bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Frequency Somatosensory Thalamocortical Oscillations and Psychopathology in Schizophrenia
Authors: Norra Christine , Waberski Till Dino , Kawohl Wolfram , Kunert Hanns Jürgen , Hock Dorothee , Gobbelé René , Buchner Helmut , Hoff Paul
Published: March 2004

Human cortical somatosensory evoked potentials (SEPs), which are presumably generated in afferent thalamocortical and early cortical fibers, reveal a burst of superimposed early (N20) high-frequency oscillations (HFOs), around 600 Hz. There is increasing evidence of an imbalance of thalamocortical systems in schizophrenic patients. In order to assess correlations between somatosensory evoked oscillations and symptoms of schizophrenia, we investigated median nerve SEPs in 20 inpatients and their age-matched and gender-matched healthy controls using a multichannel EEG. Dipole source analysis and wavelet transformation were performed before and after application of a 450-Hz high-pass filter. In schizophrenics, the maximum HFOs occurred with a significantly prolonged latency. There was also a higher amplitude (energy) in the low-frequency range of the N20 component compared with the controls. Importantly, amplitudes (energy) of HFOs were inversely correlated with symptoms of formal thought disorder and delusions. Alterations of the thalamocortical somatosensory signal processing in schizophrenia with absence of an early HFO – assumed to be of inhibitory nature – could indicate a dysfunctional thalamic inhibition with increased amplitudes of N20, paralleled by enhanced positive schizophrenic symptoms.
Platelet α2-Adrenoreceptors in Obsessive-Compulsive Disorder
Authors: Marazziti Donatella , Baroni Stefano , Masala Irene , Giannaccini Gino , Mungai Francesco , Di Nasso Elena , Cassano Giovanni B.
Published: March 2004

The need for new therapeutic targets in obsessive-compulsive disorder (OCD) prompted us to investigate the putative involvement of the norepinephrine system by means of platelet α2-adrenoreceptors in a group of 20 OCD patients and healthy control subjects, matched for sex and age. Platelet membranes were prepared according to standard protocols, and the α2-adrenoreceptors were measured by means of the specific binding of [3H]rauwolscine, a highy selective antagonist for this receptor subtype. The results, which showed no difference between patients and controls in the binding parameters of [3H]rauwolscine, suggest that the role of α2-adrenoreceptors, as reflected by the platelet model, is quite limited in OCD and may, perhaps, be restricted purely to some symptoms or dimensions such as motricity, as suggested by the higher density of α2-adrenoreceptors found in patients concomitantly affected by motor tics.
Augmentation of the Development of Behavioral Tolerance to Cannabinoid Administration through Pavlovian Conditioning
Authors: Hill Matthew N. , Gorzalka Boris B. , Choi Joyce W.
Published: March 2004

This investigation examined the effects, in female rats, of a Pavlovian conditioning paradigm on the development of tolerance to hypolocomotion induced by the cannabinoid agonist HU-210. Rats were administered HU-210 and placebo in either an associative or a nonassociative fashion. The results indicated that rats in the associative paradigm developed tolerance significantly faster than those in the nonassociative group (p < 0.03). Subsequently, once tolerance had developed, the associative group of rats was administered HU-210 and placebo in the opposite environments. There were no differences found in locomotion between the CS+ and CS– environments following administration of HU-210. However, when the placebo was administered in the CS+ environment, there was a trend towards increased activity levels (p = 0.06), suggesting withdrawal-like behavior. These findings indicate that the underlying physiological mechanisms of tolerance development in the cannabinoid system are hastened by conditioning, but that these physiological alterations are not contingent upon the associative parameters used for drug administration.
Whole Deletion of CYP2A6 Gene (CYP2A6*4C) and Smoking Behavior
Authors: Iwahashi Kazuhiko , Waga Chikako , Takimoto Takahiro
Published: March 2004

The relationship between nicotine metabolism of CYP2A6 and the smoking behavior in a Japanese population was investigated. The CYP2A6 genotypes were determined by the PCR method. There was a significant difference in the frequency of the CYP2A6*4C allele, which is a whole deleted allele for the human CYP2A6 gene, between smokers and nonsmokers. The frequency of the CYP2A6*4C allele was higher in nonsmokers than in smokers, whereas the frequency of CYP2A6*1A/*1B heterozygotes with a higher activity of nicotine metabolism was lower. In this study it was suggested that the CYP2A6*4C allele may prevent the carrier from smoking and the CYP2A6*1A/*1B heterozygote may be at risk for developing smoking behavior.
Genetics and Pathophysiology of Hyperinsulinism in Infancy
Authors: Cosgrove Karen E. , Shepherd Ruth M. , Fernandez Eva M. , Natarajan Anuja , Lindley Keith J. , Aynsley-Green Albert , Dunne Mark J.
Published: March 2004

Hyperinsulinism in infancy (HI) is a condition of neonates and early childhood. For many years the pathophysiology of this potentially lethal disorder was unknown. Advances in the genetics, histopathology and molecular physiology of this disease have now provided insights into the causes of β-cell dysfunction and revealed levels of diversity far in excess of our previous knowledge. These include defects in ion channel subunit genes and mutations in several enzymes associated with β-cell metabolism and anaplerosis. In most cases, β-cell pathophysiology leads to an alteration in the function of ATP-sensitive K+ channels. This can manifest as ‘channelopathies’ of KATP channels through gene defects in ABCC8 and KCNJ11 (Ch.11p15); or as a result of ‘metabolopathies’ through defects in the genes encoding glucokinase (GCK, Ch.7p15–p13), glutamate dehydrogenase (GLUD1, Ch.10q23.3) and short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADHSC, Ch.4q22–q26). This review focuses upon the relationship between the causes of HI and therapeutic options.
Variability in Cytochrome P450-Mediated Metabolism of Cardiovascular Drugs: Clinical Implications and Practical Attempts to Avoid Potential Problems
Authors: Molden Espen
Published: March 2004

Cytochrome P450 (CYP) enzymes play an important role in the turnover of more than 50 cardiovascular drugs (CVDs). Variable CYP activities due to genetic polymorphism or drug interactions are important sources of variability in systemic exposure of many of these drugs. The therapeutic implications are in most cases an increased response (effect/side effects) in patients with genetically determined decreased/deficient metabolic activity or during concurrent use of CYP inhibitors. Special attention with regard to safety should be paid to several coumarin-type anticoagulants, antiarrhythmics, β-receptor antagonists and HMG-CoA reductase inhibitors (statins). Prevention of potential clinical problems associated with CYP variability is easily achieved using equally effective therapeutic alternatives that are not dependent on CYP metabolism. However, if ‘CYP sensitive’ CVDs are either the preferred or only therapeutic alternatives, restrictive use of inhibitors is advisable, whereas patient genotyping prior to treatment might be a helpful tool to apply rational (individual) doses for certain agents.
Spectral Doppler Index Mapping of the Umbilicoplacental Circulation and Pregnancy Outcome
Authors: Haberman Shoshana , Bracero Luis A. , Byrne Daniel W.
Published: March 2004

Objective: To determine the value of Doppler measurements obtained by a new multigate Doppler modality, the spectral Doppler index mapping (SDIM) technique, to predict adverse outcome among pregnant women with normal conventional umbilical artery (UA) Doppler indices. Design: A cross-sectional prospective cohort study. Subjects: 183 women with well-dated singleton pregnancies who underwent prenatal ultrasound examination between 18 and 40 weeks of gestation were included in the study. At the time of the initial Doppler examination, all patients had normal UA and uterine artery Doppler indices, size appropriate for gestational age, no evidence of fetal anomalies or fetal distress. Methods: SDIM data included the distribution curves of the pulsatility indices (PI) as well as the mean of the PI detected in the placenta and in the umbilical cord. The mean PI values were also calculated using conventional spectral Doppler sonography. Logistic regression analysis was used to control for gestational age while assessing various Doppler variables in predicting outcome. Results: Adverse outcomes occurred in 26.6% of the pregnancies. In pregnancies with adverse outcome, the umbilicoplacental PI gradient was significantly lower (0.10 vs. 0.28, p < 0.003), the maximum intraplacental PI value was higher (1.28 vs. 1.16, p = 0.031), and there was a greater proportion with skewed UA distribution curves. Using forward stepwise logistic regression to compare the predictive value of the conventional Doppler ultrasound with SDIM, we found that the most accurate predictors of adverse outcome were the maximum intraplacental PI value (p < 0.028), skewed distributions (p = 0.002) and the gradient between the umbilical and intraplacental PI distributions (p = 0.006). Conclusions: Our results suggest that the SDIM system may enhance the ability of Doppler technology to predict obstetrical outcomes in patients with normal UA Doppler indices.
Transient Hyper-17-OHPnemia Unrelated to Cross-Reactions with Residual Fetal Adrenal Cortex Products
Authors: Mizuno Haruo , Ohro Yoichiro , Sugiyama Yukari , Ito Tetsuya , Hasegawa Tomonobu , Homma Keiko , Ueshiba Hajime , Ono Makoto , Togari Hajime
Published: March 2004

Objective: To clarify the pathogenesis of transient hyper-17α-hydroxyprogesteronemia, we initiated a laboratory investigation in a pre-term infant with persistently high serum 17α-hydroxyprogesterone (17-OHP) until 2 months of age. Methods: Serum 17-OHP level was measured by high-performance liquid chromatography and radioimmunoassay, and gene analysis of CYP21A2 (21-hydroxylase) was performed. Result: Serum 17-OHP level on the 29th day of life was 25.4 ng/ml, and the urinary steroid profile showed low pregnanetriolone. Gene analysis of 21-hydroxylase disclosed no mutation, and 17-OHP normalized by 3 months of age without specific treatment. Conclusion: Transient elevations in 17-OHP, which do not appear related to cross-reactions with products of a residual fetal adrenal cortex, may occur in the first few months of life.
Effects of Glycoprotein IIb/IIIa Receptor Inhibition with Tirofiban on Minor Myocardial Damage in Angiographically Successful Percutaneous Coronary Angioplasty
Authors: Okmen Ertan , Sanli Arda , Uyarel Huseyin , Dayi Sennur , Tartan Zeynep , Cam Nese
Published: March 2004

Aim: The aim of the study was to evaluate the effects of glycoprotein (GP) IIb/IIIa inhibition on minor myocardial injury characterized by cardiac troponin I (cTn-I) and cardiac troponin T (cTn-T) elevation after elective successful percutaneous coronary intervention (PCI). Methods: The study consisted of 119 consecutive patients scheduled for elective coronary balloon angioplasty with or without stent implantation. Sixty-three patients (mean age 58 ± 9.4 years) were randomized to receive standard therapy, including preprocedural aspirin, ticlopidine and intravenous heparin, and 56 patients (mean age 55 ± 9.6 years) were randomized to additionally receive intravenous tirofiban infusion. cTn-I, cTn-T and CK-MB were measured before and immediately after the procedure, and every 6 h for the first 24 h. A total of 128 stenoses were treated with PCI. Seventy of these lesions were in the standard therapy group and 58 in the tirofiban group. Results: The frequency of postprocedural abnormal cTn-I levels was significantly higher in the standard therapy group than that in the tirofiban group (37 vs. 16%; p = 0.017). Postprocedural cTn-T elevation occurred in 23% of patients in the standard therapy group and in 8% of patients in the tirofiban group (p = 0.037). The frequencies of CK-MB elevation higher than the upper limit of normal (ULN), and higher than 2 times the ULN were not significantly different between the standard therapy and tirofiban groups (12 vs. 4%, and 7 vs. 2%, respectively). Conclusions: GP IIb/IIIa inhibition may reduce the incidence of minor myocardial injury, which may also be a possible mechanism in reducing long-term cardiac events after PCI.
Angiographic Outcome in Multivessel Disease (GABI II Study) Using New Coronary Device Interventions and Comparison with GABI I Trial Results
Authors: Dietz Ulrich , Baldus Stephan , Rupprecht Hans-Jürgen , Küchler Robert , vom Dahl Jürgen , Ekinci Okan , Hamm Christian
Published: March 2004

Percutaneous coronary interventions using stents were investigated in patients with multivessel disease. Acute and long-term results were compared with those of the German Angioplasty Bypass Surgery Investigation trial in a prospective multicenter study. The study included 134 patients in whom 277 lesions were treated. Angiographic success and procedural success were achieved in 268 of 277 lesions (97%) and 118 of 134 patients (88%), respectively. Control angiography performed in 90 of 118 eligible patients (76%) exhibited restenosis in 43 of 182 lesions (24%). Multivariate regression analysis found that a diffuse lesion, the lesion and stent length, and the final luminal diameter were predictive for restenosis. Thus, immediate and long-term results of multivessel coronary intervention utilizing stents were improved compared to percutaneous transluminal coronary angioplasty of multivessel lesions. However, there is still need for improvement of long-term results, especially in particular lesion subgroups.
N-Terminal Pro-Brain Natriuretic Peptide Levels in Patients with Non-ST-Elevation Myocardial Infarction
Authors: Zeller M. , Cottin Y. , Laurent Y. , Danchin N. , L’Huillier I. , Collin B. , Desgrés J. , Ravisy J. , Janin-Manificat L. , Makki H. , Jolak M. , Beer J.C. , Dentan G. , Gambert P. , Wolf J.E.
Published: March 2004

Methods and Results: 101 patients hospitalized for acute non-ST-elevation myocardial infarction (NSTEMI) were included in the study. Median N-terminal fragment of the brain natriuretic peptide (BNP) prohormone (Nt-proBNP) plasma level was 136 (40–335) pmol/l. Patients with increasing levels of troponin I [from low (0.1–10 ng/ml), intermediate (10–40 ng/ml) to high (≧40 ng/ml) levels] had significantly increased levels of Nt-proBNP (p < 0.05). High-risk patients classified by a high PURSUIT score (i.e. supramedian) had significantly increased Nt-proBNP levels compared to patients with low scores (p < 0.001). Moreover, patients with inhospital events (death, recurrent MI or clinical heart failure: 27%) had significantly increased median levels of Nt-proBNP compared to event-free patients (184 vs. 105 pmol/l, p = 0.02). Conclusion: Our data in an unselected population of NSTEMI patients indicate that high levels of circulating Nt-proBNP levels are associated with an increased risk of early cardiovascular events.
Admission Predictors of In-Hospital Mortality and Subsequent Long-Term Outcome in Survivors of Ventricular Fibrillation Out-of-Hospital Cardiac Arrest: A Population-Based Study
Authors: Bunch Thomas J. , West Colin P. , Packer Douglas L. , Panutich Michael S. , White Roger D.
Published: March 2004

Background: Survival following out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation (VF) is poor and dependent on a rapid emergency response system. Improvements in emergent early response have resulted in a higher percentage of patients surviving to admission. However, the admission variables that predict both short- and long-term survival in a region with high discharge survival following OHCA require further study in order to identify survivors at subsequent highest risk. Methods: All patients with OHCA arrest in Olmsted County Minnesota between 1990 and 2000 who received defibrillation of VF by emergency services were included in the population-based study. Baseline patient admission characteristics in survivor and nonsurvivor groups were compared. Survivors to hospital discharge were prospectively followed to determine long-term survival. Results: Two hundred patients suffered a VF arrest. Of these patients, 145 (73%) survived to hospital admission (7 died within the emergency department) and 79 (40%) were subsequently discharged. Sixty-six (83%) were male, with an average age of 61.9 ± 15.9 years. Univariate predictors of in-hospital mortality included call-to-shock time (6.6 vs. 5.5 min, p = 0.002), a nonwitnessed arrest (75.4 vs. 92.4%, p = 0.008), in-field use of epinephrine (27.8 vs. 93.4%, p < 0.001), age (68.1 vs. 61.9 years, p = 0.017), hypertension (36.1 vs. 14.1%, p = 0.005), ejection fraction (32.4 vs. 42.4, p = 0.012), and use of digoxin (34.9 vs. 12.7%, p = 0.002). Of all these variables, hypertension [hazard ratio (HR) 4.0, 95% CI 1.1–14.1, p = 0.03], digoxin use (HR 4.5, 95% CI 1.3–15.6, p = 0.02), and epinephrine requirement (HR 62.0, 95% CI 15.1–254.8, p < 0.001) were multivariate predictors of in-hospital mortality. Nineteen patients (24%) had died prior to the survey follow-up. Five patients experienced a cardiac death, resulting in a 5-year expected cardiac survival of 92%. Multivariate variables predictive of long-term mortality include digoxin use (HR 3.02, 95% CI 1.80–5.06, p < 0.001), hypertension (HR 2.06, 95% CI 2.12–3.45, p = 0.006), and call-to-shock time (HR 1.18, 95% CI 1.01–1.38, p = 0.038). Conclusion: A combined police/fire/EMS defibrillation program has resulted in an increase of patients surviving to hospital admission after OHCA. This study confirms the need to decrease call-to-shock times, which influence both in-hospital and long-term mortality. This study also identifies the novel demographic variables of digoxin and hypertension, which were also independent risk factors of increased in-hospital and long-term mortality. Identification of these variables may provide utility in identifying those at high-risk of subsequent mortality after resuscitation.
Pericardial Pseudodiverticulum or Pseudoaneurysm due to Rupture of a Cardiac Aneurysm into the Pericardial Sac 48 Years after the First Description
Authors: Riederer Josef
Published: March 2004

A typical sequential course becomes apparent from the clinical features, the electrocardiography, echocardiography, radiological changes as well as angiographic results. This ultimately leads to an unusual complication of transmural myocardial infarction, i.e. the development of a pericardial pseudodiverticulum (less aptly described as pseudoaneurysm or false aneurysm). A timely cardiosurgical intervention may avert the otherwise fatal outcome.
DNA Vaccines Designed to Inhibit Tumor Growth by Suppression of Angiogenesis
Authors: Reisfeld Ralph A. , Niethammer A.G. , Luo Y. , Xiang R.
Published: March 2004

The development of new blood vessels, i.e. angiogenesis, is a rate-limiting step in the development of tumors since tumor growth is generally limited to 1–2 mm3 in the absence of a blood supply. Thus, the inhibition of tumor growth by attacking the tumor’s vascular supply offers a primary target for antiangiogenic intervention by DNA-based vaccines. Here, we describe two novel orally delivered DNA vaccines which suppress tumor angiogenesis and induce a robust cell-mediated immune response that provides for long-lived protection against melanoma, colon, breast and non-small-cell lung carcinoma in mouse model systems. These vaccines, which are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs, are directed against such targets as vascular endothelial growth factor receptor 2 (FLK-1) and transcription factor Fos-related antigen 1 (Fra-1). Both vaccines break peripheral T cell tolerance against these self-antigens and induce a robust T cell-mediated immune response leading to suppression of tumor angiogenesis and resulting in effective suppression of tumor growth and metastases. Such research efforts may open up new possibilities for the rational design of future DNA vaccines effective for the prevention and treatment of cancer.
Subjective Experience of Schizotropic Vulnerability in Siblings of Schizophrenics
Authors: Maggini Carlo , Raballo Andrea
Published: March 2004

Abnormal neuropsychological and cognitive functions in nonpsychotic relatives of schizophrenics are currently the subject of intense interest, mainly because of attention being focused again on the theoretical construct of schizotaxia. Contextually, in recent years the issues of subjective experiences have once again become central and respectable topics in psychopathological research. Among self-experiential disturbances, basic symptoms (BS), stemming from Jaspersian phenomenological psychopathology, are considered the first, protopathic, subjective reverberation of the neurobiological deficit of schizophrenia. Thus BS are expected to be detectable in nonpsychotic relatives of schizophrenia patients. The aim of the present study was to compare the degrees of such anomalous subjective experiences, assessed in siblings of schizophrenic patients, schizophrenia spectrum patients (schizotypals and schizophrenics) and nonclinical controls. Different profiles of BS were obtained in the samples. An increasing gradient of BS ranging from nonclinical to clinical samples, with unaffected siblings in the intermediate position, occurred for some of the BS clusters (i.e. ‘thought, language, perception and motor disturbances’ and ‘impaired bodily sensations’). Other BS clusters (i.e. ‘disorders of emotion and affect’ and ‘increased emotional reactivity’) turned out to be typical of the clinical subgroups, whereas an enhanced tolerance to normal stress significantly distinguished the sibling specimen from the other ones. The heterogeneity of these patterns suggests that BS constellations may be underpinned by different psychopathological processes and that cognitive and bodily BS may be clinical target phenotypes for schizotropic liability screening.
Psychopathological Description of Hyperventilation-Induced Panic Attacks: A Comparison with Spontaneous Panic Attacks
Authors: Nardi Antonio E. , Lopes Fabiana L. , Valença Alexandre M. , Nascimento Isabella , Mezzasalma Marco A. , Zin Walter A.
Published: March 2004

Our aim was to describe the clinical features of hyperventilation-induced panic attacks (HPA) in panic disorder patients – DSM-IV – and to compare them with their spontaneous panic attacks and with spontaneous panic attacks in panic disorder (PD) patients not sensible to the hyperventilation challenge test. We reexamined 88 previously studied PD patients when they were submitted to a hyperventilation challenge test. They were induced to hyperventilate (30 breaths/min) for 4 min and anxiety scales were applied before and after the test. A total of 51.1% (n = 45) PD patients had a panic attack after hyperventilating – HPA (χ2 = 13.11, d.f. = 1, p = 0.017). The clinical symptoms of the most severe panic attack were recorded by the HPA patient and by the PD patients not sensible to this test (non-HPA; n = 43, 48.9%) in a diary during a 1-week period and then compared. The HPA group had more respiratory symptoms (χ2 = 15.26, d.f. = 1, p < 0.001), fulfilling the criteria for the respiratory PD subtype (75.6%), the disorder started later (Mann-Whitney, p < 0.001), had a higher familial prevalence of PD (χ2 = 19.45, d.f. = 1, p = 0.036), and had more previous depressive episodes (χ2 = 18.74, d.f. = 1, p < 0.001). The HPA group had similar symptomatology in spontaneous attacks and HPA. The HPA group may be regarded as a subgroup of the respiratory panic disorder subtype with diagnostic and therapeutic implications.
Life Events and Psychopathology in a Group of Suicide Attempters
Authors: Osvath Peter , Vörös Viktor , Fekete Sandor
Published: March 2004

Researchers examined the incidence of negative life events and associated these events with psychological scales (depression, hopelessness, self-esteem and state-trait anger) in a group of suicide attempters (n = 101) within the framework of the WHO/EURO Multicenter Study on Suicidal Behavior. Certain negative life events (especially relationship problems and physical/mental abuse in childhood) turned out to be the main indicators of severe mental problems in the family of the attempters (e.g. addiction, self-destructive behavior or psychiatric hospitalization). Significant positive correlations were found between the number of events and some psychopathological symptoms like depression, hopelessness, anger and lack of self-esteem. The role of stressful life events in suicidal behavior is emphasized. Particularly traumatic events (e.g. abuse in childhood) may be involved in the development of psychological and/or biological vulnerability (stress-diathesis model) and cognitive dysfunction. Therefore, in the psychotherapy of suicide attempters, it is essential to explore and discuss negative life events.
Which Types of Aggressive Behaviour Are Associated with Suicidal and Self-Injurious Behaviour at the Time of Admission?
Authors: Grube Michael
Published: March 2004

Background: In psychiatry and psychotherapy, dealing with aggressiveness and autoaggressiveness is of great importance. Our aim was to find a link between overt aggressive and autoaggressive behaviour, which could be readily observed. Sampling and Methods: We investigated the frequency, type and intensity of aggressive, suicidal and self-injurious behaviour exhibited by 521 successively admitted psychiatric patients at the time of admission with the help of a standardised instrument (Social Dysfunction and Aggression Scale). The Social Dysfunction and Aggression Scale enables the investigation of 9 different types of overt aggressive behaviour and 2 different types of autoaggressive behaviour (suicidal vs. self-injurious behaviour). After calculating correlations between single variables, we attempted to estimate the predictive value of the different types of aggressive behaviour for suicidal and self-injurious behaviour by using ordinal regression models. In addition, the categorical information of our data was evaluated by loglinear analyses. Results: Our study showed that all degrees of aggressiveness (low, moderate, high), which are exhibited in different types of aggressive behaviour, were linked to an increased risk of self-injurious behaviour. No correlation was found, however, between overt aggressive behaviour and suicidal behaviour. Only in the subgroup of depressive disorders did we establish that the risk of aggressive behaviour was decreased and the risk of suicidal behaviour was increased at the time of admission. Conclusions: The strong relationship between aggressive behaviour and self-injurious behaviour has previously been described in specific diagnostic subgroups, but not yet in a heterogeneous population of psychiatric in-patients from a defined catchment area. We, therefore, conclude that the link between aggressive and self-injurious behaviour could be a general one. Exhibiting aggressive behaviour and self-injurious behaviour within a short time span may be the result of an increased or disinhibited aggressive potential, which is independent of a specific diagnosis. As such, it possibly represents the general consequence of a highly altered state of mind and does not seem to be linked to a specific diagnostic subgroup. In psychiatric emergency situations, the previously described close relationship between aggressive and self-injurious behaviour should be taken into account.
Circulatory and Respiratory Complications of Carbon Dioxide Insufflation
Authors: Gutt C.N. , Oniu T. , Mehrabi A. , Schemmer P. , Kashfi A. , Kraus T. , Büchler M.W.
Published: March 2004

Background: Although providing excellent outcome results, laparoscopy also induces particular pathophysiological changes in response to pneumoperitoneum. Knowledge of the pathophysiology of a CO2 pneumoperitoneum can help minimize complications while profiting from the benefits of laparoscopic surgery without concerns about its safety. Methods: A review of articles on the pathophysiological changes and complications of carbon dioxide pneumoperitoneum as well as prevention and treatment of these complications was performed using the Medline database. Results: The main pathophysiological changes during CO2 pneumoperitoneum refer to the cardiovascular system and are mainly correlated with the amount of intra-abdominal pressure in combination with the patient’s position on the operating table. These changes are well tolerated even in older and more debilitated patients, and except for a slight increase in the incidence of cardiac arrhythmias, no other significant cardiovascular complications occur. Although there are important pulmonary pathophysiological changes, hypercarbia, hypoxemia and barotraumas, they would develop rarely since effective ventilation monitoring and techniques are applied. The alteration in splanchnic perfusion is proportional with the increase in intra-abdominal pressure and duration of pneumoperitoneum. Conclusion: A moderate-to-low intra-abdominal pressure (<12 mm Hg) can help limit the extent of the pathophysiological changes since consecutive organ dysfunctions are minimal, transient and do not influence the outcome.
The Biagram Vector: A Graphical Relation between Reactance and Phase Angle Measured by Bioelectrical Analysis in Infants
Authors: Savino F. , Cresi F. , Grasso G. , Oggero R. , Silvestro L.
Published: March 2004

Background: Biagram vector is derived by plotting direct measurements of reactance and phase angle from the analyzer, which are not dependent on anthropometric characteristics of the subject and it can be considered an emerging method for evaluating the nutritional status in clinical practice. Aim: To calculate and plot the Biagram vector in a sample of healthy infants in their first year of life. Methods: 174 healthy infants (99 male, 75 female) aged under 1 year, born at full term and adequate for gestational age, were enrolled in a cross-sectional study. The sample was divided into three age groups: 0–3.99 months (group A), 4–7.99 months (group B), and 8–11.99 months (group C). Bioelectric impedance analysis (BIA) was performed by a tetrapolar single frequence phase-sensitive impedance analyzer (STA/BIA; Akern Srl, Firenze, Italy). Results: Biagram vector showed an increasing trend (p < 0.05) in the first year of life (group A: 27.9 ± 12.6; group B: 32.1 ± 9.7; group C: 37.2 ± 9.5). Females showed Biagram vector values significantly higher than males in group A (34.7 ± 15.0 vs. 24.0 ± 9.1; p < 0.05). 95% confidence ellipses of Biagram vector for each age group were calculated and plotted and a comparison of our results with published data calculated in older children was conducted. Conclusion: The bivariate analysis of BIA measurements, plotted as a vector in relation to the age, showed an increasing trend with a higher gain rate under 1 year with respect to the following age periods. These data could reflect the variation of body composition in the first years of life and could be of interest to assess the nutritional status for clinical practice.
Carnitine Supplementation Fails to Maximize Fat Mass Loss Induced by Endurance Training in Rats
Authors: Saldanha Aoki Marcelo , Rodriguez Amaral Almeida André Luís , Navarro Francisco , Bicudo Pereira Costa-Rosa Luís Fernando , Pereira Bacurau Reury Frank
Published: March 2004

Background/Aims: Carnitine is a co-factor of the enzymatic system involved in long chain fatty acid transport across the mitochondrial membrane. This physiological role of carnitine raised the hypothesis that this compound could act as a ‘fat burner’ by optimizing fat oxidation and consequently reducing its availability for storage. Our aim was to verify whether carnitine supplementation could maximize fat mass loss in trained rats. Methods: Male Wistar rats (200 g) were divided into four groups: control (C), sedentary supplemented (S), trained (T) and trained supplemented (TS). The training protocol consisted of bouts of swimming exercise (60 min·day–1) for 6 weeks. During the last 14 days, before sacrifice, the supplemented groups received a daily dose of 28 mg· kg–1 of L-carnitine. Carcass fat content, weight and fat content of adipose tissues were evaluated in all experimental groups. Results: Our results indicate that carnitine feeding, per se, failed to promote fat mass loss. Endurance training successfully induced a decrease in the fat content in the carcass (28%) and the weight of adipose tissues (retroperitoneal and mesenteric depots by 41 and 20%, respectively) in comparison to C. Despite the augmented carnitine content in the soleus mitochondria (2-fold) observed in TS, the higher content did not maximize the fat loss induced by endurance training. Conclusions: Our data strongly suggest that endurance training, rather than carnitine content, is the major factor involved in fat mass loss.
Dietary Iron Intake and Iron Status of German Female Vegans: Results of the German Vegan Study
Authors: Waldmann Annika , Koschizke Jochen W. , Leitzmann Claus , Hahn Andreas
Published: March 2004

Background: As shown in previous studies vegetarians and especially vegans are at risk for iron deficiency. Our study evaluated the iron status of German female vegans. Methods: In this cross-sectional study, the dietary intakes of 75 vegan women were assessed by two 9-day food frequency questionnaires. The iron status was analyzed on the basis of blood parameters. Results: Mean daily iron intake was higher than recommended by the German Nutrition Society. Still 42% of the female vegans <50 years (young women, YW) had a daily iron intake of <18 mg/day, which is the recommended allowance by the US Food and Nutrition Board. The main dietary sources of iron were vegetables, fruits, cereals and cereal products. Median serum ferritin concentrations were 14 ng/ml for YW and 28 ng/ml for women ≧50 years (old women, OW). In all, 40% (tri-index model (TIM) 20%) of the YW and 12% (TIM 12%) of the OW were considered iron-deficient based on either serum ferritin levels of <12 ng/ml or a TIM. Only 3 women had blood parameters which are defined as iron deficiency anemia. Correlations between serum ferritin levels and dietary factors were not found. Conclusion: Although the mean iron intake was above the recommended level, 40% (TIM 20%) of the YW were considered iron-deficient. It is suggested that especially YM on a vegan diet should have their iron status monitored and should consider taking iron supplements in case of a marginal status.
Impact of Feeding High-Iron Rice on Plasma Iron, Hemoglobin and Red Blood Cell Variables of Early-Weaned Piglets
Authors: Schaffer Sebastian , Pallauf Josef , Krawinkel Michael B.
Published: March 2004

Severe iron deficiency is a major nutritional problem encountered throughout the world. We assessed the effect of a conventionally bred, high-iron rice variety on plasma iron, hemoglobin, and red blood cell variables of early-weaned piglets during a 33-day feeding trial. 26-day-old male piglets were assigned to 3 treatment groups: group 1 = low-iron rice + low-iron supplementary feed; group 2 = high-iron rice + low-iron supplementary feed, and group 3 = low-iron rice + high-iron supplementary feed. Plasma iron, hemoglobin and red blood cell variables were measured on days 8, 16, 23, 30, and 33. Feed intake and weight gain were not significantly different between study groups. No significant differences in the iron-related parameters analyzed were found between the piglets of groups 1 and 2, except in red blood cells. Modifications regarding study design, study duration and subject’s growth rate are recommended to increase the possibility of detecting changes in the iron status triggered by diets having small differences in dietary iron.
Association of Pontine Small Infarction (Lacuna) with Disturbance of Postural Stability
Authors: Nagahori T. , Hirashima Y. , Umemura K. , Nakagawa H. , Kamisaki Y. , Origasa H. , Endo S.
Published: March 2004

Neuronal degeneration within the brainstem has been reported in patients with impaired postural stability. However, the functional significance of these abnormalities is unknown at present. In the present study, we evaluated the relationship between the presence of pontine lacunae and postural stability measured by stabilometry. A total of 209 consecutive patients without neurological signs were divided into three groups according to the territory of lacunae on magnetic resonance imaging: (1) non-lacunar group, (2) pontine lacunar group, and (3) non-pontine lacunar group. Stabilometry was performed and statokinesigram measures including each Romberg quotient were compared among the three groups. Using multivariate analysis, postural stability was found to be disturbed in the pontine lacunar group compared with the other groups. The data of stabilometry in this group were compatible with disturbance of the central controlling system for keeping postural stability. Pontine lacuna is associated with patients with postural instability. This result may be related to the deterioration of the central coordination system for posture and locomotion.
Hepatitis B Virus-Associated Nephropathy
Authors: Bhimma Rajendra , Coovadia Hoosen Mohamed
Published: March 2004

A direct causal association between hepatitis B virus (HBV) infection and the development of nephropathy remains controversial. Epidemiological studies have shown that chronic carriage of HBV in some individuals (particularly children) leads to the development of nephrotic syndrome with a strong male predominance, the commonest histological type being membranous nephropathy (MN). Spontaneous clearance of HBV antigens (particularly the HBeAg) leads to abrogation of proteinuria. The isolation of immune complexes in the kidney suggests that the pathogenesis of the disease may have an immune-complex basis. Recent studies showing expression of HBV viral antigens in kidney tissue suggest direct viral-induced pathological alterations and chronic immunologic injury. Biosocial studies have detected no correlation between HBV carriage and proteinuria using both quantitative and qualitative urinary protein analysis. Genetic studies of HLA class I and II genes showed a predisposition to MN but no similar correlation in those with milder degrees of proteinuria. These findings suggest that milder proteinuria is unrelated to HBV carriage or genetic factors but the development of nephropathy, particularly MN, in patients with chronic HBV carriage (HBsAg and/or HBV DNA positive) is based on an interaction of virus and host factors. Although the natural history of the disease tends to remission with preservation of renal function, there is considerable morbidity and a small but significant mortality. Use of naturally occurring cytokines (such as interferon-α2b) and other candidate therapies accelerates clearance of the virus and proteinuria. The most effective tool in reducing the incidence of the disease is the use of HBV vaccines.
Transvascular Passage of Macromolecules into the Peritoneal Cavity of Normo- and Hypothermic Rats in vivo: Active or Passive Transport?
Authors: Rosengren Bert-Inge , Carlsson Ola , Venturoli Daniele , al Rayyes Osama , Rippe Bengt
Published: March 2004

During the last decades there has been a debate regarding whether transvascular protein transport is an active (transcytosis) or a passive (porous) process. To separate cooling-sensitive transcytosis from passive transport processes between blood and peritoneal fluid, we induced hypothermia in rats in vivo, reducing their body temperature to 19°C. Control rats were kept at 37°C. Either human albumin, or IgG, or IgM, or LDL, radiolabeled with 125I, was given intra-arterially together with 51Cr-EDTA. During tracer administration, a 2-hour peritoneal dialysis dwell was performed. Clearance of the tracers to dialysate, and the permeability-surface area coefficient (PS) for 51Cr-EDTA and glucose were assessed. During cooling, mean arterial blood pressure (MAP) was reduced to 40% of control and plasma viscosity increased by 48.5%, while peritoneal blood flow was reduced to 10%. At 19°C, clearance of albumin to dialysate fell from 9.30 ± 1.62 (SEM) to 3.13 ± 0.28 µl/min (p < 0.05), clearance of IgG from 6.33 ± 0.42 to 2.54 ± 0.12 µl/min (p < 0.05), clearance of IgM from 3.65 ± 0.33 to 1.10 ± 0.12 µl/min (p < 0.05), and clearance of LDL from 3.54 ± 0.20 to 0.73 ± 0.06 µl/min (p < 0.05). The fall in PS for 51Cr-EDTA was from 0.320 ± 0.01 to 0.075 ± 0.003 ml/min (p < 0.05), and that for glucose from 0.438 ± 0.02 to 0.105 ± 0.01 ml/min (p < 0.05). Tissue cooling reduced large solute transport largely in proportion to the cooling-induced reductions of MAP (to 40%), and the concomitant increase in viscosity (to 67%), i.e. to ≈20–30% (0.40 × 0.67) of control, though LDL clearance was reduced further. The fall in small solute PS, in excess of the viscosity effect, mirrored the fall in peritoneal blood flow occurring during hypothermia. In conclusion, the good correlation of predicted to calculated changes suggests that the overall transendothelial macromolecular passage in vivo occurs passively, and not due to active processes.
Increased Expression of Endothelin-Converting Enzyme-1c Isoform in Response to High Glucose Levels in Endothelial Cells
Authors: Keynan Shoshana , Khamaisi Mogher , Dahan Rachel , Barnes Kay , Jackson Carolyn D. , Turner Anthony J. , Raz Itamar
Published: March 2004

Endothelin-1 (ET-1) is both a potent vasoconstrictor and mitogenic factor that has been implicated as a cause of the micro- and macrovascular complications of diabetes mellitus. The pathway by which the high-glucose environment of diabetes mediates increased levels of endothelins has not been completely elucidated but appears to involve endothelin-converting enzyme (ECE-1), which converts inactive big ET-1 to active ET-1 peptide. To determine the effect of high glucose concentrations on the expression of ECE-1, hybrid endothelial cells (EA.hy926) and human umbilical vein endothelial cells (HUVEC) were both grown in various glucose concentrations. There was a 2-fold increase in ECE-1 immunoreactivity in the EA.hy926 cell line growing in medium containing 22.2 versus 5.5 mmol/l glucose after 24 h, which rose to greater than 20-fold after 5 days. Similar results were seen with HUVEC. Bradykinin or NG-nitro-L-arginine methyl ester did not change the effect of high glucose on ECE-1 protein expression. High glucose induced a 72 and 41% increase in total protein kinase C (PKC) activity in both EA.hy926 cells and HUVEC, respectively, and a 39, 49 and 109% elevation in PKC β1, β2 and δ expression, respectively, in EA.hy926 cells. The increase in ECE-1 expression was inhibited in both cell cultures by GF109203X (5 µmol/l), a general PKC inhibitor, while addition of 10 nmol/l phorbol myristic acid to EA.hy926 cells or HUVEC growing on medium containing 5.5 mmol/l glucose increased ECE-1 expression to a level similar to that of cells conditioned in high glucose. Human ECE-1 protein exists in four different isoforms, termed 1a, 1b, 1c and 1d. Northern blot analysis revealed that only ECE-1c isoform mRNA levels increased. Immunohistochemical staining of EA.hy926 cells grown in high glucose concentrations demonstrated an increase in the ECE-1c isoform, which occurred mainly in the plasma membrane. These results showed that the PKC pathway may play an important role in the glucose-mediated induction of ECE-1 expression. The main isoform to increase in response to high glucose was ECE-1c. This enzyme may be one of the factors contributing to the elevated ET-1 peptide levels observed in diabetes.
Unique, Highly Proliferative Growth Phenotype Expressed by Embryonic and Neointimal Smooth Muscle Cells Is Driven by Constitutive Akt, mTOR, and p70S6K Signaling and Is Actively Repressed by PTEN
Authors: Mourani Peter M. , Garl Pamela J. , Wenzlau Janet M. , Carpenter Todd C. , Stenmark Kurt R. , Weiser-Evans Mary C.M.
Published: March 2004

Background—

At distinct times during embryonic development and after vascular injury, smooth muscle cells (SMCs) exhibit a highly proliferative, serum-independent growth phenotype. The aim of the present study was to evaluate the functional role of S6 ribosomal protein (S6RP) and upstream positive and negative regulators in the control of SMC serum-independent growth.

Methods and Results—

We previously reported increased expression of S6RP mRNA was associated with this unique growth phenotype. Using immunohistochemistry and Western blot analysis, we report high levels of total and phospho-S6RP and increased levels of Akt and p70S6K phosphorylation, upstream positive regulators of S6RP, in rat embryonic aortas and adult balloon-injured carotid arteries compared with quiescent adult aortas and uninjured carotid arteries. Western blot analysis demonstrated that cultured embryonic and neointimal SMCs that exhibited serum-independent growth capabilities expressed high levels of S6RP and constitutively active Akt, mTOR, and p70S6K. Pharmacological and molecular inhibition of phosphatidylinositol 3-kinase (PI3K) signaling pathways, using PI3K inhibitors, rapamycin, or dominant-negative Akt adenovirus, suppressed embryonic and neointimal SMC serum-independent growth. Finally, decreased activity of PTEN, an endogenous negative regulator of PI3K signaling, was associated with high in vivo SMC growth rates, and morpholino-mediated loss of endogenous PTEN induced a serum-independent growth phenotype in cultured serum-dependent SMCs.

Conclusions—

The possibility exists that cells that exhibit a distinct embryonic-like growth phenotype different from traditional SMCs are major contributors to intimal thickening. Growth of SMCs that exhibit this phenotype is dependent on constitutive Akt and mTOR/p70S6K signaling and is actively inhibited through the timed acquisition of the endogenously produced growth suppressor PTEN.
Opposing Roles of p47
phox
in Basal Versus Angiotensin II–Stimulated Alterations in Vascular O
2
−
Production, Vascular Tone, and Mitogen-Activated Protein Kinase Activation
Authors: Li Jian-Mei , Wheatcroft Stephen , Fan Lampson M. , Kearney Mark T. , Shah Ajay M.
Published: March 2004

Background—

NADPH oxidase is a major source of vascular superoxide (O
2
−
) production and is implicated in angiotensin II (Ang II)–induced oxidant stress. The p47
phox
subunit plays an important role in Ang II–induced oxidase activation, but its role in basal oxidase activity and vascular function is unclear.

Methods and Results—

Aortae from p47
phox−/−
and matched wild-type (WT) mice (n=9/group) were incubated ex vivo with or without Ang II (200 nmol/L, 30 minutes) and then examined for (1) NADPH-dependent O
2
−
production, (2) endothelium-dependent and -independent vascular relaxation, and (3) activation of mitogen-activated protein kinases (MAPKs). In the absence of Ang II, p47
phox−/−
vessels had slightly but significantly higher (1.3±0.1-fold;
P
<0.05) NADPH-dependent O
2
−
production than WT; impaired relaxation to acetylcholine (maximum 54±4% versus 80±3%;
P
<0.05), which was normalized to WT levels by the O
2
−
scavenger tiron or by Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride, and increased basal phosphorylation of ERK1/2, p38MAPK, and JNK compared with WT. In WT aortae, Ang II increased NADPH-dependent O
2
−
production (2.5±0.5-fold;
P
<0.05), impaired relaxation to acetylcholine (maximum 60±6% versus 80±3%;
P
<0.05), and increased ERK1/2, p38MAPK, and JNK phosphorylation (
P
<0.05). In contrast, Ang II failed to increase O
2
−
production, impair acetylcholine responses, or increase MAPK activation in p47
phox−/−
aortae.

Conclusions—

p47
phox
plays a complex dual role in the vasculature. It inhibits basal NADPH oxidase activity but is critical for Ang II–induced vascular dysfunction via activation of NADPH oxidase.