bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between Bacterial Vaginosis and Adverse Pregnancy Outcome
Authors: Diejomaoh Michael F.E. , Rotimi Vincent O. , Omu Alexander E. , Fernandes Sanjit , Al-Sweih Noura A. , Al-Yatama Majda , Malik Shameem
Published: April 2003

Objective: The main purpose of this study was to investigate the role of bacterial vaginosis (BV) in prematurity, premature rupture of membranes (PROM) and other disorders of pregnancy. Methods: High vaginal and cervical swabs were taken from pregnant women in the second and third trimesters of pregnancy and from 30 non-pregnant women. Informed consent was obtained from all potential subjects. The specimens were smeared, gram-stained and cultured on a variety of selective and non-selective media which were then incubated at the appropriate atmospheres. Vaginal pH, character of the discharge, and outcome of the amine test were noted. Ultrasound was performed to confirm gestational age and all pregnant women followed up until postpartum. Results: A total of 123 pregnant women were evaluated at the end of the study. BV was diagnosed clinically and bacteriologically in 34 women, giving a prevalence rate of 28%. BV was diagnosed in none of the 30 non-pregnant control patients. Fifty-four percent and 46% of the study population were Kuwaitis and non-Kuwaitis, respectively. The mean parity recorded was 2.24 ± 2.06. There was a positive correlation between BV and preterm labour (9/34, 27%; CI, p < 0.05), PROM (7/34, 21%: CI; p < 0.05) and preterm delivery (7/34, 21%; CI, p < 0.05). Three (9%) of the women with BV had babies with intra-uterine growth retardation compared with 1 (1%) in the 89 non-BV group (p < 0.05). Conclusion: The prevalence rate of BV among pregnant women in Kuwait is high and is significantly associated with prematurity and other disorders of pregnancy.
Measurement of the Functional Status in Juvenile Rheumatoid Arthritis: Evaluation of the Arabic Version of the Childhood Health Assessment Questionnaire
Authors: Al-Jarallah K. , Shehab D. , Al-Saeid K. , Moussa M.A.A.
Published: April 2003

Objectives: To evaluate the metric properties, reliability and validity of the translated Arabic version of the Childhood Health Assessment Questionnaire (CHAQ-A) for children with juvenile rheumatoid arthritis (JRA). Methods: The original questionnaire was translated into Arabic without modification and was applied to 38 consecutive children with JRA attending the Out-Patient Rheumatology Clinic in the main teaching hospital of Kuwait. All patients were diagnosed according to the American College of Rheumatology criteria. The questionnaire was given to each patient during a clinic visit and the retest was done after a 7- to 10-day interval. Test-retest reliability was assessed based on the intraclass correlation coefficient. The construct validity was assessed with Spearman’s correlation coefficient between the CHAQ-A and both clinical and laboratory variables of the disease activity. Results: The test-retest reliability was 0.94 for the overall score and ranged between 0.707 (grip) to 0.936 (hygiene) for the subscale score. The construct validity ranged between 0.39 (erythrocyte sedimentation rate) and 0.71 (functional class). Conclusion: This study provides evidence of the reliability and validity of the CHAQ-A in assessing patients with JRA.
Evaluation of the Different Antiphospholipid Antibodies for the Diagnosis of Antiphospholipid Syndrome
Authors: Kaushik P. , Malaviya A.N. , Al-Attiya R. , Moussa M. , Das K.C.
Published: April 2003

Objective: Antiphospholipid syndrome (APS) or Hughes syndrome is a frequently seen condition in Kuwait that is characterised by the presence of significant titres of a variety of antiphospholipid antibodies (aPL). The main clinical features of this syndrome include thrombosis (both venous and arterial), recurrent fetal wastage and thrombocytopenia. The aim of the present study was to find out the antibodies with a high predictive value for the diagnosis of APS. Methodology: The study included a total of 38 subjects. Nine of them were patients with proven primary APS, 10 with secondary APS and 19 were patients (controls) with weak clinical evidence of APS. After a complete clinical examination and routine investigations, the following categories of aPL were estimated by standard laboratory techniques: anticardiolipin antibodies of IgG and IgM isotypes (GPL and MPL, respectively), anti-β2-glycoprotein-I antibodies (anti-β2-GPI) of IgG and IgM isotypes and activated partial thromboplastin time as a surrogate for lupus anticoagulant (LAC). The tests were considered positive if the titres were more than a standard cut-off value provided by the manufacturer of the kits, and in one instance, the normal range was established in our laboratory (LAC). Results: The highest sensitivity (78.9%) and diagnostic accuracy (71.1%) were obtained by the estimation of GPL. However, excellent specificity (100%) and positive predictive value (100%) with almost as good a diagnostic accuracy (68.4%) were also obtained with anti-β2-GPI of IgG isotype. All the other tests performed poorly when compared with these two. There was no difference in the performance of these tests between primary and secondary APS. Conclusion: Of the various aPL estimated, GPL and anti-β2-GPI of IgG isotype were statistically sensitive and specific investigations for confirming the diagnosis of APS.
CT-Guided Percutaneous Drainage of Tuberculous and Non-Tuberculous Deep Pelvic Abscesses
Authors: Sheikh Mehraj , Al-Ali Adel A. , Al-Sumait Basil , Behbehani Abdulla
Published: April 2003

Objective: To assess the utility of comput- ed tomography (CT)-guided percutaneous drainage in the management of tuberculous and non-tuberculous deep pelvic abscesses. Material and Methods: Twelve patients with deep pelvic abscesses were drained under CT guidance. Nine patients were drained with an indwelling catheter of size ranging from 8 to 14 F. Needle aspiration and lavage were performed in 3 patients. Results: Successful drainage was accomplished in all the patients. A single-session catheter drainage was sufficient in all the cases. In 4 out of 12 patients the abscess was of tuberculous aetiology and all were effectively managed with indwelling catheter drainage. Conclusion: CT-guided percutaneous drainage of pelvic abscesses with appropriate chemotherapy is an easy, safe and effective alternative to surgery in the treatment of tuberculous and nontuberculous pelvic abscesses.
Thoracoscopic Upper Thoracic Sympathectomy for Upper Limb Hyperhidrosis
Authors: Farghaly M.M. , Al-Manee M.S. , Ayed A.K. , Khoursheed M.A.
Published: April 2003

Objectives: To present a 30-month experience in thoracoscopic upper thoracic sympathectomy (TUTS) in Kuwait in 20 patients with upper limb hyperhidrosis (ULH). Methods: We performed 40 TUTSs in 20 patients with bilateral ULH. The T2–4 or T2–5 sympathetic ganglia were resected in 36 cases. Only the T2–3 ganglia were resected in 4 cases due to difficult localization of the 4th ganglion. Both sides were performed simultaneously. Chest tube drainage was performed at the end of each procedure. Results: The male:female ratio was 9:1, ranging in age from 13 to 43 years (mean age 26.95 years). Two patients had bilateral dense pleural adhesions, but the procedure was successful. Most patients were discharged on the 2nd postoperative day. Follow-up at 5–30 months (mean 16.3 months) was excellent both for immediate and permanent relief of ULH. Eleven of the 15 patients with pedal hyperhidrosis also had dry feet. Two patients developed transient Horner’s eye syndrome. One patient had persistent right pneumothorax that required chest tube drainage for 7 days. Four patients developed compensatory hyperhidrosis of the trunk and upper thighs. Fifteen patients (75%) expressed complete satisfaction. Five patients (25%) reported return of some moisture to their hands and axillae. Conclusion: TUTS is minimally invasive, feasible and effective. It has a low complication rate. We recommend this procedure as the method of choice for the management of ULH.
Epidemiology of Stroke in the Netherlands from 1972 to 1994: The End of the Decline in Stroke Mortality
Authors: Reitsma Johannes B. , Limburg Martien , Kleijnen Jos , Bonsel Gouke J. , Tijssen Jan G.P.
Published: April 2003

In 1994, stroke was responsible for the death of 4,994 men and 7,601 women in the Netherlands, corresponding to 7.5% of all deaths in men and 11.4% in women. Age-adjusted stroke mortality declined by 39% for men and by 45% for women between 1972 and 1994. However, the decline in mortality levelled off after 1987. In contrast to mortality, age-adjusted discharge rates increased by 47% for men and by 28% for women during the study period. The decline in mortality was equally distributed over the age groups, while the increase in the number of hospital admissions was more pronounced in the older age groups. The analyses by diagnostic subgroups of stroke showed the importance of increasing diagnostic capabilities in the hospital setting. The use of diagnostic subgroups in national mortality data was of limited value, illustrated by the fact that 70% of all stroke deaths in 1994 belonged to the ill-defined type of stroke.
Comparative Study of the Prevalence of Dementia in Two Sicilian Communities with Different Psychosocial Backgrounds
Authors: Azzimondi Giuseppe , D’Alessandro Roberto , Pandolfo Giuseppe , Feruglio Francesco Saverio
Published: April 2003

The role of education and psychosocial environment as factors for the development of dementia is controversial. We carried out a comparative study on the prevalence of dementia among persons over 74 years of age in two Sicilian municipalities, Troina and S. Agata Militello, with different psychosocial backgrounds. A two-stage survey was performed for both samples. In stage 1 the Mini Mental Status Examination (previously validated for the cutoff score with 100% sensitivity and the highest specificity) was used to screen a 50% random sample of persons over 74 years of age. In those referred to stage 2, the diagnosis of dementia was made by a neurologist according to DSM-III R. Three hundred and sixty-five subjects were recruited in Troina and 408 in S. Agata Militello. The minimal estimates of dementia prevalence were 21.9% (21.9% men, 21.9% women) in Troina and 28.4% (26.6% men, 29.6% women) in S. Agata Militello. Although intrasample multiple logistic exact analysis (demented vs. unproven demented) indicated poor formal education and manual occupation as risk factors for dementia, and intersample comparison (Troina vs. S. Agata Militello) showed that these variables were more frequent in Troina, we did not find a higher prevalence of dementia in this community. We discuss this apparently ambiguous result and suggest that psychosocial and cultural variables might be considered multiple interacting factors with different protective or predisposing roles for dementia. Higher or lower risk could then be the result of this complex interaction in different populations.
Gene-Environment Interaction in Alzheimer’s Disease:A Potential Role for Cholesterol
Authors: Chandra Vijay , Pandav Rajesh
Published: April 2003

Alzheimer’s disease is probably a complex disease caused by an interaction of multiple environmental and genetic factors. Genetic defects include ‘causative’ genes which are rare and a ‘susceptibility’ gene (σ4 allele of apolipoprotein E) which is more common in cases. Recent research suggests that environmental factors may interact with a genetic predisposition to modify the risk of Alzheimer’s disease. An interaction between serum cholesterol levels and σ4 genotype is proposed. The evidence for this gene-environment interaction is discussed.
Prevalence of Multiple Sclerosis in the Sanitary District of Calatayud, Northern Spain: Is Spain a Zone of High Risk for this Disease?
Authors: Pina M.A. , Ara J.R. , Modrego P.J. , Morales F. , Capablo J.L.
Published: April 2003

We undertook an epidemiologic study to ascertain the prevalence of multiple sclerosis (MS) in the Sanitary District of Calatayud, in the north-east of Spain. Methods: The study was performed from October 1990 to July 1996. The total number of residents in the area was 58,591. An extensive search was carried out to identify all cases of known or suspected MS through general practitioners and specialists, sanitary authorities in the area, the reference hospital, the Spanish Multiple Sclerosis Society, the newspaper and radio. Results: April 1, 1995 was chosen as prevalence day. The crude prevalence rate for the area was 58 per 100,000 (95% CI: 39–78). The approximate annual incidence rate was 2.6/100,000 (1980–1989). Conclusions: This study and others conducted recently in Spain show that MS is more prevalent than was previously thought and afflicts at least 53–65 per 100,000 population.
A Neuroepidemiological Survey in Rural Bolivia: Background and Methods
Authors: Nicoletti Alessandra , Reggio Arturo , Bartoloni Alessandro , Failla Gaetano , Bartalesi Filippo , Roselli Mimmo , Gamboa Herlan , Salazar Esteban , Paradisi Franco , Tempera Gianna , Hall Andrew
Published: April 2003

A door-to-door survey was carried out in rural areas of the Cordillera province, Santa Cruz Department, Bolivia. A cluster sample of 10,124 inhabitants was selected. The aim was to determine the prevalence of the most common neurological diseases (epilepsy, stroke, parkinsonism and peripheral neuropathy) in this population using a modification of the World Health Organization screening instrument. 1,130 subjects screened positive and were then investigated by neurologists. In this paper we describe the background and methods of the survey and the characteristics of the population.
Relationship of Neurological Function and Age in Older Women
Authors: Sands Marti L. , Schwartz Ann V. , Brown Byron W. , Nevitt Michael C. , Seeley Dana G. , Kelsey Jennifer L.
Published: April 2003

The decline of neurological and neuromuscular function with age in older women and in subgroups of older women with selected risk factors for poor function is described using cross- sectional analyses of data on 8,080 women from the multicenter Study of Osteoporotic Fractures. All twelve performance-based tests of muscle strength, balance, gait, somatosensory discrimination and reaction time declined with increasing age. On a percentage scale, vibration threshold declined the most rapidly with age. Participants who were smokers, physically inactive, nonconsumers of alcohol, diabetics and more frequent fallers had poorer age-adjusted performance than those without these attributes. However, with a few exceptions, the rate of decline in performance with age for those with and without these characteristics did not differ significantly.
Public Health Impact of Carotid Endarterectomy
Authors: Chaturvedi Seemant
Published: April 2003

Despite the completion of several multi-center clinical trials comparing medical management and carotid endarterectomy, there is still controversy as to when carotid endarterectomy is appropriate. The volume of this surgery appears to be increasing. However, available performance data indicate that the surgical proficiency required for the clinical trials is not achieved uniformly in actual practice. Therefore, benefits of carotid endarterectomy, when considered from a public health perspective, are limited by the following: (1) endarterectomy is an expensive stroke prevention modality; (2) endarterectomy addresses the needs of only a relatively small subset of stroke patients, and (3) endarterectomy for asymptomatic patients, without clearer evidence that these individuals benefit, may decrease the cost-effectiveness of this surgical procedure.
Evidence-Based Medicine and Stroke
Authors: Goldstein Larry B.
Published: April 2003

The practice of evidence-based medicine requires the interpretation and use of best evidence from a variety of potential sources as it may apply to an individual patient. There are three critical steps in the practice of evidence-based medicine. First, high quality data from randomized controlled trials, cohort studies, epidemiological research and other sources must be obtained. These results must then be effectively disseminated to health care providers. Finally, medical professionals must implement appropriate changes in their practices. However, available data suggest that there is a gap between physicians’ existing stroke prevention and treatment practices and those supported by the results of clinical trials and other studies. New strategies such as the use of computerized decision support systems are being developed, but their impact on process of care, costs, and patient outcomes must be rigorously evalutated.
Study of HLA as a Predisposing Factor and Its Possible Influence on the Outcome of Multiple Sclerosis in the Sanitary District of Calatayud, Northern Spain
Authors: Pina M.A. , Ara J.R. , Lasierra P. , Modrego P.J. , Larrad L.
Published: April 2003

The relationship between multiple sclerosis (MS) and the HLA antigens DR2 and DQ1 is well recognised, but, in Spain, it has not been clearly defined. The aim of our study was to investigate the relationship between MS and HLA antigens in the sanitary district of Calatayud, northern Spain, and to correlate these antigens with the progression of the disease. Thirty-four patients were selected from a long-term (October 1990 to July 1996) prospective survey in the region where there was a prevalence rate of 58 per 100,000 population. The HLA antigens were determined in 31 patients. A control group of 895 people of Caucasian race was recruited from the same population. We performed serologic tests on all participants. Nucleotide typing was carried out in DR2-positive patients. The most frequent antigens in excess in MS were: A19 (odds ratio, OR: 2.29, p = 0.04), B5 (OR: 2.85, p = 0.02), B41 (OR: 7.65, p = 0.04), CW7 (OR: 3.4, p = 0.004), DR6 (OR: 6.18, p = 0.0001) and DR10 (OR: 3.4, p = 0.004). The DR2 antigen was also more frequent in MS patients (39%) than in controls (19%; OR: 2.69, p = 0.01). All positive DR2 patients showed the DR15(2) split but not the DR16(2) split. The frequency of antigens CW4 and DR1 was lower in MS patients than in controls. The CW4 antigen was detected in 12% of the patients and in 33% of the controls (OR: 0.28, p = 0.04). The DR1 antigen was found in 20% of the controls and in none of the MS patients (OR: undefined, p = 0.01). The DQ1 antigen was observed in 68% of the patients and in 50% of the controls (OR: 2.1, p = 0.07). We did not find any relationship between HLA antigens and progression of the disease. Although we found that DR2 antigen is linked to MS, we also found other antigens related to the disease. This suggests a genetic heterogeneity in our geographic area. We also concluded that the DR1 antigen may play a protective role, as it was detected in 20% of the controls and in none of the MS cases.
Stroke Survival after Discharge from an Acute-Care Hospital
Authors: Lai Sue-Min , Alter Milton , Friday Gary , Lai Sue Ling , Sobel Eugene
Published: April 2003

Background and Purpose: Survival after a stroke is likely to be best for patients well enough to be sent home but the relative risk of dying if patients do not qualify for a home discharge has not been well studied. We investigated the survival prognosis after an initial stroke depending on the facility to which the patient was discharged after an acute initial stroke. Methods: All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed up to 4 years (mean of 24 months) until death, second stroke, or the end of the study. Results: Among 662 patients who were discharged alive after hospitalization with an initial stroke, 128 (19%) went to a nursing home, 17(3%) to a short-term hospital, 140 (21%) to a rehabilitation facility, and 375 (57%) went home (discharge destination unknown for 2 patients). Compared to patients sent home after taking age, sex, selected baseline comorbidities, length of hospital stay, and neurological deficits into consideration, results from Cox proportional hazards model indicated that patients sent to a nursing home had 2.6 times greater risk of dying (95% CI = 1.81–4.15) while those who were discharged to a rehabilitation facility had a death hazards ratio of 1.1. Conclusions: Mortality was greatest in the early months after discharge and decreased thereafter. Since the analysis was adjusted for age, sex, comorbidity, length of hospital stay, and number of neurological deficits, quality of care in a nursing home setting may account for the mortality difference but other factors such as social support network and living will instructions also need to be investigated.
Effects of Cognitive Impairment and Loss of Physical Capacities onSurvival of the Elderly
Authors: Li Chung-Yi , Wu Shwu Chong
Published: April 2003

This study investigates the effects of cognitive impairment and loss of physical capacity on the survival rates of the elderly in Taiwan. Data used for this research were obtained from a longitudinal study in northern Taiwan, where 1,434 elderly respondents were randomly selected and were interviewed in 1993 and 1996. Respondents were categorized into four groups: those with physical disability, those with cognitive impairment, those with neither condition and those with both conditions. The survival rates of these four groups were analyzed and compared. The effects of cognitive impairment and physical disability were assessed separately and jointly. Within the study period, we found that elderly persons with both conditions had the lowest survival rate (0.54, 95% confidence interval (CI) 0.35–0.73), while those with neither condition had the most favorable survival rate (0.92, 95% CI 0.90–0.93). Results from the Cox proportional hazard model showed that physical disability had a significantly adverse effect on the risk of mortality (relative risk 2.5, 95% CI 1.5–4.2), while cognitive impairment did not. Our results are consistent with previous findings which have shown that the decline in physical function affects mortality more than the decline in cognitive function.
CASCADE: A European Collaborative Study on Vascular Determinants of Brain Lesions
Authors: Launer L.J. , Oudkerk M. , Nilsson L.-G. , Alperovitch A. , Berger K. , Breteler M.M.B. , Fuhrer R. , Giampaoli S. , Nissinen A. , Pajak A. , Sans S. , Schmidt R. , Hofman A.
Published: April 2003

Dementia is a highly prevalent disease that may have a cardiovascular component. White matter lesions and brain atrophy (brain abnormalities) are prevalent in dementia cases and might form part of the anatomical basis for the disease. We designed a multi-centre study, CASCADE (Cardiovascular Determinants of Dementia), to examine long-term (10–20 years) and short-term (5 years) cardiovascular risk factors for, and the cognitive consequence of, brain abnormalities. White matter lesions and atrophy are measured with magnetic resonance imaging. Cognitive function is measured with nine tests of memory and executive function. The studies included in CASCADE were ongoing and geographically spread throughout Europe to capture the cardiovascular risk gradient. In each study, a random sample of at least 100 subjects aged 65–75 years was selected who participated in the previous research examinations conducted by the respective centres. The objectives and design of the CASCADE project are described.
Risk Factors for Intracerebral and Subarachnoid Hemorrhage among Hispanics and Non-Hispanic Whites in a New Mexico Community
Authors: Bruno Askiel , Qualls Clifford
Published: April 2003

Background and Objective: A higher incidence of spontaneous intracerebral and subarachnoid hemorrhage among Hispanics than non-Hispanic whites has been measured in Bernalillo County, New Mexico. In an attempt to explain these differences, we compared historical vascular risk factors between Hispanics and non-Hispanic whites living in this community. Methods: An ongoing telephone survey, the Behavioral Risk Factor Surveillance System, collected annual data about vascular risk factors among non-institutionalized, randomly selected adults. Data covering 6 years, 1988–1993, were analyzed. Results: There were 843 Hispanic and 1,635 non-Hispanic white residents of Bernalillo County, New Mexico, who participated in this survey. Because Hispanics were significantly younger than non-Hispanic whites (37.7 vs. 43.4 years, p < 0.001), all other comparisons were adjusted for age. Prevalence of hypertension was similar between these ethnic groups (15–17%). Prevalence of alcohol drinking considered risky for abuse was similar between these ethnic groups (5–6%), but was significantly higher among Hispanic men than women (8.5 vs. 1.6%, p < 0.001). The quantity of alcohol consumption among those at risk for abuse was similar between these ethnic groups. Prevalence of current cigarette smoking was similar between these ethnic groups (22–23%), but Hispanics smoked significantly less than non-Hispanic whites (11.4 vs. 15.2 cigarettes per day, p < 0.001) and among non-Hispanic whites, men smoked significantly more than women (17.0 vs. 13.4 cigarettes per day, p = 0.001). Conclusion: The vascular risk factors which we compared between Hispanics and non-Hispanic whites do not help to explain the higher incidence of hemorrhagic strokes among the Hispanics in Bernalillo County, New Mexico. Additional risk factors for hemorrhagic strokes in these two ethnic groups should be studied.
Dietary Intake of Calcium, Magnesium and Antioxidants in Relation to Risk of Amyotrophic Lateral Sclerosis
Authors: Longnecker M.P. , Kamel F. , Umbach D.M. , Munsat T.L. , Shefner J.M. , Lansdell L.W. , Sandler D.P.
Published: April 2003

Dietary factors have long been suspected of being risk factors for amyotrophic lateral sclerosis (ALS), but few human studies have been reported. To address several of the dietary hypotheses, a case-control study of risk factors for ALS conducted in New England in 1993–1996 included an abbreviated food frequency questionnaire. We examined the dietary intake of calcium, magnesium and antioxidants among 107 ALS cases and 262 community controls. Overall, these dietary factors were not related to risk of ALS, though modestly protective associations were suggested for magnesium and lycopene.
A Single Question about Prior Stroke versus a Stroke Questionnaire to Assess Stroke Prevalence in Populations
Authors: Berger K. , Hense H.W. , Rothdach A. , Weltermann B. , Keil U.
Published: April 2003

Background: False-positive and false-negative answers to screening questions influence prevalence and incidence estimations for stroke in population studies. Despite frequent use in screening, only a few studies have examined causes and influence of incorrect self-reports. We compared the rates of false-positive and false-negative answers to a single question about prior stroke to those of the Stroke Symptom Questionnaire (SSQ), a newly developed instrument based on 6 symptom questions. Differences in stroke prevalence estimations and risk factors for incorrect reports are described. Methods: The MEMO study (Memory and Morbidity in Augsburg Elderly) examines cognitive function and neurodegenerative diseases in an elderly population (n = 384) in southern Germany. All participants filled in the symptom questionnaire, received a neurological examination and a neuropsychological test battery. Medical records were obtained for event validation of subjects positive on screening and those negative on screening with symptoms suggesting a cerebrovascular event during examination. Results: Prevalence of total stroke was 5.3% using a single screening question and 6.8% using the questionnaire. The false-negative rate was higher for the single-question approach (34.2 versus 10.5%). It was strongly influenced by gender and cognitive function. The questionnaire had a higher false-positive rate than the single question. Based on the results, we established question combinations that best served three different research scenarios (frequency estimation, risk factor analysis, control selection), relevant to stroke research in population studies. Conclusions: A single screening question for stroke in the past with event validation by medical records underestimates stroke frequency in population studies by about 30%. Use of a number of questions for key symptoms combined with a general stroke question, as in the SSQ, improves the completeness of event ascertainment and allows the detection of stroke and transient ischemic attack at the same time.
Diurnal Uptake of Circulating Interleukin-1α by Brain, Spinal Cord, Testis and Muscle
Authors: Banks William A. , Kastin Abba J. , Ehrensing Craig A.
Published: April 2003

The effects, synthesis, and release of cytokines show diurnal patterns. We used recombinant human interleukin-1α radioactively labeled with 125I (I-IL) to determine whether its uptake by brain, spinal cord, testis and muscle showed a diurnal rhythm when tested every 4 h in mice. Each tissue showed statistically significant diurnal variation in their uptakes of I-IL ranging from a nearly 10-fold difference for the spinal cord to less than a 2-fold difference for muscle. All nadirs occurred at either 04.00 or 24.00 h and all peaks at 08.00 or 12.00 h. The pharmacokinetics of intravenously injected I-IL did not show any significant variations in blood. Recombinant human tumor necrosis factor-α, which does not cross the blood-brain barrier, did not show a diurnal rhythm in its uptake by any of these tissues. This diurnal variation in the rate of uptake of cytokines by tissues could underlie differences in potency when given at different times of the day.
Role of the Brain in Interleukin-6 Modulation
Authors: Terreni Liana , De Simoni Maria Grazia
Published: April 2003

High levels of interleukin 6 (IL-6) have been found in the brain tissue or cerebrospinal fluid (CSF) in several CNS disorders including Alzheimer’s disease, AIDS dementia complex, multiple sclerois, stroke, Parkinson’s disease, traumatic brain injuries, brain tumors and CNS infections. In these diseases, IL-6 is also found in blood showing that CNS conditions can elicit a peripheral immune response. A direct secretion of IL-6 from brain to blood has been shown to be a major mechanism by which the brain activates peripheral metabolic, endocrine and immune responses. However, this communication is not straightforward and other regulatory mechanisms are likely to be there. Several lines of evidence obtained in the laboratory have shown that the brain significantly modulates IL-6 production in the periphery. Evidence will be given that: (i) central inflammatory stimuli efficiently induce peripheral IL-6; (ii) central opioids are effective modulators of peripheral IL-6, and (iii) the sympathetic nervous system represents an inhibitory pathway to peripheral IL-6.
Effects of a Long-Term Inhalation of Fragrances on the Stress- Induced Immunosuppression in Mice
Authors: Fujiwara Ryoichi , Komori Teruhisa , Noda Yasutaka , Kuraoka Terumi , Shibata Hideki , Shizuya Koji , Miyahara Satoru , Ohmori Masaki , Nomura Junichi , Yokoyama M. Mitsuo
Published: April 2003

The aim of this study was to determine the effects of the long-term application of various fragrances on the suppression of immune response induced by high-pressure stress in mice. The immune response was analyzed based on plaque-forming cell (PFC) count, using mice sensitized with sheep red blood cells. The decreased PFC involving thymic involution induced by high-pressure stress in mice was restored by exposing the stressed mice to tuberose, lemon, oakmoss and labdanum for 24 h following exposure to stress. The decreased PFC and thymic involution from stress were restored by exposure to lemon and oakmoss, but not to tuberose and labdanum when the mice were exposed to those fragrances continuously for 3 weeks before the stress was given, followed by exposure to the same fragrances for 24 h after the stress. The decreased PFC and thymic involution from stress were restored by exposure to lemon and labdanum for 24 h after the stress, but not to tuberose over 3 weeks before the stress was given. These data suggest that the neuroimmunomodulatory effects of fragrances may be affected by tolerance depending on the kinds of fragrances in the case of a long-term application.
Accelerated Maturation of the Thymic Stroma in the Progeny of Adrenalectomized Pregnant Rats
Authors: Sacedón Rosa , Varas Alberto , Jiménez Eva , Múñoz Juan José , Vicente Angeles , Zapata Agustín G.
Published: April 2003

The possible role played by glucocorticoids (GCs) in the development of thymic stromal cell components has been studied in the progeny of adrenalectomized pregnant rats (FAdx), an experimental model which ensures the absence of GCs until the establishment of the fetal hypothalamus-pituitary gland-adrenal gland axis. As previously demonstrated for thymocytes, the lack of GCs early in ontogeny results in an accelerated maturation of the thymic stromal elements. Early expression of specific cell markers for thymic epithelial cell subsets and appearance of a well-established cytokeratin-positive epithelial cytoreticulum confirmed the ultrastructural evidence of a faster maturation of the thymic epithelium in FAdx than in FSham. A similar faster and stronger pattern of both class I and class II molecule expression on the epithelial cells occurred in the former fetuses than in control ones. Changes in the pattern of expression of laminin, but not that of fibronectin, throughout thymic maturation also reflected accelerated maturation. Immunohistochemically identified thymic macrophages appeared late in both FSham and FAdx but in higher numbers in these latter indirectly demonstrating their faster development. Finally, the maturation and turnover of thymic dendritic cells showed a remarkable acceleration in the FAdx. In 15- to 16-day-old FAdx thymuses there was a high number of dendritic cells which sharply decreased in the following days suggesting a massive migration to the periphery and/or in situ cell death. In parallel a new wave of dendritic cell progenitors began to differentiate in the FAdx thymuses but not in the FSham ones. The results are discussed from the view of close relationships known to occur between thymocytes and the stromal components, although a direct effect of GCs cannot be discarded.
Use of Neuroendocrine Hormones to Promote Reconstitution after Bone Marrow Transplantation
Authors: Woody Mary A. , Welniak Lisbeth A. , Richards Susan , Taub Dennis D. , Tian Zhi-Gang , Sun Rui , Longo Dan L. , Murphy William J.
Published: April 2003

A survey of the previous literature and the data shown here indicate that neuroendocrine hormones such as growth hormone and prolactin may be of potential clinical use after bone marrow transplantation (BMT) to promote hematopoietic and immune recovery. The amounts of hormones used in our model do not promote weight gain suggesting that their lymphohematopoietic actions were independent of their anabolic effects. While the hormones may not produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. IL-2 or G-CSF), their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in the post-BMT setting. However, more work needs to be performed to understand the mechanism(s) of their action, particularly with regard to T-cell function and development.
Extracellular ATP: A Further Modulator in Neuroendocrine Control of the Thymus
Authors: Alves Luiz A. , Coutinho-Silva Robson , Savino Wilson
Published: April 2003

It is well established that the process of thymocyte differentiation and maturation occurs in the thymus, where cell-to-cell communication is essential for providing the messages to T-cell precursors. At least two pathways are important for such communication: one via membrane surface molecules and the other via soluble mediators such as cytokines and some hormones. Recently, the presence of receptors for extracellular ATP has been demonstrated on thymocytes and microenvironment cells, and putative functions for this molecule have been proposed. Herein we focus on the recent evidence which supports the view of extracellular ATP and some related nucleotides as novel intrathymic signal molecules. In addition, we discuss the possible physiological implications of such purinergic receptors for the physiology of the thymus.
Vasoactive Intestinal Peptide in Thymus: Synthesis, Receptors and Biological Actions
Authors: Delgado Mario , Martinez Carmen , Leceta Javier , Gomariz Rosa P.
Published: April 2003

Evidence summarized in this report indicates that thymocytes produce and secrete VIP. Moreover, different stimuli such as Con A, LPS and anti-TCR antibody induce a significant increase in VIP production by thymocytes. In addition, proinflammatory cytokines such as IL-1, IL-6 and TNF-α, but not IL-2, stimulate in a similar time-dependent manner VIP production by lymphocytes. We also describe the expression of VIP1 receptor and VIP2 receptor mRNA in murine thymocytes. Thus, VIP released in thymus microenvironment may modulate immune functions through direct binding to VIP receptors on thymocytes. Our functional data support that VIP through the interaction with their specific receptors affect three important aspects of thymocytes function: cytokine production, mobility and apoptosis.
Thymic Expression of the Pancreatic Endocrine Hormones
Authors: Throsby Mark , Pleau Jean-Marie , Dardenne Mireille , Homo-Delarche Françoise
Published: April 2003

The thymus plays a central role in the selection of T lymphocytes that are tolerant to ‘self’ antigens and responsive to foreign pathogens. We and others have reported the expression of the pancreatic endocrine hormones, preproinsulin, proglucagon, prosomatostatin and propancreatic polypeptide in the human and mouse thymus. While mRNA expression is very low there is evidence for the presence of the translated product. In addition, we have investigated the cell types responsible for expression. In the thymus, hormone expression is enriched in the antigen-presenting cell population. Interestingly, while proglucagon, prosomatostatin and propancreatic polypeptide appear to be expressed in a macrophage population, preproinsulin expression was restricted to dendritic cells which are more potent antigen-presenting cells. The functional significance of the endogenous expression of insulin in the thymus has been indirectly investigated using transgenic models in which the transgene is introduced by the rat insulin promoter. The data suggest that thymic expression of the transgene is critical in the induction of T-cell tolerance to the transgene in the periphery. Taken together, the evidence suggests that the low-level pancreatic hormone expression in the thymus may be involved in central tolerance to proteins of restricted expression.
Immunoneuroendocrine Connectivity: The Paradigm of the Thymus-Hypothalamus/Pituitary Axis
Authors: Savino Wilson , Arzt Eduardo , Dardenne Mireille
Published: April 2003

It is now largely established that the immune and neuroendocrine systems cross-talk by using similar ligands and receptors. In this context, the thymus-hypothalamus/pituitary axis can be regarded as a paradigm of connectivity in both normal and pathological conditions. For example, cytokines and thymic hormones modulate hypothalamic-pituitary functions: (a) interleukin (IL)-1 seems to upregulate the production of corticotropin-releasing factor and by adrenocorticotropin by hypothalamic neurons and pituitary cells, respectively; (b) thymulin enhances LH secretion. Conversely, a great deal of data strongly indicate that the hypothalamic-pituitary axis plays a role in the control of thymus physiology. Growth hormone (GH) for example, enhances thymulin secretion by thymic epithelial cells (TEC), both in vivo and in vitro, also increasing extracellular matrix-mediated TEC/thymocyte interactions. Additionally, gap junction-mediated cell coupling among TEC is upregulated by ACTH. In a second vein, it was shown that GH injections in aging mice increased total thymocyte numbers and the percentage of CD3-bearing cells, as well concanavalin-A mitogenic response and IL-6 production. In addition to mutual effects, thymus-pituitary similarities for cytokine and hormone production have been demonstrated. Cytokines such as IL-1, IL-2, IL-6, interferon-γ, transforming growth factor-β and others can be produced by hypothalamic and/or pituitary cells. Conversely, hormones including GH, PRL, LH, oxytocin, vasopressin and somatostatin can be produced intrathymically. Moreover, receptors for various cytokines and hormones are expressed in both the thymus and the hypothalamus/pituitary axis. Lastly, it is noteworthy that a thymus-pituitary connectivity can also be seen under pathological situations. In this regard, an altered HPA axis has been reported in AIDS, human falciparum malaria and murine rabies, that also show a severe thymic atrophy.
Effects of Muramyl Peptides on Macrophages, Monokines, and Sleep
Authors: Pabst Michael J. , Beranova-Giorgianni Sarka , Krueger James M.
Published: April 2003

Muramyl peptides are fragments of peptidoglycan from the cell walls of bacteria. Because of their unique chemistry, the immune system recognizes that muramyl peptides are products of bacteria, and it responds by becoming activated to resist infection. This resistance to infection is nonspecific, and extends to unrelated species of bacteria, fungi, and viruses. A key mechanism of the resistance to infection is activation of macrophages. Macrophage activation results in increased production of microbicidal oxygen radicals like superoxide and peroxide, and in increased secretion of inflammatory cytokines like interleukin-1β and tumor necrosis factor-α. These cytokines, besides activating neutrophils, B lymphocytes, and T lymphocytes, act on the central nervous system to induce physiological responses like fever and sleep. These physiological responses also aid in combating infection. Muramyl peptides also activate macrophages and other cells of the immune system to kill cancer cells. Muramyl peptides and similar agents will become more important as therapeutic agents in the future, due to increasing resistance of microbes to antibiotics, and increasing numbers of patients with immunodeficiencies.
Mouse Tumor Necrosis Factor-α Increases Brain Tryptophan Concentrations and Norepinephrine Metabolism While Activating the HPA Axis in Mice
Authors: Ando Tetsuya , Dunn Adrian J.
Published: April 2003

Endotoxin (LPS) administration has been shown to activate the hypothalamo-pituitary-adrenocortical (HPA) axis and increase cerebral catecholamine and indolamine metabolism and tryptophan concentrations. LPS stimulates the secretion of tumor necrosis factor-α (TNF-α) as well as interleukin-1 and interleukin-6. We have investigated the role of TNF-α in the LPS-induced neurochemical and neuroendocrine changes. When recombinant mouse TNF-α (mTNF-α) was injected intraperitoneally (i.p.) into mice, plasma corticosterone concentrations were elevated reaching a peak at 30 min. Two hours after injection, cerebral tryptophan concentrations were also elevated in several brain regions, as well as the ratio of brain 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) to norepinephrine (NE) in the hypothalamus. An intravenous (i.v.) injection of mTNF-α also increased cerebral tryptophan concentrations and MHPG/NE ratios at 2 h and caused a rapid and prolonged elevation of plasma corticosterone concentrations lasting for at least 2 h. We observed no significant changes in dopamine or its catabolites, or in 5-hydroxytryptamine or its major catabolite, 5-hydroxyindoleacetic acid, after either i.p. or i.v. injections. These results suggest that TNF-α may contribute to the HPA, neurochemical and behavioral responses to LPS and other stimulators of the immune system.
Olfactory Bulbectomy Provokes a Suppression of Interleukin-1β and Tumour Necrosis Factor-α Production in Response to an in vivo Challenge with Lipopolysaccharide: Effect of Chronic Desipramine Treatment
Authors: Connor Thomas J. , Harkin Andrew , Kelly John P. , Leonard Brian E.
Published: April 2003

The olfactory bulbectomized (OB) rat has been developed as an animal model of depression and exhibits several behavioural and neurochemical characteristics that are qualitatively similar to those found in clinically depressed patients. In addition to the behavioural and neurochemical abnormalities seen in OB rats, it has been reported that these animals have alterations in a number ex vivo measures of immune function many of which are reversed following chronic antidepressant treatment. In the present study we sought to examine the effects of olfactory bulbectomy on responsiveness to an in vivo immune challenge with bacterial lipopolysaccharide (LPS; 100 μg/kg, i.p.). In addition, the effect of chronic treatment with the tricyclic antidepressant desipramine (7.5 mg/kg, i.p.) on bulbectomy related behavioural changes, hypothalamic-pituitary-adrenal axis activity and immune responsiveness was evaluated. To our knowledge this is the first time that in vivo immunological responsiveness has been examined in the OB rat model of depression. OB rats exhibited a characteristic hyperactive response in a novel ‘open field’ environment, which was attenuated following chronic desipramine treatment. LPS provoked a large increase in circulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α in vehicle treated sham operated animals. Vehicle treated OB rats displayed a significant impairment in LPS-induced IL-1β (54%) and TNF-α (70%) secretion compared to their sham operated controls, an effect that was potentiated following chronic desipramine treatment. Furthermore, sham animals that were chronically treated with desipramine displayed decreases in LPS-provoked IL-1β (51%) and TNF-α (49%) secretion compared to vehicle treated counterparts. In addition, LPS-induced alterations in corticosterone and adrenal ascorbic acid concentrations were also attenuated by bulbectomy, an effect that was further enhanced following chronic desipramine treatment. In conclusion, these data provide evidence that olfactory bulbectomy in the rat impairs the ability of macrophages to produce the proinflammatory cytokines IL-1β and TNF-α following an in vivo challenge with bacterial LPS. Whilst chronic treatment with desipramine normalized the behavioural hyperactivity observed in OB rats, such treatment further impaired LPS-induced IL-1β and TNF-α secretion in bulbectomized rats.
Lipopolysaccharide-Induced Leptin Release Is Not Mediated by Nitric Oxide, but Is Blocked by Dexamethasone
Authors: Mastronardi Claudio A. , Yu Wen H. , Rettori Valeria , McCann Samuel
Published: April 2003

The adipocyte hormone, leptin, has homology with tumor necrosis factor-α (TNF-α) and the leptin receptor (OB-Rb) has homology with the interleukin(IL)-6 receptor. Lipopolysaccharide (LPS) from gram-negative bacteria stimulates the release of many pro-inflammatory cytokines, such as TNF-α, IL-1 and IL-6, among others. To test the hypothesis that LPS would also stimulate the release of leptin, LPS (0.6 mg/kg) was injected intravenously into conscious male rats bearing external jugular venous catheters. Vehicle (0.9% NaCl) was injected into control animals. Blood samples (0.3 ml) were drawn immediately before injection and every 10 min afterwards for 120 min. Plasma leptin concentrations increased gradually in the LPS-treated rats, reaching a peak at 120 min of nearly twice the starting level. To determine if this release was mediated by nitric oxide (NO), nitroarginine methyl ester (NAME), an inhibitor of NO synthase, was injected at doses of 11 or 23 mg/kg (i.v.). The lower dose decreased plasma leptin slightly, whereas the higher dose of NAME increased plasma leptin at 110 min but had no effect on LPS-induced leptin release. On the other hand, dexamethasone (DEX) (0.85 mg/kg), a synthetic glucocorticoid, injected 15 min before LPS, decreased LPS-induced leptin release by 80% (p < 0.001). The results indicate that LPS is a stimulant of leptin release, that NO has little control over basal or LPS-induced leptin release, but that glucocorticoids, epitomized by DEX, largely block LPS-induced leptin release. Increased release of leptin during infection may contribute to the decreased feeding, altered hormonal release and metabolic changes that occur during infection.