Impact of major co-morbidities on mortality and complications after gastric bypass

BACKGROUND: We hypothesized that major co-morbidities affect survival and complications after gastric bypass. METHODS: A total of 1465 patients undergoing laparoscopic and open gastric bypass between 1995 and 2002 were studied. Patients with a body mass index >or= 35 kg/m(2) and major co-morbidities (group 1, n = 1045) were compared with patients with a body mass index >or= 40 kg/m(2) with minor/no co-morbidities (group 2, n = 420). RESULTS: Group 1 patients were older (43 versus 36 years, P < 0.001) and had a greater BMI (53 versus 50 kg/m(2), P < 0.001). Early postoperative complications were greater in group 1 than in group 2 and included leaks (4.1% versus 1.2%, P < 0.0032) and wound infections (3.9% versus 1.4%, P < 0.0133). Procedure-related mortality in the series was 1.7%. Mortality was 10-fold greater in group 1 (2.3% versus 0.2%, P < 0.0032). The incidence of small bowel obstruction, incisional hernia, and pulmonary embolism was similar in the two groups. Excess weight loss was significantly greater in group 2 (68% versus 62%, P < 0.001) at 1 year. Resolution of group 1 co-morbidities was great, including hypertension in 62%, diabetes in 75%, venous stasis disease in 96%, and pseudotumor cerebri in 98%. CONCLUSION: Outcomes analysis of obesity surgery requires risk stratification. The very low mortality rates in published studies are likely explained by surgical treatment of low-risk patients with minor co-morbidities, such as those seen in group 2. However, despite the increased perioperative risk, the group 1 patients (with major co-morbidities) demonstrated dramatic resolution of their co-morbid conditions, justifying the decision to go forward with surgery. The data support a radical change in treatment philosophy in which morbidly obese individuals should be offered bariatric surgery before major co-morbid conditions develop as a strategy to decrease the operative risk.     

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Pharmacological characterization of a receptor for calcitonin gene-related peptide on rat, L6 myocytes.

1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 2 In intact cells at 37 degrees C, human and rat alpha- and beta-CGRP all activated adenylyl cyclase with EC50s of about 1.5 nM. A number of CGRP analogues containing up to five amino acid substitutions showed similar potencies. In membrane binding studies at 22 degrees C in 1 mM Mg2+, the above all bound to a single site with IC50s of 0.1-0.4 nM. 3 The fragment CGRP(8-37) acted as a competitive antagonist of CGRP stimulation of adenylyl cyclase with a calculated Kd of 5 nM. The Kd determined in membrane binding assays was lower (0.5 nM). 4 The N-terminal extended human alpha-CGRP analogue Tyro-CGRP activated adenylyl cyclase and inhibited [125I]-iodohistidyl-CGRP binding less potently than human alpha-CGRP (EC50 for cyclase = 12 nM, IC50 for binding = 4 nM). 5 The pharmacological profile of the L6 CGRP receptor suggests that it most closely resembles sites on skeletal muscle, cardiac myocytes and hepatocytes. The L6 cell line should be a stable homogeneous model system in which to study CGRP mechanisms and pharmacology.     

Is Rett syndrome a subtype of pervasive developmental disorders?

The author reviews the issue on whether Rett syndrome (RS) is a subtype of pervasive developmental disorders (PDDs). More than 200 articles of RS have been published in the last 10 years. Internal and external validities of RS have been established by several independent studies. There remains the question whether RS presents clinical features that meet the total criteria for PDDs. The available data seem to support the idea of classifying RS as a subtype of PDDs in the DSM-IV.The views expressed in this article are those of the author and do not represent the official positions of the DSM-IV Task Forces, Work Groups, or the American Psychiatric Association.     

The robustness of the "binormal" assumptions used in fitting ROC curves

The binormal form is the most common model used to formally fit ROC curves to the data from signal detection studies that employ the "rating" method. The author lists a number of justifications that have been offered for this choice, ranging from theoretical considerations of probability laws and signal detection theory, to mathematical tractability and convenience, to empirical results showing that "it fits!" To these justifications is added another, namely that even if an alternative formulation based on another underlying form (e.g., power law) or model (e.g., binomial, Poisson, or gamma type distributions) were in fact correct, the binormal fit differs so little from the true form as to be of no practical consequence. Moreover, the small lack of fit is unlikely to be demonstrated in practice: it is obscured by the much larger variation that can be attributed to sampling of cases. In addition, even if a very large sample of cases could be studied, the small number of rating categories used does not permit seemingly very different models to be distinguished from one another.     

The interferon in TLR signaling: more than just antiviral

The Toll-like receptor (TLR) system is responsible for the recognition of infectious agents leading to initiation of the primary innate, and later adaptive, immune response. Genetic technologies have enabled the discovery of new factors involved in these systems, their genetic manipulation and the global analyses of their effects on gene expression. Furthermore, this increased understanding has resulted in the need to reassess our preconceptions about the functions of well-known molecules. For example, type I interferons (IFNs), which were discovered as antiviral proteins, are now known to be produced in response to TLR activation by many pathogens, including bacteria. Should we be surprised? Has the inflammatory response unexpectedly highjacked the body's antiviral system? Or are we too easily blinkered by preconceptions from how a compound was discovered?