Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins

The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).     

105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.     

Urinary aquaporin-2 levels in healthy volunteers

SUMMARY:   Renal water handling is regulated by the release of arginine vasopressin (AVP) and the subsequent insertion of aquaporin 2 (AQP2) in the apical membrane of collecting duct cells. This in turn increases the membrane permeability to water and the passive reabsorption of water down the concentration gradient present in the medulla. Aquaporin 2 can be detected in the urine under conditions of antidiuresis. We wish to validate an assay for urinary AQP2. Fourteen volunteers participated in studies of water loading and water deprivation followed by the administration of 1-deamino-8- d -arginine vasopressin (dDAVP). Urine osmolality was measured by vapour pressure osmometry. Urinary AQP2 was measured by using a chemiluminescent assay. Baseline correlations between serum AVP levels, urinary osmolality and urinary AQP2 levels were not significant. Following the administration of dDAVP, a positive correlation between urine osmolality and urinary AQP2 was evident ( r  = 0.762). For specific conditions where renal water retention is stimulated via AVP, urinary AQP2 measurements provide a reproducible measurement of the renal actions of AVP.     

Prevention of surgical site infection by antibiotic spraying in the operative field during cardiac surgery

OBJECTIVE: Despite the many procedures introduced to prevent surgical site infection during cardiothoracic surgery, serious infections still occur. We attempted to reduce surgical site infection by spraying antibiotic solution in the operative field--a procedure since introduced at 4 other Japanese institutions. METHODS: In the latter half of 1990, we began spraying an antibiotic solution of cefazolin (1g) and gentamicin (40 mg)/40 ml of saline placed in a 50 ml syringe and dispensed through an 18 G needle bent at 60 to 80 degrees to clean the wound during surgery. RESULT: No deep surgical site infections or deaths due to infection have occurred among the 502 patients undergoing cardiothoracic surgery under cardiopulmonary bypass at our hospital. This method was used in over 2,100 cases of similar procedures at 4 other institutions. There were 3 deaths due to severe surgical site infection (0.11%). At one institution treating over 1,000 cases a year, the incidence of death due to surgical site infection decreased significantly after this method was introduced. CONCLUSION: These preliminary experiences show that spraying antibiotic solution in the operative field reduces the risk of surgical site infection in cardiothoracic surgery.     

Anticoagulation in patients with atrial fibrillation,thrombocytopenia and hematological malignancy

Journal of Thrombosis and Thrombolysis - Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We...     

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes

IntroductionDissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales.MethodsA 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications.ResultsA total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively.ConclusionsFunnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.     

An analysis of the predictors of comorbid psychopathology,gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder

Mannion, Leader, and Healy (2013) examined the frequency of comorbid disorders in children and adolescents with autism spectrum disorder and the predictors of sleep problems. This study will extend this research by investigating the predictors of comorbidity in 89 participants. Age, gender, level of intellectual disability, presence of epilepsy, attention deficit/hyperactivity disorder (AD/HD) and an anxiety disorder were determined using a self-constructed demographic questionnaire. The Autism Spectrum Disorder-Comorbid for Children (ASD-CC) was administered to informants to assess symptoms of comorbid psychopathology. The Children's Sleep Habits Questionnaire (CSHQ) and Gastrointestinal symptom inventory were administered to assess sleep problems and gastrointestinal symptoms respectively. Sleep problems predicted gastrointestinal symptoms. Level of intellectual disability predicted gastrointestinal symptoms. Specifically, those with no intellectual disability were more likely to present with gastrointestinal symptoms. Gastrointestinal symptoms in turn predicted total comorbid psychopathology score and the individual subscales of worry/depressed, avoidant behavior, conduct behavior and tantrum behavior on the ASD-CC. Gender and ASD-CC total score predicted an individual having an anxiety disorder. Specifically, being male predicted an anxiety disorder. The ASD-CC subscales of worry/depressed and avoidant behavior predicted an anxiety disorder. The implications of these findings are discussed in the study.