bluuebunny/crossref_metadata_2025 huggingface dataset:
Greater Stroke Rate during Hospitalization for Acute Heart Disease among Mexican Americans than Non-Hispanic Whites
Authors: Morgenstern Lewis B. , Pandey Dilip K. , Smith Melinda A. , Ramsey David , Labarthe Darwin R. , Nichaman Milton Z.
Published: April 2003

Background and Purpose: This study compared the risk for stroke during acute myocardial infarction (AMI), percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) between Mexican Americans (MAs) and non-Hispanic whites. Methods: We examined the age-specific rate ratios (RR) of acute stroke during hospitalization for AMI, CABG and PTCA in a population-based study in Corpus Christi, Tex. by searching the cardiac surveillance data for ICD-9 codes for stroke (430–437). ICD-9 stroke codes were validated by comparing medical chart abstraction with ICD-9 discharge diagnoses. Results: Stroke codes were found in 220 of the 5,697 admissions for AMI, CABG and PTCA. In the 45- to 59-year age-group MAs had a RR of 2.66 (95% CI 1.36–5.23) relative to non-Hispanic whites. In the 60- to 74-year age-group the RR was 1.52 (95% CI 1.11–2.08). There were no significant differences in the 25- to 44-year age-group. These ethnic relationships were found in nondiabetics but not in diabetics. Women in the 45- to 59-year age-group had a RR of 1.88 (95% CI 1.09–3.25) compared with men, but there were no significant sex differences in the 25- to 44- or 59- to 74-year age-groups. Stroke ICD-9 codes have a poor positive predictive value for acute stroke ranging from 10 to 76%. The stroke misclassifications were nondifferential with respect to ethnicity or sex. Conclusions: MAs have a higher stroke rate complicating acute heart disease in Corpus Christi. A rigorous stroke surveillance project is needed to study the burden of stroke in MAs, the United States’ largest Hispanic population.
Occupational Metal Exposures and the Risk of Parkinson’s Disease
Authors: Gorell Jay M. , Rybicki Benjamin A. , Cole Johnson Christine , Peterson Edward L.
Published: April 2003

Occupational exposure to specific metals (manganese, copper, lead, iron, mercury, zinc, aluminum and others) appears to be a risk factor for Parkinson’s disease (PD) in some, but not all, case-control studies. These epidemiological studies are reviewed. Several methodological issues that may account for the lack of unanimity of findings are discussed, and suggestions for improved case-control methodology are offered. The study of the neurological disease outcome of workers who have had long-term, well-defined occupational exposure to one or more metals is also urged, with collaborative work including industrial hygienists, occupational toxicologists, neurologists, epidemiologists and biostatisticians. Such efforts, employing state-of-the-art case and control ascertainment and enrollment from suitable population bases, neurological diagnostic rigor and exposure assessment, will help to further define the potentially important roles played by metals in PD and other neurodegenerative disorders.
Use of Latent Class Analyses for the Estimation of Prevalence of Cognitive Impairment, and Signs of Stroke and Parkinson’s Disease among African-American Elderly of Central Harlem: Results of the Harlem Aging Project
Authors: Teresi Jeanne A. , Albert Steven M. , Holmes Douglas , Mayeux Richard
Published: April 2003

A probability sample (response rate of 79.4%) of 164 African-American elderly residing in central Harlem was assessed using several standard cognitive screening measures and scales measuring stroke and Parkinson’s symptoms, respectively. Both traditional cutting scores and the methods of latent class analysis were used to estimate point prevalence. The latent class prevalence ratio estimates range from 10 to 14%. The confidence intervals for cognitive impairment ranged from 5 to 18% with an average estimate of 12%. The latent class estimate for stroke effects was 11% and for two measures of neurological signs associated with Parkinson’s disease 7 and 12%. About 2–3% of the sample were communication disordered, and 5% had significant ambulation disorder. These results indicate that a relatively large proportion of elderly community residents of central Harlem evidenced or reported health problems, any or all of which may constitute a public health challenge.
The Relationship of Migraine and Stroke
Authors: Tietjen Gretchen E.
Published: April 2003

Migraine, a common disorder of uncertain pathogenesis, is linked to ischemia in a variety of ways. In some cases the relationship is coincidental. In others, migraine may be causally related to stroke, although the mechanism of migrainous stroke, if not due to arterial dissection, is unclear. In young women, additional risk factors for stroke such as cigarette smoking, use of combined oral contraceptives and anticardiolipin antibody immunoreactivity may potentiate migraine, especially migraine with aura, as a stroke risk factor. The complexity of the relationship is highlighted in certain genetic conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and mitochondrial encephalopathy with lactic acidosis and stroke in which migraine and stroke are both prominent clinical features.
Regional and Temporal Variation in the Incidence of Multiple Sclerosis in Finland 1979–1993
Authors: Sumelahti M.-L. , Tienari P.J. , Wikström J. , Palo J. , Hakama M.
Published: April 2003

Previous surveys in Finland from the 1960s have documented an uneven geographic distribution of multiple sclerosis (MS). In the present study, the incidence of MS was studied during 1979–1993 in the western Vaasa and Seinäjoki regions and in southern Uusimaa. The overall difference between the western and southern regions persisted; 8.7 per 100,000 in the western, and 5.1 per 100,000 in the southern region. The incidence of 11.6 per 100,000 in Seinäjoki was more than twofold greater than the 5.2 per 100,000 incidence found in neighboring Vaasa. An increasing incidence trend was observed for men in Seinäjoki, and a decrease for both sexes in Vaasa, while in Uusimaa the incidence remained stable for both sexes. The different incidence trends could not be readily explained by differences in case ascertainment but suggest the effect of environmental factors that have modulated the incidence of MS during the 15-year study period.
Relationship of Family History Scores for Stroke and Hypertension to Quantitative Measures of White-Matter Hyperintensities and Stroke Volume in Elderly Males
Authors: Reed Terry , Kirkwood Sandra C. , DeCarli Charles , Swan Gary E. , Miller Bruce L. , Wolf Philip A. , Jack Lisa M. , Carmelli Dorit
Published: April 2003

White-matter hyperintensities (WMHI) are frequently associated with cerebrovascular risk factors in the elderly, particularly hypertension, and have been interpreted as a subclinical form of ischemic brain damage. WMHI, clinical stroke and blood pressures show significant genetic influences. The objective of this study was to determine whether a relationship exists between family history of stroke and/or hypertension in first degree relatives and WMHI in the elderly. WMHI and stroke (CVA) volumes were quantified from brain MRI performed on 414 white, male twins born between 1917 and 1927 (average age 72.3 ± 2.9 years). WMHI, adjusted for age and head size, was significantly correlated with the family history score (r = 0.21, p < 0.001). Dividing the family history scores into quintiles revealed significant differences in WMHI by quintile mean (p < 0.05). Subjects in the highest quintile of family history score had the highest mean WMHI. Recalculation of the family history score, by only counting relatives reported to have had a clinical stroke as a positive event, revealed a nonsignificant correlation with WMHI, but the correlation of the family history score with MRI CVA volume was significant (p < 0.05). Stepwise multivariate analysis including ApoE status, current smoking status, smoking packyear history, Doppler ankle/arm blood pressure ratios, current and long term hypertensive status and current systolic and diastolic pressures indicated that the stroke/hypertension family history score was the single best predictor (p < 0.01) of WMHI volumes. Family history was not an independent predictor of CVA volume.
Prevalence of Cognitive Impairment and Dementia as Defined by Neuropsychological Test Performance
Authors: Larrea Fernando A. , Fisk John D. , Graham Janice E. , Stadnyk Karen
Published: April 2003

The Canadian Study of Health and Aging (CSHA) provided a population-based estimate of the prevalence of dementia of 8% for those aged 65 and older. Other studies have produced both higher and lower prevalence estimates. Factors that may contribute to these differences include: the use of or the reliance on neuropsychological testing, the consideration of functional impairment as a criterion for dementia and the inclusion of the category of cognitive impairment without dementia in the diagnostic classification. We examined the impact of these methodological factors by reanalyzing the CSHA database for those individuals who completed neuropsychological testing. If the diagnosis of dementia required only impaired neuropsychological test performance, there was an increased prevalence of dementia relative to the clinical consensus diagnosis, but including the requirement of functional impairment for dementia reduced this discrepancy. The findings illustrate the need for clear operationalization of diagnostic criteria for cognitive impairment and dementia in neuroepidemiological studies.
Relationships between Cholesterol, Apolipoprotein E Polymorphism and Dementia: A Cross-Sectional Analysis from the PAQUID Study
Authors: Bonarek Mojgan , Barberger-Gateau Pascale , Letenneur Luc , Deschamps Valérie , Iron Albert , Dubroca Bénédicte , Dartigues Jean François
Published: April 2003

This study assesses the cross-sectional relationship between serum cholesterol level and dementia, controlling for apolipoprotein E (apoE) genotype, in a nested case-control study of 334 elderly French subjects aged 73 and over who participated in the PAQUID study (37 demented subjects and 297 nondemented controls). A diagnosis of dementia was established by two-step screening: (1) psychometric testing and DSM-III-R criteria and (2) neurologist’s confirmation. Cholesterol, its fractions and apoE genotype were determined from a blood sample. Elevated high-density lipoprotein cholesterol was associated with a significantly decreased risk of dementia, independent of apoE status and other potential confounding variables, suggesting that cholesterol fractions could be involved in both Alzheimer’s disease and vascular dementia.
Inter-Rater Reliability of the Diagnosis of Vascular Cognitive Impairment at a Memory Clinic
Authors: Wentzel Carolyn , Darvesh Sultan , MacKnight Chris , Shea Catherine , Rockwood Kenneth
Published: April 2003

Consensus criteria for the diagnosis of vascular dementia (VaD) are gradually being replaced with data-based criteria. We report the inter-rater reliability of a new set of empirically-derived criteria for vascular cognitive impairment (VCI). Stratified sampling, with optimal allocation, was employed to randomly select 36 patients from the Queen Elizabeth II Health Science Centre’s Memory Disability Clinic. Chart reviews were conducted independently by 4 physicians. Each physician classified the patients as having either: no cognitive impairment, VCI or Alzheimer’s disease (AD). VCI was further classified both clinically (VCI without dementia, VaD or AD with a vascular component) and radiographically (infarcts, white matter changes, single strategic stroke). The intraclass correlation coefficient (ICC) for the diagnosis by physicians of VCI or otherwise was based on a repeated-measures analysis of variance with raters as the independent variable. A significant coefficient of reliability (average ICC = 0.88, 95% CI = 0.80–0.93) was obtained (Ho: ρ ≤ 0.80, p = 0.03). Where differences in diagnosis occurred, the discrepancies most commonly resulted within the subtypes of VCI (9 cases) or between the diagnoses of AD and VCI (9 cases). Instances of diagnostic incongruity were typically due to the disagreement of a single rater (10 cases). This study demonstrates a high degree of reliability of criteria for VCI by physicians in a memory clinic, and can also be understood as an aspect of construct validation of those criteria. In the absence of a readily available biological marker for VCI, clinical criteria are necessary and can be reliably employed.
Prevalence of Parkinson’s Disease in Bulgarian Gypsies
Authors: Milanov I. , Kmetski Ts. , Lyons K.E. , Koller W.C.
Published: April 2003

We studied the prevalence of Parkinson’s disease (PD) in Gypsies and Caucasians in Bulgaria. Cases were ascertained by examination in a clinic, a screening questionnaire and a door-to-door survey in a region of Sofia, Bulgaria. The prevalence of PD in the Gypsies was found to be 16/100,000 based on 1 case compared to 137/100,000 for Caucasians with 119 cases. It is concluded that PD is rare in Bulgarian Gypsies.
Population Attributable Fraction of Stroke Incidence in Middle-Aged and Elderly People: Contributions of Hypertension, Smoking and Atrial Fibrillation
Authors: Nakayama Takeo , Yokoyama Tetsuji , Yoshiike Nobuo , Zaman Mohammad Mostafa , Date Chigusa , Tanaka Heizo , Detels Roger
Published: April 2003

We determined the population attributable fraction (PAF) of stroke due to hypertension (HT), atrial fibrillation (Af) and smoking in a Japanese community. Residents of Shibata (n = 2,302) who were surveyed initially in 1977 were followed until 1997. Two hundred and thirteen first strokes occurred. Among those 40–64 years of age, the risk ratio (RR) of Af was 11.24, followed by untreated HT (3.61), uncontrolled HT (3.69) and smoking (1.84). The PAFs, however, were 14.9% for smoking, 13.5% for untreated HT, 8.6% for uncontrolled HT and 3.6% for Af. Among those over 65 years, only Af was significant (RR 3.89) and the PAF was 6.0%. Determination of PAFs is also essential for designing effective stroke prevention programs in communities.
Case-Control Study of Meige’s Syndrome
Authors: Behari M. , Sharma A.K. , Changkakoti S. , Sharma N. , Pandey R.M.
Published: April 2003

A pilot case-control study was conducted to identify possible risk factors for Meige’s syndrome. Patients with Meige’s syndrome and age- and sex-matched controls suffering from other neurological diseases were recruited from the Movement Disorders Clinic and Neurology Outpatient Department of the All India Insititute of Medical Sciences. All participants were interviewed and information regarding psychiatric and medical illnesses, use of medications, exposure to fumes, dust and pets, characteristics such as marital status, socio-economic status, alcohol, tea/coffee use, tobacco use, betel nut chewing and family history of neurodegenerative diseases among first-degree relatives was ascertained. We found that betel nut with tobacco chewing was a significant predictor for Meige’s syndrome (adjusted odds ratio 7.4, 95% confidence interval = 1.0–59.82). The role of local irritation or the effect of some chemicals in tobacco and betel nuts needs further evaluation of the pathogenesis of Meige’s syndrome.
Relationships between Cerebrovascular Events, APOE Polymorphism and Alzheimer’s Disease in a Community Sample
Authors: Johnston Janet M. , Nazar-Stewart Valle , Kelsey Sheryl F. , Kamboh M. Ilyas , Ganguli Mary
Published: April 2003

To investigate whether the APOE*4 allele modified the relationship between cerebrovascular events and Alzheimer’s disease (AD), we collected evidence of previous stroke or transient ischemic attack (TIA) and determined APOE genotype among 102 subjects with AD and 375 nondemented subjects in a community-based study of dementia. Subjects with a history of stroke or TIA were twice as likely to have AD as subjects without such a history. However, APOE*4 carriers with a history of stroke/TIA were 5 times more likely than APOE*4 carriers without such a history to have AD (odds ratio = 5.3, 95% confidence interval = 1.4–20.9). History of stroke/TIA had little effect on the likelihood of having AD in subjects without an APOE*4 allele.
Clearance of [125I]-Tumor Necrosis Factor-α from the Brain into the Blood after Intracerebroventricular Injection in Rats
Authors: Chen Guanjie , Reichlin Seymour
Published: April 2003

To test the hypothesis that brain to blood clearance is a mechanism by which brain inflammation and damage can increase circulating acute phase cytokines, rate of transfer of [125I]-tumor necrosis factor-α ([125I]-TNF) from brain to blood was determined. Acid precipitable [125I]-TNF appeared in peripheral blood within 5 min of intracerebroventricular (i.c.v.) injection and was cleared from brain to blood following first order kinetics at a fractional rate of 0.01123 ± 0.0030/min, a value virtually identical with a previously determined clearance rate of [125I]-IL-6. Area under blood concentration curve compared with that after intravenous injection shows that 31.6 ± 5.8% of the intracerebral dose reached peripheral blood in 4 h. Elevated ratios of superior sagittal sinus to aortic blood radioactivity concentration at 1 and 3 h (1.48 ± 0.26, p = 0.042; 1.95 ± 0.39, p = 0.026, respectively) indicate that TNF-α drains from brain at least in part via the sagittal sinus. Escherichia coli lipopolysaccharide i.c.v. injection increased the rate of brain efflux of TNF-α.
A Possible Role for Acetylcholine in the Dialogue between Thymocytes and Thymic Stroma
Authors: Rinner I. , Globerson A. , Kawashima K. , Korsatko W. , Schauenstein K.
Published: April 2003

In this article we will review data suggesting that acetylcholine takes part in the mutual interplay between developing T cells and thymic epithelium, and thereby may influence the generation of the T-cell repertoire. In the first part we will recapitulate our findings according to which cholinergic agonists affect thymocyte apoptosis via a nicotinergic effect on thymic epithelial cells. In the second part we will present evidence that acetylcholine within the thymus is mainly derived from the thymocytes themselves, and that the production and release of this neurotransmitter is dependent on activation of thymic lymphocytes.
Thymus-Derived Glucocorticoids and the Regulation of Antigen-Specific T-Cell Development
Authors: Tolosa Eva , Ashwell Jonathan D.
Published: April 2003

Bidirectional interactions of both a stimulatory and inhibitory nature occur between the neuroendocrine and the immune systems, and these interactions play an important modulatory role during T-cell ontogeny. Specifically, glucocorticoids potently induce apoptosis in thymocytes and activated T cells, but can also rescue these cells from activation-induced cell death. The objective of this review is to discuss current data on the interactions of the immune system with steroid hormones in the thymus and to describe a model that includes glucocorticoids in the shaping of the peripheral T-cell antigen-specific repertoire and deals with their potential role in the generation of autoimmune disease.
Interleukin-1 Inhibits NMDA-Stimulated GnRH Secretion: Associated Effects on the Release of Hypothalamic Inhibitory Amino Acid Neurotransmitters
Authors: Feleder Carlos , Arias Pablo , Refojo Damián , Nacht Silvina , Moguilevsky Jaime
Published: April 2003

Immune system activation is often accompanied by alterations in the reproductive axis. Interleukin-1 (IL-1), a polypeptide cytokine, has been postulated as a chemical messenger between the immune and the neuroendocrine systems. Using superfused hypothalamic fragments explanted from intact male rats, we evaluated the effects of IL-1 (0.5 and 5 nM) on basal and N-methyl-D-aspartate (NMDA)-stimulated release of gonadotropin-releasing hormone (GnRH), and the associated modifications in the output of inhibitory amino acid neurotransmitters involved in the control of GnRH secretion. IL-1 did not modify basal GnRH release, but markedly restrained the stimulatory effect of NMDA on GnRH secretion. γ-Aminobutyric acid, glycine and taurine concentrations significantly increased in the superfusion medium only after pretreatment with the higher dose of IL-1 (p < 0.05). Our results indicate that this cytokine inhibits NMDA- stimulated GnRH release, affecting the activity and/or the release of hypothalamic excitatory and inhibitory amino acid neurotransmitters participating in the regulation of GnRH secretion.
Changes in the Leukocyte Distribution and Surface Expression of Adhesion Molecules Accompanied with Hypothalamically Induced Restlessness in the Cat
Authors: Mori Yoshinobu , Kaname Hitoshi , Sumida Yasuhisa , Tanaka Sansei , Kubo Chiharu , Tashiro Nobutada , Nomoto Kikuo
Published: April 2003

One type of emotional behavior called restlessness occurs when the anteromedial hypothalamus is stimulated in cats. We examined the changes in the distribution and surface expression of adhesion molecules in leukocytes accompanied with restlessness. Mature female cats were used for this study. The cats were stimulated with 60 Hz sine wave train pulses (20–90 μA, 10 s in duration, at 5-min intervals) for 60 min. Samples of blood were collected from 30 min before stimulation up to several hours after the final stimulation. The number of granulocytes increased just after stimulation, while at the same time the expression of L-selectin decreased. On the other hand, the number of CD4+ and CD8+ T lymphocytes decreased at 1–2 h after the end of the stimulation, while the expression of L-selectin increased. In addition, the expression of LFA-1 and VLA-4 did not change. These data suggest that hypothalamically elicited restlessness is thus accompanied by a leukocyte distribution change, which might be mediated by changes in the expression of L-selectin on leukocytes. Plasma cortisol increased during stimulation in restlessness. However, during in vitro culture experiments, cortisol did not alter the expression of leukocyte L-selectin which thus indicated that cortisol does not directly affect the surface expression of L-selectin. These results thus suggest that hypothalamically induced restlessness is a useful stress model for psychoneuroimmunological studies.
Cytokine Effects on Glutamate Uptake by Human Astrocytes
Authors: Hu Shuxian , Sheng Wen S. , Ehrlich Laura C. , Peterson Phillip K. , Chao Chun C.
Published: April 2003

Glutamate uptake by astrocytes has been postulated to play a neuroprotective role during brain inflammation. Using primary human fetal astrocyte cultures, we investigated the influence of selected cytokines on glutamate uptake activity. Interleukin (IL)-1β and tumor necrosis factor-α dose-dependently inhibited astrocyte glutamate uptake, whereas interferon (IFN)-γ alone stimulated this activity. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, blocked IL-1β-mediated inhibition of glutamate uptake, suggesting involvement of nitric oxide in the effect of IL-1β. IL-1 receptor antagonist protein totally reversed the inhibitory effect of cytokines, suggesting a critical role of IL-1β. The anti-inflammatory cytokine IFN-β blocked cytokine (IL-1β plus IFN-γ)-induced inhibition of glutamate uptake with a corresponding reduction in nitric oxide generation. Taken together, these findings suggest that proinflammatory cytokines inhibit astrocyte glutamate uptake by a mechanism involving nitric oxide, and that IFN-β may exert a therapeutically beneficial effect by blocking cytokine-induced nitric oxide production in inflammatory diseases of the brain.
Effect of Interleukin-11 on Body Temperature in Afebrile and Febrile Rats
Authors: Gourine Alexander V. , Rudolph Karin , Leon Lisa R. , Kluger Matthew J.
Published: April 2003

Interleukin (IL)-11 is a member of the gp130 family of cytokines. In contrast to IL-6 (another gp130 cytokine), IL-11 does not induce fever in humans. In the present study, the effect of recombinant human IL-11 (hrIL-11) injected intracerebroventricularly on body temperature of afebrile and febrile rats was studied. Results showed that: (i) hrIL-11 in doses of 5, 50 and 500 ng injected into the cerebral ventricles does not alter body temperature in rats; (ii) febrile response induced by intraperitoneal injection of E. coli endotoxin (50 µg/kg) was initiated more rapidly in rats injected with 500 ng of hrIL-11 in the cerebral ventricles, and (iii) the enhancement of the initial phase of fever induced by hrIL-11 was not accompanied by changes in plasma concentrations of IL-6 and tumor necrosis factor (TNF). These results indicate that hrIL-11 is not pyrogenic when administered into the brain ventricles. The data obtained also demonstrate that central application of hrIL-11 alters body temperature in conditions of pyrogenic stimulation, but that this effect is not due to the alterations in plasma concentrations of IL-6 or TNF. These data suggest that during the development of the systemic inflammatory response, activation of gp130 subunit becomes effective in altering body temperature.
Effect of Orchidectomy on the Age-Related Modulation of IL-1β and IL-1 Receptors following Lipopolysaccharide Treatment in the Mouse
Authors: Nanamiya Wakako , Takao Toshihiro , Asaba Koichi , De Souza Errol B. , Hashimoto Kozo
Published: April 2003

Objective: To compare the effect of orchidectomy (ODX) in 7- and 24-week-old C57BL/6 mice on the age-related responses of the cytokine interleukin (IL)-1β and its receptor to intraperitoneal injection of the bacterial endotoxin, lipopolysaccharide (LPS). Methods: We measured IL-1β concentrations in the plasma, hippocampus, hypothalamus and adrenal gland using ELISA and iodine-125-labeled recombinant human IL-1α ([125I]IL-1α) binding in the hippocampus following the intraperitoneal administration of saline or LPS. Results: There were no significant differences in the concentrations of IL-1β and its receptors in the brain and peripheral tissues between sham-operated and ODX mice in both age groups injected with saline. LPS induced significantly higher IL-1β production in the plasma and hippocampus in sham-operated 24-week-old mice than in 7-week-old mice. Coincident with the heightened IL-1β response to LPS, hippocampal [125I]IL-1α binding was lower in 24-week-old mice than in 7-week-old mice after LPS injection in the sham-operated group. The age-related differences in the IL-1β concentrations in the plasma and hippocampus and [125I]IL-1α binding in the hippocampus in response to LPS administration were abolished by ODX. Although LPS dramatically increased IL-1β levels in the hypothalamus, no significant age-related differences in IL-1β concentrations were seen, and ODX did not affect IL-1β levels. In contrast, there were no significant differences between saline- and LPS-injected 7-week-old mice in relation to concentrations in the adrenal gland. Moreover, although the adrenal IL-1β concentrations in 24-week-old mice were significantly higher than those in 7-week-old mice, ODX did not abolish these age-related differences in concentrations in the adrenal gland. Conclusions: Our data suggest the involvement of testosterone (or gonadal product) in plasma and hippocampal IL-1β regulation in relation to age, and demonstrate the importance of the gonadal development in mediating the effects of infectious challenge on the brain and immune function.
Prolonged P300 Latency in Eating Disorders
Authors: Otagaki Yoko , Tohoda Yoshikuni , Osada Masashi , Horiguchi Jun , Yamawaki Shigeto
Published: April 2003

This study investigated event-related potential (ERP) indices of information-processing in eating disorders. ERPs during an auditory two-tone discrimination task were recorded at midline at 3 sites in 28 anorexic patients, 12 low-weight bulimic patients (body mass index (BMI) under 17.5), 12 normal-weight bulimic patients (BMI over 17.5), and 40 control subjects. The P300 latency was significantly prolonged at all sites in both bulimic groups compared with that in controls, and at frontal and central electrode sites in anorexics. In contrast, the P300 amplitude did not differ between these groups at any site. The prolonged P300 latency in eating disorders suggests a task-related slowing of perceptual decisions that reflects their cognitive impairment.
Positive and Negative Syndromes, and Borna Disease Virus Infection in Schizophrenia
Authors: Iwahashi K. , Watanabe M. , Nakamura K. , Suwaki H. , Nakaya T. , Nakamura Y. , Takahashi H. , Ikuta K.
Published: April 2003

The relationship between Borna disease virus (BDV) infection and positive and negative syndromes in schizophrenia was investigated. By nested RT-PCR and Western blotting, BDV-specific RNA and anti-BDV antibodies were examined in blood from 67 schizophrenic patients (DSM-III-R) in Japan, and the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) were analyzed. There were significant (p < 0.05) differences in the composite index denoting the positive minus negative difference indicating a dominant contribution by negative items, and the proportion of negative type (positive minus negative value below zero) patients, between patients positive and negative for anti-BDV p24 antibodies. It is possible that BDV infection with induction of BDV p24 antibodies may be associated with negative syndromes in schizophrenic patients.
Interferon Alpha-Induced Depression in Chronic Hepatitis C Patients: Comparison between Different Types of Interferon Alpha
Authors: Malaguarnera M. , Di Fazio I. , Restuccia S. , Pistone G. , Ferlito L. , Rampello L.
Published: April 2003

IFN alpha treatment is able to produce dose-related side effects, such as depression, in the central nervous system. We assessed the effects on depression of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the same doses in four homogeneous groups of chronic hepatitis C patients (96 patients; 24 patients for each group). A group of 18 untreated hepatitis C patients was considered as a control group. Depression was measured using Zung’s self-rating depression scale (SDS scale) before starting IFN alpha therapy and at the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS values increased from mild to moderate depression, but never attained severe depression (SDS >70). More elevated SDS values were observed in the 1st month of treatment, with a progressive decrease during the end points above-mentioned. The recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm. Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6-month end point. Leukocyte IFN alpha seemed to present a more elevated tolerability than other IFN alpha types available for clinical practice. A very careful selection of hepatitis C patients is required before starting IFN alpha therapy.
Cortisol, Hypothermic, and Behavioral Responses to Ipsapirone in Patients with Bipolar Depression and Normal Controls
Authors: Shiah I-Shin , Yatham Lakshmi N. , Lam Raymond W. , Tam Edwin M. , Zis Athanasios P.
Published: April 2003

To examine if 5-HT1A receptor function is involved in the pathophysiology of bipolar depression, we measured the cortisol, hypothermic and behavioral responses to ipsapirone, a 5-HT1A receptor agonist, in 8 patients with bipolar depression and 26 normal controls. After obtaining blood samples for baseline cortisol levels and measuring baseline body temperature, a single dose of 0.3 mg/kg of ipsapirone was administered orally to all the subjects, and further blood and temperature readings were obtained every 30 min for 3 h. The results showed that the administration of ipsapirone led to a significant increase in cortisol release and a significant decrease in body temperature both in bipolar depressed patients and normal controls. There was no significant difference in the cortisol or hypothermic responses to ipsapirone between groups. However, there was a significant positive correlation between the Hamilton Depression Rating (HAMD) scores and the hypothermic response in the depressed patients, while the HAMD scores were not significantly correlated with the cortisol response. Comparing our findings with those of previous studies, we suggest that the alterations in 5-HT1A receptor sensitivity in depressed patients may be related to the severity of depression, and they may only occur in more severely depressed patients.
Relationship between Cognitive Function, Growth Hormone and Insulin-Like Growth Factor I Plasma Levels in Aged Subjects
Authors: Rollero Alessandro , Murialdo Giovanni , Fonzi Stefano , Garrone Simona , Gianelli Maria V. , Gazzerro Elisabetta , Barreca Antonina , Polleri Alessandro
Published: April 2003

Basal growth hormone (GH) and insulin-like growth factor I (IGF-I) as well as GH responses to GH-releasing hormone (GHRH) were studied in 22 subjects (7 females, 15 males), aged between 65 and 86 years. The study was aimed at investigating the possible correlations between the age-dependent GH-IGF-I axis decline and the cognitive function – assessed by the Mini Mental State Examination (MMSE). The relationship between hormonal data, cognition and age, body weight, body mass index (BMI), some nutritional indices (triceps skinfolds, TSF, mid-arm circumference, MAC), and physical activity – quantified by the physical functioning index (PFI) – were also analyzed. GH basal levels were within the normal range, while GH responses to GHRH were blunted in most cases. GH peaks after GHRH were directly correlated with GH basal values. IGF-I serum levels were found to be in the lower part of the reference range for adult subjects or below it. GH responses to GHRH, but not GH and IGF-I basal levels, were inversely correlated with subject age. GH secretion areas after GHRH were inversely correlated with BMI, but no further correlations between GH data and clinical or nutritional parameters were found. MMSE values directly correlated with MAC and PFI values. IGF-I levels were directly correlated with MMSE scores, being lowered in patients with more advanced cognitive deterioration, and with MAC values – the decrease of which is thought to reflect protein caloric malnutrition – but not with body weight, BMI, TSF and PFI. MMSE-related protein caloric malnutrition and decreased physical activity possibly take part in affecting IGF- I function in subjects with mild cognitive impairment and, reciprocally, IGF-I decrement might affect neuronal function.
Enlarged Cerebrospinal Fluid Spaces in Opiate-Dependent Male Patients: A Stereological CT Study
Authors: Danos Peter , van Roos Dirk , Kasper Siegfried , Brömel Thomas , Broich Karl , Krappel Christian , Solymosi Lazslo , Möller Hans-Jürgen
Published: April 2003

Computed tomography was performed in 9 male patients with a diagnosis of opiate dependence and in 9 age-matched psychiatric controls (neurotic depression). Patients with a history or diagnosis of another substance dependence (alcohol, cocaine, cannabis) were excluded from the study. The volumes of internal and external components of cerebrospinal fluid (CSF) were measured with a point-counting stereological method. Analysis of variance with age as a covariate revealed a significant enlargement of external and external CSF spaces in male patients with opiate dependence. There was no significant correlation between the length of opiate dependence and the volumes of internal and external CSF spaces. The present results suggest that opiate dependence is associated with structural brain alterations. However, the relationship between opiate dependence and structural brain changes is complex and still not well understood.
Clinical Studies on the Use of Lamotrigine in Bipolar Disorder
Authors: Calabrese Joseph , Rapport Daniel , Shelton Melvin , Kujawa Mary , Kimmel Susan
Published: April 2003

New mood stabilizers that possess efficacy in the depressed phase of bipolar disorder are needed. The use of marketed antidepressants puts bipolar patients at some increased risk for drug-induced hypomania/mania and rapid cycling. During the development of the antiepileptic, lamotrigine, the drug was observed to improve mood, alertness, and social interactions in some patients with epilepsy. These early observations provided the rationale for investigations into lamotrigine’s potential efficacy in bipolar disorder. There are now 14 open clinical reports involving a total of 207 lamotrigine-treated patients with bipolar disorder that suggest this drug possesses a broad spectrum of efficacy in the management of the depressed, hypomanic, manic, and mixed phases of bipolar disorder. In an attempt to replicate and extend these preliminary open-label prospective findings, a series of multicenter, double-blind, placebo-controlled studies evaluating the efficacy and dose-response relationships of lamotrigine in the various phases of the illness, including both acute and maintenance designs in both bipolar I and II disorder, is ongoing.
Lamotrigine in the Treatment of Schizoaffective Disorder
Authors: Erfurth Andreas , Walden Jörg , Grunze Heinz
Published: April 2003

There is accumulating evidence for the efficacy of lamotrigine in the treatment of bipolar disorder, including bipolar depression, both as monotherapy and in combination with sodium valproate. We present the cases of 3 female patients admitted to our hospital with the diagnosis of schizoaffective disorder who were treated with lamotrigine. While dosages up to 200 mg/day, resulting in serum concentrations of less than 5 mg/l, were only partially effective, 400 mg/day (with serum concentrations >10 mg/l) led to considerable mood stability, with complete remission from paranoid symptoms. We suggest that lamotrigine might be helpful in the treatment of schizoaffective disorder, probably with serum concentrations of more than 5 mg/l.
Relationship between Alcoholism and CYP2E1 C/D Polymorphism
Authors: Iwahashi K. , Ameno S. , Ameno K. , Okada N. , Kinoshita H. , Sakae Y. , Nakamura K. , Watanabe M. , Ijiri I. , Harada S.
Published: April 2003

The genotypes of the CYP2E1 loci of 35 alcoholic and 130 nonalcoholic (healthy controls) Japanese were investigated to determine the relationship between CYP2E1 (C/D) polymorphism and susceptibility to alcohol dependence. There was a significant (d.f. = 1, χ2 = 11.0, p < 0.001) difference in the CYP2E1 C gene frequency between alcohol dependents (0.41) and controls (0.28), suggesting that the C gene of CYP2E1 may be related to the risk of developing alcoholism in Japanese, whereas the frequency of the D gene was higher among controls than alcoholics. Healthy Japanese controls showed a significantly (d.f. = 1, χ2 = 30.1, p < 0.001) higher frequency of the C allele than Swedish healthy controls (0.10) did.
Auditory P50 in Schizophrenics on Clozapine: Improved Gating Parallels Clinical Improvement and Changes in Plasma 3-Methoxy-4-Hydroxyphenylglycol
Authors: Nagamoto Herbert T. , Adler Lawrence E. , McRae Kara A. , Huettl Peter , Cawthra Ellen , Gerhardt Greg , Hea Rebecca , Griffith Jay
Published: April 2003

Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizophrenic patients were studied at baseline, after 1 month on clozapine, and again after 15 ± 6.1 (SD) months of clozapine treatment. Eight subjects reached a clinically stable improved state, at which time they had significantly improved P50 auditory gating. One patient had a return of impaired gating after stopping clozapine, as did another during a clinical relapse. Decreasing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatment were correlated with improved P50 gating and improved Brief Bsychiatric Rating Scale-positive scores. This study provides further evidence that improved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year.
Antidepressants Augment Natural Killer Cell Activity: In vivo and in vitro
Authors: Frank Matthew G. , Hendricks Shelton E. , Johnson Donald R. , Wieseler JulieL. , Burke William J.
Published: April 2003

Depressed mood has been associated with reduced natural killer cell activity (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy has resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors. The present study evaluated NKCA in depressed outpatients before and during treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac®). Further, the SSRIs, fluoxetine and paroxetine (Paxil®), were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks. NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. Serum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a standard chromium release assay. Fluoxetine treatment resulted in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine. Further, fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy, suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function.
Effects of Fluoxetine and Dothiepin on 24-Hour Activity in Depressed Patients
Authors: Stanley Neil , Fairweather Diane B. , Hindmarch Ian
Published: April 2003

Psychomotor retardation is a recognised symptom of depressive illness, and improvement in psychomotor function is associated with the amelioration of the severity of depressive symptoms. Actigraphy permits behavioural activity to be continuously assessed, allowing changes in psychomotor activity to be monitored over time. A randomised, parallel-group, double-blind study was conducted in 14 general practice patients with a diagnosis of major depression. This pilot study was designed to investigate the utility of actigraphy in this patient population and to investigate possible differences between fluoxetine and dothiepin in their effects on 24-hour behavioural activity monitored for the first 10 days of treatment. Patients taking dothiepin (75 mg rising to 150 mg in the second week, nocte) were found to be significantly (p < 0.05) less active over the course of the day compared to those treated with fluoxetine (20 mg, mane). This lower level of behavioural activity in the dothiepin group was particularly noticeable in the early morning (06:00–08:00 h).
Variations in CSF Monoamine Metabolites According to the Season of Birth
Authors: Chotai Jayanti , Åsberg Marie
Published: April 2003

The cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) as well as their ratios and correlations were analyzed in relation to the season of birth. The sample consisted of 241 drug-free patients participating in psychobiological programs and comprising the DSM-III-R diagnoses of mood, anxiety and adjustment disorders. Significant season-of-birth variations were found even after adjusting for sex, age, height, the diagnostic category and the month of lumbar puncture. Those born during February to April had significantly lower values of 5-HIAA. Values of HVA and of the ratios HVA/5-HIAA and HVA/MHPG were significantly higher for those born during October to January. Correlation coefficients also showed season-of-birth variations. These results may provide an important link for the season-of-birth variations reported for several neuropsychiatric disorders.
Contingent Negative Variation and Attention in Schizophrenic and Depressed Patients
Authors: Heimberg D.R. , Naber G. , Hemmeter U. , Zechner S. , Witzke W. , Gerhard U. , Dittmann V. , Holsboer-Trachsler E. , Hobi V.
Published: April 2003

Contingent negative variation (CNV) is supposed to be a psychophysiological indicator of attention and arousal. Both have been reported to be deteriorated in schizophrenic and depressed patients. Thirty-four patients with major depression, 43 patients with schizophrenia and 49 healthy subjects were investigated during acute illness with a complex three-stimulus go/no-go task which requires different states of attention: trials consisted of three complex figures that were tachistoscopically presented. Three identical figures had to be confirmed by pressing a button (target condition). CNV was measured: (1) after the first figure waiting for the second (baseline condition), (2) after two identical figures waiting for the third (response-relevant condition), (3) after two different figures waiting for the third (response-irrelevant condition). The response-relevant condition compared to baseline significantly intensified CNV in healthy controls and to a minor extent in depressed patients but not in schizophrenics. In the response-relevant conditions in healthy controls, CNV was significantly reduced compared to the response-relevant condition. This clear discrimination between response-relevant and response-irrelevant conditions was not observed in either group of patients. Thus, the applied CNV paradigm was able to discriminate schizophrenic and depressed patients from healthy controls. Furthermore, subtle differences between schizophrenic and depressed patients were detected, reflected by the different CNV development across experimental conditions.