bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomic Side Effects of Botulinum Toxin Type B Treatment of Cervical Dystonia and Hyperhidrosis
Authors: Dressler Dirk , Benecke Reiner
Published: April 2003

Recently, botulinum toxin type B (BT-B) has become available to treat muscle hyperactivity in cervical dystonia (CD). When we started the clinical use of BT-B, we noticed a side effect profile not seen with botulinum toxin type A (BT-A) before. Altogether 30 consecutive patients were included in this open controlled study. 24 patients were treated for CD with 11,310 ± 2,616 mouse units (MU) of BT-B (NeuroBloc®) and 6 for focal hyperhidrosis (HH) with 4,000–10,000 MU. In 5 of them, BT-A (Botox®) was used additionally for comparison of effectiveness. In CD, side effects consisted of dryness of mouth (total 21, duration 4.4 ± 2.0 weeks, 10 severe, 7 moderate, 4 mild), accommodation difficulties (7), conjunctival irritation (5), reduced sweating (4), swallowing difficulties (3), heartburn (3), constipation (3), bladder voiding difficulties (2), head instability (1), dryness of nasal mucosa (1) and thrush (1). In HH, side effects consisted of accommodation difficulties (4), dryness of mouth (2) and conjunctival irritation (1). Autonomic side effects occur far more often after BT-B than after BT-A. Their localization suggests systemic BT-B spread. BT-B should be applied carefully in patients with pre-existent autonomic dysfunction, additional anticholinergic treatment and in conditions where anticholinergics are contraindicated.
Reduction of Surgery-Induced Peritoneal Adhesions by Continuous Release of Streptokinase from a Drug Delivery System
Authors: Yagmurlu A. , Barlas M. , Gursel I. , Gokcora I.H.
Published: April 2003

Postoperative abdominal adhesions may lead to intestinal obstruction and infertility. The effect of continuous release of streptokinase to the peritoneal cavity on postoperative adhesions was examined under experimental conditions. Peritoneal adhesions were induced in rats and the animals were further treated by intraperitoneal administration of streptokinase solution, polyhydroxybutyrate-co-hydroxyvalerate (PHBV) membrane alone and streptokinase loaded PHBV membrane and compared to sham operated and untreated groups. Formation of adhesions was evaluated by quantitative macroscopic grading, histopathologically with light microscopy, on the following week. Streptokinase loaded PHBV prevented postoperative adhesion formation in 90% of the cases. PHBV membrane alone also reduced the severity of adhesions due to its anti-adhesive properties. Histopathological examination revealed limited foreign body reaction due to PHBV. Continuous streptokinase activity in the peritoneal cavity during early post-surgical period prevents postoperative adhesion.
High Leptin Levels Are Associated with Stroke
Authors: Söderberg Stefan , Stegmayr Birgitta , Ahlbeck-Glader Christine , Slunga-Birgander Lisbeth , Ahrén Bo , Olsson Tommy
Published: April 2003

Background and Purpose: Leptin, an important hormone for body weight regulation, may be involved in the pathogenesis of cardiovascular manifestations of obesity. We tested whether leptin may be an independent risk marker for stroke in a case-referent study. Methods: Definitive acute stroke events, defined by MONICA criteria, were identified from October 1, 1995 to April 30, 1999. Referents without known cardiovascular disease were randomly selected from a population census. Patient characteristics were taken from hospital files and leptin was analyzed in stored samples. Logistic regression analysis was used to determine possible differences in leptin levels between groups. Results: One hundred and thirty-seven cases with ischemic stroke and 69 cases with hemorrhagic stroke were identified. In comparison with referents, male patients with stroke had significantly higher leptin levels. Both male and female stroke patients had increased blood pressure compared with the referents. In multivariate analyses, high leptin levels were associated with both ischemic (OR = 4.89; 95% CI: 1.89–12.62) and hemorrhagic (OR = 3.86; 95% CI: 1.13–13.16) stroke in men, and with ischemic stroke in women (OR = 4.10; 95% CI: 1.45–11.62). The combination of high leptin levels and increased blood pressure (systolic or diastolic) was associated with a strong positive interaction in males with hemorrhagic stroke. Conclusion: Leptin may be an important link for the development of cerebrovascular disease in the insulin resistance syndrome in men.
Gebären im Wasser
Authors: Schröcksnadel H. , Kunczicky V. , Meier J. , Brezinka C. , Oberaigner W.
Published: April 2003

Fragestellung und Methoden: In einer retrospektiven Fall-Kontroll-Studie wurden 265 in einer Universitätsklinik und einem Bezirkskrankenhaus in Österreich durchgeführte Wassergeburten (aus Schädellage) und ein auf Alter, Gestationsalter und Parität gematchtes Kollektiv von Spontangeburten (ohne operative Intervention) hinsichtlich der wichtigsten fetomaternalen geburtshilflichen Parameter verglichen. Ergebnisse: 4,3% aller Geburten der Universitätsklinik und 13% der Geburten des Bezirkskrankenhauses fanden im Wasser statt. Österreichische Frauen und Frauen mit höherer Schulbildung waren bei dieser Geburtsform häufiger vertreten. Die Dauer der verschiedenen Phasen der Geburt wurde durch die Entbindung im Wasser nicht wesentlich verändert. Die Nabelarterien-pH-Werte der im Wasser geborenen Kinder (Median 7,29 bzw. 7,35) waren besser als die der Kontrollgruppe (Median 7,26), was auf einer positiven Selektion der im Wasser entbundenen Frauen beruhen dürfte. Die Zahl an Episiotomien im Wasser (14 bzw. 4%) war deutlich niedriger als an Land (48%). Umgekehrt fanden sich im Wasser deutlich mehr Dammrisse 1. und 2. Grades (36 bzw. 41%) und Labienrisse (23 bzw. 21%) als in der Kontrollgruppe (Dammrisse 23%; Labienrisse 7%). Bei im Wasser entbundenen Frauen war weniger Schmerzmedikation nötig (8 bzw. 9%) als in der Kontrollgruppe (64%). Das Hämoglobin im Wochenbett war nach Wassergeburt nicht unterschiedlich zur Kontrollgruppe. Die mütterliche und kindliche infektiöse Morbidität war nach Wassergeburt nicht erhöht. Schlussfolgerungen: Bei gesunder Mutter und gesundem Kind am Termin in Schädellage ist (unter Wahrung entsprechender Kriterien an Abteilungen mit spezifischer Infrastruktur) die Entbindung im Wasser als sicher anzusehen.
Prediction of Left Ventricular Functional Recovery by Dobutamine Echocardiography, F-18 Deoxyglucose or 99mTc Sestamibi Nuclear Imaging in Patients with Chronic Myocardial Infarction
Authors: Lund Gunnar K. , Freyhoff Jörg , Schwaiger Markus , Lübeck Martin , Lund Christian H. , Buchert Ralph , Sheehan Florence H. , Meinertz Thomas , Nienaber Christoph A.
Published: April 2003

Background: Currently, several modalities are available to predict viability, however, studies comparing various modalities validated by functional recovery after revascularization are scarce. This study analyzed the relative merits of low-dose dobutamine echocardiography, F-18 deoxyglucose (FDG) positron emission tomography (PET) and 99mTc sestamibi single-photon emission computed tomography to predict functional recovery after revascularization in patients with chronic myocardial infarction. Methods: Patients with chronic coronary occlusion (duration: 3.1 ± 4.8 years) and impaired left ventricular function (ejection fraction: 42 ± 13%) underwent low-dose dobutamine echocardiography (20 µg/kg/min), FDG-PET and 99mTc sestamibi imaging before revascularization. Revascularization was performed irrespective of any viability data. Follow-up angiography was obtained 4.8 ± 2.5 months after revascularization. Results: Viability analysis was performed in 34 patients with patent target vessel at follow-up, of whom 9 (27%) exhibited functional recovery on left ventricular angiography. For dobutamine echocardiography, improvement of ≧2 adjacent akinetic segments resulted in improved sensitivity of 89% and specificity of 80% to predict functional recovery. For glucose metabolism, FDG uptake >55% was an optimal threshold yielding a sensitivity of 89% and a specificity of 68%. With respect to perfusion, 99mTc sestamibi uptake >60% was the best cutoff resulting in a sensitivity and a specificity of 56 and 88%, respectively. A concordant match of FDG >55% and of 99mTc sestamibi >50% resulted in optimized sensitivity (78%) and specificity (80%) with dual imaging. Conclusions: Recovery of chronically dysfunctional myocardium can be predicted with high accuracy by stimulation of contractile reserve or by concordant match of preserved glucose metabolism and residual perfusion.
Coronary Artery Bypass Surgery in Heart Failure Patients with Chronic Reversible and Irreversible Myocardial Dysfunction: Effect on Heart Rate Variability
Authors: Wiggers Henrik , Bøtker Hans Erik , Egeblad Henrik , Christiansen Evald Høj , Toftegaard Nielsen Torsten , Mølgaard Henning
Published: April 2003

It is unknown whether surgical revascularization of viable and chronic reversibly dysfunctional myocardium in patients with heart failure is associated with a favorable effect on the autonomic control of heart rate. We studied 38 coronary artery bypass surgery (CABG) patients with an ejection fraction of 36 ± 7%. Before CABG, the patients underwent 48-hour ambulatory electrocardiographic monitoring to measure heart rate variability (HRV), echocardiography to assess left ventricular function, and positron emission tomography and low-dose dobutamine echocardiography to assess viability. Six months after CABG, ambulatory electrocardiographic monitoring and echocardiography were repeated to assess HRV and recovery of left ventricular function. In spite of viable myocardium and recovery of left ventricular function following CABG, HRV indices were reduced 6 months postoperatively. A potential prognostic benefit gained by revascularizing patients with viability may occur in spite of deteriorated autonomic control of heart rate.
Tumor Cell Dissemination during Laparoscopy: Prevention and Therapeutic Opportunities
Authors: Steinert Ralf , Lippert Hans , Reymond Marc A.
Published: April 2003

Port-site recurrences (PSRs) are abdominal wall recurrences that occur in the subcutaneous tissue within a trocar site after cancer laparoscopy and are not associated with peritoneal carcinomatosis. In order to develop PSRs, viable tumor cells must be liberated from the primary tumor, be transported to a wound, and find there a favorable environment for growth. The short clinical delay in the occurrence of PSRs and their size suggest massive cell seeding into the abdominal wall. Traumatic handling of the tumor, slipping of trocars, liquid projection, as well as poor extraction techniques can all cause implantation of malignant cells into the subcutaneous tissue. Such contact can also occur postoperatively if the trocar channels remain open. Some histologies (e.g. gallbladder adenocarcinoma), the presence of ascites and advanced tumor stage are risk factors for PSRs. Further conditions – including the use of gas – might also play a limited role. The first preventive measure is the correct indication for a laparoscopic approach. Several techniques have been demonstrated to prevent PSRs in the animal model: (a) fixation of trocars to the abdominal wall; (b) prevention of leakage; (c) careful specimen handling; (d) reducing trauma to the abdominal wall; (e) specimen isolation before extraction from the abdominal cavity; (f) trocar-site irrigation with a cytotoxic solution, and (g) closure of peritoneum. Further innovative therapies are currently under investigation. In the clinical setting, correct indication, surgical expertise and application of prophylactic measures seem to be the best way to prevent the occurrence of PSRs.
The Social Cost of Alcohol, Tobacco and Illicit Drugs in France, 1997
Authors: Fenoglio Philippe , Parel Véronique , Kopp Pierre
Published: April 2003

Aim, Design and Setting: The economic costs of alcohol, tobacco and illicit drugs to French society are estimated using a cost of illness framework. Measurements: For the cause of disease or death (using ICD-9 categories), pooled relative risk estimates from meta-analyses were combined with prevalence data by age and gender to derive the proportion attributable to alcohol, tobacco and/or illicit drugs. The resulting estimates of attributable deaths and hospitalizations were used to calculate the associated health care, law enforcement, productivity and other costs. The results were compared with those of other studies, and sensitivity analyses were conducted by alternative ways of measuring risk attribution and costs. Findings: The use of alcohol, tobacco and illicit drugs cost more than 200 billion francs (FF) in France in 1997, representing 3,714 FF per capita or 2.7% of the gross domestic product (GDP). Alcohol is the drug that gives rise to the greatest cost in France, i.e. 115,420.91 million FF (1.42% of GDP) or an expenditure per capita of 1,966 FF in 1997. Alcohol takes more than half of the social cost of drugs to society. The greatest share of the social cost of alcohol comes from the loss of productivity (57,555.66 million FF), due to premature death (53,168.60 million FF), morbidity (3,884.0 million FF) and imprisonment (503.06 million FF). Tobacco leads to a social cost of 89,256.90 million FF, that is an expenditure per capita of 1,520.56 FF or 1.1% of GDP. Productivity losses amount to 50,446.70 million FF, with losses of 42,765.80 million FF as a result of premature death and 7,680.90 million FF linked to morbidity. Health care costs for tobacco occupy second place at 26,973.70 million FF. Illicit drugs generate a social cost of 13,350.28 million FF, that is an expenditure per capita of 227.43 FF or 0.16% of GDP. Productivity losses reach 6,099.19 million FF, with 5,246.92 million FF linked to imprisonment and 852.27 million FF to premature death. The cost of enforcing the law for illicit drugs occupies second place at 3,911.46 million FF, followed by health care costs of 1,524.51 million FF. Conclusion: Substance abuse exacts a considerable toll from French society in terms of illness, injury, death and economic costs.
Gender Differences in the Prevalence of Symptom Disorders and Personality Disorders among Poly-Substance Abusers and Pure Alcoholics
Authors: Landheim A.S. , Bakken K. , Vaglum P.
Published: April 2003

Objective: Gender differences in the prevalence of Axis I and II disorders in poly-substance abusers and pure alcoholics and between these two groups are explored. Method: A consecutive sample (n = 260) of in- and out-patients from two Norwegian counties were assessed by CIDI (Axis I disorders) and MCMI-II (Axis II disorders). Results: Major depression, post-traumatic stress disorder (PTSD), and eating disorders were significantly more prevalent in women than in men. A significantly higher prevalence of antisocial, passive-aggressive, and borderline personality disorders (PD) was observed among poly-substance abusers, whereas pure alcoholics were found to have dependent PDs more often. Female poly-substance abusers differed significantly from all other substance abusers by suffering more often from major depression, simple phobia, PTSD and borderline PD. Male poly-substance abusers more often presented antisocial PD and less often Cluster C disorders than all other substance abusers. Female pure alcoholics more often had major depression and Cluster C disorders than all other substance abusers. Male pure alcoholics presented less often with Axis I disorders, major depression, and PTSD, but more often with Cluster A disorders, in particular schizoid PD, than all other substance abusers. Conclusion: The pattern of comorbid disorders is clearly different between male and female poly-substance abusers and pure alcoholics. This implies that these four subgroups have important differences in their treatment needs.
The Influence of Typical and Atypical Neuroleptic Drugs in the Production of Interleukin-2 and Interferon-Gamma in vitro
Authors: Rudolf Sebastian , Peters Marion , Rothermundt Matthias , Arolt Volkert , Kirchner Holger
Published: April 2003

Alterations of cytokine levels represent the most consistent finding from studies concerning the involvement of the immune system in the etiology of schizophrenia. These results have been discussed controversially due to the potential influence of drug treatment on cytokine production and on the experimental procedures used for cytokine measurement. In the present study, the influences of typical and atypical neuroleptic drugs (haloperidol and clozapine) as well as a tricyclic antidepressive drug (amitriptyline) on cytokine levels (IL-2 and IFN-γ) were examined in vitro in a whole blood assay under various conditions of phytohemagglutinin (PHA) stimulation and drug incubation. Stimulation was enhanced by haloperidol and clozapine, but not by the antidepressant, meaning that the results of decreased cytokine levels seen in earlier studies in schizophrenic patients cannot be explained through drug influences alone. Furthermore, our findings allow us to conclude that, in contrast to the antidepressant drug, the typical and atypical neuroleptic drugs seem to influence the examined cytokine levels.
Serum Leptin and Cholesterol Levels in Patients with Bipolar Disorder
Authors: Atmaca Murad , Kuloglu Murat , Tezcan Ertan , Ustundag Bilal , Bayik Yilmaz
Published: April 2003

Low cholesterol levels have been reported in patients with manic episodes. Leptin seems to be strongly associated with lipid metabolism. In the present study, therefore, serum total cholesterol and leptin levels were compared in 16 patients with manic episodes, 16 with bipolar I disorder in full remission and 16 healthy controls. The serum total cholesterol and leptin levels were measured and Young Mania Rating (YMRS) and Hamilton Depression Rating Scales (HAM-D) were administered for each subject. Both the patients with manic episodes and the patients with bipolar I disorder in full remission had markedly low serum cholesterol and leptin levels compared with controls, though the difference was more obvious in patients with manic episodes. In addition, there were negative correlations between YMRS scores and serum cholesterol or leptin levels in the patients with manic episodes. Our results suggest that the patients with manic episodes and those with bipolar I disorder in full remission seem to be associated with decreased serum cholesterol and leptin levels.
Chronic Kidney Disease and the Transplant Recipient
Authors: Gill John S. , Pereira Brian J.G.
Published: April 2003

The recent Kidney Disease Outcomes Quality Initiative (K/DOQI) classification of chronic kidney disease (CKD) includes transplant recipients. Although there are important differences between kidney transplant recipients (KTRs) and patients with native kidney disease, the inclusion of KTRs along with other CKD patients is an important step to improve long-term outcomes among transplant recipients. In this article we discuss the applicability of the K/DOQI classification of CKD to transplant recipients and the importance of premature patient death with graft function as a cause of graft loss. The implementation of a comprehensive program of CKD care beginning prior to transplantation and continuing after graft failure is discussed as a strategy to improve patient outcomes and specific areas of concern for KTRs are highlighted.
Impact of Codon Usage Modification on T Cell Immunogenicity and Longevity of HIV-1 Gag-Specific DNA Vaccines
Authors: Bojak Alexandra , Wild Jens , Deml Ludwig , Wagner Ralf
Published: April 2003

In this study, we analyzed the in vitro expression, potency and longevity of immune responses induced in a Balb/c mouse model by a synthetic HIV-1 gag gene exhibiting a codon usage that was adapted to that of highly expressed mammalian genes (syngag). In contrast to a vector containing the wild-type (wt) gag gene, the syngag construct enabled highly efficient Gag expression in both human and rodent cell lines in complete absence of Rev and Rev-responsive element. Immunization of Balb/c mice with the wt gag plasmid DNA induced only weak and inconsistent humoral immune responses. Mice vaccinated by syngag but not wt gag developed substantial and highly consistent Gag-specific antibody titers showing a clear T helper 1 polarization even with low doses of DNA. Moreover, vaccinated mice developed a strong Gag-specific cellular immune response, including cytotoxic T cells, which was not observed in wt gag-immunized animals. Both humoral and cellular immunity were efficient and lasted for more than 20 weeks. Furthermore, the induction of the humoral as well as the cellular immune response was independent of the immunization route (intramuscular or subcutaneous). These results clearly show the advantages of codon-optimized genes with respect to the expression and immunogenicity of plasmid DNA constructs, making them promising vaccine candidates for further studies.
A Short Introduction to Papillomavirus Biology
Authors: Streeck Rolf E.
Published: April 2003

In this report, the tropism of papillomaviruses, the structure of virions, the function of viral proteins and the use of pseudovirions for the analysis of the immune response against papillomaviruses and the search for the viral receptor are briefly described.
Influence of Changes in Dietary Fatty Acids during Pregnancy on Placental and Fetal Fatty Acid Profile in the Rat
Authors: Amusquivar Encarnación , Herrera Emilio
Published: April 2003

To determine whether the composition of long-chain polyunsaturated fatty acids (PUFA) could be modified in the fetus by maternal dietary fatty acids, pregnant Sprague-Dawley rats were fed semipurified diets that differed only in the non-vitamin lipid component. The diets contained either 10 g palm, sunflower, olive or fish oil (FOD)/100 g diet. A total of 5–6 rats were studied in each group. At day 20 of gestation, corresponding to 1.5 days prior parturition, the fatty acids in maternal adipose tissue were closely related to the fatty acid composition in the corresponding diet. An important proportion of arachidonic acid (AA) appeared in maternal liver and plasma, although it was lower in the FOD than in the other groups. Except for saturated fatty acids, the proportion of individual fatty acids in the placenta correlated linearly with that in maternal plasma. Also, PUFA in fetal plasma and liver showed significant correlations with PUFA in maternal plasma. Again, AA showed the lowest proportion in the plasma and liver of the FOD group. Therefore, the maternal dietary fatty acid composition influences maternal and fetal plasma and tissue composition, and an increase in dietary ω–3 fatty acids decreases the amount of AA in maternal and fetal tissues.
Initial Lithium and Valproate Combination Therapy in Acute Mania
Authors: Reischies Friedel M. , Hartikainen Jukka , Berghöfer Anne
Published: April 2003

Early onset of treatment efficacy is especially important for severe mania syndromes. Lithium has usually a delayed onset of response, which is disadvantageous for inpatient treatment of severe mania. Valproate is effective in treating acute mania and has sedative properties. It has, however, a response rate of approximately only two thirds. Therefore, the initial combination of valproate and lithium was evaluated in a prospective case series of 12 patients, and a retrospective analysis was carried out for 5 patients in comparison with a pretreatment period when lithium therapy was applied without valproate. Outcome criterion for analysis was the latency of response and remission, as well as the amount of neuroleptics used for additional sedation. Patients had a mania syndrome-severity score comparable with the mean mania score of the bipolar manic patients treated in the same unit. All patients under the combination treatment responded. The response occurred within a shorter time compared with the lithium pretreatment episode, which is statistically marginally significant, and the use of neuroleptic medication could be markedly reduced from 18,601.6 mg chlorpromazine equivalents to 3,927.6 mg (p < 0.025). The initial valproate-lithium combination therapy seems to be a safe and effective way to treat severe mania syndromes in the clinic.
Electronic Diary for Bipolar Patients
Authors: Schärer L.O. , Hartweg V. , Hoern M. , Graesslin Y. , Strobl N. , Frey S. , Biedermann C. , Walser S. , Walden J.
Published: April 2003

Long-term monitoring methods providing an overview of the course of bipolar disorder of individual patients are a clinical necessity at least for patients who require a combination therapy with drugs that have only proven their efficacy for monotherapy. The Life Chart Method (LCM) of the NIMH is an adequate method for this purpose. Unfortunately, due to data entry and management requirements, it is too expensive for everyday clinical use. The ‘electronic diary for patients with bipolar disorder’ is meant to provide a method to minimize the effort for detailed long-term monitoring of patients with bipolar affective disorder and thus make it available for the everyday clinical use for every bipolar patient.
Genetic Characterization of a Porcine H1N2 Influenza Virus Strain Isolated in Germany
Authors: Schrader Christina , Süss Jochen
Published: April 2003

We examined selected influenza virus strains from various outbreaks of respiratory diseases among pigs in Germany. Besides H3N2 and H1N1 subtypes presently circulating in Europe, an H1N2 influenza virus was isolated in 2000. Sequence analysis of hemagglutinin, neuraminidase and matrix genes indicated that this virus is a reassortant of human H1N1 and human H3N2 strains with an internal gene, the M gene of avian origin. It is a result of a multiple reassortment event.
Vibration and Its Effects on the Body
Authors: Issever Halim , Aksoy Cihan , Sabuncu Hilmi , Karan Ayse
Published: April 2003

Objectives: To assess the effects of machine-induced vibration on workers and to determine effective precautions for vibration-induced trauma. Subjects and Methods: The study group consisted of 114 workers who were randomly selected: 50 rock drill workers and 64 truck heavy vehicle operators. Fifty-four office workers were designed as controls. The study and control groups were age-matched. All subjects were interviewed to determine subjective symptoms using a 38-item questionnaire designed by the Medical Committee of Vibration Disease, Japanese Association of Industrial Health. Results: The complaints of pain in the fingers, sensitivity to cold, numbness and pain of fingers at night, weakness of static position, wrist-elbow pain, difficulty in bending and stretching elbow, pain in shoulder when holding up arms, lower back pain, sleeping disturbance and hearing difficulty were significantly higher in rock drillers than heavy vehicle operators and office workers (p < 0.05–0.01). Conclusion: Permanent vibration exposures cause negative physical effects that may lead to occupational diseases. In order to be protected against whole-body and hand-arm vibrations, technical and medical measures must be taken into account.
Asymptomatic Massive Hypertriglyceridemia in an Octogenarian
Authors: Cicero Arrigo F.G. , Panourgia Maria Panagiota , Nascetti Simona , Sangiorgi Zina , Gaddi Antonio
Published: April 2003

Objective: To report the case of an 85-year-old man with asymptomatic massive hypertriglyceridemia (MHTG). Clinical Presentation and Intervention: Our case was a non-smoker, healthy 85-year-old Caucasian male, with no excessive alcohol intake and no evidence of an excessive sedentary lifestyle, body mass index = 23.2 kg/m2, BP = 125/85 mm Hg and plasma triglyceride (TG) >1,000 mg/dl. The MHTG was an incidental finding at the age of 70. He had no cardiovascular disease, xanthomas, xanthelasmas or keratic precipitate. During the last 15 years, his average TG plasma levels showed a significant variability independent of specific diet treatment and fibrate therapy. Liver ultrasound examination excluded hepatomegaly and fatty degeneration. Carotid artery ultrasound showed only intimal thickening in both carotid bifurcations. Conclusion: In this patient, MHTG had been silent for many years, with no evidence of coronary heart disease and liver fatty degeneration, both typical complications present in MHTG subjects with low high-density lipoprotein. Hence, this case must be considered as a rarity.
Survival of Allografted Pancreatic Islets in the Subretinal Space in Rats
Authors: Inoue Makoto , Maeno Takatoshi , Hatchell Diane L.
Published: April 2003

The purpose of this study was to determine whether the subretinal space would provide immune privilege for pancreatic islet transplantation. Islets from outbred Sprague Dawley (SD) rats were isolated by collagenase digestion, and about 200 handpicked islets were transplanted into the subretinal space of SD rats. Similar grafts were transplanted into the subconjunctival space of SD rats as controls. Transplanted eyes were enucleated after 2 to 60 days, fixed and embedded in paraffin for immunoperoxidase staining of insulin, glucagon, and CD8+ lymphocytes. Clinical examination of rat eyes revealed minimal or no inflammation in the anterior chamber or vitreous at any time point. Fifteen of 19 subretinal allografts survived up to 60 days. Few CD8+ lymphocytes were present in the subretinal grafts and the endocrine cells stained intensely for insulin and glucagon at all time points. In contrast, CD8+ lymphocytes were present in subconjunctival grafts in rats by day 14 and all grafts were destroyed by day 21. These results suggest that the subretinal space provides immune privilege for islet allotransplantation by preventing massive lymphocyte infiltration.
Assessment of Regional Acute Stroke Unit Care in Italy: The PROSIT Study
Authors: Sterzi Roberto , Micieli Giuseppe , Candelise Livia
Published: April 2003

Background/Objectives: The aim of this study was to survey acute in-hospital stroke services in seven Italian regions. Methods: Regional hospital discharge registers were searched to identify hospital services that record at least 50 acute stroke discharges per year and the doctors in charge of these services were interviewed. Results: Only 31 (7%) out of 447 services could be classified as stroke units (SUs). Of these, only 9 (29%) were found to have vital function monitoring systems available for all patients. The most striking differences between SUs and mixed stroke services emerged when comparing staff/patient ratios in the two types of unit. Conclusions: There are still not enough SUs in Italy, and fewer than 10% of stroke patients can be admitted to such units.
Anti-Inflammatory Effects of α-Melanocyte-Stimulating Hormone in Celiac Intestinal Mucosa
Authors: Colombo Gualtiero , Buffa Roberto , Bardella Maria Teresa , Garofalo Letizia , Carlin Andrea , Lipton James M. , Catania Anna
Published: April 2003

Objectives: The peptide α-melanocyte-stimulating hormone (α-MSH) possesses potent anti-inflammatory activities and has been previously implicated in the endogenous control of inflammatory reactions. The aim of the present research was to determine whether α-MSH and its receptors participate in a localized anti-inflammatory response in the duodenal mucosa of celiac patients. Methods: Three series of experiments were performed, using duodenal biopsy pairs from 53 adult celiac patients and 14 normal subjects, in order to determine: (1) mucosal immunoreactivity for α-MSH and melanocortin receptors (MCRs), and gene expression of α-MSH precursor pro-opiomelanocortin and MCRs; (2) α-MSH and inflammatory cytokine production by duodenal specimens in vitro, and the influence of synthetic α-MSH on such cytokine production, and (3) the influence of stimulation with gliadin (the subfraction of gluten that is toxic to patients with celiac disease) on α-MSH and cytokine production in vitro and the effect of α-MSH on gliadin-stimulated cytokine production. Results: Elements of a localized anti-inflammatory influence based on α-MSH and its receptors were found: duodenal mucosa showed immunostaining for α-MSH and two of its receptor subtypes, MC1R and MC5R. α-MSH and MC1R immunoreactivity was more intense in specimens from celiac patients. Release of interleukin 6 from gliadin-stimulated duodenal mucosa was inhibited by synthetic α-MSH in vitro. Conclusions: Presence of α-MSH and its receptors in celiac mucosa suggests the presence of a local reaction to control the inflammatory response elicited by gliadin. In selected cases of refractory celiac disease, treatment with exogenous peptides might be considered.
The Trough Effect: Implications for Speech Motor Programming
Authors: Lindblom Björn , Sussman Harvey M. , Modarresi Golnaz , Burlingame Elizabeth
Published: April 2003

While the existence of the trough effect is unquestioned, its theoretical significance is unknown. A multifaceted instrumental approach – spectrographic, cineradiographic, and vocal tract modeling – was used to document the trough effect in open (V.CV) and closed (VC.V) syllable forms using a symmetrical vowel context surrounding labial stops. Collectively, the results document the trough phenomeon as a momentary deactivation of tongue and/or lip movement after V1 and continuing into the stop closure. This empirical event suggests a segment-by-segment activation pattern as opposed to a diphthongal vowel-to-vowel trajectory with an independent and superimposed consonantal gesture. Quantitative models of VCV coarticulation must incorporate the trough effect in order to more effectively capture the kinematic properties of speech.
Comparison of Conjunctival and Nasal Provocation Test in Allergic Rhinitis to House Dust Mite
Authors: Riechelmann Herbert , Epple Barbara , Gropper Gunther
Published: April 2003

Background: Nasal allergen provocation tests (NPTs) are useful in confirming the diagnosis of allergic rhinitis, if data obtained by clinical history, skin tests and specific IgE determinations are not conclusive. Since NPTs are laborious, conjunctival provocation tests (CPTs) appear as an attractive alternative. The concordance of CPTs and NPTs with house dust mite allergen extract in sensitized and nonsensitized subjects should be evaluated. Methods: 50 otherwise healthy subjects with self-reported house dust mite allergy and positive skin prick tests and serum specific IgE to Dermatophagoides pteronyssinus and 45 sex- and age-matched healthy controls without allergic symptoms were included. For NPTs, 100 µl allergen extract [10,000 allergy units (AU/ml)] were applied to the less congested nasal cavity. A clinical symptom score and active anterior rhinomanometry were employed to assess the response. For CPTs, 50 µl low-concentrated D. pteronyssinus extract (1,000 AU/ml), and if negative, 50 µl normally concentrated extract (10,000 AU/ml) were applied to the lower conjunctival sac. The response was assessed employing clinical symptom scores. Results: NPTs and CPTs yielded concordant results in 90% of the subjects successfully tested (Cohen’s kappa = 0.78, p < 0.0001). The diagnostic efficacy of the CPT, with the NPT as the reference method, was 89%, whether or not conjunctival symptoms had been reported in addition to rhinitis symptoms. Both techniques were judged almost equally uncomfortable. Conclusion: CPTs are an acceptable alternative to NPTs in patients with allergic rhinitis to house dust mite, even if they have no conjunctival symptoms.
Serum Estradiol Levels after 4 Days of Ovarian Hyperstimulation in Oocyte Donors Are Predictive of Embryo Quality and Clinical Outcomes
Authors: Peña Joseph E. , Chang Peter L. , Thornton, II Melvin H. , Sauer Mark V.
Published: April 2003

Objective: To determine whether estradiol (E2) levels after 4 days of ovarian hyperstimulation in leuprolide-downregulated cycles are predictive of embryo quality and pregnancy outcome in oocyte donation. Material and Methods: Retrospective analysis of 287 consecutive oocyte donation cycles performed at a university assisted reproduction therapy program between January 1996 and December 2000. Oocyte donors and recipients followed a non-varied standard synchronization regimen. A serum E2 (day-5 E2) was obtained from egg donors the morning after leuprolide acetate downregulation and 4 days after hMG/FSH administration. Day-5 E2 was categorized into 3 groups: group I <75 pg/ml; group II 75–350 pg/ml, and group III ≧350 pg/ml. All embryo transfers were performed 3 days after oocyte recovery. Results: Elevated day-5 E2 levels were directly correlated with higher average embryo scores, greater number of oocytes retrieved, and greater number of embryos available for transfer and cryopreservation. Improved pregnancy outcomes were also noted for group III (day-5 E2 level >350 pg/ml). Conclusion: After 4 days of gonadotropin stimulation, an E2 level of >350 pg/ml is most predictive of higher embryo grade and pregnancy outcome in oocyte donation.
Primary NK/T Cell Lymphoma of the Testis
Authors: Kim Yong Bae , Chang Sei Kyung , Yang Woo-Ick , Hahn Jee Sook , Koom Woong Soup , Shim Su Jung , Park Won , Lee Kang Kyoo , Suh Chang Ok , Kim Gwi Eon
Published: April 2003

We report a case of aggressive ‘nasal type’ natural killer (NK)/T cell lymphoma initially presenting as a testicular tumor in a Korean man, which quickly took a fatal course by widespread dissemination. Histologically, the testicular mass showed a diffuse dense infiltrate of medium-sized and atypical large lymphoid cells with angiocentric and angiodestructive infiltration and areas of coagulative necrosis on hematoxylin-eosin stained sections. Immunophenotyping by immunohistochemistry yielded surface markers consistent with NK/T cell lymphoma. The Epstein-Barr virus genome was detected by in situ hybridization. During involved-field irradiation and chemotherapy following radical orchiectomy, the tumor disseminated shortly to the skin and soft tissue of his anterior chest wall and central nervous system (CNS). Identical lymphoid infiltrates were present in the patient’s skin. CNS involvement was interpreted as having a leptomeningeal seeding. To the best of our knowledge, this is the 9th reported case of confirmed NK/T cell lymphoma arising from the testis. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.
The Role of the Data Safety and Monitoring Committee in Stroke Trials
Authors: Asplund Kjell
Published: April 2003

There are many good reasons why any human experiment should have appropriate oversight. In clinical trials, the data safety and monitoring committee (DSMC) serves to protect the interests of the patients. In stroke trials, its members usually together represent a broad expertise in neurology, internal medicine, cardiology and biostatistics. Independency and integrity are key words, especially in the relationship to the sponsor of the trial. The DSMC members should have no long-term financial strings to the sponsor, and they should not be personally involved in patient recruitment and evaluation. The DSMC provides recommendations to the steering committee of the trial on whether to continue or to stop patient recruitment and on protocol amendments that may be necessary to protect the safety of the patients.
A novel family-specific translocation t(2;20)(p24.1;q13.1) associated with recurrent abortions: molecular characterization and segregation analysis in male meiosis
Authors: Trappe R. , Böhm D. , Kohlhase J. , Weise A. , Liehr T. , Essers G. , Meins, M. , Zoll B. , Bartels I. , Burfeind P.
Published: April 2003

In the present study, we present a novel reciprocal translocation t(2;20)(p24.1;q13.1) and its segregation in a three generation family. The rate of miscarriages (50%) in pregnancies from male translocation carriers could be explained by unbalanced translocation-bearing spermatozoa found with a frequency of approximately 55% in the entire sperm population of a t(2;20)(p24.1;q13.1) carrier. These imbalanced spermatozoa mainly present as 2, der(20) and der(2), 20 missegregated (approximately 46%) while adjacent 2 and 3:1 segregation patterns account for approximately 5% and 4% of imbalances, respectively. While the translocation is associated clearly with an increased risk of early abortions (7/12) in both male and female carriers, no malformed livebirths were observed. Our results suggest complete embryonic lethality of imbalanced offspring. With respect to a high rate of segregation to 2, der(20) and to der(2), 20 imbalanced spermatozoa in male translocation carriers and with respect to known cases of partial trisomy 2p and 20q we consider that their corresponding monosomies result in fetal loss. This is the first study reporting multiple abortions associated with partial monosomy 20q13.1→qter and 2pter→p24.1 and the first report on the frequency of chromosomal imbalances in gametes of a male t(2;20)(p24.1;q13.1) heterozygote.
Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q
Authors: Kostiner D.R. , Nguyen H. , Cox V.A. , Cotter P.D.
Published: April 2003

Terminal inversion duplications of the short arm of chromosome 8 are one of the more common chromosome rearrangements in humans. We report an infant with multiple congenital anomalies, in whom karyotype analysis showed a terminal inversion duplication of 8p including additional material at the distal end of the derivative chromosome, shown to be of chromosome 18q origin. Terminal inversion duplications of 8p are the result of meiotic recombination between inverted olfactory gene receptor repeats in 8p. This recombination generates a dicentric intermediate that breaks during anaphase, and the broken chromosome end is stabilized by telomere healing or telomere capture. The origin of the telomeric region in the majority of constitutional chromosome deletions studied to date was shown to be from telomere healing; the de novo addition of telomeric repeats. In the proband a cytogenetically detectable piece of chromosome 18q was present on the distal end of the derivative 8, suggesting that this chromosome was stabilized by telomere capture of 18q. FISH analyses of additional cases may yield information as to whether telomere capture or telomere-healing events are the predominant mechanism of chromosome stabilization in terminal inversion duplications of 8p.
“Ag-NORs” are not always true NORs: new evidence in mammals
Authors: Dobigny G. , Ozouf-Costaz C. , Bonillo C. , Volobouev V.
Published: April 2003

In spite of uncertainty about the biochemical processes involved, silver staining is a widely used technique for assessing the locations of active NORs in eukaryotic genomes in general, and in mammalian genomes in particular. However, following a previous study of hedgehog chromosomes, we present here a second example from two gerbil species (Rodentia, Muridae), which have several clear Ag-positive signals that do not correspond to 28S rDNA clusters. Although this pattern may be characteristic of particular genomes displaying unusual heterochromatic features, our study casts doubt upon the reliability and universality of Ag-staining for detecting active NORs.
Role of Ghrelin in the Control of Growth Hormone Secretion in Prepubertal Rats: Interactions with Excitatory Amino Acids
Authors: Pinilla Leonor , Barreiro M. Luz , Tena-Sempere Manuel , Aguilar Enrique
Published: April 2003

Ghrelin is a 28-amino-acid peptide, with an essential n-octanoyl modification at Ser3, that elicits growth-hormone (GH) secretion in rats and humans. At present, the mechanisms of ghrelin action and its interactions with other systems controlling GH secretion remain poorly characterized. In this context, the present study was undertaken to obtain information about ontogeny and possible gender differences in the GH-releasing activity of ghrelin, and to delineate its primary site(s) of action at the hypothalamus and/or pituitary. In addition, the interactions between ghrelin and other relevant signals in the control of GH secretion, such as excitatory amino acids (EAAs), nitric oxide (NO) and serotonin, were assessed. Experiments were carried out in infantile-prepubertal animals, when GH pulsatility is not yet established. Systemic administration of ghrelin (25 nmol/rat, i.p.) to 5-, 10- and 23-day-old male and female rats increased plasma GH levels from day 10 onwards. This action was NO dependent, since it disappeared in 23-day-old males after pretreatment with an inhibitor of NO synthase (NAME). Similarly, central infusion of ghrelin (3 nmol/rat, i.c.v.) elicited GH responses in 10- and 23-day-old animals significantly higher than after systemic administration. By contrast, in vitro challenge of pituitary tissue with increasing doses of ghrelin (10–9–10–7M) failed to enhance GH release into the incubation medium, whereas stimulation with GH-releasing hormone (GHRH; 10–7M) or GHRP-6 (10–7M) was effective. Finally, effects of ghrelin were blocked by pretreatment with MK-801 and NBQX antagonists of EAA ionotropic receptors and after manipulation of endogenous serotoninergic tone. In addition, the potent releasing activity of EAA agonists NMDA and AMPA was blunted by pretreatment with D-Lys3-GHRP-6, a selective antagonist of the cognate ghrelin receptor, i.e. the GH-secretagogue receptor. In conclusion, our results demonstrate that GH-releasing activity of ghrelin appears early in the infantile period, is NO dependent and involves a primary hypothalamic site of action. The data also demonstrate for the first time the existence of a cross-talk between ghrelin and other neurotransmitter systems, such as EAAs and serotonin, in precise control of GH secretion.
Eluate Derived by Extracorporal Antibody-Based Immunoadsorption Elevates the Cytosolic Ca2+ Concentration in Podocytes via B2 Kinin Receptors
Authors: Fischer Karl-Georg , Huber Tobias Bruno , Henger Anna , Fink Edwin , Schwertfeger Eckhard , Rump Lars Christian , Pavenstädt Hermann
Published: April 2003

Background/Aim: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported. Methods: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca2+ concentration ([Ca2+]i) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay. Results: FSGS eluates increased the [Ca2+]i levels concentration dependently (EC50 0.14 mg/ml; n = 3–19). 1 mg/ml eluate increased the [Ca2+]i values reversibly from 82 ± 12 to 1,462 ± 370 nmol/l, and then they returned back to 100 ± 16 nmol/l (n = 19). The eluate-induced increase of [Ca2+]i consisted of an initial Ca2+ peak followed by a Ca2+ plateau which depended on the extracellular Ca2+ concentration. The eluate-induced increase of [Ca2+]i was inhibited by the specific B2 kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC50 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on [Ca2+]i. A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent [Ca2+]i increase in podocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations. Conclusion: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the [Ca2+]i level of podocytes via B2 kinin receptors.