Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.     

Effect of cyclosporine on adrenocortical response to injury and infection.

The effects of cyclosporine administration on the adrenocortical response to the severe stress of burn wound sepsis were studied in Wistar rats. Animals were treated with cyclosporine (10 mg/kg/day) or saline by gavage for 10 days, then subjected to 30% scald burns with wound inoculation with Pseudomonas. Animals were sacrificed on Postburn Days (PBDs) 1, 4, and 7 for determination of serum corticosterone and ACTH levels and adrenal weights and histology. Adrenal glands from animals sacrificed on PBD 7 were also analyzed for DNA, RNA, and protein content. Cyclosporine treatment without injury had no significant effect on body weight gain, adrenal mass, or baseline ACTH or corticosterone levels. During sepsis, cyclosporine-treated animals demonstrated a significantly diminished adrenocortical response compared to those given only saline. Serum corticosterone levels in the cyclosporine group were 45, 53, and 62% lower on PBDs 1, 4, and 7, respectively, than in saline-treated controls (P < 0.01 on each day). ACTH levels were 43 and 36% lower in cyclosporine-treated animals on PBDs 4 and 7, respectively, compared to the saline-treated group (P < 0.05 on each day). Adrenal hyperplasia occurred in both groups by PBD 7, but increases in adrenal mass and in histologic changes associated with hyperplasia (lipid depletion, vascular dilation) were less pronounced in cyclosporine-treated animals compared to those receiving saline, while adrenal composition remained similar between the two groups. Thus, cyclosporine administration is associated with an attenuated adrenocortical response to the stress of sepsis due to diminished circulating levels of ACTH.     

Effects of a new excitotoxic amino acid, dysiherbaine, on cultured Müller cells]

PURPOSE: To determine pharmacological response of dysiherbaine on cultured Müller cells considering the glutamate receptor functions. Dysiherbaine is a new excitotoxic amino acid, which was recently isolated from the water extract of a certain sponge. SUBJECTS AND METHOD: Retinas of adult rabbits were used to prepare the Müller cells. Intracellular calcium ion concentration ([Ca2+]i) analysis was done by fluorophotometry with calcium indicator, Fura-2 AM. RESULTS: A transient increase of [Ca2+]i was observed following the administration of dysiherbaine (2.5 microM -2.5 mM), but it was not observed in the extracellular calcium-free solution. This increase was blocked by the non NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). A dysiherbaine-induced increase in [Ca2+]i following preincubation of the NMDA glutamate receptor antagonist, (5 R, 10 S)-(+)-5-methyl-10, 11-dihydro-5 H-dibenzo [a, d] cyclohepten-5, 10-imine hydrogen maleate (MK 801) was seen in the same number of Müller cells as without the antagonist. CONCLUSION: Dysiherbaine appears to act primarily as a non NMDA glutamate receptor agonist having a secondary action as a NMDA glutamate receptor agonist.     

Insulin-receptor autoantibody detected by the human placental membrane method: six patients with insulin-receptor autoantibody in japan

Insulin-receptor antibodies were detected in six patients out of 61 diabetics from all over Japan during 1975 to 1979 using the human placental membrane method. These 61 patients were divided into three categories: (1) Those whose diabetes control needed more than 80 units of insulin a day; (2) those whose fasting IRI was higher than 50 microU/ml even with glucose intolerance; and (3) those who had hypoglycemia of unknown origin. Controls consisted of 11 serum samples from 11 healthy women and six diabetics treated with insulin and thus having insulin antibodies in their sera. The sera from healthy subjects did not suppress 125I-insulin binding with human placental membrane in either the direct or the preincubation method. 125I-insulin binding in the direct method was markedly suppressed, however, by the sera of insulin-treated diabetics, although no such suppression was observed with the preincubation method. In six of the 61 subjects (two males and four females), inhibition of binding was proved by both direct and preincubation methods for the protein fraction of the sera, particularly for the IgG fraction in five cases. Three of the six had Sj?gren syndrome; one of these also had acanthosis nigricans. Four of the six showed insulin resistance, and two did not. A follow-up showed that antibodies decreased relatively quickly in three of the six cases, with the degree of inhibition paralleling patients' clinical courses.     

Trauma in the neighborhood: a geospatial analysis and assessment of social determinants of major injury in North America

Objectives. We sought to identify and characterize areas with high rates of major trauma events in 9 diverse cities and counties in the United States and Canada.Methods. We analyzed a prospective, population-based cohort of injured individuals evaluated by 163 emergency medical service agencies transporting patients to 177 hospitals across the study sites between December 2005 and April 2007. Locations of injuries were geocoded, aggregated by census tract, assessed for geospatial clustering, and matched to sociodemographic measures. Negative binomial models were used to evaluate population measures.Results. Emergency personnel evaluated 8786 major trauma patients, and data on 7326 of these patients were available for analysis. We identified 529 (13.7%) census tracts with a higher than expected incidence of major trauma events. In multivariable models, trauma events were associated with higher unemployment rates, larger percentages of non-White residents, smaller percentages of foreign-born residents, lower educational levels, smaller household sizes, younger age, and lower income levels.Conclusions. Major trauma events tend to cluster in census tracts with distinct population characteristics, suggesting that social and contextual factors may play a role in the occurrence of significant injury events.Injury is a major public health problem and one of the most common reasons for emergency department visits, health care expenses, morbidity, and mortality.^1–4 Although a growing body of literature has assessed individual-level injury factors and outcomes, relatively little research has evaluated how broader geographic, environmental, social, and cultural factors influence the occurrence of injury.Better understanding such macroscopic influences may improve health policy strategies for injury prevention, including community planning to reduce violence, defining the interplay between contextual and individual-level injury factors, efficient deployment of emergency medical service (EMS) resources, and more targeted public health efforts to reduce injury-related morbidity and mortality. Geographic information systems (GIS) analysis has been suggested as a novel tool in evaluating such geospatial and contextual components of injury events,^5–7 yet the number of GIS-based injury studies remains relatively sparse.Injury disproportionately affects individuals in certain racial, ethnic, and socioeconomic groups.^8–10 However, whether such differences function through individual-level mechanisms or are indicative of larger societal and environmental influences is unknown. Previous geospatial injury studies evaluated intentional injury (i.e., assault)^11–13 and violent crime¹⁴ rates, falls among the elderly,⁷ pedestrian injuries,^15,16 and trauma system patients.¹⁷ These studies suggested that the locations where injuries occur are not random and that certain environmental (e.g., density of alcohol outlets), demographic, socioeconomic (e.g., poverty), and racial/ethnic factors, as well as time of day, are associated with higher injury and crime rates.However, previous research has been limited to single geographic areas, patients with certain mechanisms of injury, and hospitalized patients.^7,11–17 It remains unclear whether similar geospatial clustering exists among patients affected by additional injury mechanisms across diverse regions and communities and whether specific environmental and sociocultural factors can reliably identify high-risk populations.We sought to identify geospatial clusters of major trauma patients accessing 911 emergency services and to characterize socioeconomic, cultural, and demographic population measures in such locations across 9 diverse North American sites. These sites were Birmingham, Alabama; Dallas, Texas; Milwaukee, Wisconsin; Pittsburgh, Pennsylvania; Portland, Oregon; King County, Washington; Ottawa, Ontario; Toronto, Ontario; and Vancouver, British Columbia. Our overall aim was to combine both geospatial and population information to evaluate the contextual basis and broader social determinants of serious injury.     

Prospective validation of the Parkland Grading Scale for Cholecystitis

Background

The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes.

Expression and regulation of tumor suppressor gene maspin in human bladder cancer

Maspin is a member of serine protease inhibitor family with tumor suppressing activity for breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of maspin in human bladder cancer. We evaluated maspin expression in 65 series of bladder cancer samples (22 transurethral resection (TUR) and 43 radical cystectomy) and studied the regulatory mechanism of maspin gene activation in bladder cancer cells. Maspin expression was immunohistochemically detected in four (18.2%) patients with TUR and 22 (51.2%) patients with radical cystectomy whereas no expression was observed in normal transitional cells located at tumor-free area in bladder. The maspin expression was significantly correlated with the development of muscle invasive bladder cancer (P=0.00008). Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive bladder cancer cell lines as well as maspin-negative RT4 cells. Furthermore, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin in RT4 cells. Our results indicate that maspin may contribute to bladder cancer development and that DNA methylation and histone deacetylation may be important for regulating maspin gene activation in bladder cancer cells.