Intraspinal anomalies in myelomeningocele

This study reports the results of MRI analysis of the spinal cord in 83 patients with myelomeningocele. 63 patients had a "tethered cord" or a "suspected tethered cord". In 14 cases we found a "hydro-/syringomyelia". In only 2 cases there were no pathological findings. The influence especially of the "tethered cord" and the "hydro-/syringomyelia" on the development of deformities of the locomotor apparatus is discussed. Concerning this problem the experience reported in the literature is not sufficient enough to make final statements. However, in cases of deterioration of the neurological status in patients with myelomeningocele the influence of intraspinal anomalies should be considered giving rise to further diagnostic examinations.     

Antitumor-activity and toxicity of continuous-infusion versus bolus administration of bleomycin in 2 heterotransplanted human testicular cancer cell-lines

The continuous infusion of the glycopeptide antibiotic cytotoxic agent bleomycin in comparison to bolus application has been postulated to be associated with increased antitumour activity and decreased toxicity, particularly pulmonary fibrosis. In the treatment of patients with testicular cancer, bleomycin is an essential agent and is currently used in continuous infusion and bolus application schedules in cisplatin-based combination therapy regimens. The current study addresses the antitumour activity and general toxicity of bleomycin given as continuous intraperitoneal infusion versus bolus application in human testicular cancer cell lines heterotransplanted into nude mice. Maximally tolerated doses for each administration route, defined as being the LD20 were applied (8.7 or 17.5 mg/kg days 1-7 continuous intraperitoneal infusion via osmotic mini pump or 40 mg/kg intraperitoneal bolus application on days 1, 5, 9). Bleomycin demonstrated antitumour efficacy at all concentrations used in comparison to untreated controls. There was no significant difference in antitumour activity between continuous or bolus application of bleomycin when the same cumulative doses were compared. Neither was there any difference with respect to bleomycin toxicity with 11 +/- 4 or 12 +/- 5% losses of body weight for continuous infusion regimens compared to 13 +/- 3% for bolus application. In a small subgroup of mice histological examination of the lungs demonstrated no signs of pulmonary fibrosis. In summary, using an established testicular cancer xenograft model in nude mice bolus application of bleomycin was as active as continuous infusion of this drug with no apparent difference in overall toxicity. Current standard treatment regimens using bolus application of bleomycin should not be altered without necessary reasons. Bleomycin pulmonary toxicity needs to be studied in clinical trials taking into account possible drug interactions in combination chemotherapy regimens and additional risk factors for pulmonary toxicity.     

Effects of various HTK solution regimens on proteinuria after renal transplantation in dogs

Investigations were carried out by means of an autologous, heterotopic model for kidney transplantation applied to dogs. Duration of cold ischemia was 48 h. Four experimental groups were arranged. During the first 20 min following revitalization of the transplanted kidney, group 1 (HTK solution/80 cm perfusion height) showed a significant glomerular and tubular malfunction. In group 2 (HTK solution/120 cm perfusion height), only four urinary proteins with molecular weights of 25 kDa, 67 kDa, 100 kDa and >100 kDa were found. The excretion of higher molecular proteins receded over the 20-min period of observation. In both group 3 (HTK/aspartate solution) and group 4 (HTK/tryptophan solution) the quantity of excreted glomerular and tubular protein was well above that of group 2. As opposed to the Tryptophan group, a complete restoration of renal function was observed in the Aspartate group after 4 weeks. In general, the standard HTK protective solution delivered with 120 cm perfusion pressure gave the most favorable results, with the lowest levels of proteinuria and a satisfactory recovery of renal function after revitalization.     

Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients

Patients with polycystic ovarian syndrome (PCOS) have higher miscarriage rates. It is postulated that this is caused by a lower rate of mature oocytes, and a lower quality of embryos. Retrospectively we analysed 51 intracytoplasmic sperm injection (ICSI) cycles of 31 PCOS patients. These data were compared to age-matched controls (105 cycles) during the same period. All patients of both groups received gonadotrophin-releasing hormone (GnRH) agonists prior to gonadotrophin treatment. The rate of metaphase II oocytes (MII) was not different. However, the mean absolute number of normally fertilized oocytes was significantly higher in PCOS patients (5.00 versus 3.56, P < 0.01), due to a higher number of oocytes retrieved. More embryos were transferred by cycle in the PCOS group (2.69 versus 2.17, P < 0.05), with a higher cumulative embryo score. The overall and multiple pregnancy rate showed no differences and the clinical abortion rate was lower (21 versus 41.67%, P < 0.05) in the controls. Our findings demonstrate that negative factors unconnected to oocyte morphology must be present in PCOS patients. It is possible that only cytoplasmic, not nuclear, maturity is influenced in these patients.     

Genetics of male subfertility: consequences for the clinical work-up

Major principles of genetic failures, chromosomal alterations and the most common syndromes associated with male subfertility should be taken into account before medical therapy and sophisticated techniques of assisted fertilization are applied to help a couple conceive. This review addresses the most common genetic reasons for male subfertility or infertility with special regard to the importance for the clinical work-up in daily routine and the potential risks for the conceptus.     

In vivo imaging of the human zonular apparatus with high-resolution ultrasound biomicroscopy

· Background: To investigate the potential of high-resolution ultrasound biomicroscopy (UBM) for studying the zonular apparatus of human beings in vivo. · Methods: Using transducer frequencies of 34 MHz and 50 MHz, criteria were developed to identify transcorneal and transscleral sections that allowed reproducible identification of the different fiber groups of the zonular architecture. For that purpose, 10 volunteers between the ages of 14 and 41 years underwent high-resolution ultrasound biomicroscopy under conditions of consensual far- and near-accommodation. The online video recordings of the respective UBM investigations were afterwards analyzed image by image. Good visibility of zonular fibers was obtained when the ultrasound wave propagation comprised an angle close to 90° with the fiber orientation and when the oscillations of the UBM scan had a strict radial orientation towards the limbus and avoided, simultaneously, the ciliary processes. · Results: In all the volunteers, high-resolution ultrasound biomicroscopy imaged the zonular fiber groups known from histology. In addition, it detected fibers that do not follow the course of the inner ciliary body surface but take a direct route from the ora serrata to the lens. It also demonstrated that fibers that seem to change direction at crossings with other fibers. Under conditions of near-accommodation, the zonular fibers showed signs of relaxation. · Conclusions: High-resolution ultrasound biomicroscopy seems well suited for in vivo investigations of the zonular apparatus and of accommodation in man. The results support the fundamental features of the Helmholtz theory on accommodation. Received: 8 June 1998 Revised version received: 7 September 1998 Accepted: 14 September 1998     

Cloning of a phospholipase C-δ1 of rabbit skeletal muscle

Summary The phospholipase C isoform responsible for the increase in the total myoplasmic inositol 1,4,5-trisphosphate concentration during tetanic contraction of isolated skeletal muscle and its mechanism of activation is not known. We have cloned and sequenced a phospholipase C cDNA of rabbit skeletal muscle coding for a protein of 745 amino acids with a molecular mass of 84 440 kDa. The deduced amino acid sequence exhibits the phospholipase C-specific domains X and Y which according to current knowledge very likely represent the catalytic centre of the enzyme. An overall sequence homology of 88% to the phospholipase C-1 of rat brain suggests that the encoded protein represents a phospholipase C-1 isoform of rabbit skeletal muscle. Northern blot analysis shows, that this phospholipase C- is dominantly expressed in skeletal muscle, less strongly in smooth muscle (uterus) and lung and weakly in heart, kidney and brain. In the N-terminal part of the primary structure a consensus sequence for a canonical EF-hand Ca²⁺ binding domain can be identified together with a short positively charged motif which recently has been suggested to be essential for the binding of phosphatidylinositol 4,5-bisphosphate. If these two domains which are unique for phospholipase C- are sufficient in establishing a mechanism for the activation of the enzyme, inositol 1,4,5-trisphosphate formation in skeletal muscle could be the consequence of an increase in myoplasmic Ca²⁺.     

Serum ferritin and the iron status of Canadians.

Serum ferritin concentration was determined in 1105 Canadians aged 1 to 90 years. Geometric mean values (ng/ml) were as follows: children 1 to 4 years old, 12; children 5 to 9 years old, 15; adolescent girls, 17; adolescent boys, 18; women 20 to 39 years, 23; women 65 years and older, 52; men 20 to 39 years, 93; and men 40 and older, 92. Ranges were side in all age groups, reflecting variations in size of body iron stores. From analysis of the ferritin values it is highly probably that iron stores were greatly reduced in approximately 25% of children, 30% of adolescents, 30% of menstruating women, 60% of pregnant women and 3% of men. Iron-deficiency anemia was noted in only 2% of subjects. If "normality" requires more than small amounts of storage iron to meet physiologic demands, the study results suggest a high probability of iron deficiency in 60% of the pregnant women and in 19% of the other subjects; but if normality is defined as maintenance of adequate iron stores for erythropoiesis, the prevalence of iron deficiency was zero in the pregnant women and 2% in the other subjects.