bluuebunny/crossref_metadata_2025 huggingface dataset:
Bardet-Biedl Syndrome: Clinical, Endocrinological and Imaging Evaluation of Three Unrelated Bedouin Children
Authors: Saleh Samir I. , Mady Samir A. , Al-Ghanem Mohammed M. , Farag Talaat I.
Published: April 2003

Objective and Importance: Bardet-Biedl syndrome (BBS) is a heterogeneous disorder; clinical dissimilarities do exist among patients. Cases of BBS have been reported with hypertension, diabetes mellitus and renal disease, while others were reported with hepatic disease. Here, we are reporting 3 newly diagnosed unrelated Bedouin children, evaluated for the presence of an endocrine disorder. Clinical Presentation: Our patients were 2 males and 1 female. These patients are obese with a voracious appetite, postaxial polydactyly and mentally retarded. Pigmentary retinopathy was found in the older children and hypogenitalism is apparent in the older male child who is also hypertensive. The clinical, endocrinological and imaging evaluation data are compared with previously published cases. Also, phenotypic variability and genetic heterogeneity of BBS pleiotropic gene are briefly discussed. Conclusion: The results of hormonal studies in our cases showed no endocrinological dysfunction, except for the presence of hypogonadism. Although no specific treatment is available, an early evaluation of BBS cases can be the first step in initiating symptomatic management and preventive measures for the patient and the family.
Imaging of the Pituitary Gland in Cushing’s Disease
Authors: Gupta Renu , Gambhir Manpreet , Ammini A.C.
Published: April 2003

Objective: To evaluate the sensitivity of computed tomography (CT) and magnetic resonance imaging (MRI) of the pituitary gland in detecting pituitary adenomas in patients with Cushing’s disease. Methods: Twenty-five patients aged 8–55 years (average age 30 years), clinically and biochemically diagnosed as having Cushing’s disease, were evaluated with a contrast-enhanced CT scan and MRI of the pituitary gland. Contrast-enhanced CT scans of direct 2-mm-thick coronal sections were performed. Pre- and post-enhanced MRI of the pituitary gland was performed on a 1.5-tesla superconducting magnet, taking 2-mm-thick sections in the sagittal and coronal planes. Results: MRI revealed adenomas in 16 patients (12 microadenomas and 4 macroadenomas). Twelve (75%) adenomas were delineated more clearly on post-gadolinium MRI scans. Nine (56%) adenomas were better delineated on coronal images. Out of 16 adenomas identified on the MRI, only 5 were seen on the CT scan. All patients underwent trans-sphenoid surgery and the MRI findings were confirmed. Conclusion: Contrast-enhanced MRI is the preferred modality for the detection of ACTH-secreting adenomas, which are difficult to visualize on CT scans due to their small size. A focal hypointense lesion is the commonest finding on T1-weighted images and, if identified on coronal sections, is the most sensitive diagnostic criterion. However, a negative MRI does not exclude the presence of a microadenoma.
Association of Major Histocompatibility Complex with Psoriasis vulgaris in Adult Kuwaitis
Authors: Mahmoud Fadia , Alsaleh Qasem , Abul Habib , El-Naby Hussein Hassab , Al Harbi Saleh
Published: April 2003

Objective: The association of the major histocompatibility complex (MHC) with psoriasis vulgaris has been reported in different ethnic groups. However, an identification of human leukocyte antigen (HLA) genes that determine susceptibility to the disease has not been reported previously among the Arabs of the Arabian Peninsula. This study was conducted with the objective of establishing any correlation between psoriasis and the expression of HLA class I and class II in a Kuwaiti population. Methods: Expression frequencies of the MHC were measured in 26 Kuwaiti patients with psoriasis, and 60 control individuals were matched for age, sex and ethnic background. Tissue typing for class I and class II antigens was carried out by lymphocytotoxicity assays. Results: HLA-CW6, DQ2 and DQ7 were significantly increased in patients compared to controls (p = 0.0002, 0.0044 and 0.0004, respectively), while HLA-B7, DR5 and DR52 were significantly decreased (p = 0.002, 0.0004, 0.019, respectively). Conclusion: These findings suggest that psoriasis is associated with HLA-CW6, DQ2 and DQ7 in the Kuwaiti population. Further studies to investigate the association of distinct HLA with psoriasis vulgaris based on the RNA levels are under way.
Spinal Extradural Hydatid Cyst
Authors: Sheikh M. , Osman M.
Published: April 2003

Objective and Importance: Hydatid disease of the bones is uncommon. Spinal hydatid disease presenting with compressive neuropathy is very rare. This case is presented for the rarity of this condition. Clinical Presentation: An adult male patient with previously treated hydatid cyst of the liver presented with symptoms of spinal nerve root compression. MRI of the spine revealed an extradural cyst which was treated with surgical excision. Conclusion: Patients with a known history of hydatidosis should be suspected of spinal hydatid when presenting with symptoms or signs of cord or nerve root compression.
Cytotoxic Factor in Dengue Haemorrhagic Fever
Authors: Chaturvedi U.C. , Agarwal R. , Misra A. , Mukerjee R. , Kapoor S. , Nagar R.
Published: April 2003

Objective: Cytotoxic factor is a unique pathogenesis-associated cytokine that is produced in mice (mCF) and man (hCF) during dengue virus infection. This study was undertaken to investigate the prevalence of hCF and its relationship to the duration and severity of the illness, and to ascertain its role, if any, in the pathogenesis of dengue fever (DF) and dengue haemorrhagic fever (DHF). Methods: Peripheral venous blood was collected from the patients of various grades and on different days after the onset of clinical illness. Sera were collected from a total of 333 cases, and analysed for the presence of hCF by inhibition ELISA and dot blot tests. Result: The positivity for hCF was 100% in cases of DHF grades III and IV, while overall positivity was seen in 295 out of 333 (88%) cases studied. Sera collected from the 1st to the 20th day of illness were positive for hCF. This was not seen at later periods. A majority of cases (52%) were below 15 years of age and peak positivity of 96% was noticed in the age-group of 11–15 years. The mean inhibition value of the ELISA was lowest (40 ± 8%) in cases of DF and was highest (70 ± 10%) in DHF grade IV, and the peak titres were found on the first 4 days of the illness. Conclusion: The findings show the presence of hCF in the majority of cases. It is detectable up to the 20th day of illness and may suggest an association of higher levels of hCF with the onset and severity of the illness.
Vitamin A Status in Healthy Kuwaiti Newborn and Their Mother Pairs Selected from a Local Hospital Population
Authors: Molla AbdulMajid , Hamoud Majeda Sabri , Jalil WasfiAbdul , Molla Ayesha , Sharma P.N. , Srivastava BrahmSwaroop
Published: April 2003

Objectives: Both clinical and subclinical vitamin A deficiency has substantial impact on the mortality and morbidity of infectious diseases among children. We prospectively studied the serum retinol level in 200 neonates and their mothers at the Al-Adan Hospital in Kuwait. Methods: Five millilitres each of cord blood and maternal venous blood were collected at the time of delivery. Serum was separated and transported under specified conditions to the laboratory. Serum retinol was estimated using high performance liquid chromatography. Results: Mean serum retinol levels of both babies and mothers were found to be adequate, being 48 and 57 µg/dl, respectively. Significant correlation (p < 0.01) was obtained between serum retinol levels for the babies and their mothers. Conclusion: The results of this study demonstrate that vitamin A deficiency is not present among the neonates and their mothers studied. A larger population survey is recommended in some high risk areas of Kuwait.
Sonographic Features of Salivary Gland Tumours
Authors: Al-Tamami Mohi , Al-Naqeeb Nail , Kovacs Agnes , Dashti Hussein , Patrick John Madda
Published: April 2003

Objective: High resolution ultrasonography (US) has played a significant role in the study of salivary gland (SG) pathology and has surpassed sialography in the study of SG tumours. This report discusses the sonographic features of SG tumours examined during the last 5 years. The value of these features as diagnostic indicators of the nature (benign or malignant) and histotype of these tumours is assessed. Methods: High resolution ultrasonography was used in the study of 83 cases of salivary tumours, 78 of which were of the parotid gland and 5 of the submandibular gland. Sixty-six (80%) of these tumours were benign. An US scanner with a 7.5-MHz real-time linear probe was used. The diseased SG was examined in multiple planes to fully delineate and locate the lesions and to characterize their sonographic features. Results: US detected and correctly located all tumours. The sonographic features of the various tumour categories studied are presented with special emphasis on diagnostically significant ones. The value of these features as diagnostic indicators of the nature (benign or malignant) and the histotype of these tumours is assessed. In this study, the rate of correct US identification of tumour benignity was 100% in a group of 15 adenolymphomas and 12 benign non-epithelial tumours, and 94% in a group of 34 pleomorphic adenomas. Five cases of recurrent pleomorphic adenoma were also studied. Correct US identification of malignancy was achieved in 82% of malignant tumours (15 carcinomas and 2 isolated primary non-Hodgkin’s lymphomas of the parotid gland). US identification of the specific tumour histotype was quite successful in the case of benign tumours with an accuracy of 84% in pleomorphic adenoma, 93% in adenolymphoma, and 100% in vascular tumours and lipoma. Only 1 of the 17 malignant tumours (a carcinomatous pleomorphic adenoma) was specifically identified. Conclusion: Based on the diagnostic capabilities of US revealed in this study as well as its operational advantages, US is strongly recommended as the first-line imaging procedure for all masses at the SG regions, to be followed by US-guided fine needle aspiration biopsy particularly for equivocal cases.
A Rare Bone Dysplasia and Chronic Lung Disease
Authors: Dawson K.P. , Al-Gazali L.I. , Bakalinova D.
Published: April 2003

Objective: To illustrate the development of chronic lung disease in an 11-year-old child with spondylo-meta-epiphyseal dysplasia-abnormal calcification type. Method: Historical review and radiological investigation by high resolution computerized tomography of the thorax. Results: Severe bronchiectasis with a mosaic perfusion pattern was demonstrated. The onset of lung disease was insidious in the absence of a history of recurrent respiratory infection and symptoms. Conclusion: We postulate that the rigidity of the chest wall led to restrictive lung disease. Children with this type of dysplasia need careful monitoring of their respiratory status during their early years.
Static Image Telepathology in Routine Surgical Pathology Diagnosis: A Report on the First Experience in the Arab World from Kuwait
Authors: Francis I.M. , Junaid T.A. , Dajani Y.F.
Published: April 2003

Objective: Telepathology (TP) diagnosis is currently practiced in several countries. The present study presents the first documented experiment of static-image TP in Kuwait and the Arab world. Materials and Methods: Paraffin or frozen tissue sections of 100 cases of routine surgical pathology consisting of 40 malignancies, 10 benign neoplasms and 50 nonneoplastic conditions were studied. Diagnostic microscopic images captured by a microscope-attached digital camera were selected by a pathologist in each case and sent with the clinical history to a second pathologist via E-mail across the Internet. The diagnosis was sent back to the referring pathologist via E-mail. The specificity, sensitivity and diagnostic accuracy of TP was calculated. Results: For malignant versus benign lesions, the diagnostic accuracy was 97% with 3 false-negative and no false-positive results (100% specificity). Correct diagnosis by exact category was 92%. The deferral rate awaiting special stains was 5%, immunohistochemistry 6%, and extra images 2%. In 2 cases (2%), there was a request for original tissue glass slides. Conclusion: A simple E-mail-based TP system provides a high diagnostic accuracy for routine surgical pathology diagnosis. It can be utilized either as a primary or a secondary diagnostic tool.
Comparison between DNA Image Analysis and Cytology in the Assessment of Spermatogenesis
Authors: Al-Salim A. , Francis I. , Al-Juwaiser A. , Abdulla M. , John B.
Published: April 2003

Objective: The aim of the study is to evaluate the DNA image analysis of smears in assessing spermatogenesis and to compare it to routine fine-needle aspiration cytology (FNAC). Methods: A total of 33 testicular needle aspirates from azoospermic infertile patients were blindly studied by 2 different cytologists separately; one studied the FNAC and the other evaluated the DNA contents. DNA image analysis was done on Feulgen-stained cytology smears. The generated DNA histogram was compared to cytology results. Results: Twenty-three (69.7%) testes showed complete agreement between the image analysis and cytology mainly in the presence of sperms, while 10 (30.3%) testes showed discrepancy between the DNA image analysis and cytology, mainly in the syndrome with Sertoli cells only and spermatogenic arrest. Conclusions: DNA image analysis of testicular aspirates is an objective and reliable method in assessing spermatogenesis, while cytology is a relatively subjective method and observer dependent. The discrepancy may be explained by cytologist inter- and intra-observer variability in evaluating spermatogenesis in the FNAC specimens.
Causal Factors and Management Options of Infertility in Kuwait
Authors: Omu A.E. , Al-Qattan F. , Ismail A.A. , Al-Taher S.I. , Al-Busiri N. , Bandar A.
Published: April 2003

Objective: To determine the main causes and management options of infertility in Kuwait. Methodology: Clinical evaluation, hormone profile of LH, FSH, prolactin and testosterone and midluteal phase progesterone, tubal patency tests, semen analysis and antisperm antibodies were assessed. Treatment included medical and surgical induction of ovulation. Male factor infertility was treated with antibiotics and immunosuppression when indicated, and empirically with antioxidants. Results: The main cause of female infertility was ovarian dysfunction (40.7%) with predominance of polycystic ovarian syndrome (52.9%), anovulatory regular cycles (25%) and hyperprolactinaemia (14.3%). Male factor accounted for infertility in 40.2% of the couples, with asthenozoospermia in 34.3%, oligozoospermia in 29.2% and azoospermia in 8.2%. Immuological tubal factors and endometriosis occurred in 9.8, 5.9 and 5.6%, respectively, and unexplained infertility in 8.5%. Both spouses were involved in 36.5% of the couples. Clomiphene citrate was the commonest agent for induction of ovulation with an 80% success rate. Bromocriptine, gonadotropins and laparoscopic ovarian cautery had success rates of 71, 69, and 80%, respectively. Treatment outcome in male factor infertility was variable. Conclusion: Ovarian dysfunction and male factor infertility are the dominant factors responsible for infertility in Kuwait. Induction of ovulation has a good prognosis of 40–80% success rate. Tubal factor infertility is uncommon in Kuwait.
Status of Risk Factors for Vascular Dementia
Authors: Skoog Ingmar
Published: April 2003

The two most common causes of vascular dementia (VAD) are dementia evolving in connection with multiple small or large strokes and dementia related to ischemic white-matter lesions (WMLs) of the brain. The knowledge about risk factors for these disorders is still scarce. Besides sharing risk factors with stroke, dementia with multiple small or large brain infarcts is also associated with non-vascular risk factors such as high alcohol consumption, psychological stress in early life, lower formal education, blue collar occupation, and occupational exposures. Risk factors for dementia in stroke victims include stroke-related and non-stroke related risk factors. Non-stroke-related factors are similar to those found in Alzheimer’s disease. The main risk factors for ischemic WMLs are hypertension or increased blood pressure, but WMLs have also been associated with a number of other vascular risk factors. In recent years, Alzheimer’s disease (AD) has also been reported to be associated with vascular risk factors, including hypertension, coronary heart disease, atrial fibrillation, diabetes mellitus, and WMLs. Although these associations may reflect an overdiagnosis of AD in cases with silent cerebrovascular disease, or that cerebrovascular disease increases the possibility that individuals with Alzheimer lesions will express a dementia syndrome, there are also alternative explanations. AD and cerebrovascular disease may for instance share similar risk factors or etiologic pathways. The pathogenetic implications for the association between AD and vascular factors need to be further explored. There is also a need for more studies on risk factors for VAD and risk factors for dementia in stroke samples, as well as studies on non-vascular risk factors for ischemic WMLs.
Disposition after Acute Stroke: Who Is Not Sent Home from Hospital?
Authors: Lai Sue-Min , Alter Milton , Friday Gary , Lai Sue-Ling , Sobel Eugene
Published: April 2003

Background: Known demographic and clinical characteristics of stroke survivors that affect selection of the facility to which they are discharged after hospitalization for an acute stroke are, for the most part, not population based and therefore may be unrepresentative. We present an analysis of such characteristics using the Lehigh Valley stroke cohort which is population based. Method: We enrolled patients within 1 month of onset of their initial acute stroke who were hospitalized between 1987 and 1989 at one of the eight hospitals in the Lehigh Valley, and 662 patients were discharged alive. The facility to which they were discharged was known for 660. Data on age, sex, presence of five selected comorbidities (hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus and transient ischemic attacks), length of hospitalization and neurologic deficits from the stroke were systematically collected on standardized forms. Polytomous logistic regression was used to determine the factors associated with not being discharged home. Relative risk (RR) associated with discharge to a nursing or rehabilitation facility for each independent predictor was calculated using as the referent, those who went home. Results: Older age was a statistically significant predictor of not being sent home (RR = 1.2 for nursing home placement), but gender and living with a spouse were not. Having a selected comorbidity did not increase the RR of not being sent home regardless of the type, nor did risk of not being sent home increase with more than one illness. Considering neurologic deficits from the stroke, patients with lower extremity weakness had a 2.6- and 3.5-fold risk of being sent to a nursing or a rehabilitation facility, respectively, compared to those without such weakness while for those with upper extremity weakness, the RR was 1.5 and 4.9, respectively. Language deficit imposed a RR of 3.1 and 2.3 of going to a nursing or rehabilitation facility, respectively. Right facial weakness also emerged as a significant risk factor for not being discharged home, perhaps because of its association with language deficit. The longer a patient was hospitalized after a stroke, the less likely it was that such a patient would go home (RR = 1.1/hospitalization day). Conclusion: Using population-based data on stroke survivors, our study showed the characteristics of patients who are less likely to be discharged home and, instead, are discharged to a nursing or a rehabilitation facility. Data like ours which were population based may be useful in discharge planning for stroke patients by policy makers and health care providers.
Pitfalls in Neuroepidemiologic Research
Authors: Anderson Dallas W. , Rocca Walter A. , Rosário Joana A.
Published: April 2003

In neuroepidemiologic research, there are many pitfalls to trap unwary investigators, whether the project is a survey, a case-control study, or some other type of study. We briefly discuss pitfalls relating to: research preliminaries (e.g., failure to decide on study objectives); personnel and training (e.g., deficient training); data collection (e.g., ineffective supervision); data ownership and data sharing (disagreement about how the data will be used), and report preparation (e.g., failure to interpret results in the context of uncertainties arising from the design and implementation of the research). Awareness of these pitfalls will reduce the likelihood of flawed or ineffective neuroepidemiologic research.
Preventable Neurological Diseases Worldwide
Authors: Bergen Donna C.
Published: April 2003

Neuropsychiatric disorders make up a large proportion of medical conditions causing disability and death worldwide. This paper reviews the most significant neurological disorders, emphasizing the preventability of most of them. The worldwide impact of cerebrovascular disease, protein-energy malnutrition causing cognitive impairment, tetanus, dementia, meningitis, and epilepsy is summarized. The burden of neurological dysfunction as a complication of tuberculosis, measles, road accidents, congenital anomalies, malaria, falls, war, violence, alcohol, HIV, diabetes, syphilis, and rheumatic heart disease might also be lessened by preventive measures. As in other health problems, major risk factors are poverty, poor access to health care, and social instability.
Seizure Disorders in Preschool Children in a Serbian District
Authors: Pavlovic Milen , Jarebinski Mirjana , Pekmezovic Tatjana , Levic Zvonimir
Published: April 2003

All children born in 1989 and 1990 in the district of Kruševac in Central Serbia (population 140,000) were followed to the end of 1995. The total number of children was 3,102. The cumulative incidence of febrile seizures was 25.1/1,000, that of single febrile seizures 3.9/1,000 and that of epilepsy (i.e. recurrent afebrile seizures) 6.5/1,000. The peak age-specific rate of the first febrile and the first afebrile seizure was in the second year of life (11.6/1,000 and 2.9/1,000, respectively). Among 20 cases of epileptic children, the most common type of seizure was the generalized type – 14 cases (70%), while 6 children (30%) suffered from partial seizures. Of these epileptic children, there were 7 children (35%) with associated neurological abnormalities and/or mental retardation, including one with tuberous sclerosis. Thirteen of the total number of epilepsy cases were considered as having active epilepsy (i.e. still having had seizures and/or being on antiepileptic therapy). The calculated point prevalence rate was 4.2/1,000 on December 31, 1995.
Stroke in Young Adults: Progress and Opportunities
Authors: Kittner Steven J.
Published: April 2003

The epidemiology of stroke in young adults has been a relatively neglected area of study considering its relative prevalence in clinical practice; the relationship of oral contraceptive use, pregnancy, and migraine to stroke risk; and the importance of prognosis when stroke occurs at a young age. In addition, stroke in young adults can be used as a model system for understanding stroke incidence trends, the excess stroke risk experienced by African-Americans, and novel risk factors for stroke, including the genetic basis for stroke risk.
Antihypertensive Medication Compliance in African-American Stroke Patients: Behavioral Epidemiology and Interventions
Authors: Friday Gary H.
Published: April 2003

Hypertension is a major cause of stroke in the African-American community, and lack of control of hypertension appears to be common. Improving compliance to antihypertensive therapy in African-American stroke patients could have a significant impact on recurrent stroke rates. Little is known about factors affecting compliance in this community and which interventions would be effective in improving compliance. Health behavior models which assess the patient’s perception of stroke and hypertension, barriers to the desired behavior, perception of ability to perform the behavior, perception of others’ acceptance of the behavior and the patient’s behavioral stage could be used to tailor interventions to improve compliance. A plan to improve compliance should take into account the target population’s baseline rates of compliance, perception of need for intervention and risk factors for noncompliance.
A Brief Cognitive Screening Battery for Dementia in the Community
Authors: Belle Steven H. , Mendelsohn Aaron B. , Seaberg Eric C. , Ratcliff Graham
Published: April 2003

Screening community samples for dementia often necessitates administering a cognitive test battery by trained personnel. Because diagnostic examinations are expensive, a useful screening battery must be highly specific in addition to having high sensitivity. The Monogahela Valley Independent Elders Survey (MoVIES) includes a random sample of community-dwelling participants at least 65 years of age who were screened using an extensive test battery of cognitive tests that required over 30 min to administer. Classification and Regression Trees (CART) was used to identify a subset of the battery that could be administered quickly and which maintained high levels of sensitivity and specificity for a diagnosis of dementia. The Short and Sweet Screening Instrument (SASSI) is a brief battery consisting of three standard cognitive tests that can be administered in approximately 10 min. Compared to the full battery, it was more sensitive (94% vs. 90%) and had comparable specificity (91% vs. 92%) for dementia in this sample.
How Is Creutzfeldt-Jakob Disease Acquired?
Authors: Alter Milton
Published: April 2003

Creutzfeldt-Jakob disease (CJD) is one of several related disorders collectively called prion diseases. These disorders affect man and animals and are now known to be caused by the abnormal configuration of a naturally occurring protein, PrPc. By mechanisms still not well understood, this natural protein is converted into a pathologic variant, PrPsc. The disease is ‘acquired’ spontaneously perhaps by posttranslational conversion of a PrPc into a PrPsc population. This sporadic form of CJD has been reported worldwide with a frequency of 1/million. Other modes of acquisition include the following: ingestion of brain tissue from deceased victims through ritual cannibalism at burial ceremonies formerly (and no longer) practiced by New Guinea Highlanders; iatrogenically, through corneal transplants from infected donors, inoculation of human growth hormone and gonadotropin prepared from infected human pituitary glands; from inadequately sterilized depth electrodes introduced neurosurgically into the brain during workups of patients with epilepsy, and applications of infected dura mater in neurosurgical procedures. Most recently, an infected bovine source (bovine spongiform encephalopathy) has been implicated and produces a new variant of CJD. Clusters of CJD in families in some populations have been recognized which are inherited in Mendelian fashion. These clusters are related to mutations of the PRNP gene in specific codons (e.g. codon 200). Homozygosity for these mutations increases the chances of manifesting the disease. Other potential methods of acquisition, such as by blood transfusion, surgical sutures, tonometers, consumption of hog brain or other organs and tissue, remain unproven.
Neurologic Recovery after Penetrating Craniocerebral War Injury
Authors: Puntarić Dinko , Soldo-Butković Silva , Vladetić Mirjana , Prgomet Drago
Published: April 2003

From June 1, 1991, until December 31, 1992, 116 patients with penetrating craniocerebral war injuries inflicted at the east Slavonian front were treated at the Osijek University Hospital. There were 26 (22.4%) gunshot wounds and 90 (77.6%) wounds inflicted by explosive devices and projectiles. Four years after the injury, a study of the survivors’ condition was carried out. No difference was recorded in the survival rate between the patients with gunshot wounds compared with explosive wounds. Rehabilitation produced good results in the survivors, in the prevention of both acute and chronic complications and permanent damage. Older age, lower Glasgow Coma Scale, and level of consciousness were found to be prognostic indicators of outcome.
Recent Trends of Stroke Mortality in Hong Kong: Age, Period, Cohort Analyses and the Implications
Authors: Yu Tak-Sun Ignatius , Tse Lap-Ah , Wong Tze-Wai , Wong Siu-lan
Published: April 2003

This study describes the time trend of cerebrovascular disease (CVD) mortality during the period 1976–1995 in Hong Kong and explores the period and birth cohort effects using Poisson regression models with correction for overdispersion of data. A clear downward trend was observed for age-adjusted CVD mortality rate in both sexes. It decreased from 84 per 100,000 to 41 per 100,000 among men (a 51% drop), and from 56 per 100,000 to 35 per 100,000 among women (a 38% drop). The rate of decline was in general greater in the second decade and among males, resulting in a significant downward trend for the male-to-female rate ratio. Both the period of death and the birth cohort showed a significant effect on the reduction in mortality rates, but the latter seemed to have a more substantial influence. However, an increasing trend was observed among younger males in the second decade, and the protective cohort effect seemed to be waning for the more recent cohorts in both sexes. Closer monitoring of the situation in the next years is warranted.
Epidemiology of Reye’s Syndrome, United States, 1991–1994: Comparison of CDC Surveillance and Hospital Admission Data
Authors: Sullivan Kevin M. , Belay Ermias D. , Durbin Randy E. , Foster David A. , Nordenberg Dale F.
Published: April 2003

This investigation describes the epidemiology of Reye’s syndrome (RS) during 1991–1994 and compares two different sources of information in the United States. Estimates of the incidence of RS from the Centers for Disease Control and Prevention (CDC) are compared with hospital inpatient data from approximately one third of the hospitals from HCIA, Inc. During 1991–1994, 48 RS cases were reported to the CDC and 93 RS hospitalizations based on HCIA data. When the HCIA data are extrapolated to the US population, there were an estimated 284 hospitalizations. Cases reported from both data sources were similar in distribution by onset, age, and sex. CDC data probably underestimate the incidence of RS due to incomplete reporting and HCIA data may overestimate it because not all cases were known to meet the CDC case definition. The true annual incidence of RS during the study years was probably between 0.2 and 1.1 cases per million population <18 years of age.
Peripheral Sympathetic Denervation Alters Both the Primary and Memory Cellular Immune Responses to Herpes simplex Virus Infection
Authors: Leo Nicole A. , Callahan Tracy A. , Bonneau Robert H.
Published: April 2003

Numerous studies have sought to delineate the impact of neuroendocrine function on overall immune responsiveness. Using various murine models, we and others have previously shown that both adrenal-dependent and adrenal-independent mechanisms associated with psychological stress modulate components of both the primary and memory cellular immune responses to herpes simplex virus type 1 (HSV-1) infection. We have extended these studies by determining the impact of 6-hydroxydopamine (6-OHDA)-mediated peripheral sympathetic denervation on both responses. C57BL/6 mice treated with 6-OHDA (200 mg/kg) exhibited reduced generation of both primary lymph node- and splenic-derived cytotoxic T lymphocytes (CTL) following a local (footpad) and systemic HSV infection, respectively. 6-OHDA also suppressed activation of HSV-specific memory CTL (CTLm). In both models, alterations in cytokine production and lymphocyte subset distribution were also observed. Administration of 6-OHDA also resulted in substantial but transient activation of the hypothalamic-pituitary-adrenal (HPA) axis as was indicated by a dramatic elevation of serum corticosterone and hypothalamic Fos expression. Moreover, the corticosterone levels were directly correlated with the extent of CTLm activation. Together, these findings suggest that peripheral sympathetic denervation alters immune function through activation of the HPA axis.
IL-1-Alpha and TNF-Alpha Differentially Regulate CD4 and Mac-1 Expression in Mouse Microglia
Authors: Yu Naichen , Zhang Xiaohong , Magistretti Pierre J. , Bloom Floyd E.
Published: April 2003

The regulatory effects of the proinflammatory cytokines, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were investigated on CD4 and Mac-1 expression in mouse microglial cultures. The identity of the microglia in cultures was confirmed by multiple indices including morphology, uptake of acetylated low-density lipoprotein and lectin RCA 120 staining. Microglia growing on a monolayer of astrocytes (astrocyte-supported microglia) were both CD4- and Mac-1 positive (out of 94.5% Mac-1-positive cells, 85.3% were also CD4 positive). When astrocyte-supported microglia were replated directly onto culture dishes (plate-supported microglia), the percentage of CD4- and Mac-1-positive cells decreased to 12–29 and 20–25% resepctively. The addition of IL-1α or TNF-α to plate-supported microglia led to an upregulation of Mac-1 expression in a time- and dose-dependent manner with different EC50s (0.5 ng/ml for IL-1α and 2 ng/ml for TNF-α) but exhibited similar time-to-peak responses (over 12 h). The addition of IL-1α, but not TNF-α, also led to an increase in CD4 expression on plate-supported microglia with a similar dose response and time course. IL-1α treatment gave rise to an increase in the level of CD4 mRNA as assessed by RT-PCR. The possibility that cell proliferation was responsible for the observed effects on microglia was excluded by an analysis of 3H-thymidine incorporation. Our results suggest that cultured mouse microglia express CD4 molecules which can be upregulated by IL-1α while Mac-1 can be upregulated by both IL-1α and TNF-α.
Expression of Chemokines RANTES, MIP-1α and GRO-α Correlates with Inflammation in Acute Experimental Autoimmune Encephalomyelitis
Authors: Glabinski Andrzej R. , Tuohy Vincent K. , Ransohoff Richard M.
Published: April 2003

Experimental autoimmune encephalomyelitis (EAE) is an investigator-initiated disorder that serves as an animal model for the common human demyelinating disease multiple sclerosis. Both diseases are typified by disseminated perivascular and submeningeal cuffs in the central nervous system (CNS). It was shown recently that chemokines are integral to the pathogenesis of EAE. In the present study we analyzed the gene expression of three chemokines, RANTES, MIP-1α and GRO-α, at the onset of acute EAE, and correlated that expression with the intensity of inflammatory changes in the CNS. We showed that all three chemokines are upregulated simultaneously with symptom onset of acute EAE, and that chemokine expression correlates with the intensity of inflammation in the CNS. This consistent relationship supports the hypothesis that chemokines are relevant to leukocyte accumulation in CNS parenchyma.
Bacterial Endotoxin Induces Fos Immunoreactivity in Primary Afferent Neurons of the Vagus Nerve
Authors: Gaykema Ron P.A. , Goehler Lisa E. , Tilders Fred J.H. , Bol John G.J.M. , McGorry Molly , Fleshner Monika , Maier Steven F. , Watkins Linda R.
Published: April 2003

Subdiaphragmatic vagotomy inhibits brain-mediated illness responses to peripherally administered bacterial endotoxin, including fever, hyperalgesia, sickness behavior, and activation of the hypothalamic-pituitary-adrenal axis. However, direct evidence implicating vagal afferents specifically in conveying information about peripheral immune activation to the brain is still lacking. This study assessed whether (1) endotoxin induces the expression of the functional activation marker Fos in the vagal sensory ganglia, and (2) vagotomy abrogates endotoxin-induced Fos expression in these ganglia. Male rats, which had previously received vagotomy or sham surgery, were injected intraperitoneally or intravenously with either endotoxin or saline. Fos immunolabeling was absent in saline-treated rats. In contrast, scattered cells within the vagal sensory ganglia showed Fos immunoreactivity after both intraperitoneal and intravenous endotoxin administration in sham-operated rats. Vagotomy abolished Fos expression after intraperitoneal endotoxin administration, whereas after intravenous administration Fos expression was strongly attenuated, but not eliminated. These findings implicate vagal afferents as a potential signaling pathway to brain regions that generate illness responses to pro-inflammatory mediators.
Neuroimmunopathogenesis of ts1 MoMuLV Viral Infection
Authors: Lynn William S. , Wong Paul K.Y.
Published: April 2003

Newborn mice infected with ts1, a mutant of the Moloney murine leukemia virus, develop neuroimmunodegeneration with death and damage of thymocytes, astrocytes, and motor neurons by 24–38 days. T cells, B cells, and astrocytes, but not neurons, are infected by the virus. Primary splenocytes and thymocytes isolated from age-matched infected or control mice, when incubated in serum-deficient media containing phytohemagglutinin-L, either homotypically aggregate and survive or swell, expose their inner membrane phospholipids, and then shrink as they fragment their nuclei and excrete DNA-containing hypoploid minicells. In our present studies, the rates of these apoptotic changes were greatly increased in the infected cells. This thymocyte death was ameliorated in vitro by addition of Th2 cytokines, but not by Th1 cytokines, or by redox agents. In contrast, death of splenocytes, which were already mitogenically activated in vivo by the virus, was prevented by Th1 and Th2 cytokines plus redox support. In vivo, this ts1-induced neuroimmunodegenerative syndrome could be completely prevented by the immunomodulator polyinosine-cytosine and partially prevented by cytokines or redox modifiers. Viral titer primarily in the brain was also diminished by polyinosine-cytosine therapy. These observations indicate that the cell death in T cells and neurons in these ts1-infected neonatal mice can be prevented in vitro and in vivo by appropriate upregulation of the immune system.
Inhibition of Systemic Inflammation by Central Action of the Neuropeptide α-Melanocyte- Stimulating Hormone
Authors: Delgado Hernàndez René , Demitri Maria Teresa , Carlin Andrea , Meazza Cristina , Villa Pia , Ghezzi Pietro , Lipton James M. , Catania Anna
Published: April 2003

The neuropeptide α-melanocyte stimulating hormone (α-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central α-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-α and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of α-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central α-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central α-MSH. Intraperitoneal administration of the small dose of α-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central α-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central α-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by α-MSH could be used to treat systemic inflammation.
Central Sympathetic Modulation of Tissue Cytokine Response to Hemorrhage
Authors: Molina Patricia E. , Abumrad Naji N.
Published: April 2003

Hemorrhage is associated with altered immune responses as well as with early increases in circulating levels and tissue content of proinflammatory cytokines. The present study determined the effects of central chemical sympathectomy on the early increase in tissue content of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) following fixed-pressure (40 mm Hg) hemorrhage as well as on the associated activation of the opiate and glucocorticoid systems. Conscious unrestrained nonheparinized male Sprague-Dawley rats were randomized to receive either 6-hydroxydopamine intracerebroventricularly or equal volumes of saline (5 µl). Half of the animals in each group underwent hemorrhage followed by fluid resuscitation with lactated Ringer’s solution, and were sacrificed at completion of the resuscitation period. Hemorrhage elevated TNF-α and IL-6 content in spleen (30–47%) and lung (∼40%). Central chemical sympathectomy did not alter tissue cytokine content or circulating levels of β-endorphin and corticosterone. However, central chemical sympathectomy attenuated the hemorrhage-induced increase in lung and spleen TNF-α, enhanced the IL-6 response in spleen and blunted the rise in circulating β-endorphin levels. These results demonstrate central modulation of the inflammatory and opiate responses to hemorrhagic stress.
Neuropeptide Y Counteracts Interferon-Alpha-Induced Anorexia
Authors: Turrin Nicolas P. , Flynn Mark C. , Plata-Salamán Carlos R.
Published: April 2003

Interferon-α (IFN-α) immunotherapy is associated with significant adverse neurological effects, including anorexia, which can be a limiting factor in immunotherapy. Thus, it is important to develop strategies that could ameliorate IFN-α-induced neurological manifestations without significantly affecting its immunomodulating properties. In this study, we tested the hypothesis that an endogenous feeding-enhancing peptide, neuropeptide Y (NPY), could inhibit IFN-α-induced anorexia in rats. The results show that IFN-α induced significant anorexia when administered centrally into the third cerebral ventricle at an immunotherapeutically relevant dose (1,350 IU/rat). Heat-inactivated IFN-α had no effect. NPY (5.0 µg/rat) counteracted the IFN-α-induced anorexia when administered 3 or 10 h following IFN-α, or when it was concomitantly administered with IFN-α. The data suggest that NPY and its agonists could represent a potential novel intervention for IFN-α immunotherapy-associated anorexia.
Differential Regulation of Interleukin-1 Receptor Antagonist by Proopiomelanocortin Peptides Adrenocorticotropic Hormone and β-Endorphin
Authors: Kovalovsky Damián , Pereda Marcelo Páez , Stalla Günter K. , Holsboer Florian , Arzt Eduardo
Published: April 2003

We have previously described the regulation of interleukin-1 receptor antagonist (IL-1ra) protein secretion and expression by IL-1, glucocorticoids and corticotropin-releasing hormone in monocytes in culture. In the present work, we analyze the direct effect of adrenocorticotropic hormone (ACTH) and β-endorphin on the expression and secretion of IL-1ra by human monocytes in culture. ACTH exerted a dose-dependent inhibitory effect on lipopolysaccharide (LPS)-induced IL-1ra production and mRNA expression. Basal IL-1ra levels were not affected by treatment with any ACTH dose. In contrast, on human monocytes, β-endorphin at concentrations as low as 10 pg/ml produced an increase of basal IL-1ra protein secretion and mRNA expression, this effect being reverted by pretreatment with naloxone. No effect of β-endorphin was observed either in IL-1ra mRNA expression or protein secretion when cells were treated with LPS. The different effects of ACTH and β-endorphin could account for their differential contribution to the inflammatory response: while ACTH contributes to the glucocorticoid overall control of the inflammatory response, β-endorphin exerts an inhibitory tone on the resting IL-1 system. Because IL-1ra is essential in setting the level of monocyte and inflammatory response its differential regulation by the HPA axis hormones contributes to regulating the IL-1/inflammatory temporal response.
Castration of Sexually Immature Rats Affects Sympathetic Innervation of the Adult Thymus
Authors: Leposavić Gordana , Ugrešić Nenad , Pejčić-Karapetrović Branka , Mićić Mileva
Published: April 2003

It has been hypothesized that maturational processes within the hypothalamo-pituitary-gonadal (HPG) axis and thymus are reciprocally regulated via neural pathways. To test this hypothesis, in the thymi of adult rats orchidectomized (ORX) at age of 1 (ORX-1), 7 (ORX-7) and 30 days (ORX-30): (i) noradrenaline (NA), dopamine (DA) and serotonin (5-HT) contents and acetylcholinesterase (AChE) activity were measured and (ii) the distribution of monoamine- and AChE-containing nerves and cells was examined by a sucrose phosphate glyoxylic acid (SPG) method and enzyme histochemistry, respectively. In all groups of ORX rats, the thymus weight was significantly increased over that in sham-ORX control rats. In the ORX-1 rats, the increase in the thymus weight was accompanied by a proportional increase in the content of both catecholamines and 5-HT; consequently the concentration of each of them remained unaltered. In these animals, the density of both SPG-stained thymus nerve fibers and cells also remained unchanged. In the ORX-7 rats, the rise in the thymus weight was followed by a proportional increase in the content of all monoamines, except for NA which was reduced. Therefore, in these rats neither the thymus concentrations of DA nor that of 5-HT differed from controls, while the concentration of NA was significantly decreased. The reduction in both NA content and concentration reflected a diminished density of SPG-positive nerve profiles. In the ORX-30 rats, the increase in thymus weight was neither paralleled by a proportional increase in the DA content nor in 5-HT, while the content of NA was decreased. Thus, in their thymi the concentration of both NA and DA, as well as that of 5-HT, were significantly reduced. In parallel with these changes, a decreased density of thymic SPG-positive nerve fibers and cells was found. In all ORX rats, the pattern of intrathymic distribution of SPG-positive fibers and cells remained unchanged. Orchidectomy affected neither the activity of AChE (expressed per gram of tissue) nor the density of AChE-positive nerves and cells in the thymus. As the changes in the density of adrenergic nerve fibers in the thymus from ORX rats were not followed by similar alterations in the density of AChE-containing nerve fibers, it does not seem likely that NA and AChE are colocalized in the thymus nerve fibers. The results also suggest that there is a critical period during ontogenesis when changes within the HPG axis evoked by orchidectomy can affect the sympathetic nerve input to the rat thymus and therefore, most likely, development and function of the organ.