Editorial

Ohne Zusammenfassung     

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.     

Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing.

The aim of this study was to investigate the effect of a moderate soft tissue trauma to the course of fracture healing in a standardized animal model. Thirty-eight Wistar rats were randomly divided into a fracture group (F, n = 19) and a group with a fracture and a soft tissue trauma (F + STT, n = 19). The fracture and the soft tissue trauma were created using an impact device with a standardized energy. All fractures were stabilized by two Kirschner wires. Three rats were measured for blood flow and sacrificed at days 1, 3, 7, and 14, and seven rats at day 28, from both groups. A three-point bending test was performed on the healed tibia after 28 days. During the first 24 h there was a reduction in blood flow, which was more pronounced in the F + STT group than in the F group. From histological sections, the shape of the callus formation, as well as the tissue distribution of newly formed bone, fibrous cartilage and fibrous connective tissue were determined. Distinctly more periosteal new bone formed and a larger callus formed at days 3 and 7 in group F compared to group F + STT. However, by days 14 and 28, the ossification and overall callus size no longer showed differences between the two groups. A fast recovery of blood flow and callus formation took place in the F + STT group, which led to similar histological and biomechanical results in fracture healing observed after 28 days between the two groups.     

HMO membership, treatment, and mortality risk among prostatic cancer patients.

OBJECTIVES. Treatment and mortality risk were compared between prostate cancer patients receiving care in fee-for-service settings and those receiving care in a health maintenance organization (HMO). METHODS. Two samples were obtained from a population-based tumor registry. Patients in the first sample (n = 201) were interviewed shortly after diagnosis to obtain data on income, education, overall health status, and expenditures for health status, and expenditures for health care. These data were combined with information from the tumor registry on cancer stage, age, treatment, place of residence, and source of care. Only tumor registry data were obtained for most patients in the second sample (n = 962). For both samples, survival time was monitored for up to 80 months. RESULTS. Multivariate analysis of data from the interviewed sample indicated that HMO patients were less likely to receive surgery but more likely to receive radiation therapy than were those in fee-for-service settings. Mortality risk was lower for the HMO patients than for those in fee-for-service plans. Findings based on the second sample were nearly identical. CONCLUSIONS. This study suggests that HMOs may offer important advantages to lower-income patients at risk for specific life-threatening diseases.     

Risk factors associated with venous thromboembolic events in patients with malignancy.

Malignancy is a major risk factor for venous thromboembolic events, but not all patients with malignancy develop such events. This study attempts to identify risk factors in patients with malignancy who develop venous thromboembolic events. In the current study, 566 consecutive patients without venous thromboembolic events and 416 patients with, admitted to University of Michigan with malignancy between 1992 and 2000, were identified using International Classification of Diseases-9 Clinical Modification codes. Data on potential risk factors was obtained from the University of Michigan Cancer Registry and the medical record. Univariate and multivariate analysis was used to identify factors associated with venous thromboembolic events and mortality. The mean patient age was 45.6 years with a mean survival of 7.8 years from cancer diagnosis. Venous thromboembolic events were associated with solid tumors (odds ratio 5.0; 95% confidence interval 1.7-14.9; P = 0.004), infection (4.9; 1.2-19.8; P = 0.03), and increasing age (1.05; 1.03-1.08; P < 0.001). While leukopenia (4.2; 1.2-14.6; P = 0.02) was associated with an increased incidence of venous thromboembolic events, neutropenia was not. Sex, type of therapy, and cancer stage were not independently associated with venous thromboembolic events. Survival was decreased in patients with venous thromboembolic events (5.9 versus 9.2 years, P < 0.0001). Solid tumors (3.9; 1.8-8.4; P = 0.001), infection (3.3; 1.1-9.9; P = 0.03), advanced stage (1.6; 1.2-2.1; P = 0.001), and increasing age (1.02; 1.0-1.04; P = 0.01) were associated with decreased survival. Patients with malignancy who have solid tumors, advanced age, infection, and leukopenia have a significantly increased risk of venous thromboembolic events.     

The costs of atopy and asthma in children: Assessment of direct costs and their determinants in a birth cohort

The aim of this study was to estimate costs accrued by the health care of children with asthma in comparison to children with atopic eczema and seasonal rhinitis and to investigate cost determinants. From the multicenter cohort study (MAS-90), we selected children with an asthma, atopic eczema and/or seasonal rhinitis diagnosis during the first 8 years of life, and overall 8-year health care utilization was estimated retrospectively by reviewing medical records. Asthma treatment (n = 76) incurs an average cost of US$ 627 per year, 44% due to hospital stays. Atopic eczema treatment (n = 91) cost on average US$ 219 and seasonal rhinitis (n = 69) US$ 57 per year. In asthma and atopic eczema, costs increase significantly with disease severity. Allergy diagnostics use accounts for only 1% of total costs. Costs for asthma and atopic eczema treatment are highest in those years when topical steroids are used for the first time, but decrease with every further year of steroid use. A remarkable 25% of asthmatic children with severe symptoms were not treated according to national guidelines, so that most steroid treatment was initiated during the first hospital stay. In the case of asthma, total direct costs increased until the 3rd year of the disease, and then decreased with further years of diagnosis, while steroid use continued to increase. These results indicate a 'learning effect' in the treatment of asthma and atopic eczema for each patient as well as considerable cost-saving potential by preventing severe asthma. Moreover, the importance of considering cost-driving factors and using cohort or longitudinal designs in cost-of-illness approaches is emphasized.     

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.