Effects of aprotinin on endothelium-dependent relaxation of large coronary arteries

Objective: Aprotinin is widely used in heart surgery for reduction of intraoperative blood loss. But recent reports presenting results from rat aorta experiments claimed that aprotinin selectively impairs endothelium-dependent relaxation (EDR) as well as basal NO availability in concentrations similar to doses routinely used in cardiovascular surgery. An impairment of coronary EDR by aprotinin would be a great danger for any cardiothoracic intervention. We therefore tested the influence of aprotinin in the coronary arteries of a non-rodent species. Methods: Fresh coronary arteries of pigs were obtained from the local slaughterhouse and transported to our laboratory in cold oxygenated Krebs–Henseleit solution. Five-millimeter long rings were consecutively tested with or without aprotinin in concentrations of 500 KIU/ml (n = 7) or 1000 KIU/ml (n = 6) in oxygenated normothermic Krebs–Henseleit solution. PGF₂ (10 μmol/l) was used for inducing contraction and substance P (10 nmol/l) for inducing EDR, which was calculated in percentage of the precontraction. Indomethacin (10 μmol/l) was added in all measurements to eliminate the influence of prostaglandins. In additional similar experiments (n = 5), the influence of 1000 KIU/ml aprotinin on the EDR caused by the endothelium-derived hyperpolarizing factor (EDHF) was tested using l-NNA (300 μmol/l) to block all NO formation. Results: The EDR of pig coronaries (82 ± 5% or 80 ± 5% of the precontraction in the control tests before and after aprotinin exposure) was not significantly changed by 500 KIU/ml aprotinin (78 ± 7%). A small, but significant reduction of less than 1/10 of the EDR was induced by 1000 KIU/ml aprotinin (74 ± 5%). After accounting for l-NNA for NO blockage, no aprotinin-related difference remained (59 ± 6% vs 60 ± 6% in controls). Conclusion: For clinically relevant concentrations of aprotinin up to 500 KIU/ml, no significant reduction of the EDR can be found in epicardial coronary arteries of the pig. For higher doses of 1000 KIU/ml, a reduction in NO production seems to be the cause of the small but significant reduction of the EDR by aprotinin. Therefore, danger for impairment of coronary EDR by aprotinin at clinical dosage levels, as suggested by studies on rat aortas, seems to be absent in coronary arteries of a large mammalian model.     

In vivo study of degradation of poly-(D,L-) lactide and poly-(L-lactide-co-glycolide) osteosynthesis material]

AIMS. Comparison of the degradation of poly(D,L)lactide (Resorb X) or poly(lactide-co-glycolide) (LactoSorb) in vivo. MATERIAL AND METHODS. LactoSorb and Resorb X osteosynthesis plates were fixed at the lateral aspect of the femora of 26 Chinchilla rabbits using the respective osteosynthesis screws. After intraperitoneal injection of fluorochromes the screw plate bone blocks were resected after 1, 6, 12, 14, 16, 21, 26 months and radiologic, histologic as well as fluorescence microscopic examinations were carried out. RESULTS. Newly formed bone was detectable above and beneath the polymers 1 month after the implantation. The implants were totally covered by newly formed bone after 6 months. While the LactoSorb screws were found to be as birefringent as after 1 month, in the Resorb X screws a continuous resorption by phagocytizing marrow cells starting from the periphery was detectable. Resorb X was totally resorbed in histologic slides 12 months after implantation, while total resorption of LactoSorb lasted 14 months; both polymers were replaced by marrow cells. Bone remodeling was not finished 26 months after implantation in both polymers. CONCLUSION. Resorption of Resorb X was finished earlier than the resorption of LactoSorb. Both materials were found by fluorescence microscope to be completely resorbed after 12 or 14 months, but bone remodeling of the screw holes was not yet finished 26 months after implantation.     

High abundances of neurotrophin 3 in atopic dermatitis mast cell

Background  

Neurotrophin 3 (NT-3) is a member of the neurotrophin family, a group of related proteins that are known to regulate neuro-immune interactions in allergic diseases. Their cellular sources and role in the recruitment of mast cell precursors in atopic dermatitis have not been characterized in detail so far.     

Untersuchungen zur Effizienz der notärztlichen Therapie bei Patienten mit Schädel-Hirn- bzw. Polytrauma Ein Beitrag zur Qualitätssicherung in der Notfallmedizin

For cardio-pulmonary resuscitation there are standardized treatment concepts, but there have been few prospective investigations examining the efficacy of prehospital advanced trauma life support and its effect on the outcome in patients with severe head injury and multiple trauma treated within the German emergency system. The results of this study underline the importance of intensive prehospital treatment and highlight some problems that should be taken into account in future in the training of emergency physicians. Methods. A total of 179 patients with cerebral trauma were investigated. Data obtained included demographic and logistic data of the patients and the emergency physicians, diagnoses and treatment at the scene of the accident and state of the patient on admission in each case. Having divided the patients into three groups by severity of the trauma, we distinguished between sufficient and insufficient treatment and assessed infusion therapy, ventilatory support, positioning and immobilization, and analgesic and sedative therapy. For statistical analysis of the data we used χ²-test and Fisher's exact test. P<0.05 was considered significant. Results. There were 102 patients who had sustained a cerebral trauma without other life-threatening lesions (score 1), 40 with multiple trauma (score 2) and 37 with multiple trauma (score 3). On average 2.4?IV lines were established and the patients received 1186±765?cc of crystalloid in addition to 801±411?cc of colloid fluids. In all groups, patients who received adequate infusion therapy had a better outcome; even in the group with score 1 significantly fewer had a fatal outcome. In all, 167 (93%) patients had endotracheal tubes placed, and in 150 cases (84%) ventilatory therapy was considered sufficient. The proportion of score 1 patients with sufficient ventilatory support who had a fatal outcome was significantly lower than that in the group with insufficient treatment. In patients with multiple trauma we could not separate the benefits of sufficient respiratory therapy and infusion therapy. In only 54% of the cases a vacuum mattress was used and in only 41% the patients were positioned with the upper part of the body elevated by 30°. These were 28 patients (16%) who received neither analgesics nor sedatives. Regardless of the quality of prehospital treatment of isolated head injury, a Glasgow Coma Scale (GCS) score lower than 5 involved a very high mortality and all patients with a GCS score of 9 or more survived. In the group with GCS scores between 5 and 8, however, significantly more of the patients who received adequate treatment survived (82.5% vs 40%). Conclusions. The present study confirms that sufficient advanced trauma life support can improve the outcome of trauma victims with cerebral trauma. Adequate infusion and respiratory therapy reduce the mortality among such patients significantly. In patients with multiple trauma a clear positive effect of generous infusion therapy also is evident. The clearest effect of sufficient prehospital treatment is seen in patients with isolated cerebral trauma and a GCS score between 5 and 8. These results demonstrate the importance of advanced trauma life support and show emphatically that the so-called scoop-and-run strategy should be abandoned when resources are available for extended preclinical emergency treatment. On the other hand, we detected some problem areas in the prehospital treatment of trauma victims, such as positioning, immobilization and drug therapy with analgesics and sedatives. These findings allow us to pinpoint specific points that should be stressed in the training of emergency physicians and paramedics.     

Prospective study of the occurrence of monoclonal gammapathies following bone marrow transplantation in young children

We have prospectively studied the occurrence of monoclonal serum immunoglobulins in 38 recipients of BMT. Patients were young children with primary immunodeficiencies (n = 31), other inherited diseases (n = 4), leukemia (n = 2), or aplastic anemia (n = 1). Twenty-nine received an HLA-nonidentical marrow and nine an HLA-identical marrow. Serum monoclonal immunoglobulins were detected by the immunofixation method. Monoclonal immunoglobulins were found in 26 patients. Monoclonal components were more frequently detected in patients with primary severe T cell deficiencies (21/25) rather than in the other patients (6/13). In 7 of 29 recipients of HLA-nonidentical transplants, versus 0 out of 9 recipients of HLA-identical transplants, serum monoclonal immunoglobulins were found associated with a B lymphocyte proliferation syndrome due to an Epstein-Barr virus infection. In this group, monoclonal immunoglobulins were detected early, prior to the onset of the clinical syndrome. The simultaneous occurrence of several monoclonal immunoglobulins was more frequent in these patients, while monoclonal immunoglobulin concentrations increased faster, especially those of IgM isotype. These characteristics may allow in patients at risk (recipients with primary T cell immunodeficiencies and receiving HLA-nonidentical transplantation) an earlier diagnosis of B lymphocyte proliferative syndrome that may eventually lead to early and more efficient therapy.     

Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development.

Hodgkin disease (HD) is characterized by a small number of putative malignant cells [Hodgkin and Reed-Sternberg (HRS) cells] among a background of lymphocytes and histiocytes. The lineage of HRS cells is still elusive and a clonal origin of these rare cells has not formally been demonstrated. We isolated HRS cells by micromanipulation from histological sections of three cases of Hodgkin lymphoma (each representing a distinct subtype of the disease) and analyzed individual cells for immunoglobulin variable (V) gene rearrangements by PCR. In each of the three cases a single heavy-chain V (VH) (and in one case, in addition, a kappa light-chain) gene rearrangement was amplified from the HRS cells, identifying these cells as members of a single clone. A potentially functional VH rearrangement was obtained from a case of nodular sclerosis HD. Somatic mutations and intraclonal diversity in the VH genes indicate a germinal center B-cell origin of the HRS cells in a case of lymphocyte-predominant HD, whereas in a case of mixed-cellularity HD the sequence analysis revealed only nonfunctional V gene rearrangements, suggesting a pre-B-cell origin. This indicates that HRS cells can originate from B-lineage cells at various stages of development.     

Investigations of the acute toxic, cytogenetic, and embryotoxic activity of buminafos.

The organophosphorus herbicide buminafos (O,O-dibutyl-(1-butylaminocyclohexyl)-phosphonate) was tested for its acute toxic, cytogenetic, and embryotoxic activity on different strains of mice. The oral LD50 value for male NMRI mice was determined to be 3500 mg/kg. Single oral doses of 175, 1000, and 2000 mg/kg did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of male NMRI mice. After oral administration of 500 and 1000 mg/kg buminafos to pregnant Halle:DBA and Halle:AB mice at Days 6-15 of gestation no embryotoxic effects were observed. The cytogenetic inactivity of buminafos in the bone marrow chromosome assay corresponds to negative findings in other mutagenicity tests.