Emotional numbing: A possible endorphin-mediated phenomenon associated with post-traumatic stress disorders and other allied psychopathologic states

Numbeing of general responsiveness associated with post-traumatic stress disorders is postulated to represent a psychobiological response to overwhelming stress mediated by a hypersecretion of the endogenous opiate system. Evidence for the hypothesis is inferential and is based on: (1) similarities between behavioral symptoms of the numb state and the effects of opioids on animals and man; (2) the stress induced analgesia phenomenon, an endorphin mediated response leading to reduction of pain and fear; (3) Solomon's Opponent Process Theory, which offers a conceptual framework for understanding how the numb response can become the dominant psychopathologic disturbance in a chronic condition. Catastrophe theory models are introduced to describe and explain the relationship of emotional nonresponsiveness to rage and other affective states. In addition, other psychiatric states in which flat affect, apathy, and social withdrawal predominate are highlighted as phenomenologically and dynamically similar to the numb state and are posited to also be regulated by the endogenous opiate system.     

Long-term persistence of anti-diphtheria toxin antibodies among adults in Israel

Vaccination against diphtheria has essentially led to the disappearance of the disease in Israel. However, in other countries with high immunization coverage, isolated cases and small outbreaks have occurred in adults. Immunity following vaccination or natural exposure to toxigenic strains ofC. diphtheriae is conferred by serum antibodies to diphtheria toxin. Since booster doses of diphtheria toxoid are recommended every ten years in adults, this raises the question of persistence of protective levels Of anti-diphtheria toxin antibodies. In this study we assessed a possible age-related decline in anti-diphtheria toxin antibodies among adults in Israel. The study population comprised random samples in three age groups: 263 male recruits aged 18–19 years, 116 male reserve soldiers aged 25–35 years and 153 aged 41–51 years. Anti-diphtheria toxin antibody levels were measured by means of ELISA. Results indicate that 64.3% (95% CI=58.5–70.1%) of those aged 18–19 had anti-diphtheria toxin levels in excess of 0.1 IU ml^–1, whereas the corresponding figures for ages 25–35 and 41–51 were 32.8% (95% CI=24.2–41.3%) and 15% (95% CI=9.4–20.7%). However, even in the oldest age group, 95.4% (95% CI=90.8–98.1%) had antibodies above the presumed protective level of 0.01 IU ml^–1. Although these results indicate a significant age-related decline in anti-diphtheria toxin antibodies in vaccinated subjects, most had apparently protective levels. The absence of cases suggests that vaccine-induced immunity is long-lasting. However the immune status of the population should be carefully monitored.     

Environmental and Economic Evaluation of the Massachusetts Smoke-free Workplace Law

An environmental and economic evaluation of the smoke-free law in Massachusetts provides a broad appreciation of how a state-wide smoking ban affects the health of patrons and workers as well as the industries that are commonly concerned about the effects of smoking bans on business. The aim of this study is to evaluate environmental and economic effects of the statewide Massachusetts statewide Smoke-Free Workplace Law. Before and after the smoking ban, air quality testing was conducted in a sample (n = 27) of hospitality venues and state-wide economic changes were assessed. Compliance, in terms of patronage was measured by person-counts. Environmental outcomes were respirable suspended particles (RSP) less than 2.5 microns in diameter (PM_2.5). Economic outcomes were meals tax collections, employment in the food services and drinking places and accommodations industries. On average, levels of respirable suspended particles (RSPs) less than 2.5 microns in diameter (PM_2.5) decreased 93% in these venues after the Massachusetts Smoke-free Workplace Law went into effect. No statistically significant changes were observed among the economic indicators. This evaluation demonstrates that the state-wide Massachusetts law has effectively improved indoor air quality in a sample of Massachusetts venues and has not negatively affected several economic indicators. Support for this report was provided by the Flight Attendant Medical Research Institute.     

Elastase of U-937 Monocytelike Cells: COMPARISONS WITH ELASTASES DERIVED FROM HUMAN MONOCYTES AND NEUTROPHILS AND MURINE MACROPHAGELIKE CELLS

As an approach to facilitating the understanding of proteinases associated with monocytes we have studied U-937 monocytelike cells. Elastase activity was identified in U-937 cell extracts and compared to monocyte elastase activity, neutrophil elastase, and the elastase activity from a continuous line of murine macrophagelike cells (P388D1). Serine proteinase activity which solubilized ¹⁴C-labeled elastin accounted for >90% of the neutral proteinase activity of both U-937 cells and monocyte extracts. U-937 cell and monocyte elastase activities were similar catalytically, resembling neutrophil elastase. U-937 cells and monocytes showed other similarities: (a) both had activities reacting with [³H]diisopropylfluorophosphate that migrated in sodium dodecyl sulfate (SDS) polyacrylamide gels at ~30,000 and 60,000 daltons and (b) both contained material that cross-reacted with antiserum raised to neutrophil elastase. Preliminary characterization of U-937 cell elastase activity by affinity chromatography and ion-exchange chromatography suggested the presence of at least two distinct elastases. Minimal elastase activity was found in U-937 cell-conditioned medium, indicating that the activity is not spontaneously released by the cells. In contrast to the elastase activity associated with U-937 cells and monocytes, the elastase activity associated with P388D1 cells was a metalloproteinase and was found principally in the culture medium. These results indicate (a) U-937 cells will be useful for further investigation of proteinases associated with normal monocytes; (b) monocytes and U-937 cells contain material with catalytic and immunologic similarities to neutrophil elastase; (c) monocyte elastase activity differs from elastase activity secreted by murine macrophages and murine macrophagelike cells of the P388D1 line.     

Posttransplant anti-glomerular basement membrane nephritis in related males with Alport syndrome

This report describes the development of anti-glomerular basement membrane (GBM) glomerulonephritis after kidney transplantation in related males with Alport syndrome. Antibodies in sera from one of these patients stained normal GBM, Bowman's capsule, tubular basement membranes, and epidermal basement membranes but did not stain tissues from an unrelated Alport male. The target antigen was found to be a 26 kd peptide of the noncollagenous domain of basement membrane collagen. This study provides further evidence of the importance of abnormalities of basement membrane collagen in the pathogenesis of the Alport nephropathy. We speculate that certain mutations at the Alport locus, such as large intragenic deletions or frame-shift mutations, may be associated with failure to develop immune tolerance to epitopes on this 26kd peptide. In the setting of permissive immune response and regulation, transplantation of a normal kidney may result in the generation of anti-GBM antibodies.     

Treatment of pilonidal sinus disease using fibrin glue as a sealant

Abstract. Background Complete excision is the preferred treatment for pilonidal sinus disease. We describe a new technique of excision and tension–free primary closure of pilonidal sinus disease, combined with application of fibrin glue in order to obliterate the dead space and to promote wound healing.Methods A curved incision of the carried out, 2–3 cm lateral to the opening of the sinus, done under general or spinal anesthesia, and a thick flap was created by undercutting the medial edge and advancing it across the midline. The sinus was completely excised with all of its extensions. The flap was then sutured back to its original place by several interrupted monofilament mattress sutures. Then, 2–4 ml of fibrin glue was injected through the original pilonidal sinus opening to the sinus bed in order to obliterate the dead space.Results Thirty patients with pilonidal sinus disease were treated by this technique. In four patients, there was a temporary purulent discharge through the opening of the sinus, and there were no other complications. The mean period for returning to daily activities and to work for patients was 11 days (SD=6 days). No infection or recurrent disease was noticed during the follow–up period (23±3 months).Conclusions Complete excision with tensionfree closure with fibrin glue application may be a useful technique for the treatment of pilonidal sinus disease.     

Quantitative upper airway endoscopy with swept-source anatomical optical coherence tomography

Minimally invasive imaging of upper airway obstructions in children and adults is needed to improve clinical decision-making. Toward this goal, we demonstrate an anatomical optical coherence tomography (aOCT) system delivered via a small-bore, flexible endoscope to quantify the upper airway lumen geometry. Helical scans were obtained from a proximally-scanned fiber-optic catheter of 820 μm outer diameter and >2 mm focal length. Coupled with a long coherence length wavelength-swept light source, the system exhibited an SNR roll-off of < 10 dB over a 10 mm range. Operating at 10 rotations/s, the average accuracy of segmented cross-sectional areas was found to be −1.4 ± 1.0%. To demonstrate the capability of this system, aOCT was performed on a pediatric airway phantom and on ex vivo swine trachea. The ability for quantitative endoscopy afforded by this system can aid in diagnosis, medical and surgical decision making, and predictive modeling of upper airway obstructive disorders.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.3890) Medical optics instrumentation, (170.2150) Endoscopic imaging     

Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin

Techniques for fast noninvasive control of neuronal excitability will be of major importance for analyzing and understanding neuronal networks and animal behavior. To develop these tools we demonstrated that two light-activated signaling proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2 (ChR2), could be used to control neuronal excitability and modulate synaptic transmission. Vertebrate rhodopsin couples to the Gi/o, pertussis toxin-sensitive pathway to allow modulation of G protein-gated inward rectifying potassium channels and voltage-gated Ca2+ channels. Light-mediated activation of RO4 in cultured hippocampal neurons reduces neuronal firing within ms by hyperpolarization of the somato-dendritic membrane and when activated at presynaptic sites modulates synaptic transmission and paired-pulse facilitation. In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently to induce immediate action potentials, which precisely follow the ChR2 activation up to light stimulation frequencies of 20 Hz. To demonstrate that these constructs are useful for regulating network behavior in intact organisms, embryonic chick spinal cords were electroporated with either construct, allowing the frequency of episodes of spontaneous bursting activity, known to be important for motor circuit formation, to be precisely controlled. Thus light-activated vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal function within ms to s in a precise, reversible, and noninvasive manner in cultured neurons and intact vertebrate spinal cords.     

Radiolabeled leukocyte imaging in inflammatory bowel disease: a prospective blinded evaluation

BACKGROUND/AIMS: Nuclear medicine scintigraphies have been reported to assist in making the diagnosis of inflammatory bowel disease. This work aimed to assess the role of radiolabeled leukocyte scintigraphy for the diagnosis of suspected inflammatory bowel disease. METHODOLOGY: Forty-six adult patients were referred for labeled leukocyte scintigraphy for the evaluation of active abdominal pain. The patient population included inpatients and outpatients, with known or suspected inflammatory bowel disease. The nuclear medicine staff was blinded to the patient's specific complaints. RESULTS: The labeled leukocyte scintigraphy was positive in 11 of the 15 patients eventually determined to have Crohn's disease. Four of the 15 were false negatives. All four of the ulcerative colitis patients had normal scans. There were no false-positive scans. The positive predictive value was thus 100%, the negative predictive value was 77%, and the sensitivity and specificity were 58% and 100% respectively for Crohn's disease. CONCLUSIONS: We found radiolabeled leukocyte scintigraphy helpful in prospective, blinded assessments of patients with non-stricturizing or non-fistulizing forms of Crohn's disease. Scintigraphy may be more justified for reassessments rather than in making an initial diagnosis. The scans were of value in Crohn's disease but not for ulcerative colitis.     

Differing proliferative responses in proximal and distal colons of growing rats fed food eaten by adenoma patients

Animal dietary studies related to human colorectal carcinogenesis are usually based on AIN-76A diet, which is dissimilar to human food in source, preparation, and content. Our aim was to examine colonic epithelial proliferation in rats fed a diet based on the mean daily food intake of adenoma patients. Foods were prepared as reported by the adenoma patients and dehydrated; 64 Sprague-Dawley rats were fed either “human adenoma” or AIN-76A diet and every eight weeks, eight from each group were sacrificed. Both groups gained weight equally, had no colonic histological changes, but during the study showed progressive lengthening of colonic crypts (P<0.01) and decreased proliferation (P<0.05) in distal colons. Compared to controls, rats fed human adenoma diet had significantly longer crypts (P<0.01) and more labeled cells (P<0.05) at 32 weeks; overall they had increased proliferation (P<0.01), most significantly in the distal colon. Thus, food eaten by adenoma patients induced hyperproliferative changes in the rat colon during growth and maturity, especially the distal colon, as found in humans at risk for neoplasia.