bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of Endothelin Receptors Attenuates End-Organ Damage in Homozygous Hypertensive Ren-2 Transgenic Rats
Authors: Dvořák Pavel , Kramer Herbert J. , Bäcker Angela , Malý Jan , Kopkan Libor , Vaněčková Ivana , Vernerová Zdena , Opočenský Martin , Tesař Vladimír , Bader Michael , Ganten Detlev , Janda Jan , Červenka Luděk
Published: August 2004

Background/Aims: A growing body of evidence suggests that the interplay between the endothelin (ET) and the renin-angiotensin systems (RAS) plays an important role in the development of the malignant phase of hypertension. The present study was performed to evaluate the role of an interaction between ET and RAS in the development of hypertension and hypertension-associated end-organ damage in homozygous male transgenic rats harboring the mouse Ren-2 renin gene (TGRs) under conditions of normal-salt (NS, 0.45% NaCl) and high-salt (HS, 2% NaCl) intake. Methods: Twenty-eight-day-old homozygous male TGRs and age-matched transgene-negative male normotensive Hannover Sprague-Dawley (HanSD) rats were randomly assigned to groups with NS or HS intake. Nonselective ETA/B receptor blockade was achieved with bosentan (100 mg/kg/day). Systolic blood pressure (BP) was measured in conscious animals by tail plethysmography. Rats were placed into metabolic cages to determine proteinuria and clearance of endogenous creatinine. At the end of the experiment the final arterial BP was measured directly in anesthetized rats. Kidneys were taken for morphological examination. Results: All male HanSD fed either the NS or HS diet exhibited a 100% survival rate until 180 days of age (end of experiment). The survival rate in untreated homozygous male TGRs fed the NS diet was 41%, which was markedly improved by treatment with bosentan to 88%. The HS diet reduced the survival rate in homozygous male TGRs to 10%. The survival rate in homozygous male TGRs on the HS diet was significantly improved by bosentan to 69%. Treatment with bosentan did not influence either the course of hypertension or the final levels of BP in any of the experimental groups of HanSD rats or TGRs. Although the ET-1 content in the renal cortex did not differ between HanSD rats and TGRs, ET-1 in the left heart ventricle of TGRs fed the HS diet was significantly higher compared with all other groups. Administration of bosentan to homozygous male TGRs fed either the NS or HS diet markedly reduced proteinuria, glomerulosclerosis and attenuated the development of cardiac hypertrophy compared with untreated TGR. Conclusions: Our data show that nonselective ETA/B receptor blockade markedly improves the survival rate and ameliorates end-organ damage in homozygous male TGRs without significantly lowering BP.
Characteristics of Heart Period Variability in Intubated Very Low Birth Weight Infants with Respiratory Disease
Authors: Smith Sandra L. , Doig Alexa K. , Dudley William N.
Published: August 2004

Background: Heart period variability provides a measure of balance between the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). Since the PNS develops during the final weeks of gestation, premature infants have an overriding SNS. Spectral power analysis of heart period variability reveals two main frequency regions, the low frequency region (LF) representing primarily SNS activity and the high frequency region (HF) representing PNS activity. Objectives: To identify the characteristics of heart period power in the LF and HF regions in very low birth weight (VLBW) infants in the neonatal intensive care unit across gestational age groups and between sleep and awake states. Methods: Data were collected from 16 intubated and mechanically ventilated VLBW infants with respiratory disease. Using spectral analysis techniques, heart period power in the two main frequency regions was extracted. Results: HF power did not improve with gestational age as expected. LF power did increase with age, albeit nonsignificantly. LF and HF power were not significantly different between awake and sleep states. Conclusions: The results of this preliminary study suggest that PNS tone does not improve with gestational age in VLBW infants with respiratory disease. The intensive care environment may stimulate a sympathetic response in these infants and disrupt normal PNS development.
Hypoglycemia-Dependent β2-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?
Authors: Schwab K.O. , Menche U. , Schmeisl G. , Lohse M.J.
Published: August 2004

To evaluate the influence of the incidence and unawareness of hypoglycemia on lymphocyte β2-adrenoceptor densities, we measured β2-adrenoceptor density using [125I]-iodocyanopindolol and CGP 12177 before and after 1 week of treatment optimization in 33 adults with type-1 diabetes mellitus. Diabetes treatment of all patients was modified to improve their glycemic control. During this week, all patients had to complete a protocol with 7 daily glucose measurements, one of which was at night. The subjective symptoms were evaluated in case of hypoglycemia. A significant correlation between a hypoglycemia incidence below (but not above) the threshold of 2.75 mmol/l (50 mg/dl) and β2-adrenoceptor densities on lymphocytes was found after the study week (r = –0.72, p < 0.00001). Nine patients suffering from hypoglycemia unawareness had a significantly higher incidence of hypoglycemia (p < 0.002) and lower β2-adrenoceptor densities on lymphocytes compared to 24 patients who recognized all of their hypoglycemic episodes (p < 0.004). We conclude that downregulation of β2-adrenoceptor densities on lymphocytes occurs as a result of recurrent hypoglycemia defined as glucose levels of <2.75 mmol/l. β2-Adrenoceptor densities are decreased in patients with subjective hypoglycemia unawareness and might contribute to the reduced β-adrenergic sensitivity in this subgroup of patients.
Assessment of Hepatic Glucose Metabolism by Indirect Calorimetry in Combination with a Non-Invasive Technique Using Naturally Enriched 13C Glucose in Healthy Children and Adolescents
Authors: Selz Roxane , Jornayvaz François R. , Tappy Luc , Woringer Virgile , Theintz Gérald E.
Published: August 2004

The metabolic fate of hepatic glucose can be best studied using invasive techniques such as tracer infusions and frequent blood sampling which have been revealed to be impractical in the pediatric age group. The aim of this study was to develop a non-invasive method based on indirect calorimetry and expired 13CO2 monitoring in order to gain insight into the mechanisms leading to impaired glucose tolerance in children and teenagers. As a first step, net glucose oxidation (NGO) and energy expenditure (EE) were measured in 47 subjects (range 7.5–17.3 years) of whom 18 were prepubertal (P1), 11 in early puberty (P2–P3) and 18 in late puberty (P4–P5) after 3-hourly loads of 180 mg/kg of oral maize glucose containing naturally enriched 13C. Isotope analysis allowed to calculate exogenous and endogenous glucose oxidation (EXGO, ENGO) and, hence, to derive TGS and NGS, that is glycogen turnover. NGO and EE decreased significantly with pubertal progression, reflecting higher metabolism at younger ages, whereas EXGO remained constant. TGS did not change significantly whereas NGS showed a significant negative correlation with pubertal progression: this can be explained by the fact that glycogenolysis exceeded glycogen synthesis in this experimental setting. This non-invasive method appears to be a promising tool to study the fate of hepatic glucose and therefore glycogen turnover in children at risk of developing glucose intolerance and/or type 2 diabetes.
Compound Heterozygous and Homozygous Mutations of the TSHβ Gene as a Cause of Congenital Central Hypothyroidism in Europe
Authors: Karges Beate , LeHeup Bruno , Schoenle Eugen , Castro-Correia Cintia , Fontoura Manuel , Pfäffle Roland , Andler Werner , Debatin Klaus-Michael , Karges Wolfram
Published: August 2004

Background: Thyroid hormones are crucial for normal growth and central nervous system development. In recent years, germline variants of the TSHβ subunit gene have been identified as a cause of congenital TSH deficiency. Methods: We performed a genetic and clinical study in children from four European countries diagnosed with congenital isolated central hypothyroidism. Results: TSHβ gene analysis revealed compound heterozygosity for 145C→T (Q49X) and 313delT (C105Vfs114X) in 1 infant and homozygous mutation 313delT (C105Vfs114X) in 5 patients. Although all presented with typical symptoms of hypothyroidism, diagnosis and treatment was delayed until 3–5 months in 5 of 6 patients. In a longitudinal sibpair analysis, thyroxine substitution initiated immediately after birth was effective to prevent developmental delay and growth retardation. Conclusion: Clinical awareness is required to detect hypothyroidism due to TSHβ mutations, which is not identified by TSH-based newborn screening. TSHβ variants C105Vfs114X and Q49X are the most frequent cause of this severe disorder in Europe, now for the first time observed in compound heterozygous state.
Do Birth Variable Data Predict Melatonin Production in 8- to 9-Year-Old Children? Analysis of Excreted 6-Sulfatoxymelatonin
Authors: Griefahn Barbara , Blaszkewicz Meinolf , Bröde Peter , Remer Thomas
Published: August 2004

Hypotheses: A cross-sectional study on urinary excretion of 6-sulfatoxymelatonin (aMT.6S) in young adults suggests a relation between melatonin production and body size at birth. As individual melatonin production remains stable during childhood and adolescence, this melatonin-birth size relation should also exist in children. Methods: Daily urinary output of aMT.6S of 147 healthy white children (78 boys, 69 girls), 8 or 9 years of age, was quantified by ELISA and related to birth variable data. Results: Contrary to expectation, aMT.6S output was not related to the ponderal index at birth but a moderate positive association with body mass index at the age of 8–9 years was seen. Conclusion: This study in children contradicts previous findings in adults. As no obvious reason can be identified for this discrepancy, further research (particularly a longitudinal study) is recommended to clarify whether birth variable data may predict melatonin production in certain circumstances during or after puberty.
Human Amniotic Fluid Glycoproteins Expressing Sialyl Lewis Carbohydrate Antigens Stimulate Progesterone Production in Human Trophoblasts in vitro
Authors: Jeschke Udo , Mylonas Ioannis , Richter Dagmar-Ulrike , Streu Annett , Müller Heiner , Briese Volker , Friese Klaus
Published: August 2004

Background: Progesterone is thought to mediate immune modulator effects by regulating uterine responsiveness. The aim of the study was to clarify the effect of transferrin and glycodelin A (former name PP14) as sialyl Lewis X-expressing glycoproteins on the release of progesterone by trophoblast cells in vitro. Methods: Cytotrophoblast cells were prepared from human term placentas by standard dispersion of villous tissue followed by a Percoll gradient centrifugation step. Trophoblasts were incubated with varying concentrations (50–300 µg/ml) of human amniotic fluid- and serum-transferrin as well as with glycodelin A. Culture supernatants were assayed for progesterone, human chorionic gonadotropin (hCG) and cortisol by enzyme immunometric methods. Results: The release of progesterone is increased in amniotic fluid transferrin- and glycodelin A-treated trophoblast cell cultures compared to untreated trophoblast cells. There is no relation between transferrin and the hCG or cortisol production of trophoblast cells. Conclusion: The results suggest that sialyl Lewis carbohydrate antigen-expressing amniotic fluid glycoproteins modulate the endocrine function of trophoblasts in culture by upregulating progesterone production.
Safety Aspects of Infliximab in Inflammatory Bowel Disease Patients
Authors: Seiderer Julia , Göke Burkhard , Ochsenkühn Thomas
Published: August 2004

Background: Infliximab, a chimeric anti-tumour necrosis factor monoclonal antibody with potent anti-inflammatory effects, represents an effective treatment option in patients with severe inflammatory bowel disease (IBD). Serious side-effects of such an immunomodulating therapy are speculated and therefore we reviewed our clinical experience in a retrospective safety study looking upon a single cohort of 100 IBD patients from a large German University Hospital. Methods: 100 patients with severe Crohn’s disease (n = 92), ulcerative colitis (n = 7) or indeterminate colitis (n = 1) treated with infliximab (5 mg/kg) from January 2000 to December 2003 were retrospectively analysed for acute and subacute adverse events by chart review. Results: Overall, infliximab therapy was generally well tolerated. No fatal complications, malignancies, autoimmune diseases, neurologic or cardiovascular complications were observed in the cohort during the study period. Overall, adverse events were observed in 10 patients: 2 patients showed an acute infusion reaction, 1 patient a serum sickness-like reaction, in 4 patients a bacterial or viral infection occurred, in 1 patient pancytopenia and 2 patients developed surgical complications. Only 6 patients with adverse events required admission to hospital. A case of tuberculosis after infliximab was not found. The lack of adverse side-effects was associated with young median age and infrequent comorbidities of the cohort. Conclusion: Regarding its strong immunomodulating capacity, infliximab appears to be an efficient and relatively safe therapeutic option for patients with severe IBD. However, the use of infliximab requires careful screening and close patient monitoring to identify patients at risk and the infrequent, but sometimes serious complications of infliximab.
Mutually Distinctive Gradients of Three Types of Intestinal Alkaline Phosphatase along the Longitudinal Axis of the Rat Intestine
Authors: Shidoji Yoshihiro , Kim Soon Hie
Published: August 2004

Background/Aims: A descending gradient of alkaline phosphatase (AP) activity is well known to exist in the rat intestine. To understand the physiological role(s) of intestinal AP (IAP), we examined in detail the distribution of IAP subtypes along the longitudinal axis of the rat intestine. Methods: The consecutive 2-cm segments of the upper intestine were analyzed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by staining for IAP activity. The reverse transcription-polymerase chain reaction was conducted to assess the relative levels of tissue mRNA for the 2 distinct genes of rat IAP, rIAP-I and rIAP-II. Results: A descending gradient of IAP activity was found along the upper small intestine, where 3 bands of the activity, termed types 1, 2 and 3 from the anode were located on SDS-PAGE gels. Along the longitudinal axis, types 1 and 3 showed ascending and descending gradients, respectively; whereas type 2 had a broad uniform distribution. The mRNA level for rIAP-I showed an ascending distribution, and that of rIAP-II, a descending one. Type 3 IAP was drastically diminished in duodenum of cysteamine-ulcer rats, but type 1 remained constant. Conclusion: These distinctive gradients of IAP subtypes may provide a clue to scrutinize the physiological significance of AP in the rat intestine, which is a flow system with polarity.
Patients with Subjective Food Hypersensitivity: The Value of Analyzing Intestinal Permeability and Inflammation Markers in Gut Lavage Fluid
Authors: Arslan Gülen , Kahrs Gudrun Elise , Lind Ragna , Frøyland Livar , Florvaag Erik , Berstad Arnold
Published: August 2004

Background/Aim: Subjective food hypersensitivity is prevalent in the general population. The aim of this study was to seek objective evidence of food hypersensitivity by analyzing intestinal permeability and inflammation markers in gut lavage fluid. Methods: Fifty-two patients with abdominal complaints self-attributed to food hypersensitivity were examined by skin prick test, serum IgE analysis, double-blind, placebo-controlled food challenge (DBPCFC), and intestinal lavage. The results were compared with those of 44 patients without food hypersensitivity. Neither the patients nor the controls had organic diseases that could explain their symptoms. Intestinal lavage was performed by administering 2 liters of isotonic polyethylene glycol (molecular weight 3,350 daltons) solution containing 50 µCi of [51Cr]EDTA through a nasoduodenal tube. The first clear fluid passed per rectum was collected and analyzed for histamine, eosinophilic cationic protein (ECP), tryptase, and calprotectin. The intestinal permeability was assessed by determining the 5-hour urinary excretion of [51Cr]EDTA. Calprotectin was also analyzed in native faecal samples. Results: The ECP concentration in gut lavage fluid was significantly higher in the patients than in the controls (p = 0.007), but the overlap between groups was large. Food hypersensitivity was confirmed by positive DBPCFC in only 4 patients. On average, histamine and ECP concentrations were high in these patients. Tryptase, intestinal permeability, and faecal and lavage calprotectin levels were normal. Conclusions: Very few patients had objective evidence of food hypersensitivity. Analyzing intestinal permeability and inflammation markers in gut lavage fluid did not contribute to the diagnosis, but further studies on histamine and ECP are warranted.
N-Acetylcysteine Administration during the First Week of Life Does Not Improve Lung Function in Extremely Low Birth Weight Infants
Authors: Sandberg Kenneth , Fellman Vineta , Stigson Lennart , Thiringer Klara , Hjalmarson Ola
Published: August 2004

Oxygen toxicity is thought to be an important factor involved in development of bronchopulmonary dysplasia (BPD) in the very preterm infant. Glutathione (GSH) plays a major role in the antioxidant defense system in the preterm lung and there are theoretical implications that N-acetylcysteine (NAC) treatment could improve its function. The purpose of this study was to investigate whether NAC treatment during the first week of life to preterm infants improved neonatal lung function as a measure of lung injury. The study was part of a multi-center Nordic controlled trial with prophylactic intravenous NAC treatment (16–32 mg/kg/day) for 6 days in newborn infants with birth weights 500–999 g. Lung mechanics, with calculations of compliance and resistance of the respiratory system, together with measurements of functional residual capacity and indices of gas mixing efficiency in the lung, were performed in 33 preterm infants (18 received NAC and 15 placebo) before discharge from the NICU. Median (range) gestational age was 25 (24–28) weeks in the NAC-treated infants and 25 (24–29) in the placebo group. Corresponding mean (SD) birth weights were 0.774 (0.11) and 0.761 (0.12) kg respectively. Lung function measurements did not show any significant differences between NAC-treated infants compared to placebo when examined before discharge from the NICU. We conclude that prophylactic NAC treatment to extremely low birth weight infants during the first week of life does not improve lung function at term.
Prevalence of Neurological Disorders in Bangalore, India: A Community-Based Study with a Comparison between Urban and Rural Areas
Authors: Gourie-Devi M. , Gururaj G. , Satishchandra P. , Subbakrishna D.K.
Published: August 2004

A population-based neuroepidemiological survey of 102,557 individuals in urban and rural Bangalore in Southern India was conducted to determine the prevalence and pattern of neurological disorders. The study population included subjects from urban (51,502) and rural (51,055) areas, identified through a two-stage stratified random sampling method. Trained social workers administered the screening questionnaire, which had been tested and validated in an earlier pilot study and a neurologist examined the individuals who screened positive. Adults, children (<15 years) and elderly adults (>60 years) constituted 61, 34 and 5% of the study group, respectively. There was a distinct difference in education, occupation and income levels between urban and rural areas with all these parameters being lower in the rural population. In the surveyed population, 3,206 individuals with neurological disorders were detected resulting in crude and age-adjusted prevalence rates of 3,126 and 3,355 per 100,000 population, respectively. The prevalence rate among children, middle-aged (31–40 years) and elderly adults was 2,653, 3,932 and 5,012 per 100,000 population, respectively. The prevalence of neurological disorders among women (3,617) was higher compared with men (2,657). The prevalence rate in urban and rural populations was 2,190 and 4,070/1,00,000, respectively, implying that neurological disorders were twice as frequent in rural areas as in urban areas. The prevalence rates per 100,000 population of the most frequent disorders in the descending order of frequency were: headache (1,119), epilepsy (883), febrile convulsions (330), cerebrovascular disorder (150), and mental retardation (142). This large-scale population-based survey provides data that will be crucial for developing hospital and community-based neurological services in India and other developing countries.
Relation between Motorcycle Helmet Use and Cervical Spinal Cord Injury
Authors: Lin Mau-Roung , Tsauo Jau-Yih , Hwang Hei-Fen , Chen Chih-Yi , Tsai Lung-Wen , Chiu Wen-Ta
Published: August 2004

A case-control study was conducted to determine the relationship between motorcycle helmets, including type (i.e. partial or full coverage) and fastening status (i.e. loose or firm), and cervical spinal cord injuries (SCIs) in Taiwan. Based on a nationwide registry consisting of 396 motorcycle riders with traumatic SCIs during the 4-year period from July 1992 to June 1996, 229 subjects injured at cervical levels were defined as cases and 167 injured at other spinal levels as controls. Furthermore, additional information on the type and fastening status of the helmet was collected by telephone interview, and 147 subjects, including 79 with cervical and 68 with noncervical lesions, responded. Results of the logistic regression model show that neither different helmet types nor fastening status increased the occurrence of cervical SCIs when motorcycle riders were involved in severe crashes.
Incidence of Myasthenia gravis in the Province of Ferrara
Authors: Casetta I. , Fallica E. , Govoni V. , Azzini C. , Tola M. , Granieri E.
Published: August 2004

Background: The reported annual incidence of myasthenia gravis (MG) ranges from 0.25 to 15 per million. The sex- and age-related pattern of disease incidence is still debated. Methods: An intensive descriptive study was performed in the province of Ferrara (mean population 360,950 people) over the period 1985 through 2000. Results: The average crude annual incidence rate was 2 per 100,000. We confirm a female preponderance in the total population, particularly in the youngest age groups. Conclusions: We observed an early increase in incidence in females, partly due to thymoma-associated MG, while MG without thymoma showed increasing incidence with age nonsignificantly different in the two sexes.
Childhood Infections as Risk Factors for Multiple Sclerosis: Belgrade Case-Control Study
Authors: Pekmezovic Tatjana , Jarebinski Mirjana , Drulovic Jelena
Published: August 2004

The aim of this case-control study was to analyze the role of childhood infections and vaccinations in patients with MS in the Belgrade population. The study group comprised 110 cases with definite MS according to Poser’s criteria, in whom onset symptoms occurred up to 2 years prior to the interview. An equal number of controls, individually matched by sex, age and area of residence, was recruited from patients with various nonautoimmune neurological disorders. Measles (OR = 2.6, 95%CI 1.4–5.0), chickenpox (OR = 3.0, 95%CI 1.5–6.0), rubella (OR = 2.4, 95%CI 1.2–4.7), whooping cough (OR = 1.9, 95%CI 0.8–4.4), and mumps (OR = 1.8, 95%CI 0.8–4.5), at age ≤7 years, were more frequently reported by MS cases. The total number of childhood viral infections (including measles, rubella, chickenpox, and mumps) at age ≤7 years was significantly higher in MS cases than in controls (OR = 1.8, 95%CI 1.4–2.5). Concerning vaccinations, no statistically significant differences were found between groups. According to multivariate analysis, rubella (OR = 2.5, 95%CI 1.4–4.4, p = 0.001) and measles (OR = 2.4, 95%CI 1.3–4.3, p = 0.003) at age ≤7 years were significantly related to MS.
Buffalo Metropolitan Area and Erie County Stroke Study: Rationale, Design, and Methods
Authors: Qureshi Adnan I. , Kirmani Jawad F. , Sayed Muhammad A. , Siddiqui Amir M. , Safdar Adnan , Pande Ravi U. , Ahmed Shafiuddin , Ferguson Richard , Hershey Linda A. , Qazi Khalid J.
Published: August 2004

Objectives: The primary objective of this study was to define the incidence, disability, and death associated with stroke in the Buffalo metropolitan area and Erie County. This area has the highest stroke rate in New York State and therefore represents an ideal site to develop a successful model for prevention and management of stroke. Design: A cross-sectional design to study all new and recurrent strokes that occurred in the calendar year 2000 in the geographical location of Buffalo metropolitan area and Erie County. Patients and Data Collected: A retrospective review of an estimated 5,000 patients with new stroke will be performed at regional hospitals and the coroner’s office to determine the stroke subtypes, cerebrovascular risk factors, diagnostic investigations, treatment provided, and outcome. The total population residing in Buffalo in the year 2000 is available through the recent census. The study will also evaluate the quality of care provided for stroke patients including effectiveness of primary and secondary stroke prevention measures within this geographical region. Conclusions: We believe that this information will assist in allocation of resources and implementation of steps to improve stroke prevention and treatment.
Racial Disparities in Subarachnoid Hemorrhage Mortality: Los Angeles County, California, 1985–1998
Authors: Schievink Wouter I. , Riedinger Mary , Jhutty Tajinder K. , Simon Paul
Published: August 2004

We examined the racial distribution of subarachnoid hemorrhage (SAH) mortality in a unique multiracial community. Mortality rates for SAH among the residents of Los Angeles County were calculated from death certificate data (1985–1998). Residential postal zones were classified into three strata as a measure of socioeconomic status. The number of SAH deaths was 2,897. The age-adjusted SAH mortality rate was 1.9 in whites, 2.7 in Hispanics, 3.0 in Asians and 3.7 in blacks. In those younger than 70 years of age, the SAH mortality rate among blacks was 2.2 times that of whites and 1.8 times that of Hispanics and Asians. The SAH mortality rate declines after age 70 in blacks. The SAH mortality rate was higher in women than in men in all races and it was highest in elderly Asian women (23.5 per 100,000). An inverse relationship was observed between income and SAH mortality rates in all racial groups except whites.
Multiple Sclerosis in Southern Europe: Monreale City, Italy
Authors: Ragonese Paolo , Salemi Giuseppe , D’Amelio Marco , Gammino Matilde , Aridon Paolo , Savettieri Giovanni
Published: August 2004

Background: Several follow-up studies showed increasing prevalence and incidence rates for multiple sclerosis (MS). Objective: To ascertain, throughout a follow-up study, the incidence and prevalence of MS in the city of Monreale, Sicily, southern Italy. Methods: We calculated crude and age- and sex-specific prevalence rates on December 31, 2000, and determined incidence rates for the period January 1, 1992 to December 31, 2000. Results: The prevalence of MS was 71.2 per 100,000 population (48,5/100,000 in men; 93,0/100,000 in women). The incidence rate of MS for the period 1992–2000 was 4.0/100,000 per year. Conclusion: This study showed a nonsignificant increase in MS incidence rates in Monreale city for 1992–2000 compared to 1981–1991. Prevalence rates were similar to those of the previous follow-up study. Intervals between onset of symptoms and diagnosis seemed shorter than in prior studies. There is no evidence that the high prevalence and incidence rates have changed in this interval but numbers are too small for firm statements. These findings indicate that in Monreale city MS prevalence is stable and confirm Sicily as a high-risk area for MS.
Door-to-Door Survey of Major Neurological Diseases in Rural Ecuador – The Atahualpa Project: Methodological Aspects
Authors: Del Brutto Oscar H. , Idrovo Luis , Santibáñez Rocío , Díaz-Calderón Enrique , Mosquera Aurelio , Cuesta Fausto , Navas Carlos
Published: August 2004

We carried out a door-to-door survey to assess the prevalence, incidence, risk factors and possible etiology of major neurological diseases in Atahualpa, a rural village located in the coastal region of Ecuador. A total of 2,548 individuals were interviewed with standardized screening questionnaires to detect suspected cases of epilepsy, stroke and dementia, and they underwent a serum immunoblot test for the detection of anticysticercal antibodies (phase I). Positive individuals and a random sample of negative subjects were examined by neurologists (phase II). Then, patients with clinically confirmed disease and a control group of healthy subjects were further evaluated with complementary examinations (phase III). Here, we describe the methodology of this field study that may be used as a model for the evaluation of neurological disorders in rural communities of developing countries.
Health and Psychosocial Status of Patients with Turner Syndrome after Transition to Adulthood: The Belgian Experience
Authors: Verlinde F. , Massa G. , Lagrou K. , Froidecoeur C. , Bourguignon J.P. , Craen M. , De Schepper J. , Du Caju M. , Heinrichs C. , François I. , Maes M.
Published: August 2004

Background: Most girls with Turner syndrome (TS) are intensively followed by paediatricians, but are lost to follow-up when they reach adulthood. To gain insight into the adult medical and psychosocial situation, we performed a survey in young adult TS patients. Patients and Methods: A questionnaire concerning current health status, education, occupation and living situation was sent to 160 young adult TS women, all treated during childhood with GH and oestrogen if needed. Results: We received 102 completed questionnaires. Mean ± SD age at reception of the questionnaire was 23.4 ± 3.3 years, height 153.3 ± 5.2 cm, body mass index 23.7 ± 4.9 kg/m². Age and auxological parameters were comparable between responders and non-responders. Thirteen (12.7%) responders were not under regular medical care; 15 (14.7%) were seen by a general practitioner, while 28 (27.4%) needed several specialists. Forty-one (40.2%) patients reported health problems. The most frequently reported problem was hypertension (10.7%), followed by hypothyroidism (5.8%) and back problems (4.9%). Twenty-four (23.5%) of the 41 patients were taking medication for the indicated health problems. Twenty-six (25.5%) women had undergone spontaneous puberty; 16 of them reported spontaneous menstruations while 10 received oestrogen replacement therapy. Of the 76 women with induced puberty, 11 (14.5%) were not taking any oestrogen anymore. Compared with the general population, more TS women attended university and more obtained higher education. Forty-six women (45.1%) were working full-time, 7 (6.9%) were unemployed, and 4 (3.9%) received an allocation. Seventy (68.6%) patients were still living with their parents, while 18 (17.6%) were living together or married, and 14 (13.7%) were living alone. Conclusions: The transition of adolescents with TS to adult medical care is not optimal in Belgium. Although 40.2% of these young women reported health problems, 12.7% did not consult any physician. Many TS women did not take oestrogen replacement therapy. A specialized multidisciplinary approach for adults with TS is needed in order to optimize health and psychosocial status in these women.
Improving the Screening Power of the Cognitive Abilities Screening Instrument, Chinese Version
Authors: Tsai Rung-Ching , Lin Ker-Neng , Wu Kuan-Ying , Liu Hsiu-Chih
Published: August 2004

The purpose of this study was to find means to increase the power of the Cognitive Abilities Screening Instrument, Chinese version (CASI C-2.0) in the screening of dementia. In assessing the performance of the CASI in dementia screening, it is a common practice to determine a cutoff score for the total CASI score and report the respective sensitivity and specificity. In this paper, we showed that an alternative scoring system, i.e., a weighted sum of the scores from the 9 domains in the CASI C-2.0, may improve its effectiveness in screening. In particular, short-term memory and orientation appeared to be the 2 most relevant domains and their combined score was shown to be more effective than the total score in screening dementia. We also showed that such a scoring system could be kept the same across examinees with different demographic backgrounds. With the weighted scoring system of the 9 domains for patients from the targeted population, we hope to make the CASI a clinically more powerful tool in screening dementia.
Undiagnosed Diseases in Patients with Dementia – A Potential Target Group for Intervention
Authors: Löppönen Minna K. , Isoaho Raimo E. , Räihä Ismo J. , Vahlberg Tero J. , Loikas Saila M. , Takala Timo I. , Puolijoki Hannu , Irjala Kerttu M. , Kivelä Sirkka-Liisa
Published: August 2004

Objective: To study undiagnosed diseases in older people with and without dementia. Design: Cross-sectional population-based study in Lieto, southwestern Finland. Participants: All the inhabitants aged 64 and more in Lieto. Participation rate was 82% (n = 1,260). Measurements: Dementia and its subtypes were diagnosed according to prevailing criteria. Medical conditions were assessed in clinical examinations and from medical records. Results: 112 patients with dementia were found; 66% of them had at least 1 undiagnosed disease compared to 48% of the non-demented group (p = 0.041). The demented subjects had more undiagnosed hypercholesterolaemia (p = 0.039) and undiagnosed hypothyroidism (p = 0.032) than the controls. Conclusion: Undiagnosing is more common among patients with dementia. Screening strategies should be developed further to find these patients.
The Contribution of Dementia to the Disablement Process and Modifying Factors
Authors: Barberger-Gateau Pascale , Alioum Ahmadou , Pérès Karine , Regnault Antoine , Fabrigoule Colette , Nikulin Misha , Dartigues Jean-François
Published: August 2004

The objective of this study was to examine the impact of dementia on disability progression and mortality, and to analyze the modifying effect of risk factors and extra-individual factors. A sample of 3,403 participants in the PAQUID study was followed for 10 years. Disability was assessed on a 4-grade scale: no disability, disabled only on the Rosow-Breslau scale, disabled on the Rosow-Breslau scale and on instrumental activities of daily living (IADL) scales, and disabled on the Rosow-Breslau, IADL and activities of daily living (ADL) scales. A Markov model was used to estimate the effect of explanatory variables on disability and mortality. Controlling for age, gender, education, place of residence, medical care and informal support, dementia had a strong significant effect on progression to IADL and then to ADL disability. Dementia did not increase the risk of death, once disability was taken into account, except from the lowest disability grade.
Increased Lymphocyte Dopamine β-Hydroxylase Immunoreactivity in Alzheimer’s Disease: Compensatory Response to Cholinergic Deficit?
Authors: Giubilei Franco , Calderaro Caterina , Antonini Giovanni , Sepe-Monti Micaela , Tisei Paolo , Brunetti Ercole , Marchione Francesca , Caronti Brunella , Pontieri Francesco E.
Published: August 2004

There is growing interest in the characterization of peripheral blood lymphocytes (PBL) as a biological tool with which to investigate changes in the neurotransmitter-receptor system in neurodegenerative disorders. Here we show a slight decrease in acetylcholinesterase (AChE) and a significant increase in dopamine β-hydroxylase (DBH) immunoreactivity in the PBL of patients with probable Alzheimer’s disease (AD). Therapy with AChE inhibitors completely reversed the increase in DBH immunoreactivity. We hypothesize that the increase in DBH immunoreactivity may represent a compensatory response to cholinergic impairment. Our findings suggest that neurochemical interactions between the noradrenergic and cholinergic systems may be measured at a peripheral level in AD.
Efficacy and Safety of Pantoprazole versus Ranitidine in the Treatment of Patients with Symptomatic Gastroesophageal Reflux Disease
Authors: van Zyl J. , van Rensburg C. , Vieweg W. , Fischer R.
Published: August 2004

Background/Aim: Gastroesophageal reflux disease (GERD) is a prevalent disease associated with a high symptom burden and a reduced quality of life. This multicenter, randomized, double-blind study compared relief from key GERD symptoms (heartburn, acid eructation, and pain on swallowing) and from other gastrointestinal symptoms (epigastric pain, vomiting, nausea, flatulence, retching, and retrosternal feeling of tightness) and safety profiles of the proton pump inhibitor pantoprazole and the H2 antagonist ranitidine in patients suffering from symptomatic GERD. Methods: The patients [338 intention-to-treat (ITT) population; 284 per-protocol (PP) population] received 20 mg pantoprazole (once daily in the morning) plus ranitidine placebo (once daily in the evening; ITT n = 167, PP n = 136) or pantoprazole placebo (once daily in the morning) plus 300 mg ranitidine (once daily in the evening; ITT n = 171, PP n = 148) for 28 days. The primary efficacy criterion (ITT and PP populations) was relief from key GERD symptoms (heartburn, acid eructation, and pain on swallowing) after 28 days of treatment. Secondary criteria (PP) included relief from key GERD symptoms on day 14, relief from all gastrointestinal symptoms on days 14 and 28, and relief from key GERD symptoms on days 14 and 28. Safety evaluations included adverse events and laboratory assessments. Results: Significantly more pantoprazole-treated patients were free from key GERD symptoms at day 28 (68.3%, n = 114) as compared with ranitidine-treated patients (43.3%, n = 74; 95% confidence interval for odds ratio 1.84–4.51). Pantoprazole was also significantly more efficacious in controlling all gastrointestinal symptoms of GERD. By day 28, 51.5% (n = 70) of the pantoprazole-treated patients were completely symptom free versus 31.1% (n = 46) of the ranitidine-treated patients (95% confidence interval for odds ratio1.45–3.83). Both treatments were well tolerated. Conclusion: Pantoprazole is significantly superior to ranitidine in the treatment of key and associated gastrointestinal symptoms of GERD and is well tolerated.
Segment-Specific Effects of Cardiovascular Risk Factors on Carotid Artery Intima-Medial Thickness in Women at Midlife
Authors: Schott Laura L. , Wildman Rachel P. , Brockwell Sarah , Simkin-Silverman Laurey R. , Kuller Lewis H. , Sutton-Tyrrell Kim
Published: August 2004

Objective—

We investigated associations between segment-specific carotid intima-medial thickness (IMT) and cardiovascular risk factors collected before menopause for insight into mechanisms of atherosclerosis development.

Methods and Results—

Participants were 453 healthy women (aged 46 to 58 years) enrolled in a dietary and physical activity randomized clinical trial. Ultrasound scan measures were taken ≈2.7 years after baseline in the common carotid artery (CCA), bifurcation (bulb), and internal carotid artery (ICA) segments. When scanned, 84% remained premenopausal. In linear regression models adjusted for age, menopausal status, and intervention group, measures independently (
P
<0.05) and positively associated were as follows: baseline weight (β=0.007 per 5 kg), systolic blood pressure (SBP; β=0.008 per 10 mm Hg), and age (β=0.02 per 5 years) with CCA IMT; smoking (β=0.08), weight (β=0.009), and SBP (β=0.02) with bulb IMT; and apoprotein B (β=0.01 per 0.1 g/L) with ICA IMT. Differential effects in a repeated measures model with all 3 IMT locations showed these risk factors to have segment-specific positive associations. The effect of weight was strongest in the CCA, smoking and SBP were specific to the bulb, and apoprotein B was strongest in the ICA segment.

Conclusion—

Analyses indicate that cardiovascular risk factors may differentially affect IMT in the CCA, bulb, and ICA segments of healthy middle-aged women.
Effects of Cardiac Resynchronization Therapy on Myocardial Perfusion Reserve
Authors: Knaapen Paul , van Campen Linda (C.)M.C. , de Cock Carel C. , Götte Marco J.W. , Visser Cees A. , Lammertsma Adriaan A. , Visser Frans C.
Published: August 2004

Background—

Cardiac resynchronization therapy (CRT) is a relatively new treatment strategy for patients with heart failure and mechanical asynchrony. Reported effects of CRT on regional myocardial blood flow (MBF) are conflicting, and effects on hyperemic MBF are scarce. The aim of the present study was to assess serial changes of MBF and MBF reserve in patients receiving a biventricular pacemaker.

Methods and Results—

Fourteen patients with heart failure (NYHA class III or IV; left ventricular ejection fraction <35%), QRS width >120 ms, and sinus rhythm were studied (mean age, 58±10 years; 8 men). MBF and hyperemic MBF were measured at baseline, 3 months after biventricular pacing (CRT on), and after cessation of pacing (CRT off) with PET and H
2
15
O. CRT had no significant effect on resting MBF (baseline versus CRT on versus CRT off: 0.82±0.25 versus 0.69±0.24 versus 0.74±0.24 mL · min
−1
· mL
−1
;
P
=NS). Hyperemic MBF increased during CRT (1.91±1.03 versus 2.66±1.66 versus 1.92±1.06 mL · min
−1
· mL
−1
;
P
=0.01 by MANOVA), as did MBF reserve (2.25±1.00 versus 3.76±2.38 versus 2.49±0.94 mL · min
−1
· mL
−1
;
P
=0.023). CRT (reversibly) resulted in a more homogeneous distribution of regional resting MBF as demonstrated by the septal-to-lateral ratio. The decrease in the ratio of left ventricular end-diastolic volume to left ventricular mass, as a reflection of wall stress, was related to the increase in hyperemic MBF (
r
=0.53,
P
<0.05). Left ventricular ejection fraction increased from 25±7% to 37±9% (
P
<0.01).

Conclusions—

Resting MBF is unaltered by CRT despite an increase in left ventricular function. However, the distribution pattern of resting MBF becomes more homogeneous. Hyperemic MBF and consequently MBF reserve are enhanced by CRT.
Association of Human Connexin40 Gene Polymorphisms With Atrial Vulnerability as a Risk Factor for Idiopathic Atrial Fibrillation
Authors: Firouzi Mehran , Ramanna Hemanth , Kok Bart , Jongsma Habo J. , Koeleman Bobby P.C. , Doevendans Pieter A. , Groenewegen W. Antoinette , Hauer Richard N.W.
Published: August 2004

Alterations in distribution, density, and properties of cardiac gap junctions, which mediate electrical coupling of cardiomyocytes, are considered potentially arrhythmogenic. We recently reported 2 linked polymorphisms within regulatory regions of the gene for the atrial gap junction protein connexin40 (Cx40) at nucleotides −44 (G→A) and +71 (A→G), which were associated with familial atrial standstill. The present study examined whether these Cx40 polymorphisms were associated with increased atrial vulnerability in vivo and arrhythmia susceptibility. In 30 subjects without structural heart disease, of whom 14 had documented sporadic paroxysmal atrial fibrillation (AF) and 16 had no AF history, inducibility of AF was assessed using an increasingly aggressive atrial stimulation protocol. Coefficient of spatial dispersion of refractoriness (CD) was calculated. CD was defined as the SD of 12 local mean fibrillatory intervals recorded at right atrial sites, expressed as a percentage of the overall mean fibrillatory interval. Cx40 genotypes were determined by direct DNA sequencing. Subjects were stratified according to normal or increased CD with a cutoff value of 3.0, because CD >3.0 was previously shown to be strongly associated with enhanced atrial vulnerability. The prevalence of the minor Cx40 allele (−44A) and −44AA genotype was significantly higher in subjects with increased dispersion (n=13) compared with those with CD ≤3.0 (n=17;
P
=0.00046 and
P
=0.025; odds ratios of 6.7 and 7.4) and a control population (n=253;
P
=0.00002 and
P
=3.90×10
−7
). Carriers of −44AA genotype had a significantly higher CD compared with those with −44GG genotype (6.37±1.21 versus 2.38±0.39,
P
=0.018), whereas heterozygotes had intermediate values (3.95±1.38, NS). All subjects with increased CD had a history of idiopathic AF compared with only 1 subject with normal CD. The −44A allele and −44AA genotype were significantly more frequent in subjects with prior AF than in those without (
P
=0.0019 and
P
=0.031; odds ratios 5.3 and 6.2). This study provides strong evidence linking Cx40 polymorphisms to enhanced atrial vulnerability and increased risk of AF. The full text of this article is available online at http://circres.ahajournals.org.
Targeted Disruption of
hesr2
Results in Atrioventricular Valve Anomalies That Lead to Heart Dysfunction
Authors: Kokubo Hiroki , Miyagawa-Tomita Sachiko , Tomimatsu Hirofumi , Nakashima Yasumi , Nakazawa Makoto , Saga Yumiko , Johnson Randy L.
Published: August 2004

Genes involved in the Notch signaling pathway have been shown to be critical regulators of cardiovascular development. In vitro studies have revealed that the Notch signaling pathway directly regulates transcription of hairy and enhancer of split-related (
hesr
) genes, encoding basic helix-loop-helix transcription factors. To assess the functional role of
hesr
genes in cardiovascular development, we generated mice with a targeted disruption of the
hesr2
gene and used echocardiography to analyze heart function of the mutant mice. In the early postnatal period, a majority of
hesr2
homozygous mice die as a result of congestive heart failure accompanied by pronounced heart enlargement. Transthoracic echocardiography on 5-day-old homozygous mice revealed tricuspid and mitral valve regurgitation and a dilated left ventricular chamber with markedly diminished fractional shortening of the left ventricle. The hemodynamic anomalies were accompanied by morphological changes, such as dysplastic atrioventricular (AV) valves, a perimembranous ventricular septal defect, and a secundum atrial septal defect. AV valve regurgitations attributable to dysplasia of the AV valves were most likely responsible for the heart dysfunction in
hesr2
homozygous mice. These observations indicate that the Notch signaling target
hesr2
plays an important role in the formation and function of the AV valves. In addition,
hesr2
activity may be important for proper development of cardiomyocytes, thereby assuring normal left ventricular contractility. Because of the unique spectrum of cardiac anomalies expressed by
hesr2
-null mice, they represent a useful model system for elucidating the genetic basis of heart dysfunction.