The effects of UV-B irradiation on the corneal endothelium

Rabbit eyes, in vivo and in vitro, were exposed to UV-B irradiation at 300 nm, from a mercury arc lamp with an 11 nm bandpass filter. Radiant exposure ranged from 0.1 J/cm2 to 0.5 J/cm2. In vivo, swelling of the cornea resulted over a 12 to 40 hr period, the extent and duration being directly related to exposure. Recovery of normal thickness was complete within four days. Corneas removed at 18 hr after exposure recovered normal thickness during a five hour perfusion period, except for those most heavily exposed. When removed at 42 hr post exposure all corneas thinned to almost normal thickness. SEM showed the endothelial cells of exposed eyes to have either exaggerated villi on the surface and a disorganized mosaic or, after higher exposures, to be devoid of villi and have loose, flap like cell borders and large "blebs." After exposure of isolated corneas mounted for perfusion, swelling again ensued and similar changes were observed in the appearance of the cells, except that "blebs" were not found. No significant changes were observed in the metabolic components ATP, ascorbate and glutathione, nor was there any indication of lipid peroxidation. At higher in vivo exposures, the aqueous humor did show a decrease in ascorbate concentration and an increase in protein content, which probably result from a breakdown of the blood-aqueous barrier. UV-B irradiation may cause or promote changes in the endothelium associated with aging, but the one time radiant exposures of the magnitude used in this study, appear to have no severe or permanently toxic effects.     

Machine Learning Predicts the Fall Risk of Total Hip Arthroplasty Patients Based on Wearable Sensor Instrumented Performance Tests

BackgroundThe prevalence of falls affects the wellbeing of aging adults and places an economic burden on the healthcare system. Integration of wearable sensors into existing fall risk assessment tools enables objective data collection that describes the functional ability of patients. In this study, supervised machine learning was applied to sensor-derived metrics to predict the fall risk of patients following total hip arthroplasty.MethodsAt preoperative, 2-week, and 6-week postoperative appointments, patients (n = 72) were instrumented with sensors while they performed the timed-up-and-go walking test. Preoperative and 2-week postoperative data were used to form the feature sets and 6-week total times were used as labels. Support vector machine and linear discriminant analysis classifier models were developed and tested on various combinations of feature sets and feature reduction schemes. Using a 10-fold leave-some-subjects-out testing scheme, the accuracy, sensitivity, specificity, and area under the receiver-operator curve (AUC) were evaluated for all models.ResultsA high performance model (accuracy = 0.87, sensitivity = 0.97, specificity = 0.46, AUC = 0.82) was obtained with a support vector machine classifier using sensor-derived metrics from only the preoperative appointment. An overall improved performance (accuracy = 0.90, sensitivity = 0.93, specificity = 0.59, AUC = 0.88) was achieved with a linear discriminant analysis classifier when 2-week postoperative data were added to the preoperative data.ConclusionThe high accuracy of the fall risk prediction models is valuable for patients, clinicians, and the healthcare system. High-risk patients can implement preventative measures and low-risk patients can be directed to enhanced recovery care programs.     

Clinical prediction models to predict the risk of multiple binary outcomes: a comparison of approaches

Clinical prediction models (CPMs) can predict clinically relevant outcomes or events. Typically, prognostic CPMs are derived to predict the risk of a single future outcome. However, there are many medical applications where two or more outcomes are of interest, meaning this should be more widely reflected in CPMs so they can accurately estimate the joint risk of multiple outcomes simultaneously. A potentially naïve approach to multi‐outcome risk prediction is to derive a CPM for each outcome separately, then multiply the predicted risks. This approach is only valid if the outcomes are conditionally independent given the covariates, and it fails to exploit the potential relationships between the outcomes. This paper outlines several approaches that could be used to develop CPMs for multiple binary outcomes. We consider four methods, ranging in complexity and conditional independence assumptions: namely, probabilistic classifier chain, multinomial logistic regression, multivariate logistic regression, and a Bayesian probit model. These are compared with methods that rely on conditional independence: separate univariate CPMs and stacked regression. Employing a simulation study and real‐world example, we illustrate that CPMs for joint risk prediction of multiple outcomes should only be derived using methods that model the residual correlation between outcomes. In such a situation, our results suggest that probabilistic classification chains, multinomial logistic regression or the Bayesian probit model are all appropriate choices. We call into question the development of CPMs for each outcome in isolation when multiple correlated or structurally related outcomes are of interest and recommend more multivariate approaches to risk prediction.     

Preliminary observations on the application of the multiple inocula (replicator) method for carbon substrate utilization studies of Alcaligenes faecalis.

The use of the replicator technique in evaluating carbon source utilization by 55 cultures of Alcaligenes faecalis was examined. Six of the 20 substrates tested were utilized by the bacterial cultures. In this study, the reproducibility of the technique was 100%.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

An evaluation of three methods for determining colloid osmotic pressure

Plasma colloid osmotic pressure (COP) is an important determinant in edema formation. Three methods for assessing the COP were evaluated. Direct measurement of COP using the 4420 Wescor Colloid Osmometer was compared to the estimation of COP from both serum total protein and total serum solids (TSS) determinations. Blood samples from twenty adult patients (mean age = 64 years) undergoing cardiopulmonary bypass surgery were collected for COP assessment. Sample collection was performed prior to heparinization/hemodilution, during hypothermic bypass and at the conclusion of bypass following protamine administration. The results obtained from each method were analyzed by a two-way analysis of variance. The Bonferroni technique was used for comparison of sample means when the difference was significant (p less than 0.05). Correlations were reported by linear regression analysis. A statistically significant difference (p less than 0.01) was found between the three methods. A regression equation for the estimation of COP from total serum solids is offered: COP = (3.02 * TSS) + 0.65. Prospective clinical testing between the direct COP measurement and the estimation of COP from TSS using the equation (n = 38) revealed a significant correlation (R2 = .932) and no significant difference between the two (p greater than 0.05).     

Comparison of gaseous microemboli counts in arterial, simultaneous and venous heat exchange with a hollow fiber membrane oxygenator

Potential sources of gaseous microemboli during cardiopulmonary bypass are varied. However, it is known that membrane oxygenators generate fewer gaseous microemboli than bubble oxygenators and that bubblers cannot utilize arterial heat exchange without generating significant gaseous microemboli during rewarming. A membrane oxygenator utilizing simultaneous gas and heat exchange raises the concern that concurrent gas and heat exchange would result in a higher production of gaseous microemboli compared to conventional venous heat exchange devices. This in vitro study compared venous, simultaneous, arterial and control (venous) heat exchanger gaseous microemboli counts during rewarming. No significant difference was found between the four heat exchangers when comparing inlet and outlet gaseous microemboli counts. This in vitro study suggests that there is no difference in gaseous microemboli generation when varying the position of the heat exchanger in the extracorporeal circuit incorporating a microporous membrane oxygenator.     

EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs     

Life-long absence of sexual drive in a woman associated with 5-dihydrotestosterone deficiency

A case of a woman who presented with life-long absence of sexual drive is reported. Although her history contained psychological factors that might have been etiologic in her presentation, she had not responded to sex therapy or cognitive-behavior psychotherapy undertaken at other clinics. When seen by the author, she was found to have poorly developed external genitalia. The only abnormality discovered on endocrinological evaluation was a reduced level of 5 dihydrotestosterone. Treatment with dihydrotestosterone gel applied to her vulva generated sexual drive and her ability to become sexually aroused.