J. Wesley Alexander

The process of microbial translocation

The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.

Bisphenol a at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes

Background The incidence of obesity has risen dramatically over the last few decades. This epidemic may be affected by exposure to xenobiotic chemicals. Bisphenol A (BPA), an endocrine disruptor, is detectable at nanomolar levels in human serum worldwide. Adiponectin is an adipocyte-specific hormone that increases insulin sensitivity and reduces tissue inflammation. Thus, any factor that suppresses adiponectin release could lead to insulin resistance and increased susceptibility to obesity-associated diseases. Objectives In this study we aimed to compare a) the effects of low doses of BPA and estradiol (E2) on adiponectin secretion from human breast, subcutaneous, and visceral adipose explants and mature adipocytes, and b) expression of putative estrogen and estrogen-related receptors (ERRs) in these tissues. Methods We determined adiponectin levels in conditioned media from adipose explants or adipocytes by enzyme-linked immunosorbant assay. We determined expression of estrogen receptors (ERs) α and β, G-protein–coupled receptor 30 (GPR30), and ERRs α, β, and γ by quantitative real-time polymerase chain reaction. Results BPA at 0.1 and 1 nM doses suppressed adiponectin release from all adipose depots examined. Despite substantial variability among patients, BPA was as effective, and often more effective, than equimolar concentrations of E2. Adipose tissue expresses similar mRNA levels of ERα, ERβ, and ERRγ, and 20- to 30-fold lower levels of GPR30, ERRα, and ERRβ. Conclusions BPA at environmentally relevant doses inhibits the release of a key adipokine that protects humans from metabolic syndrome. The mechanism by which BPA suppresses adiponectin and the receptors involved remains to be determined.

Immunonutrition: the role of ω-3 fatty acids ☆

The dietary fatty acids of the ω-3 series are rapidly incorporated into cell membranes and profoundly influence biological responses. These lipids influence membrane stability, membrane fluidity, cell mobility, the formation of receptors, binding of ligands to their receptors, activation of intracellular signaling pathways either directly or through the formation of eicosanoids, gene expression, and cell differentiation. In general, eicosanoids formed from the ω-3 fatty acids are much less potent in causing biological responses than those formed from the ω-6 fatty acids, including stimulation of cytokine production and inflammatory responses. In well-controlled clinical studies, consumption of ω-3 fatty acids has resulted in reduction of cardiovascular diseases including arrhythmias and hypertension, protection from renal disease, improvement in rheumatoid arthritis, improvement in inflammatory bowel diseases, reduced episodes of rejection, and protection from infection. The interactions between the ω-3 fatty acids and pharmacologic drugs that alter intracellular signaling pathways are only now being studied.

History of the Medical Use of Silver

BACKGROUND Silver has been used extensively throughout recorded history for a variety of medical purposes. METHODS A review of the literature in English was undertaken, primarily using PUBMED, to identify the medical uses of silver before the clinical introduction of antibiotics in the 1940s. RESULTS Silver has been used for at least six millennia to prevent microbial infections. It has been effective against almost all organisms tested and has been used to treat numerous infections and noninfectious conditions, sometimes with striking success. Silver also has played an important role in the development of radiology and in improving wound healing. CONCLUSION Silver was the most important antimicrobial agent available before the introduction of antibiotics.

Differential Effects of Three Enteral Dietary Regimens on Selected Outcome Variables in Burn Patients

A modular tube feeding recipe (MTF) was designed to meet the unique nutritional needs of burn patients, applying principles previously documented in our burned guinea pig model. MTF, a high-protein, low-fat, linoleic acid-restricted formulation is enriched with omega-3 fatty acids, arginine, cysteine, histidine, vitamin A, zinc, and ascorbic acid. Fifty patients, 3 to 76 years of age with burns ranging from 10 to 89% total body surface area were prospectively randomized into three groups which blindly compared MTF to two enteral regimens widely utilized in the nutritional support of burns. Age, percent total and third-degree burn, resting energy expenditure, and calorie and protein intake were similar in all groups. Data analysis demonstrated significant superiority of MTF in the reduction of wound infection (p less than 0.03) and length of stay/percent burn (p less than 0.02). MTF was also associated with a decreased incidence of diarrhea, improved glucose tolerance, lower serum triglycerides, reduced total number of infectious episodes and trends toward improved preservation of muscle mass, although statistical significance was not achieved. Seventy percent of deaths occurred in the group supported with an inherently large dose of fat and linoleic acid. Combining these observations, it is believed that MTF is effective in modulating an improved response to burn injury.

Updated Recommendations for Control of Surgical Site Infections

Objective:The objective of this study is to provide updated guidelines for the prevention of surgical wound infections based upon review and interpretation of the current and past literature. Background:The development and treatment of surgical wound infections has always been a limiting factor to the success of surgical treatment. Although continuous improvements have been made, surgical site infections continue to occur at an unacceptable rate, annually costing billions of dollars in economic loss caused by associated morbidity and mortality. Methods:The Centers for Disease Control (CDC) provided extensive recommendations for the control of surgical infections in 1999. Review of the current literature with interpretation of the findings has been done to update the recommendations. Results:New and sometimes conflicting studies indicate that coordination and application of techniques and procedures to decrease wound infections will be highly successful, even in patients with very high risks. Conclusions:This review suggests that uniform adherence to the proposed guidelines for the prevention of surgical infections could reduce wound infections significantly; namely to a target of less than 0.5% in clean wounds, less than 1% in clean contaminated wounds and less than 2% in highly contaminated wounds and decrease related costs to less than one-half of the current amount.

Effect of Glutamine on Phagocytosis and Bacterial Killing by Normal and Pediatric Burn Patient Neutrophils

Glutamine is essential for the function of lymphocytes and macrophages, where it serves, among other things, as a source of energy. Little information is available concerning the fuel that polymorphonuclear cells use for their metabolic and bactericidal functions. It was the purpose of this study to determine whether glutamine would enhance the in vitro bactericidal function of normal neutrophils and whether the amino acid would restore the observed impaired function in burn patients to or above the normal level. Twelve burn patients with total body surface area burns ranging from 32% to 87% were studied. At various postburn times, neutrophils were isolated and their ability to kill Staphylococcus aureus in the presence and absence of glutamine was determined and compared with that in normal subjects. Glutamine enhanced the bactericidal function of normal neutrophils. In every patient, at all but two postburn times, glutamine caused an improvement in the observed abnormal neutrophil bactericidal function and often restored it to or slightly above the normal level. Glutamine had no effect on the expression of C3b receptors (CR1 or CD35) or on phagocytosis by the cells. This study confirms the beneficial effects of glutamine in at least one arm of the immune system and adds evidence for the possible advantage of including this amino acid in the diets of burn and other trauma patients.

Role of Suture Materials in the Development of Wound Infection

THE SEARCH for an ideal suture material suitable for all purposes has been pursued by surgeons since the time of Pare. None has been found, however, and despite numerous investigations concerning tissue reaction, handling qualities, holding strength, etc., surprisingly little has been written concerning the ability of various types of suture material commonly in use to resist bacterial infection after their introduction into contaminated wounds. Several investigators have compared the incidence of infection in wounds closed with various suture materials both experimentally and clinically. Halsted,5 in 1913, expressed a strong preference for the use of silk in clean surgical wounds, but stated that it should be avoided in contaminated or infected ones. Whipple,8 in 1933, strongly advocated the use of silk in repair of clean wounds, indicating that the incidence of infection was actually less than when chromicized catgut was used. In 1937, Shambaugh and Dunphy7 studied the comparative incidence of infection in contaminated wounds closed with silk or with chromicized catgut in dogs. The wounds were contaminated either with feces or an uncounted staphylococcal culture. They found that infection actually occurred less frequently with silk than with catgut, and there was little problem with extrusion of the silk. In 1940, Elkin4 published a clinical study which compared the incidence of infection between silk and catgut in both clean and potentially infected cases. Infection occurred considerably more frequently in the catgut group than in the silk group in both categories. It was not stated whether chromic catgut or plain catgut was used in that particular study. Nonetheless, the methods of preparation and sterilization of catgut materials have changed considerably since that time, leaving some doubt about the present-day application of these studies. James and MacLeod6 performed a more complete study in 1961, implanting small pieces of contaminated suture material subcutaneously into mice. Although their problems included extrusion of suture material and only fair quantitation of the numbers of viable organisms introduced, much significant information was obtained. Their experiments indicated that silicone-treated silk was similar to untreated silk in the ability to withstand contamination and that cotton and merseline sutures resembled silk. Nylon, however, withstood contamination somewhat better than the other materials tested. Catgut and steel wire could not be evaluated because of the problem of extrusion. They concluded that the degree of enhancement of infection by the suture material roughly paralleled the inflammatory reaction caused by the suture material itself. Elek and Conen,3 in their studies with normal human subjects observed that approximately 1,000,000 staphylococci were

Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end-stage renal disease and transplant patients: a pilot study

Abstract:  Background:  Promising data regarding the safety and efficacy of gastric bypass surgery (GBS) as an option to address obesity in the transplant population are emerging. The data lack on how GBS may alter the pharmacokinetics (PK) of modern immunosuppression. The objective of this study was to describe the alterations in the PK of modern immunosuppressants and the GBS population.

PROTEINURIA FOLLOWING TRANSPLANTATION: Correlation With Histopathology And Outcome

A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (>2 g/ 24 hr) developed. Renal histology was available in all 77 patients. Twenty-one patients had received kidneys from living-related donors, the remaining 56 from cadaveric donors. The cause of proteinuria in these 77 patients was as follows: transplant glomerulopathy (30), allograft glomerulonephritis (22), chronic rejection (21), renal vein thrombosis (2), diabetic glomerulosclerosis (1), and hypertensive nephrosclerosis (1). Of the 22 patients who developed glomerulonephritis in the transplanted kidney, 6 had recurrent disease (3—membranous glomerulopathy, 2—focal sclerosis and hyali- nosis, 1—membranoproliferative glomerulonephritis); 6 developed de novo glomerulonephritis; and in 10 the type of glomerulonephritis could not be classified as recurrent or as de novo because of lack of characterization of the original kidney disease. Renal vein thrombosis occurred in association with other lesions in an additional 5 cases (3—chronic rejection; 2—membranous glomerulopathy). In follow-up only 23.4% (18 of 77) of the patients maintained prolonged graft function; the majority of grafts being lost within one year of the development of persistent, heavy proteinuria. Of the 18