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Biomedical subjects

R Berger

Publications and source records attributed to R Berger.

At least 109 records · Page 6Linked to original sources
PubMed2000

ACE inhibitor dosage at the time of listing predicts survival.

BACKGROUND: To be listed for heart transplantation (HTx), optimization of the dosage of angiotensin converting enzyme (ACE) -inhibitors is recommended worldwide even though this issue has not been thoroughly investigated in the pre-transplantation cohort. OBJECTIVE: The aim of this database study was to analyze the prognostic impact of a pre-defined high vs a low ACE inhibitor dose range at the time of listing for elective HTx in addition to various previously established prognostic factors. METHODS: Medical records from 237 patients (84% male, mean age 54 years) admitted between January 1995 and January 1998 from 25 different centers in Austria were reviewed. Forty-seven percent were taking > or =75 mg captopril, > or =20 mg enalapril, > or =20 mg lisinopril or > or =5 mg ramipril daily ("high-dose" group) and 53% received smaller doses ("low-dose" group). RESULTS: No significant differences between groups were detected at baseline except that patients with higher ACE inhibitor doses were more likely to take nitrates, beta-blockers and amiodarone, received higher furosemide doses and had higher serum gamma-glutamyl transferase levels. Follow-up was 328 days (248 SD) with 16% deaths in the "high-dose" group vs 288 days (270 SD) with 25% deaths in the "low-dose" group. Kaplan-Meier survival curves demonstrated a significant difference over time between the two treatment groups (P = 0.03). Furthermore, dichotomized ACE inhibitor treatment at the time of listing was the strongest independent single predictor of mortality (P = 0.01) with only blood pressure (P = 0.02), alanine transaminase (P = 0.02) and left ventricular end diastolic diameter (P = 0.02) providing additional prognostic information. To explain these findings several factors have to be considered a) greater benefit with higher ACE inhibitor doses b) sicker patients receiving lower ACE inhibitor doses and c) more experienced heart failure care of the "high-dose" group. CONCLUSIONS: Heart transplantation candidates who, for whatever reason, receive ACE-inhibitors below the recommended dosages, are at increased mortality risk and thus merit greater scrutiny.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effect of beta 1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril.

BACKGROUND: The survival benefit of beta-blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of beta-blockers added on high dose angiotensin converting enzyme inhibitors has not been reported. AIMS: To investigate the effect of atenolol, a hydrophilic, selective beta1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind placebo-controlled trial. METHODS: One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction < or = 25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12. 5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89+/-11 mg/day, range 50-100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events. RESULTS: After 395+/-266 days interim analysis revealed a significant difference between the atenolol and placebo group (log rank P<0.01) and the trial was concluded. Twenty-seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations were due to worsening heart failure (5 in the atenolol group, 12 in the placebo-group, P=0.05) and 10 due to arrhythmias (1 in the atenolol group vs. 9 in the placebo group, P<0.01) CONCLUSIONS: The data suggest that in patients with advanced left ventricular dysfunction, beta-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.

Adrenergic beta-Antagonists↗
PubMed2000

Permeation studies in vitro and in vivo of potential radiopharmaceuticals with affinity to neuro receptors.

PURPOSE: To check the influence of structural characteristics on their permeation through the blood-brain barrier (BBB), a set of radioactive [99mTc]chelates bearing amine groups was synthesized and tested in vitro as well as in vivo. METHODS: Compounds with different log P and pKa values were obtained by complex forming reactions of [99mTc]pertechnetate with varying substituents. Transport was studied in rats and mice, as well as in an ECV304 cell culture model. RESULTS: In vitro higher permeation was found for compounds with electron attracting substituents in beta-position to the amine group (pKa values 7.4 to 8.3) than for those with more basic amine groups (pKa values > 8.9) even for similar log DH 7.4. In vivo brain uptake between 0.8 and 4.8% of the injected dose (ID) per organ was found for the former, whereas <0.4% ID were present for the latter. CONCLUSIONS: Three structurally diverse classes of [99mTc]chelates showed distinct patterns with regard to brain uptake in vivo and BBB permeability in vitro which could not be predicted by their lipophilicity alone. The close correlation between the data from rats and mice and those obtained with cell cultures render the ECV304 cells an attractive model for the screening of new compounds.

Animals↗
PubMed2000

Interstitial telomere repeats in translocations of hematopoietic disorders.

Cytogenetic and fluorescence in situ hybridization studies have shown the presence of telomeric repeats in translocation present in three patients with hematopoietic malignancies. One had jumping translocations, involving 1q12 and 2q, 16p, and 19q. These sequences were detected by FISH only in derivative chromosomes t(1;16) and t(1;19) in the first patient, and t(1;7) in the second. They were not seen in derivative t(1;2) and t(7;8), respectively. Interstitial telomeric sequences were observed in der(2)t(1;2) in about half of the metaphases in the third patient. The instability of interstitial telomeric DNA repeats in translocations is shown by the present findings. Moreover it supports the hypothesis that the presence of interstitial telomere repeats is not sufficient to make it functional.

Aged↗
PubMed2000

An in vitro method for predicting the efficacy of WBC separation using different starch preparations and anticoagulant ratios.

BACKGROUND: Separation of blood components depends on a number of factors, including the viscosity of the plasma and the number and size of the various cellular elements. To enhance granulocyte collection, it is common practice to alter the plasma environment by the addition of sedimenting agents such as hydroxyethyl starch. Recently, because of its prolonged persistence in the circulation, the higher-molecular-weight form of hydroxyethyl starch, Hespan (HP), has been replaced by the lower-molecular-weight form, pentastarch (PS). However, the yield appears to be lower. A rapid in vitro approach was used to permit comparison of the efficiency of separation of WBCs by the use of PS and HP and different ratios of anticoagulants that also alter the sedimenting characteristics of blood. STUDY DESIGN AND METHOD: Blood from individual persons was collected into sodium citrate at ratios of 1:8, 1:12, and 1:16. Samples were evaluated either before or after the addition of PS or HP and after centrifugation. RESULTS: The addition of HP increased the sedimentation rate to at least four times that of plasma (10.9 vs. 47.9 mm); PS approximately doubled the rate. Viscosity was altered by the introduction of either starch. These changes (ranging from a rate of 4.2 in HP with a 1:16 anticoagulant to 3.6 in PS with a 1:8 ratio of anticoagulant) reflected the anticipated effects of anticoagulant dilution and carbohydrate addition. Granulocyte recovery was highest, with a 1:12 anticoagulant ratio in all tests with HP producing the greatest yield (HP, 101%; PS, 89%; control, 78%). CONCLUSION: HP is far more effective than its lower-molecular-weight substitute PS in the generation of granulocytes in the buffy coat of whole blood. This method provides a simple, rapid, in vitro approach to evaluating the separating efficiency of solutions.

Anticoagulants↗
PubMed2000

A missense mutation in FIC1 is associated with greenland familial cholestasis.

Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G-->A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation.

Adenosine Triphosphatases↗
PubMed2000

Cardiopulmonary resuscitation with a hydraulic-pneumatic band.

Improved blood flow during cardiopulmonary resuscitation (CPR) has been shown to enhance survival from cardiac arrest. Chest compression with a circumferential pneumatic vest enhances blood flow, but the size, weight, and energy consumption of the inflation system limit its portability and, thereby, have made clinical studies difficult. The purpose of this investigation was to study an improved circumferential chest compression device that uses a constricting band that is pneumatically actuated. The constricting band applies its force to a hydraulic cushion that contacts the anterior and lateral aspects of the chest. The hydraulic cushion transfers the circumferential constriction to inward force. CPR was performed on subjects 5 mins after induction of ventricular fibrillation, with the hydraulic-pneumatic band system (HB-CPR), with a pneumatic vest system (PV-CPR), and with standard manual CPR (S-CPR), each done for 2 mins in randomized order. Aortic and right atrial pressures were measured with micromanometers. Coronary perfusion pressure was calculated as the mean difference between the aortic and right atrial pressures during the release phase of chest compression. Aortic pressure and coronary perfusion pressure with HB-CPR and PV-CPR were improved over S-CPR, and HB-CPR produced comparable pressures to those of PV-CPR. The system for performing HB-CPR, however, was substantially lighter (10 vs. 50 kg) and consumed less energy (300 vs. 1000 watts) than that for PV-CPR. Thus, HB-CPR appears to produce a similar improvement in hemodynamics over S-CPR as PV-CPR but may be more portable than PV-CPR. Therefore, HB-CPR may allow larger scale testing of circumferential chest compression approaches.

Animals↗
PubMed2000

Histopathology of the inferior turbinate with compensatory hypertrophy in patients with deviated nasal septum.

OBJECTIVE: To measure the dimensions, composition, and possible structural and/or histopathological changes of the compensatory hypertrophic inferior turbinate in patients with deviated nasal septum. STUDY DESIGN: A prospective, nonrandomized, and morphometric study. METHODS: Nineteen patients with deviated nasal septum and compensatory hypertrophy of the inferior turbinate in the contralateral nasal cavity underwent surgery for correction of nasal obstruction. Patients' specimens were compared with those of a control group consisting of 10 inferior turbinates removed at autopsy. Quantitative measurements of the inferior turbinate histological sections were carried out and included the width of the layers and morphometric calculations of the relative proportions of the soft tissue constituents. Also, qualitative study was performed to detect pathological changes. RESULTS: Of all layers, the inferior turbinate bone underwent a twofold increase in thickness and manifested the most significant expansion (P < or =.001), whereas the contribution of the mucosal layers to the inferior turbinate hypertrophy was modest. The morphometric analysis revealed a larger proportion of venous sinusoids in hypertrophic turbinates, but the difference was small and statistically insignificant. Qualitative assessment disclosed normal mucosal architecture in all inferior turbinates with compensatory hypertrophy. Eleven remained intact, while eight disclosed mild to moderate pathological changes. CONCLUSIONS: The data gathered in the present study are of importance to the decision-making process regarding turbinate surgery. The significant bone expansion and the relative minor role played by the mucosal hypertrophy would support the decision to excise the inferior turbinate bone at the time of septoplasty.

Adolescent↗
PubMed2000

Analysis of the pattern of initiation of sustained ventricular arrhythmias in patients with implantable defibrillators.

INTRODUCTION: The purpose of this study was to analyze the pattern of initiation of sustained ventricular arrhythmias in patients with varying types of underlying structural heart disease. METHODS AND RESULTS: The study group consisted of 90 patients with an implantable cardioverter defibrillator. Cardiovascular diagnoses included coronary artery disease in 64 patients (71%). The patients were divided into four groups based on the type and severity of structural heart disease. Two hundred sixty episodes of sustained ventricular arrhythmias were analyzed. The mean coupling interval of the initiating beat of all ventricular arrhythmias was 523 +/- 171 msec. The coupling interval of the initiating beat was longer in patients with impaired ventricular function, particularly those with nonischemic dilated cardiomyopathy. The prematurity index was similar regardless of the type of underlying structural heart disease. However, the prematurity index was shorter in patients with polymorphic ventricular tachycardia (VT) compared to those with monomorphic VT. A pause was observed more commonly before the onset of polymorphic VT/ventricular fibrillation than sustained monomorphic VT. Two hundred twenty-two (85%) of the arrhythmia episodes were initiated by a late-coupled premature beat, 33 (13%) were initiated by an early-coupled premature beat, and 5 episodes (2%) were initiated with a short-long-short sequence. The pattern of initiation of the ventricular arrhythmias was similar in all patient groups and for both monomorphic and polymorphic tachycardias. CONCLUSION: These findings demonstrate that sustained ventricular arrhythmias typically are initiated by late-coupled ventricular premature depolarizations, regardless of the type or severity of underlying structural heart disease or resultant arrhythmia.

Adult↗
PubMed2000

Lipopolysaccharides do not alter metabolic disturbances in hippocampal slices of fetal guinea pigs after oxygen-glucose deprivation.

The aim of the present study was to clarify whether endotoxins [lipopolysaccharides (LPS)] have a toxic effect on fetal brain tissue after cerebral ischemia, while excluding their effect on the cardiovascular system. Experiments were therefore performed on hippocampal slices prepared from mature fetal guinea pigs. In particular, we studied the influence of LPS on nitric oxide production, energy metabolism, and protein synthesis after oxygen-glucose deprivation (OGD). Incubating hippocampal slices in LPS (4 mg/L) for as long as 12 h did not alter cGMP tissue concentrations significantly. However, 10 min after OGD of 40-min duration, cGMP tissue concentrations were substantially increased in relation to controls, and this increase was almost completely blocked by the application of 100 microM N:(omega)-nitro-L-arginine, indicating that nitric oxide synthase was activated after OGD in fetal brain tissue. Again, LPS did not have any effect on cGMP tissue concentrations after OGD. Furthermore, addition of LPS altered neither protein synthesis nor energy metabolism measured 12 h after OGD. We therefore conclude that, apart from their well-known influence on the cardiovascular system, LPS do not alter metabolic disturbances in hippocampal slices of fetal guinea pigs 12 h after OGD. A direct toxic effect of LPS on immature brain tissue within this interval does not therefore seem to be very likely. However, delayed activation of LPS-sensitive pathways that may be involved in cell death, or damage limited to a small subgroup of cells such as oligodendrocyte progenitors, cannot be fully excluded.

Adenosine Triphosphate↗
PubMed2000

Perinatal brain injury.

Perinatal brain damage in the mature fetus is usually brought about by severe intrauterine asphyxia following an acute reduction of the uterine or umbilical circulation. The areas most heavily affected are the parasagittal region of the cerebral cortex and the basal ganglia. The fetus reacts to a severe lack of oxygen with activation of the sympathetic-adrenergic nervous system and a redistribution of cardiac output in favor of the central organs (brain, heart and adrenals). If the asphyxic insult persists, the fetus is unable to maintain circulatory centralization, and the cardiac output and extent of cerebral perfusion fall. Owing to the acute reduction in oxygen supply, oxidative phosphorylation in the brain comes to a standstill. The Na+/K+ pump at the cell membrane has no more energy to maintain the ionic gradients. In the absence of a membrane potential, large amounts of calcium ions flow through the voltage-dependent ion channels, down an extreme extra-/intracellular concentration gradient, into the cell. Current research suggests that the excessive increase in levels of intracellular calcium, so-called calcium overload, leads to cell damage through the activation of proteases, lipases and endonucleases. During ischemia, besides the influx of calcium ions into the cells via voltage-dependent calcium channels, more calcium enters the cells through glutamate-regulated ion channels. Glutamate, an excitatory neurotransmitter, is released from presynaptic vesicles during ischemia following anoxic cell depolarization. The acute lack of cellular energy arising during ischemia induces almost complete inhibition of cerebral protein biosynthesis. Once the ischemic period is over, protein biosynthesis returns to preischemic levels in non-vulnerable regions of the brain, while in more vulnerable areas it remains inhibited. The inhibition of protein synthesis, therefore, appears to be an early indicator of subsequent neuronal cell death. A second wave of neuronal cell damage occurs during the reperfusion phase. This cell damage is thought to be caused by the postischemic release of oxygen radicals, synthesis of nitric oxide (NO), inflammatory reactions and an imbalance between the excitatory and inhibitory neurotransmitter systems. Part of the secondary neuronal cell damage may be caused by induction of a kind of cellular suicide programme known as apoptosis. Interestingly, there is increasing evidence from recent clinical studies that perinatal brain damage is closely associated with ascending intrauterine infection before or during birth. However, a major part of this damage is likely to be of hypoxic-ischemic nature due to LPS-induced effects on fetal cerebral circulation. Knowledge of these pathophysiological mechanisms has enabled scientists to develop new therapeutic strategies with successful results in animal experiments. The potential of such therapies is discussed here, particularly the promising effects of intravenous administration of magnesium or postischemic induction of cerebral hypothermia.

Apoptosis↗
PubMed2000

Prostate vascular flow: the effect of ejaculation as revealed on transrectal power Doppler sonography.

OBJECTIVE: The objective of our study was to determine the effect of ejaculation on prostate vascular flow. SUBJECTS AND METHODS: Using power Doppler technology, we performed four transrectal sonographic examinations before and immediately, 6 hr, and 24 hr after ejaculation in 10 healthy volunteers. Images were assessed by three independent observers. RESULTS: Ninety-seven percent of the images ranked as having the least flow were from the baseline examination. There was a significant difference between the rankings when categorized into the four time sets (mean score for the baseline group was 1.1, whereas for the immediate, 6-, and 24-hr postejaculation groups it was 2.5, 2.9, and 2.4, respectively (p<0.0001). The only statistically significant difference was between the baseline and the three remaining groups. Interobserver agreement was high, with the chance-corrected measure of agreement of 0.78. CONCLUSION: Transrectal sonography revealed that prostate vascular flow increases dramatically after ejaculation and remains elevated for at least 24 hr. This observation should be considered when power Doppler sonography is used to assess for potential hyperemia in patients suspected of having prostate abnormalities.

Adult↗
PubMed2000

[Comparison between the old and new evaluation mode in the dichotic discrimination test].

The dichotic discrimination test for children could make an important contribution to the diagnosis of central auditory processing disorders. With previous test procedures and their interpretation it was not possible to get the auditory discrimination ability in only one grade. To evaluate this ability, it was necessary to measure the degree of comprehension in each ear as well as the required noise level. The evaluation cannot be used for statistical results because there are too many parameters. Moreover, results apparently similar can come from varying abilities. We are therefore working on a new method to evaluate dichotic hearing more accurately. By using a constant noise level and only evaluating positively those hearing pairs which have been repeated correctly, we arrive at one single grade. The dichotic discrimination test was administered to 46 children with auditory perception disorders and the results evaluated according to both, the previous and new evaluation system. According to the new evaluation, a maximum of 20 correct responses is possible. The average number of correct responses was significantly lower than by the previous evaluation system. The standard deviation increased from 16% on the left side and 13% in the right to 24%, or five word-pairs. The difference is even clearer when the test is subdivided into four performance ranges, each of 25%. Of all the children examined, 85% fell in the upper performance range according to the previous evaluation. No child was in the lowest performance range. According to the new evaluation, only 56.5% of the children were in the upper performance range, while three children, that is 6.5%, were in the lowest performance range. This difference, P = 0.0002, is highly significant. Our results demonstrate clearly that on the basis of the new evaluation system the measurement of dichotic ability is possible, for the first time. We consider the new evaluation method to be an improvement in determining dichotic discrimination and in comparing it with other abilities. To check the validity, further independent testing should be carried out and results compared with those obtained from children without auditory perception disorders.

Auditory Perceptual Disorders↗
PubMed1999

A DNA immunization model study with constructs expressing the tick-borne encephalitis virus envelope protein E in different physical forms.

We have conducted a DNA immunization study to evaluate how the immune response is influenced by the physical structure and secretion of the expressed Ag. For this purpose, we used a series of plasmid constructs encoding different forms of the envelope glycoprotein E of the flavivirus tick-borne encephalitis virus. These included a secreted recombinant subviral particle, a secreted carboxyl-terminally truncated soluble homodimer, a nonsecreted full-length form, and an inefficiently secreted truncated form. Mice were immunized using both i.m. injection and Gene Gun-mediated application of plasmids. The functional immune response was evaluated by determining specific neutralizing and hemagglutination-inhibiting Ab activities and by challenging the mice with a lethal dose of the virus. As a measure for the induction of a Th1 and/or Th2 response, we determined specific IgG subclasses and examined IFN-gamma, Il-4, and Il-5 induction. The plasmid construct encoding a secreted subviral particle, which carries multiple copies of the protective Ag on its surface, was superior to the other constructs in terms of extent and functionality of the Ab response as well as protection against virus challenge. As expected, the type of Th response was largely dependent on the mode of application (i.m. vs Gene Gun), but our data show that it was also strongly influenced by the properties of the Ag. Most significantly, the plasmid encoding the particulate form was able to partially overcome the Th2 bias imposed by the Gene Gun, resulting in a balanced Th1/Th2 response.

Animals↗
PubMed1999

[Dose-intensive chemotherapy with continuous infusion 5-fluorouracil].

54 patients with advanced malignancy refractory to chemotherapy were studied to evaluate efficacy and toxicity of continuous infusion of 5-fluorouracil (5FU) given for 3 weeks. We report results of the first 156 courses given in combination with other drugs. 19 (37%) of the 54 responded, including 3 (6%) with complete response. Toxicity was acceptable, with mucositis in 13 (26%) and 3 (6%) with grade II-III toxicity. Results and toxicity profile were compatible with further disease-oriented studies using this dose-intensive program.

Adolescent↗