Substance abuse and schizophrenia: effect on symptoms but not on neurocognitive function.

The authors compare symptoms and neuropsychological test performance in DSM-III schizophrenic patients who reported prior substance abuse (N = 38) with those in patients who reported no such abuse (N = 25) to determine the impact of substance abuse on the psychopathology of schizophrenia. Positive and negative symptom scores were derived from the Schedule for Affective Disorders and Schizophrenia. Sixty neuropsychological measures drawn from commonly used tests of intelligence, memory, learning, fluency, and problem solving were calculated. Separate analyses were performed on patients in a psychotic episode who were free of neuroleptics (N = 27) and on those taking maintenance neuroleptics (N = 36). Among unmedicated patients, those who reported prior substance abuse had significantly higher thought disorder scores. Among neuroleptic-medicated patients, hallucination and delusion scores were significantly higher in the patients who reported prior substance abuse. The substance abuse followed withdrawal from social relations and preceded the onset of positive symptoms. None of the neuropsychological tests discriminated between abusers and nonabusers.     

Detection of moderate and severe coronary artery stenosis with technetium-99m tetrofosmin myocardial single-photon emission tomography

The aim of this study was to determine the diagnostic accuracy of technetium-99m tetrofosmin myocardial imaging for the localization of coronary artery stenoses of different degrees of severity. Stress-rest single-photon emission tomography (SPET) was performed on separate days in 80 patients (64 males, 16 females; mean age 61 years; 43 patients with previous myocardial infarction; 18 patients with pharmacological stress), within 6 months of coronary angiography. Scintigraphic images were blindly and independently evaluated by three observers. Coronary stenosis was defined as a >50% narrowing in luminal diameter; severe stenosis was defined as a proximal stenosis of >75% or a peripheral stenosis of >90%. Coronary angiography revealed normal coronary arteries or insignificant coronary stenosis in 13 patients and significant coronary stenoses in 67 patients. The sensitivity and specificity of ^99mTc-tetrofosmin SPET in respect of severely stenosed vessels were, respectively, 80% and 65% for the left anterior descending artery (LAD), 100% and 46% for the right coronary artery (RCA) and 58 and 78% for the left circumflex artery (LCx) territories. Considering all the significantly stenosed vessels, a significant decrease in sensitivity was observed for LAD territories (to 59%, P=0.05), and a nonsignificant decrease for RCA (88%) and LCx (47%) territories while specificity values remained essentially unchanged. No significant changes in sensitivity or specificity were observed when regions with previous myocardial infarction were excluded. In conclusion, the sensitivity of ^99mTc-tetrofosmin SPET for the localization of individual stenosed vessels is only moderate when all significant stenoses are considered, but the ability of this technique to predict the location of severe coronary artery stenoses seems satisfactory, with the exception of the low specificity in respect of RCA territories. Received 26 April and in revised form 7 June 1997     

Measurement errors in epidemiological studies of human papillomavirus and cervical cancer.

Measurement errors have been an important concern in studies of human papillomavirus (HPV) and anogenital cancers. Misclassification of HPV infection status is a possible explanation for incoherent findings in previous epidemiological studies purporting to show an etiological role for HPV in cervical cancer. Even low levels of misclassification of HPV infection can cause severe underestimation of HPV prevalence in field surveys, bias the association between HPV and sexual activity, and impair the ability to control statistically the relation between sexual activity and neoplasia by viral status. The present report focuses on aspects that have not been elaborated in two previous studies (Kaldor, 1989; Franco, 1991). Emphasis is given to effects of measurement errors of HPV infection status in biasing the association with cervical neoplasia under more complex scenarios, e.g., differential misclassification between cases and controls in a case-control study, and non-differential misclassification of both viral infection and cervical neoplasia in cross-sectional cytology surveys and cohort studies. Some simple numeric formulae are given that allow the correction of prevalence rates and epidemiological measures of effect, such as the odds ratio and the relative risk, under the latter conditions of misclassification constraint. These formulae have been used to correct estimates from recent epidemiological studies using hypothetical misclassification scenarios in order to obtain clues on the magnitude of the underlying relationship between HPV and cervical cancer.     

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Quality of case management of sexually transmitted diseases: comparison of the methods for assessing the performance of providers.

This article examines the reliability and validity of direct observation of patient-provider encounters, interviews with providers, and use of patients simulating sexually transmitted diseases (STD) as methods for assessing the quality of STD case management in developing countries. Data were collected during an STD health facility survey in Malawi; the performance of 49 providers was observed, and the providers were also interviewed; 20 of them were visited by a simulated patient complaining of urethral discharge. Agreement (based on the kappa statistic) was generally poor between direct observation and provider-interview data, and also between direct observation and simulated-patient data. In contrast, percentage agreements between direct observation and simulated-patient data were often high. Multiple observations on providers indicated that a provider''s behaviour is not consistent across several patients. Simulated-patient data are probably the best in reflecting normal performance, but their feasibility for routine quality assessment is limited because the provider''s behaviour is not consistent and would require multiple data points. Direct observation data are the best option for assessing quality if the results are assumed to reflect better than normal levels of quality of care. Data from interviews with providers should be viewed with caution, because they may reflect provider knowledge and not necessarily performance.     

The afferent innervation of the thymus gland in the rat

The afferent nervous supply to the thymus gland has been investigated by means of the retrograde transport of horseradish peroxidase. It has been shown that the thymus receives an afferent supply from the nodose ganglia of the vagus and from the dorsal root ganglia C₁–C₇. The afferent innervation of the right and left thymic lobes is bilaterally organized; the fibers of a small celled population of nodose ganglion neurons cross outside the thymus and those of a larger celled population cross within the thymus gland. The functional implications of these findings are discussed in the context of central nervous system-immune system interactions.     

Segmentectomies in the management of liver tumors

Between 1982 and 1986, liver segmentectomies were performed in 19 patients with liver tumors, including ten hepatocellular carcinomas, six liver metastases, one cholangiocarcinoma, and two benign tumors. During surgery, patients received a mean (+/- 1 SD) of 1050 +/- 150 mL of packed red blood cells and 860 +/- 80 mL of fresh-frozen plasma. There were no operative deaths. The only complication was a prolonged leakage of ascites through the abdominal drain in one patient with cirrhosis. Seven patients with hepatocellular carcinoma were still alive at this writing, with a follow-up ranging from two months to four years. The four patients with metastases from colorectal carcinomas were alive after follow-up times ranging from six to 24 months. These results suggest that liver segmentectomy is a safe procedure and should be considered as the operation of choice for resection of limited liver tumors.     

Temporal sequence of gene expression leading caudal prosencephalon to develop a midbrain/hindbrain phenotype.

Transplantation of prosomeres 1-2 into the cerebellar plate were used, by using chick/quail chimeras, to analyse the temporal sequence of the genetic cascade leading the graft to develop a midbrain/hindbrain phenotype. Our results show that (1) at Hamburger and Hamilton (HH) stage 13, Pax2 and En2 are already induced within the graft, before all other genes of the cascade, whereas misexpression of Fgf8 is also observed within the contiguous host cerebellar plate; (2) within the graft, Otx2 repression and Gbx2 induction (see Hidalgo-Sánchez et al. [1999] Development 126:3191-3203) are secondary events that affect, from stages HH14-15, the areas in contact with the host Gbx2/Fgf8-expressing cerebellar plate; (3) at these stages, the repressed Otx2 territory extends beyond the areas induced to express Gbx2, with the two territories not abutting before HH17-18; (4) Fgf8 expression becomes progressively induced within the Otx2-repressed/Gbx2-induced territory, starting at HH15-16. Our results support the hypothesis that the host-Gbx2/graft-Otx2 interface could trigger the genetic cascade induced within the graft and that the Gbx2-induced domain could play a key role during the establishment of the induced intragraft midbrain/hindbrain boundary.