bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Wild-Type Recombinant Bet v 1a as a Candidate Vaccine against Birch Pollen Allergy
Authors: Batard Thierry , Didierlaurent Alain , Chabre Henri , Mothes Nadine , Bussières Lætitia , Bohle Barbara , Couret Marie-Noëlle , Ball Tanja , Lemoine Pierrick , Focks Tejkl Margarete , Chenal Alexandre , Clément Gilles , Dupont Francis , Valent Peter , Krauth Marie-Theres , André Claude , Valenta Rudolf , Moingeon Philippe
Published: February 2005

Background: We describe the production in Escherichia coli as a recombinant protein of clinical grade wild-type Bet v 1a (rBet v 1a), to be used as a candidate vaccine against birch pollen allergy. Methods: This recombinant protein was purified by hydrophobic interaction and ion exchange chromatography and characterized by SDS-PAGE, immunoprint and circular dichroism in parallel with natural Bet v 1 (nBet v 1) purified from a birch pollen extract. We also compared rBet v 1 and nBet v 1 for their capacity to induce histamine release from basophils and to stimulate T lymphocyte proliferation. Results: rBet v 1a appears in SDS-PAGE as an 18-kDa monomeric protein, whereas purified nBet v 1 comprises a mixture of isoforms (resolving as three distinct bands and six spots after 1-dimensional and 2-dimensional electrophoresis, respectively). Both recombinant and natural purified Bet v 1 molecules are recognized by IgE from birch pollen-allergic patients as well as anti-Bet v 1 murine monoclonal antibodies, suggesting that the recombinant protein is correctly folded in a native configuration. Circular dichroism analysis confirmed that the two Bet v 1 molecules exhibit similar 3-dimensional structures, even if rBet v 1a appears more compact and stable in thermodenaturation/renaturation experiments. Both rBet v 1 and nBet v 1 induce the degranulation of sensitized basophils and proliferation of Bet v 1-specific T lymphocytes in a similar manner. Conclusions: On the basis of these structural and biological properties, rBet v 1a is a valid candidate vaccine against birch pollen allergy, currently evaluated in humans.
Effect of Maternal Dietary Cow’s Milk on the Immune Response to β-Lactoglobulin in the Offspring: A Four-Generation Study in Mice
Authors: Brix Susanne , Christensen Hanne Risager , Barkholt Vibeke , Frøkiær Hanne
Published: February 2005

Background: Evaluation of immune responses to food proteins in animal models requires that the animals are not already sensitized or orally tolerized against the proteins in question. Since maternal transfer of specific immune responses has been observed, breeding of animals on an antigen-free diet for several generations may be necessary to obtain immunologically naïve animals. Methods: To determine the most appropriate breeding conditions of mice to be used in immunological studies on food proteins, we examined immune responses towards β-lactoglobulin (BLG) in mice bred on a milk-containing diet (F0) and then for three generations (F1–F3) on a commercially available milk-free diet. The specific antibody and cell-proliferative response to BLG was compared in non-immunized and immunized BALB/c mice, and in mice orally tolerized to BLG prior to immunization. Results: The immune response to BLG in the F1 generation deviated from the response observed in the F0 and F2/F3 generations. Importantly, trace amounts of BLG detected in the commercial milk-free diet did not induce oral tolerance. Conclusions: The study showed that breeding mice on an antigen-free diet for at least two generations is required to attain animals appropriate for immunological studies of food proteins. Although the small quantity of BLG in the milk-free diet did not induce detectable oral tolerance in the present study, it is strongly recommended that the potential effect of contaminating dietary antigen is considered in future studies on food proteins.
A New Immunomodulatory Function of Low-Viscous Konjac Glucomannan with a Small Particle Size: Its Oral Intake Suppresses Spontaneously Occurring Dermatitis in NC/Nga Mice
Authors: Onishi Nobukazu , Kawamoto Seiji , Nishimura Masaru , Nakano Toshiaki , Aki Tsunehiro , Shigeta Seiko , Shimizu Hisao , Hashimoto Kunihiko , Ono Kazuhisa
Published: February 2005

Background: Konjac glucomannan (GM) is a well-known dietary fiber with various beneficial functions: the higher viscosity displayed the stronger potency. However, the high-viscous GM powders, ordinary konjac powder and highly purified GM were mostly unsuitable for the application to various food industries. Our aims are to develop new physiological functions of low-viscous GM powder, pulverized GM or re-granulated fine GM, using a murine model of atopic dermatitis. Methods: Male 4-week-old NC/Nga mice were fed for 8 weeks on diets containing 5% of two high-viscous and two low-viscous GM powders, respectively. Results: Striking suppression against the aggravation of dermatitis, the increase in scratching behaviors, and the rise in IgE levels was recognized only in mice fed on the pulverized GM diet, but not in mice fed on the other GM diets or a control diet. Eczema prevention in the fine GM-fed mice was accompanied by a significant decrease in their plasma IFN-γ levels, a positive regulatory cytokine for atopic skin inflammation. Conclusion: Only the pulverized GM possessed the ability to suppress the development of dermatitis in NC/Nga mice. This is the new immunomodulatory function of low-viscous GM with a small particle size.
Quality of Life during Pollen Season in Patients with Seasonal Allergic Rhinitis with or without Asthma
Authors: Laforest Laurent , Bousquet Jean , Pietri Guilhem , Sazonov Kocevar Vasilisa , Yin Donald , Pacheco Yves , van Ganse Eric
Published: February 2005

Objectives: We studied the evolution of generic and rhinoconjunctivitis-specific quality of life (QOL) during pollen season in patients with isolated seasonal allergic rhinitis (SAR) and those with asthma and concomitant SAR (AS+SAR). Generic QOL between groups was also compared at pollen peak. Methods: A prospective cohort study was conducted in Southern France in 2002. Outpatients aged 18–60, regularly visiting respiratory physicians for SAR, were recruited before the grass (grass cohort) or ragweed pollination period (ragweed cohort). Before the pollination period (baseline) and at peak pollination, patients completed French versions of the Mini Rhinoconjuctivitis Quality of Life Questionnaire (Mini-RQLQ) and physical and mental Short Form-12 (SF-12) scores (PCS and MCS) to determine rhinoconjunctivitis and generic QOL. Results: Totals of 83 and 52 patients were included in the SAR and AS+SAR groups, respectively (mean age = 35.4; 56.4% females). Mini-RQLQ scores indicated slightly worse QOL in the A+SAR group at inclusion, which significantly deteriorated at the time of pollen peak, both in the SAR (p < 0.0001) and AS+SAR groups (p = 0.003). In univariate analysis, significantly higher SF-12 PCS (meaning better QOL) were observed at pollen peak in the SAR compared with the AS+SAR group (p = 0.0008), while the difference for SF-12 MCS was more limited (p = 0.05). Results were confirmed in multivariable analyses adjusting for gender, allergy medication use at pollen peak, cohort of inclusion (grass/ragweed) and comorbid conditions. Conclusions: Significant deterioration in rhinoconjunctivitis-specific QOL was observed through the pollination period in patients with SAR and AS+SAR. At pollen peak, AS+SAR patients experienced significantly worse physical functioning than patients with SAR alone.
Impact of Sublingual Immunotherapy on Specific Antibody Levels in Asthmatic Children Allergic to House Dust Mites
Authors: Bahceciler Nerin N. , Arikan Cigdem , Taylor Alison , Akdis Mubeccel , Blaser Kurt , Barlan Isil B. , Akdis Cezmi A.
Published: February 2005

Objective: To evaluate the clinical outcome and changes in allergen-specific antibodies during sublingual immunotherapy (SLIT) in house dust mite (HDM)-allergic asthma patients and to compare levels of allergen-specific antibodies in HDM-allergic patients before and after treatment with that of healthy controls. Method: Thirty-one asthma patients allergic to HDM were studied. Patients in groups I (n = 17) and II (n = 14) received SLIT with a standardized Dermatophagoides pteronyssinus plus Dermatophagoides farinae 50/50 extract for 6 and 12 months, respectively. A group of healthy children (n = 8) were enrolled as controls. Patients in both groups were evaluated at the start and at the end of treatment according to daily symptom and medication scores, lung function and skin prick tests, PC20, blood eosinophil count, and Der-p-1-specific IgE, IgA, IgG1 and IgG4 levels. Results: Drug consumption decreased significantly in both groups. Furthermore, PC20 and forced expiratory flow between 25 and 75% of vital capacity of patients in group II improved significantly. Although specific IgA, IgG1 and IgG4 levels did not change throughout the treatment period, total eosinophil count and specific IgE decreased significantly in both groups. According to baseline measurements, specific IgA levels of patients in groups I and II were significantly lower than that of controls. This difference disappeared at the end of the treatment period in both groups. Conclusion: SLIT seems to be effective in ameliorating clinical symptoms, drug consumption and bronchial hyperreactivity, and results in downregulation of Der-p-1-specific IgE production. Furthermore, at the end of SLIT, specific IgA levels, which were decreased compared to healthy controls initially, did no longer differ between patients and controls.
Catatonia: Disappeared or Under-Diagnosed?
Authors: van der Heijden F.M.M.A. , Tuinier S. , Arts N.J.M. , Hoogendoorn M.L.C. , Kahn R.S. , Verhoeven W.M.A.
Published: February 2005

Background: Over the last century, especially during the latter half, the prevalence of the diagnosis of catatonic schizophrenia decreased considerably. Several explanations for this phenomenon have been put forward. Sampling and Methods: The present study investigated the frequency of the diagnosis of catatonic schizophrenia in a large sample of admitted psychiatric patients (n = 19,309). In addition, the presence of catatonic symptoms was studied in a sample of patients with schizophrenia (n = 701) and in a group of consecutively admitted psychotic patients (n = 139). In these two groups the effect of the diagnostic procedures on the recognition of catatonia was examined. Results: The diagnosis of catatonic schizophrenia dropped from 7.8% in 1980–1989 to 1.3% in 1990–2001 (p < 0.001). In addition, a possible under-diagnosis of catatonic schizophrenia was found in an independent sample of patients with schizophrenia. Application of a systematic catatonia rating scale in patients admitted with acute psychosis identified a bimodally distributed catatonic dimension. At least 18% of these patients fulfilled the criteria for catatonia. Interestingly, the catatonic subgroup used atypical antipsychotic compounds more frequently (p < 0.05). Conclusions: The results suggest that changes in diagnostic criteria and the diagnostic procedure itself are responsible for the under-recognition of catatonia.
Reports on Defense Styles in Depression
Authors: Bronnec Marie , Corruble Emmanuelle , Falissard Bruno , Reynaud Michel , Guelfi Julien-Daniel , Hardy Patrick
Published: February 2005

Introduction: ‘State effect’ of depression on personality makes its assessment during depression difficult. Many clinicians do not only refer to the patient, but use additional information sources, especially reports from close informants. Our hypothesis was that an informant could assess the defensive functioning of the depressed patient. The objective of this study was to investigate the validity of the informants’ assessment of defense styles in depressed patients. Methods: Sixty-three inpatients with DSM-IV major depression as primary diagnosis were included. They were administered the Defense Style Questionnaire (DSQ) at admission (D0) and 28 days after treatment (D28) according to their current state. At the same time, informants rated an adapted version of the DSQ (INF-DSQ), according to the patient’s current (D0 and D28) and premorbid defensive functioning (D0). Otherwise, severity of depression was assessed using the 17-item Hamilton Depression Rating Scale at D0 and D28. Results: Agreement between patient’s and informant’s DSQ scores was moderate, both at D0 and D28, even if comparison of mean defense scores does not show significant difference. Mature defense scores significantly increased between D0 and D28, whereas immature defense scores significantly decreased, with both the DSQ and INF-DSQ. During the episode, informants are able to discriminate premorbid from current D0 defenses, but not from current D28 defenses. Conclusion: Even if this study has strong limitations, our results argue for the interest of close informants to assess premorbid personality. Before it could be validated, the INF-DSQ should be further studied in other subgroups of patients, especially its ability to give accurate descriptions of patient’s premorbid defenses during an acute episode.
Perceived Relationships with Parents and Paranoid Delusions: Comparisons of Currently Ill, Remitted and Normal Participants
Authors: Rankin Peter , Bentall Richard , Hill Jonathan , Kinderman Peter
Published: February 2005

Background: Paranoid delusions are associated with abnormal attributions and abnormal beliefs about the self. Some researchers have also reported an association between paranoid beliefs and abnormal attachment representations. Sampling and Methods: Perceptions of relationships with the family of origin were measured in 14 currently ill paranoid patients, 9 remitted paranoid patients and 15 healthy controls, using two methods: the Parental Bonding Instrument (PBI), and the Relationship with Family of Origin Scale (REFAMOS), an interview-based assessment. Results and Conclusions: On the PBI, both currently ill and remitted patients reported low parental care and overprotectiveness during childhood. Similar negative accounts of relationships with parents during the 16–20 years age period, and also at the time of assessment, were elicited from both the ill and remitted patients on the REFAMOS. These findings might reflect the influence of illness on patients’ perceptions of their parents. However, the fact that the remitted patients did not differ from the currently ill patients raises the possibility that dysfunctional relationships are a common feature of the history of paranoid patients, perhaps contributing to the development of paranoid thinking.
Diagnostic Stability in Depressive Disorder as according to ICD-10 in Clinical Practice
Authors: Kessing Lars Vedel
Published: February 2005

Background: The diagnostic stability of the ICD-10 diagnosis of depressive disorder has not been investigated in clinical practice. Sampling and Methods: All patients who were diagnosed with depressive disorder at least once in a period from 1994 to 2002 in psychiatric out- or inpatient settings in Denmark were identified in a nationwide register. Results: A total of 39,741 patients were diagnosed with depressive disorder at least once; among these, 81% were diagnosed at the first contact. In approximately 56% of patients, the initial diagnosis of depressive disorder eventually changed during follow-up mainly to the schizophrenic spectrum (16%), but also to personality disorders (9%), neurotic, stress-related and somatoform disorders (8%) and to bipolar disorder (8%). Among the 18% of patients who were later diagnosed with depressive disorder, 23% initially had a diagnosis of adjustment disorder. Conclusions: When the ICD-10 diagnoses are used in clinical practice, the diagnosis of depressive disorder has a low stability over time. These findings emphasize the need for a longitudinally based diagnostic process in the diagnostic systems.
Indication for Psychotherapy in Offspring of a Parent Affected by a Chronic Somatic Disease (e.g. Multiple Sclerosis)
Authors: Steck B. , Amsler F. , Schwald Dillier A. , Grether A. , Kappos L. , Bürgin D.
Published: February 2005

Based on the transcripts of video-recorded, semi-structured interviews with 41 offspring (aged 6–18 years) of parents with multiple sclerosis, we evaluated the indication for psychotherapy. These results were then compared with the previously determined coping ability of each child/adolescent. Psychotherapy was indicated for 22 out of the 41 children/adolescents. There was a significant relation between the indication for psychotherapy and the children’s inability to cope with the parental disease.The present findings confirm the risk of mental health problems in children of somatically ill parents. In our sample, half of the children and adolescents were estimated to benefit from individual psychotherapy, which might enhance their ability to cope with the parental illness.
Capgras’ Syndrome of Time
Authors: Aziz V.M. , Warner N.J.
Published: February 2005

The delusion that the usual passage of time has been changed and that time has been interfered with or is repeating itself is rare. Four patients with the delusion of warped time are presented and the significance of the symptom is discussed. The perception of the passage of time and its disorders is discussed.
Chronic Mild Hyperhomocysteinemia Induces Aortic Endothelial Dysfunction but Does Not Elevate Arterial Pressure in Rats
Authors: Miao Chao-Yu , Villeneuve Nicole , Brunel-Jacquemin Christine , Petit Christine , Guillaumin Jean-Philippe , Gransagne Denis , Briant Cyril , Vilaine Jean-Paul , Vanhoutte Paul M.
Published: February 2005

Mild hyperhomocysteinemia is prevalent in the general population and has been linked to endothelial dysfunction and high arterial pressure (AP) in clinical studies. The present study was designed to determine whether a rise in AP was induced by mild hyperhomocysteinemia and whether the potential rise in AP is secondary or prior to endothelial dysfunction. Experiments were performed in a rat model of mild hyperhomocysteinemia induced by oral administration of homocysteine for 1–4 months. Aortic endothelial dysfunction was observed 2 months after homocysteine treatment while endothelium-independent vasodilation was normal. In parallel, homocysteine treatment increased phenylephrine-induced contraction in aortas with endothelium, but did not modify the contraction in aortas without endothelium, suggesting a decrease of basal NO production. In conscious unrestrained rats, AP was not significantly different 1, 2, 3 and 4 months after homocysteine treatment. In correlation, endothelial function of a resistance vessel (mesenteric artery), mainly non-NO nonprostanoid factor mediated, was preserved, indicating that homocysteine treatment only affected the NO pathway. In conclusion, mild hyperhomocysteinemia alone is not sufficient to elevate arterial blood pressure, at least in the rat model. Aortic endothelial dysfunction produced by mild hyperhomocysteinemia is independent of hemodynamic factors.
Prevalence of Antibody to Hepatitis E Virus among Haemodialysis Patients in Taiwan: Possible Infection by Blood Transfusion
Authors: Lee Chin-Cheng , Shih Yung-Luen , Laio Chao-Sheng , Lin Su-Mei , Huang Mei-Mei , Chen Chiung-Ju , Chen Chao-Ping , Chang Chun-Lien , Chen Li-Ru , Tschen Shu-Yuan , Wang Chwan-Heng
Published: February 2005

Background/Aims: A higher prevalence of anti-hepatitis E virus (HEV) in non-endemic viral hepatitis such as in Germany has been reported in our previous study. The aim of this study was to assess the seroepidemiology of HEV among haemodialysis (HD) patients in Shin-Kong Hospital, Taiwan, and to evaluate whether there was an increased risk of infection and exposure to HEV even in an area of endemic viral hepatitis. Methods: Serum samples obtained from 400 Taiwanese patients on chronic HD (group 1), 400 sex- and age-matched healthy subjects (group 2) and hospital patients (group 3) were tested for the IgG anti-HEV. Results: The prevalence of anti-HEV among the HD patients and the healthy controls were 31 and 8.9%, respectively. The difference (22%) was statistically significant (p < 0.01). In comparison, the anti-HEV in hospital patients was 16%. Conclusion: The study indicated a significantly higher risk of HEV infection among patients on chronic HD in endemic regions of viral hepatitis such as Taiwan. Mostly because of anaemia, HD patients usually received packed transfusion (red blood cells) if their haemoglobin was low. It is possible that HEV infection may be transmitted through blood transfusions in an endemic area. In such areas, appropriate strategies should be adopted to prevent the risk of HEV among HD patients.
Pharmacokinetics of the Antineoplastic Drug Mitomycin C in Regional Chemotherapy Using the Aortic Stop Flow Technique in Advanced Pancreatic Carcinoma
Authors: Meyer Frank , Ridwelski Karsten , Gebauer Thomas , Grote Reinhard , Martens-Lobenhoffer Jens , Lippert Hans
Published: February 2005

Background: An isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects in comparison with systemic palliative chemotherapy. The aim of the present study was to investigate the pharmacokinetics of mitomycin C utilizing the aortic stop flow technique with commercially available tools in patients with advanced pancreatic carcinoma. Methods: Seventeen patients with unresectable or metastasized pancreatic carcinoma (diagnosed by histological investigation) underwent a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m2 mitomycin C (MitomedacTM, medac, Hamburg, Germany) 22 times. Cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. Results: The mitomycin C concentration was 10 times higher within the regional compared with the systemic compartment at its maximum. The area under the curve was 4.02 times greater. Toxicity was considerable, i.e. WHO grade I/II in 8 of 17 cases, and III/IV in 9 of 17 cases. Two treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission, 2 partial remissions). In 3 subjects, stable disease was registered, and in 11 individuals, tumor progression. The median survival was 4.1 months. Conclusion: Though high concentrations of the cytostatic drug were achieved within the regional compartment, the aortic stop flow technique was associated with a high toxicity rate but no improvement of tumor response and survival in comparison with systemic chemotherapy. Despite its pharmacokinetic advantages, the aortic stop flow technique is currently not recommendable for routine use.
The Effect of the Doxycycline-Rifampicin and Levamisole Combination on Lymphocyte Subgroups and Functions of Phagocytic Cells in Patients with Chronic Brucellosis
Authors: Dizer Ufuk , Hayat Levent , Beker Can Murat , Görenek Levent , Özgüven Volkan , Pahsa Alaaddin
Published: February 2005

Background: Brucellosisis one of the important health problems for both humans and animals in Turkey since agriculture and stock raising appears to be the most important means of subsistence. Investigations on the pathogenesis of brucellosis reveal that the etiologic agent can survive in phagocytic cells, and cell-mediated immunity plays an important role in immunity against bacteria. Methods: In this study, we investigated whether supplementation of levamisole, a well-known antihelminthic agent with immune-stimulating activity to conventional antibiotic therapy, would improve the anergy against Brucella. Results: The results of our study reveal that a 6-week course of levamisole as a supplement to conventional antibiotic therapy in chronic brucellosis is not superior to conventional antibiotic treatment alone with respect to lymphocyte subgroup ratios and phagocytic function. Conclusion: In chronic brucellosis, levamisole administered as a supplement concomitantly with conventional antibiotic therapy has no immunostimulating effect on the basis of the lymphocyte subgroups ratios measured and the ability of phagocytosis in the present study. Further large clinical and laboratory trials are necessary to investigate the immunological and physiological effects of levamisole on TH1 subtypes and cytokine secretion.
Imatinib Blocks Spontaneous Mechanical Activities in the Adult Mouse Small Intestine: Possible Inhibition of c-Kit Signaling
Authors: Shimojima Naoki , Nakaki Toshio , Morikawa Yasuhide , Hoshino Ken , Kitajima Masaki
Published: February 2005

Interstitial cells of Cajal (ICCs) are postulated to serve as pacemakers that physiologically generate electrical slow waves in the gastrointestinal tract. Imatinib is a novel and potent inhibitor of c-Kit tyrosine kinase and a new therapeutic agent for gastrointestinal stromal tumors (GIST) which presumably arise from ICCs. The effects of imatinib on the basal rhythmic mechanical activities of small intestinal circular muscles were investigated in ring preparations of the gut. The small intestinal rings of BALB/c mice exhibited spontaneous contractile activity at a rate of 40.8 ± 4.9 contractions/min. Imatinib (1– 81 µmol/l) dose-dependently abolished spontaneous contractile activity in the 9- to 27-µmol/l concentration range. Contraction was restored by washing imatinib out with a fresh buffer. High K+-induced contraction was not affected by imatinib, suggesting that the drug does not have nonspecific inhibitory actions on the smooth muscles. The small intestinal rings of adult W/Wvmice, which lack a functional c-Kit activity,exhibited only small and irregular spontaneous contractions. These results demonstrate that imatinib affects bowel contractions, and suggest that the c-Kit signaling of ICCs plays an essential role in the spontaneous movements in circular muscles of the mouse small intestine.
Communication between the Perilymphatic Scalae and Spiral Ligament Visualized by in vivo MRI
Authors: Zou Jing , Pyykkö Ilmari , Bjelke Börje , Dastidar Prasun , Toppila Esko
Published: February 2005

We evaluated the transport of Gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) through the round window (RW) membrane into the perilymphatic space with 4.7-T MRI in an animal study and 1.5-T MRI in humans. After administration of Gd-DTPA-BMA onto the intact RW membrane of guinea pig, Gd-DTPA-BMA uptake was observed in the basal turn and part of the second turn within 40 min. The scala tympani, scala vestibuli, the fibrous part of the spiral ligament and semicircular canal all showed uptake of Gd-DTPA-BMA. All turns of the cochlea were filled with Gd within 10 min in the perforated RW membrane administration group and within 30 min in the intravenous administration group. In patients who accepted middle ear injection of Gd-DTPA-BMA, uptake was observed within 2 h in the basal turn and semicircular canal. After 12 h the apex did still not show any uptake. Gd-DTPA-BMA is transported from the RW to the semicircular canal, the scala tympani and scala vestibuli without passing the helicotrema.
Auditory and Electrophysiological Patterns of a Unilateral Lesion of the Lateral Lemniscus
Authors: Cho Tae-Hee , Fischer Catherine , Nighoghossian Norbert , Hermier Marc , Sindou Marc , Mauguière François
Published: February 2005

Auditory disorders resulting from focal brainstem lesions are rarely symptomatic. Isolated lesions of the inferior colliculus have previously been reported, whereas no detailed description of a localized involvement of the lateral lemniscus is yet available. We report a unilateral lesion of the lateral lemniscus by a bleeding in a cavernoma. Symptoms included strictly contralateral tinnitus and auditory impairment, with normal pure-tone and speech audiometry. Conversely, the dichotic listening test revealed an extinction of contralateral ear input. The brainstem auditory evoked potentials disclosed a reduced and delayed wave V only after contralateral ear stimulation, while the middle latency evoked potentials were normal. This observation shows that a unilateral lesion of the lateral lemniscus can produce auditory symptoms. The dysfunction of auditory pathways is associated with specific electrophysiological abnormalities that can be assessed by evoked potential recording.
Does the Bone-Anchored Hearing Aid Have a Complementary Effect on Audiological and Subjective Outcomes in Patients with Unilateral Conductive Hearing Loss?
Authors: Hol Myrthe K.S. , Snik Ad F.M. , Mylanus Emmanuel A.M. , Cremers Cor W.R.J.
Published: February 2005

Objectives: To study the effect of a bone-anchored hearing aid (BAHA) in patients with unilateral conductive hearing loss. Study Design: Prospective evaluation on 18 subjects. Methods:Aided and unaided binaural hearing was assessed in the sound field using a sound localization test and a speech recognition in noise test with spatially separated sound and noise sources. The patients also filled out a disability-specific questionnaire. Patients: 13 out of the 18 subjects had normal hearing on one side and acquired conductive hearing loss in the other ear. The remaining 5 patients had a unilateral air-bone gap and mild symmetrical sensorineural hearing loss. Results:Sound localization with the BAHA improved significantly. Speech recognition in noise with spatially separated speech and noise sources also improved with the BAHA. Fitting a BAHA to patients with unilateral conductive hearing loss had a complementary effect on hearing. Questionnaire results showed that the BAHA was of obvious benefit in daily life. Conclusions: The BAHA proved to be a beneficial means to optimize binaural hearing in patients with severe (40–60 dB) unilateral conductive hearing loss according to audiometric data and patient outcome measures.
Variation in Outcomes after Percutaneous Coronary Intervention in the United States and Predictors of Periprocedural Mortality
Authors: Mukherjee Debabrata , Wainess Reid M. , Dimick Justin B. , Cowan John A. , Rajagopalan Sanjay , Chetcuti Stanley , Grossman Paul M. , Upchurch Gilbert R.
Published: February 2005

The objective of this study was to characterize variation in mortality rates across hospitals performing percutaneous coronary intervention (PCI) in the United States. For this purpose, data (n = 735,022) from the Nationwide Inpatient Sample from 1996 to 2001 were analyzed. The primary outcome for the analysis was postprocedural in-hospital mortality. Mortality rates were calculated by race, gender, geographic region, comorbid status and hospital volume. There were significant variations in mortality across gender groups, comorbid status, regions and by hospital volume status. Independent predictors of mortality in this large cohort were older age, female gender, lower income and lower hospital volume. The data suggests targets for quality improvement initiatives for patients undergoing PCI particularly in the elderly, females, lower income patients and low volume hospitals. Even in the contemporary era of adjunctive pharmacological therapies and ubiquitous use of stents, hospital volume remains a significant independent predictor of in-hospital mortality.
Fetal Growth Velocities in Hong Kong Chinese Infants
Authors: Fok T.F. , Hon K.L. , So H.K. , Wong E. , Ng P.C. , Chang A. , Lau J. , Chow C.B. , Lee W.H.
Published: February 2005

Few studies have investigated the velocities of fetal growth. The aim of the present study was to determine the pattern of ‘fetal’ growth velocities in a Chinese population. The gestation-specific measurements of the body weight, body length and head circumference in a representative sample of 5,045 male and 4,484 female newborns delivered between 26 and 42 weeks of gestation at 12 hospitals in Hong Kong were obtained. Peak growth velocity occurred before 30 weeks of gestation for head circumference, at week 30 for length and at week 30 for weight. When compared with data obtained from a French population, a significant difference in the growth velocity for body weight was observed below 32 weeks between French and Chinese infants, suggesting an ethnic difference in fetal growth of this parameter.
Effect of Cevimeline on Salivary Components in Patients with Sjögren Syndrome
Authors: Suzuki Kimihiro , Matsumoto Mitsuyo , Nakashima Masahiro , Takada Kunio , Nakanishi Takashi , Okada Makoto , Ohsuzu Fumitaka
Published: February 2005

The aim of this study is to clarify the effects of cevimeline on various components in human saliva, such as immunoglobulin A (IgA), lysozyme, α-amylase and squamous cell carcinoma (SCC) antigen. Twelve female patients with Sjögren syndrome (SS) and 14 healthy women were enrolled. After the first saliva collection, one capsule (30 mg) of cevimeline was administered to each subject. Saliva was collected again after 90 min. The salivary flow rate and concentration of each component were measured. In both groups the salivary flow rate and amylase concentration were significantly increased by cevimeline. The lysozyme and IgA concentrations did not change significantly in both groups. The SCC antigen concentration did not change significantly in the SS group, but it decreased significantly in the control group. The secretion rates of amylase and IgA showed significant increases in both groups. The secretion rate of lysozyme significantly increased only in the control group, while the secretion rate of SCC significantly increased only in the SS group. Cevimeline augments not only the salivary flow rate but also the secretion rate of some digestive and/or defense factors from infections. It may be beneficial for SS patients to continue taking cevimeline to prevent oral infections, and other serious sequelae.
Frameless Stereotactic Ventricular Shunt Placement for Idiopathic Intracranial Hypertension
Authors: Woodworth Graeme F. , McGirt Matthew J. , Elfert Peter , Sciubba Daniel M. , Rigamonti Daniele
Published: February 2005

Introduction: Cerebrospinal fluid (CSF) shunting effectively reverses symptoms of idiopathic intracranial hypertension (IIH). Lumboperitoneal (LP) shunts have traditionally been used in patients with IIH due to a frequently undersized ventricular system. However, the advent of image-guided stereotaxis has enabled effective ventricular catheter placement in patients with IIH. We describe the first large series of frameless stereotactic ventriculoperitoneal (VP) shunting for patients with slit ventricles and IIH. Methods: We describe the frameless stereotactic VP shunting technique for IIH in 32 procedures. Outcomes following shunt placement, time to shunt failure, and etiology of shunt failure are reported. Results: A total of 21 patients underwent 32 ventricular shunting procedures (20 VP, 10 ventriculoatrial, 2 ventriculopleural). One hundred percent of shunts were successfully placed into slit ventricles, all requiring only one pass of the catheter under stereotactic guidance to achieve the desired location and CSF flow. There were no procedure-related complications and each ventricular catheter showed rapid egress of CSF. All (100%) patients experienced significant improvement of headache immediately after shunting. Ten percent of ventricular shunts failed at 3 months after insertion, 20% failed by 6 months, 50% failed by 12 months, and 60% failed by 24 months. Shunt revision was due to distal obstruction in 67%, overdrainage in 20%, and distal catheter migration or CSF leak in 6.5%. There were no shunt revisions due to proximal catheter obstruction or shunt infection. Conclusions: In our experience treating patients with IIH, frameless stereotactic ventricular CSF shunts were extremely effective at treating IIH-associated intractable headache, and continued to provide relief in nearly half of patients 2 years after shunting without many of the shunt-related complications that are seen with LP shunts. Placing ventricular shunts using image-guided stereotaxis in patients with IIH despite the absence of ventriculomegaly is an effective, safe treatment option.
Serum Uric Acid Independently Predicts Mortality in Patients with Significant, Angiographically Defined Coronary Disease
Authors: Madsen Troy E. , Muhlestein Joseph B. , Carlquist John F. , Horne Benjamin D. , Bair Tami L. , Jackson Jeffrey D. , Lappe Jason M. , Pearson Robert R. , Anderson Jeffrey L.
Published: February 2005

Background: Uric acid is a nontraditional risk factor implicated in the development of coronary artery disease (CAD). This study prospectively evaluated the predictive value of serum uric acid (SUA) levels for mortality after angiographic diagnosis of CAD. Methods: Blood samples were collected from 1,595 consecutive, consenting patients with significant, angiographically defined CAD (stenosis 70%). Baseline and procedural variables were recorded and levels of SUA were measured. Patients were followed to death or to the time of contact (mean 2.6 years, range 1.8–5.0 years). Results: Patients averaged 65 ± 11 years of age, 78% were male and 170 subjects died during the follow-up period. In univariate analysis of prospectively defined quintiles, SUA predicted all-cause mortality (fifth quintile vs. first four quintiles: hazard ratio 1.9, p < 0.001). In multivariable Cox regression controlling for 20 covariables, independent predictive value for mortality was retained by SUA (hazard ratio 1.5, confidence interval 1.02–2.1, p = 0.04). In subgroup analysis based on diuretic use status, SUA independently predicted mortality among patients not using diuretics, while SUA was not a significant predictor of mortality among those who used diuretics. Conclusions: In patients with significant, angiographically defined CAD, SUA predicted mortality independent of traditional risk factors. This suggests that elevated SUA may be a risk factor for mortality in patients with significant cardiovascular disease and may be a stronger secondary than primary risk factor in CAD.
Troponin Elevation After Percutaneous Coronary Intervention Directly Represents the Extent of Irreversible Myocardial Injury
Authors: Selvanayagam Joseph B. , Porto Italo , Channon Keith , Petersen Steffen E. , Francis Jane M. , Neubauer Stefan , Banning Adrian P.
Published: February 2005

Background—

Although troponin elevation after percutaneous coronary intervention (PCI) is common, uncertainties remain about the mechanisms of its release and its relationship to the volume of myocardial tissue loss. Delayed-enhancement MRI of the heart has been shown to reliably quantify areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac troponin release, we studied the incidence and extent of new irreversible injury in patients undergoing PCI and correlated it to postprocedural changes in cardiac troponin I.

Methods and Results—

Fifty patients undergoing PCI were studied with preprocedural and postprocedural (24 hours) delayed-enhancement MRI for assessment of new irreversible myocardial injury. Cardiac troponin I measurements were obtained before PCI and 24 hours after PCI. Of these 50 patients, 24 underwent a further third MRI scan at a median of 8 months after the procedure. Mean patient age was 64±12 years. After the procedure, 14 patients (28%) had evidence of new myocardial hyperenhancement, with a mean mass of 6.0±5.8 g, or 5.0±4.8% of total left ventricular mass. All of these patients had raised troponin I levels (range 1.0 to 9.4 μg/L). Thirty-four patients (68%) had no elevated troponin I and no evidence of new myocardial necrosis on MRI. There was a strong correlation between the rise in troponin I measurements at 24 hours and mean mass of new myocardial hyperenhancement, both early (
r
=0.84;
P
<0.001) and late (
r
=0.71;
P
<0.001) after PCI, although there was a trend for a reduction in the size of PCI-induced myocardial injury in the late follow-up scan (
P
=0.07).

Conclusions—

In the setting of PCI, patients demonstrating postprocedural elevation in troponin I have evidence of new irreversible myocardial injury on delayed-enhancement MRI. The magnitude of this injury correlates directly with the extent of troponin elevation.
Noninvasive Assessment of Blood Flow Based on Magnetic Resonance Global Coherent Free Precession
Authors: Klem Igor , Rehwald Wolfgang G. , Heitner John F. , Wagner Anja , Albert Timothy , Parker Michele A. , Chen Enn-Ling , Kim Raymond J. , Judd Robert M.
Published: February 2005

Background—

Magnetic resonance global coherent free precession (GCFP) is a new technique that produces cine projection angiograms directly analogous to those of x-ray angiography noninvasively and without a contrast agent. In this study, we compared GCFP blood flow with “gold standards” to determine the accuracy of noninvasive GCFP blood flow measurements.

Methods and Results—

The relationship between GCFP blood flow and true blood flow defined by invasive ultrasonic flow probe and by phase contrast velocity encoded MRI (VENC) was studied in anesthetized dogs (n=6). Blood flow was controlled by use of a hydraulic occluder around the left iliac artery. GCFP images were acquired by selectively exciting the abdominal aorta and visualizing temporal blood flow into the iliac arteries. GCFP flow was similar to ultrasonic blood flow at baseline (131.3±44.8 versus 114.8±34.2 mL/min), during occlusion (10.8±5.1 versus 6.5±7.2 mL/min), during reactive hyperemia (191.4±100.7 versus 260.3±138.7 mL/min), during the new resting state (135.5±52.4 versus 117.8±24.1 mL/min), and during partial occlusion (61.4±36.4 versus 49.3±13.1 mL/min,
P
=NS for all). Results comparing GCFP flow with VENC were similar. Statistical analysis revealed that GCFP flow was related to mean blood flow assessed by the flow probe (
P
<0.0001) and by VENC (
P
<0.0001). In the control right iliac artery, conversely, GCFP measurements were unaffected throughout all left iliac interventions (
P
=NS).

Conclusions—

GCFP blood flow is linearly related to true blood flow for a straight, cylindrical blood vessel without branches. Although more complex geometries imply a qualitative rather than a quantitative relationship, the data nevertheless suggest that GCFP may serve as the basis for a new form of noninvasive stress testing.
Targeted Proteolysis Sustains Calcineurin Activation
Authors: Burkard Natalie , Becher Jan , Heindl Cornelia , Neyses Ludwig , Schuh Kai , Ritter Oliver
Published: February 2005

Background—

Calcineurin (CnA) is important in the regulation of myocardial hypertrophy. We demonstrated that targeted proteolysis of the CnA autoinhibitory domain under pathological myocardial workload leads to increased CnA activity in human myocardium. Here, we investigated the proteolytic mechanism leading to activation of CnA.

Methods and Results—

In patients with diseased myocardium, we found strong nuclear translocation of CnA. In contrast, in normal human myocardium, there was a cytosolic distribution of CnA. Stimulation of rat cardiomyocytes with angiotensin (Ang) II increased calpain activity significantly (433±11%;
P
<0.01; n=6) and caused proteolysis of the autoinhibitory domain of CnA. Inhibition of calpain by a membrane-permeable calpain inhibitor prevented proteolysis. We identified the cleavage site of calpain in the human CnA sequence at amino acid 424. CnA activity was increased after Ang II stimulation (310±29%;
P
<0.01; n=6) and remained high after removal of Ang II (214±17%;
P
<0.01; n=6). Addition of a calpain inhibitor to the medium decreased CnA activity (110±19%;
P
=NS; n=6) after removal of Ang II. Ang II stimulation of cardiomyocytes also translocated CnA into the nucleus as demonstrated by immunohistochemical staining and transfection assays with GFP-tagged CnA. Calpain inhibition and therefore suppression of calpain-mediated proteolysis of CnA enabled CnA exit from the nucleus.

Conclusions—

Ang II stimulation of cardiomyocytes increased calpain activity, leading to proteolysis of the autoinhibitory domain of CnA. This causes an increase in CnA activity and results in nuclear translocation of CnA. Loss of the autoinhibitory domain renders CnA constitutively nuclear and active, even after removal of the hypertrophic stimulus.
Artifact-Free Coronary Magnetic Resonance Angiography and Coronary Vessel Wall Imaging in the Presence of a New, Metallic, Coronary Magnetic Resonance Imaging Stent
Authors: Spuentrup Elmar , Ruebben Alexander , Mahnken Andreas , Stuber Matthias , Kölker Christian , Nguyen Trung Hieu , Günther Rolf W. , Buecker Arno
Published: February 2005

Background—

Coronary in-stent restenosis cannot be directly assessed by magnetic resonance angiography (MRA) because of the local signal void of currently used stainless steel stents. The aim of this study was to investigate the potential of a new, dedicated, coronary MR imaging (MRI) stent for artifact-free, coronary MRA and in-stent lumen and vessel wall visualization.

Methods and Results—

Fifteen prototype stents were deployed in coronary arteries of 15 healthy swine and investigated with a double-oblique, navigator-gated, free-breathing, T2-prepared, 3D cartesian gradient-echo sequence; a T2-prepared, 3D spiral gradient-echo sequence; and a T2-prepared, 3D steady-state, free-precession coronary MRA sequence. Furthermore, black-blood vessel wall imaging by a dual-inversion-recovery, turbo spin-echo sequence was performed. Artifacts of the stented vessel segment and signal intensities of the coronary vessel lumen inside and outside the stent were assessed. With all investigated sequences, the vessel lumen and wall could be visualized without artifacts, including the stented vessel segment. No signal intensity alterations inside the stent when compared with the vessel lumen outside the stent were found.

Conclusions—

The new, coronary MRI stent allows for completely artifact-free coronary MRA and vessel wall imaging.
Aliskiren, a Novel Orally Effective Renin Inhibitor, Provides Dose-Dependent Antihypertensive Efficacy and Placebo-Like Tolerability in Hypertensive Patients
Authors: Gradman Alan H. , Schmieder Roland E. , Lins Robert L. , Nussberger Juerg , Chiang Yanntong , Bedigian Martin P.
Published: February 2005

Background—

Stopping the detrimental effects of the renin-angiotensin system at the most upstream point of the cascade offers theoretical advantages for cardiovascular protection. This study compares the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren with placebo and an active comparator.

Methods and Results—

The study was a randomized, multicenter, double-blind, placebo-controlled, active-comparator 8-week trial in patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure [DBP] ≥95 and <110 mm Hg). After a 2-week, single-blind placebo run-in, 652 patients were randomized to receive double-blind treatment with once-daily oral doses of aliskiren (150, 300, or 600 mg), irbesartan 150 mg, or placebo. Aliskiren 150, 300, and 600 mg effectively lowered both trough mean sitting DBP and systolic blood pressure (SBP) (
P
<0.001 versus placebo for both variables). The least-squares mean reductions in trough DBP were 9.3±0.8, 11.8±0.8, and 11.5±0.8 mm Hg, respectively, versus 6.3±0.8 mm Hg for placebo, and the least-squares mean reductions in trough SBP were 11.4±1.3, 15.8±1.2, and 15.7±1.2 mm Hg, respectively, versus 5.3±1.2 mm Hg for placebo. The antihypertensive effect of aliskiren 150 mg was comparable to that of irbesartan 150 mg (8.9±0.7 and 12.5±1.2 mm Hg, least-squares reduction in mean sitting DBP and SBP, respectively, for irbesartan). Aliskiren 300 and 600 mg lowered mean sitting DBP significantly more than irbesartan 150 mg (
P
<0.05). Aliskiren showed safety and tolerability comparable to those of placebo and irbesartan; the incidence of adverse events and number of patients discontinuing therapy were similar in all groups.

Conclusions—

Once-daily oral treatment with aliskiren lowers blood pressure effectively, with a safety and tolerability profile comparable to that of irbesartan and placebo, in patients with mild-to-moderate hypertension. Aliskiren 150 mg is as effective as irbesartan 150 mg in lowering blood pressure.