Correction of congenital diaphragmatic hernia in utero IX: fetuses with poor prognosis (liver herniation and low lung-to-head ratio) can be saved by fetoscopic temporary tracheal occlusion

BACKGROUND/PURPOSE: Fetuses with congenital diaphragmatic hernia (CDH) who have a "poor prognosis" with postnatal treatment now can be identified on the basis of liver herniation, early diagnosis (before 25 weeks' gestation) and a low lung-to-head ratio (LHR). Because complete in utero repair proved unsuccessful for this group, the strategy of temporary tracheal occlusion was developed to gradually enlarge the hypoplastic fetal lung. The purpose of this study is to compare the outcome of patients in the poor-prognosis group treated by one of three methods: (1) standard postnatal care, (2) fetal tracheal occlusion via open hysterotomy, and (3) the recently developed video-fetoscopic (Fetendo) technique of tracheal occlusion without hysterotomy. METHODS: In the past 3 years, 34 of 86 fetuses with an isolated left CDH met criteria for the poor-prognosis group. Thirteen families chose postnatal treatment at an extracorporeal membrane oxygenation (ECMO) center, 13 underwent open fetal tracheal occlusion, and eight underwent fetoscopic tracheal occlusion. RESULTS: The survival rate was 38% in the group treated by standard postnatal therapy, 15% in the open tracheal occlusion group, and 75% in the Fetendo group. There were less postoperative pulmonary complications noted in mothers who underwent the Fetendo procedure versus the open tracheal occlusion. All but one Fetendo clip patient had a striking physiological response demonstrated by sonographic enlargement of the small left lung that was documented postnatally by plain radiographs and its subjective appearance during repair of the CDH. In contrast, only 5 of the 13 open tracheal occlusion patients demonstrated lung growth. CONCLUSION: Fetuses with a left CDH who have liver herniation and a low LHR are at high risk of neonatal demise and appear to benefit from temporary tracheal occlusion when performed fetoscopically, but not when performed by open fetal surgery.     

A systems model for low vision rehabilitation. II. Measurement of vision disabilities

BACKGROUND: This study presents and tests a method of measuring vision disabilities. Based on the model presented in the first paper of this series, cognitive and motor activities ("tasks") are organized in a hierarchy that identifies the tasks' behavioral goals (purposes) and the social objectives the goals serve. Two latent variables important to the definition of vision disability are identified: "value of living independently" and "visual ability for independent living." The basic principles of the Rasch measurement model are reviewed, and Rasch models are used to measure the two variables that define vision disability. The need for rehabilitation to meet each goal is represented by "rehabilitative demand," a mathematical function of the measurements made of the value and difficulty of achieving each goal independently. METHODS: Over 400 patients with low vision rated both the importance and difficulty of independently achieving each of 24 goals. Rasch analysis was used to derive interval measures of the social value of each goal, the value that individual patients placed on each goal relative to the derived social definition of independence, the visual ability required to achieve each goal without help, and the visual ability of individual patients to live independently. A rehabilitative demand function was ascertained from the judgments of 17 AAO Diplomates in Low Vision through triadic comparisons and multidimensional scaling. RESULTS: Self-care had the greatest "social value" for independence; performing music had the least. Recreational reading required the greatest "visual ability" to accomplish independently; self-care required the least. Rehabilitative demand was linear with value and nonmonotonic with difficulty. CONCLUSIONS: Rehabilitative demand, an algorithm for defining vision disability, incorporates interval measures of visual ability and the value of independent living estimated from patient-based assessments, a social scale of the value of activities relative to independent living, and a consensus opinion of low vision experts on the prioritization of the need for rehabilitation.     

Comparison of CT and MR imaging in staging of neck metastases

OBJECTIVE: To determine whether adaptive cytoprotection exists in human intestinal cells under in vitro conditions and what role, if any, endogenous prostaglandins or calcium may play in mediating this protective response. SUMMARY BACKGROUND DATA: Adaptive cytoprotection can be defined as that process whereby the administration of a low concentration of a damaging agent, termed a "mild irritant," which by itself is not injurious, can attenuate gastrointestinal mucosal injury subsequently induced by the application of higher concentrations of the same or other necrotizing agents. Despite substantial investigation, the mediator or mediators of adaptive cytoprotection remain poorly understood. METHODS: Postconfluent Caco-2 cells were used in all experiments. Cellular death was quantitated using a dual-component fluorescent assay. Changes in intracellular calcium concentration were quantitated by measuring fluorescent signal changes of the single wavelength calcium indicator (Fluo-3). Finally, prostaglandin E2 release into the media was quantitated by radioimmunoassay. RESULTS: Pretreatment of Caco-2 cells with low concentrations of ethanol (mild irritant) significantly attenuated injury induced by higher damaging concentrations of ethanol. The protection conferred by the mild irritant was directly dependent on both the concentration of the irritant used and the duration of exposure and was abrogated when cells were pretreated with an endogenous prostaglandin inhibitor (indomethacin) or if the mild irritant was administered in calcium-free media. Cells exposed to ethanol had a significant and concentration-dependent increase in intracellular calcium concentration, an effect that was highly related to cellular injury. Pretreatment with a mild irritant significantly decreased intracellular calcium increases induced by not only ethanol but also by a calcium ionophore (A23187). Cells treated with low concentrations of ethanol demonstrated no significant elevation in prostaglandin E2 release. CONCLUSIONS: Adaptive cytoprotection induced by ethanol exists in human colonocytes under in vitro conditions independent of mucosal blood flow, neural innervation, or circulating humoral factors. The authors' data suggest that this response does not require endogenous prostaglandin synthesis but may involve processes whereby intracellular calcium accumulation is prevented.     

Plasma-derived proteins in airway defence, disease and repair of epithelial injury

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.     

Extension of a typology of alcohol dependence based on relative genetic and environmental loading

Mild, severe, and dyssocial subtypes of alcohol dependence, previously identified among Caucasian men from the Epidemiologic Catchment Area study, were also identified among Caucasian men and women with DSM-IV alcohol dependence from the National Longitudinal Alcohol Epidemiologic Survey (n = 2,703; 1,746 respectively). These subtypes were not identified among African American and Hispanic American men or women with DSM-IV alcohol dependence. Among Caucasians with alcohol dependence, the subtypes were characterized by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales developed in a prior twin study. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales. These subtypes also showed the expected distinctions in clinical characteristics. The severe subtype showed greater comorbid drug dependence and major depression, more treatment seeking, and a higher prevalence of parental alcoholism. The severe subtype also showed significantly greater genetic influence adjusted for overall severity of alcohol dependence (genetic ratio). Only the severe subtype showed a pattern of scale scores and clinical characteristics suggestive of substantial genetic influence. The present study indicates a robustness of the typology originally developed among DSM-III alcohol-dependent Caucasian men by empirical extension of the subtypes to a different sample of Caucasian men and, separately, Caucasian women. The use of this typology may aid in distinguishing between Caucasian alcohol-dependent individuals on the basis of relative genetic influence, enabling genetic, behavioral, and epidemiological investigations to reduce genetic or environmental "noise" and better focus on specific aspects of alcohol dependence.     

Effect of fenfluramine on food intake, mood, and performance of humans living in a residential laboratory

Five male and four female normal weight research volunteers, participating in 13-day residential studies, received oral fenfluramine (20, 40 mg) or placebo at 09:30 and 17:00. Food intake, performance, and subjective ratings were measured throughout the day. Carbohydrate intake was manipulated by providing lunch meals high (males: 120 g; females: 80 g) or low (males: 25 g; females: 16 g) in carbohydrate on 8 days; on the remaining days subjects self-selected lunch. Total caloric intake (approximately 2800 Kcal) did not differ among the low- and high-carbohydrate, and self-selected lunch conditions when subjects received placebo, indicating caloric compensation. Total carbohydrate intake was significantly less, however, when subjects consumed the low-carbohydrate lunch compared to the other lunch conditions. Fenfluramine significantly decreased total caloric intake (approximately 500 kcal) by decreasing meal size, not number, only when subjects consumed the low-carbohydrate lunch. Fenfluramine was only an effective anorectic drug when subjects consumed a lunch with fewer calories and a lower carbohydrate:protein ratio than self-selected baseline. Also, fenfluramine improved performance on a range of computer tasks and increased ratings of "Alert," "Friendly," and "Talkative," while decreasing ratings of "Tired" and "Irritable."     

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).     

Yb:YAG absorption at ambient and cryogenic temperatures

We have performed absorption measurements and generated absorption cross sections as a function of wavelength for the laser material YAG doped with ytterbium at 300, 175, and 75 K. This data was generated to enable a direct comparison of the absorption intensity and linewidths at room and cryogenic temperatures, and in particular near the temperature of liquid nitrogen at 77 K. The data have been used to compute universal absorption contour plots that display absorption as a function of the incident light center wavelength and optical thickness (doping density times penetration depth) for a number of bandwidths, and assuming that the spectrum of the incident light can be described as a Gaussian. Curves are presented for both 300 and 75 K, and may be used to optimize the absorption and laser efficiency.     

Cartilage degeneration in relation to repetitive pressure: case study of a unilateral hip hemiarthroplasty patient

The mitochondrial, inner-membrane-associated, reversible NADPH-->NAD transhydrogenase of adult Hymenolepis diminuta physiologically couples matrix-localized, NADP-specific "malic" enzyme with NADH-dependent anaerobic electron transport. Employing submitochondrial particles (SMP) as the source of enzyme activity and both spectrophotometric and fluorometric assessments, the present study made evident that in its catalysis of transhydrogenation between NADPH and NAD, the cestode enzyme engages in the concomitant transmembrane translocation of protons. As assessed spectrophotometrically, the catalysis of NADPH-dependent NAD reduction by H. diminuta SMP was stimulated significantly by carbonyl cyanide 3-chlorophenylhydrazone (CCCP), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), as well as by the protonophoric anthelmintic, niclosamide. In addition, N,N'-dicyclohexylcarbodiimide (DCCD) markedly diminished SMP-catalyzed hydride ion transfer between NADPH and NAD. The catalysis by SMP of concomitant, transhydrogenase-mediated proton translocation was evaluated more directly via fluorometric assays using 8-anilino-1-napthalenesulfonic acid (ANS) as the probe. These latter evaluations revealed a transhydrogenase-dependent enhancement of ANS fluorescence in accord with an intravesicular accumulation of protons. ANS fluorescence was quenched rapidly when the assay system was supplemented with CCCP, FCCP, or niclosamide. Consistent with the helminth transhydrogenase acting as a proton pump, transhydrogenase-mediated enhanced fluorescence also was inhibited by DCCD. Considered collectively, these data indicated, apparently for the first time for any invertebrate system, that the transhydrogenase, in catalyzing the NADPH-->NAD reaction, acts in the translocation of protons from the matrix to the intermembrane space mitochondrial compartment.