Expression of alpha-defensin-1 in chronic hyperplastic candidosis

BACKGROUND: Chronic hyperplastic candidosis (CHC) represents a chronic opportunistic candida infection. We clarified the presence, localization and participation of alpha-defensin-1 in host response against chronic candidal stimulus. METHODS: Immunohistochemically stained CHC biopsies (n = 10) were compared to candida negative idiopathic leukoplakia (n = 10). RESULTS: In CHC alpha-defensin-1 was detected in neutrophils intravascularly, in lamina propria and in the epithelium, in part in intraepithelial microabscesses. Staining intensity of individual neutrophils varied and was associated with peri- and extracellular staining, in particular in the superficial epithelial cell layers. In controls only very few homogeneously staining neutrophils were detected intravascularly without any extracellular alpha-defensin-1 deposition. CONCLUSIONS: Neutrophils form microabscesses and respond to Candida by activation and release of alpha-defensin-1 to peri- and extracellular matrix. This together with the epithelial cell migration from the basal layer to epithelial surface leads to alpha-defensin-1 rich protective shield in the most superficial epithelial cell layers.     

117Care of the Thermally Injured Breast

Introduction : Thermal injury to the female breast is one of the most challenging aspects of aesthetic burn surgery today. As the ability to provide coverage for large body surface injuries has progressed greatly in recent years; attention can now be directed towards achieving aesthetically pleasing results. Breast reconstruction in the burn patient can be accomplished in several ways. In planning the reconstruction, one must account for gender, age, and stage of breast development at the time of injury. The following is the treatment protocol utilized at our institution. After determining the level of injury the injured area is cleansed and treated with topical anti‐microbial agents such as Silvadene. If the decision is made to excise and graft the injured area one of two algorithms is followed. The first choice involves excising the burn and placing a split thickness skin graft to the area involved. This is done by placing a sheet graft and using aerosolized fibrin sealant to affix it to the wound bed. If the burn involves deeper elements of tissue then a second approach is taken which includes excision of the burn down to the level of fascia with preservation of the breast mounds and the nipple areola complex (NAR). The (NAR) is spared excision and allowed to heal. Reconstruction of the (NAR) can be deferred for a secondary procedure depending upon the response to primary healing. A split thickness skin graft is then applied to the area of injury. Again a sheet graft is preferred and fibrin sealant is utilized to improve graft fixation and contour. We attribute our excellent results to the sheet grafts and fibrin sealant used. It should be noted that the increased vascularity of the breast fat when compared to fat located elsewhere in the body allows the grafts to adhere and survive on this generally difficult to graft surface. Methods : We identified five female patients at our institution over the last 18 months with thermal injuries to the breasts. Each patient was placed into one of the two treatment algorithms. Results : The five patients had excellent outcomes. Breast mounds and symmetry were preserved. Further development of the breast was allowed in each patient. One patient even underwent a breast augmentation after surviving a 50% TBSA injury. Proper use of fibrin sealant and sheet grafts account for the excellent results seen at this institution. Conclusion : Following careful evaluation of the burned female breast cosmetically and functionally acceptable results can be attained when following our institution’s protocol for breast reconstruction in the female burn victim.     

Acquired Resistance of Escherichia coli to Complement Lysis by Binding of Glycophosphoinositol-Anchored Protectin (CD59)

Protectin (CD59) is a glycophosphoinsitol (GPI)-anchored defender of human cells against lysis by the membrane attack complex of complement. In this study, we examined whether protectin released from human cell membranes can incorporate into the surface of gram-negative bacteria. Analysis by using radiolabeled protectin, immunofluorescence, flow cytometry, and whole-cell enzyme-linked immunosorbent assay demonstrated that protectin bound to nonencapsulated Escherichia coli EH237 (Re) and EH234 (Ra) in a calcium-dependent manner. The incorporation required the GPI-phospholipid moiety since no binding of a phospholipid-free soluble form of protectin was observed. Mg²⁺ did not enhance the binding, and a polysialic acid capsule prevented it (strain IH3080 [O18:K1:H8]). Bound protectin inhibited the C5b-9 neoantigen expression on complement-treated bacteria. Protection against complement lysis was observed in both a colony counting assay and a bioluminescence assay, where viable EH234 bacteria expressing the luciferase gene emitted green light in the presence of the luciferine substrate. In general, two- to four-times-higher serum concentrations were needed to obtain 50% lysis of protectin-coated versus noncoated bacteria. The results indicate that protectin can incorporate in a functionally active form into the cell membranes of the two nonencapsulated deep rough E. coli strains studied.     

Oral infections and systemic disease—an emerging problem in medicine

The relationship between oral and general health has been increasingly recognised during the past two decades. Several epidemiological studies have linked poor oral health with cardiovascular disease, poor glycaemic control in diabetics, low birth-weight pre-term babies, and a number of other conditions, including rheumatoid arthritis and osteoporosis. Oral infections are also recognised as a problem for individuals suffering from a range of chronic conditions, including cancer and infection with human immunodeficiency virus, as well as patients with ventilator-associated pneumonia. This review considers the systemic consequences of odontogenic infections and the possible mechanisms by which oral infection and inflammation can contribute to cardiovascular disease, as well as the oral conditions associated with medically compromised patients. A large number of clinical studies have established the clinical efficacy of topical antimicrobial agents, e.g., chlorhexidine and triclosan, in the prevention and control of oral disease, especially gingivitis and dental plaque. The possible risks of antimicrobial resistance are a concern, and the benefits of long-term use of triclosan require further evaluation. Oral infections have become an increasingly common risk-factor for systemic disease, which clinicians should take into account. Clinicians should increase their knowledge of oral diseases, and dentists must strengthen their understanding of general medicine, in order to avoid unnecessary risks for infection that originate in the mouth.     

Morbidity and mortality in elderly trauma patients

BACKGROUND: Despite an increasing incidence, relatively few studies have examined the factors that predict morbidity and mortality in older patients and several reports have found standard predictors such as the Injury Severity Score to be less useful in this patient population. Similarly, the effect of skeletal injury has not been examined with regard to complications and mortality. The purpose of this study was to review a large multicenter experience with elderly trauma patients to isolate factors that might predict morbidity and mortality. The potential effect of skeletal long-bone injury was of particular interest. METHODS: The charts of all patients older than 60 years who were admitted to one of four Level I trauma centers after sustaining blunt trauma were reviewed. Mechanisms of injury included in the study were motor vehicle crash, pedestrian struck, fall from a height, and crush injury. Slip-and-fall injuries were excluded. A total of 326 patients met inclusion criteria. Variables studied included age, sex, mechanism of injury, Injury Severity Score (ISS), Revised Trauma Score, Glasgow Coma Scale (GCS) score, blood transfusion, fluid resuscitation, surgery performed (laparotomy, long-bone fracture stabilization, both), and timing of surgery. Outcome variables measured included incidence of adult respiratory distress syndrome, pneumonia, sepsis, myocardial infarction, deep venous thromboembolism, gastrointestinal complications, and death. chi2, logistic regression, t test, and nonparametric analyses were done as appropriate for the type of variable. RESULTS: The average age of the patients was 72.2+/-8 years. Overall, 59 patients (18.1%) died, of whom 52 of 59 survived at least 24 hours. Statistical significance for continuous variables (p < 0.05) using univariate analysis was reached for the following factors for the patients who died: higher ISS (33.1 vs. 16.4), lower GCS score (11.5 vs. 13.9), greater transfusion requirement (10.9 vs. 2.9 U), and more fluid infused (12.4 vs. 4.9 L). Logistic regression analysis was performed to determine the factors that predicted mortality. They included (odds ratios and p values in parentheses) transfusion (1.11, p = 0.01), ISS (1.04, p = 0.008), GCS score (0.87, p = 0.007), and fluid requirement (1.06, p = 0.06). Regarding surgery, orthopedic surgery alone had an odds ratio of 0.53, indicating that orthopedic patients was less likely to die than patients who did not undergo any surgery. Patients who underwent only a general surgical procedure were 2.5 times more likely to die (p = 0.03) and patients who underwent both general and orthopedic procedures were 1.5 times more likely to die (p = 0.32) than patients who did not require surgery. Early (< or =24 hours) versus late (>24 hours) surgery for bony stabilization did not have a statistical effect on mortality (11% early vs. 18% late). Two patients in need of bony stabilization, however, died before these procedures were performed. With regard to complications, regression analysis revealed that ISS predicted adult respiratory distress syndrome, pneumonia, sepsis, and gastrointestinal complications; fluid transfusion predicted myocardial infusion; and need for surgery and transfusion requirements predicted sepsis. These complications, in turn, were significant risk factors for mortality. This large series of elderly patients demonstrates that mortality correlates closely with ISS and is influenced by blood and fluid requirements and by GCS score. The institution-specific mortality was the same when adjusted for ISS. The need for orthopedic surgery and the timing of the surgery was not a risk factor for systemic complications or mortality in this series. CONCLUSION: Mortality is predicted by ISS and by complications in older patients. Seventy-seven percent of the orthopedic injuries were stabilized early, but the timing of surgery did not have any statistical effect on the incidence of complications or mortality. (ABSTRACT TRUNCA     

Health-related quality of life in adults with hearing impairment before and after hearing-aid rehabilitation in Finland

Objective: The aim of this study was to evaluate health-related quality of life (HRQoL) in adults with hearing impairment in Finland before and after hearing rehabilitation. Design: The study was prospective with hearing-aid rehabilitation as the intervention. The data was collected, using the 15D instrument, before and six months after hearing-aid rehabilitation. The data was analysed using t-tests and multiple linear regression methods. Study sample: The study sample included 949 adults with hearing impairment, and the control group included a sample of age- and gender-standardized general population. Results: The study population had significantly poorer HRQoL on most dimensions of the 15D when compared to the control group both before and after hearing-aid rehabilitation. Hearing-aid rehabilitation resulted in improved mean scores on the dimensions of hearing and in the overall 15D score that were statistically significant, although the mean improvement in the overall score was marginal. Self-reported hearing ability can better predict the change in HRQoL, as a result of a hearing aid, when compared with measured hearing sensitivity. Conclusions: The study supports the hypothesis that on average, use of a unilateral hearing aid results in improved subjective hearing and marginal improvement in HRQoL in adults with hearing impairment.     

Compliance with treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, progressive, debilitating disease that demands continuous therapy with multiple medications. Noncompliance with disease-modifying drugs may cause disease flares, preventable functional impairment, unnecessary treatment changes, and loss of health care resources. The aim of the current study was to explore self-reported compliance with treatment and the factors contributing to this compliance using a representative sample of an RA patient population in Estonia. Two thousand patients diagnosed with RA were randomly selected from the Estonian Health Insurance Fund database. The eligible response rate of the study was 60%. Using prestructured questionnaires, the following information about the disease and treatment was evaluated: self-reported compliance with treatment, reasons for noncompliance, disease history, sociodemographic variables, health care utilization, and satisfaction with health care providers. The self-reported compliance rate was 80.3%, reflecting the percentage of patients who reported that they always took their medications exactly as described. The most often reported reasons for noncompliance were side effects and fear of side effects. Compliance was found to be the lowest in a group of younger and active patients with higher income. Higher frequency of visits to the rheumatologist, satisfaction with health care providers, and sufficient information about RA treatment correlated with better compliance.     

Fermentative 2‐carbon metabolism produces carcinogenic levels of acetaldehyde in Candida albicans

Acetaldehyde is a carcinogenic product of alcohol fermentation and metabolism in microbes associated with cancers of the upper digestive tract. In yeast acetaldehyde is a by‐product of the pyruvate bypass that converts pyruvate into acetyl‐Coenzyme A (CoA) during fermentation. The aims of our study were: (i) to determine the levels of acetaldehyde produced by Candida albicans in the presence of glucose in low oxygen tension in vitro; (ii) to analyse the expression levels of genes involved in the pyruvate‐bypass and acetaldehyde production; and (iii) to analyse whether any correlations exist between acetaldehyde levels, alcohol dehydrogenase enzyme activity or expression of the genes involved in the pyruvate‐bypass. Candida albicans strains were isolated from patients with oral squamous cell carcinoma (n = 5), autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) patients with chronic oral candidosis (n = 5), and control patients (n = 5). The acetaldehyde and ethanol production by these isolates grown under low oxygen tension in the presence of glucose was determined, and the expression of alcohol dehydrogenase (ADH1 and ADH2), pyruvate decarboxylase (PDC11), aldehyde dehydrogenase (ALD6) and acetyl‐CoA synthetase (ACS1 and ACS2) and Adh enzyme activity were analysed. The C. albicans isolates produced high levels of acetaldehyde from glucose under low oxygen tension. The acetaldehyde levels did not correlate with the expression of ADH1, ADH2 or PDC11 but correlated with the expression of down‐stream genes ALD6 and ACS1. Significant differences in the gene expressions were measured between strains isolated from different patient groups. Under low oxygen tension ALD6 and ACS1, instead of ADH1 or ADH2, appear the most reliable indicators of candidal acetaldehyde production from glucose.     

Decreased susceptibility of Candida albicans to azole antifungals: a complication of long-term treatment in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS1) is an autosomal recessive disease exceptionally common in Finland. Most patients have chronic oral candidiasis from early childhood and this infection has been shown to be carcinogenic. Hence, patients receive repeated treatment and prophylactic courses of antifungals throughout life. In Finland, 92 patients have been diagnosed with APECED and 66 of them are currently alive. Our aim was to study the effect of long-term azole treatment on the candidal colonization of APECED patients and the influence on antifungal susceptibilities. METHODS: We evaluated the culture reports from 1994 to 2004 of 56 APECED patients followed in Helsinki University Central Hospital. Candida albicans strains of all 11 patients initially reported resistant (n = 27) and 12 patients reported susceptible (n = 16) to fluconazole were re-analysed for their susceptibility to fluconazole. Antifungal usage was analysed up to 30 years back. RESULTS: A total of 162 fungal cultures had been performed. Of these, 75% had been reported positive for Candida and 63% for C. albicans. Eleven patients (31.4%) had been reported to harbour at least once a C. albicans strain resistant to fluconazole. Re-analysis of the stored C. albicans strains originally reported to be resistant to fluconazole revealed a mean MIC of 19.5 mg/L. CONCLUSIONS: Multiple courses (>6) of fluconazole annually and low dose prophylaxis are major risk factors for persistent colonization with C. albicans with decreased susceptibility in APECED patients.