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PubMed2004

[The duodenal epithelium in duodenal diseases].

The purpose of the study was to define duodenal epithelial function in duodenal diseases and to assess the potentialities of correction of detected dysfunctions. The electrical properties (EPs) of the duodenal epithelium were explored in patients with primary chronic duodenitis, duodenal peptic ulcer (DPU) on an exacerbation and in the late postoperative period after selective proximal vagotomy. Mucosal biopsy specimens were obtained at fibrogastroduodenoscopy with biopsy forceps and placed in a sign-alternating field with the parameters, adequate bioelectric epitheliocytic characteristics: 28 V at a voltage sign change rate of 1 Hz, and a current strength of 200 microA. Bioelectrical cell reactions (nuclear fluctuation amplitude) were recorded by light microscopy using a MOB-1A ocular micrometer at minutes 10, 30, and 60 of the onset of electrical field action. A significant reduction was found in the amplitude of duodenal epithelial nuclear fluctuations in the examinees, which was most pronounced in DPU on an exacerbation. Duodenal epithelial EPs were shown to undergo regular changes during therapy and may serve as an additional test in evaluating the efficiency of therapy.

Chronic Disease↗
PubMedDate not supplied

Virus isolations from pet birds submitted for importation into the United States.

From October 1973 to September 1981, 2,882,111 birds were offered for importation into the United States. All were quarantined for 30 days, and specimens were submitted to the laboratory for virus-isolation studies. Viruses were isolated from specimens from 26.3% (598/2,274) of the quarantined lots of birds. Viscerotropic velogenic Newcastle disease virus (VVNDV) was isolated from 141 lots. Nonviscerotropic velogenic Newcastle disease virus (VNDV) was isolated from six lots. All VVNDV- and VNDV-positive lots were refused entry. The percentage of lots refused entry declined from 31.6% in 1974 to 2.9% in 1981. Mesogenic Newcastle disease virus (NDV) was isolated from three lots, and lentogenic NDV was isolated from 23 lots. Lots positive for mesogenic and lentogenic NDV were allowed to enter the United States. Hemagglutinating (HA) viruses other than NDV were isolated from 24.5% (373/1,521) of the lots imported through privately owned quarantine facilities. Of the 8,563 HA viruses isolated, 1,558 were selected for identification. Forty-six percent were identified as paramyxovirus (PMV)-2, 34% were PMV-3, and 20% were influenza A viruses possessing the hemagglutinin subtypes H3, H4, H7, and H10 and the neuraminidase subtypes N1, N6, N7, and N8. The frequency of PMV-2 and PMV-3 isolations fluctuated from year to year, whereas the frequency of isolations of influenza A viruses decreased from 64% in 1974 to 0.2% in 1981. Viruses that did not agglutinate chicken red blood cells were isolated from 52 lots. Psittacine herpesvirus (Pacheco's disease) was isolated from 25 lots of psittacines. Viruses identified by electron microscopy as reoviruses were isolated from 24 lots.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Supraventricular paroxysmal tachycardia as a pediatric cardiologic emergency].

Seven cases with the diagnosis of supraventricular paroxysmal tachycardia, confirmed by the electrocardiogram were included in the study. Their ages fluctuated from 19 days to 14 years, with predominance of small infants. The etiology was varied. They were managed with digitalis and conversion to sinusal rhythm in a short term. The drug was maintained to prevent relapses and/or heart failure. No mortality issued. We recommend the use of digitalis as selective drug because it may be readily obtained and its appication and response are sure. The clinical findings and results agree with the literature reviewed.

Adolescent↗
PubMed1993

[Quality of event data in detection of unwanted drug side-effects in general practice of established physicians].

Since 1986, the Federal Health Office (BGA) has supported the model project "Monitoring Adverse Drug Reactions (ADRs) in the Surgeries of Office-Based Physicians". The project itself is being carried out by the Institute for Health Systems Research in Kiel. The aim of the project is to develop a method for the systematic monitoring of the risks involved with selected new drugs. This should also facilitate the determining of the incidence rate of ADRs as well as reveal as yet unknown ADRs. Several conclusions can be drawn when examining the quality of event data when monitoring ADRs through office-based physicians. The documentation quality of the transferred data fluctuates from surgery to surgery. In order to obtain valid outcomes, the data should be thoroughly examined and checked by consulting the participating surgery. When quantifying known events with a suspected ADR, the Sentinel approach leads to reliable results. When monitoring drug therapies through office-based physicians, risk situations can be monitored and assessed more easily under everyday conditions. When assessing the quality of event data with regard to disclosing hitherto unknown, potential ADRs, the character of the individual surgery is of utmost importance. The object of the research project is to examine cause-effect associations which have nothing whatsoever to do with the participating physicians themselves but which reflect interactions between drugs and patients.

Adverse Drug Reaction Reporting Systems↗
PubMed1996

[Bioavailability of two verapamil formulations following repeated administration in steady-state conditions. An open, two-period, crossover study].

The relative bioavailability of a new formulation of verapamil (CAS 52-53-9, Veramex 40) in comparison to a standard formulation was investigated in an open two-period cross-over study in 16 healthy volunteers under steady state conditions of 7 days duration each. For the estimation of verapamil a selective HPLC-method was used with fluorescence detection after direct injection and enrichment by column switching enabling a simultaneous separation and analysis of verapamil and N-norverapamil. The bioavailability was estimated using areas under the concentration-time curves (AUC), maximum serum concentrations (Cmax) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVAlog). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference substance, thereafter slightly higher plasma levels up to 7 h were observed after the test substance. The individual plasma profiles had a similar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean relative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concentrations for verapamil and N-norverapamil were 50.0 and 49.7 ng/ml, respectively. After the standard formulation the corresponding values were 50.4 and 50.3 ng/ml. The mean PTF-values for verapamil and N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, respectively. The 90% confidence intervals for AUC, Cmax and PTF for verapamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, Cmax and PTF. Therefore bioequivalence between both formulations can be stated.

Adult↗
PubMed1999

Interventions to achieve tonic exposure to levodopa: delaying or preventing the onset of motor complications.

Variations in levodopa delivery and subsequent dopamine exposure may lead to motor fluctuations and dyskinesias in patients with Parkinson's disease, as the therapeutic window for levodopa narrows with disease progression. Long-term exposure to the oscillations in levodopa-derived dopamine also is suggested to cause postsynaptic changes within the dopaminergic system, leading to further reductions in the drug's efficacy. The need to extend the actions of levodopa led to the development of the catechol-O-methyltransferase (COMT) inhibitors, which are the newest agents introduced to manage the symptoms of Parkinson's disease. Entacapone and tolcapone are two potent, selective, and reversible COMT inhibitors that effectively augment levodopa's pharmacokinetics by increasing area under the plasma concentration versus time curve and plasma elimination half-life without significantly affecting peak levodopa concentrations. This enhanced pharmacokinetic effect results in marked improvements in patients' clinical response. In patients experiencing end-of-dose wearing-off, the addition of either entacapone or tolcapone led to improvements in "on" time, "off" time, and the Unified Parkinson's Disease Rating Scale scoring system, even though many patients already were receiving optimum dosages of various other antiparkinsonian drugs. In patients with stable responses to long-term levodopa, addition of tolcapone significantly reduced the onset of motor fluctuations. These data, combined with the potential for delaying the onset of motor fluctuations, suggest that COMT inhibition may enhance levodopa's short- and long-term efficacy.

Antiparkinson Agents↗
PubMed2005

Quantifying stochastic outcomes.

A system consisting of two species in a fluctuating environment, when the interspecies competition for resources is strong, will have a stochastic outcome: only one of the species will survive, but there is no a priori way of knowing which one this will be. It is natural in such a situation to ask what will be the probability of one or another of the species surviving. This probability is calculated as a function of the average growth rates and the strengths of the interaction between the species and of the randomness. This is an example of a class of stochastic problems in which multiple final states are available for occupation. We refer to the choice of final states as state selection, and the probabilities of final states being occupied as state-selection probabilities. The calculation of these probabilities is carried out in the context of a model of the system which consists of two coupled stochastic differential equations. By reformulating these equations in terms of path integrals, the powerful methods based on the use of optimal paths may be utilized to calculate the probability of one outcome or the other. The analytical results obtained by using this technique agree well with numerical simulations when both species have the same growth rate. Although the method adopted rests on the assumption that the strength of the fluctuations, D , is small, remarkably the analytic results are still found to be in good agreement with the numerical results when D is of order 1.

Journal Article↗
PubMed1999

Molecular dynamics simulations of human glutathione transferase P1-1: conformational fluctuations of the apo-structure.

We have investigated by molecular dynamics simulations the conformational fluctuations of the monomer of human apo-glutathione transferase P1-1. After attainment of steady-state dynamics, the structural fluctuations involve mainly the protein segments that participate also in the holo-apo transition discussed in the accompanying article (Stella et al., 1999:37:1-9.). The most mobile region is the C-terminal segment of helix 2. In contrast, helices 1, 6, 7, and 8 constitute a relatively rigid protein core. An "essential dynamics" analysis of the simulation shows that the largest fluctuations involve specific regions of glutathione transferases. In such regions, atomic motions are correlated. Motions of helix 2 are accounted for by the second most prominent principal component, which reveals a fluctuation between two distinct conformations. The residues that constitute the H-site undergo a breathing motion, possibly relevant during the binding of hydrophobic cosubstrates. Based on our simulation, several experimental findings can be rationalized, including the viscosity-dependent reactivity of Cys 47 and Cys 101 as well as the selective proteolysis of the peptide bond between Lys 44 and Ala 45. We have also modeled the structural changes that lead to the formation of an intrachain disulfide bridge between cysteines 47 and 101 and to the inactivation of the enzyme. The resulting structure maintains essentially the native fold except for helix 2, which closes the G-site. Proteins 1999;37:10-19.

Apoproteins↗
PubMed1983

Subdural effusions re-appearing after shunts in patients with non-tumoural stenosis of the aqueduct.

Three patients shunted for non-tumoural stenosis of the aqueduct suffered from progressive clinical symptoms about four months after the shunting. Computed tomography (CT) showed bilateral subdural effusions. The effusions were evacuated, and the shunts revised. One month later all patients suffered from symptoms of increased intracranial pressure, and CT showed enlargement of the supratentorial cerebral ventricles. The effusions had disappeared. After shunt revision the symptoms decreased again. The fluctuation in the ventricular size, the thickness of the subdural effusions, and the clinical deterioration were related to the change in the opening pressure of the shunt valve in all patients. Patients with large supratentorial cerebral ventricles (Evans index over 0.40) should be monitored by intraventricular pressure recording in order to select the exact opening pressure of the shunt valve before inserting a relieving shunt; a clinical check-up and a CT examination should be carried out about three months after the operation in order to investigate any changes in the function of the shunt.

Adult↗
PubMed2001

Surface ozone trends in Hong Kong in 1985-1995.

Ozone trends in Hong Kong were assessed from the ozone data recorded at three urban stations and one station in the new development area. Three parameters were selected as the robust trend indicators in the study: monthly mean, monthly averaged daily 1-h maximum, and number of annual hours > 120 microg m(-3). As the ozone data displayed obvious seasonal variation, using deseasonalized monthly average parameters to estimate the ozone trends could smooth out the influence of seasonal fluctuations. The detection of an increase of more than 10% per year in ozone concentration at one station was particularly alarming. Effects of meteorological factors, control programmes of ozone precursors, and long-range transport on the ambient ozone level were examined in the study.

Air Pollutants↗
PubMed1999

New, selective catechol-O-methyltransferase inhibitors as therapeutic agents in Parkinson's disease.

Levodopa remains the most effective drug for Parkinson's disease (PD). However, its benefits are limited owing to extensive metabolism by catechol-O-methyltransferase (COMT), especially if levodopa is used in combination with peripheral dopa-decarboxylase inhibitors. A new generation of potent, orally active, selective, and reversible COMT inhibitors has become available recently. Among these, tolcapone and entacapone have been best characterised. Preclinical and clinical studies have shown that COMT inhibitors markedly enhance levodopa availability and prolong its plasma half-life. In recent large clinical trials they proved to be able to ameliorate motor fluctuations, reduce disability, and decrease levodopa requirements in PD patients. The tolerability profiles of entacapone and tolcapone are good. COMT inhibition promises to become an important means of extending the benefits of levodopa therapy in PD.

Animals↗
PubMed1997

Folate and folate-binding protein content in dairy products.

Recent findings suggest a protective role for folates in the reduction of neural tube defects and possibly also coronary heart disease and cancer. Consequently, an increase in the daily intake of folates is warranted, which emphasizes the need for quantitative as well as qualitative measurements of dietary folates. Milk plays an important part in the food chain in many Western countries today. Several studies suggest that folate-binding proteins might have an impact on folate absorption and therefore their concentrations are also important. The mean concentration of the predominant form of folate, 5-methyltetrahydrofolate (5-CH3THF), was determined using HPLC in thirteen selected dairy products; skim milk powder, two pasteurized milks, UHT milk, two fermented milks, three whey products and four different cheeses. All results were corrected for recovery by spiking the samples with 5-CH3THF. Effects of storage of dairy products on 5-CH3THF concentrations were also investigated; generally small and insignificant fluctuations were found, except for hard cheese, in which 5-CH3THF decreased significantly. There was a significant seasonal variation in the folate concentration of pasteurized milk which peaked in the summer months. The concentrations of folate-binding protein in skim milk powder and pasteurized milk analysed using an enzyme-linked immunosorbent assay were similar. UHT milk and fermented milk, both of which are processed at temperatures > 90 degrees C, contained significantly lower concentrations of folate-binding protein.

Animals↗
PubMed1997

Structure of a glycoconjugate in solution and in complex with an antibody Fv fragment.

By use of heteronuclear (13C, 1H) NMR methods, the three-dimensional structure and dynamics of the glycoconjugate estrone-3-glucuronide (E3G) uniformly 13C enriched in the glucuronic acid moiety has been probed both in free solution and in association with an anti-E3G antibody single-chain Fv fragment. The glycan is found to exist in multiple conformations in free solution, with particularly large torsional fluctuations about the glycosidic linkage psi. Resonance assignments and distance restraints for the glycoconjugate in the bound state were obtained from heteronuclear proton-carbon-carbon-proton-COSY and isotope-edited NOESY techniques, respectively. Quantitation of the NOE data with a full-relaxation matrix approach showed that the antibody selects a conformation from the solution repertoire which does not correspond with either of the two lowest energy conformations of the free glycan, and the internal energy of the glycan in the bound state is estimated to be at most approximately 15 kcal/mol higher than the global minimum energy conformation. The glucuronide moiety undergoes a stacking interaction with an aromatic ring in the binding site, and both ring-current shifts and nuclear Overhauser effects computed from the predicted bound-state conformation are in good agreement with experiment. The bound-state conformation is also in good agreement with preliminary x-ray data on a related complex.

Carbohydrate Conformation↗
PubMed2005

Non-Gaussian fluctuations arising from finite populations: Exact results for the evolutionary Moran process.

The appropriate description of fluctuations within the framework of evolutionary game theory is a fundamental unsolved problem in the case of finite populations. The Moran process recently introduced into this context in Nowak, [Nature (London) 428, 646 (2004)] defines a promising standard model of evolutionary game theory in finite populations for which analytical results are accessible. In this paper, we derive the stationary distribution of the Moran process population dynamics for arbitrary 2 x 2 games for the finite-size case. We show that a nonvanishing background fitness can be transformed to the vanishing case by rescaling the payoff matrix. In contrast to the common approach to mimic finite-size fluctuations by Gaussian distributed noise, the finite-size fluctuations can deviate significantly from a Gaussian distribution.

Adaptation, Physiological↗
PubMed1996

Cochlear hearing loss and the processing of modulation: effects of temporal asynchrony.

Temporal coincidence and envelope correlation among components of a complex sound are informative cues for the perceptual organization of that sound. Listeners with hearing loss of cochlear origin often exhibit reductions in temporal processing of stimuli with randomly fluctuating envelopes. The purpose of this study was to examine the performance of such listeners on auditory grouping tasks which rely on temporal cues. The first experiment examined temporal asynchrony effects in a comodulation masking release (CMR) task. Performance was poorer than normal and appeared to be associated with reduced frequency selectivity. However, the pattern of asynchrony effects was the same as normal. The second experiment examined temporal asynchrony effects in a task based on envelope comparison interference. On this task, performance was similar to that for normal-hearing listeners. It was concluded that listeners with hearing loss of cochlear origin are comparable to normal-hearing listeners in their ability to make use of relatively gross temporal asynchrony cues.

Adult↗
PubMed1996

Use of methods from chaos theory to quantify a fundamental dysfunction in the behavioral organization of schizophrenic patients.

OBJECTIVE: This study aimed to quantify the complexity of behavioral sequences of patients with schizophrenia and comparison subjects by using methods from nonlinear dynamical systems theory. METHOD: A simple choice task consisting of predicting 500 random right or left appearances of a stimulus was used to obtain binary response sequences in 22 patients with schizophrenia and 16 comparison subjects. Dynamical entropy was measured and the fluctuation spectrum of local subsequence entropies calculated to quantify the degree of interdependency between consecutive responses of patients and comparison subjects. RESULTS: The response sequences generated by the schizophrenic patients exhibited a higher degree of interdependency than those of comparison subjects. Moreover, schizophrenic patients exhibited significantly less consistency in their response selection and ordering, characterized by a greater contribution of both highly perseverative and highly unpredictable subsequences of responses within a test session. CONCLUSIONS: The result of the biological abnormality underlying schizophrenia may not be a simple increase or decrease of neuropsychological or neurobiological functions. Instead, the observed abnormalities in behavioral patterns reflect a quantifiable dysregulation and disorganization of these functions.

Adult↗
PubMed2005

Mizoribine pulse therapy for a pediatric patient with steroid-resistant nephrotic syndrome.

A 12-year-old Japanese boy was referred to our hospital with a 2-month history of persistent proteinuria. Despite urinary protein excretion in the nephrotic range, associated with hypoproteinemia, the patient did not complain of any disability. A percutaneous renal biopsy revealed minor glomerular abnormalities, without any evidence of immune complex deposition. Therapy with prednisolone (60 mg/day) was initiated, and while the proteinuria decreased after 4-week therapy, elevated urinary protein excretion persisted thereafter, at 1-2 g/day. Because of the steroid-resistant proteinuria, mizoribine (MZR), was started at 150 mg/day (3 mg/kg), administered as a single daily dose an immunosuppressive agent, in combination with prednisolone. Although there was some fluctuation in the urinary protein excretion, heavy proteinuria persisted for the next 4 weeks. The peak blood level of MZR was 0.9 microg/ml. Since we have previously reported the efficacy and safety of oral MZR pulse therapy, which is associated with higher peak serum MZR levels than conventional MZR therapy in selected patients with lupus nephritis, we adopted MZR pulse therapy for this patient, after obtaining informed consent. MZR was started at the daily dose of 300 mg (6 mg/kg), administered as a single dose before breakfast, twice a week (on Monday and Thursday). The peak blood level of MZR then increased to 1.29 microg/ml. Thereafter, despite a gradual reduction of the concomitantly administered prednisolone dose, the urinary protein excretion decreased rapidly to around 0.3 g/day and remained at this level thereafter. No adverse effects of MZR were observed. Based on these clinical observations, we suggest that oral MZR pulse therapy may be the treatment of choice in selected patients of steroid-resistant nephrotic syndrome, in addition to those of lupus nephritis.

Child↗
PubMed1997

Mortality associated with selegiline in Parkinson's disease. What do the available data mean?

A recent study by the Parkinson's Disease Research Group of the United Kingdom revealed higher mortality in patients with Parkinson's disease who were treated with selegiline (deprenyl) compared with those who were not. In this article, the methodological limitations of the UK study are discussed. Although several problems exist with this study, the mortality rate was correct, since the data were obtained from a verifiable source. The question then is whether or not the higher mortality rate can be ascribed to selegiline. It is difficult to find answers to this question in the study data, and we will have to wait for the study authors' final report. No other studies have reported higher mortality with selegiline. However, when prescribing selegiline in patients with early-stage Parkinson's disease, it is important to provide them with all the available information so that treatment decisions can be made jointly. Meanwhile, the best indication for selegiline appears to be motor fluctuations in patients with moderately advanced Parkinson's disease.

Antiparkinson Agents↗