Chemical and physical characterization of a novel poly(carbonate urea) urethane surface with protein crosslinker sites

A major complication which occurs with implantable polyurethane biomaterials is bioincompatibility between blood and the biomaterial surface. Development of a novel biodurable polyurethane surface to which biological agents, such as growth factors or anticoagulants could be covalently bound, would be beneficial. The purpose of this study was to synthesize a novel poly(carbonate urea) urethane polymer with carboxylic acid groups which would serve as "anchor" sites for protein attachment. Physical characteristics such as tensile strength, initial modulus, ultimate elongation, tear strength, water/alcohol uptake and water vapor permeation were then evaluated and compared to other biomedical-grade polyurethanes. Covalent linkage of the blood protein albumin to this novel surface was then examined. A biodurable polycarbonate-based polyurethane containing carboxylic acid groups (cPU) was synthesized using a two step procedure incorporating the chain extender 2,2-bis(hydroxymethyl)-propionic acid (DHMPA). Tensile strength of this cPU film was 2.7 and 2.6 fold greater than both a polycarbonate-based polyurethane synthesized with a 1,4-butanediol chain extender (bdPU) and Mitrathane (Mit) controls, respectively. The cPU polymer also possessed 7.8 and 31 fold greater structural rigidity upon evaluation of initial modulus as compared to the bdPU and Mit, respectively. Ultimate elongation for the bdPU films was slightly higher than the cPU and Mit films, which had comparable elongation properties. The force required to tear the bdPU film was 1.9 and 32 fold greater than the cPU and Mit films, respectively. Alcohol solution uptake by all of the polyurethane segments increased with increasing alcohol concentrations, with the cPU having the greatest uptake. Water uptake was minimal for all the polyurethanes examined and was not affected by altering pH. Water vapor permeation was lowest for the cPU films as compared to both bdPU and Mit. Swelling the cPU in 50% ethanol prior to evaluation slightly increased water vapor permeation through the films. Covalent linkage of the radiolabelled blood protein albumin (125I-BSA) to the cPU segments incubated with the heterobifunctional crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) was greatest in the higher percent of ethanol as compared to controls. These results serve as foundation for developing a novel poly(carbonate urea) urethane with physical characteristics comparable to other medical-grade polyurethanes while having protein binding capabilities.     

Correction of deficiencies in flexible fiberoptic sigmoidoscope cleaning and disinfection technique in family practice and internal medicine offices

We describe a 27-year-old primigravida suffering from cystic fibrosis. Her chest was colonised with Burkholderia cepacia and she was in respiratory failure for which she required constant nasal intermittent positive pressure ventilation. In view of her rapid deterioration, Caesarean section was performed under epidural anaesthesia at 25 weeks gestation. A live 790-g boy was delivered. Post-operatively she made steady progress for 5 days although still requiring nasal ventilatory support. Thereafter she developed pneumonia and required tracheal intubation and ventilation on the eighth day. Her increasing hypoxaemia and pulmonary hypertension failed to respond to any therapy including inhaled nitric oxide and she died on the tenth postoperative day.     

Infectious disease mortality among adults by race and socioeconomic status: metropolitan Ohio, 1989-1991

The data presented here are part of an on-going longitudinal study of the relationship between socioeconomic status and mortality in the major metropolitan centers of Ohio. Using a Standardized Mortality Ratio, we find that mortality in the seven-city urban aggregate exceeds that of the rest of the state by 39 per cent for the nonwhite population and only 1 per cent for the white population. Further, for the nonwhite population, living in a high income area has no discernible health benefit for nonwhites as compared to whites. On the other hand, for the AIDS virus, there is a clear inverse association between economic status and mortality from AIDS. It is clear that the interrelationship among race, economic status, and health continues to be a complex one on which further research is needed.     

Perseverations during paired-associate learning in Huntington''s disease

Raw 30-MHz intravascular ultrasound data have been captured from postmortem coronary arteries (n = 4) to develop radio frequency analysis techniques for the characterisation of atherosclerotic plaque. Digitised data acquired from positions (n = 8) within diseased sections of artery were compared with the corresponding histology and radiology. Scan-converted images were used to locate regions of interest (ROI = 33) within areas of tissue composition: loose fibrotic tissue (LFT), dense fibrotic tissue (DFT) and calcium (CA). A range of parameters was extracted from the normalised power spectrum of each ROI within the bandwidth 17-42 MHz. Significant discrimination between LFT/DFT and between LFT/CA was provided by maximum power and spectral slope (dBMHz-1). However, the greatest discriminative power was given by the y-axis (0 Hz) intercept of the spectral slope: LFT/DFT (p = 0.001); LFT/CA (p = 0.0001); and DFT/CA (p = 0.089).     

Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.     

13C-urea breath test in Helicobacter pylori diagnosis and eradication. Correlation to histology, origin of ''false'' results, and influence of food intake

Obliterative or constrictive bronchiolitis is characterized by narrowing of the small airways, due to submucosal and peribronchiolar fibrosis, with chronic obstruction. The vast majority of cases of bronchiolitis obliterans are associated with other diseases and only few cases are idiopathic. We report on the main computed tomography (CT) methods used study obliterative bronchiolitis, the CT findings and the differential diagnosis with other diseases. The dynamic study of alveolar ventilation with CT uses inspiratory and expiratory CT or high-resolution CT (HRCT), spiral dynamic CT or HRCT with advanced image display, ultrafast CT. In abnormal cases HRCT shows direct and indirect signs of small airways disease. The most common (> 80%) sign of obliterative bronchiolitis is the so-called mosaic oligohemia, with low attenuating lobules, caused by air trapping and best seen on expiratory CT, associated with blood flow redistribution to more normal lobules; this finding simulates the ground-glass pattern from infiltrative lung disease. Differential diagnosis is more difficult in the presence of true ground-glass patterns associated with diffuse bronchiolar obstruction and also with mosaic oligohemia due to pulmonary vascular disease and pulmonary emphysema. HRCT can distinguish these diseases and dynamic CT is more sensitive than functional tests in detecting regional abnormalities and air trapping. The combination of HRCT, rapid volumetric scanning and advanced image display is a powerful tool study the normal and abnormal features of bronchiolar function and alveolar ventilation.     

Early detection of visual field progression in glaucoma: a comparison of PROGRESSOR and STATPAC 2

AIM: To compare the performance of PROGRESSOR (pointwise linear regression) and STATPAC 2 (comparison with baseline values) in detecting early deterioration in the visual fields of glaucoma patients. METHODS: Visual field series from 19 untreated normal tension glaucoma eyes which were deteriorating on clinical grounds were analysed by PROGRESSOR and STATPAC 2. Progression criteria for PROGRESSOR were (1) inner points: slope < -1 dB/year, p < 0.05 and (2) edge points: slope < -2 dB/year, p < 0.05. Criteria for STATPAC 2 were p < 0.05 change probability for any point on three consecutive fields. Detection time was defined as the time interval between the initial field and the first field in which at least one progressing point was identified. Detection times produced by the two techniques were compared. RESULTS: PROGRESSOR and STATPAC 2 agreed on progression in all 19 eyes. Mean detection time for PROGRESSOR was 1.077 (SD 0.985) years and for STATPAC 2 was 2.161 (1.357) years. PROGRESSOR detected progression sooner than STATPAC 2 in 18 eyes (p < 0.01), Wilcoxon matched pairs signed rank test). PROGRESSOR detected progression earlier by a mean of 1.085 (0.936) years. CONCLUSIONS: PROGRESSOR consistently detected progression earlier than STATPAC 2. The PROGRESSOR software is a useful tool for the early detection of visual field deterioration in glaucoma.     

Active transport of nitrofurantoin across the mammary epithelium in vivo

Nitrofurantoin is a commonly used urinary tract antibiotic that has been found at high concentrations in human milk. In vivo studies in rats were carried out to determine the mechanism by which this drug crosses the mammary epithelium. Lactating rats were gavage-fed with nitrofurantoin, and their milk and plasma levels of the antibiotic were measured at intervals up to 8 hr. The average milk-to-plasma (M/P) ratio, calculated from the areas under the milk and plasma curves, respectively, was 23 compared with a ratio predicted to be about 0.3 on the basis of lipid partitioning and protein binding determinations. M/P ratios for two nitrofurantoin congeners were also calculated. The neutral compound furazolidone had a M/P ratio of about 1, as predicted, whereas the basic compound furaltadone had a M/P ratio of 3.49 compared with a predicted ratio of 1.4. These data suggest that nitrofurantoin and, to a lesser extent, furaltadone are actively transported across the mammary epithelium into milk.     

Abrogation of glomerular injury in nephrotoxic nephritis by continuous infusion of interleukin-6

Interleukin-6 (IL-6) has been reported to have pro- and anti-inflammatory effects. It has also been shown to cause mesangial cell proliferation in vitro and has been suggested as a mediator of injury in proliferative nephritis. We have assessed the effects of continuous infusion of human recombinant (hr) IL-6, by osmotic minipump, on the degree of glomerular injury, and on glomerular and interstitial cell proliferation, in the accelerated autologous phase of nephrotoxic nephritis. Two groups of rats were pre-immunized with 1 mg of normal rabbit IgG in Freund's complete adjuvant. One week later, nephritis was induced by an intravenous injection of 1 ml of rabbit nephrotoxic serum. One day before the induction of nephritis, group 1 (N = 9) was subcutaneously implanted with osmotic minipumps filled with 50 micrograms (200 microliters) of IL-6 (equivalent to a dose of 6 micrograms/day), while in group 2 (N = 11) the minipumps were filled with 200 microliters of normal saline. In group 3 (N = 6) normal rats were infused with 50 micrograms of IL-6 alone. The rats were killed seven days after implantation of minipumps. The administered hrIL-6 was detectable in the circulation within the pathophysiological range, and induced a hepatic acute phase response, as assessed by alpha 2-macroglobulin levels. Continuous treatment with IL-6 resulted in a significant reduction in albuminuria (from 195 +/- 37 mg/20 hr to 60 +/- 15 mg/20 hr on day 1, and from 494 +/- 52 mg/20 hr to 238 +/- 30 mg/20 hr on day 7, P < 0.002) and in the prevalence of glomerular capillary thrombosis (from 19 +/- 3% to 5 +/- 1%, P < 0.002). There was also a reduction in macrophage infiltration (ED1 + ve cells from 524 +/- 34 to 466 +/- 14 per 50 glomeruli, P < 0.02) and activation (ED3 + ve cells from 106 +/- 13 to 42 +/- 5 per 50 glomeruli, P < 0.002). Immunohistology showed fewer interstitial Ia + ve cells (OX3 and OX4) in the IL-6 treated group. Similar results were obtained in a second set of experiments in which the IL-6 treatment was extended until day 14. Kidney sections taken from nephritic rats infused with IL-6 showed no increase in glomerular or interstitial cell proliferation when stained with antibodies to proliferating cell nuclear antigen. There was no difference in the deposition of rabbit IgG or rat IgG along the glomerular basement membrane (GBM), and the titer of rat anti-rabbit IgG was similar in the IL-6 and control treated rats. Infusion of IL-6 alone in normal rats had no functional or pathological effects. In conclusion, these results show that IL-6 has powerful anti-inflammatory effects in a rat model of anti-GBM nephritis, and does not induce mesangial cell proliferation in vivo.