Studies of the distribution of lipofuscin in the retinal pigment epithelium using high-resolution TV laser scanning ophthalmoscopy

BACKGROUND: The fundus autofluorescence imaging technique has been modified allowing improved image resolution (768 x 572 pixel). We present results of fundus autofluorescence studies using this technique. MATERIALS AND METHODS: Fundus autofluorescence was studied in 286 eyes of 143 patients with retinitis pigmentosa, macular dystrophies and age-related macular degeneration using a confocal laser scanning ophthalmoscope prototype (Zeiss, Oberkochen; excitation wavelength: 488 nm, cut-off filter at 521 nm). RESULTS: The spatial distribution of autofluorescence was different in all diseased eyes investigated compared to the normal pattern of fundus autofluorescence. Each disorder showed a specific fundus autofluorescence appearance. CONCLUSIONS: The advanced technique of imaging fundus autofluorescence allows detailed studies of the lipofuscin distribution. In vivo analysis of the dynamics of accumulation and degradation of lipofuscin in eyes with tapeto-retinal dystrophies and age-related macular disease may contribute to elucidation of the pathogenesis of these disorders.     

Effects of estrogen on tight junctional resistance in cultured human umbilical vein endothelial cells

OBJECTIVE: To study the effects of estrogen on transendothelial paracellular permeability in women. METHODS: Human umbilical vein endothelial cells (HUVEC) obtained from women were grown on filters. The paracellular permeability characteristics were determined in terms of changes in the permeability to the polar acid pyranine (Ppyr) and as changes in the transendothelial electrical resistance (RTE). Tight junctional resistance characteristics were assayed by lowering luminal NaCl and measuring the dilution potential, and were expressed as the ratio of monoion mobility uCl/uNa (cation selectivity). RESULTS: Low extracellular calcium and hyperosmolarity increased Ppyr and decreased RTE. The former but not the latter condition abolished the endothelium-specific cation selectivity. Treatment with 10 nM of estradiol-17 beta had no effect on RTE, but it increased the cation selectivity. The effect of estradiol required 1-6 hours' incubation with the hormone; it was dose dependent and saturable, with a median effective concentration of estradiol of 1 nM. Diethylstilbestrol, but not estriol, could mimic the effect of estradiol, and the estrogen receptor antagonist ICI-182, 780 blocked it. CONCLUSION: Cultured HUVEC cells form patent tight junctions. Estrogens increase the cation selectivity across HUVEC cultures. The effect of estrogen may be mediated by an estrogen receptor. These effects may be important for vasculoprotection in cases of sudden changes in ions levels across the capillary wall, such as ischemia or reperfusion.     

Attenuation of the polypeptide 7B2, prohormone convertase PC2, and vasopressin in the hypothalamus of some Prader-Willi patients: indications for a processing defect

7B2 is a neuroendocrine chaperone interacting with the prohormone convertase PC2 in the regulated secretory pathway. Its gene is located near the Prader-Willi syndrome (PWS) region on chromosome 15. In a previous study we were able to show 7B2 immunoreactivity in the supraoptic nucleus (SON) or the paraventricular nucleus (PVN) in only three of five PWS patients. Here we report that in contrast with five other PWS patients, the neurons in the hypothalamic SON and PVN of the two 7B2-immunonegative PWS patients also failed to show any reaction using two antibodies directed against processed vasopressin (VP). On the other hand, even these two cases reacted normally with five antibodies that recognize different parts of the VP precursor. This finding pointed to a processing defect. Indeed, the same patients had no PC2 immunoreactivity in the SON or PVN, whereas PC1 immunoreactivity was only slightly diminished. In conclusion, in the VP neurons of two PWS patients, greatly reduced amounts of 7B2 and PC2 are present, resulting in diminished VP precursor processing.     

Abnormal motion displacement thresholds are associated with fine scale luminance sensitivity loss in glaucoma

This study tests the hypothesis that abnormal motion displacement thresholds coexist with scotomas on a finer spatial scale than is measurable by conventional Humphrey perimetry. Eighteen patients with primary open angle glaucoma in one eye, and 18 age matched normal controls underwent motion displacement threshold testing and high spatial resolution perimetry. The motion displacement thresholds were significantly elevated in the glaucoma eyes, in 73% this exceeded normal limits. Ten glaucoma eyes had normal Humphrey 24-2 field nearest the motion test site: of these seven had abnormally elevated motion displacement thresholds and six had fine scale threshold depressions detected with high spatial resolution perimetry. This result suggests that glaucomatous elevations of motion displacement threshold may be present in areas of normal Humphrey 24-2 field, and this may coexist with measurable scotomas beyond the resolution of conventional Humphrey perimetry in some, but not all patients.     

Bioelectromagnetic applications for multiple sclerosis

There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.     

Physiochemical methods for pharmacokinetic and residue analysis of chloramphenicol and degradation products in dairy cows

The disposition of chloramphenicol after intramammary and intravenous administration was followed through determinations of chloramphenicol in blood and milk by means of high-performance differential pulse polarography. The concentration-time curves obtained reflected the different modes of administration, and allowed calculation of some pharmacokinetic parameters. The results of the polarographic determination in blood agreed fairly well with those of the microbiological assay in serum. Several body fluids and tissues of the cows were examined for residues of chloramphenicol and degradation products, both by the microbiological method and by high-performance liquid chromatography with ultraviolet detection. In urine, chloramphenicol and chloramphenicol glucuronide were found; in the other fluids and tissues only now and then a trace of chloramphenicol or a degradation product was detected. From these results it appears that chloramphenicol and degradation products are eliminated rapidly and completely after intravenous or intramammary application. No accumulation of degradation products occurred.     

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.