Prevalence and prevention of mental health problems in an energy-affected community

Energy-impacted communities experience rapid population growth due to energy resource production. A high prevalence of psychological and social problems are frequently reported in such communities. The present research employed a standardized instrument and random sampling in a community needs assessment to document high prevalence of problems in an energy-impacted town that has attempted to plan for rapid growth. At least 35 percent of the men and 25 percent of the women randomly sampled in the community reported elevated levels of psychological distress; 48 percent of the men admitted to alcohol problems. How the local mental health center utilized the needs assessment results to improve services, obtain funding for needed programs, and generally promote the community's quality of life is described. Recommendations for social planning that go beyond the brick and mortar approach to community planning are provided; prevention services are recommended above traditional remedial mental health services for such circumstances.Tom Bougsty, Ph.D., and Prudy Marshall, Ph.D., are both at the SEW Mental Health Center in Cheyenne WY. Ernest Chavez, Ph.D., is at the Colorado State University at Fort Collins, CO. Requests for reprints should be directed to the first author at 118 W. 4th Ave., Cheyenne, WY 82001.     

Changes in inositol 1,4,5-trisphosphate mass in agonist-stimulated human neutrophils

Changes in the endogenous synthesis of inositol 1,4,5-trisphosphate (IP₃) mass have been quantitated in human peripheral neutrophils stimulated with FMLP, LTB₄ and PAF using a recently described, highly specific radioreceptor assay. Each agonist induced a concentration-dependent synthesis of IP₃ which was detectable within 10 seconds after stimulation. IP₃ production was short-lived, returning to basal levels within 90 seconds. The maximal stimulated level of IP₃ in response to FMLP and LTB₄ was 30–50 pmoles/10⁷ neutrophils. PAF was more effective (100 pmoles IP₃/10⁷ neutrophils). The response to FMLP was inhibited by pertussis toxin, but was unaffected by cholera toxin. Pretreatment with cytochalasin B did not enhance IP₃ synthesis. These findings are generally consistent with previous studies employing [³H]myo-inositol-prelabeled cells, and provide one of the first measurements of IP₃ synthesis by mass in agonist-stimulated human neutrophils.     

The well-baby clinic

The termwell-baby clinic (literally, a clinic that concerns itself with healthy infants) is probably better known in the United States, where such clinics exist, than in central Europe, where, on the whole, they do not. For the convenience of readers accustomed to it a formal definition is proffered: A well-baby clinic is a service center, with emphasis on physical and mental hygiene and prophylaxis, where mothers are seen with their young, healthy infants and helped to understand and manage the infant's unfolding maturation [1: p. 5] and development [1: p. 5]. This may serve to differentiate well-baby clinics, on the one hand, from clinics for sick children and child guidance clinics (usually resorted to after disturbances have emerged) and, on the other hand, from maternity and child welfare clinics, whose primary object is to safeguard physical health. (Maternity and child welfare clinics are also known as family health clinics, child health clinics, and infant welfare clinics. The extent to which they can cater to the psychological needs of mother and infant depends on their staff's training.)This paper forms part of a research project entitled Childhood Pathology: Impact on Later Mental Health, which is being conducted at the Hampstead Child-Therapy Course and Clinic, London. The project is financed by National Institute of Mental Health Grant MH-05683-11. Appreciation is expressed to Anna Freud, Elizabeth Model, Professor A. J. Solnit, and Dr. Josefine Stross for their valuable suggestions. The authors acknowledge with gratitude the freedom to quote from the Well-Baby Clinic's annual reports, compiled by the clinic's pediatrician, Dr. Josefine Stross, with the active help of her past assistants, Annemarie Curson, Manna Friedmann, and Joyce Robertson, and her present assistants, Irene Freud and E. Model.This paper was originally published in German, in volume 2 of theJahrbuch der Psychohygiene, Ed. Gerd Biermann, Ernst Reinhardt Verlag, München/Basel, 1974.     

Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging.

PURPOSE: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET). (18)F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of (18)F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake. EXPERIMENTAL DESIGN: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue:blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane. RESULTS: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r = 0.24), with highly significant differences among the different tumor types (P < 0.005). CONCLUSIONS: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific.     

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer.

PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.     

Soft tissue sarcomas of adults: state of the translational science.

Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.     

Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival

Background: Clearance of large molecules from the interstitialspace is an important function of lymphatics andis affected by local pathologic changes.Objective: To determine if the clearance rate ofinterstitially injected albumin is correlated to tumour characteristicsand outcome in women with invasive breast cancer.Method: In a consecutive series of women comingto biopsy for suspected breast cancer, technetium-tagged albuminwas injected into the tissue adjacent to thepalpable mass. The isotope disappearance rate was measuredover two hours. Also assessed were the maximumvessel density (MVD – using Factor VIII polyclonalantisera), the proliferation rate (using Ki-67 antisera), nodestatus, tumour size, histologic and nuclear grade, mitoticrate, and p53 and c-erbB-2 oncoproteins. All patientswere followed until relapse and for a minimumof 10 years.Results: In multivariate analysis, an association between relapse-freesurvival and isotope clearance rate was suggested (p= 0.024). The best outcome was seen inpatients with the least isotope clearance. Node status,size, histologic and nuclear grade, and mitotic ratecorrelated with survival. MVD did not correlate withsurvival and was inversely related to the isotopeclearance rate. Tumour proliferation rate, and the c-erbB-2and p53 oncoproteins did not relate to outcome.Conclusion: The role of lymphatics in breast canceris difficult to study. Measurement of interstitial clearancemay be a useful technique and could bea prognostic factor.     

Neonatal adrenal congestion: a sonographic-pathologic correlation

We reviewed the clinical, sonographic and pathologic findings in eight neonates in whom diffuse enlargement and abnormal echogenicity of the adrenal glands was documented sonographically. Four of the patients suffered from perinatal asphyxia and two others required mechanical ventilation for other reasons. Six patients died and one suffers from severe development delay, cerebral palsy and failure to thrive. Sonographically, the glands were enlarged, their surface was smooth and there was loss of the central echogenic stripe. Diffuse sinusoidal congestion was found histologically in all five in whom autopsies were performed. These sonographic findings represent part of the spectrum of adrenal changes in neonatal asphyxia and other causes of perinatal stress, and may be associated with poor outcome because of other sequelae of asphyxia. Received: 12 March 1998 Accepted: 8 June 1998     

Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.     

Stigma, discrimination, and HIV/AIDS knowledge among physicians in Barbados.

OBJECTIVE: To determine the extent of clinical knowledge of HIV/AIDS that physicians in Barbados have and their attitudes towards persons living with HIV/AIDS. METHODS: In 2000 the Barbados Association of Medical Practitioners conducted a survey in order to assess its members' views on HIV/AIDS issues. Over a two-month period 203 physicians (76% of all those practicing in the country) were interviewed. The survey included physicians working in private practice and the public sector. They were surveyed individually concerning their attitudes towards counseling as well as their clinical knowledge, perception of safe practices, fear of occupational exposure, views on ethical issues, experience treating HIV/AIDS patients, and background with HIV/AIDS continuing education. RESULTS: In comparison to physicians who had graduated in later years, physicians who had graduated in 1984 or earlier had seen fewer HIV/AIDS clients, had lower levels of knowledge about the disease, were more likely to test for HIV/AIDS without informed consent, and were less likely to have ever attended a continuing education training course on HIV/AIDS. Overall, knowledge of the clinical indications of HIV/AIDS was low, and 76% of the physicians did not think they had adequate counseling skills. Over 80% of the physicians were comfortable looking after HIV/AIDS patients. While 95% of the physicians would not release HIV test results without a patient's consent, 33% would test, without consent, a seriously ill patient, and 15% would test without consent a patient upon whom they had to perform an invasive procedure if they perceived the patient to be from a high-risk population such as gay men or commercial sex workers. Only 53% of the physicians had attended an HIV/AIDS in-service training program between 1995 and 1999. CONCLUSIONS: Physician training in Barbados should focus on all aspects of HIV/AIDS care, including clinical and emotional factors. Attendance at such training should be mandatory for public sector physicians, and medical school curricula need to be examined to ensure their HIV/AIDS content is current and comprehensive.