bluuebunny/crossref_metadata_2025 huggingface dataset:
Principle Mechanisms Underlying Venous Thromboembolism: Epidemiology, Risk Factors, Pathophysiology and Pathogenesis
Authors: Kroegel Claus , Reissig Angelika
Published: April 2003

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are distinct but related aspects of the same dynamic disease process known as venous thromboembolism (VTE). An estimated 200,000 new cases occur in the United States every year, including 94,000 with PE, resulting in an incidence of 23 per 100,000 patients per year-cases. Without treatment, pulmonary embolism is associated with a mortality rate of approximately 30%, causing nearly 50,000 deaths per year. Moreover, based on post-mortem studies, two-thirds of the patients with pulmonary emboli remain undiagnosed. Clinically, PE may present as (1) isolated dyspnea, (2) pleuritic pain and/or hemoptysis, and (3) circulatory collapse. However, clinical history and examination can be notoriously misleading in reaching a diagnosis. A number of acquired etiologic risk factors (predispositions) are associated with a tendency to develop VTE. These include increasing age, immobilization, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, as well as certain types of oral contraception and hormone replacement therapy. In addition, a variety of genetic risk factors, such as factor V Leiden, protein S or C deficiency have also been identified. However, in at least half of the instances, no predisposing factors can be identified (idiopathic PE). In the majority of cases thromboemboli originate in the deep veins of the calf or pelvis. The pathogenic conditions for VTE comprise a triad of factors and include (1) venous stasis, (2) hypercoagulable states, and (3) vascular endothelium injury. Occlusion of pulmonary arteries has variable and transient clinical and pathophysiologic consequences, involving both mechanical and reflex effects of vascular occlusion with a consecutive perfusion defect as well as the release of vasoactive and other inflammatory mediators. The objectives of this article are to present an overview of the etiologic and pathogenic factors promoting VTE as well as the pathophysiologic and inflammatory processes following PE.
Age and Sex Differences in the Treatment of Patients with Initial Acute Myocardial Infarction: A Community-Wide Perspective
Authors: Harrold Leslie R. , Lessard Darleen , Yarzebski Jorge , Gurwitz Jerry H. , Gore Joel M. , Goldberg Robert J.
Published: April 2003

Purpose: The goal of this observational study was to examine overall and age-specific differences between women and men in the use of five beneficial cardiac medications in patients hospitalized with acute myocardial infarction (AMI) from a community-wide perspective. The objectives of our study were to determine whether women are treated differently than men and whether age acts as a potential effect modifier of any observed associations. Subjects: A total of 2,461 women and 3,454 men with validated AMI comprised the study sample. Methods: Our study was an observational investigation of metropolitan Worcester (Mass., USA) residents who were hospitalized with initial AMI in all area hospitals during 12 1-year periods between 1975 and 1999. Four age-specific subgroups (<55, 55–64, 65–74 and ≧75 years) were studied. Results: Differences in the use of angiotensin-converting enzyme (ACE) inhibitors, aspirin, β-blockers, lipid-lowering medications and thrombolytic agents during hospitalization for AMI were examined. The results of a multivariable regression analysis indicated that women were significantly less likely to receive aspirin and ACE inhibitors as compared to men. There were no significant gender differences in the prescribing of the other cardiac medications. Increasing age in both women and men was associated with a reduced likelihood of receiving effective cardiac therapies including aspirin, β-blockers, lipid-lowering therapy and thrombolytic agents. Conclusions: These data suggest that the reasons for the marked age-related differences, in men and women, in the use of cardiac medications be more systematically explored. Previously observed gender differences in the management of patients with AMI essentially no longer exist.
Mechanical Complications after Myocardial Infarction Reliably Predicted Using C-Reactive Protein Levels and Lymphocytopenia
Authors: Widmer Anouk , Linka André Z. , Attenhofer Jost Christine H. , Buergi Barbara , Brunner-La Rocca Hans Peter , Salomon Franco , Seifert Burkhardt , Jenni Rolf
Published: April 2003

We assessed the accuracy of C-reactive protein (CRP) levels and lymphocyte counts to predict a mechanical complication (MC) after myocardial infarction (MI). Within 10 years, we identified 36 patients with 39 echocardiographically confirmed MC within 30 days of MI: ventricular septal defect (17 cases), papillary muscle rupture (10 cases), and left ventricular free wall rupture (12 cases). They were compared to 41 controls with an uncomplicated hospital course after MI. Peak CRP levels and minimum relative lymphocyte counts obtained within 96 h of the acute MI (AMI) and before diagnosis of the complication were compared with clinical parameters. Prior to the MC, peak CRP levels were significantly higher (p < 0.001) and relative lymphocyte counts lower (p < 0.001) than in controls while creatine kinase levels did not differ (p = nonsignificant). Using multivariate logistic regression, the following score was identified to have excellent prognostic significance for MC: CRP (mg/l) – 10 × Lyc (%). The area under the receiver-operating characteristic curve was 0.90 ± 0.05 (p < 0.001). Combined use of CRP levels and relative lymphocyte counts may be helpful in accurately predicting an MC after AMI and should therefore be routinely assessed.
CO2 Laser Treatment of Warts in Immunosuppressed Patients
Authors: Läuchli Severin , Kempf Werner , Dragieva Galya , Burg Günter , Hafner Jürg
Published: April 2003

Background: A large proportion of chronically immunosuppressed patients suffer from recalcitrant viral warts. Furthermore, the incidence of nonmelanoma skin cancer is clearly elevated in this patient group and human papillomavirus is most likely to play a causal role in these neoplasms. Objective: To analyze the effectiveness of treatment of viral warts with the CO2 laser in immunosuppressed patients. Methods: Multiple viral warts of 13 patients with immunosuppression, a majority of them renal allograft recipients, were treated with CO2 laser in local or regional anesthesia. In case of recurrences, the lesions were treated again after 3 months. Results: 12 of 13 patients experienced dramatic improvement after 1–3 treatment sessions, 6 of these patients showed full remission. Side effects such as postoperative pain or scarring were minimal. Conclusion: CO2 laser treatment of recalcitrant warts in immunosuppressed patients shows promising results which are comparable to those in immunocompetent hosts. This offers a welcome enlargement of the array of therapies in this otherwise difficult-to-treat group of patients and may contribute to the reduction of risk factors for nonmelanoma skin cancer.
Premenstrual Deterioration of Skin Symptoms in Female Patients with Atopic Dermatitis
Authors: Kiriyama Keiko , Sugiura Hisashi , Uehara Masami
Published: April 2003

Background: Although it has been recognized that women with atopic dermatitis often show menstrual-cycle-associated skin deterioration, information about this subject is meager. Objective: To clarify the clinical features of the monthly worsening of atopic dermatitis. Methods: A total of 286 Japanese women with atopic dermatitis were interviewed to see whether the menstrual cycle had any influence upon their skin lesions, and whether they had symptoms of premenstrual syndrome. Patients suffering from monthly skin deterioration were then observed during and after the monthly worsening. Results: Of the 286 patients interviewed, 134 (47%) had monthly skin deterioration, most of which occurred in the premenstrual week. There was individual difference in severity of the monthly skin worsening. All patients with the premenstrual skin aggravation had symptoms of premenstrual syndrome. Conclusions: Premenstrual worsening of skin lesions occurs in approximately half of women with atopic dermatitis. The premenstrual skin deterioration is related to the premenstrual syndrome.
Cytokine Gene Expression in Regenerating Haematopoietic Tissues of Mice after Cyclophosphamide Treatment
Authors: Pšenák O. , Šefc L. , Sýkora V. , Chang K.T. , Nečas E.
Published: April 2003

The goal of the study was to investigate changes in expression of selected growth factors tentatively involved in regeneration of haematopoietic tissues (bone marrow and spleen) following cyclophosphamide (CY) damage in the mouse. The bone marrow (BM) and spleen were examined separately, since the regenerating pattern for haematopoietic progenitor cells (HPC) markedly differs in these two haematopoietically active organs after CY. Cytokines assumed to have a stimulatory effect on HPC – stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (flt3-ligand), thrombopoietin (TPO), stromal cell-derived factor 1 (SDF-1), oncostatin M (OSM) –, a suppressive effect on HPC proliferation – macrophage inflammatory protein-1α (MIP-1α), transforming growth factor-β1 (TGFβ1), tumour necrosis factor-α (TNFα) – and to be involved in migration of HPC (SCF, flt3-ligand, MIP1α, SDF-1) were examined at the level of mRNA expression by means of real-time RT-PCR. The expression of a particular cytokine appears to be similar in both BM and spleen of untreated mice. CY administration changed the expression pattern of the studied genes in BM and spleen. In BM, the levels of mRNAs for SCF and SDF-1 were increased and that for TGFβ1 decreased at time intervals at which HPC are known to proliferate intensively during BM regeneration. In contrast, stimulated proliferation of HPC in spleen was accompanied by increased expression of flt3-ligand and oncostatin M. Upon mobilization of HPC from BM into blood after CY, the expression of SCF, TPO, SDF-1 and TGFβ1 tends to decrease in BM. Accumulation of HPC in spleen is accompanied by increased mRNA for flt3-ligand and OSM. Our findings demonstrate that different cytokines may be involved in the proliferation and mobilization/homing of HPC during recovery after CY damage in BM and spleen.
Transient Elevation of Platelet Count in Patients with Chronic Idiopathic Thrombocytopenic Purpura: Association with Infection
Authors: Matano Sadaya , Kyoda Katsunori , Yamazaki Hiroto , Sugimoto Tatsuho
Published: April 2003

Platelet count occasionally increases after infection in patients with chronic idiopathic thrombocytopenic purpura (ITP). We report 5 such patients. Three of them were males. Between November 1992 and December 2001, increased platelet counts were observed 9 times in 5 patients with chronic ITP. Corticosteroids were administered during 7 episodes; splenectomy was performed to treat 3 episodes. Antibiotics were administered in the course of 6 episodes to treat complicating infection. Platelet counts showing 1.4- to 24-fold increases have been observed. Median duration from the onset of infection until peak platelet count was 14 days. However, platelet count finally decreased to the initial level in all episodes. These findings suggest that infection is associated with the elevation of platelet count in some patients with chronic ITP, although this phenomenon is transient.
Progressive Nonfluent Aphasia and Subsequent Aphasic Dementia Associated with Atypical Progressive Supranuclear Palsy Pathology
Authors: Boeve B. , Dickson D. , Duffy J. , Bartleson J. , Trenerry M. , Petersen R.
Published: April 2003

We describe a right-handed man who developed progressive nonfluent aphasia and apraxia of speech beginning at age 71. By age 74 he had behavioral changes, aphasic dementia, as well as mild parkinsonism; extraocular movements were normal except for mild limitation of upgaze. Serial neuropsychometric testing and single photon emission computed tomography (SPECT) scans showed progressive changes reflecting left>right cerebral hemisphere dysfunction. Neuropathologic examination revealed findings characteristic of progressive supranuclear palsy (PSP) except that the cortical pathology was more widespread than is typical of PSP. We conclude that the clinical manifestations in this case were more similar to the syndrome of progressive nonfluent aphasia with subsequent aphasic dementia and mild parkinsonism, rather than those of PSP. Hence, PSP can present clinically as an atypical dementing syndrome dominated by progressive aphasia/apraxia of speech.
Mutation Screening and Association Analysis of the Parkin Gene in Parkinson’s Disease Patients from South-West China
Authors: Peng Rong , Gou Yinru , Yuan Qiang , Li Tao , Latsoudis Helen , Yuan Guanggu , Luo Deru , Liu Xiehe , Collier David A.
Published: April 2003

Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson’s disease (PD) and parkinsonism, especially when the onset occurs at a young age. In this study, we screened 25 ‘early-onset’ (<49 years at onset) and 91 later-onset PD patients from a Han Chinese population from South-West China for deletions and mutations in the Parkin gene. We found no deletions or point mutations in exons 1–12 of the Parkin gene using direct sequence analysis and only detected the common Ser167Asn polymorphism. We analysed Ser167Asn in 116 patients with sporadic PD and 124 controls, matched for age and gender. There were significant differences in allele and genotype frequency between PD patients, with the 167Asn allele more common in cases than controls (46.6 vs. 35.1%; χ2 = 6.54, p = 0.011, odds ratio = 1.61, 95% confidence interval, CI, 1.10–2.37), as was the 167Asn genotype (17.3 vs. 11.3%; p = 0.04). The frequency of the 167Ser genotype was significantly lower in PD patients than in controls when compared with that of the other two genotypes combined (χ2 = 7.84, p = 0.005, odds ratio = 0.46, 95% CI 0.25 – 0.82). No significant differences in the frequencies of the allele and genotypes were found between patients classified into two groups according to symptoms at onset (χ2 = 0.191, p = 0.66, odds ratio = 1.12, 95% CI 0.65–1.95; χ2 = 0.24, p = 0.887) or age of onset (p = 0.787). In summary, homozygous deletion mutations and point mutations in exons 1–12 of the Parkin gene were not detected in this Han Chinese population, although we cannot exclude compound heterozygous deletions. In addition, our study suggests that the variant 167Asn increases the risk of developing PD.
The Scribe of Stroke Trials
Authors: van Gijn J.
Published: April 2003

The responsibility for reports about drug trials in medical journals should lie with the clinicians in the steering committee, not with the industrial sponsor. Examples of undue influence of sponsors on the conduct and analysis are the choice of surrogate outcome events, changes in the protocol during the trial, discontinuation of the study, post hoc analyses and suppression of publication. Since this essay was written, the International Committee of Medical Journal Editors (‘Vancouver Group’) has issued the condition that authors of submitted manuscripts should guarantee their independence in data analysis and reporting. Nevertheless, this ‘security check’ occurs at a late stage and may not apply to journals that are less well known. Institutional Review Boards should routinely take the matter of independence into account. Also, European guidelines should be rewritten to reflect these fundamental issues rather than a multitude of details. In fact not sponsors or physicians but patients and the general public are the true owners of trial data.
Expression and Cellular Localisation of Renal Endothelin-1 and Endothelin Receptor Subtypes in Autosomal-Dominant Polycystic Kidney Disease
Authors: Ong Albert C.M. , Newby Linda J. , Dashwood Michael R.
Published: April 2003

The major factors influencing the rate of progression of chronic renal disease in autosomal-dominant polycystic kidney disease (ADPKD) are unknown and there are currently no effective treatments for slowing the progression of chronic renal failure in ADPKD patients. As a first step in investigating the potential role of endothelin-1 (ET1) and its receptors (ETA and ETB) in the pathophysiology of progression in ADPKD, we have studied their expression and cellular localisation in ADPKD kidney. Immunoreactive ET1 was detected in cyst epithelia, mesangial cells and vascular smooth muscle cells suggesting continuing ET1 synthesis in the cystic kidney. Compared to healthy controls, ETA mRNA was 5–10-fold higher in ADPKD cystic kidney. In cystic kidney, neo-expression of ETA receptors was found overlying glomeruli and cysts and markedly increased in medium-sized renal arteries by microautoradiography. This is the first study to demonstrate a specific upregulation of ETA receptors in human renal disease. Future studies should address whether ETA selective antagonists may be effective in slowing renal disease progression in ADPKD.
Reversible Angiotensin II-Mediated Albuminuria in Rat Kidneys Is Dynamically Associated with Cytoskeletal Organization
Authors: Clavant Steven P. , Forbes Josephine M. , Thallas Vicki , Osicka Tanya M. , Jerums George , Comper Wayne D.
Published: April 2003

Angiotensin II (ANG II) is intimately involved in normal renal function, and is estimated to exist at a normal physiological range of 6–10 nM within the renal tubules. The potential role that intrarenal ANG II may play in renal disease was assessed by perfusing isolated rat kidneys with or without excess intratubular levels of ANG II, which may mimic changes in the intrarenal RAS under pathological conditions. The effects of increased systemic ANG II were also determined by infusing rats with ANG II by osmotic pump. In isolated perfused kidneys, ANG II significantly and specifically increased the fractional clearance of albumin to clinical levels, as determined by using radiolabelled albumin. This effect was reversible, as removing ANG II from the perfusate caused the albumin fractional clearance to decrease to pre-ANG II exposure levels. The increase in fractional clearance of albumin was not correlated with renal hemodynamic changes, nor glomerular permeability alterations as measured by the fractional clearance of 36 Å Ficoll and immunoglobulin G. Immunochemical analysis using anti-α-tubulin antibody of perfused kidney sections revealed that ANG II caused a marked disruption of tubular epithelial cytoskeletal components, through disassembly and reorganization of α-tubulin. This disruption was reversible. In vivo, osmotic pump delivery of ANG II at less potent dosage caused a proteinuria (Biuret) and an albuminuria (radioimmunoassay) in rats, from as early as 2 days after pump implantation. These results demonstrate that ANG II may reversibly induce clinical levels of albuminuria. These data point to an important role for renal tubules and the intratubular lumen concentrations of ANG II in the renal processing of albumin.
Spectral karyotype analysis of colon cancer cell lines of the tumor suppressor and mutator pathway
Authors: Melcher R. , Koehler S. , Steinlein C. , Schmid M. , Mueller C.R. , Luehrs H. , Menzel T. , Scheppach W. , Moerk H. , Scheurlen M. , Koehrle J. , Al-Taie O.
Published: April 2003

Background and aims: Microsatellite instability (MSI) is characterized by the size variation of microsatellites in tumor DNA as compared to matching normal DNA due to defects in the mismatch repair system. To examine the chromosomal differences in microsatellite-stable (MSS) and -unstable (MSI) tumors in detail, we analyzed MSS (Caco-2, Colo-205, SW948) and MSI (HCT-15, HCT-116, LoVo) cell lines by spectral karyotyping (SKY). Methods: SKY is a sensitive method to detect chromosome aberrations by visualizing each chromosome in a different color. Metaphases were hybridized with a SKY probe mixture. Images were visualized with the SpectraCube system and analyzed with the SKYview imaging software. Results: The average number of chromosomes was 49 in LoVo, 45 in HCT-116, 46 in HCT-15, 71 in Colo-205, 89 in Caco-2 and 66 in SW-948. Three aberrant chromosomes were detected in LoVo, three in HCT-116, two in HCT-15, seventeen in Colo-205, fourteen in Caco-2 and nine in SW948. Conclusion: The karyotypes of MSS colon cancer cells displayed complex numerical and structural aberrations. In contrast the chromosomes of MSI colon cancer cells were mostly unaltered but displayed a few isolated numerical and structural aberrations. We speculate that these isolated aberrations may be specifically involved in the pathogenesis of MSI tumors.
The evolutionary conservation of the mammalian peroxidase genes
Authors: Sakamaki K. , Ueda T. , Nagata S.
Published: April 2003

Myeloperoxidase (MPO), eosinophil peroxidase (EPX) and lactoperoxidase (LPO) are mammalian peroxidase enzymes possessing similar structures and functions. Here, we demonstrate that the genes encoding these molecules form a cluster on mouse chromosome 11. Genomic sequence analysis revealed that the mouse Lpo gene has similar genomic organization to the corresponding human gene. Our data strongly suggest the evolutionary conservation of mammalian peroxidase genes.
Autobiographical Memory in Major Depression: A Comparison between First-Episode and Recurrent Patients
Authors: Nandrino Jean-Louis , Pezard Laurent , Posté Alexa , Réveillère Christian , Beaune Daniel
Published: April 2003

Autobiographical memory in depression is characterized by an increase in general memory evocation. The aim of this study is to compare autobiographical memory in patients with a first depressive episode and in recurrent patients before and after recovery, using Williams’ and Scott’s autobiographical memory test. Our results show an increase of the number of general memories only with positive cue words in both groups of patients during the depressive episode. After clinical improvement, this specificity remains in recurrent patients who, in addition, recall more general memories for negative words. By contrast, patients with a first depressive episode are no longer different from controls. These results show both an overgeneralization and a deficit in positive memory access during the depressive episode, whatever the number of previous episodes. Moreover, recurrence chronically modifies access to emotional memories.
The Challenge of Neuroscience: Psychiatry and Phenomenology Today
Authors: Fuchs Thomas
Published: April 2003

The paper illustrates the present role of phenomenological psychopathology by outlining its methods and focusing on some of its major issues: embodiment or body scheme, intentionality, time consciousness and intersubjectivity. The application of these categories to the analysis of psychotic disorders is demonstrated. Special emphasis is given to the relationship between phenomenology and cognitive neuroscience, a relationship that has been variously viewed as ‘mutual constraint’ or as ‘mutual enlightenment’. This is where a new cooperation linking phenomenology, psychopathology and cognitive science begins to emerge. Phenomenology offers a methodically developed theory of human subjectivity that is indispensable to any attempt to understand, explore and treat psychiatric disorders.
‘Brain Fag’ Symptoms in Apprentices in Nigeria
Authors: Morakinyo Olufemi , Peltzer Karl
Published: April 2003

The ‘brain fag’ syndrome, which was first reported from West Africa in 1960 among students, has been shown to occur very widely in African students in western educational systems south of the Sahara. This study investigated the distribution of its symptoms in a group of apprentices chosen by convenient sampling from Ile-Ife, a university town about 240 km northeast of Lagos in Nigeria. The subjects who (in contrast) were training under an indigenous form of education – the African apprenticeship system – consisted of 183 (69.8%) males, and 79 (30.2%) females, in the age range of 13–26 years (mean ± SD 18.2 ± 3.0 years). Questionnaires were interview-administered to collect data on the sociodemographic, economic, and family background, English language proficiency, and the degree of the presence of brain fag symptoms. Results indicated a generally low rate of brain fag symptoms among these different types of apprentices. A relationship between proficiency in English, but not socioeconomic status, with brain fag symptoms was found. In the case of the Nigerian apprentices investigated here, brain fag symptoms were not significantly associated with the method of training learning (which is dependent mainly on verbal instructions in the vernacular from their bosses, and vicarious learning by observing the boss at work). The implications of these findings for two of the theories advanced for the pathogenesis of the brain fag syndrome were discussed.
Typus melancholicus Personality Type and the Five-Factor Model of Personality
Authors: Kronmüller Klaus-Thomas , Backenstrass Matthias , Kocherscheidt Karen , Hunt Aoife , Unger Jörg , Fiedler Peter , Mundt Christoph
Published: April 2003

Personality traits are significant factors in the development and course of depression. Apart from the classical five-factor model of personality, other personality constellations, such as Tellenbach’s Typus melancholicus, have been described in association with depressive disorder. Several instruments have been developed to assess the Typus melancholicus personality (TMP). A systematic comparison of these instruments has not been done to date. The goal of this study was the comparison of four questionnaires used in assessing TMP. Four TMP questionnaires were compared and their relationship to the five-factor model of personality was examined among 264 psychiatric patients and normal controls. It was found that the TMP type represents a trait distinct from those of the five-factor model. TMP inventories had only moderate concurrent validity. The single TMP scales focus on different aspects of the TMP, despite their common core. Both the five-factor personality traits and the TMP scales were able to differentiate a group of depressed patients from control groups. The results show that TMP is not one trait but a personality trait constellation. This leads to the conclusion that a number of dimensions must be taken into consideration in the construction of a TMP inventory. This multidimensionality contributes to the refinement of the TMP concept and differentiates its therapeutic implications.
Distribution of Fluorescence following Injection of Recombinant Adeno-Associated Virus Encoding Green Fluorescent Protein into the Paraventricular Nucleus
Authors: Ward Helen , Gardiner James , Kong Wing May , Murphy Kevin , Bloom Stephen
Published: April 2003

We have used recombinant type 2 adeno-associated virus to deliver the gene encoding green fluorescent protein into the central nervous system of adult rats. Gene expression, determined by fluorescent microscopy, was observed not only at the site of injection but also in axons following known neuroanatomical pathways. We have demonstrated a spread of enhanced green fluorescent protein from the paraventricular nucleus of the hypothalamus into the median eminence and neurohypophysis. Cell bodies containing enhanced green fluorescent protein were also visualized in the paraventricular nucleus contralateral to the side of injection. These findings suggest that gene transfer by recombinant adeno-associated virus could be used as a tool to investigate hypothalamic-pituitary interactions and, elsewhere in the central nervous system, to trace axonal pathways.
Familial Isolated Unilateral Large Vestibular Aqueduct Syndrome
Authors: Ramírez-Camacho Rafael , García Berrocal José Ramón , Arellano Beatriz , Trinidad Almudena
Published: April 2003

Large vestibular aqueduct syndrome (LVAS) is one of the most frequent inner ear malformations. It is associated with varying degrees of hearing loss, that may be progressive, sudden or fluctuant; nevertheless normal hearing in cases with LVAS has been described. Although unilateral LVAS has been described, all patients show clinical and radiological findings in both ears, in contrast to the family presented here, where 2 siblings are affected by unilateral sensorineural hearing loss associated with ipsilateral LVAS, with an autosomal recessive pattern. In order to search for the origin of this inner ear malformation, mutations in genes GJB2 (connexin-26 gene), PDS (Pendred’s syndrome gene) and mitochondrial 12sRNA were studied, without positive results. In this paper we hypothesize the probable embryological origin for this malformation.
Characteristics of Fricatives and Sentence Duration after Cochlear Implantation
Authors: Hamzavi Jafar S. , Schenk Barbara S. , Pok Stefan M. , Moosmueller Sylvia , Baumgartner Wolf-Dieter , Deutsch Werner A.
Published: April 2003

Ten postlingually deafened patients (5 male, 5 female) were examined after cochlear implantation to measure improvements in their quality of speech. Parameters such as the spectral maximum of fricatives and the duration of utterances were analysed in speech recordings taken at regular intervals after implantation. The speech samples were recorded in an audiological chamber. Parameters were analysed using STx (S-Tools Software). Frequency analyses based on the fast Fourier transform and spectral estimation methods, as well as fundamental frequency and formant extraction (cepstrum, LPC = linear prediction coding) and digital filter implementations were prepared. The results indicate a tendency towards improvement in the spectral maximum of the fricatives and affricates and a shortening of the duration of the fricative parts in affricates and of sentences in nearly all our subjects. These results showed the restored auditory feedback produced by cochlear implantation to have a favourable effect on speech production.
Novel NCCT Gene Mutations as a Cause of Gitelman’s Syndrome and a Systematic Review of Mutant and Polymorphic NCCT Alleles
Authors: Reissinger Annette , Ludwig Michael , Utsch Boris , Prömse Astrid , Baulmann Johannes , Weisser Burkhard , Vetter Hans , Kramer Herbert J. , Bokemeyer Dirk
Published: April 2003

Background: Gitelman’s syndrome (GS) is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria and these phenotypic features have been shown to be attributable to mutations in the gene encoding the thiazide-sensitive Na/Cl cotransporter (NCCT). Until now, 55 different mutations have been reported and most of the families affected with GS exhibit autosomal recessive inheritance. Methods: All 26 exons of the human NCCT  gene were investigated in 2 German NCCT-deficient patients and their families. Mutation detection was performed by either direct automated sequencing of polymerase chain reaction (PCR)-amplified DNA products or by sequence analysis of cloned PCR products. Results: In a 47-year-old German GS female a novel non-conservative missense mutation (S314F) and a complex deletion/insertion in the NCCT gene were found to be associated with the disorder. A further novel non-conservative substitution (S402F) together with a frequently observed R209W exchange were found in a 19-year-old German GS female. Conclusions: The observation of a compound heterozygote state in both females affected and the absence of a GS phenotype in their relatives carrying a single mutant allele is consistent with an autosomal recessive pattern of inheritance.
An Automated Program to Screen Databases for Members of Protein Families
Authors: Zhou Xiaofeng , Hvorup Rikki N. , Saier Jr. Milton H.
Published: April 2003

We have developed a program, ScreenTransporter (ST), to screen for potential members of recognized transporter families. This program uses Blastpgp as the engine to search a nonredundant database, NRDB90, based on an adjustable E-value cut-off as well as adjustable protein size criteria. Additional parameters can be integrated in later versions. ST is convenient for easily obtaining nonredundant members of transporter families starting from several homologous query sequences. The program can be applied to any protein family.
High Prevalence of Calcified Silent Neurocysticercosis in a Rural Village of Mexico
Authors: Fleury A. , Gomez T. , Alvarez I. , Meza D. , Huerta M. , Chavarria A. , Carrillo Mezo R.A. , Lloyd C. , Dessein A. , Preux P.M. , Dumas M. , Larralde C. , Sciutto E. , Fragoso G.
Published: April 2003

Human neurocysticercosis (NC) is a parasitic disease caused by Taenia solium when its larvae lodge in the central nervous system. NC prevalence estimates are obscured by the variable and often asymptomatic clinical picture. While infection depends on exposure, severity is possibly related with various host factors (immunity, genes and gender). This epidemiological study of cranial CT scans in an endemic rural community found that 9.1% of apparently healthy subjects had calcified lesions and were completely asymptomatic. Silent NC cases did not correlate with the exposure factors tested but showed family aggregation and higher rates of positive serology. Thus, NC prevalence may be higher than currently considered and host-related factors appear to be involved in infection and pathogenesis.
Priapism Caused by Infection and an Inflammatory Process in the Pelvic Region
Authors: van den Ouden D. , Boks S.S. , Sinnige H.A.W.
Published: April 2003

Priapism caused by an inflammatory process is rare. We report on a 25-year-old man with priapism due to an infiltration in the pelvic region, enclosing the right sacral plexus. Blood cultures revealed Staphylococcus aureus to be the causal organism. Treatment consisted of parenteral antibiotics, aspiration of the corpora cavernosa and injection of epinephrine, resulting in a flaccid penis and full recovery of potency after 3 weeks. A literature review was conducted for infection and inflammatory processes as a cause for priapism.
Another Look at Allergies to Fragrances: Frequencies of Sensitisation to the Fragrance Mix and Its Constituents
Authors: Schnuch A. , Geier J. , Uter W. , Frosch P.J.
Published: April 2003

Background: Sensitisation to fragrances is generally diagnosed with the fragrance mix (FM), which should sensitively detect contact allergy to its single compounds (SCs). Objective: To study the frequency of sensitisation to the FM and to the SCs, and to evaluate the sensitivity of the FM to diagnose sensitisation to SCs. Methods: During a 4-year period, 4,900 patients were patch tested with the FM (8% pet.) and with its 8 SCs (1% pet.) by departments of dermatology participating in the multicentre project Information Network of Departments of Dermatology. Results: The overall frequency of sensitisation of the FM was 20.2%, that of SCs ranged from 6.8% (oak moss) to 0.6% (α-amylcinnamic aldehyde). Based on our results, we propose 3 groups of SCs according to their importance relative to the frequency of sensitisation: oak moss and iso-eugenol are considered very important, geraniol and α-amylcinnamic aldehyde appear less important in terms of frequency of sensitisation and the remaining allergens can be regarded as important. In 61% of the + reactions to the FM, no positive reaction to any SC was observed, whereas most ++ and +++ reactions to the FM were accompanied by a positive SC test result (69.1 and 93.6%, respectively). In contrast, a negative reaction to the FM was strongly associated with negative reactions to the SCs. Overall, the sensitivity of the FM was high (86.7, 95% confidence interval, CI: 83.7–89.3), but the positive predictive value was low (53.8, 95% CI: 50.6–56.9). Conclusion: The FM is a sensitive diagnostic tool to detect contact allergy to its single fragrance constituents. However, a + reaction to the FM without a history of fragrance allergy should be interpreted with caution. Epidemiological and regulatory discussions should address this important aspect, because the frequency of sensitisation as expressed by overall positive reactions (+ to +++) to the FM can be misleading.
Visualization of Ischaemic Penumbra Using a Computed Tomography Perfusion Method
Authors: Cheung Raymond T.F. , Cheng Pui W. , Lui Wai M. , Leung Gilberto K.T. , Lee Ting-Yim
Published: April 2003

A computed tomography (CT) perfusion imaging and a diffusion/perfusion magnetic resonance imaging (MRI) were performed in a 51-year-old man at 15 and 15.5 h of onset of left middle cerebral artery infarction, respectively. The established infarct, as revealed by the diffusion-weighted MRI, had low values of cerebral blood flow (CBF) and cerebral blood volume (CBV) on the CT perfusion study. The ischaemic penumbra, as reflected by the perfusion-diffusion mismatch on MRI, had reduced CBF, prolonged mean transit time (MTT) and compensated CBV. Spontaneous bleeding occurred in the medial part of the left lentiform nucleus, immediately following decompressive craniectomy. CT measurements of CBF, CBV and MTT may visualize the ischaemic penumbra and explain the site of bleeding after surgical decompression.
Reduced Rate of Microembolism by Optimized Aortic Cannula Position Does Not Influence Early Postoperative Cognitive Performance in CABG Patients
Authors: Müllges Wolfgang , Franke Dorothea , Reents Wilko , Babin-Ebell Jörg , Toyka Klaus V.
Published: April 2003

Background and Purpose: The number of microemboli as measured by Doppler ultrasound during coronary artery bypass grafting (CABG) can be reduced by positioning the arterial cannula into the aorta descendens. The aim of this study was to prospectively evaluate whether this alternative aortic cannulation procedure leads to better neuropsychologic outcome early after surgery along with embolus reduction. Methods: Sixty patients with elective CABG were randomized to either using a short aorta ascendens cannula or an elongated cannula placed in the aorta descendens. All patients were tested by seven neuropsychologic tests preoperatively. Intraoperative embolus detection could be performed by transcranial Doppler in 32 patients. The neuropsychologic tests could be repeated serially until the 9th postoperative day in 54 patients. Patient groups did not differ in terms of preoperative psychometric performance and of the surgical characteristics except cannula positioning. All data were analyzed by a blinded assessor. Results: Neuropsychologic test scores showed in all individual patients a transient decline with subsequent recovery, but did not differ significantly between the groups except for the letter cancellation test at discharge favoring the patients with the longer cannula (102.3 ± 11.6 vs. 94.5 ± 11.5 mean ± SD; p = 0.025). In the subgroup who had Doppler sonography, neuropsychologic test scores did not differ between the groups. However, microembolic signals were markedly reduced in patients with the elongated cannula (median 174.5 vs. 413.0; p = 0.011). Conclusions: Though reducing brain microembolism, use of an elongated aortic cannula does not appear to influence overall cognitive performance early after CABG in this pilot study.
Acute Inflammatory Events and Ischemic Stroke Subtypes
Authors: Nencini Patrizia , Sarti Cristina , Innocenti Rinaldo , Pracucci Giovanni , Inzitari Domenico
Published: April 2003

Background: Recent studies have suggested that previous infection may be a risk factor for ischemic stroke mainly in young and middle-aged patients. The present study sought to further investigate the association between recent inflammatory events (IE) and ischemic stroke without age restriction and to determine the role of recent IE in different ischemic stroke subtypes. Methods: We performed a case-control study with 93 consecutive hospitalized stroke patients and 200 (107 hospital and 93 community) controls. Acute IE, both infective and non-infective, occurring in the previous 30 days were assessed using a standard questionnaire. The TOAST criteria were used for ischemic stroke subtypes classification. Results: Acute IE in the previous 30 and 7 days were significantly and independently associated with ischemic stroke (37/93 vs. 47/200; OR 2.23, 95% CI 1.26–3.96 and 17/93 vs.16/200; OR 2.45, 95% IC 1.11–5.39, respectively). Stratifying for stroke subtypes, acute IE significantly and independently increased the risk of atherothrombotic (OR 5.72, 95% CI 2.14–15.25) and cardioembolic stroke (OR 3.02, 95%CI 1.20–7.63). Conclusions: Acute IE increase the risk of acute ischemic stroke of atherothrombotic and cardioembolic type independently of other predisposing factors. Implications for daily clinical practice, in relation to prevention and treatment of IE in patients at risk, have to be explored.
A Statistically Valid Alternative to the TDT
Authors: Wittkowski Knut M. , Liu Xin
Published: April 2003

Objective: To present an alternative linkage test to the transmission/disequilibrium test (TDT) which is conservative under the null hypothesis and generally more powerful under alternatives. Methods: The exact distribution of the TDT is examined under both the null hypothesis and relevant alternatives. The TDT is rewritten in an alternate form based on the contributions from each of the three relevant parental mating types. This makes it possible to show that a particular term in the estimate is an exact tie and thus to rewrite the estimate without this term and to replace the multinomial ‘variance estimate’ of Spielman et al. [Am J Hum Genet 1993;52:506–516] by the binomial variance. Results: The resulting test is shown to be a stratified McNemar test (SMN). The significance level attained by the SMN is shown to be conservative when compared to the asymptotic χ2 distribution, while the TDT often exceeds the nominal level α. Under alternatives, the proposed test is shown to be typically more powerful than the TDT. Conclusion: The properties of the TDT as a statistical test have never been fully investigated. The proposed test replaces the heuristically motivated TDT by a formally derived test, which is also computationally simple.
A Case of Large Mucinous Adenocarcinoma Arising in a Long-Standing Fistula-in-Ano
Authors: Erhan Yamac , Sakarya Aslan , Aydede Hasan , Demir Akif , Seyhan Ahmet , Atici Emre
Published: April 2003

Background: Chronic anal fistulas are not rare conditions, however, the development of a carcinoma in a long-standing fistula-in-ano is rare. Methods: The case of a 77-year-old male with a large perianal mucinous adenocarcinoma arising in a long-standing fistula-in-ano is presented. Results: Perianal biopsy revealed mucinous adenocarcinoma. Abdominal CT, double contrast barium examination and flexible sigmoidoscopy revealed no other tumoral lesion in the colon and rectum. Conclusion: The patient underwent abdominoperineal resection including wide tumor excision on the gluteal region. The final reconstruction was performed by bilateral gracilis musculocutaneous flaps. Due to clinical and histopathological evidence it was thought that a curative resection had been performed. To date he is clinically disease free.
Plasma Lipids and Lipoprotein Changes after Biliopancreatic Diversion for Morbid Obesity
Authors: Brizzi P. , Angius M.F. , Carboni A. , Cossu M.L. , Fais E. , Noya G. , Maioli M. , Tonolo G.
Published: April 2003

Background: The reduction in plasma cholesterol with increase in large and lower dense LDL (pattern A) obtained by statins is usually associated with a prompt reduction in cardiovascular risk, but after bariatric surgery for morbid obesity a delay of some years is observed. No data regarding LDL pattern are available in obese subjects after biliopancreatic surgery. Objective: To evaluate the modifications in LDL composition and LDL density after biliopancreatic surgery. Subjects: 29 patients (17 type 2 diabetics (type 2) and 12 non-diabetics (ND)) with BMI <35, who failed previous attempts to decrease weight by diet, were studied before and 6 months after biliopancreatic diversion for morbid obesity. Measurements: In all subjects, besides fasting circulating lipids, glucose and insulin, LDL and VLDL composition were determined and LDL density was evaluated as well. Results: After surgery we observed a significant reduction of all circulating lipids, including apolipoprotein (Apo) B. The decrease was more marked for total cholesterol (–41%) than for triglycerides (–28%), without a significant difference between type 2 and ND. After surgery, LDL presented a marked decrease in the percentage of cholesterol (from 36 to 32%) with a marked increase in the percentage of triglycerides (from 13 to 18%), without appreciable modification of ApoB. After surgery, 1 patient changed from pattern B to A, while 2 patients previously pattern A became pattern B. Also a decrease in HDL and ApoAI was evident in all the subjects with an increase in the VLDL-1. Conclusions: Our data indicate that after biliopancreatic diversion, the plasma lipid profile improves along with improvement of plasma glucose and insulin sensitivity, but the LDLs become richer in triglycerides. It is possible that the greater atherogenicity of these LDLs is compensated by an improvement in the general metabolic condition.
Hereditary Benign Telangiectasia: Videocapillaroscopic Findings
Authors: De Angelis Rossella , Bugatti Leonardo , Del Medico Patrizia , Filosa Giorgio
Published: April 2003

In this article, we provide a detailed depiction of capillary changes at the nailfold and labial mucosa in a patient with hereditary benign telangiectasia. To the best of our knowledge, no such extensive capillaroscopic documentation of this entity has been made previously.
Creatine Supplementation Affects Glucose Homeostasis but Not Insulin Secretion in Humans
Authors: Rooney Kieron B. , Bryson Janet M. , Digney Alison L. , Rae Caroline D. , Thompson Campbell H.
Published: April 2003

Aims: In this study, it was investigated whether the glucose homeostasis is affected by dietary creatine supplementation. For this purpose, the plasma glucose concentration and the plasma insulin response to an oral glucose load were measured in creatine-supplemented vegetarians. Methods: The subjects were supplemented with either 5 g of creatine monohydrate (creatine-treated group, CREAT) or 5 g of maltodextrin (control group, CON) per day for 42 days. On days 0 and 43, blood samples were collected before as well as 10, 20, and 30 min following an oral glucose load and analyzed for plasma creatine, insulin, and glucose levels. Results: Creatine supplementation resulted in an increase in plasma creatine (CREAT 92.7 ± 14.6 µM vs. CON 31.2 ± 3.2 µM; p = 0.001). There was a trend (p = 0.07) towards elevated fasting plasma glucose levels following creatine supplementation, while the plasma glucose response to the glucose load was enhanced (CREAT 168.2 ± 5.3 mM· min vs. CON 129.6 ± 14.7 mM ·min; p = 0.05). There was no difference observed in the plasma insulin response to the glucose load between the groups. Conclusion: This study shows that creatine supplementation may result in abnormalities in glucose homeostasis in the absence of changes in insulin secretion.
Spontaneous Rupture of an Aneurysmal Intrarenal Arteriovenous Fistula
Authors: Mori Kenichi , Koga Shigehiko , Nishikido Masaharu , Shono Takefumi , Ashizawa Kazuto , Sakamoto Ichiro , Yamashita Shuji , Kanetake Hiroshi
Published: April 2003

We present a 65-year-old woman who was found to have a spontaneous rupture of an aneurysmal intrarenal arteriovenous fistula. To our knowledge, the present case is only the 3rd reported in the literature. The preferred method of treatment of ruptures of arteriovenous fistulae is embolization. However, the process of choosing among embolization, surgery, or a combination of both procedures must be individualized for each patient based on vital signs and symptoms.