Quantitative gas chromatography-mass spectrometry determination of pentaerythrityl tetranitrate metabolites pentaerythrityl trinitrate, pentaerythrityl dinitrate and pentaerythrityl in human plasma

Assay methods based on gas chromatography/mass spectroscopy (GC-MS) may be used to measure PE1N (pentaerithrityl mononitrate, CAS 1607-00-7), PE2N (pentaerithrityl dinitrate, CAS 1607-01-8) and intermediate pentaerithrityltrinitrate (PE3N, CAS 1607-17-6) in human plasma. Based on this method a simplified method to quantify the metabolites of PETN (pentaerithrityl tetranitrate, CAS 78-11-5, Pentalong) is described. In the present study a consistent method to extract the metabolites of human plasma and following derivatisation is described. Since PE1N can be quantified up to 150 ng/ml, PE2N and PE3N up to 30 ng/ml in human plasma, a dilution of the plasma samples can be avoided. The mean recovery rate is not so high as in other described methods, and inaccuracy is about 10%. Therefore a calibration range between 0.2-30 ng/ml of PE2N and 1-150 ng/ml of PE1N has to be considered. The described method offers an alternative and applicable option to quantify the PETN-metabolites and elucidate their part as NO-donors.     

Activity and acceptability of piribedil in Parkinson's disease: a multicentre study

Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.1, SD 0.6 (43–79) years with a 2.1, SD 0.2 (1–15) year history of Parkinson's disease. Mean disease stage was 1.82 (1–4) by the Hoehn and Yahr classification. Tremor was the predominant clinical feature in 42 patients; the remaining 71 patients displayed the full parkinsonian syndrom. Trivastal 50 mg LP was prescribed stepwise up to doses of 150–250 (207, SD 6.4) mg/day at the end of 3 months. No concomitant antiparkinsonian medication was given. Patients were clinically assessed at 1, 2 and 3 months on the Webster scale, a specific tremor scale and the HARD depression scale. Mean results were as follows in the 90 patients completing the study. On the Webster scale, tremor fell from 1.7 to 1 (–41%,P<0.001), bradykinesia=" from=" 1.5=" to=" 0.8=">P<0.001) and=" rigidity=" from=" 1.3=" to=" 0.9=">P < 0.001);=" on=" the=" specific=" scale,=" rest=" tremor=" decreased=" in=" daily=" duration=" and=" amplitude=" from=" 3.9=" to=" 2.4=">P < 0.001)=" and=" from=" 2.9=" to=" 2.1=">P < 0.001),=" respectively.=" the=" 32=" patients=" in=" whom=" tremor=" was=" the=" predominant=" feature=" improved=" their=" total=" score=" on=" the=" webster=" scale=" from=" 5.8=" to=" 4.7=">P<0.05) and=" their=" tremor=" score=" from=" 1.7=" to=" 1.2=">P < 0.05).=" the=" 58=" patients=" with=" the=" full=" parkinsonian=" syndrom=" improved=" their=" total=" webster=" score=" from=" 11.8=" to=" 6.9=">P < 0.001).=" eight=" of=" the=" ten=" items=" on=" the=" scale=" were=" significantly=" reduced,=" from=" between=" 33%=" (facial=" expression)=" to=" 53%=" (manual=" bradykinesia).=" the=" depression=" rating=" fell=" from=" 10.2=" to=" 7.3=">P < 0.001),=" the=" most=" marked=" improvement=" being=" in=" mood=" and=" inhibition.=" in=" conclusion,=" monotherapy=" with=" trivastal=" 50=" mg=" lp=" at=" a=" mean=" dose=" of=" 200=" mg/day=" is=" effective=" within=" 1=" month=" regarding=" the=" major=" features=" of=" parkinson's=">     

Spine deformity index (SDI) versus other objective procedures of vertebral fracture identification in patients with osteoporosis: a comparative study

Radiologic identification of vertebral fractures is most important in the diagnosis and monitoring of patients with spinal osteoporosis. Different methods, using vertebral height measurements for fracture identification, have therefore been developed. We compared four methods for fracture identification in spinal x-rays of 62 female patients with primary osteoporosis. The methods of Hedlund and Gallagher, Melton et al., and Davies et al. are based on the ratio of heights within one vertebra or of the height ratios of adjacent vertebrae; all three methods result in counting the number of vertebral fractures. The fourth method of Minne et al. relates anterior, middle and posterior heights of the vertebrae between T5 and L5 to the respective heights of T4. The relative vertebral heights of patients with osteoporosis are compared to the respective relative heights (anterior, middle, and posterior) of normal subjects (T5-L5). This allows the identification of fractured vertebrae, as well as a quantification of the extent of deformation due to these fractures (spine deformity index, SDI). The same measurement data of 62 spinal x-rays of anterior, middle, and posterior heights between T4 and L5 were used to detect vertebral fractures by the four different methods. Correlation between the number of identified fractures by the different methods ranged between r = 0.56 and 0.83. On the other hand, we found a remarkable difference in the mean number of identified fractures and a discrepancy in the identification of single vertebrae as fractured or not. All four methods revealed an accumulation of fractures in the midthoracic area and in the region of transition from thoracic to lumbar spine. Vertebral fractures as identified by SDI were not detected by the other three methods in 12-29% of the cases, even if vertebral height reduction was more than 6 mm. The reliability of each method was examined by the determination of "decreasing" number of fractures during follow-up. A decrease in the number of fractures was found in about 25% patients, if using the three methods that count only the number of fractures. We obtained a 3.6% decrease in the number of fractures using the fourth method. Furthermore, the decrease in SDI values in follow-up was within the range of variance. We therefore believe that SDI and related procedures are reliable in quantifying spinal osteoporosis and monitoring during follow-up.     

The natural history of somatosensory and autonomic nerve dysfunction in relation to glycaemic control during the first 5 years after diagnosis of Type 1 (insulin-dependent) diabetes mellitus

Summary The natural evolution of neural dysfunction was studied prospectively over 5 years following diagnosis of Type 1 (insulin-dependent) diabetes in 32 patients aged 12–36 years. Motor and sensory nerve conduction velocities, heart rate variation at rest and during deep breathing, and pupillary function were measured at diagnosis and after 3,12, 24,48, and 60 months. Thermal and vibration sensation thresholds were determined after 24, 48, and 60 months of diabetes. Mean HbA₁ levels of months 3–60 within the normal range of <8.3% (7.3±0.2%) were observed in 13 patients (Group 1), while a mean HbA₁ of months 3–608.3% (10.0±0.3%) was found in 19 patients (Group 2). Mean nerve conduction was significantly diminished in Group 2 as compared with Group 1 in at least 4 out of 6 nerves tested during months 12–60 (p<0.05). Both tests of heart rate variation were significantly impaired in Group 2 as compared with Group 1 after 24 and 60 months (p<0.05), but no differences in pupillary function were observed between the groups. Thermal discrimination but not vibration perception thresholds on the foot were significantly higher in Group 2 than in Group 1 at 40 and 60 months (p<0.05). Abnormalities in nerve conduction, thermal discrimination, and heart rate variation, but not vibration perception threshold and the pupillary function tests were significantly more frequent in Group 2 than in Group 1 at 60 months (p<0.05). After 60 months, none of the patients of Group 1, but 6 and 4 patients of Group 2 developed subclinical or symptomatic neuropathy, respectively (p<0.05). These findings suggest that the evolution of subclinical and symptomatic neuropathy during the first 5 years after diagnosis of Type 1 diabetes may be predicted by poor glycaemic control and prevented by near-normoglycaemia.     

Chemical modification of membrane proteins by brominated taurodehydrocholate in isolated hepatocytes; relationship to the uptake of cholate and of phalloidin and to the sensitivity of hepatocytes to phalloidin

Summary In vitro treatment of isolated rat hepatocytes with brominated taurodehydrocholic acid (BTC) reduced their sensitivity against phalloidin and inhibited the uptake of phalloidin as well as of cholate in an irreversible and concentration dependent manner. BTC was taken up itself by liver cells; this process was inhibited by 4,4-diisothiocyano 2,2-stilbene disulfonate (DIDS).When hepatocytes were incubated with ³⁵S-BTC their plasma membranes contained five labeled protein species with molecular weights of 67,000, 49,000, 38,000, 32,000 and 24,000 as shown by SDS-electrophoresis. No marked difference was observed when isolated plasma membranes from livers were directly treated with the affinity label. DIDS suppressed covalent binding of ³⁵S-BTC to membrane components drastically. Incubation of phalloidin insensitive AS-30D ascites hepatoma cells with ³⁵S-BTC did not result in a chemical modification of the above five proteins. This agrees with an earlier observation that hepatoma cells are unable to take up phalloidin and bile acids (Petzinger et al. 1979; Rufeger and Grundmann 1977; Kroker et al. 1978).Abbreviations used BTC brominated taurodehydrocholic acid - ³⁵S-BTC ³⁵S labeled brominated taurodehydrocholic acid - DIDS 4,4-diisothiocyano 2,2-stilbene disulfonate - [³H]DMP [³H]demethylphalloin This work was supported by the Deutsche Forschungsgemeinschaft     

28. Primärer und sekundärer Hyperparathyreoidismus

Zusammenfassung Beim primären, autonomen Hyperparathyreoidismus führt die Parathormon (PTH)-Überproduktion zu Symptomen am Skelet und (infolge Hypercalciämie) an Nieren, intestinalen Organen, Zentralnervensystem u. a. Beim sekundären Hyperparathyreoidismus werden die Nebenschilddrüsen durch chronische Hypocalciämie (bei Niereninsuffizienz infolge Phosphatstau und Störung des Vitamin D-Stoffwechsels) stimuliert, Behandlungsbedürftigkeit ergibt sich bei Skeletschäden. Für die Diagnostik stehen Calcium-, PTH- u. a. blutchemische Bestimmungsmethoden zur Verfügung, sie werden ergänzt durch Röntgenologie und Knochenhistologie.Mit Unterstützung der Deutschen Forschungsgemeinschaft, SFB 87 Endokrinologie, Ulm     

Stellenwert der Sonographie in der Frühdiagnostik des Nierenzellkarzinoms

The importance of ultrasonography in early detection of renal cell carcinoma was analyzed for 1854 patients, who were operated from 1975 to 1997. The 5-year survival rate of all patients amounts to 75%, the 10- and 20-year survival rate was 68% and 64%. While from 1975 to 1986 tumor symptoms like hematuria (30%), abdominal pain (19%) and palpable mass (3%) lead to diagnosis of renal cell carcinoma in 56% of all cases, there were only 26% from 1987 to 1997. 83% of asymptomatical tumors from 1987 to 1997 were accidentally detected by means of ultrasonography in a kidney independent examination. These tumors are significantly smaller (5.5 cm) than the tumors of symptomatical patients (7.8 cm) and show often a significantly lower local tumor stage, a better tumor grade, frequently lymph nodes, which are free of tumor infiltration and more rarely distant metastasis. The 5-year survival rate of patients with incidental tumors, detected by ultrasonography (82%) was significantly better (log rank < 0.001) in comparison with the symptomatical patients (72%). These results verify 1. The effectivity of ultrasonography in early diagnosis of renal cell carcinoma and 2. The advantage of survival on patients with early tumor detection. That's why asymptomatic patients, who selected under risk factors should be examinated by ultrasonography consistently too.     

The role of growth factors in wound healing

Growth factors are mediators with essential importance for undisturbed repair process after wounding. The well coordinated concert of these substances is necessary for healing with complete restoration of function and morphology. These complex mechanisms are disturbed during secondary and delayed repair. The result is protracted healing course and inferior scar quality--either hypo- or hypertrophic. Local and systemic application of these growth factors seems to add important instruments for therapeutic use in the treatment of chronic wounds. Knowledge from experimental research is encouraging, although the exact mechanisms of synergistic action are not completely understood. However, the results from clinical use in controlled studies do not meet these expectations by far. The main reasons for this dilemma are thought to be little understanding in the complex interactions of these substances. In fact, different wound entities seem to reveal different cytokine profiles during the course of repair. Further intensive research therefore is required for the rational use of growth factors in the clinical setting.