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Biomedical subjects

S Köhler

Publications and source records attributed to S Köhler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Successful epilepsy surgery in catastrophic postencephalitic epilepsy.

The authors studied prognostic factors for surgical treatment in 22 patients with intractable postencephalitic epilepsy. A small subgroup of patients (9/22) had a positive outcome after resective surgery. They had a higher functional level after encephalitis as measured by Glasgow Outcome Score, a longer time interval between encephalitis and onset of seizures, and localization of ictal EEG to one temporal lobe. The other patients had devastating seizures with poor outcome after surgery.

Adolescent↗
PubMed2000

Shockwave application in calcifying tendinitis of the shoulder--prediction of outcome by imaging.

This prospective study examined 62 patients (65 shoulders) with chronic courses of calcifying tendinitis of the shoulder before and after low-energy extracorporeal shockwave application (ESWA) in order to identify variables associated with the outcome of this treatment. Before ESWA, radiographs and contrast-enhanced magnetic resonance imaging (MRI) of the affected shoulders were obtained in order to document the size and morphology of the calcifications and the contrast media reactions in areas of interest (deposit, synovia, bursae), respectively. In addition, a clinical evaluation was performed. After ESWA (mean follow-up 18.2 months), clinical evaluations of all 65 shoulders revealed an increase in the Constant score from 44% to 78% (p < 0.0001). While size (p = 0.61) and morphology (p = 0.7) of the deposits before ESWA were not associated with the clinical outcome, negative contrast reactions around the deposits (p) = 0.0001), synovia (p = 0.0049) and bursae (p < 0.01) were associated with improved clinical outcomes. After the total study group was divided into two groups, one with Constant scores > or = 75% (n = 43) and the other with scores < 75% (n = 22), the positive predictive value (ppv), specificity (sp) and sensitivity (se) were determined for the negative reaction around the deposit (ppv: 0.94; sp: 0.95; se: 0.38), synovia (ppv: 0.84; sp: 0.82; se: 0.49) and bursae (ppv: 0.86; sp: 0.86; se: 0.44). In 5 cases (7.7%), surgery of the affected shoulder during the follow-up period was performed. No major side-effects were seen in the study group. In conclusion, our results suggest that in patients with chronic calcifying tendinitis, the absence of contrast enhancement, especially around the deposit, is a strong predictive parameter of a positive clinical outcome of ESWA.

Adult↗
PubMed2000

Episodic encoding and recognition of pictures and words: role of the human medial temporal lobes.

In the present PET study, we examined brain activity related to processing of pictures and printed words in episodic memory. Our goal was to determine how the perceptual format of objects (verbal versus pictorial) is reflected in the neural organization of episodic memory for common objects. We investigated this issue in relation to encoding and recognition with a particular focus on medial temporal-lobe (MTL) structures. At encoding, participants saw pictures of objects or their written names and were asked to make semantic judgments. At recognition, participants made yes-no recognition judgments in four different conditions. In two conditions, target items were pictures of objects; these objects had originally been encoded either in picture or in word format. In two other conditions, target items were words; they also denoted objects originally encoded either as pictures or as words. Our data show that right MTL structures are differentially involved in picture processing during encoding and recognition. A posterior MTL region showed higher activation in response to the presentation of pictures than of words across all conditions. During encoding, this region may be involved in setting up a representation of the perceptual information that comprises the picture. At recognition, it may play a role in guiding retrieval processes based on the perceptual input, i.e. the retrieval cue. Another more anterior right MTL region was found to be differentially involved in recognition of objects that had been encoded as pictures, irrespective of whether the retrieval cue provided was pictorial or verbal in nature; this region may be involved in accessing stored pictorial representations. Our results suggest that left MTL structures contribute to picture processing only during encoding. Some regions in the left MTL showed an involvement in semantic encoding that was picture specific; others showed a task-specific involvement across pictures and words. Together, our results provide evidence that the involvement of some but not all MTL regions in episodic encoding and recognition is format specific.

Adult↗
PubMed2000

Remote spatial memory in an amnesic person with extensive bilateral hippocampal lesions.

The hippocampus may have a time-limited role in memory, being needed only until information is permanently stored elsewhere, or this region may permanently represent long-term allocentric spatial information or cognitive maps in memory. To test these ideas, we investigated remote spatial memory in K.C., a patient with bilateral hippocampal lesions and amnesia for autobiographical events. In his spatial knowledge, general aspects were preserved, but details were lost, a pattern that resembled his memory loss in other domains. K.C. performed normally on allocentric spatial tests of his neighborhood and the world. He had difficulty, however, in recognizing and identifying non-salient neighborhood landmarks, and in recognizing city locations on world maps. This suggests that the hippocampus is not crucial for maintenance and retrieval of remotely formed spatial representations of major landmarks, routes, distances and directions, but is necessary for specifying location details, regardless of when they were acquired.

Amnesia↗
PubMed2000

Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia.

AIM: To assess the efficacy and safety of enteric coated capsules containing a fixed combination of 90 mg peppermint oil and 50 mg caraway oil (PCC; Enteroplant) in patients with functional dyspepsia. METHODS: A total of 96 out-patients received one capsule twice daily of PCC or placebo for 28 days. Primary efficacy variables were the intra-individual change in (i) pain intensity and (ii) sensation of pressure, heaviness and fullness between days 1 and 29, and the investigators' rating of (iii) global improvement (Clinical Global Impressions [CGI] item 2) on day 29. A global type I error of alpha=0.05 was controlled by a priori ordering of hypotheses. RESULTS: All patients were evaluable for efficacy and safety. On day 29, the average intensity of pain was reduced by 40% vs. baseline in the PCC group and by 22% in the placebo group. With regards to pressure, heaviness and fullness, a 43% reduction was observed for PCC vs. 22% for placebo. In CGI item 2, 67% (PCC) vs. 21% (placebo) of the patients were described as much or very much improved. In all three target parameters, the superiority of PCC over placebo was statistically significant. Six patients (PCC: 5; placebo: 1) reported adverse events, either unrelated to the trial, or attributable to an aggravation of the disease under investigation. Eructation with peppermint taste did not occur. CONCLUSION: These results demonstrate the good tolerability and the favourable risk-benefit ratio of PCC for the treatment of functional dyspepsia.

Adult↗
PubMed2000

[Quality management in diabetology by the PC software program DIQUAL].

Today, effective therapies for patients with diabetes mellitus. However, these therapeutic strategies are often not or incorrectly applied. Following these discrepancies for health care providers, it is mandatory to document the efficacy of diabetes treatment. However, it is hard to prove the outcome of diabetes care because of unsuitable documentation, missing parameters and different definitions of quality indicators. The computer programme DIQUAL was developed to improve the diabetes management on the diabetes ward, the diabetes out-patient department and for the documentation of outcome quality. DIQUAL is a patient database and offers structured data collecting and administration, text processing, referring letters, application and list functions, internal and external quality control, as well as cohort or cross-section analysis, data export function for nation wide data collection, system internal plausibility check and extension modules for scientific studies. On the basis of DIQUAL, the first nation wide comparison of outcome quality in the routine treatment of type 1 diabetes was possible. In 1998, we analysed the original data of 1789 patients from 32 district and university hospitals on the basis of the therapeutic goals. HbA1C decreased 1.8% and the incidence of severe hypoglycaemia was lowered to the half. There was a substantial improvement of processes in the health care institutions and the quality of information transmission to the general practitioners. This system of measurement and improvement of quality is also suitable for other areas in health care and medicine.

Ambulatory Care↗
PubMed2000

Clinical findings, imaging characteristics and outcome in catastrophic post-encephalitic epilepsy.

OBJECTIVES: The aim of this study is to characterize the clinical features and prognostic factors for intractable, post-encephalitic epilepsy. METHODS: We studied retrospectively 42 patients (26 men) evaluated between 1982 and 1999. MRI, neuropsychological findings, interictal and ictal scalp EEG were reviewed for all patients. Fifteen patients had additional stereo EEG (SEEG) studies. RESULTS: The mean age at encephalitis was 17 years (SD = 15.5); etiology was identified in 18 patients. During the acute illness, 79% had status epilepticus (SE) or recurrent seizures and 76% were in coma; mean Glasgow outcome scale (GOS) was 3.6 (SD = 0.8). The mean latency to seizure onset was 0.8 years (SD = 1.9). The majority (72%) presented with complex partial seizures with or without secondary generalization. According to interictal epileptiform findings and the predominant seizure onset pattern as found on scalp EEG, patients were unilateral temporal (UTLE) = 8, bilateral temporal (BTLE) = 12, and extratemporal/multifocal or generalized (ETMFE) = 22 patients. MRI atrophy and/or signal changes were unilateral temporal in 7 (18%), bilateral temporal in 5 (13%), multilobar/diffuse in 20 (51%), and absent in 7 (18%). ANOVA revealed significant differences in mean GOS between UTLE versus BTLE and ETMFE (4.7 versus 3.2 versus 3.6; p < 0.0001), but not in age at encephalitis. Latency to the first unprovoked seizure was shorter in patients with ETMFE compared to UTLE and BTLE (p < 0.01). Surgery was performed in 24 patients. The best outcome was obtained in UTLE (7/8 class I and II). In the others, outcome was poor in the majority (13/16 class III and IV). CONCLUSION: There is a small subgroup of patients with postencephalitic UTLE for whom the outcome is favorable. The majority of our patients had multifocal seizure onset with BTLE and ETMFE, and poor outcome after surgical treatment.

Adolescent↗
PubMed2000

Extracorporeal shock wave application for chronic plantar fasciitis associated with heel spurs: prediction of outcome by magnetic resonance imaging.

OBJECTIVE: To clarify morphologic features associated with the clinical outcome of extracorporeal shock wave application (ESWA) in chronic plantar fasciitis. METHODS: In this prospective study 43 patients (48 heels) with chronic courses of plantar fasciitis were clinically examined before and after repetitive low energy ESWA. Standard radiographs of the affected heels were obtained before ESWA to document the existence of a calcaneal heel spur. Magnetic resonance imaging (MRI) was performed before ESWA to evaluate abnormalities of the plantar fascia, the surrounding soft tissue structures, and bone marrow edema of the calcaneus. RESULTS: After ESWA (mean followup 19.3 mo), clinical evaluation of all 48 heels revealed a statistically significant decrease in the mean visual analog scale score from 74.5 to 25.4. Using the Roles and Maudsley score (RM), an established scoring system for categorizing results of treatment following ESWA for patients with plantar fasciitis, patients could be divided into 2 groups, i.e., satisfactory clinical outcome of ESWA (grades 1 and 2 by RM scale; n = 36 heels) and unsatisfactory outcome (grades 3 and 4 by RM scale; n = 12 heels). While thickness of plantar aponeurosis, soft tissue signal intensity changes, and soft tissue contrast medium uptake did not correlate with clinical outcome, the presence of a calcaneal bone marrow edema was highly predictive for satisfactory clinical outcome (positive predictive value 0.94, sensitivity 0.89, specificity 0.8). CONCLUSION: This study indicates that in patients with chronic plantar fasciitis, the presence of calcaneal bone marrow edema on pretherapeutic MRI is a good predictive variable for a satisfactory clinical outcome of ESWA.

Adult↗
PubMed1999

X-ray diffraction moiré topography as a means to reconstruct relative displacement fields in weakly deformed bicrystals.

X-ray diffraction topographs of wafers produced by separation by implanted oxygen (SIMOX) show moiré fringes in both reflection and transmission geometry. These fringes reveal deformations of the order of 10(-6) to 10(-8) between the layer and the substrate of the SIMOX material. A new method for a quantitative analysis of moiré fringes is developed and allows reconstruction with a high sensitivity of the three components of the relative displacement field between layer and substrate directly from a set of topographs. This method is used for the interpretation of moiré topographs of entire 4 in SIMOX wafers and of regions around crystal defects. Finally, the capabilities of an analysis of moiré fringes are compared with those of the usual diffraction topo-graphy.

Journal Article↗
PubMed1999

Trypanosoma brucei: improved detection of nuclear transcripts reveals a genomic position effect on nuclearly accumulating NEO RNAs visualized in stably transformed cells.

Köhler, S. 1999. Trypanosoma brucei: Improved detection of nuclear transcripts reveals a genomic position effect on nuclearly accumulating NEO RNAs visualized in stably transformed cells. Experimental Parasitology 92, 249-262. An improved fluorescent in situ hybridization method was used to visualize accumulations of nuclear RNA in procyclic Trypanosoma brucei that were stably transformed with a bacterial gene encoding neomycin phosphotransferase (NEO). In both wild-type trypanosomes and NEO transformants, nuclear accumulations of endogenous RRNAs were restricted to a ring-shaped subcompartment (nucleolus) of the nucleus. A nucleolar localization was also illuminated for NEO RNAs of trypanosomal transformants mediating their NEO transcription from the endogenous RRNA gene cluster of the T. brucei genome. In contrast, stably transformed trypanosomes generating their NEO transcripts from protein-coding areas of the T. brucei genome displayed a single dot-like accumulation of NEO transcripts, which was located in close proximity to the trypanosomal nucleolus. This pattern was observed in transformants employing either the promoter region of a protein-coding PARP transcription unit or the trypanosomal RRNA promoter for NEO transcription. Apparently, the exact location of nuclearly accumulating NEO transcripts varied among different trypanosomal transformants and relied explicitly on the genomic position of the NEO gene. These results imply that T. brucei possesses distinctive pathways for its nuclear RNA metabolism, which is consistent with a spatio-functional organization of the parasite's nucleus.

Animals↗
PubMed1999

Buffering processes in a boreal dissolved organic carbon-rich stream during experimental acidification.

The role of organic acids on surface water acidity as well as their buffering during anthropogenic acidification and subsequent recovery was studied in a field experiment on a total organic carbon (TOC)-rich stream draining the Svartberget catchment in northern Sweden. H(2)SO(4) was added to the stream to increase SO(4)(2-) concentration by 90 microeq l(-1) for 30 h. About 60% of the added H(+) was buffered by protonation of organic acids, another 20% was buffered by base cations released from the surface of the stream channel and only ca. 20% of the added acid remained unbuffered. TOC concentrations (27 mg l(-1)), and site density of carboxylic groups--8.6 microeq (mg TOC)(-1)--remained stable during the experiment. Two models of organic acid dissociation (a triprotic model and a monoprotic pH-dependent pKa model) were fitted to the experimental results. These models explained the observed variations in organic anions, but the model parameters were quite different from those reported by studies in Northern America and Central Europe. This experiment had substantially more buffering effect of TOC between pH 4.4 and 5.3, which is an environmentally important pH range.

Journal Article↗
PubMed1999

Phase II study with 5-fluorouracil and ginkgo biloba extract (GBE 761 ONC) in patients with pancreatic cancer.

The aim of the study was to evaluate the efficacy and tolerability of as well as the quality of life under treatment with 5-fluorouracil (CAS 51-21-8, 5-FU) combined with parenteral GBE 761 ONC (i.e. the ginkgo biloba special extract EGb 761) in patients with pancreatic cancer. Forty-eight patients with locally or metastatic advanced pancreatic cancer were treated within a phase II study. The treatment was repeated every three weeks until progression. Response to therapy was evaluated after 2 and 4 treatment courses. Thirty-two patients were evaluable for response. Progressive disease was observed in 22 (68.8%) patients, no change in 7 (21.9%) patients and partial response in 3 (9.4%) patients (overall response = 9.4%). GBE 761 ONC was well tolerated. Adverse events which occurred during the study consisted mainly of myelosuppression and gastrointestinal symptoms and were judged as 5-FU-related or consisted of liver toxicity, respectively, and were judged as tumour-related. These results suggest a good benefit-risk ratio of the combination of 5-FU and GBE 761 ONC in the treatment of pancreatic cancer. In comparison with the results of studies with either 5-FU or gemcitabine as single agents the combination of 5-FU/GBE 761 ONC shows comparable response rates. The toxicity of the 5-FU/GBE 761 ONC combination was low. This combination therapy therefore warrants further clinical investigation, such as a controlled clinical trial against 5-FU or gemcitabine monotherapy.

Adolescent↗
PubMed1999

Constitutive and inducible expression of green fluorescent protein in Brucella suis.

A gene fusion system based on plasmid pBBR1MCS and the expression of green fluorescent protein was developed for Brucella suis, allowing isolation of constitutive and inducible genes. Bacteria containing promoter fusions of chromosomal DNA to gfp were visualized by fluorescence microscopy and examined by flow cytometry. Twelve clones containing gene fragments induced inside J774 murine macrophages were isolated and further characterized.

Animals↗
PubMed1999

Early acidification of phagosomes containing Brucella suis is essential for intracellular survival in murine macrophages.

Brucella suis is a facultative intracellular pathogen of mammals, residing in macrophage vacuoles. In this work, we studied the phagosomal environment of these bacteria in order to better understand the mechanisms allowing survival and multiplication of B. suis. Intraphagosomal pH in murine J774 cells was determined by measuring the fluorescence intensity of opsonized, carboxyfluorescein-rhodamine- and Oregon Green 488-rhodamine-labeled bacteria. Compartments containing live B. suis acidified to a pH of about 4.0 to 4.5 within 60 min. Acidification of B. suis-containing phagosomes in the early phase of infection was abolished by treatment of host cells with 100 nM bafilomycin A(1), a specific inhibitor of vacuolar proton-ATPases. This neutralization at 1 h postinfection resulted in a 2- to 34-fold reduction of opsonized and nonopsonized viable intracellular bacteria at 4 and 6 h postinfection, respectively. Ammonium chloride and monensin, other pH-neutralizing reagents, led to comparable loss of intracellular viability. Addition of ammonium chloride at 7 h after the beginning of infection, however, did not affect intracellular multiplication of B. suis, in contrast to treatment at 1 h postinfection, where bacteria were completely eradicated within 48 h. Thus, we conclude that phagosomes with B. suis acidify rapidly after infection, and that this early acidification is essential for replication of the bacteria within the macrophage.

Ammonium Chloride↗
PubMed1999

[Peppermint oil-caraway oil fixed combination in non-ulcer dyspepsia--comparison of the effects of enteric preparations].

223 patients with non-ulcer dyspepsia (dysmotility type dyspepsia or essential/idiopathic dyspepsia, also in combination with irritable bowel syndrome) were included in a prospective, randomised, reference- and double-blind controlled multicentre trial to compare two different preparations of a fixed combination of peppermint oil and caraway oil. The aim of the trial was to evaluate the equivalence of the efficacy and tolerability of these two preparations. The test formulation consisted of the drug combination in an enteric coated capsule containing 90 mg peppermint oil and 50 mg caraway oil, while an enteric soluble formulation containing 36 mg peppermint oil and 20 mg caraway oil was used as the reference. The main target item defined was the "difference in pain intensity between the beginning and the end of therapy", measured by the patient on a visual analogue scale (0 = no pain, 10 = extremely strong pain). In 213 patients (n = 108 on the test preparation, n = 105 on the reference preparation) with mean pain intensity baseline measurements of 6.1 points in the test preparation group and 5.9 points in the reference group a statistically significant decline in pain intensity was observed in the two groups (-3.6 resP. -3.3 points; p < 0.001; two-sided one-sample t-test). Equivalent efficacy of both preparations was demonstrated (p < 0.001; one-sided t-test for equivalence). With respect to concomitant variables, the results in both groups were also similar. Regarding "pain frequency", the efficacy of the test preparation was significantly better (p = 0.04; two-sided t-test for difference). Both preparations were well tolerated. Despite the higher dose, the adverse event "eructation with peppermint taste" was less frequent in the group treated with the test formulation, due to the enteric coated capsule preparation.

Adult↗
PubMed1999

[Monoclonal anti-idiotype antibodies in immunotherapy of ovarian carcinoma (MAb ACA125) and breast carcinoma (MAb ACA14C5)].

Anti-idiotypic antibodies, which imitate a tumor-associated antigen by their variable region, offer an elegant method for the induction of a specific immune response, when used as a surrogate antigen for immunization. We generated anti-idiotypic antibodies imitating 2 different tumor-associated antigens. I. CA125 for ovarian carcinomas and II. 14C5, a tumor-associated cell substrate adhesion molecule on breast cancer cells, whereas the first approach could be introduced in a first clinical trial and the second was evaluated in an immunocompetent animal model. For the induction of an immune response against CA125, 18 patients with advanced ovarian cancer (n = 6) or heavily pretreated recurrences (n = 12) were immunized with the anti-idiotypic antibody MAb ACA125. Patients were treated with 2 mg anti-idiotype antibody every two weeks for 4 injections i.m. and then monthly. 12 of 18 patients demonstrated an anti-anti-idiotypic (Ab3) response, which was to a lower extent also directed against CA125 and 9 of 18 patients developed a CA125 specific cellular immune response by their peripheral blood lymphocytes. Based on this data a follow-up clinical trial in advanced ovarian cancer patients with minimal residual disease in an adjuvant approach after primary therapy was started to evaluate the effect of the immune response on the progression free survival. For immunotherapy of breast cancer, we generated a murine monoclonal anti-idiotypic antibody (MAb ACA14C5), which imitates a cell substrate adhesion molecule on breast cancer cells. The anti-idiotype was introduced in an immunocompetent animal to prove his capability on induction of an immune and tumor response. The results showed a highly significant difference in the tumor growth of the ACA14C5 treated group in contrast to the controls starting the immunization on day 6 after tumor cell application with 10 of 12 animals being cured from their tumor burden. Prophylactic immunization against the invasion antigen of breast cancer by anti-idiotypic antibodies showed protection against increasing tumor burden. However, in the situation of established tumors only minor responses could be detected. Vaccination with anti-idiotypic antibodies comprises an effective method for induction of a specific immune response against non-immunogenic tumor-associated antigens and should be therefore considered in immunological approaches to tumor therapy, where the primary structure and sequence of the antigen, e.g. CA125, is up to now not available.

Antibodies, Monoclonal↗
PubMed1998

Yersinia enterocolitica impairs activation of transcription factor NF-kappaB: involvement in the induction of programmed cell death and in the suppression of the macrophage tumor necrosis factor alpha production.

In this study, we investigated the activity of transcription factor NF-kappaB in macrophages infected with Yersinia enterocolitica. Although triggering initially a weak NF-kappaB signal, Y. enterocolitica inhibited NF-kappaB activation in murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y. enterocolitica prevented prolonged degradation of the inhibitory proteins IkappaB-alpha and IkappaB-beta observed by treatment with lipopolysaccharide (LPS) or nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica mutants revealed a striking correlation between the abilities of these strains to inhibit NF-kappaB and to suppress the tumor necrosis factor alpha (TNF-alpha) production as well as to trigger macrophage apoptosis. When NF-kappaB activation was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF-alpha secretion. Y. enterocolitica also impaired the activity of NF-kappaB in epithelial HeLa cells. Although neither Y. enterocolitica nor TNF-alpha could induce HeLa cell apoptosis alone, TNF-alpha provoked apoptosis when activation of NF-kappaB was inhibited by Yersinia infection or by the proteasome inhibitor MG-132. Together, these data demonstrate that Y. enterocolitica suppresses cellular activation of NF-kappaB, which inhibits TNF-alpha release and triggers apoptosis in macrophages. Our results also suggest that Yersinia infection confers susceptibility to programmed cell death to other cell types, provided that the appropriate death signal is delivered.

Animals↗