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Biomedical subjects

R Hahn

Publications and source records attributed to R Hahn.

At least 19 recordsLinked to original sources

Cytokine activity assay by means of proliferation measured in plane convex microtiter wells.

A new assay to measure cell proliferation by turbidimetric evaluation of cultures in specially designed microtiter plates was set up. The IL-2-dependent proliferation of CTLL-2 cell line was used as a model. The novel microtiter plate detection system, the General Cell Screening System (GCSS) was used for the evaluation of the cell proliferation assay. The test system utilizes the population growth rate (mu) of the cells. The tests were performed in specially designed microtiter plates which were read in a scanning spectrophotometer. These results were compared with colorimetric assays, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) as substrates. In contrast to conventional methods, the presently described system is not an end-point method, this means that cell growth can be observed over a certain period and is not limited to a single moment during the period of cell growth. Another advantage is the reduction of manual manipulations and the avoidance of toxic or radioactive substances and organic solvents. Therefore, a higher number of samples can be analyzed compared to other methods. The range for detection was 0.015-10 units IL-2 per well, and the accuracy is in the range of < 0.005 standard deviation.

Animals

[Combined "3-in-1"/sciatic nerve block. Block effectiveness, serum level and side effects using 700 mg mepivacaine 1% without and with adrenaline and prilocaine 1%].

UNLABELLED: A high dose of local anaesthetic is necessary for the combined "3-in-1"/sciatic nerve block. Prilocaine is recommended for its low toxicity. However, in some patients prilocaine results in pronounced methaemoglobin formation due to toludine. Little has been known hitherto about the use of high-dose mepivacaine for the combined 3-1/sciatic nerve block. This study was undertaken to compare the use of 700 mg mepivacaine 1% and of 700 mg prilocaine 1%. METHODS: The study was approved by the ethics committee of our hospital. Once their informed consent had been obtained in writing 3 x 20 patients (ASA 1-2) undergoing planned surgery on the foot or ankle joint were enrolled in the study. The patients were randomized to the following three groups on a double-blind basis: group 1,700 mg mepivacaine without epinephrine; group 2,700 mg mepivacaine with 0.2 mg epinephrine (1:350,000); group 3,700 mg prilocaine 1%. Arterial blood samples for determination of local anaesthetic serum levels were collected over a 120-min period. We determined methaemoglobin and oxygen saturation before and 120 min after the blockade and continued these measurements for 6 h in group 3. At 15-min intervals, all patients were questioned about early signs of toxicity. The perioperative monitoring including blood pressure, ECG and pulse oximetry. Data were analysed using ANOVA and Student's t-test, P < 0.05 considered statistically significant. RESULTS: The blocking efficacy did not differ among the groups (groups 1, 2, 3:90%, 95%, 90%). The maximum mepivacaine serum level in group 1 was 3.91 micrograms/ml +/- 0.95 and 2.94 micrograms/ml +/- 0.58 in group 2 (Fig. 2). Over the entire observation period the addition of epinephrine resulted in a significant reduction of the serum level (between 60.3% at t = 15 min and 19.7% at t = 120 min). In the prilocaine group the maximum serum level was 2.07 micrograms/ml +/- 0.56, significantly less than in either mepivacaine group. No patient showed signs or symptoms of local anaesthetic toxicity. In the prilocaine group there was wide variation in methaemoglobin formation among the patient, with a median of 10.1% (Fig. 3, Table 3). Three patients showed a maximum methaemoglobinemia between 16% and 17%. Five patients were still cyanotic after 6 h when they were transferred to the ward. The fractional SaO2 values amounted to 88% (median) with a minimum of 80.3%. CONCLUSION: Both mepivacaine 1% and prilocaine 1% are appropriate local anaesthetics for the combined 3-in-1/sciatic nerve block at a dose of 700 mg. There was no difference in the blocking efficacy. No patient showed clinical signs or symptoms of a local anaesthetic toxicity. Following prilocaine we are sometimes faced with high methaemoglobinemia, which may necessitate prolonged monitoring.

Adult

Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development.

Neurotrophin 3 (Nt3) is one of five neurotrophin growth factors which shape the development of the nervous system by regulating neuronal survival and differentiation. Peripheral neuronal subpopulations expressing the TrkC receptor tyrosine kinase respond to Nt3 with enhanced survival, mitogenesis or cell migration and these neurons are lost in homozygous Nt3 null (-/-) mutant mice. The unexplained perinatal lethality in the Nt3-/- mice, however, suggests a wider function for this neurotrophin. Here we report that Nt3 is essential for the normal development of atria, ventricles, and cardiac outflow tracts. Histological and echocardiographic image analysis of Nt3-/- animals reveal severe cardiovascular abnormalities including atrial and ventricular septal defects, and tetralogy of Fallot, resembling some of the most common congenital malformations in humans. The observed defects are consistent with abnormalities in the survival and/or migration of cardiac neural crest early in embryogenesis and establish an essential role for neurotrophin 3 in regulating the development of the mammalian heart.

Amino Acid Sequence

High reproducibility in the interpretation of intraoperative transesophageal echocardiographic evaluation of aortic atheromatous disease.

Intraoperative decisions are often based on interpretation of results from transesophageal echocardiography (TEE). One such area is the intraoperative evaluation of atheromatous disease of the thoracic aorta and subsequent classification or grading. These grading schemes are predictive of stroke after cardiac surgery. Since intraoperative strategies may be modified based on this TEE aortic atheroma grading, assessment of the interobserver variability of TEE findings between observers is essential. Forty TEE videotape segments imaging three portions of the thoracic aorta (ascending, arch, descending) were selected from 189 reports of a larger cohort. Three independent, blinded observers, experienced in TEE, evaluated these examinations for atheroma severity. If a TEE segment had insufficient data, "uninterpretable" was recorded. Weighted kappa coefficients of agreement were calculated on the three data sets. Mean weighted kappa coefficients for the three observers A, B, and C were 0.69, 0.74, and 0.72, for the ascending, arch, and descending aorta segments, respectively, representing excellent agreement. We have demonstrated uniformly high agreement for interpretation of TEE, which indicates the excellent reproducibility of TEE grading and stratification of aortic atheroma. Reproducibility within and across specialties and institutions is essential for widespread application of TEE for evaluation of the thoracic aorta.

Aged

Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide versus diethylstilbestrol.

PURPOSE: Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone. Therapy with diethylstilbestrol (DES), leuprolide, or bilateral orchiectomy has been reported to be equivalent. DES is the cheapest preparation, but has the potential for serious cardiovascular or thromboembolic complications. Flutamide is a novel antiandrogen with fewer side effects. PATIENTS AND METHODS: The Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, randomized study to compare the efficacy of flutamide (250 mg three times daily) to DES (1 mg three times daily) as the primary hormonal therapy for patients with stage D2 prostate cancer. Patients were stratified by performance status, disease sites, and history of cardiovascular disease at randomization. RESULTS: Forty-eight patients received DES and 44 flutamide. Patient characteristics were evenly distributed between the two treatments. The overall response rate was similar (DES, 62%; flutamide, 50%). Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3% of patients on DES and in 17.6% on flutamide (P = .051). Other toxicities were similar between the two treatment arms. However, DES produced significantly longer time to treatment failure (26.4 v 9.7 months, P = .016) and longer survival than flutamide (43.2 v 28.5 months, P = .040). CONCLUSION: As the primary hormonal therapy for stage D2 prostate cancer, DES caused more serious cardiovascular or thromboembolic complications than flutamide. Despite this, flutamide was not as active an initial agent as DES. However, the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined, and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies.

Administration, Oral

The effect of Chelidonium majus herb extract on choleresis in the isolated perfused rat liver.

The total ethanolic extract, the phenolic and the alkaloidal fraction of the herb of Chelidonium majus L. (Papaveraceae) were tested for their choleretic activity using the isolated perfused rat liver. The total extract significantly caused chloresis by increasing the bile acid independent flow (BAIF); the observed weak activity of both fractions, tested each and as combination, however, was not significant.

Animals

Adhesion of a glass ionomer cement to human radicular dentine.

The adhesion of cements to root canal surfaces is a crucial factor for strengthening non-vital teeth--weakened due to extensive loss of tooth structure--by cemented posts. The aim of this study was to determine the tensile strength of a glass ionomer cement (Ketac-Cem) on root canal walls following pretreatment with conditioners. Upon cleaning and shaping, 56 straight root canals--divided into seven groups--were conditioned with one of the following solutions: NaOCl (1%) + EDTA (20%), H3PO4 (37%), HNO3 (2.5%), citric acid (6%), polyacrylic acid (10% and 20%) and NaCl (0.9%) as control. Standardized dentine cylinders were prepared out of the coronal half of each root perpendicular to the root axis and subsequently split. The exposed root canal areas were coated with Ketac-Cem. Using an universal testing machine a tensile force was applied to Ketac-Cem up to fracture. Pretreatment with EDTA-NaOCl provided the strongest bond strength (2.2 MPa). The median values for the other conditioning solutions ranged from 1.2 to 1.9 MPa. The significantly weakest bond (0.5 MPa) was recorded for NaCl. The elimination of the smear layer appeared to be an essential factor in order to improve the adhesion.

Acid Etching, Dental

Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study.

PURPOSE: To compare 1 year of therapy with continuous cyclophosphamide, methotrexate, fluorouracil (5-FU), vincristine, and prednisone (CMFVP) with a short course of treatment with a doxorubicin-based regimen in the postsurgical adjuvant treatment of patients with hormone receptor-negative, node-positive breast cancer. PATIENTS AND METHODS: Five-hundred thirty-one eligible women with hormone receptor-negative, node-positive breast cancer were randomized to receive either 1 year of therapy with CMFVP or 20 weeks of therapy with four 5-week courses of treatment with 5-FU, doxorubicin, cyclophosphamide, and methotrexate (FAC-M). RESULTS: At a median follow-up time of 4.9 years, the two treatment arms cannot be demonstrated to be different with respect to overall survival (stratified log-rank, P = .27). The 5-year survival rate is 64% on the CMFVP arm and 61% on the FAC-M arm. CMFVP produces marginally superior disease-free survival (P = .06). The estimated 5-year disease-free survival rate is 55% for patients treated with CMFVP as opposed to 50% for patients treated with FAC-M. CONCLUSION: Neither regimen was shown to be superior in terms of overall survival. Because the disease-free survival produced by CMFVP is marginally superior to that produced by FAC-M, we do not recommend FAC-M for further investigation or for routine use. Possible implications of this study are discussed in the context of other adjuvant chemotherapy trials.

Adult

Plasma atrial natriuretic peptide concentration and renin activity during overhydration with 1.5% glycine solution in conscious sheep.

We estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls. Glycine infusions resulted in a four-fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP-stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the "transurethral resection (TUR) syndrome." The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow-up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration. The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance.

Analysis of Variance

Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma: an Eastern Cooperative Oncology Group trial.

PURPOSE: This multicenter cooperative group phase I/II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 micrograms subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25% of all drugs was performed. RESULTS: Six complete responses and 15 partial responses were observed (60%; 95% confidence interval, 42% to 76%). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23%) early deaths were observed. CONCLUSION: This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VACI therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.

Aged

The conservative management of a discolored pulpless premolar: a case report.

Endodontically treated premolars may discolor with time, impairing the esthetic appearance. Frequently combined with large defects, they are subject to an increased risk of fracture. The restoration of such teeth with a cast post and core and a separate porcelain-fused-to-metal crown results in additional loss of intact tooth structure. A case is presented in which the cavity of a discolored, pulpless maxillary premolar was restored, without further loss of tooth substance, with an adhesively luted porcelain inlay after intracoronal bleaching, a technique traditionally used to lighten discolored, pulpless anterior teeth.

Adult

High-resolution XANES studies on vanadium-containing haloperoxidase: pH-dependence and substrate binding.

High-resolution X-ray absorption vanadium K-edge spectra were recorded for samples of vanadium-containing bromoperoxidase from the brown alga, Ascophyllum nodosum, at pH 9, 7, 5 and 4, as well as for enzyme samples containing the substrates, hydrogen peroxide and bromide. The well-resolved features of the XANES spectra are discussed. The pH-dependence of the structure of the active site has been studied revealing no significant change of the absorption features. We were able to detect an interaction of H2O2 with the vanadium site of the bromoperoxidase using XAS spectroscopy, whereas addition of bromide causes no energy shift of the XANES spectrum. The possible role of vanadium during the enzymatic reaction is discussed on the basis of our results.

Binding Sites

Immuno- and lectin histochemistry of epithelial subtypes and their changes in a radiation-induced lung fibrosis model of the mini pig.

Cell types of lung epithelia of mini pigs have been studied using a panel of monoclonal and polyclonal antibodies against cytokeratins (CKs) and vimentin and three lectins before and after radiation-induced fibrosis. In normal tissues, CK18 specific antibodies reacted above all with type II alveolar epithelial cells, while CK7 and pan CK-specific antibodies stained the whole alveolar epithelium. In bronchial epithelial cells, CKs 7, 8, 18 and focally CKs 4 and 13 as well as vimentin were found. Cell specificity of the CK pattern was confirmed by double label immunofluorescence using type II cell-specific Maclura pomifera (MPA) lectin, type I cell specific Lycopersicon esculentum (LEA) lectin and capillary endothelium-binding Dolichos biflorus (DBA) lectin. In experimental pulmonary fibrosis, enhanced coexpression of CK and vimentin was observed in bronchial epithelium. Subtypes of alveolar epithelial cells were no longer easily distinguishable. CK18 was found to be expressed in the entire alveolar epithelium. The gradual loss of the normal alveolar epithelial marker, as seen by the binding of MPA to type I-like cells, of LEA to type II-like cells and the partial loss of MPA-binding to type II cells, was paralleled by the appearance of CK4, typical for squamous epithelia, and the occurrence of DBA-binding in epithelial cells. Implications of these results for general concepts of intermediate filament protein expression and lectin binding in the fibrotic process are discussed.

Animals

Microbial accumulation and vitality on different restorative materials.

A new technique using standardized test facings was designed to evaluate interdental plaque accumulation on different restoration materials. In 10 volunteers, a total of 40 samples, including enamel, two different ceramics and a bonding composite, were inserted one by one into a precision attachment in an experimental inlay bordering on either the lower second premolar or the lower first molar. Bacterial accumulation on each approximal specimen was allowed to mature for 3 d. Following microbiological processing of the plaque samples, total bacterial counts, colony forming units and the bacterial vitality were determined. The results revealed different accumulation rate patterns. Both ceramics accumulated less plaque with a reduced vitality compared to enamel, while the bonding composite showed no significant differences compared to the natural tooth substance. No significant differences were detected when comparing the two examined ceramics.

Adult

A three-generational presentation of separation anxiety in childhood with agoraphobia in adulthood.

School phobia belongs to a family of childhood anxiety states that appear to be related to adult forms of anxiety disorders, particularly to panic disorder with agoraphobia. School phobia appears to affect at least 5 percent of elementary school children and 2 percent of middle school children. Many of these children would be classified under the current DSM-III-R system of nomenclature as suffering from separation anxiety disorder. The present study is related to the elaboration of a three-generation family presentation of separation anxiety disorder manifesting itself as school phobia in childhood, which evolves toward panic disorder with agoraphobia in young adulthood and diffuse anxiety with hypochondriacal features in later life. All 13 genetically related members of the family investigated have been afflicted. The children with separation anxiety disorder and school phobia in this family who have been treated with imipramine have shown a resolution of anxiety symptoms that has allowed their successful return to school. The information from this family would fit into a model that describes a spectrum of anxiety disorders that present with different manifestations of overt psychopathology throughout the life cycle. We hope to follow this family prospectively over the next 30 years.

Adolescent

Microstructure and strength analysis of ultrasonically shaped ceramics.

In this study, the influence of a new ultrasonic shaping procedure on the surface quality, microstructure, bending strength and fatigue behaviour of a feldspathic porcelain was investigated. A total of 120 standardized (ISO 6872) autoglazed, ground, lapped and ultrasonically machined porcelain test bars were analyzed. Another 24 equiformat experimental alumina ceramics, which were ultrasonically machined, as well as 24 nontreated fload glass specimen served as controls. It could be shown that the porcelain removal process with diamond grinding wheels yielded a rough surface microrelief and lead to structural subsurface damage, decreasing bending strength and fatigue behaviour. In contrast, ultrasonic shaping resulted in a smoother surface and prevented damage to the subsurface layer of the machined brittle porcelain, although, the smoothest surfaces were achieved by lapping. Both bending strength and fatigue behaviour of the conventional dental porcelain were increased by ultrasonic machining. However, the fracture toughness of the experimental alumina was substantially higher and was not subjected to a decrease in fatigue.

Aluminum Oxide