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C Hoffmann

Publications and source records attributed to C Hoffmann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Structure-activity relationship of cytoplasmic 5'-nucleotidase substrate sites.

Various 5'-nucleotidases (EC 3.1.3.5) exist in vertebrate tissues. The sequence and cDNA cloning of the membrane-bound ecto-5'-nucleotidase (e-N) and one of the cytosolic isoenzymes, IMP-preferring (c-N-II), but not the cytosolic AMP-preferring form (c-N-I), have been reported. While c-N-II has a broad tissue distribution, c-N-I is found only in vertebrate heart. The published data on substrate specificity involve mainly the naturally occurring nucleoside monophosphates, without a systematic structure-activity relationship study. In the present study we have used a series of AMP and IMP analogues to examine the structure-activity relationship for c-N-I and c-N-II in detail. The rank order of activity of the test compounds differed substantially between c-N-I and c-N-II. c-N-I and c-N-II varied with respect to the following interactions with substrate: (1) hydrogen-bond formation with the substituent in the 6-position of the purine ring (a donor-type with c-N-I and an acceptor-type with c-N-II); and (2) hydrophobic attraction of the 6-position unsubstituted purine ring (more pronounced with c-N-I than with c-N-II). No better substrate than 5'-AMP was found for c-N-I. We propose that c-N-I functions as an AMP-binding protein in the myocardial cell with an important role during ischaemic ATP breakdown when AMP accumulates rapidly.

5'-Nucleotidase↗
PubMed1996

[Surgery versus radiotherapy in Ewing's sarcoma with good prognosis. Analysis of the CESS-86 data].

PURPOSE: The evaluation of radiotherapy and surgery as exclusive local treatment in comparably selected subgroups of patients with Ewing's sarcoma on the basis of the CESS 86-data. PATIENTS AND METHODS: In the German multicenter Ewing's sarcoma study CESS 86, treatment consisted of four 9-week-courses of VACA- or VAIA-chemotherapy plus local therapy. VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin) was given in low-risk extremity tumors with a tumor volume below 100 cm3. High-risk patients with central lesions or a tumor volume > 100 cm3 received VAIA (ifosfamide instead of cyclophosphamide). Local therapy started after one complete chemotherapy course in week 10. Based on an individual decision in each patient, local therapy was either radical surgery or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy. Because of poor results with radiotherapy in a preceding study, it was intended to restrict irradiation to patients with small lesions. RESULTS: Hundred and seventy-seven protocol patients were recruited from January 1986 through June 1991 and 176 received local therapy: 39 underwent radical surgery, 44 received definitive radiotherapy and 93 were treated with resection and postoperative irradiation. The median tumor volume was higher in patients with radiotherapy as compared to combined local treatment or radical surgery, 156 cm3 versus 140 cm3 versus 102 cm3. The overall 5-year survival after radiotherapy and surgery was nearly identical, 63% versus 67% for the whole group 75% versus 65% in tumors < 100 cm3 volume and 65% versus 67% in tumors with 100 cm3 to 600 cm3 volume, respectively. CONCLUSIONS: With regard to tumor volume, the most important single prognostic factor in Ewing's sarcoma, irradiated patients were poorer selected than surgically treated patients despite the fact that a selection of good-risk patients for radiotherapy was intended. The nearly identical survival figures after surgery and radiotherapy suggest that radiotherapy is as effective as surgery if selection of patients is comparable.

Adult↗
PubMed1995

Acquired von Willebrand disease in malignant peripheral neuroectodermal tumor (PNET).

In week 12 of the EICESS 92 protocol a 12-year-old boy with pelvic PNET developed acquired von Willebrand disease: bleeding time was prolonged (> 15 min) and von Willebrand factor antigen (54%) and ristocetin cofactor activity (50) were reduced. Platelet aggregations with thrombin and collagen and the number of major platelet glycoproteins/per platelet did not differ from the controls. After Haemate P (Behring Werke, Marburg, Germany) bleeding time normalized and surgery could be performed without occurrence of bleeding episodes. Three weeks after surgery bleeding time, ristocetin cofactor activity, and von Willebrand factor antigen increased to normal paediatric values. Without occurrence of further bleeding episodes the patient received another 10 courses of polychemotherapy (EICESS 92).

Bone Neoplasms↗
PubMed1995

Nitric oxide mediates microvascular permeability in the isolated perfused rat mesentery?

The permeability influencing effect of nitric oxide was studied by means of an isolated perfused mesentery preparation in combination with a intravital/fluorescence microscopic set up. As a fluorescent marker served FITC-dextran mol wt 70,000 daltons. Tissue treatment was performed by application of NO-donors like SNP or GTN. Additionally the effects of bradykinin, L-nitroarginine or the combination of both were tested in regard to a permeability modulation. The results point out that NO-donors did not enhance microvascular permeability, whereas the permeability increasing effect of bradykinin is mediated by an NO-independent pathway.

Animals↗
PubMed1995

Ewing's sarcoma of the ribs. A report from the cooperative Ewing's sarcoma study.

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.

Adolescent↗
PubMed1995

[The magnetic resonance tomography of Ewing's sarcomas: the morphology and tumor extension].

PURPOSE: The morphology and delineation of Ewing sarcoma in magnetic resonance imaging was investigated. METHODS AND MATERIALS: Magnetic resonance images (spin-echo techniques; T1-w pre/post gadolinium, T2-w) of 59 patients as part of a multicenter study were evaluated retrospectively. Qualitative image analysis was performed: signal intensity (point of reference extraosseous: muscle, intraosseous: bone marrow), enhancement patterns, lesion delineation and differentiation between tumor and oedema. RESULTS: Signal intensity: T1-w: extraosseous: 75% isointense, intraosseous: 92% hypointense; T2-w extraosseous: 100% hyperintense, intraosseous: 93% hyperintense. Enhancement pattern: 97% both extra- and intraosseous. Best delineation intraosseous in T1-w (53% good, 36% very good), extraosseous in gadolinium enhanced T1-w (46% good, 37% very good) and T2-w (55% good, 33% very good). Differentiation between tumour and oedema was intraosseous not possible, extraosseous in T2-w in 61%. CONCLUSION: Morphology of Ewing sarcoma in magnetic resonance imaging is rather uniform. The lesion is intra- and extraosseous sharply delineated, though tumour and oedema can be rarely differentiated.

Adolescent↗
PubMed1995

Comparative bioavailability of metronidazole formulations (Vagimid) after oral and vaginal administration.

Bioavailability of Vagimid 500 tablets (film coated, 500 mg metronidazole) and absorption of metronidazole into the systemic circulation after vaginal administration of Vagimid vaginal tablets (100 mg metronidazole) relative to respective listed references were studied in 16 female healthy volunteers (age 21-37 years, weight 45-67 kg, height 158-179 cm). Metronidazole and its main hydroxylated metabolite were measured using an HPLC-method with detection limits of 0.025 and 0.25 micrograms/ml (for vaginal and oral studies), respectively. Extent of absorption was assessed by AUC0-infinity (bioequivalence range 0.80-1.25), rate of absorption by Cmax/AUC0-infinity (bioequivalence range 0.70-1.43). Geometric means and 90%-confidence intervals of the ratios of these primary characteristics were calculated using a multiplicative model. Vagimid 500 tablets were bioequivalent to the reference formulation with regard to extent and rate of absorption of metronidazole because of AUC0-infinity = 0.995 (0.84-1.18) and Cmax/AUC0-infinity = 1.11 (0.94-1.30). The absorption of metronidazole into the systemic circulation after vaginal administration of Vagimid vaginal tablets caused maximal serum concentrations between 433 and 1,156 ng/ml after 8-20 h which are bactericidal only for the most susceptible anaerobic germs and which are most likely only of marginal importance for drug safety.

Absorption↗
PubMed1995

[Subjective evaluation criteria in psychiatric care--methods of assessment for research and general practice].

Evaluation of psychiatric care is an important task in research and in routine conditions. It requires definition of criteria. Subjective criteria are, for different reasons, of increasing interest. Subjective quality of life, subjective needs for help and support and patients' assessment of psychiatric treatment are regarded as particularly relevant criteria. We present and briefly discuss instruments for assessment of these criteria, that are new at least in the German language. Results of a first cross-sectional study in a community care setting are reported. Regarding quality of life healthy groups were examined too. The findings suggest that the instruments are usefully applicable and that they may produce plausible results.

Adult↗
PubMed1995

Reference tables for the intrasubject coefficient of variation in bioequivalence studies.

Bioequivalence studies are usually performed as crossover studies and, therefore, information on the intrasubject coefficient of variation is needed for sample size planning. However, this information is usually not accessible in publications on bioequivalence studies, and only the pooled inter- and intrasubject coefficient of variation for either test or reference formulation is reported. It is the purpose of the present communication to provide reference values of the intrasubject coefficient of variation for various previously investigated drugs. The presentation includes pertinent pharmacokinetic characteristics for immediate- and extended-release formulations in single- and multiple-dose crossover studies.

Administration, Oral↗
PubMed1995

Relative bioavailability of different valproic acid formulations.

Relative bioavailability of valproic acid after oral administration of 2 Convulsofin (test) tablets each containing 300 mg calcium valproate (263.4 mg valproic acid) was studied versus 2 references (2 dragees each of 300 mg calcium valproate, ref.A, 600 mg sodium valproate in liquid form (258.7 mg valproic acid), ref.B). The controlled, randomized, clinical trial was performed in 16 healthy volunteers (12 males, 4 females, body weight 58-100 kg, Broca index 0.85-1.15) according to a 3-period changeover design with 7 days wash-out between 2 periods. Valproic acid was measured in serum with a GC method. Pharmacokinetic evaluation was done by compartment free methods. Test was considered bioequivalent with ref.A or ref.B with reference to extent of absorption if the 90% confidence interval of their AUC ratio was within the range of 0.80-1.25, and with respect to rate of absorption if the 90% confidence intervals of Cmax/AUC ratios were within 0.70-1.43. The point estimators (90% confidence limits) of the AUC ratios of test/ref.A and test/ref.B were 0.952 (0.882-1.028) and 1.063 (0.989-1.141), respectively. The point estimators (90% confidence limits) of Cmax/AUC ratios were 1.005 (0.923-1.094, test/ref.A) and 0.915 (0.845-0.991, test/ref.B). The following Cmax ratios were calculated: 0.957 (0.866-1.057, test/ref.A) and 0.972 (0.886-1.067, test/ref.B). No serious and unexpected adverse events were observed during the clinical trial. Test was bioequivalent with the 2 reference formulations ref.A and ref.B with respect to extent and rate of absorption. However, according to the secondary criterion tmax test tablets were more rapidly bioavailable than ref.A dragees (tmax-difference: -2.6 (-4.8 to -0.3 h) but more slowly (tmax-difference:+0.8 (-1.3 to +2.9 h) than ref.B juice.

Absorption↗
PubMed1994

Effects of acidosis and alkalosis on mechanical properties of hypertrophied rat heart fiber bundles.

Effects of alkalosis (pH 7.4) or acidosis (pH 6.8) on the intrinsic mechanical properties of control and pressure-overloaded rat hearts were studied in Triton X-100-treated left ventricular fiber bundles. In control bundles, Ca sensitivity [pCa required for one-half maximal response (pCa50)] was 5.520 +/- 0.012 at pH 7.1. Alkalosis increased it by 0.357 +/- 0.018 pCa unit, whereas acidosis decreased it by 0.365 +/- 0.014 pCa unit with no change in Hill coefficient. Maximal tension was decreased by acidic pH and increased by alkaline pH. Stiffness was measured by the response to quick length changes. Acidosis decreased maximal stiffness but increased the stiffness-to-force ratio, whereas alkalosis increased maximal stiffness but had no effect on stiffness-to-force ratio, suggesting that acidosis decreased the force generated per cross bridge. Alkalosis increased the time constant of tension recovery following a quick stretch from 10.6 +/- 0.66 to 17.45 +/- 1.83 ms, suggesting a decreased cross-bridge cycling rate. Pressure overload induced by thoracic aortic stenosis for 4-6 wk led to a 200% cardiac hypertrophy associated with a shift from fast to slow ventricular myosin. pCa50 of hypertrophied bundles was not different from control (5.541 +/- 0.012). Ca sensitivity was increased by 0.383 +/- 0.008 in alkaline medium and decreased by 0.325 +/- 0.009 in acidic medium. Stiffness-to-force ratio was decreased in acidic pH, and the time constant of tension recovery was increased from 31.0 +/- 0.4 to 34.9 +/- 0.25 ms by alkalosis. In hypertrophied bundles, maximal tension was decreased by acidic pH but not changed by alkalosis. These results show that in the small pH range of our study 1) pH changes have symmetrical effects on Ca sensitivity in both control and hypertrophied bundles, 2) a decrease or an increase in H+ concentration does not have symmetrical effects on the mechanics of the cross bridges, and 3) changes in the phenotype of contractile proteins induced by aortic stenosis do not influence Ca sensitivity, only moderately influence the response to pH changes, and mainly affect the cross-bridge cycling rate.

Acidosis↗
PubMed1993

[Initial findings using dynamic magnetic resonance tomography in the diagnosis of inflammatory diseases of the sacroiliac joint].

Up to now 42 patients with clinically suspected diagnosis of sacroiliitis (including 19 patients with confirmed spondylitis ankylosans) and 12 healthy volunteers were examined via magnetic resonance tomography. In oblique sections parallel to the plane of the sacrum the signal intensity patterns from normal and pathological tissues of the sacroiliac articulations were evaluated by plain T1-weighted spin-echo sequences and T2*-weighted FLASH sequences. In addition we used a dynamic FLASH measurement following intravenous application of gadolinium-DTPA for quantitative calculation of signal-time courses. This method has proved to be capable of definitely differentiating normal findings of sacroiliac articulations from inflammatory changes (p = 0.0001) and also enables quantification of the inflammatory activity.

Adult↗
PubMed1993

Mechanical properties of rat cardiac skinned fibers are altered by chronic growth hormone hypersecretion.

Chronic growth hormone (GH) hypersecretion in rats leads to increased isometric force without affecting the unloaded shortening velocity of isolated cardiac papillary muscles, despite a marked isomyosin shift toward V3. To determine if alterations occurred at the level of the contractile proteins in rats bearing a GH-secreting tumor (GH rats), we examined the mechanical properties of skinned fibers to eliminate the early steps of the excitation-contraction coupling mechanism. We found that maximal active tension and stiffness at saturating calcium concentrations (pCa 4.5) were markedly higher in GH rats than in control rats (tension, 52.9 +/- 5.2 versus 38.1 +/- 4.6 mN.mm-2, p < 0.05; stiffness, 1,105 +/- 120 versus 685 +/- 88 mN.mm-2.microns-1, p < 0.01), whereas values at low calcium concentrations (pCa 9) were unchanged. In addition, the calcium sensitivity of the contractile proteins was slightly but significantly higher in GH rats than in control rats (delta pCa 0.04, p < 0.001). The crossbridge cycling rate, reflected by the response to quick length changes, was lower in GH rats than in control rats (62.0 +/- 2.6 versus 77.4 +/- 6.6 sec-1, p < 0.05), in good agreement with a decrease in the proportion of alpha-myosin heavy chains in the corresponding papillary muscles (45.5 +/- 2.0% versus 94.6 +/- 2.4%, p < 0.001). The changes in myosin heavy chain protein phenotype were paralleled by similar changes of the corresponding mRNAs, indicating that the latter occurred mainly at a pretranslational level. These results demonstrate that during chronic GH hypersecretion in rats, alterations at the myofibrillar level contribute to the increase in myocardial contractility observed in intact muscle.

Animals↗
PubMed1991

[Clinical pharmacokinetics of lidocaine after intraoral nerve block].

Aim of this study was to show the time course of plasma concentrations of 2% lignocaine with adrenalin at a concentration of 1:100,000. Four retinated third molars were removed in one session in 23 patients. For local anaesthesia in each patient we used 10 ml of Xylocaine 2% (Astra), which is commonly used in dentistry. The plasma-concentration was measured for the first 30 minutes after injection of the local anaesthetic using high pressure liquid chromatography (HPLC). Our results suggest that partially intravascular injection could not be avoided although careful aspiration was carried out before injecting. Neither subjective nor objective adverse central nervous effects were seen in our patients. Nevertheless we consider a peripheral intravenous cannula and ECG-monitoring strongly recommended in all major operations under local anaesthesia.

Adolescent↗