Formative evaluation of a telemedicine model for delivering clinical neurophysiology services part I: utility, technical performance and service provider perspective.

BACKGROUND: Formative evaluation is conducted in the early stages of system implementation to assess how it works in practice and to identify opportunities for improving technical and process performance. A formative evaluation of a teleneurophysiology service was conducted to examine its technical and sociological dimensions. METHODS: A teleneurophysiology service providing routine EEG investigation was established. Service use, technical performance and satisfaction of clinical neurophysiology personnel were assessed qualitatively and quantitatively. These were contrasted with a previously reported analysis of the need for teleneurophysiology, and examination of expectation and satisfaction with clinical neurophysiology services in Ireland. A preliminary cost-benefit analysis was also conducted. RESULTS: Over the course of 40 clinical sessions during 20 weeks, 142 EEG investigations were recorded and stored on a file server at a satellite centre which was 130 miles away from the host clinical neurophysiology department. Using a virtual private network, the EEGs were accessed by a consultant neurophysiologist at the host centre for interpretation. The model resulted in a 5-fold increase in access to EEG services as well as reducing average waiting times for investigation by a half. Technically the model worked well, although a temporary loss of virtual private network connectivity highlighted the need for clarity in terms of responsibility for troubleshooting and repair of equipment problems. Referral quality, communication between host and satellite centres, quality of EEG recordings, and ease of EEG review and reporting indicated that appropriate organisational processes were adopted by the service. Compared to traditional CN service delivery, the teleneurophysiology model resulted in a comparable unit cost per EEG. CONCLUSION: Observations suggest that when traditional organisational boundaries are crossed challenges associated with the social dimension of service delivery may be amplified. Teleneurophysiology requires a governance and management that recognises its socio-technical nature.

Formative evaluation of a telemedicine model for delivering clinical neurophysiology services part II: the referring clinician and patient perspective.

BACKGROUND: Feedback from service users will provide insight into opportunities for improvement so that performance can be optimised. In the context of a formative evaluation referring clinician and patient satisfaction with a teleneurophysiology service was examined during a 20 week pilot period. METHODS: Questionnaire surveys of referring clinicians and patients were conducted. RESULTS: Fifteen (58%) clinicians responded to the first part of a postal survey which examined their satisfaction with traditional clinical neurophysiology services. Nine (35%) responded to a second part which assessed their experience with the teleneurophysiology service. Teleneurophysiology improved satisfaction with waiting times, availability of results and impact on patient management. There was unanimous support from the clinicians for the permanent development of a teleneurophysiology service, although 2 cautioned this could delay establishing a neurology service in their region.Eighty-two percent (116/142) of patients responded to a survey of their satisfaction with teleneurophysiology. This was compared to a previous report of 322 patients' experience with traditional CN services in Ireland. Waiting times for appointment were shorter for the former group who supported the telemedicine model recognising that it reduced the travel burden and need for overnight journeys. The two groups were equally anxious about the investigation although the teleneurophysiology patients received more prior information. CONCLUSION: This study illustrates that teleneurophysiology is an acceptable model of service delivery for its primary customers. Their feedback is important in informing appropriate design and governance of such innovative models of health service provision.

Integrating clinical theory and practice in an epilepsy-specific electronic patient record.

This study's objective was to assess the usability of the epilepsy history module of the electronic patient record, developed at Beaumont Hospital, and to identify opportunities for improvement. Observation, interview and document analysis methods were used. Results indicated that the module was useable but the design did not work as well in practice as anticipated by theory. The next iteration of the module included identified enhancements; this iteration is currently in use.

Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy.

CONTEXT: The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy. OBJECTIVE: The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy. DESIGN: This was a prospective longitudinal study. SETTING: The study was conducted at HIV clinics in Seattle, Washington. PARTICIPANTS: The study population included 31 HIV-infected and 12 control subjects. INTERVENTIONS: Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen. MAIN OUTCOME MEASURES: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue. RESULTS: Subjects who developed lipoatrophy (n=10) had elevated fasting triglycerides [3.16 (sd 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (sd 1.27)x10(-4) min(-1)/microU.ml] after 12 months, whereas those without lipoatrophy (n=21) did not show any metabolic complications [triglycerides 1.32 (sd 0.58) mmol/liter, P=0.01 vs. lipoatrophy; insulin sensitivity 3.52 (sd 1.91)x10(-4) min(-1)/microU.ml, P=0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident. CONCLUSIONS: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

Using tagging data and aerial surveys to incorporate availability bias in the abundance estimation of blue sharks (Prionace glauca).

There is worldwide concern about the status of elasmobranchs, primarily as a result of overfishing and bycatch with subsequent ecosystem effects following the removal of top predators. Whilst abundant and wide-ranging, blue sharks (Prionace glauca) are the most heavily exploited shark species having suffered marked declines over the past decades, and there is a call for robust abundance estimates. In this study, we utilized depth data collected from two blue sharks using pop-up satellite archival tags, and modelled the proportion of time the sharks were swimming in the top 1-meter layer and could therefore be detected by observers conducting aerial surveys. The availability models indicated that the tagged sharks preferred surface waters whilst swimming over the continental shelf and during daytime, with a model-predicted average proportion of time spent at the surface of 0.633 (SD = 0.094) for on-shelf, and 0.136 (SD = 0.075) for off-shelf. These predicted values were then used to account for availability bias in abundance estimates for the species over a large area in the Northeast Atlantic, derived through distance sampling using aerial survey data collected in 2015 and 2016 and modelled with density surface models. Further, we compared abundance estimates corrected with model-predicted availability to uncorrected estimates and to estimates that incorporated the average time the sharks were available for detection. The mean abundance (number of individuals) corrected with modelled availability was 15,320 (CV = 0.28) in 2015 and 11,001 (CV = 0.27) in 2016. Depending on the year, these estimates were ~7 times higher compared to estimates without the bias correction, and ~3 times higher compared to the abundances corrected with average availability. When the survey area contains habitat heterogeneity that may affect surfacing patterns of animals, modelling animals' availability provides a robust alternative to correcting for availability bias and highlights the need for caution when applying "average" correction factors.

Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.

BACKGROUND: Weight loss causes changes in appetite and energy expenditure that promote weight regain. Ghrelin is a hormone that increases food intake in rodents and humans. If circulating ghrelin participates in the adaptive response to weight loss, its levels should rise with dieting. Because ghrelin is produced primarily by the stomach, weight loss after gastric bypass surgery may be accompanied by impaired ghrelin secretion. METHODS: We determined the 24-hour plasma ghrelin profiles, body composition, insulin levels, leptin levels, and insulin sensitivity in 13 obese subjects before and after a six-month dietary program for weight loss. The 24-hour ghrelin profiles were also determined in 5 subjects who had lost weight after gastric bypass and 10 normal-weight controls; 5 of the 13 obese subjects who participated in the dietary program were matched to the subjects in the gastric-bypass group and served as obese controls. RESULTS: Plasma ghrelin levels rose sharply shortly before and fell shortly after every meal. A diet-induced weight loss of 17 percent of initial body weight was associated with a 24 percent increase in the area under the curve for the 24-hour ghrelin profile (P=0.006). In contrast, despite a 36 percent weight loss after gastric bypass, the area under the curve for the ghrelin profile in the gastric-bypass group was 77 percent lower than in normal-weight controls (P<0.001) and 72 percent lower than in matched obese controls (P=0.01). The normal, meal-related fluctuations and diurnal rhythm of the ghrelin level were absent after gastric bypass. CONCLUSIONS: The increase in the plasma ghrelin level with diet-induced weight loss is consistent with the hypothesis that ghrelin has a role in the long-term regulation of body weight. Gastric bypass is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of the procedure.

Changes in plasma amino Acid levels do not predict satiety and weight loss on diets with modified macronutrient composition.

OBJECTIVE: Serotonin mediates satiety in the central nervous system. Brain serotonin content depends on the plasma ratio of tryptophan (Trp) to large neutral amino acids (LNAA) and may be affected by diet composition. We examined whether high-carbohydrate or high-protein diets induce satiety and weight loss by altering plasma concentrations of these amino acids. METHODS: In study 1 (n = 16, BMI = 27.0 +/- 2.3), we compared plasma Trp and LNAA concentrations averaged over 24 h after 2 weeks of consuming isocaloric diets containing either 45 or 65% of total energy as carbohydrate. In study 2 (n = 19, BMI = 26.2 +/- 2.1), we made the same measurements following diets containing either 15 or 30% of total energy as protein. To assess satiety in both studies, we recorded caloric intake and weight changes during a subsequent 12-week period of ad libitum consumption of the experimental diets. RESULTS: Ad libitum caloric intake fell by 222 +/- 81 kcal/day with a 3.7 +/- 0.6 kg weight loss at 12 weeks in study 1. Ad libitum caloric intake fell by 441 +/- 63 kcal/ day with a 4.9 +/- 0.5 kg weight loss at 12 weeks in study 2. The 24-hour averaged plasma concentration of Trp and the Trp:LNAA ratio were unaffected by the isocaloric increase in carbohydrate or protein consumption that preceded the ad libitum administration of the 2 diets. CONCLUSION: An increase in either carbohydrate or protein intake increases satiety and leads to significant weight loss, however, these effects are not mediated by an increase in plasma concentration of Trp or the Trp:LNAA ratio.

New insights into ocean sunfish (Mola mola) abundance and seasonal distribution in the northeast Atlantic.

The ocean sunfish, Mola mola, is the largest teleost fish in the world. Despite being found in all oceans of the world, little is known about its abundance and factors driving its distribution. In this study we provide the first abundance estimates for sunfish in offshore waters in the northeast Atlantic and the first record of extensive sunfish presence in these waters year-round. Abundance estimates and predictive distributions for sunfish in approximately 300,000 km² of the northeast Atlantic were derived from large scale offshore aerial surveys in 2015-2016 using distance sampling techniques. Generalized additive models of sunfish density were fitted to survey data from 17,360 km of line transect effort resulting in minimum abundance estimates of 12,702 (CI: 9,864-16,357) in the summer (Density = 0.043 ind/km²) and 8,223 individuals (CI: 6,178-10,946) (Density = 0.028 ind/km²) in the winter. Density surface models predicted seasonal shifts in distribution and highlighted the importance of the mixed layer depth, possibly related to thermoregulation following deep foraging dives. The abundance estimate and estimated daily consumption of 2,600 tonnes of jellyfish in the northeast Atlantic highlights the need to re-assess the importance of this species in the pelagic ecosystem, and its role in top-down control of jellyfish blooms.

Plasma C-reactive protein concentration is not affected by isocaloric dietary fat reduction.

OBJECTIVE: There is a strong correlation between plasma C-reactive protein (CRP) concentration and risk of cardiovascular death. Low-fat diets have been recommended for maintenance of cardiovascular health, and it is known that a low-fat diet associated with weight loss lowers CRP concentration. However, it remains unclear whether dietary fat has an effect independent from weight change on markers of inflammation. METHODS: Sixteen overweight subjects who were 46 +/- 14 y old were placed on a weight-maintaining baseline diet consisting of 35% fat, 45% carbohydrate, and 20% energy as protein. After 2 wk, subjects were switched to an isocaloric low-fat diet consisting of 15% fat, 65% carbohydrate, and 20% protein for another 2 wk. For the final 12 wk of the study, subjects consumed the same 15% fat diet ad libitum. At the end of each diet phase, CRP was measured by a high-sensitivity CRP assay. RESULTS: The weight of subjects remained stable during the first 4 wk of isocaloric diets. Plasma CRP concentrations after 2 wk on the weight-maintaining 35% fat diet and 2 wk on the isocaloric 15% fat diet were not significantly different (median +/- interquartile range 1.42 +/- 3.30 and 1.59 +/- 3.29 mg/L, respectively). Three months of ad libitum low-fat diet consumption resulted in a 4.1 +/- 0.7 kg weight loss associated with a decrease in CRP concentration to 1.17 +/- 2.03 mg/L (P = 0.03). CONCLUSION: Loss of body weight decreases CRP concentration, but a decrease in dietary fat without a concurrent change in body weight does not affect CRP concentration in overweight healthy subjects.

A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations.

BACKGROUND: Ad libitum, low-carbohydrate diets decrease caloric intake and cause weight loss. It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake. OBJECTIVE: We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake. DESIGN: Appetite, caloric intake, body weight, and fat mass were measured in 19 subjects placed sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve (AUC) for insulin, leptin, and ghrelin. RESULTS: Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (+/-SE) spontaneous energy intake decreased by 441 +/- 63 kcal/d, body weight decreased by 4.9 +/- 0.5 kg, and fat mass decreased by 3.7 +/- 0.4 kg with the ad libitum, high-protein diet, despite a significantly decreased leptin AUC and increased ghrelin AUC. CONCLUSIONS: An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.

Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans.

The gut peptide, ghrelin, may participate in the control of energy homeostasis and pituitary hormone secretion in humans, stimulating both food intake and, at pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight loss regulate ghrelin levels, but less is known about the relationship of ghrelin to body composition, aging, menopausal status, and lipid metabolism. Therefore, 60 adult men and women of widely varying ages and weights were characterized in terms of body composition and levels of ghrelin, glucose, insulin, lipids, and cortisol. Fasting ghrelin levels correlated positively with age and negatively with BMI and fat cell size, but were not related to fat mass, intraabdominal fat, or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels (r = -0.39; P = 0.002), insulin resistance as determined by the quantitative insulin sensitivity check index (r = 0.38; P = 0.003), and high-density lipoprotein cholesterol levels (r = 0.33; P = 0.009). Meal-induced ghrelin suppression correlated with the postprandial rise in insulin (r = 0.39; P < 0.05). Ghrelin levels were similar in men and women and did not vary by menopausal status or in association with cortisol levels. Our data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin.

Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans.

Plasma ghrelin levels rise before meals and fall rapidly afterward. If ghrelin is a physiological meal-initiation signal, then a large oral caloric load should suppress ghrelin levels more than a small caloric load, and the request for a subsequent meal should be predicted by recovery of the plasma ghrelin level. To test this hypothesis, 10 volunteers were given, at three separate sessions, liquid meals (preloads) with widely varied caloric content (7.5%, 16%, or 33% of total daily energy expenditure) but equivalent volume. Preloads were consumed at 0900 h, and blood was sampled every 20 min from 0800 h until 80 min after subjects spontaneously requested a meal. The mean (+/- SE) intervals between ingestion of the 7.5%, 16%, and 33% preloads and the subsequent voluntary meal requests were 247 +/- 24, 286 +/- 20, and 321 +/- 27 min, respectively (P = 0.015), and the nadir plasma ghrelin levels were 80.2 +/- 2.8%, 72.7 +/- 2.7%, and 60.8 +/- 2.7% of baseline (the 0900 h value), respectively (P < 0.001). A Cox regression analysis failed to show a relationship between ghrelin profile and the spontaneous meal request. We conclude that the depth of postprandial ghrelin suppression is proportional to ingested caloric load but that recovery of plasma ghrelin is not a critical determinant of intermeal interval.

Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet.

Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 +/- 57 vs. 580 +/- 56 ng/ml.24 h; P = NS). Body weight decreased from 74.6 +/- 2.4 to 70.8 +/- 2.7 kg on the ad libitum 15% F diet (P < 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.

Socio-technical considerations in epilepsy electronic patient record implementation.

PURPOSE: Examination of electronic patient record (EPR) implementation at the socio-technical interface. This study was based on the introduction of an anti-epileptic drug (AED) management module of an EPR in an epilepsy out-patient clinic. The objective was to introduce the module to a live clinical setting within strictly controlled conditions to evaluate its usability and usefulness. METHODS: Qualitative and quantitative methods were employed in an observational field study. A purposeful sample of specialists in epilepsy care (2 doctors and 2 nurses) was recruited. Perception of usefulness and ease of use of the AED module, impact on work processes, and accuracy of use were evaluated using feedback meetings, evaluation forms, ethnographic analysis and data validation techniques. Emerging issues were grouped into three key themes: human, organisational and technological. RESULTS: The electronic patient record use was studied for 49 patients over the course of 18 out-patient clinics. While participants varied in their approach to interacting with the AED module, they expressed satisfaction with its usability and performance. The necessary co-existence of the paper and electronic record, and changes to customary work practice were considered the biggest challenges. 82% accuracy in the use of the electronic record was determined. CONCLUSIONS: Achieving successful electronic patient record implementation is complex. While technical challenges exist, it is possibly more important to acknowledge the social considerations. Initially, an increase in medical record fragmentation and disruption to workflow can arise with the introduction of the technology. Realising the benefits of electronic patient records will require the management of a lengthy transition phase.

Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum.

BACKGROUND: The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. METHODS: We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein. RESULTS: Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations (P < 0.001) and tended to increase triglyceride levels (P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma (P < 0.001 for both).Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding. CONCLUSIONS: Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.

Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma.

OBJECTIVE: We attempted to elucidate possible pathogenetic mechanisms in scleroderma by analysis of gene expression patterns of purified monocytes and lymphocytes, as well as protein profiles of cytokines and growth factors. METHODS: Expression analysis was performed on messenger RNA (mRNA) from cells that had been purified with magnetic beads. Plasma samples from the same patients were used for multiplex cytokine analysis. Potential sources of proteins were also examined by in situ hybridization of skin specimens. RESULTS: A total of 1,800 genes from monocytes and 863 genes from CD4+ T cells were differentially expressed in scleroderma patients. As observed by other investigators using unfractionated peripheral blood cells from patients with autoimmune connective tissue diseases, the cell type-specific analyses of our scleroderma samples showed expression of genes suggesting the presence of interferon-alpha (IFNalpha), despite the apparent absence of this cytokine in plasma. IFNalpha RNA was, however, expressed at enhanced levels in vascular and perivascular cells in scleroderma skin samples. While levels of interleukin-1alpha (IL-1alpha) and IL-16 were among 10 proteins found to be significantly elevated in scleroderma patients, none of the large panel of plasma cytokines we analyzed correlated with the expression levels of putative IFN response genes. CONCLUSION: The pattern of up-regulation of mRNA in both the monocytes and CD4 lymphocytes of scleroderma patients, together with the detection of IFNalpha RNA in the microvasculature, suggests that leukocytes respond to this cytokine locally in the vessels. Detection of high levels of IL-1alpha and IL-16 in plasma and the independence of these protein levels from the IFN signature, implicates an independent contribution of other cytokines to immune activation and/or inflammation in scleroderma.

Absence of hypersensitivity to glucocorticoids in antiretroviral-associated lipodystrophy.

OBJECTIVE: The lipodystrophy syndrome, which is associated with the use of antiretroviral drugs in some human immunodeficiency virus (HIV)-infected individuals, bears a striking similarity to the fat redistribution observed in Cushing's disease. Although urinary free cortisol excretion and glucocorticoid receptor binding affinity are not elevated in subjects with lipodystrophy, glucocorticoid action at the cellular level has not been examined in affected individuals. The objective of this study was to determine whether tissue sensitivity to glucocorticoids is increased in subjects with lipodystrophy taking protease inhibitors. RESEARCH METHODS AND PROCEDURES: Subjects included 11 HIV-infected men on protease inhibitor therapy with lipodystrophy and 10 control HIV-infected men not on protease inhibitor therapy and without lipodystrophy. Trunk to extremity fat ratio was measured by DXA. Dexamethasone suppression of peripheral blood mononuclear cell proliferation was measured as an index of tissue sensitivity to glucocorticoid action. RESULTS: Compared with the control group, subjects with lipodystrophy had a significant elevation of the trunk to extremity fat ratio [median (interquartile range): 2.9 (1.3) vs. 1.6 (1.2); p < 0.05]. The concentration of dexamethasone resulting in 50% maximal suppression of proliferation was 11.7 nM (9.3 nM) in subjects with lipodystrophy and 19.6 nM (9.7 nM) in control subjects (p = not significant), and the percentage minimal proliferation was 4% (12%) and 17% (18%) in the two groups, respectively (p = not significant). DISCUSSION: Despite the Cushingoid appearance of affected individuals, these data suggest that body fat redistribution in antiretroviral-associated lipodystrophy does not arise through an increase in postreceptor glucocorticoid signaling.