Improved estimates of discordance ratios in twin studies

In the study of monozygotic twins relative to disease and risk factors, particular interest focuses on the subset who are discordant for some suspected risk factor (for example, smoking), since such twins constitute a natural case-control pair. In such studies, questionnaires designed to identify the status of all twin pairs are sometimes error prone and can yield misleading estimates of the concordance-discordance ratios. Greater efforts to verify the characteristics of apparently discordant pairs than to verify those of apparently concordant pairs can result in the 'unequal ascertainment' fallacy. Using the results of a questionnaire with known error rates and the 'apparent' frequencies yielded, we present unbiased, maximum likelihood estimates of the 'true' proportions of concordant and discordant pairs. concordant and discordant pairs. We also present approximate covariances among these estimates.     

The relationship between maternal needs and priorities in a neonatal intensive care environment

AIM: The aim of this study was to investigate the nature and organization of maternal needs and priorities in a neonatal unit. BACKGROUND: The relationship between maternal needs and priorities appears to be an under studied area in neonatal nursing. METHODS: A quantitative survey was carried out based on 209 mothers with premature infants. Two self-assessment schedules were used: critical care maternal needs inventory (J. Leske, Heart and Lung 15, 27-42) and a ranking scale. The data were analysed with multivariate analysis. FINDINGS: Data analysis revealed clear priorities in maternal needs. In particular the need for accurate infant related information was a priority for 93% of the mothers. Good communication practices with professionals were also valued. The mothers displayed altruistic behaviour, and self-related needs took second place. It is proposed that maternal needs demonstrate a hierarchical organization. CONCLUSION: It is important for nurses to consider the individual needs of the mothers, simply because the satisfaction of these needs is essential for maternal well-being.     

Steroid trials in the assessment of reversibility of air flow limitation: a survey of current clinical practice of chest physicians

To evaluate how steroid trials are currently used in the assessment of reversibility of air flow limitation, a postal questionnaire was sent to 355 consultant members of the British Thoracic Society working in England and Wales; 253 questionnaires were returned (71% response rate). Two respondents did not undertake steroid trials; of the remaining 251, 75% prescribed 30-40 mg oral prednisolone, with the commonest treatment period being 2 weeks. A high dose steroid inhaler was sometimes used as an alternative by 31% of respondents. Although 71% of respondents made lung function measurements on several occasions before starting steroids and 76% made measurements during treatment, 78% assessed patients on only one occasion at the end of the trials to ascertain its outcome. Weight, blood pressure and glycosuria were measured less frequently after the steroid treatment compared to the pre-trial period. Blood glucose and serum electrolytes were infrequently measured both before and after treatment. Wide variations exist in steroid trial regimens and current practice may neither provide definitive evidence of treatment benefit nor an adequate safeguard for patients against potential side-effects.     

Typifications. The first step for clinical diagnosis in psychiatry

Reigning views on psychiatric nosology regard as "too subjective" certain features of diagnosis which respected psychiatrists have reported and several empirical studies have confirmed. We describe two of these persistent "mysteries" of psychiatric nosology: rapid diagnoses and the praecox feeling. We then demystify these mysteries by explicating the workings of "typification" in the diagnostic process. The criteria of disorders which are provided by classification manuals, such as DSM-III, are shown to presuppose such typifications. Psychiatric typification, although a preconceptual skill, can be rendered fully scientific and objective.     

Expressions of resistance and cross-resistance in teniposide-resistant L1210 cells

Summary Resistance to teniposide (VM-26) by VM-26 selected resistant L1210 cells in culture was attributed to alterations in the flux of VM-26 across the plasma membrane and to functions of homogeneously staining regions that appeared on one or more chromosomes. In the present study, electrophoresis of membrane-cytosol fractions of these resistant sublines demonstrated a protein band, M_r 22 kd, that was not evident in similar fractions of drugsensitive L1210 cells or three revertant sublines. The distribution of this protein among various cellular fractions could be altered by manipulation of the concentration of calcium ions. A representative subline, LIa5 M, was observed to have vesicles that reacted with Sudan black B stain, an indication of altered lipid metabolism. The LIa5 M subline was cross-resistant to etoposide, vincristine, doxorubicin, amsacrine, and actinomycin D. Concentrations of VM-26 that inhibited cell division to the same extent caused an accumulation of fewer cells in the G₂ stage of cell division in LIa5 M cultures than in L1210 cultures. These observations indicate that the LIa5 M subline expressed multiple drug resistance, as well as changes in the expression of cytotoxicity to VM-26.This investigation was supported by Research Project Grant CA 35319, by Cancer Center Support (CORE) Grant CA 21765 from the National Cancer Institute, and by the American Lebanese Syrian Associated Charities.Recipient of research support from a training grant, American Cancer Society Grant IN-85-06, to the University of Tennessee Center for the Health Sciences     

Lung cancer and occupation in New Mexico

The association between occupation and lung cancer risk was examined in a population-based, case-control study of 506 patients (333 males and 173 females) and 771 control (499 males and 272 females) subjects in New Mexico. A personal interview was used to obtain lifetime occupational and smoking histories and self-reported history of exposures to specific agents. High-risk jobs were identified in advance of data analysis and linked with industrial and occupational codes for hypothesis testing. For females, lung cancer risk was not associated with employment history, but power was limited. For males, elevated risks were found for the uranium mining industry [odds ratio (OR) = 1.9; 95% confidence internal (CI) = 0.8-4.9], underground miners (OR = 2.1; 95% CI = 1.1-3.7), painters (OR = 2.7; 95% CI = 0.8-8.9), and welders (OR = 3.2; 95% CI = 1.4-7.4). For self-reported exposure to any of 18 agents, only the OR for exposure to "other metals" was elevated. The population attributable risk in males was estimated as 14% for employment in any high-risk industry or occupation with an OR above 1 in this study.     

Microiontophoresis of cocaine, desipramine, sulpiride, methysergide, and naloxone in habenula and parafasciculus

The effects of microiontophoretically applied cocaine, desipramine (DES), sulpiride (SUL), methysergide (METH), and naloxone (NAL) on the responses of physiologically identified single neurons in the habenula (Hab) and parafasciculus thalami nucleus (PF) were examined in rats. Three cell types were identified in both nuclei on the basis of the responses obtained following noxious stimulation that were classified as "nociceptive-on," "nociceptive-off," and "nonnociceptive" cells. Administration of cocaine generally resulted in a decrease in the firing rate of nociceptive-on and nonnociceptive neurons in both Hab and PF. In contrast, cocaine generally induced an excitation in the baseline firing of the nociceptive-off cells. Cocaine application concomitant with noxious stimulation prevented the evoked responses of the nociceptive-on and the nociceptive-off cells. DES, when applied alone, was found to induce excitation in neuronal discharge of all three cell types in both sites. Combined application of cocaine with DES resulted in no observable change in discharge frequency for the nociceptive-on and nonnociceptive cells, while inducing an additive excitatory effect on the nociceptive-off cells. SUL, in contrast, induced no observable effect on baseline firing when given alone, yet consistently antagonized cocaine-induced effects on all three cell types. Finally, METH and NAL induced no effects on baseline firing or cocaine-induced modifications in neuronal discharge frequency.     

Delayed oligodendrocyte degeneration induced by brief exposure to hydrogen peroxide.

An in vitro model system of cultured oligodendrocytes was used to determine the susceptibility of these cells to oxidative stress induced by 15 min exposure to millimolar concentrations of hydrogen peroxide (H2O2). Following the exposure, the cells were incubated in normal growth medium, and analyzed at different time points. Although no cell loss was observed during the exposure period, there was a progressive depletion of adherent cells during the postexposure period as seen from either the number of recoverable nuclei, or from total RNA content of the cultures. Both the rate and the extent of cell deletion was directly dependent on H2O2 concentration. Cell death was preceded by structural alterations in the nuclear envelope resulting in "fragile" nuclei which disintegrated during isolation. Northern blot analysis showed that the expression of myelin-specific genes was rapidly downregulated in H2O2-treated cells. On the other hand, the expression of antiapoptotic gene, bcl-2 featured massive but transient upregulation. Oligodendrocyte degeneration also featured genomic DNA degradation into high molecular weight fragments, which are likely to represent cleaved chromosomal loops. The results demonstrate vulnerability of oligodendrocytes to oxidative stress that induces rapid degeneration and ultimately leads to delayed cell death. This feature is highly relevant to oligodendrocyte damage and depletion following ischemic, traumatic, or inflammatory insults to the central nervous system (CNS).     

Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat

Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.