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Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 109 records · Page 6Linked to original sources
PubMed2001

Rare indications for a Kausch-Whipple procedure.

OBJECTIVES: To find out whether the Kausch-Whipple operation is adequate for the cure of rare tumours of the pancreatic head. DESIGN: Retrospective study. SETTING: University hospital, Germany. PATIENTS: Of 640 patients who had Kausch-Whipple procedures between 1972 and 1998 we found 42 (6.6%) who were operated on for rare tumours of the pancreatic head. RESULTS: Among these 42 patients 12 had functioning and non-functioning endocrine tumours, 11 had adenomas that were not locally resectable, 6 had leiomyosarcomas or oncocytomas, 4 had cystadenocarcinomas, 3 had acinar cell carcinomas, 2 had primary lymphomas, and 3 had metastases to the pancreatic head. Operative treatment (such as extended resection), postoperative course, and survival time after operation varied. Patients with adenomas had the most favourable mean survival time of 106.5 months. Among patients with cancer, those with endocrine malignancies had the best outcome with a mean survival duration of 58.3 months.

Adult↗
PubMed2001

Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS; MIM SACS 270550) is frequent in northeastern Québec. Two causal mutations have been identified in the 11.7-kb single exon sacsin gene by sequence-based analyses. Mutation g.6594delT (DeltaT) was reported in 96% of the patients whereas a g.5254C --> T nonsense mutation has been observed only in 2 families. Here we report a reliable and inexpensive method to detect more than 95% of the ARSACS disease alleles from northeastern Québec using allele-specific oligonucleotide (ASO) hybridization. This procedure is being incorporated into the diagnosis of ARSACS, as well as being used for carrier detection in at-risk families from northeastern Québec.

Alleles↗
PubMed2001

Oxygen radical generation by emigrated, intra-abdominal, and circulating PMNLs during human secondary peritonitis.

The purpose of the study was to characterize oxygen radical generation by emigrated, intraabdominal and circulating polymorphonuclear leukocytes (ePMNLs and cPMNLs) during peritonitis, as well as to assess any differences between oxygen radical production in patients with low Mannheim peritonitis index (MPI < 26, group 1) or high Mannheim peritonitis index (MPI > or = 26, group 2). Lucigenin-enhanced chemiluminescence was used to determine spontaneous and stimulated (FMLP, PMA, and A23 187) oxygen radical generation by ePMNLs and cPMNLs. In group 1 spontaneous and stimulated oxygen radical generation by emigrated PMNLs was markedly enhanced compared to circulating PMNLs (e.g., spontaneous oxygen radical generation: 30.3 +/- 11.8 cpm/cPMNLs versus 107 +/- 46 cpm/ePMNLs, P < 0.05) . In group 2 oxygen radical generation by cPMNLs markedly increased within 48 h after diagnosis of peritonitis and surgery, contrary to radical generation by ePMNLs (e.g., A23 187-stimulated oxygen radical generation 993.7 +/- 350 cpm/cPMNLs versus 285.6 +/- 77 cpm/ePMNLs, P < 0.05. In conclusion, cPMNLs and ePMNLs exhibit marked polymorphism in their capacity to generate oxygen radicals in response to secondary peritonitis. Severe peritonitis (MPI - 26) was associated with a strong increase in oxygen radical generation by cPMNLs without a parallel activity being manifest by ePMNLs.

Abdomen↗
PubMed2001

The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma.

Interleukin (IL)-4 and IL-13 are key proinflammatory cytokines in asthma. Studies in transgenic mice show that both cytokines cause inflammation, but only IL-13 causes subepithelial fibrosis, a characteristic feature of asthma. We compared the in vitro profibrogenic effects of IL-4 and IL-13 using bronchial fibroblasts from asthmatic subjects. In the presence of transforming growth factor (TGF)-beta the cells transformed into contractile myofibroblasts and expressed alpha-smooth muscle actin and procollagen I. IL-4 and IL-13 also stimulated proliferation, but were relatively ineffective in promoting myofibroblast transformation. TGF-beta was more potent than the cytokines in stimulating release of endothelin-1 and vascular endothelial growth factor, whereas IL-4 and IL-13 were more potent stimuli for eotaxin release. Although neither IL-4 nor IL-13 induced profibrotic responses, both cytokines caused a corticosteroid-insensitive stimulation of TGF-beta2 release from primary bronchial epithelial cells. These data indicate that epithelial activation by IL-13 or IL-4 plays a critical role in initiating remodeling through release of TGF-beta2. TGF-beta2 then activates the underlying myofibroblasts to secrete matrix proteins and smooth muscle and vascular mitogens to propagate remodeling changes into the submucosa. In contrast, direct activation of submucosal fibroblasts by IL-4 and IL-13 has a proinflammatory effect via eotaxin release and recruitment of eosinophils into the airways.

Actins↗
PubMed2001

Mild-to-moderate uncomplicated hypertension: further analysis of a cost-effectiveness study of five drugs.

A cost-effectiveness model was designed to explore the effect of adding a new angiotensin-II inhibitor, telmisartan, to the therapeutic options for treating mild-to-moderate uncomplicated hypertension. Incorporating the cost of drugs, physician visits, and adverse-event treatments, the model concluded that availability of telmisartan on formulary may shorten the mean time and costs to control. The stability of the initial findings over a range of sensitivity analyses lends credence to the model conclusions that availability of telmisartan on formulary improves the therapeutic options of care for hypertension.

Adrenergic beta-Antagonists↗
PubMed2001

Analysis of the raffinose family oligosaccharide pathway in pea seeds with contrasting carbohydrate composition.

Raffinose family oligosaccharides (RFOs) are synthesized by a set of galactosyltransferases, which sequentially add galactose units from galactinol to sucrose. The accumulation of RFOs was studied in maturing seeds of two pea (Pisum sativum) lines with contrasting RFO composition. Seeds of the line SD1 accumulated stachyose as the predominant RFO, whereas verbascose, the next higher homolog of stachyose, was almost absent. In seeds of the line RRRbRb, a high level of verbascose was accumulated alongside with stachyose. The increase in verbascose in developing RRRbRb seeds was associated with galactinol-dependent verbascose synthase activity. In addition, a galactinol-independent enzyme activity was detected, which catalyzed transfer of a galactose residue from one stachyose molecule to another. The two enzyme activities synthesizing verbascose showed an optimum at pH 7.0. Both activities were almost undetectable in SD1. Maximum activity of stachyose synthase was about 4-fold higher in RRRbRb compared with SD1, whereas the activities of galactinol synthase and raffinose synthase were only about 1.5-fold higher in RRRbRb. The levels of galactinol synthase and stachyose synthase activity were reflected by steady-state levels of corresponding mRNAs. We suggest that the accumulation of verbascose in RRRbRb was controlled by a coordinated up-regulation of the last steps of verbascose biosynthesis.

Disaccharides↗
PubMed2000

Giant resonances in the doubly magic nucleus 48Ca from the (e, e'n) reaction.

The 48Ca(e,e(')n) reaction has been investigated for excitation energies 11-25 MeV and momentum transfers 0.22-0.43 fm(-1) at the superconducting Darmstadt electron linear accelerator S-DALINAC. Electric dipole and quadrupole plus monopole strength distributions are extracted from a multipole decomposition of the spectra. Their fragmented structure is described by microscopic calculations allowing for coupling of the basic particle-hole excitations to more complex configurations. Comparison of the excitation spectrum of the residual nucleus 47Ca with statistical model calculations reveals a 39(5)% contribution of direct decay to the damping of the giant dipole resonance.

Journal Article↗
PubMed2000

CGS 21680 exerts marked antidystonic effects in a genetic model of paroxysmal dyskinesia.

The effect of the adenosine A(2A) receptor agonist CGS 21680 (2-carboxyethyl)phenylethylamino]-5'-N-ethylcarbonyamido-ade nosine) on severity of dystonia was examined in genetically dystonic hamsters which exhibit attacks of dystonic and choreoathetotic disturbances in response to mild stress. CGS 21680 significantly reduced the severity of dystonia (0.5, 1.0 and 2.0 mg/kg i.p.). The marked antidystonic effects of CGS 21680 in the hamster model suggest that this compound may represent an interesting candidate for the therapy of paroxysmal dystonia. Furthermore, the present data indicate that the precipitating effect of caffeine in patients with paroxysmal dystonia is probably due to its adenosine receptor antagonistic action.

Adenosine↗
PubMed2000

Deficit of striatal parvalbumin-reactive GABAergic interneurons and decreased basal ganglia output in a genetic rodent model of idiopathic paroxysmal dystonia.

The underlying mechanisms of various types of hereditary dystonia, a common movement disorder, are still unknown. Recent findings in a genetic model of a type of paroxysmal dystonia, the dt(sz) mutant hamster, pointed to striatal dysfunctions. In the present study, immunhistochemical experiments demonstrated a marked decrease in the number and density of parvalbumin-immunoreactive GABAergic interneurons in all striatal subregions of mutant hamsters. To examine the functional relevance of the reduction of these inhibitory interneurons, the effects of the GABA(A) receptor agonist muscimol on severity of dystonia were examined after microinjections into the striatum and after systemic administrations. Muscimol improved the dystonic syndrome after striatal injections to a similar extent as after systemic treatment, supporting the importance of the deficiency of striatal GABAergic interneurons for the occurrence of the motor disturbances. The disinhibition of striatal GABAergic projection neurons, as suggested by recent extracellular single-unit recordings in dt(sz) hamsters, should lead to an abnormal neuronal activity in the basal ganglia output nuclei. Indeed, a significantly decreased basal discharge rate of entopeduncular neurons was found in dt(sz) hamsters. We conclude that a deficit of striatal GABAergic interneurons leads by disinhibition of striatal GABAergic projection neurons to a reduced activity in the entopeduncular nucleus, i.e., to a decreased basal ganglia output. This finding is in line with the current hypothesis about the pathophysiology of hyperkinesias. The results indicate that striatal interneurons deserve attention in basic and clinical research of those movement disorders.

Action Potentials↗
PubMed2000

A member of a gene family on Xp22.3, VCX-A, is deleted in patients with X-linked nonspecific mental retardation.

X-linked nonspecific mental retardation (MRX) has a frequency of 0.15% in the male population and is caused by defects in several different genes on the human X chromosome. Genotype-phenotype correlations in male patients with a partial nullisomy of the X chromosome have suggested that at least one locus involved in MRX is on Xp22.3. Previous deletion mapping has shown that this gene resides between markers DXS1060 and DXS1139, a region encompassing approximately 1.5 Mb of DNA. Analyzing the DNA of 15 males with Xp deletions, we were able to narrow this MRX critical interval to approximately 15 kb of DNA. Only one gene, VCX-A (variably charged, X chromosome mRNA on CRI-S232A), was shown to reside in this interval. Because of a variable number of tandem 30-bp repeats in the VCX-A gene, the size of the predicted protein is 186-226 amino acids. VCX-A belongs to a gene family containing at least four nearly identical paralogues on Xp22.3 (VCX-A, -B, -B1, and -C) and two on Yq11.2 (VCY-D, VCY-E), suggesting that the X and Y copies were created by duplication events. We have found that VCX-A is retained in all patients with normal intelligence and is deleted in all patients with mental retardation. There is no correlation between the presence or absence of VCX-B1, -B, and VCX-C and mental status in our patients. These results suggest that VCX-A is sufficient to maintain normal mental development.

Amino Acid Sequence↗
PubMed2000

Paradoxical aggravation of paroxysmal dystonia during chronic treatment with phenobarbital in a genetic rodent model.

Recent studies in mutant hamsters (dt(sz)), an animal model of primary paroxysmal dystonia, indicated that altered function of the gamma-aminobutyric acid (GABA)ergic system plays a critical role in the pathogenesis of dystonia. In the present study, dt(sz) hamsters were chronically treated with phenobarbital, which has been found to exert antidystonic effects in mutant hamsters after acute administration. In untreated dt(sz) hamsters, the severity of dystonia follows an age-dependent time course with a maximum between the 30th and 40th day of life, followed by a continuous decline of severity until complete remission occurs at the age of about 70 days. In contrast to acute effects, chronic treatment with phenobarbital via drinking water starting at an age of 21 days (i.e., after weaning) worsened dystonia and retarded the spontaneous remission. The unexpected prodystonic effect was more marked after administration of higher doses and when chronic treatment with phenobarbital started at an age of 1 day (neonatal administration via breast milk). After withdrawal of phenobarbital at the age of 70 days, the severity rapidly declined in all treated groups. When phenobarbital was readministered 1 week later, the hamsters again exhibited severe dystonia. The mechanism of these unexpected findings is unknown. Tentatively, activity-dependent GABA-mediated excitation caused by chronic treatment with phenobarbital may be important for the prodystonic effects under pathological conditions in dt(sz) hamsters.

Aging↗
PubMed2000

Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype.

North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22.

Adult↗
PubMed2000

Piracetam and levetiracetam, two pyrrolidone derivatives, exert antidystonic activity in a hamster model of paroxysmal dystonia.

The effects of the nootropic drug piracetam and its analogue, the antiepileptic drug levetiracetam (ucb L059) on severity of dystonic attacks were studied in a mutant hamster model of idiopathic generalized dystonia. Both drugs significantly decreased the severity of dystonia. In contrast to seizure models, in which levetiracetam is much more potent as an anticonvulsant than piracetam, the antidystonic potency of levetiracetam was only moderately higher than that of piracetam. The antidystonic activity of piracetam and levetiracetam was not associated with any behavioral side effects. The data indicate that piracetam and levetiracetam are interesting novel treatments for idiopathic dystonia.

Animals↗
PubMed2000

First experimental evidence for chaos-assisted tunneling in a microwave annular billiard

We report on first experimental signatures for chaos-assisted tunneling in a two-dimensional annular billiard. Measurements of microwave spectra from a superconducting cavity with high frequency resolution are combined with electromagnetic field distributions experimentally determined from a normal conducting twin cavity with high spatial resolution to resolve eigenmodes with properly identified quantum numbers. Distributions of quasidoublet splittings serve as basic observables for the tunneling between whispering gallery-type modes localized to congruent, but distinct tori which are coupled weakly to irregular eigenstates associated with the chaotic region in phase space.

Journal Article↗
PubMed2000

Parametric X rays observed under bragg condition: boost of intensity by a factor of Two

Parametric x rays (PXR) produced by bombarding silicon and diamond crystals with electrons of 30 to 87 MeV were detected at 180 degrees relative to the direction of the electron beam. It was found that the dependence of the intensity on the orientation of the crystal agrees with the predictions of the kinematical theory of PXR. The absolute intensity is twice as large as predicted. These findings can be explained considering dynamical effects that govern the x-ray crystal interaction. Additionally, x rays caused by self-diffracted transition radiation have been observed.

Journal Article↗
PubMed2000

The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results.

By including immunohistochemical parameters the WHF Task Force for the Definition of Acute and Chronic Myocarditis expanded the light microscopical Dallas criteria of myocarditis. The rapid development of new molecular biological techniques such as polymerase chain reaction (PCR) and in-situ hybridization has improved our understanding of the underlying etiological and pathophysiological mechanisms in inflammatory heart disease. Treatment of dilated cardiomyopathy with inflammation is still controversial, however. The American Myocarditis Treatment Trial could not demonstrate a significant difference in the improvement of ejection fraction between patients with active myocarditis in the cyclosporine/prednisolone treated group when compared to placebo. In the European Study of Epidemiology and Treatment of Inflammatory Heart Disease (ESETCID) patients with acute or chronic myocarditis are treated specifically according to the etiology of the disease. Patients are screened not only for infiltrating cells, but also for the presence of persisting viral genome (enterovirus, cytomegalovirus and adenovirus). By investigating endomyocardial biopsies of 3,055 patients ongoing inflammatory processes in the heart could be found in 17.2%. Only 182 showed a reduced ejection fraction below 45% fulfilling the entrance criteria for the ESETCID trial. These data imply that in symptomatic patients inflammatory heart muscle disease has to be considered regardless of left ventricular function and that endomyocardial biopsy can be an important tool for diagnosis. Virus could be detected in 11.8% (enterovirus 2.2%, cytomegalovirus 5.4%, adenovirus 4.2%). These first epidemiological results of this prospective randomized study demonstrate that viral persistence may contribute to the pathogenesis of inflammatory heart muscle disease, and that in chronic myocarditis viral persistence occurs in a smaller percentage of patients compared to previously published studies which were performed on highly selected patients.

Cardiomyopathies↗
PubMed2000

Laparoscopic hernioplasty versus conventional hernioplasty (Shouldice): results of a prospective randomized trial.

The results of our randomized trial of 176 patients comprising primary hernias [Shouldice versus transabdominal preperitoneal approach (TAPP)] showed only slight advantages for the laparoscopically operated group compared to the conventionally operated group: less subjective pain (significant only on fifth postoperative day, p < 0.05), reduced analgesic requirement (significant only on third postoperative day, p < 0.05), significantly shorter duration of hospitalization (4 days vs. 6 days, p < 0.05) and faster return to work (27 days vs. 34 days, NS). Regarding the incidence of recurrences, there was no significant difference between the groups (two recurrences vs. one recurrence) within a follow-up period of 2 years. Postoperative morbidity was similar and the total cost was less for the TAPP group.

Female↗