Low 25-hydroxyvitamin D level is independently associated with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: We sought to explore associations between serum 25-hydroxyvitamin D [25(OH)D] levels and non-alcoholic fatty liver disease [NAFLD] in an integrated healthcare delivery system in the U.S. METHODS AND RESULTS: Six hundred and seven NAFLD cases were randomly matched 1:1 with controls for age, sex, race and season of measurement. Conditional logistic regression was used to evaluate if serum 25(OH)D levels were associated with increased odds of NAFLD (diagnosed by ultrasound) after adjusting for body mass index and history of diabetes, renal, peripheral vascular and liver diseases (model 1) and also for hypertension (model 2). Mean (SD) serum 25(OH)D level was significantly lower in the group with NAFLD as compared with that in the matched control group (75 ± 17 vs. 85 ± 20 nmol/L [30 ± 7 vs. 34 ± 8 ng/mL], P<0.001). Inadequate 25(OH)D status progressively increased the odds of NAFLD when classified categorically as sufficient (25(OH)D 75 nmol/L [>30 ng/mL], reference group), insufficient (37-75 nmol/L [15-30 ng/mL]; adjusted odds ratio [OR]: 2.40, 95% confidence interval [CI]: 0.90-6.34) or deficient (<37 nmol/L [<15 ng/mL]; adjusted OR: 2.56, 95% CI: 1.27-5.19). When modeled as a continuous variable, increased log10 25(OH)D was inversely associated with the risk of prevalent NAFLD (adjusted OR: 0.25, 95% CI: 0.064-0.96, P=0.02). CONCLUSION: Compared with matched controls, patients with NAFLD have significantly decreased serum 25(OH)D levels, suggesting that low 25(OH)D status might play a role in the development and progression of NAFLD.

Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.

AIMS: Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. METHODS: Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. RESULTS: Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. CONCLUSIONS: ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.

Association of the SLC30A8 missense polymorphism R325W with proinsulin levels at baseline and after lifestyle, metformin or troglitazone intervention in the Diabetes Prevention Program.

AIMS/HYPOTHESIS: Individuals with impaired glucose tolerance have increased proinsulin levels, despite normal glucose or C-peptide levels. In the Diabetes Prevention Program (DPP), increased proinsulin levels predicted type 2 diabetes and proinsulin levels were significantly reduced following treatment with metformin, lifestyle modification or troglitazone compared with placebo. Genetic and physiological studies suggest a role for the zinc transporter gene SLC30A8 in diabetes risk, possibly through effects on insulin-processing in beta cells. We hypothesised that the risk allele at the type 2 diabetes-associated missense polymorphism rs13266634 (R325W) in SLC30A8 would predict proinsulin levels in individuals at risk of type 2 diabetes and may modulate response to preventive interventions. METHODS: We genotyped rs13266634 in 3,007 DPP participants and examined its association with fasting proinsulin and fasting insulin at baseline and at 1 year post-intervention. RESULTS: We found that increasing dosage of the C risk allele at SLC30A8 rs13266634 was significantly associated with higher proinsulin levels at baseline (p = 0.002) after adjustment for baseline insulin. This supports the hypothesis that risk alleles at SLC30A8 mark individuals with insulin-processing defects. At the 1 year analysis, proinsulin levels decreased significantly in all groups receiving active intervention and were no longer associated with SLC30A8 genotype (p = 0.86) after adjustment for insulin at baseline and 1 year. We found no genotype × treatment interactions at 1 year. CONCLUSIONS/INTERPRETATION: In prediabetic individuals, genotype at SLC30A8 predicts baseline proinsulin levels independently of insulin levels, but does not predict proinsulin levels after amelioration of insulin sensitivity at 1 year.

Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program.

AIMS/HYPOTHESIS: The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated gene (FTO) and the rs7566605 SNP located 10 kb upstream of the insulin-induced gene 2 gene (INSIG2) have been proposed as risk factors for common obesity. METHODS: We tested for genotype-treatment interactions on changes in obesity-related traits in the Diabetes Prevention Program (DPP). The DPP is a randomised controlled trial of 3,548 high-risk individuals from 27 participating centres throughout the USA who were originally randomised to receive metformin, troglitazone, intensive lifestyle modification or placebo to prevent the development of type 2 diabetes. Measures of adiposity from computed tomography were available in a subsample (n = 908). This report focuses on the baseline and 1 year results. RESULTS: The minor A allele at FTO rs9939609 was positively associated with baseline BMI (p = 0.003), but not with baseline adiposity or the change at 1 year in any anthropometric trait. For the INSIG2 rs7566605 genotype, the minor C allele was associated with more subcutaneous adiposity (second and third lumbar vertebrae [L2/3]) at baseline (p = 0.04). During follow-up, CC homozygotes lost more weight than G allele carriers (p = 0.009). In an additive model, we observed nominally significant gene-lifestyle interactions on weight change (p = 0.02) and subcutaneous (L2/3 [p = 0.01] and L4/5 [p = 0.03]) and visceral (L2/3 [p = 0.02]) adipose areas. No statistical evidence of association with physical activity energy expenditure or energy intake was observed for either genotype. CONCLUSIONS/INTERPRETATION: Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle intervention.

Dysfunction of the autonomic nervous system activity is responsible for gastric myoelectric disturbances in the irritable bowel syndrome patients.

The pathogenesis of the irritable bowel syndrome (IBS) is still unsolved. Lately most attention has been focused on visceral hypersensitivity related to dysfunction of the autonomic nervous system (ANS). The aim of this study was to evaluate changes in the ANS activity and gastric motility in constipation-predominant IBS patients using the heart rate variability (HRV) and gastric myoelectric activity (EGG) recording. 23 patients (45+/-13 yrs) matching Manning criteria and 30 healthy volunteers (47+/-5 yrs) participated in the study. EGG and HRV in fasted and fed subjects with fasted serum catecholamine levels were measured in both groups. Fasting IBS pts showed gastric dysrrhythmia (29+/-14% vs. 11+/-7%), DP was 128.860 +/- 112.000 vs. 46.000+/- 23.200microV2, DF 2.37+/-0.8 vs. 2.9+/-0.2cpm. Feeding (300 kcal) improved dysrrhythmia to 20+/-13% vs. 8+/-5%, DP decreased to 74.500+/-57.720 vs. 165.600+/-89.000microV(2) and DF increased to 2.53+/-0.7 vs. 3.2+/-0.3cpm. In fasted and fed IBS pts SWC (channels 3-4) was about 60+/-11 vs. 84+/-8% and 68+/-14 vs. 92+/-8% respectively. In IBS pts resting HRV parameters were lower (LF - 650.3 vs. 811.6 ms2; HF - 508.8 vs. 854.6 ms2); with higher LF/HF ratio in IBS patients (1.52 vs. 1.2). The serum fasting level of adrenaline and noradrenaline in IBS pts were higher 1.28+/-0.06 vs. 0.65+/-0.05 nmol/L, and 3.54+/-1.2 vs. 2.89+/- 08 nmol/L, p<0.05 respectively. Increased sympathetic drive in IBS pts reflected by high catecholamine levels and LH/HF ratio is responsible for gastric dysrrhythmias and low DF and coupling. Meal has negligible effect on EGG parameters improvement. The ANS dysfunction observed in IBS patients is most probably responsible for disturbances in gastric myoelectric activity presented as gastric dysrrhythmias resulting in gastric emptying delay and dyspeptic symptoms.

Metabolism of leukotriene B4 via reduction into dihydro-leukotriene B4 in human monocytes, alveolar macrophages, and U-937 cells.

The biological effects of leukotriene B4 (LTB4) within the microenvironment are controlled by rapid inactivation. In this regard human granulocytes convert LTB4 into omega-oxidated products (20-OH-LTB4 and 20-COOH-LTB4); moreover, we recently described the formation of unpolar metabolites of LTB4 in human tonsillar and lung macrophages. By means of high performance liquid chromatography (HPLC) we identified the main metabolite of LTB4 as dihydro-LTB4 (5,12-dihydroxyeicosatrienoic acid). Studies on a lymphocyte (74-78%), monocyte (19-22%), and basophil (less than 4%) containing cell fraction isolated from peripheral blood as well as peripheral monocytes purified by elutriation centrifugation revealed evidence that these cells metabolize LTB4 to a very low degree if incubated immediately after isolation. However, after culture for 24-72 h these cells showed a strongly increased capacity to metabolize LTB4. The pattern of metabolites in this cell fraction was identical to bronchoalveolar macrophages (purity greater than 95%). Similarly, the LTB4-reductase was expressed in differentiated human monocytic U-937 cells almost 5-7 h after the addition of dimethylsulfoxide (1.3%) or phorbol-myristate-acetate (16 nM). The expression of this pathway was blocked in the presence of cycloheximide (10 micrograms/ml) whereas actinomycin (3.8 micrograms/ml) had no effects. Dihydro-LTB4 was further metabolized by granulocytes probably via omega-oxidation; therefore, several metabolites could be detected by radioactive high performance liquid chromatography (HPLC) after incubation of bronchoalveolar cells consisting of macrophages and granulocytes with 3H-LTB4. Our data provide evidence for a unique role of macrophages to control the level of LTB4 by generation as well as metabolism into dihydro-LTB4.

Effect of physician specialty on outcomes in diabetic ketoacidosis.

OBJECTIVE: More than 100,000 people are hospitalized annually in the U.S. with diabetic ketoacidosis (DKA). Outcome differences have not been examined for these patients based on whether their primary care provider is a generalist or a diabetes specialist. The objective of this study was to investigate hospital charges and hospital length of stay (LOS) for patients with DKA according to the specialty of their primary care provider. RESEARCH DESIGN AND METHODS: We investigated all patients with a primary diagnosis of DKA during a 3.5-year period (n = 260) in a large urban teaching hospital. Hospital charges and LOS were studied regarding the specialty of the primary care provider. Demographic factors, severity of illness, laboratory data, and readmission rates were compared. RESULTS: Patients cared for by generalists and endocrinologists had a similar case mix and severity of DKA. The age-adjusted mean LOS for patients of generalists was 4.9 days (95% CI 4.5-5.4), and the mean LOS for patients of endocrinologists was 3.3 days (2.6-4.2) (P < 0.0043). Mean hospital charges differed (P < 0.0001) with an age- and sex-adjusted mean for patients of endocrinologists of $5,463 ($4,179-7,141) and a mean for patients of generalists of $10,109 ($9,151-11,166). The additional charges incurred by generalists were due in part to patients undergoing more procedures. No differences in diabetes-related complications occurred during admission, but the endocrinologist-treated group had a lower readmission rate for DKA during the study period than the generalist-treated group (2 vs. 6%, respectively) (P = 0.03). CONCLUSIONS: Endocrinologists provide more cost-effective care than generalists do when serving as primary care providers for patients hospitalized with DKA.

Unrecognized diabetes among hospitalized patients.

OBJECTIVE: To evaluate the hospital care rendered to hyperglycemic individuals who did not have a diagnosis of diabetes before admission. RESEARCH DESIGN AND METHODS: A total of 1,034 consecutively hospitalized adult patients at a 750-bed inner-city teaching hospital were evaluated. Patients with one or more plasma glucose values > 200 mg/dl were identified by the laboratory data system on a daily basis. Patients without a diagnosis of diabetes at the time of admission were evaluated to determine if and how physicians addressed the hyperglycemia, whether a new diagnosis of diabetes was made during admission, and whether follow-up was planned to address the hyperglycemia. RESULTS: After excluding patients who were admitted for a primary diagnosis of diabetes, 37.5% of all hyperglycemic medical patients and 33% of hyperglycemic surgical patients were without a diagnosis of diabetes at the time of admission. These patients had a mean peak glucose of 299 mg/dl, and 66% had two or more elevated values during their hospitalization. Fifty-four percent received insulin therapy, and 59% received bedside glucose monitoring, yet 66% of daily patient progress notes failed to comment on the presence of hyperglycemia or diabetes. Diabetes was documented in only three patients (7.3%) as a possible diagnosis in the daily progress notes. CONCLUSIONS: Despite marked hyperglycemia, most medical records made no reference to the possibility of unrecognized diabetes. Given the average delay of a decade between the onset and diagnosis of type 2 diabetes, further evaluation of hyperglycemic hospitalized patients may present an important opportunity for earlier detection and the initiation of therapy.

Glycemic control in diabetic American Indians. Longitudinal data from the Strong Heart Study.

OBJECTIVE: To describe glycemic control and identify correlates of elevated HbA1c levels in diabetic American Indians participating in the Strong Heart Study, which is a longitudinal study of cardiovascular disease in American Indians in Arizona, Oklahoma, South Dakota, and North Dakota. RESEARCH DESIGN AND METHODS: This analysis is based on data from the baseline (1989-1992) and first follow-up (1994-1995) examinations of the Strong Heart Study. The 1,581 diabetic participants included in this analysis were aged 45-74 years at baseline, were diagnosed with diabetes before and at baseline, and had their HbA1c levels measured at follow-up. HbA1c was used as the index of glycemic control. Characteristics that may affect glycemic control were evaluated for cross-sectional and longitudinal relationships by analysis of covariance and multiple regression. RESULTS: There was no significant difference between median HbA1c at baseline (8.4%) and at follow-up (8.5%). Sex, age (inversely), and insulin and oral hypoglycemic agent therapy were significantly related to HbA1c levels in both the cross-sectional and longitudinal analyses. Current smoking, prior use of alcohol, and duration of diabetes were significant only for the cross-sectional data. Baseline HbA1c significantly and positively predicted HbA1c levels at follow-up. Comparison of HbA1c by therapy type shows that insulin therapy produced a significant decrease in HbA1c between the baseline and follow-up examinations. CONCLUSIONS: Glycemic control was poor among diabetic American Indians participating in the Strong Heart Study. Women, patients taking insulin or oral hypoglycemic agents, and younger individuals had the worst control of all the participants. Baseline HbA1c, and weight loss predicted worsening of control, whereas insulin therapy predicted improvement in control. Additional therapies and/or approaches are needed to improve glycemic control in this population.

Effects of sex and ethnicity on responses to a low-fat diet: a study of African Americans and whites.

The effects of sex and ethnicity on plasma lipoprotein changes that occur with low-fat diets were studied in 34 African American subjects (20 women, 14 men) and 29 white subjects (13 women, 16 men) aged 25-62 y with moderate hypercholesterolemia. A baseline diet containing 37% fat (15% saturated) was compared with four experimental diets containing 30% fat (10% saturated) with reciprocally varying contents of polyunsaturated and monounsaturated fatty acids. Diets were fed for 6 wk each, and all food and beverages provided and compliance were intensively monitored. Body weight and physical activity were held constant. Lowering of total and low-density-lipoprotein cholesterol were similar between women and men and between African Americans and whites. Small differences were observed between women and men in the extent of high-density lipoprotein lowering and triacylglycerol elevations. Additionally, African American subjects had slightly higher triacylglycerol elevations than did white subjects. Results suggest that men and women of varied ethnic backgrounds should respond similarly to cholesterol-lowering diets. Studies are required to develop strategies for achieving dietary changes that consider diverse eating patterns and cultural barriers to dietary adherence.

Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group.

Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol.

Pseudomyxoma peritonei in women: a clinicopathologic analysis of 30 cases with emphasis on site of origin, prognosis, and relationship to ovarian mucinous tumors of low malignant potential.

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by the accumulation of abundant mucinous material within the peritoneal cavity and associated with a mucinous tumor of the gastrointestinal tract or ovaries. Recently there has been considerable debate over the primary site of origin of the tumor associated with PMP in women. Some investigators have proposed a primary site in the ovaries, whereas others favor the gastrointestinal tract or the peritoneum. Another confusing issue has been the nature of the ovarian mucinous tumors associated with PMP. Although these neoplasms may be frankly malignant, more often they show minimal cytologic atypia and epithelial proliferation and have been classified as borderline or low malignant potential tumors. In order to address the issues of site of origin and nature of the associated ovarian mucinous tumors, we studied 68 cases of PMP in women, 30 of whom had mucinous tumors involving the ovaries. All 30 of these cases had an associated mucinous appendiceal or intestinal tumor. The PMP cases with ovarian tumors were compared with 30 ovarian mucinous tumors of low malignant potential (LMP). Based on the analysis of the primary ovarian mucinous LMP tumors, a set of criteria was formulated and used to determine the probable site of origin of PMP in the 30 women with mucinous tumors involving the ovaries. The following gross and microscopic features of the ovarian tumor were considered to be inconsistent with a primary ovarian origin: (1) surface involvement with or without superficial stromal involvement only; (2) adenocarcinoma with signet ring cell differentiation, with a previously diagnosed or concurrent appendiceal tumor of similar morphology; (3) bilateral adenocarcinoma consistent with colonic or appendiceal morphology; and (4) unilateral adenocarcinoma consistent with colonic or appendiceal morphology with a history of a colonic or appendiceal adenocarcinoma. When any one of these features was present the ovarian tumor was diagnosed as secondary. The following additional features also were considered to be more typical of secondary ovarian involvement: (1) normal or only slightly enlarged ovaries; (2) bilateral ovarian involvement; (3) simple or only focally proliferative mucinous epithelium with abundant extracellular mucin in cases with predominantly surface involvement of the ovaries, with or without a history of/or concurrent appendiceal adenoma; (4) multifocal or extensive pseudomyxoma ovarii in cases with stromal involvement, with or without a history of/or concurrent appendiceal adenoma; (5) ruptured appendiceal adenoma and unruptured ovarian tumor of similar histology; and (6) presence of an associated mucinous intestinal tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Laser Doppler imaging determines need for excision and grafting in advance of clinical judgment: a prospective blinded trial.

INTRODUCTION: Clinicians' judgment as to which burns require excision and grafting remains one aspect of burn care without objective measurements. This study presents a prospective, blinded trial to assess decision to operate by laser Doppler imaging (numerical criteria) versus the clinical judgment of an experienced burn surgeon. METHODS: A number of 23 patients were enrolled in this prospective trial and 41 representative wounds of indeterminate depth were selected for observation. Daily determination of need to operate (burn depth) was made by a single burn surgeon. Laser Doppler imager (LDI) scans of the same wounds were simultaneously obtained, and not revealed to the clinician. Data analysis compared quickness of decision to operate by LDI to the clinician's judgment. Concurrence of decisions by either method was compared. RESULTS: A total of 23 patients and 41 wounds were analyzed. LDI and the surgeon agreed in determination of wound depth 56% of the time (23/41, P=0.031). Biopsy confirmation was obtained for 21 wounds. The surgeon's determination of burn depth was accurate in 71.4% of wounds biopsied (15/21). When the LDI scan median flux indicated need for excision, it was 100% accurate (7/7). When both the surgeon and the LDI were correct in assessing wound depth, LDI would have saved median number of 2 days (minimum=0, maximum=4). CONCLUSION: LDI allowed for earlier, objective determination of need to operate. Concurrence with clinical judgment in this blinded study was excellent. LDI should be seen as an effective aid to clinical judgment when contemplating excision of burns with indeterminate depth.

Serum lactate and base deficit suggest inadequate resuscitation of patients with burn injuries: application of a point-of-care laboratory instrument.

Urinary output of 30 to 50 ml/hr and mean arterial pressure of more than 70 mm Hg continue to be the yardsticks by which patients with burn injuries are resuscitated. We designed this prospective, descriptive study to compare these parameters with serial base deficit and serum lactate values, which have been found to be sensitive indicators of adequate fluid resuscitation in trauma patients. The sample group consisted of 53 patients, consecutively admitted to the burn intensive care unit, who had 15% or more total body surface area burns. No changes in resuscitation protocol were implemented. Within the 48-hour period after admission, 2 ml heparinized venous blood samples were collected and analyzed every 2 to 4 hours, and vital signs, urinary output, fluid type, and volume administered were documented each hour. Urinary output and mean arterial pressure were maintained at more than 30 ml/hr and more than 70 mm Hg, respectively. Partial correlations between the traditional resuscitation variables and serum lactate and base deficit were low. On average, serum lactate and base deficit remained abnormally high during the study period. These new parameters may be used to improve the fidelity with which burn shock resuscitation is undertaken. Further studies of these parameters and how they may be used as endpoints in fluid resuscitation are needed.

Intraoperative blood salvage in excisional burn surgery: an analysis of yield, bacteriology, and inflammatory mediators.

The diminution of intraoperative hemorrhage remains a fundamental goal of the burn surgeon. We hypothesized that intraoperative blood salvage during burn excisions would be feasible if predicated on yield, bacteriology, and concentration of inflammatory mediators in the washed product. Reinfusion of culture-positive blood has a clear precedent in the trauma literature. Eight operations with immediate and complete collection of shed blood into a cell-saver device were prospectively studied. A median salvage rate of 43% of total shed red blood cells was estimated to have been recovered. Actual volumetric measurement of intraoperative blood loss was achieved. Bacterial contamination was consonant with the abdominal trauma experience. The levels of C3a, C5a, TNF alpha, and IL-1 beta in the final cell-saver product were all found to be at clinically insignificant levels.

Microvascular assessment of burn depth conversion during varying resuscitation conditions.

Conversion of partial- to full-thickness injuries, even after the burning has stopped, remains a significant clinical problem. We developed a rat model with a wide range of burn depths to study this phenomenon by microvascular assessment. Fifty-four male Sprague-Dawley rats weighing 460 g on average were studied. Real-time tissue monitoring of pH, paCO2, and paO2 was achieved by placement of a continuous blood gas monitor transducer in the aorta. Ten, 2-cm x 2-cm burns were created on each animal with milled aluminum templates (100 degrees C) with varying contact times. Conversion of burn depth in these wounds was documented by serial laser Doppler imager scanning over a 5-hour period. Animals received Ringer's lactate resuscitation at 0, 2, 4, 6, and 8 ml/kg/%burn. Serial laser Doppler scanning directly demonstrated progressive loss of perfusion to partial-thickness burns dependent upon the amount of fluid resuscitation. Conversion of partial- to full-thickness burns in this rat model (documented by laser Doppler microvascular assessment) was dependent upon how the animals were resuscitated.

The 2003 Carl A Moyer Award: real-time metabolic monitors, ischemia-reperfusion, titration endpoints, and ultraprecise burn resuscitation.

Real-time metabolic monitoring of varied vascular beds provides the raw data necessary to conduct ultraprecise burn shock resuscitation based on second-by-second assessment of regional tissue perfusion. It also illustrates shortcomings of current clinical practices. Arterial base deficit was continuously monitored during 11 clinical resuscitations of patients suffering burn shock using a Paratrend monitor. Separately, in a 30% TBSA rat burn model (N = 70), three Paratrend monitors simultaneously recorded arterial blood gas and tissue pCO2 of the burn wound and colonic mucosa during resuscitation at 0, 2, 4, 6, and 8 ml/kg/%TBSA. Paratrend data were analyzed in conjunction with previously reported laser Doppler images of actual burn wound capillary perfusion. With current clinical therapy, continuous monitoring of arterial base deficit revealed repetitive cycles of resolution/worsening/resolution during burn shock resuscitation. In the rat model, tissue pCO2 in both burn wounds and splanchnic circulation differed depending on the rate of fluid resuscitation (P <.01 between sham and 0 ml/kg/%TBSA and between 2 ml/kg/%TBSA and 4 ml/kg/%TBSA). Burn wound pCO2 values correlated well with laser Doppler determination of actual capillary perfusion (rho = -.48, P <.01). The following conclusions were reached: 1). Gratuitous and repetitive ischemia-reperfusion-ischemia cycles plague current clinical therapy as demonstrated by numerous "false starts" in the resolution of arterial base deficit; 2). in a rat model, real-time monitoring of burn wound and splanchnic pCO2 demonstrate a dose-response relationship with rate of fluid administration; and 3). burn wound and splanchnic pCO2 are highly correlated with direct measurement of burn wound capillary perfusion by laser Doppler imager. Either technique can serve as a resuscitation endpoint for real-time feedback-controlled ultraprecise resuscitation.

Digital photography: enhancing communication between burn therapists and nurses.

Burn rehabilitation therapists rely on nursing staff to follow through with the positioning and splinting programs. To communicate more effectively, a communication tool that consisted of digital photos and written instructions was created. Microsoft Word and Nikon View software were used to design the communication tool. The purpose of the study was to assess the perceived effectiveness of a communication tool between burn therapists and burn nurses for splinting and positioning. Thirty-two surveys were distributed to burn nursing staff to assess their perception of the communication tool (digital photographs with written instructions) compared with previous methods of instructions (without digital photographs). Seventy-three percent of nurses felt the communication tool with verbal instructions were the best methods of communicating splinting and positioning needs. All respondents felt that the rehabilitation staff should continue to use the communication tool.

Women with HIV: living with symptoms.

This exploratory study used a semistructured interview to describe women's experiences coping with HIV-symptoms, their descriptors of their worst and best days, and their attempts to control symptoms. A convenience sample of 44 women, largely women of color, of lower socioeconomic status, unemployed, seeking treatment in one of six outpatient clinics in Los Angeles, were interviewed. Fatigue, the most frequently reported worst symptom, was present in 98% of these women. Feeling physically sick and having negative mood were mentioned most often in descriptions of worst days; being active, feeling physically healthy, and having positive mood were descriptors of best days. Of the total, 59% used rest/sleep to control symptoms, and this often was used in conjunction with healthy diet. The results of this study reveal aspects of women's day-to-day experiences with HIV-related symptoms.