Latency and the lung cancer epidemic among United States uranium miners

The latency of occupational cancer was a key factor in the recent epidemic of lung cancer among U.S. uranium miners. A review of the epidemic and analysis of latency periods with a near lifetime follow-up found that among former and nonsmokers, the mean mid-induction latent period is nearly a constant at about 25 y, regardless of age at starting or magnitude of exposure. Among cigarette smokers, the mean is shorter (about 19 y). It is not influenced by age at start of smoking, amount smoked, or magnitude of exposure, but there is a marked shortening as the age at start of radiation exposure rises. These latency variables affect lifetime risk models. By disregarding the European radon mine exposures and waiting for strong evidence of lung cancer among U.S. uranium miners (ignoring the exposures occurring while waiting during the latency period), the epidemic became inevitable.     

Consistency of primary brain tumor diagnoses and codes in cancer surveillance systems

High-quality cancer registry data are essential for assessing trends in incidence rates. This study evaluated the consistency of brain tumor surveillance data using a random sample of cases from the Connecticut Tumor Registry. Three neuropathologists independently and blindly reviewed tumor slides from 204 cases and a nosologist blindly reviewed and assigned International Classification of Diseases for Oncology (ICD-O) codes to 326 cases. For the pathology review, absolute concordance was as high as 81% for all primary brain tumors. Absolute concordance rates were high for nerve sheath (89%), meningioma (95%), and pituitary (95%) tumors. Rates were much lower for malignant tumors. ICD-O coding of malignant brain tumors is of relatively high quality with the exception of mixed gliomas and unspecified tumors. A high level of consistency for nonmalignant brain tumor diagnoses suggests that rates for these tumors, when actively reported to a surveillance system, can be of high quality.     

Reliability of information collected by proxy in family studies of Alzheimer's disease

The study evaluated the reliability of data obtained from proxy informants. The index subjects in this study were 81 nondemented participants in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) study. These index subjects and 159 proxy informants, identified by the index subjects, participated in the study. The kappa statistic with multiple raters per subject (for dichotomous variables) and the intraclass correlation coefficient (for continuous variables) were used to measure reliability. Among proxy respondents who provided answers, there was excellent agreement between proxy responses and the responses of the index subjects (0.7 < or = kappa < or =0.9), with the exception of questions about head injury (kappa = 0.4). A large proportion (>90%) of the proxy informants in this study were able to provide information on most items. Higher nonresponse rates (as high as 30%) were observed for medication history and women's health questions. This study supports the reliability of proxy responses for most categories of questions that are elicited in typical epidemiological studies, including the MIRAGE study.     

A survey of psychiatric group practice administrators: what does the future hold.

Twenty Psychiatric Group Practice (PGP) Administrators were surveyed regarding their perceptions of the advantages and disadvantages of PGP's, and their opinions were sought regarding the future of such groups. Their responses are examined in this article. Many of the current factors in the healthcare environment that may influence the expansion of PGP's are detailed. The result is a prediction of a trend toward PGP's in the future.     

The use of 2 health-related quality-of-life measures in a sample of persons infected with human immunodeficiency virus.

The purpose of this analysis was to examine the ability of the MOS-HIV (Medical Outcomes Study-Human Immunodeficiency Virus) Health Survey and the EuroQol Group's EQ-5D questionnaire to discriminate between subjects in predefined disease-severity groups on the basis of clinical-indicator status (i.e., CD4 cell counts, HIV type 1 [HIV-1] RNA copies). This study used medical records of and instruments completed by 242 HIV-infected patients. The ability of the health-related quality-of-life instruments to discriminate between subjects stratified by disease severity was assessed by means of receiver-operating characteristic (ROC) curve analysis. The EQ-5D (P<.05) and MOS-HIV physical health summary (PHS) scores (P<.01) were able to discriminate between groups of subjects stratified by disease severity on the basis of either CD4 cell counts or HIV-1 RNA copies. These findings provide further evidence of the validity of the use of EQ-5D and the MOS-HIV questionnaire and suggest that they may be practical tools for the monitoring of health status from the HIV-infected patient's perspective.     

GABAA receptor-mediated activation of L-type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas.

PURPOSE: The human hypothalamic hamartoma (HH) is a rare, intrinsically epileptogenic lesion associated with gelastic seizures, but the underlying mechanisms remain unclear. Here, we examined the role of GABAA receptors in surgically resected HH tissue. METHODS: HH tissue slices (350 microm) were studied using cellular electrophysiological, calcium imaging, and immunocytochemical techniques. RESULTS: Two neuronal cell types were seen: small (10-16 microm) spontaneously firing GABAergic neurons and large (20-28 microm) quiescent neurons. In gramicidin-perforated patch recordings, muscimol (30 microM) induced membrane depolarization in 70% of large (but not small) neurons and a concomitant rise in intracellular calcium. These responses were blocked by bicuculline methiodide (50 microM). Depolarizing neurons also exhibited more positive reversal potentials (Emuscimol) and significantly higher intracellular chloride concentrations compared to those that hyperpolarized. The cation chloride co-transporters NKCC1 and KCC2 were coexpressed in the majority of large neurons, but fluorometric measurements revealed that 84% of large HH neurons expressed solely or relatively more NKCC1. Bumetanide (20 microM), a NKCC1 antagonist, partially suppressed muscimol-induced excitation in large neurons. Concordant with robust expression of CaV1.2 and CaV1.3 subunits in HH neurons, the L-type calcium channel blocker nifedipine (100 microM) prevented muscimol-induced neuronal excitation. CONCLUSIONS: GABAA receptor-mediated excitation, due in part to differential expression of NKCC1 and KCC2 and subsequent activation of L-type calcium channels, may contribute to seizure genesis in HH tissue. Given the ready availability of L-type calcium channel blockers, our results have clinical ramifications for the treatment of seizures associated with HH lesions.     

β-Endorphin alters the course of central nervous system disease induced by a temperature-sensitive vesicular stomatitis virus in reconstitued nude mice

A 100 plaque forming unit (pfu) dose of a temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31 KS5, engendered a slowly progressive paralytic central nervous system (CNS) disease that killed all BALB/c nude mice within 28 days. Reconstitution of nude mice with 10⁷ syngeneic splenocytes 24 h before intracerebral inoculation with tsG31 KS5 VSV, however, protected 92% of the animals from death. When these reconstituted animals were injected intracerebroventricularly with 14 pmol of β-endorphin 24 h after reconstitution with splenocytes and 24 h befor inoculation with tsG31 KS5 VSV, only 72% of the animals survived. Furthermore, whereas 40% of the afflicted reconstituted nude mice given intracerebroventricular injections of sterile water were able to recover from the symptoms of disease, those surviving animals which received β-endorphin were unable to do so. A single intravenous injection of 14 pmol β-endorphin, or repeated postinfection administration of 28 pmol of β-endorphin intravenously into nude mice reconstituted with syngeneic splenocytes, which were pretreated with β-endorphin, did not alter the course of CNS disease induced by tsG31 KS5 VSV. The effect induced by intracerebroventricular injection of β-endorphin as antagonized by naloxone, but not by the neuropeptide fragment β-endorphin-(1–27). A simultaneous intracerebroventricular injection of reconstituted nude mice with 1220 pmol of naloxone and 14 pmol of β-endorphin resulted in a 89% survival rate, and 33% of the afflicted animals were able to overcome the symptoms of the disease induced by tsG31 KS5 VSV. Intracerebroventricular injection of reconstituted nude mice with 330 pmol of β-endorphin-(1–27) and 14 pmol of β-endorphin resulted in a 72% survival rate and the surviving animals were unable to improved appreciably the clinical status of their disease. Injection of reconstituted nude mice with either 1220 pmol of naloxone or 330 pmol of β-endorphin-(1–27) alone did not alter the course of the CNS disease in any way. A single intracerebroventricular injection of 29 pmol of another psychoactive peptide, [Des-Tyr]-endorphin, 24 h after reconstitution of nude mic with splenocytes and 24 h prior to infection with virus, resulted in 74% survival; and 39% of the afflicted animals were able to recover from the clinical symptoms.