Contribution of glucose tolerance and plasma insulin levels to the relationships between body fat distribution and plasma lipoprotein levels in women.

Numerous interrelated metabolic and morphological variables such as plasma insulin levels, glucose tolerance and abdominal obesity are associated with changes in plasma lipoprotein levels. The present study was undertaken to differentiate, using a multivariate approach, the respective contributions of plasma glucose and insulin levels, obesity and regional adipose tissue distribution to the variance in plasma lipoproteins. The study group was composed of 69 healthy premenopausal women (age 35.4 +/- 5.0 years (mean +/- s.d.); percent body fat 40.7 +/- 10.1). Indices of carbohydrate metabolism showed significant univariate correlations with triglyceride (TG) and/or cholesterol (CHOL) content of plasma VLDL, LDL and HDL (P less than 0.05). Multivariate analyses indicated that the explained variance in plasma VLDL-TG (R2 x 100 = 44 percent, P less than 0.05) and LDL-apoprotein (apo) B levels (R2 x 100 = 33.1 percent, P less than 0.08) was entirely accounted for by indices of carbohydrate metabolism and body fat distribution, whereas total body fatness added no significant contribution to these models. Multivariate analyses also revealed that the best possible regression model to predict the variation in plasma HDL2-CHOL levels only included computed tomography-derived deep abdominal adipose tissue area (P less than 0.0001). All other variables were unable to further improve the explained variance in plasma HDL2-CHOL levels. In partial correlation analyses, indices of carbohydrate metabolism and the waist-to-hip circumference ratio (WHR) remained significantly correlated with plasma VLDL-TG and LDL-apo B levels after adjustment of VLDL-TG and LDL-apo B for either insulin and glucose levels, or for the WHR (P less than 0.08). After correcting for deep abdominal fat accumulation, no significant correlation was observed between indices of carbohydrate metabolism and plasma HDL2-CHOL levels whereas deep abdominal fat showed significant correlations with HDL2-CHOL levels (P less than 0.05) after correction for indices of carbohydrate metabolism. These results suggest that both disturbances in glucose-insulin homeostasis and abdominal obesity are significantly associated with changes in plasma VLDL-TG and LDL-apo B levels and that these associations are partly independent from each other. These results also indicate that mechanisms other than disturbances in glucose homeostasis and hyperinsulinemia are responsible for the association between the level of deep abdominal fat and plasma HDL2-CHOL levels.     

Estimated daily energy expenditure and blood lipids in adolescents: the Québec Family Study.

PURPOSE: To examine the association between estimated daily energy expenditure and blood lipids in a sample of adolescents. METHODS: The sample consisted of 415 males and 356 females aged 10-19 years, mainly French Canadian, recruited from the greater Quebec City area through the media as part of Phase I of the Quebec Family Study. Estimates of daily energy expenditure (DEE) were obtained with a 3-day physical activity record. Blood lipids were measured by standard procedures. The sample was stratified into three activity groups (least active, less than 25th percentile of DEE; moderately active, 25-74th percentile of DEE; and most active, 75th percentile or greater of DEE), and also by clinical cutpoints for blood lipids. Analysis of covariance, controlling for age and fatness, was conducted to compare blood lipids within gender across activity groups. Logistic regression analysis, controlling for age and fatness, was used to estimate the relative risk of being classified with an undesirable level of a blood lipid parameter on the basis of the DEE. RESULTS: Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were not significantly different across activity groups in males or females. High-density lipoprotein cholesterol (HDL-C) was significantly different across activity groups in males (p <.05) and females (p <.05), but the pattern of variation was different between genders. In males, the TC/HDL-C and LDL-C/HDL-C ratios decreased between the moderately active and most active groups (p <.05). Significant differences remained when subcutaneous fatness was considered as a covariate. The results from logistic regression analysis indicated that the odds ratios for low HDL-C levels was significant only in low DEE girls (odds ratio 2.83) compared with high DEE girls. CONCLUSIONS: The results suggest that increased energy expenditure and physical activity are associated with higher levels of HDL-C in adolescents of both sexes.     

Is there a role for laparoscopic appendectomy in pediatric surgery?

Although laparoscopic procedures are currently in vogue in general surgery, the role of this approach in children has not been prospectively evaluated in the United States using the new instrumentation now available to us. To assess the value of laparoscopic appendectomy (LA) in childhood, we prospectively compared 14 LAs with 50 open appendectomies (OA) over 6 months in a single children's hospital. Antibiotic usage was at the discretion of the surgeon regardless of the procedure performed and was not different between groups. LA was performed under the direction of a single laparoscopy-trained surgeon and patient selection was based on parental consent. A three-puncture LA technique was used; children from this group were allowed to return to full activities as soon as they were comfortable. There were no significant differences between groups for severity of disease, age, weight, hospital cost, or complications. The types of complications that developed were comparable in both groups. The percent of complicated appendicitis (gangrene or perforation) was 32% in the OA group and 36% in the LA group. Patients in the LA group spent significantly fewer days in the hospital and returned to unrestricted activities (school, athletics, etc) faster than patients in the OA group. LA is approximately $1,000 more expensive than OA, the differences being easily explainable by the cost of the disposable supplies necessary for the procedure (laser fibers, trocars, etc), but because of the shorter hospital stay in the LA group the mean total cost for each group was comparable. These data suggest that although there appears to be no cost advantage, LA shortens the hospital stay and allows children to return to unrestricted activity sooner than OA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.

Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.

Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects.     

Body composition of patients on a very low-protein diet: a two-year survey with DEXA.

BACKGROUND: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). METHODS: Thirteen stable patients (8 men; age, 55 +/- 12 years; glomerular filtration rate (GFR), 15 +/- 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. RESULTS: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 +/- 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months (P =.02, paired t-test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years (P <.05). CONCLUSION: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass.     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Self-perception and action in infancy

By 2–3 months, infants engage in exploration of their own body as it moves and acts in the environment. They babble and touch their own body, attracted and actively involved in investigating the rich intermodal redundancies, temporal contingencies, and spatial congruence of self-perception. Recent research is presented, which investigats the spatial and temporal determinants of self-perception and action infancy. This research shows that, in the course of the first weeks of life, infants develop an ability to detect intermodal invariants and regularities in their sensorimotor experience, which specify themselves as separate entities agent in the environment. Recent observations on the detection of intermodal invariants regarding self-produced leg movements and auditory feedback of sucking by young infants are reported. These observations demonstrate that, early in development and long before mirror self-recognition, infants develop a perceptual ability to specify themselves. It is tentatively proposed that young infants’ propensity to engage in self-perception and systematic exploration of the perceptual consequences of their own action plays an important role in the intermodal calibration of the body and is probably at the origin of an early sense of self: the ecological self.     

A complementarity-determining region peptide of an anti-desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence

The sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity-determining region of the F12 heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen-combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH-CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self-antigen binding mechanism for some autoantibodies.