Blood coagulation activation and fibrinolysis during a downhill marathon run.

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.     

Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Boerhaave’s syndrome: Primary repair vs. esophageal resection—Case reports and meta-analysis of the literature

Boerhaave’s syndrome is a life-threatening disease with a high mortality. With regard to the heterogeneity of treatment strategies, no comparative studies exist and recommendations remain controversial. Seventeen cases of Boerhaave’s syndrome operated on between 1989 and 2000 at our hospital were reviewed retrospectively to compare the time period between perforation and diagnosis, and the morbidity and mortality among the different treatment options. In addition, we conducted a meta-analysis of the literature including all series containing five or more patients and compared the findings with our own data. Our patients with a perforation history of less than 12 hours showed significantly fewer signs of sepsis compared to patients with a history of more than 12 hours. In a comparison of patients with primary repair vs. patients treated with esophageal resection or an exclusion operation, no differences were found. In the literature, patients with a long period of perforation (more than 24 hours) were treated more often with an esophageal resection than patients with primary repair. In cases of Boerhaave’s syndrome, primary suturing of the esophageal perforation should be reserved only for those patients presenting within 12 hours after perforation. In all other cases, depending on the extent of the tissue damage, a two-stage esophageal resection with cervical esophagostomy and gastrostomy is recommended as the safest treatment.     

Normative values of bone parameters of children and adolescents using digital computer-assisted radiogrammetry (DXR).

PURPOSE: To verify whether estimation of bone mineral density (BMD) using digital X-ray radiogrammetry (DXR) is possible on children and to determine normative values of both such a DXR-BMD estimate and a corresponding metacarpal index (DXR-MCI) on. PATIENTS AND METHODS: In retrospect, X-rays were selected of the hands of 200 healthy Caucasian children (120 boys and 80 girls, aged 4-18 yr). The involved children were selected among a larger group of children submitted to the surgical department of our institute for evaluation of a suspected fracture after an occurred trauma. All children with a verified fracture or a chronic bone-related disease, including bone age retardation or acceleration, were excluded from the study. Furthermore, only conventional X-rays with the same film and capture parameters were included. The images were scanned and analyzed using the Pronosco X-posure system V.2 (Sectra Pronosco, Denmark). DXR-BMD, DXR-MCI, and a porosity index (DXR-PI) were automatically calculated using the midshafts of the metacarpals II-IV. Mean values of DXR-BMD and DXR-MCI were calculated separately for girls and boys in 2-yr intervals. RESULTS: In the present study the system has been demonstrated to be capable of calculating DXR-BMD from conventional X-rays of the hand from children down to approx 6 yr of age. This ability depended somewhat on the diameter and the length of the involved metacarpals. The success rate was higher for large bones than for small bones. The system succeeded in analyzing the images of 110 boys and 68 girls. Values of DXR-BMD were observed to increase with age from 0.40 g/cm2 to 0.62 g/cm2 in the male group and from 0.39 g/cm2 to 0.54 g/cm2 in the female group. Girls aged 11-12 yr had a higher DXR-BMD than did boys, corresponding to the earlier entry to puberty of girls. Standard deviations (SDs) reached values of up to 0.05 g/cm2. DXR-MCI increased with age from 0.36 to 0.47 for boys and from 0.34 to 0.49 for girls with a maximum SD of 0.06. The correlation between DXR-BMD and age was r=0.83 and r=0.84 for boys and girls, respectively. The corresponding correlations for DXR-MCI was lower, with observed correlations of r=0.63 (boys) and r=0.68 (girls), respectively, with p<0.01 in all cases. The DXR-PI did not reveal a significant correlation to age (r=-0.31 and r=0.04. respectively) and showed SDs marginally higher than the calculated mean values. CONCLUSION: The newly available DXR-methodology seems to offer the ability to determine DXR-BMD and DXR-MCI in children starting with a bone age of 6. This possibility may be of special relevance for children suffering from chronic bone diseases that require repeated X-rays of the hand (e.g. to determine bone age). The acquired normative data suggest that the measurements are of clinical value owing to low age-dependent variability (SDs) relative to an observed high increase with age. The clinical value of the porosity index (DXR-PI) remains uncertain and is limited owing to a high inter-individual variability.     

„Gesundheit“ im Studiengang „Pflege und Gesundheit“ an der FH Hamburg - Profil- und Bedarfsschätzung

At the Fachhochschule Hamburg, a new curriculum on ‘nursing and health’ will be started in summer 1996. This paper informs about ‘health’ in the new curriculum, and the intended emphasis on epidemiology and health promotion. Then the present state of health science instruction in Germany is characterized, and the historical development of interest in this subject. Finally, the short- and long-term need for public health professionals for the north-western part of Germany is estimated.     

Quantitative autoradiography of 11 different transmitter binding sites in the basal forebrain region of the rat--evidence of heterogeneity in distribution patterns.

The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.     

How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.