Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.     

Possibilities for frequency adjusted heart stimulation

In the sick sinus syndrome, in sinu-atrial conduction defects or in atrial flutter or fibrillation a stress-adapted, frequency-adapted stimulation cannot be obtained by the processing of the atrial potential. Here one depends on partly extracardiac parameters which contain informations about the metabolic and stress situation, respectively. A survey of the parameters for a frequency-adapted stimulation discussed at present is given and a critical valuation of them is carried out. It is shown that all parameters up to now experimentally and clinically, respectively, tested are more or less problematic and that the way out of the difficulty most consist in deriving the controlled variable for a stress adapted stimulation rate from several parameters.     

Value of small bowel double contrast enema in clinical interventions

The double contrast enema is the most effective morphological screening method for the evaluation of the whole small bowel. Its sensitivity is 85%, its specifity 96.7%. In specific clinical problems the number of pathological roentgen findings rises: from 34.4% when all indications are taken into consideration to 58% in indications specific to the small intestine such as Morbus Crohn or the malabsorption syndrome. Search for tumours and the double contrast of the small bowel in unclear gastro-intestinal bleeding are unproductive. The weak point of this screening method is the lower part of the small intestine. Therefore, the selective peroral or retrograde analysis of the terminal ileum supplement the contrast method. A precondition for good results is an adequate technical standard. Besides the clinical results some technical results are therefore discussed such as contrast medium quantities, examination and X-ray time, radiation exposure and influences on the image quality.     

Female and male partner age and menotrophin requirements influence pregnancy rates with human menopausal gonadotrophin therapy in combination with intrauterine insemination

This study analyses the influence of female and male patient age and human menopausal gonadotrophin (HMG) requirements on clinical pregnancy rates and live birth rates with ovulation stimulation using HMG in combination with intrauterine insemination (IUI). In this study, 363 consecutive HMG/IUI treatment cycles in 184 patients carried out at a university fertility centre were analysed in a retrospective fashion. The main outcomes measured were clinical pregnancy rates and live birth rates. Increased female partner age (> or = 35) and male partner age (> or = 40) were found to negatively influence pregnancy rates with HMG/ IUI therapy. In addition, this study demonstrated a critical threshold of HMG requirements beyond which pregnancy did not occur. No pregnancies occurred in treatment cycles requiring > 25 ampoules (1875 IU) of menotrophins to achieve follicular maturity, irrespective of patient age. In conclusion, female partner age, male partner age, and HMG requirements all significantly influence pregnancy rates with HMG/IUI therapy.