bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress in Understanding GJB2-Linked Deafness
Authors: Gualandi Francesca , Martini Alessandro , Calzolari Elisa
Published: June 2004

Mutations in the GJB2 gene (encoding for Connexin 26 protein) represent a leading cause of genetic hearing impairment. Extensive epidemiological and molecular studies have been reported, describing GJB2 mutations type, frequency and distribution. Moreover, several aspects of GJB2 mutations pathogenic effects have been elucidated taking advantage of in vitro and in vivo experimental approaches. Progress through reported studies is reviewed, highlighting recent major achievements in this field. Attention is focused on different unresolved questions regarding GJB2 deafness pathogenesis and genotype-phenotype relationships. Clarification of these important clues will significantly increase our understanding of the molecular basis of hearing loss and will improve the effectiveness of diagnosis and counselling of this frequent disease.
Ethical Aspects of Genetic Testing in the Workplace
Authors: Holtzman Neil A.
Published: June 2004

The European Group on Ethics and New Technologies, which advises the European Commission, has published an opinion paper on ethical aspects of genetic testing in the workplace. The paper goes well beyond the usual ethical issues, presenting a summary of genetic testing in the workplace in the United States and Europe and criteria for appropriate testing. Unlike many other documents on ethics, it pays close attention to the problem of false-positive and false-negative test results. Although no genetic tests are currently appropriate for screening workers or applicants for jobs in which occupational hazards exist, inappropriate testing has occurred and regulations are needed to ensure that only appropriate testing is used in the future. Workers or their representatives should be involved in deciding when and how genetic testing in the workplace is done.
How Should Preconceptional Cystic Fibrosis Carrier Screening Be Provided? Opinions of Potential Providers and the Target Population
Authors: Poppelaars Francis A.M. , Henneman Lidewij , Adèr Herman J. , Cornel Martina C. , Hermens Rosella P.M.G. , van der Wal Gerrit , ten Kate Leo P.
Published: June 2004

Background: Since the identification of the cystic fibrosis (CF) gene, large-scale CF carrier screening has become possible. One possible target group is couples planning a pregnancy (preconceptional screening), providing a maximum number of reproductive options and a minimum of time constraints. Objectives: To identify obstacles in the implementation of a preconceptional CF carrier screening programme, to find out how potential providers and the target population think the screening should be implemented, and to determine whether potential providers think they are able to provide the screening programme. Methods: A survey was conducted among 200 general practitioners (GPs), 134 Municipal Health Service (MHS) workers and 303 recently married couples. Results: 52% (102/197) of the eligible GPs participated, 84% (113/134) of the MHS workers and 70% (380/544) of the individuals planning a pregnancy. In general, potential providers and the target population had a positive attitude towards CF screening. Preferred methods of informing the target population were: in leaflets, during a GP consultation for those people seeking advice before pregnancy, and sending a personal invitation to all people of reproductive age. Potential providers believed that they would be able to provide the screening programme. Important perceived obstacles were the absence of a preconceptional care setting, high workload, and lack of financial resources. Conclusion: Different intervention strategies will be necessary to overcome the obstacles in the implementation. The positive attitude towards CF carrier screening in combination with the willingness of the potential providers to participate in the screening programme will make it easier to overcome the obstacles.
Parents’ Satisfaction with Medical and Social Assistance Provided to Children with Down Syndrome: Experience in Estonia
Authors: Reimand Tiia , Uibo Oivi , Zordania Riina , Palmiste Veronika , Õunap Katrin , Talvik Tiina
Published: June 2004

Objective: Parents of children with mental or physical disabilities have been assumed to live more stressful lives than other parents, and people with Down syndrome (DS) may get second-rate care because of their diagnosis. The aim of this work is to investigate the extent of parents’ satisfaction with medical and social services in Estonia provided for the DS individuals and their families. Methods: From 1999 to 2001, fifty-nine DS families answered questionnaires in which we inquired about their satisfaction with medical and social assistance. Results: We found that satisfaction with the quality of the information about DS is low, and most of the parents are not satisfied with the social benefits and rehabilitation options. Conclusions: The DS families need more medical information about this syndrome. The medical staff has to learn more about how to deliver bad news and how to support parents. More work needs to be done in the area of rehabilitation options and social assistance.
Chemotherapy Is More Active against Proximal than Distal Gastric Carcinoma
Authors: Higuchi Katsuhiko , Koizumi Wasaburo , Tanabe Satoshi , Saigenji Katsunori , Ajani Jaffer A.
Published: June 2004

Objective: Patients with localized proximal gastric carcinoma (PGC) have a poorer outcome than those with distal gastric carcinoma (DGC) following curative resection. However, it remains uncertain whether the location of the primary tumor influences the effect of chemotherapy in advanced gastric carcinoma. Methods: We assessed 270 eligible patients with unresectable, advanced gastric carcinoma who had received first-line chemotherapy between 1989 and 2001. We defined PGC as carcinoma located in the upper one third, and DGC as carcinoma located in the lower two thirds of the stomach. Results: Of the 270 patients, 91 (33.7%) had PGC, and 179 (66.3%) had DGC. The response rate of the primary lesion was 58.6% (51/87) in the PGC group and 35.1% (59/168) in the DGC group (p < 0.01). The overall response rate for all sites was 55.6% (50/90) in the PGC group and 39.0% (69/177) in the DGC group (p = 0.01). The median survival time was 318 days in the PGC group and 251 days in the DGC group (p = 0.0336). A multivariate analysis revealed that performance status, extent of disease, and location of the primary lesion were significantly related to survival. Conclusions: Our data suggest that the response rate and survival time after first-line chemotherapy in advanced gastric carcinoma are better in patients with PGC than in those with DGC.
Estimating the Probability of Cancer with Several Tumor Markers in Patients with Colorectal Disease
Authors: Carpelan-Holmström Monika , Louhimo Johanna , Stenman Ulf-Håkan , Alfthan Henrik , Järvinen Heikki , Haglund Caj
Published: June 2004

Objective: The purpose of this study was to evaluate and compare serum tumor markers, carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and hCGβ, and their value in the diagnosis of malignant colorectal disease. Methods: The serum concentrations of the markers were measured in 204 patients with colorectal cancer and in 104 inpatients with benign colorectal disease. The combined use of the markers was evaluated with a logistic regression analysis. Results: When all five markers were evaluated in the same model, only CEA and CA 72-4 provided significant diagnostic information (p < 0.001), indicating that their combination improves the accuracy. The probability of cancer for each patient was calculated entering CEA and CA 72-4 in the logistic regression model. Receiver-operating characteristic curves were constructed, and the difference in the area under the curve (AUC) values was determined between the markers and the calculated probability of cancer. Of the individual markers, the highest AUC was observed for CEA (AUC = 0.746). The difference in the AUC between CEA and CA 72-4 (AUC = 0.716) was insignificant (p = 0.492), but between CEA and the other three markers it was significant (p < 0.015). The calculated probability of cancer index, based on a combination of CEA and CA 72-4, had a significantly higher AUC (AUC = 0.804) than CEA alone (AUC = 0.746; p = 0.046). Conclusions: The diagnostic value of CA 72-4 was additive to that of CEA in colorectal cancer, and both markers contributed with significant diagnostic information. As a diagnostic test, the probability of cancer calculated with logistic regression provided higher accuracy than any of the markers alone, implying that it might be a useful diagnostic tool.
Effects of Carnitine Supplementation on Muscle Metabolism by the Use of Magnetic Resonance Spectroscopy and Near-Infrared Spectroscopy in End-Stage Renal Disease
Authors: Vaux E.C. , Taylor D.J. , Altmann P. , Rajagopalan B. , Graham K. , Cooper R. , Bonomo Y. , Styles P.
Published: June 2004

Background/Aim: A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function. Methods: In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks. Results: There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-Carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment. Conclusions: The study failed to show any significant effect of 16 weeks’ L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.
Malnutrition Is Associated with Increased Blood Pressure in Childhood
Authors: Sesso Ricardo , Barreto Genia P. , Neves Janaina , Sawaya Ana L.
Published: June 2004

Background/Aims: Protein-energy malnutrition remains a major public health problem in many countries. Scanty information is available about the effects of malnutrition during childhood on blood pressure (BP). Methods: In a cross-sectional study we assessed the BP of 172 children older than 2 years living in shantytowns in São Paulo city. Ninety-one children were malnourished (height-for-age or weight-for-age Z-score below –1 of the NCHS references); 20 had recovered from malnutrition after an average time of 6.4 years, and 61 were non-malnourished controls. Results: A greater percentage of children in the malnourished and recovered groups had increased systolic or diastolic BP (>95th percentile of the Update of the 2nd Task Force references) after adjusting for age, sex and height, compared to the controls (29, 20 and 2%, respectively, p < 0.001). Mean diastolic BP, adjusted for age, sex, race, weight, height and birth weight, was significantly increased in malnourished and recovered children compared to controls (65.2 ± 0.6, 66.5 ± 1.5, and 61.8 ± 0.8 mm Hg, respectively, p < 0.01). Conclusions: BP is increased in malnourished children and in those who recovered from malnutrition after an average period of 6 years. Malnutrition occurring during childhood may represent a risk factor for increased BP later in life.
Localization of Discoidin Domain Receptors in Rat Kidney
Authors: Lee Rutha , Eidman Keith E. , Kren Stefan M. , Hostetter Thomas H. , Segal Yoav
Published: June 2004

Background/Aim: The discoidin domain receptors (DDRs) DDR1 and DDR2 are cardinal members of a receptor tyrosine kinase subfamily, activated by collagens. They are candidate effectors in tissue injury and fibrosis. We investigated the DDR expression in normal and remnant rat kidneys. Methods: The DDR expression in kidney and other tissues was examined by indirect immunofluorescence, immunoblotting, and ribonuclease protection assays. The expression patterns in remnant and control kidneys were compared at 2-, 4-, and 8-week time points, following induction of injury. Results: DDR1 is expressed in basolateral membranes of select nephron segments, from the connecting tubule to the renal papilla. DDR2 is expressed in apical membranes of select nephron segments, from the loop of Henle to the macula densa. The DDR1 protein expression is upregulated within the glomeruli of remnant kidneys. The distribution of DDR2 in remnant kidneys is similar to that in controls. The DDR mRNA levels in remnant and control kidneys were not significantly different, at any time point. Conclusions: The DDR1 localization in the rat kidney is consistent with roles in cell-matrix interactions. Upregulation within glomeruli of remnant kidneys suggests the possibility of additional roles in kidney injury. The DDR2 localization in adult rat kidneys is inconsistent with roles in cell-matrix interactions.
Role of Haptoglobin Phenotype in End-Stage Kidney Disease
Authors: Burbea Zvi , Nakhoul Farid , Rosenberg Shai , Zoabi Roaa , Skorecki Karl , Hochberg Irit , Miller-Lotan Rachel , Benchetrit Sidney , Weissgarten Joshua , Knecht Aaron , Tovbin David , Levy Nina S. , Levy Andrew P.
Published: June 2004

Background: We recently reported that haptoglobin (Hp) phenotype 1-1 is protective against the development of nephropathy in normal creatinine diabetics. In the present study, we sought to determine if Hp phenotype also plays a role in renal deterioration by determining Hp phenotypes in a consecutive series of patients with chronic renal failure (CRF) in hemodialysis (HD) and predialysis clinics. Methods: Three hundred and ninety-two patients on HD for less than 2 years and 182 predialysis patients (creatinine clearance time [CCT] <35 ml/min) were subjected to Hp phenotyping. Age, gender and presence of diabetes or hypertension were recorded. Patients were stratified according to age (above and below 60 years) and severity of renal dysfunction (CRF or HD). Results: We observed a markedly lower prevalence of the Hp 1-1 phenotype in HD patients under 60 years of age compared to patients with CRF or compared to the general population. This was not due to differences in the threshold for dialysis initiation among patients with different Hp types or to decreased survival of patients with Hp 1-1 prior to entering HD. In HD patients 60 years and over, Hp 1-1 prevalence was increased, as observed with other diseases in this age group. Conclusions: The prevalence of Hp 1-1 is decreased in HD patients less than 60 years of age. This may be due to a fundamental difference in the rate of renal deterioration in patients with different Hp types. In addition, Hp 1-1 may provide a protective effect against mortality in elderly patients.
The Primitive Streak, the Caudal Eminence and Related Structures in Staged Human Embryos
Authors: Müller F. , O'Rahilly R.
Published: June 2004

The caudal region of the trunk was reassessed in 52 serially sectioned human embryos of stages 8–23, 42 of which were controlled by precise graphic reconstructions. The following observations, new for the human, are presented. (1) The neurenteric canal is an important landmark because rostral to it the neural plate of stages 8, 9, and the main part of the notochord develop, whereas caudal to it the neural plate of stages 10–12 and the caudal portion of the notochord are formed. All somites at stages 9–11 and probably also at stage 12 arise rostral to the site of the neurenteric canal. (2) A ‘chordoneural hinge’ can be detected in stages 10 and 11, where the caudal part of the neural plate gives off cells that probably participate in the production of mesenchyme. (3) When apparent disappearance of the epiblast is used as a criterion, then the primitive streak seems to end during stage 9. (4) The caudal eminence, derived from the primitive streak and covered by ectoderm, forms at stage 10 caudal to the site of the former neurenteric canal and persists as a terminal cap to at least stage 14, although formation of mesenchyme continues in stages 15 to 17 or 18. (5) As the region rostral to the site of the neurenteric canal grows because of the development of somites, the caudal eminence is shifted caudally. (6) The caudal eminence is most active developmentally during stage 13, when most of the required (ca 6 out of 9) pairs of somites appear. (7) The eminence produces the caudal part of the notochord and, after closure of the caudal neuropore, all caudal structures, but it does not produce even a temporary ‘tail’ in the human. (8) A temporal overlap results between primary and secondary development in the caudal part of the notochord. (9) Primary development begins very early with the formation of the inner cell mass at stage 3, and includes the development of the somites rostral to the neurenteric canal, whereas secondary development, with the exception of the notochord caudally, commences at stage 12. (10) Primary neurulation lasts from stage 8 to stage 12, secondary from stage 12 to stages 17 or 18. (11) Secondary development and secondary neurulation are characterized morphologically by direct formation of structures (notochord, postcloacal gut, neural cord/neural tube) from mesenchyme.
General Innervation Pattern and Sensory Corpuscles in the Scapholunate Interosseous Ligament
Authors: Hagert Elisabet , Ljung Björn-Ove , Forsgren Sture
Published: June 2004

The scapholunate interosseous ligament (SLIL) is biomechanically important in maintaining wrist motion and grip strength in the hand, but its possible sensory role in the dynamic muscular stability of the wrist joint has not been examined. The aim of this study was to use immunohistochemical methods to analyze the general innervation and the possible existence of sensory corpuscles in the SLIL. The ligament was excised in its entirety from 9 patients. Antibodies against the low-affinity p75 neurotrophic receptor (p75) were used to reveal sensory corpuscles as well as general innervation. Furthermore, antibodies against the general nerve marker protein gene product 9.5 (PGP 9.5) and the glial marker S-100 were used to additionally depict innervation and corpuscular structures. Blood vessels occurred in areas interspersed throughout the homogenous collagenous structure. In these vascularized areas, the SLIL was found to be supplied with nerve fascicles and sensory corpuscles of both the Ruffini and lamellated type. p75 immunoreactivity (IR) was detected in association with the nerve fascicles and the corpuscles, particularly in their capsule. S-100 IR was found in the Schwann cells in the central regions of the corpuscle, and PGP 9.5 IR marked the axonal structures in the corpuscles. New information on neurotrophin receptor distribution in ligaments has been obtained here. The presence of nerve fascicles and particularly sensory corpuscles in the SLIL suggests that the ligament has a proprioceptive role in the stability of the wrist. The marked p75 IR further indicates that neurotrophins play a part in a proprioceptive system in the ligament, given the importance of neurotrophins in maintaining sensory function.
Altered Vascular Remodeling in Osteopontin-Deficient Atherosclerotic Mice
Authors: Ström Åsa , Franzén Ahnders , Wängnerud Christel , Knutsson Ann-Katrin , Heinegård Dick , Hultgårdh-Nilsson Anna
Published: June 2004

Background: Osteopontin (OPN) is a cell-binding phosphoprotein with proposed functions in atherosclerosis. The aim of this study was to examine how OPN deficiency affects the atherosclerotic process. Methods: ApoE/LDL receptor/OPN triple knockout (ALO) mice were generated by crossing OPN null mice with ApoE/LDL receptor-deficient (AL) mice. Analysis were made on tissue sections from the aortic arch of 8-, 20- and 34-week female AL and ALO mice and included morphometric measurements, collagen staining, TUNEL staining and immunohistochemistry with antibodies to OPN, macrophages and proliferating cellular nuclear antigen (PCNA). Results: Lesion and media areas were significantly smaller and collagen accumulation in lesions was significantly reduced in 34-week-old ALO mice compared with AL mice. The numbers of proliferating and apoptotic cells were increased in lesions of 34 weeks old ALO mice. Furthermore, the plasma levels of SAA and total cholesterol were significantly decreased in 34 weeks old ALO mice. Conclusions: The present study shows that OPN deficiency reduces atherogenesis in atherosclerotic mice. The results corroborate and extend recently published findings and also include novel data on the role of OPN in the process of remodeling, inflammation and lipid metabolism.
Treatment of Ataxia in Cortical Cerebellar Atrophy with the GABAergic Drug Gabapentin
Authors: Gazulla José , Errea José M. , Benavente Isabel , Tordesillas Carlos J.
Published: June 2004

The aim of this work was to investigate the efficacy of the GABAergic drug gabapentin in the treatment of the cerebellar signs caused by cortical cerebellar atrophy (CCA). Ten patients with CCA received gabapentin in single doses of 400 mg in an open-label study; thereafter, daily administration of 900–1,600 mg of gabapentin was continued during at least 4 weeks. An ataxia scale based on clinical findings was used to evaluate the cerebellar signs at baseline and after administration of the drug. A statistically significant improvement of the ataxia scores was found after single doses of 400 mg of gabapentin and after the administration of 900–1,600 mg of this drug during 4 weeks, as compared to the results obtained at baseline. An important clinical amelioration was also evident. Gabapentin has been demonstrated to be capable of improving the cerebellar signs in cases of CCA, after single doses and after continued administration of the drug during 4 weeks. GABAergic enhancement or supplementation could play an important role in the treatment of diseases of the cerebellar cortex associated with a deficit of GABA.
A Study of Promoter and Intronic Markers of ApoI/Fas Gene and the Interaction with Fas Ligand in Relapsing Multiple Sclerosis
Authors: Lucas Miguel , Zayas María D. , De Costa Alzenira F. , Solano Francisca , Chadli Amal , Dinca Luminita , Izquierdo Guillermo
Published: June 2004

We studied the association between multiple sclerosis (MS) and a novel single nucleotide polymorphism (SNP), A/T(735)G/C, localized in intron IV of the ApoI/Fas gene, which is recognized by the restrictase MaeI. Fas-MaeI genotypes were screened in chromosomes of 215 healthy individuals and 312 relapsing MS patients of Spanish extraction. We also analyzed the interaction of this new intragenic marker with others previously associated with MS: class II HLA-DRB1*1501, Fas-MvaI and Fas ligand. The distribution of Fas-MaeI genotypes was in equilibrium in the control cohort, while a significant disequilibrium was observed in the patient group (χ2 = 16; p = 0.0003). Fas-MaeI genotypes were statistically different in the MS and control groups, but the allele frequencies were not. Sharing of MvaI/MaeI genotypes of the promoter/intron IV region did not differ between patients and controls. We failed to find different frequencies of ApoI/Fas genotypes in the population of MS carriers of the class II HLA-DRB1*1501 allele. The case/control comparative study showed a relative risk (OR close to 1.6) of MS in individuals harboring the T and A alleles of Fas- MaeI and Fas ligand, respectively. In conclusion, our findings suggest a weak association between the intronic marker Fas-MaeI and MS and a relative interaction with Fas ligand in an MS cohort of South Spanish extraction.
Magnetic Resonance Imaging and Neuropathology Findings in the Goat Nervous System following Hyperbaric Exposures
Authors: Blogg S.L. , Loveman G.A. , Seddon F.M. , Woodger N. , Koch A. , Reuter M. , Gennser M. , White M.G.
Published: June 2004

Divers may be at risk of long-term CNS damage from non-symptomatic hyperbaric exposure. We investigated the effect of severe, controlled hyperbaric exposure on a group of healthy goats with similar histories. Thirty goats were exposed to various dive profiles over a period of 5 years, with 17 experiencing decompression sickness (DCS). Brains were scanned using magnetic resonance (MR) imaging techniques. The animals were then culled and grossly examined, with the brain and spinal cord sent for neuropathological examination. No significant correlation was found between age, years diving, DCS or exposure to pressure with MR-detectable lesions in the brain, or with neuropathological lesions in the brain or spinal cord. However, spinal scarring was noted in 3 animals that had suffered from spinal DCS.
Dominant Ipsilateral Posterior Cerebral Artery on Magnetic Resonance Angiography in Acute Ischemic Stroke
Authors: Lee Ju-Hun , Han Sun-Jung , Kang Woo-Youl , Lee Ki Hyeong , Yu Kyung-Ho , Song Hong-Ki , Lee Byung-Chul
Published: June 2004

Background: In acute infarction involving the anterior circulation, the ipsilateral posterior cerebral artery (PCA) often appears to be longer than the contralateral PCA on magnetic resonance angiography. We described this finding as dominant ipsilateral PCA (DIPCA). We sought to find the frequency of DIPCA and its predictors. Methods: We recruited 164 consecutive individuals with acute infarct involving the anterior circulation, and analyzed their radiological and clinical features. Results: DIPCA was noted in 27 patients (16.5%). It was more frequent in patients with than in patients without steno-occlusive disease of the ipsilateral anterior circulation (30.5 vs. 2.4%, p < 0.001). Multivariate analysis revealed a significant relationship between the severity of arterial lesions in the ipsilateral anterior circulation and DIPCA (p = 0.039). Conclusions: DIPCA may reflect increased leptomeningeal collateral flow via the ipsilateral PCA, and its development may be dependent on the stenotic anterior circulation.
Impact of Applying NINDS-AIREN Criteria of Probable Vascular Dementia to Clinical and Radiological Characteristics of a Stroke Cohort with Dementia
Authors: Tang Wai Kwong , Chan Sandra S.M. , Chiu Helen F.K. , Ungvari Gabor S. , Wong Ka Sing , Kwok Timothy C.Y. , Mok Vincent , Wong K.T. , Richards Polly S. , Ahuja Anil T.
Published: June 2004

Background: There are no data concerning the relative representation of clinical vascular risk factors and radiological lesions in cases that have been ruled in and ruled out for probable vascular dementia (VaD) according to NINDS-AIREN criteria. Methods: Three months after their index stroke, a psychiatrist interviewed patients and made a diagnosis of VaD according to both DSM-IV and NINDS-AIREN criteria for probable VaD. Patients who fulfilled the DSM-IV criteria for VaD were divided into two groups: those who were ruled in and ruled out according to NINDS-AIREN criteria as probable VaD. Demographic characteristics, vascular risk factors, clinical features of the index stroke and radiological findings were then compared between the two groups. Results: Of the 297 patients screened, 56 (18.8%) had a DSM-IV diagnosis of dementia. Among these demented patients, 55 (98.2%) and 22 (39.3%) fulfilled DSM-IV and NINDS-AIREN diagnosis of VaD, respectively. The concordance and level of agreement (kappa statistic) between DSM-IV and NINDS-AIREN diagnoses were 40% and 0.02, respectively. Reasons of failure to meet NINDS-AIREN criteria included the lack of temporal relationship between dementia and stroke (n = 20), the absence of focal neurological signs and/or radiological evidence of stroke (n = 6) and both of the above (n = 7). There was no significant difference between the above two groups in terms of demographic data, features of index stroke, vascular risk factors and CT scan findings, except that leukoaraiosis (p = 0.021) and bilateral lesions (p = 0.015) were more frequent in subjects diagnosed according to NINDS-AIREN criteria of probable VaD. The difference between these two groups with respect to the number of lesions was borderline for significance (p = 0.052). Conclusions: The use of NINDS-AIREN criteria for VaD for case selection in poststroke dementia research may exclude a number of subjects with VaD.
Extended Single Nucleotide Polymorphism and Haplotype Analysis of the elastin Gene in Caucasians with Intracranial Aneurysms Provides Evidence for Racially/Ethnically Based Differences
Authors: Krex Dietmar , König Inke R. , Ziegler Andreas , Schackert Hans K. , Schackert Gabriele
Published: June 2004

Background: There is growing evidence that genetic variants have an impact on the pathogenesis of intracranial aneurysm (IA). Recently, the genetic locus around the elastin gene (7q11) has been identified as linked to IA in a Japanese population. Our aim was to confirm these results in Caucasian populations. Methods: We conducted a case-control study in 120 Caucasian patients with IA and 172 controls to investigate 8 single nucleotide polymorphisms (SNPs) and various haplotypes within the elastin gene, which were frequently found and associated with the phenotype in the Japanese populations. Real-time PCR and melting curve analysis were used for the detection of genotypes. Results: Allele frequencies and genotypes were equally distributed between Caucasian cases and controls. We failed to identify haplotypes that are associated with the phenotype in our population, which is in contrast to the Japanese study. However, allele frequencies in control populations differ between Caucasians and Japanese. Conclusions: We found no association between SNPs and haplotypes of the elastin gene and the occurrence of IA in our Caucasian populations. However, our data provide strong evidence for racial/ethnic differences in the association of SNP and specific haplotypes of the elastin gene with the phenotype. There might be other genetic variants of the elastin gene associated with IA in Caucasians.
Early Motor Evoked Potentials in Acute Stroke: Adjunctive Measure to MRI for Assessment of Prognosis in Acute Stroke within 6 Hours
Authors: Wöhrle Johannes C. , Behrens Stephan , Mielke Orell , Hennerici Michael G.
Published: June 2004

Background: In acute stroke, a magnetic resonance (MR) perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch (PWI>DWI mismatch) may indicate tissue at risk for infarction and poor prognosis. However, different to early enthusiasm about this surrogate marker, its validity has shown several drawbacks in individual patients. Rather than relying on imaging, we evaluated motor evoked potentials (MEP) as a measure of cerebral function in the acute stroke setting. Methods: Thirteen patients with acute hemiparetic stroke underwent time to peak PWI and DWI within 6 h after onset as well as recordings of early MEP of first dorsal interosseous muscles. Outcome was assessed by the Unified Neurological Stroke Scale and Barthel Index at day 42. Results: Of 8 patients with PWI>DWI mismatch, 4 patients with normal MEP had a good clinical outcome and 4 patients with absent or pathological MEP had an unfavourable outcome (p < 0.05, Fisher’s exact test). In all patients without PWI>DWI mismatch, MEP findings predicted clinical outcome. Normal MEP at day 0 – but not PWI/DWI findings – significantly correlated with a good clinical outcome. Conclusions: Early MEP recordings in acute stroke patients provide valid prognostic information; they may become more useful for specific treatment decisions than presently available MRI surrogate parameters.
How to Write a Research Paper
Authors: Alexandrov Andrei V.
Published: June 2004

Background: Busy strokologists often find little time for scientific writing. They sometimes develop a mental condition equivalent to that known by neurologists as writer’s cramp. It may result in permanent damage to academic career. This paper provides advice how to prevent or treat this condition. Methods: Prepare your manuscript following the IMRaD principle (Introduction, Methods, Results, and Discussion), with every part supporting the key message. When writing, be concise. Clearly state your methods here, while data belong to Results. Successful submissions combine quality new data or new thinking with lucid presentation. Results: Provide data that answer the research question. Describe here most important numeric data and statistics, keeping in mind that the shorter you can present them, the better. The scientific community screens abstracts to decide which full text papers to read. Make your point with data, not arguments. Conclusions: Conclusions have to be based on the present study findings. The time of lengthy and unfounded speculations is over. A simple message in a clearly written manuscript will get noticed and may advance our understanding of stroke.
Can We Predict Early Recurrence in Acute Stroke?
Authors: Leira Enrique C. , Chang Ku-Chou , Davis Patricia H. , Clarke William R. , Woolson Robert F. , Hansen Michael D. , Adams Jr. Harold P.
Published: June 2004

Background: The prevention of early recurrent stroke, which worsens outcomes after a cerebral infarction, is a major objective for acute stroke therapy. The ability to predict which patients are at risk for early recurrence would be useful for both the management and design of clinical trials. Methods: Using the prospective database with the 1,266 stroke patients admitted in the TOAST study, we analyzed all the patients who had suffered either a transient ischemic attack (TIA) or a recurrent stroke within 3 months after stroke, and their possible association with 20 selected clinical variables. Both univariate and stepwise regression analyses were performed. Results: Sixty-two patients (4.9%) had a second stroke, and 47 patients (3.7%) had at least one TIA. No particular high-risk period was observed. Early recurrent stroke was associated with the large artery atherosclerosis subtype. A prior history of TIA increased the odds for recurrent stroke (OR = 2.52; 1.16–5.46) or poststroke TIA (OR = 3.46; 1.59–7.48). In addition, patients who had a TIA after the stroke had a 17% chance of having an early recurrent stroke, as compared with 4.4% among those that did not (p = 0.001). Conclusion: Our present ability to identify patients at risk for early recurrence based on baseline clinical features remains limited. While the presence of TIA before or after the stroke denotes a subgroup of acute stroke patients at higher risk for early recurrence in the first 3 months, no other factors reliably identify high-risk patients.
Impact and Influences on Caregiver Outcomes at One Year Post-Stroke
Authors: Smith Lorraine N. , Norrie John , Kerr Susan M. , Lawrence I. Maggie , Langhorne Peter , Lees Kennedy R.
Published: June 2004

Background and Purpose: Four outcome measures of carer stress and coping at one year post-stroke were identified: carer general health, anxiety, depression and perception of stress. Methods: Each outcome was assessed using valid and reliable instruments. In addition, we collected demographic data from both carers and patients which could reasonably be expected to influence carer stress and coping (e.g. age, deprivation levels) as well as information specific to the caring role. Results: Carers were found to be more anxious than previously reported. Neither satisfaction with caring nor the adoption of helpful coping strategies were associated with positive carer outcomes but, nevertheless, carers were not reluctant to care. The SF-36 is a useful predictor of carer stress, in particular the vitality score. Conclusions: Patient data are not sufficient to predict carer general health at one year. At one year, both patients and carers are more anxious than depressed. And there may be a group of patients and carers who can be characterised as borderline anxious and/or depressed and who warrant specific attention to prevent carer burnout.
Surgical Treatment of Achalasia: Current Status and Controversies
Authors: Abir Farshad , Modlin Irvin M. , Kidd Mark , Bell Robert
Published: June 2004

Objective: To review the current management of achalasia, and the controversies regarding the different treatment options. Methods: A review of the literature was performed. The key words used were esophageal achalasia, Heller myotomy, endoscopic balloon dilatation, laparoscopic Heller myotomy, and fundoplication. Results: Patients who fail medical therapy (e.g. pharmacologic therapy, botulinum toxin, balloon dilatation) should be considered for surgical therapy for the management of achalasia. Currently, numerous surgical procedures exist for the treatment of achalasia (transabdominal cardiomyotomy, thoracoscopic or open transthoracic cardiomyotomy, and laparoscopic Heller myotomy with an antireflux procedure). Conclusions: Laparoscopic Heller myotomy is generally accepted as the operative procedure of choice for achalasia. However, controversy exists as to whether a concomitant antireflux procedure is necessary, and if so, what type should be performed. Given the deleterious effects of postoperative reflux, and the facility of including an antireflux procedure at the time of the myotomy, there is merit in undertaking an antireflux procedure at the time of the laparoscopic Heller myotomy.
Favourable Prognostic Factors in a Large UK Experience of Adenocarcinoma of the Head of the Pancreas and Periampullary Region
Authors: Jarufe N.P. , Coldham C. , Mayer A.D. , Mirza D.F. , Buckels J.A.C. , Bramhall S.R.
Published: June 2004

Aims: To present the surgical experience in a regional unit, analysing the post-operative outcome, and determining risk factors for survival after pancreaticoduodenectomy for periampullary and pancreatic head carcinoma. Methods: Data were collected on 251 patients with pancreatic head adenocarcinoma (133), ampullary carcinomas (88) and distal common bile duct (30), between 1987 and 2002. Survival was calculated using the Kaplan-Meier method. Clinical, surgical and histopathological records were examined by univariate and multivariate analysis to identify the independent prognostic predictors of survival. Results: Median actuarial survival for carcinoma of the pancreatic head, ampulla and distal bile duct were 13.4, 35.5 and 16 months, respectively; p < 0.0001. On univariate analysis for the whole series, the age ≤60, tumour of the head of the pancreas, lymph node positive, resection margin R1, poorly differentiated tumours, and portal vein invasion significantly decreased survival. On multivariate analysis, poor tumour differentiation, surgical margin, lymph node metastases, and age independently influence survival. Mortality and morbidity were 4.8 and 29.9%, respectively. Conclusions: Pancreaticoduodenectomy for pancreatic and periampullary tumours is the only therapy that may cure patients and can be performed safely in centres with significant experience.
Development of an Early Diagnostic System Using Fuzzy Theory for Postoperative Infections in Patients with Gastric Cancer
Authors: Sakaguchi Satoru , Takifuji Katsunari , Arita Seizaburo , Yamaue Hiroki
Published: June 2004

Background: Early prediction of infection following surgery for gastric cancer may permit earlier intervention. Aim: The aim was to develop an early diagnostic system for postoperative infection. Methods: Clinical and laboratory data were analyzed in 180 patients who had surgery for gastric cancer at the Wakayama Medical University Hospital (January 1992 to December 1994). Of these, 60 patients developed a postoperative infection. A predictive system was then devised using fuzzy theory and evaluated in a second set of 137 patients who underwent surgery for gastric cancer at Wakayama Medical University and 10 other associated hospitals (August 1995 to January 1997). Results: The system identified seven parameters grouped into six rules and entered into a fuzzy logic system to predict either infection or non-infection. (1) Blood loss, and extent of resection; (2) the febrile pattern during days 2 to 4; (3) differential leukocyte count on day 4; (4) C-reactive protein level on day 4; (5) time sequential vectors during days 1–4 for the band cell neutrophil count, and (6) leukocyte count. The sensitivity was 86% (24/28), the specificity was 90% (98/109), the negative predictive value was 96% (98/102), the positive predictive value was 69% (24/35) and the overall accuracy was 80% (122/137). Conclusion: Fuzzy theory can provide early prediction of postoperative infection using standard clinical and biochemical parameters. The clinical utility of this system needs to be determined in future studies.
Postmenopausal Hormone Therapy Is Associated With Atherosclerosis Progression in Women With Abnormal Glucose Tolerance
Authors: Howard Barbara V. , Hsia Judith , Ouyang Pamela , Van Voorhees Lucy , Lindsay Joseph , Silverman Angela , Alderman Edwin L. , Tripputi Mark , Waters David D.
Published: June 2004

Background—

Abnormal glucose tolerance (AGT; diabetes or impaired glucose tolerance) is associated with increased risk of cardiovascular disease, especially in women. Cardiovascular disease rates in women increase after menopause. The Women’s Health Initiative found that postmenopausal hormone therapy (PHT) increased the risk of cardiovascular disease and that effects in diabetic women did not differ from those in women without diabetes. In this study, we hypothesized that PHT would have a worse effect on disease among women with AGT.

Methods and Results—

We randomly assigned 423 postmenopausal women with angiographically defined atherosclerosis (321 women had exit angiograms) with (n=140) or without (n=181) AGT to receive estrogen, estrogen plus progestin, or a placebo for 2.8±0.9 years. LDL was lower and HDL and triglycerides were higher after PHT in non-AGT and AGT women, but more adverse changes occurred in C-reactive protein and fibrinogen in women with AGT (
P
=0.11 and
P
=0.02 for interactions). PHT had no effect on fasting glucose or insulin concentrations in women without AGT, but in women with AGT, fasting glucose levels, insulin concentration, and insulin resistance as assessed by the HOMA (homeostasis model) calculation decreased slightly (
P
=0.28,
P
=0.25,
P
=0.14 for interaction, respectively). Atherosclerotic progression was greater in women with AGT. Atherosclerotic progression in previously nondiseased segments was enhanced by PHT to a greater extent in women with AGT (
P
=0.11 for interaction).

Conclusions—

PHT is associated with a worsening of coronary atherosclerosis and exacerbation of the profile of inflammatory markers in women with AGT. Therefore, PHT is not warranted for use in diabetic women. Further study is needed to explore the improvement in insulin resistance and glycemia that appears to occur with PHT in women with AGT.
Strain-Dependent Vascular Remodeling
Authors: Korshunov Vyacheslav A. , Berk Bradford C.
Published: June 2004

Background—

Atherosclerosis of the carotid artery, called intima-media thickening (IMT), is a form of vascular remodeling that is an important predictor for cardiovascular events and has a strong genetic component.

Methods and Results—

Recently, we established a mouse model of vascular remodeling based on partial ligation of the carotid, which is relevant to the “Glagov phenomenon.” We hypothesized that there would be genetically determined differences in outward remodeling and IMT induced by carotid flow alterations. We compared vascular remodeling among 5 inbred strains of mice. Despite similar changes in flow among the strains in the left carotid artery (LCA), we observed dramatic differences in remodeling of the partially ligated LCA relative to control. The smallest IMT volume (26±3 μm
3
) was found in C3H/HeJ mice, and the largest were in SJL/J (59±10 μm
3
) and FVB/NJ (81±6 μm
3
). Shear stress did not differ after ligation among strains. Lumen area decreased only when stenosis was ≥55%. IMT correlated significantly with outward remodeling among inbred strains (except C3H). There were significant strain-dependent differences in remodeling index (measured as vessel area/IMT), which suggest fundamental alterations in sensing or transducing hemodynamic signals among strains. Among hemodynamic factors, low shear stress and high heart rate were predictive for IMT. Specifically, heart rate (bpm: C3H, 592±6; SJL, 649±6; FVB, 683±7) but not systolic blood pressure (mm Hg: C3H, 116±2; SJL, 119±1; FVB, 136±1) was predictive.

Conclusions—

The present study indicates that performing a genetic cross of these strains and total genome scan should identify genes that mediate vascular remodeling.
Acute Improvement in Global and Regional Left Ventricular Systolic Function After Percutaneous Heart Valve Implantation in Patients With Symptomatic Aortic Stenosis
Authors: Bauer Fabrice , Eltchaninoff Hélène , Tron Christophe , Lesault Pierre-François , Agatiello Carla , Nercolini Deborah , Derumeaux Geneviève , Cribier Alain
Published: June 2004

Background—

The newly developed percutaneous heart valve (PHV) implantation technique decreases transaortic pressure gradient in patients with aortic stenosis. PHV replacement effects on left ventricular (LV) global and regional systolic function are currently unknown.

Methods and Results—

Eight patients with severe aortic stenosis had 2D echocardiography at baseline and 24 hours after PHV implantation to evaluate changes in LV volume and LV ejection fraction. Regional function, ie, both peak systolic anterior and posterior wall tissue velocity, as well as strain and strain rate imaging, were measured by tissue Doppler imaging from a short-axis view. At 24 hours, a significant reduction in transaortic mean pressure gradient (from 46±15 to 8±3 mm Hg;
P
<0.0001) was accompanied by an increase in aortic valve area (from 0.59±0.11 to 1.69±0.11 cm
2
;
P
<0.0001). LV end-diastolic volume remained unchanged (102±36 to 101±12 mL;
P
=NS), whereas LV ejection fraction increased (48±18% to 57±12%;
P
<0.01). Improvement in posterior wall displacement (posterior wall tissue velocity increased from 2.2±0.5 to 4.4±1.0 cm/s
−1
;
P
=0.0003) and deformation (strain rate imaging increased from 1.0±0.3 to 1.9±0.7 s
−1
,
P
=0.009, and strain increased from 11±5% to 17±9%;
P
=0.02) were observed.

Conclusions—

Immediately after PHV replacement, improvement of LV global and regional systolic function was evidenced by tissue Doppler imaging.