November 1984, 120 patients with Stages IIIb and IVa squamous cell carcinoma of the cervix were randomized to receive either standard irradiation or standard irradiation and misonidazole. Irradiation consisted of 46 Gy to the pelvis plus a 10 Gy parametrial boost followed by intracavitary brachytherapy or external irradiation boost to the primary tumor. Misonidazole was administered at 400 mg/m2 daily, 2-4 h before irradiation. Patients in the 2 treatment groups were evenly distributed by stage, Karnofsky Performance Status, and positive para-aortic lymph nodes. RESULTS: Sixty-one patients were treated with irradiation alone, and 59 patients received irradiation and misonidazole. Complete response in the pelvis occurred in 44 (75%) of those treated with irradiation and in 38 (64%) of those treated with irradiation and misonidazole. The progression-free survivals were 22% at 5 years for the control group, and 29% at 5 years for the misonidazole group. At the time of last follow-up, 18 patients in the control arm were free of disease, and in the experimental arm, 19 were free of disease. The patterns of failure for those treated with irradiation alone were local-only in 9 patients, distant-only in 8 patients, and local and distant in 11 patients. The patterns of failure for those receiving irradiation and misonidazole were local-only in 3 patients, distant-only in 8 patients, and local and distant in 8 patients. The maximum toxicity experienced per patient was grade 3 in 18%, grade 4 in 8%, and no grade 5 toxicity for those treated with irradiation alone compared to 8%, 2%, and 2%, respectively, for the experimental arm. CONCLUSION: There were no statistically significant differences in pelvic response, disease-free survivals, patterns of failure, or toxicity for the irradiation alone group or for the irradiation and misonidazole group as administered in this study for patients with Stages IIIb and IVa squamous cell carcinoma of the uterine cervix.     

Poly(ethylene glycol)-containing hydrogels in drug delivery.

The use of hydrogels as carriers for protein delivery has been a subject of significant recent research. In our recent work, we have shown that diffusion controlled delivery of proteins from hydrogels containing poly(ethylene glycol) (PEG) can be possible and controlled by the three-dimensional structure. In addition, a number of these hydrogel carriers are mucoadhesive and can be used for protein delivery. PEG star polymer gels have also been prepared by gamma-irradiation and have been used for protein delivery with and without molecular imprinting. The presence of a large number of functional groups in a small volume makes these polymers important for use in biological and pharmaceutical applications. PEG star polymer hydrogels were synthesized using gamma-irradiation and were characterized using swelling techniques. Equilibrium swelling studies were conducted to investigate the effects of molecular weight, number of star arms, concentration, and radiation dose.     

All cause mortality and its determinants in middle aged men in Finland, The Netherlands, and Italy in a 25 year follow up.

STUDY OBJECTIVE--The aims were (1) to compare all cause mortality in population samples of different cultures; and (2) to cross predict fatal event by risk functions involving risk factors usually measured in cardiovascular epidemiology. DESIGN--The study was a 25 year prospective cohort study. The prediction of all cause mortality was made using the multiple logistic equation as a function of 12 risk factors; the prediction of months lived after entry examination was made by the multiple linear regression using the same factors. POPULATION SAMPLES--There were five cohorts of men aged 40-59 years, from Finland (two cohorts, 1677 men), from The Netherlands (one cohort, 878 men), and from Italy (two cohorts, 1712 men). SETTING--The Finnish cohorts came from geographically defined rural areas, the Dutch cohort from a small town in central Holland, and the Italian cohorts from rural villages in northern and central Italy. MEASUREMENTS AND MAIN RESULTS--All cause mortality was highest in Finland (557 per 1000), and lower in The Netherlands (477) and in Italy (475). The solutions of the multiple logistic function showed the significant and almost universal predictive role of certain factors, with rare exceptions. These were age, blood pressure, cigarette smoking, and arm circumference (the latter with a negative relationship). Similar results were obtained when solving a multiple linear regression equation predicting the number of months lived after entry examination as a function of the same factors. The prediction of fatal events in each country, using the risk functions of the others, produced limited errors, the smallest one being -2% and the largest +11%. When solving the logistic model in the pool of all the cohorts with the addition of dummy variables for the identification of nationality, it also appeared that only a small part of the mortality differences between countries is not explained by 12 available risk factors. CONCLUSIONS--A small set of risk factors seems to explain the intercohort differences of 25 year all cause mortality in population samples of three rather different cultures.     

Indian hedgehog supports definitive erythropoiesis

Indian hedgehog (Ihh) has been reported to stimulate haematopoiesis ex vivo. In this study we studied the consequences of loss of function of Ihh for murine haematopoietic development. Ihh has no essential role in primitive erythropoiesis, but it is required in a non cell autonomous fashion for definitive erythropoieisis. Many components of the hedgehog signaling pathway are present in the fetal liver, with Ihh and Gli1 being most highly expressed in the stroma and Ptc1 being most highly expressed in haematopoietic stem and progenitor cells. Ihh knockout HSC and progenitor cell populations are produced in normal numbers in vivo and respond normally to haematopoietic cytokines in vitro, but terminal erythroid differentiation is defective leading to fatal anemia in mid gestation in many Ihh knockout embryos. These loss-of-function studies are consistent with previous gain-of-function studies which show Ihh can induce blood from ectoderm or expand HSCs in stroma-dependent culture.     

Bridging the two cultures of dual diagnosis: research and service

Common goals for research and service in dual diagnosis are identified. Three major barriers to the integration of research and service are explored: (a) differences in culture, (b) negative history, and (c) competition for limited resources. Applied research concerning diagnosis, treatment, behavioral recording, and organization and management development can encourage greater cooperation. To promote the integration of the research and service, joint conferences and publications are recommended as well as graduate training programs and agencies that emphasize both research and service. A vigorous policy initiative is needed to obtain private and public support for integrating research and service in dual diagnosis.     

Endobronchial Mycobacterium avium-intracellulare infection in a patient with AIDS

The pulmonary manifestations of AIDS are well described in the medical literature; however, MAI infection presenting as an endobronchial lesion has not, to our knowledge, been reported in a patient with AIDS. We report a unique case of an AIDS patient who developed endobronchial polypoid lesions secondary to MAI infection. Complications resulting from these lesions included hemoptysis and later bronchiectasis.     

Gentamicin-resistant Pseudomonas aeruginosa: Mayo Clinic Experience, 1970-1976.

During the period 1970 through 1976, there were 144 patients from whom gentamicin-resistant Pseudomonas aeruginosa (minimum inhibitory concentration [MIC], more than 5 microgram/ml) was isolated. In 20(21 percent) of the 95 patients who acquired such organisms within our institutions, the occurrence was considered clinically significant. Factors that favored the appearance of gentamicin-resistant P. aeruginosa included prolonged hospitalization, previous antibiotic treatment, increased gentamicin usage, underlying disease, and instrumentation (70 percent). Virulence of gentamicin-resistant isolates appeared less than that of susceptible organisms, with bacteremia due to these isolates occurring in only three cases. Resistant isolates with MICs for gentamicin of 8 to 16 microgram/ml were more susceptible to tobramycin than to amikacin, whereas isolates with MICs for gentamicin of 64 microgram/ml or greater were more susceptible to amikacin than to tobramycin. Eighty percent of all strains were susceptible to 128 microgram/ml or less of carvenicillin. Favorable results occurred in 12 or 13 cases treated with gentamicin plus carbenicillin, whereas treatment with either of these agents alone resulted in failure or relapse in 7 of 14 cases.