Deficiency of inducible and endothelial nitric oxide synthase results in diminished bone formation and delayed union and nonunion development.

BACKGROUND: Between 5% and 10% of all fractures fail to heal adequately resulting in nonunion of the fracture fragments. This can significantly decrease a patient's quality of life and create associated psychosocial and socio-economic problems. Nitric oxide (NO) and nitric oxide synthases (NOS) have been found to be involved in fracture healing, but until now it is not known if disturbances in these mechanisms play a role in nonunion and delayed union development. In this study, we explored the role of endothelial and inducible NOS deficiency in a delayed union model in mice. MATERIALS AND METHODS: A 0.45mm femur osteotomy with periosteal cauterization followed by plate-screw osteosynthesis was performed in the left leg of 20-24week old wild type, Nos2(-/-) and Nos3(-/-) mice. Contralateral unfractured legs were used as a control. Callus volume was measured using micro-computed tomography (µCT) after 28 and 42days of fracture healing. Immuno histochemical myeloperoxidase (MPO) staining was performed on paraffin embedded sections to assess neutrophil influx in callus tissue and surrounding proximal and distal marrow cavities of the femur. After 7 and 28days of fracture healing, femurs were collected for amino acid and RNA analysis to study arginine-NO metabolism. RESULTS: With µCT, delayed union was observed in wild type animals, whereas in both Nos2(-/-) and Nos3(-/-) mice nonunion development was evident. Both knock-out strains also showed a significantly increased influx of MPO when compared with wild type mice. Concentrations of amino acids and expression of enzymes related to the arginine-NO metabolism were aberrant in NOS deficient mice when compared to contralateral control femurs and wild type samples. DISCUSSION AND CONCLUSION: In the present study we show for the first time that the absence of nitric oxide synthases results in a disturbed arginine-NO metabolism and inadequate fracture healing with the transition of delayed union into a nonunion in mice after a femur osteotomy. Based on these data we suggest that the arginine-NO metabolism may play a role in the prevention of delayed unions and nonunions.

[Inhibins and Activin A in hypertensive Disorders of Pregnancy and HELLP-Syndrome]. / Inhibine und Aktivin A bei hypertensiven Schwangerschaftserkrankungen und HELLP-Syndrom.

OBJECTIVE: Are serum concentrations of the ovarian glycoproteins inhibin A, inhibin B, pro-alpha-C and activin A different in normotensive, chronical hypertensive or pregancies complicated by preeclampsia or HELLP-syndrome? What are the clinical consequences? METHODS: Serum concentrations of inhibin A, inhibin B, pro-alpha-C, and activin A of 99 women (37 normotensive patients, 23 patients with chronical hypertension, 25 women with preeclampsia and 14 patients with HELLP-syndrome) at different stages of pregnancy were determined by high specific ELISAS. RESULTS: During pregnancy serum levels of all parameters increased continually and fell rapidly within parturition. Activin A and inhibin B levels showed significant higher serum concentrations in patients with preeclampsia and - even more pronounced - in patients with HELLP-syndrome. Normotensive and chronically hypertensive patients were not different. CONCLUSION: Activin A and inhibin A appear to be viable candidates as laboratory parameters for detection of pregnancy induced hypertension. Maybe furthermore both parameters will allow the discrimination between chronic hypertension and hypertension induced by pregnancy.

Sonographic prognostic factors in prenatal diagnosis of SCT.

OBJECTIVE: A subset of fetuses with sacrococcygeal teratomas (SCT) develops hydrops caused by high-output heart failure. Identification of fetuses at risk for hydrops is important because surgical intervention may reverse the pathophysiology of the disease. The aim of this study was to evaluate sonographic prognostic factors regarding tumor morphology and vascularity associated with the development of hydrops in utero. METHODS: Over a 10-year period, we identified 7 fetuses with SCT diagnosed antenatally and managed at the University of Mainz. We retrospectively reviewed the charts of mothers and infants and recorded data on prenatal diagnosis, tumor size and localization, perinatal management, neonatal care, and fetal outcome. RESULTS: The diagnosis of SCT was made in all cases by ultrasound. The median gestational age at the time of initial diagnosis was 23 weeks. In 3 cases, signs of fetal heart failure were detected by ultrasound. Pathological blood flow in the venous system was further noted in 2 cases. One fetus developed hydrops. The mean gestational age at delivery was 35 weeks, depending on the presence or absence of maternal or fetal complications. Six infants were delivered by cesarean section, and 1 by vaginal delivery. After fetal stabilization, surgery was performed in 5 of 7 cases. Inadequate ventilation secondary to prematurity was a contributing factor to death in 1 fetus. One fetal intrauterine death occurred at 27 weeks of gestation. CONCLUSION: Pregnancies with antenatally diagnosed fetal SCT necessitate frequent monitoring to ensure the detection of fetal/maternal complications by ultrasound and Doppler ultrasound. The most important prognostic criteria were cardiomegaly, fetal hydrops, and increased preload indexes of the fetal venous system as sign of fetal heart failure. Many studies show that the occurrence of pulsations in the umbilical vein of a hydropic fetus correlates with a poor fetal outcome. The decision on the optimal time of delivery should therefore be made by a multidisciplinary team of specialists.

Trophoblast tissue culture of human intrauterine and ectopic pregnancies and treatment with methotrexate.

The application of drugs for conservative treatment of patients with ectopic pregnancy has been used worldwide for several years. In-vitro studies, however, are very few. We therefore examined the effects of methotrexate on trophoblast tissue cultures derived from intrauterine and ectopic pregnancies. Methotrexate was administered either 12 h or 6 days after initiation of the culture. Human chorionic gonadotrophin (HCG) levels were measured in the culture medium. All cultures showed secretion of HCG within the first 16 days. Methotrexate concentrations less than 3.8 x 10(-4) mol/l had no effect on HCG secretion. Cultures of ectopic pregnancies required a concentration about 10x higher to induce an equivalent reduction of HCG levels compared to intrauterine pregnancies. A few intrauterine and ectopic pregnancies showed no reduction of HCG values after treatment. These results suggest that data obtained from studies on intrauterine pregnancies may not be transferable to ectopic pregnancies in all instances. In some regimens approximately 8 days are required before the effect becomes measurable. In combination with our clinical data, we therefore recommend not to repeat a methotrexate dose too early in treatment of patients with ectopic pregnancies. The possibility that non-responding patients could exist should be kept in mind.

[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. / Die Effektivität von Cisplatin allein und in Kombination im Rahmen der Primärtherapie des Ovarialkarzinoms. Ergebnisse einer prospektiven Multizenterstudie.

The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.

[Contamination of milk after teat redisinfection with iodophores]. / Zur Kontamination der Milch nach Zitzennachdesinfektion mit Jodophoren.

The passage of iodine to milk after drug redisinfection with iodophores developed in the GDR and the Polish People's Republic has been studied by labelling these preparations with iodine-131. The iodine contents found in the milk lay below the internationally indicated limits of tolerance. Therefore, from the hygienic-toxicological point of view, the use of these iodophore variants might be considered safe, provided that they were employed properly.

[Management of functional sterility using clomiphene and cyclophenyl at the Karl-Marx-Stadt District Hospital Gynecologic Clinic]. / Beitrag zur Behandlung der funktionellen Sterilität mit Clomiphen und Cyclophenyl an der Frauenklinik des Bezirkskrankenhauses Karl-Marx-Stadt.

We report on 39 barren patients suffering from anovulatory cycle disturbances or corpus luteum inadequacies. Them were given treatment in the Gynecological Hospital of Karl-Marx-Stadt County at Karl-Marx-Stadt in the past few years and were administered Clomiphendihydrogencitrate or Cyclophenyl to provoke ovulation. Before and during therapy, the total of estrogenes and pregnanediol were determined in the 24h-urine every two days. The clinical data and the results of the hormone investigations were analysed, and an attempt was made to derive a forecast from the estrogene and pregnanediol secretion so as to be able to form an opinion on the positive or negative result of the treatment.