Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components.

BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.

Albert Edwin William (LOMA) Miles (1912-2008) extracts from personal letters on dental matters.

Professor Miles (1912-2008) was a key player establishing dentistry as an academic subject. In the many letters he wrote to Helen Liversidge and me, he describes his involvement as Hon. Curator of the Odontological Museum, Editor Archives of Oral Biology, Assistant scientific editor of the BDJ. He writes about his association with Robert Maxwell and the Pergamon Press and his interests and friendships.

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy - A focus on energy expenditure.

OBJECTIVE: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. METHODS: Diet-induced obese male Sprague-Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. RESULTS: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. CONCLUSIONS: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Neural and humoral changes associated with the adjustable gastric band: insights from a rodent model.

BACKGROUND: Bariatric surgical procedures, including the laparoscopic adjustable gastric band (LAGB), are currently the only effective treatments for morbid obesity, however, there is no clear understanding of the mechanisms underpinning the efficacy of LAGB. The aim of this study is to examine changes in activation of the sensory neuronal pathways and levels of circulating gut hormones associated with inflation of an AGB. DESIGN AND RESULTS: The trajectory within the central nervous system of polysynaptic projections of sensory neurons innervating the stomach was determined using the transsynaptically transported herpes simplex virus (HSV). Populations of HSV-infected neurons were present in the brainstem, hypothalamus and cortical regions associated with energy balance. An elevation of Fos protein was present within the nucleus of the solitary tract, a region of the brainstem involved in the control of food intake, following acute and chronic band inflation. Two approaches were used to test (1) the impact of inflation of the band alone (on a standard caloric background) or (2) the impact of a standard caloric meal (on the background of the inflated band) on circulating gut hormones. Importantly, there was a significant elevation of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) following oral gavage of a liquid meal in animals with pre-inflated bands. There was no impact of inflation of the band alone on circulating GLP-1, PYY or ghrelin in animals on a standard caloric background. CONCLUSION: These data are consistent with the notion that the LAGB exerts its effects on satiety, reduced food intake and reduced body weight by the modulation of both neural and hormonal responses with the latter involving an elevation of meal-related levels of GLP-1 and PYY. These data are contrary to the view that the surgery is purely 'restrictive'.

The mechanism of weight loss with laparoscopic adjustable gastric banding: induction of satiety not restriction.

Laparoscopic adjustable gastric banding (LAGB) has rapidly emerged as a popular bariatric procedure because of its safety, efficacy, durability and adjustability. Despite widespread use, there is limited understanding of how it induces weight loss. Previously, it has been classified as a restrictive procedure, physically limiting the patient to a small meal that subsequently slowly empties into the distal stomach. However, the tiny pouch of stomach created above the LAGB appears to be unable to accommodate even the smallest of meals. Therefore, the key mechanism has been hypothesized to be the induction of satiety via, as yet, undefined pathways. The critical question remains: what are the key physiological changes that lead to satiety and weight loss? In successful LAGB patients, a consistent intraluminal pressure at the level of the LAGB of 26.9 ± 19.8 mm Hg is observed. Studies using semi-solid swallows combined with intraluminal pressure recordings have demonstrated that semi-solid transit across the resistance of the LAGB is mediated by repeated esophageal peristaltic contractions (mean 4.5 ± 2.9) that produce episodic flow, interspersed by reflux events. Failed transit results in obstruction and regurgitation, whereas dilatation of the supraband stomach induces severe and intolerable reflux. Overall gastric emptying does not appear to be significantly altered following LAGB. Focused investigations have shown that the supraband stomach is empty of an ingested meal 1-2 min after intake ceases. Considerable progress has been made in understanding the mechanical physiological effects of the LAGB on esophageal and proximal gastric function. These have been correlated with patient outcomes and sensations. On the basis of recent data, it appears that the LAGB activates the peripheral satiety mechanism without physically restricting the meal size. Therefore, it should not be classified as a restrictive procedure. The precise mechanism of weight loss with the LAGB remains to be delineated.

A rodent model of adjustable gastric band surgery-implications for the understanding of underlying mechanisms.

BACKGROUND: Bariatric surgery is currently the only anti-obesity therapy that can deliver weight loss of up to 20-30% of body weight. Laparoscopic adjustable gastric banding (LAGB) and Roux-en-y gastric bypass are the most commonly performed of these surgeries. The mechanisms by which LAGB initiates an increase in satiety remain completely unknown. The aim of this study is to establish a rodent model of adjustable gastric banding (AGB) that will enable investigation of these mechanisms. METHODS: Sprague-Dawley rats were implanted with adjustable gastric bands immediately below the gastro-esophageal junction around the glandular stomach. This band, as in humans, can be inflated via an exteriorized port resulting in an incremental impact on the stomach. RESULTS: Rats with an incremental inflation of the AGB showed a clear stepwise reduction in food intake and body weight. Normal food intake and body weight gain were restored with band deflation. Barium-assisted X-ray of the stomach showed the formation of a small gastric pouch proximal to the inflated band in a manner analogous to the human LAGB. CONCLUSIONS: This is the first animal model of the AGB that allows incremental inflation for optimal tightening of the band in the conscious animal with corresponding effects on food intake and body weight. This model will allow measurement of acute and chronic neural and hormonal changes following activation of the band in the conscious animal and will provide the potential to inform and improve surgical approaches that are at the forefront of obesity treatments.

X-ray Photographs of a Solar Active Region with a Multilayer Telescope at Normal Incidence.

An astronomical photograph was obtained with a multilayer x-ray telescope. A 4-centimeter tungsten-carbon multilayer mirror was flown as part of an experimental solar rocket payload, and successful images were taken of the sun at normal incidence at a wavelength of 44 angstroms. Coronal Si-XII emission from an active region was recorded on film; as expected, the structure is very similar to that observed at O-VIII wavelengths by the Solar Maximum Mission flat crystal spectrometer at the same time. The small, simple optical system used in this experiment appears to have achieved a resolution of 5 to 10 arc seconds.

A fibre-coupled UHV-compatible variable angle reflection-absorption UV/visible spectrometer.

We present a novel UV/visible reflection-absorption spectrometer for determining the refractive index, n, and thicknesses, d, of ice films. Knowledge of the refractive index of these films is of particular relevance to the astrochemical community, where they can be used to model radiative transfer and spectra of various regions of space. In order to make these models more accurate, values of n need to be recorded under astronomically relevant conditions, that is, under ultra-high vacuum (UHV) and cryogenic cooling. Several design considerations were taken into account to allow UHV compatibility combined with ease of use. The key design feature is a stainless steel rhombus coupled to an external linear drive (z-shift) allowing a variable reflection geometry to be achieved, which is necessary for our analysis. Test data for amorphous benzene ice are presented as a proof of concept, the film thickness, d, was found to vary linearly with surface exposure, and a value for n of 1.43 ± 0.07 was determined.

Systematic review and meta-analysis: non-invasive detection of non-alcoholic fatty liver disease related fibrosis in the obese.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a significant disease burden in obesity. Liver fibrosis is an important prognostic factor in NAFLD, and detection is vital. The pathophysiological changes of obesity can alter the accuracy of non-invasive NAFLD tests. We aimed to review current evidence for common non-invasive tests for NAFLD-related fibrosis in obesity. METHODS: We systematically searched for studies assessing the diagnostic accuracy of 11 biomarker panels and elastography techniques for NAFLD-related fibrosis in obesity. Meta-analyses were performed where possible. RESULTS: Thirty-eight studies were identified assessing the selected tests in obese populations. Simple biomarker panels (e.g. NAFLD fibrosis score) were the most validated. Evidence showed better accuracy of complex biomarker panels (NAFLD fibrosis score: summary receiver operator characteristic [SROC] 0.795-0.813 vs. enhanced liver fibrosis: SROC 0.962); however, these were poorly validated in obesity. Elastography techniques were better studied and had high diagnostic accuracy (transient elastography: SROC 0.859; magnetic resonance elastography: SROC 0.965) but were limited by BMI-dependent failure. Limited evidence was found to validate the accuracy of any test in exclusively obese populations. CONCLUSION: In obese subjects, complex biomarker panels and elastography have been reasonable to good accuracy for NAFLD-related fibrosis; however, these methods have not been well validated. Further study in this high-risk population is needed.

Psychologic and neuroendocrine response to methylphenidate.

The value of neuroendocrine techniques for providing information regarding the pathophysiology of psychotic disorders is largely dependent on clarification of the relationships among psychologic state, neural activity, and neuroendocrine regulation. This study presents a strategy for examining the interface between neurochemical activity, psychologic state, and neuroendocrine regulation. Psychologic state and serum growth hormone (GH) and cortisol were monitored following administration of methylphenidate hydrochloride, a drug that appears to preferentially affect central dopamine regulation. While individuals varied in both their endocrine and psychologic responses to methylphenidate, the general effects were GH elevation, euphoria, and activation with elation, the most pronounced psychologic effect. Subjects who showed GH elevation became elated while those who did not show a GH response did not become elated. Elation and GH release following administration of methylphenidate may be mediated by the same neurochemical events.

Response to dexamethasone and subtype of depression.

This study examines the utility of the dexamethasone suppression test (DST) in identifying a clinically meaningful subtype of depression. Forty-nine inpatients who met research diagnostic criteria for major depressive disorder underwent DSTs and standard clinical assessments and ratings. Half of those with primary depression showed escape from dexamethasone suppression and are referred to as nonsuppressors, while few of those with secondary depression had this response. Most of the nonsuppressors were rated as having a good response to treatment, while only one third of the suppressors were rated as having a good response to treatment. These data suggest that pituitary adrenal disinhibition as assessed by the DST is selectively associated with primary depression. The DST may be a marker of a depressive subtype with a specific pathophysiology or pathogenesis.

Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database.

The assumption that depressed patients who are assigned to placebo in antidepressant clinical trials are exposed to substantial morbidity and mortality is not based on research data. We assessed suicides, suicide attempts, and depressive symptom reduction in studies of 7 new antidepressants using the Food and Drug Administration database. Among 19,639 participating patients, 34 committed suicide (0.8% per year), and 130 attempted suicide (2.9% per year). Rates of suicide and attempted suicide did not differ significantly among the placebo- and drug-treated groups. Annual rates of suicide and attempted suicide were 0.4% and 2.7% with placebo, 0.7% and 3.4% with active comparators, and 0.8% and 2.8% with investigational antidepressants, respectively. Symptom reduction was 40.7% with investigational drugs (n = 4,510), 41.7% with active comparators (n = 1,416), and 30.9% with placebo (n = 2,805). These data may help inform discussions about the use of placebo in antidepressant clinical trials.

Differential effects of neuroleptic agents on the pituitary-gonadal axis in men.

Previous studies showing inconsistent effects of neuroleptic agents on the pituitary-gonadal system suggest that the drugs may differ in their effects on this system. Serum testosterone, luteinizing hormone (LH), prolactin, and neuroleptic levels were measured in 42 male schizophrenic patients during long-term treatment with thioridazine hydrochloride, trifluoperazine hydrochloride, chlorpromazine hydrochloride, and other neuroleptic agents and in six drug-free patients. Serum testosterone and LH values were significantly lower in patients taking thioridazine than in those taking other neuroleptic drugs. The relatively high serum neuroleptic levels in patients taking thioridazine may account for its differential effect on the pituitary-gonadal system.

Psychological functioning of bipolar manic-depressives in remission.

Several dimensions of psychological functioning of bipolar manic-depressives in remission were investigated. The following hypotheses were examined: (1) During remission, these individuals exhibit psychological maladjustment or a lack of positive mental health. (2) Bipolar manic-depressives are characterized by strong external orientations. The Personal Orientation Inventory, Marlowe-Crowne Social Desirability Scale, Levenson's Internal and Powerful Others Locus of Control Scales, and the Embedded Figures Test were administered to matched groups of 35 bipolar manic-depressives and 35 normal comparison subjects. Discriminant analysis disclosed no significant differences between the two groups on measures of positive mental health and on measures of external orientation. The relationship between these results and the etiology and treatment of manic-depressive disorder is briefly discussed, as well as the contradiction these findings pose to current views of this disorder pervasive among professional and lay populations.

Low serum neuroleptic levels predict relapse in schizophrenic patients.

Relapse occurs in a substantial proportion of schizophrenic patients treated with neuroleptics. The determinants of relapse have been elusive. In our study, low serum neuroleptic levels identified patients who had a relapse during a six-month period. Neuroleptic levels were measured by radioreceptor assay in 61 schizophrenic men and their clinical status was assessed in the subsequent six months. Ten patients had relapses, four showing a worsening of chronic psychotic symptoms and six showing eruption of psychotic symptoms after a period of remission. These ten patients had significantly lower normalized neuroleptic levels than those whose conditions remained stable. The lowest neuroleptic levels occurred in patients who had relapses after a period of remission. Serum neuroleptic levels in drug-responsive patients appear to be a critical determinant of remission. If these observations are replicated, a rational basis may be provided for prescribing and monitoring neuroleptic treatment and perhaps for preventing relapse.

The dexamethasone suppression test and pituitary-adrenocortical function.

The dexamethasone suppression test (DST) as now commonly carried out in psychiatric settings yields "abnormal" results in many conditions including the healthy state. To determine whether the DST accurately identifies patients with physiologically meaningful increases in pituitary-adrenocortical activity, we compared DST results to baseline urinary cortisol level. Thirty-four psychiatric inpatients underwent a 24-hour urine collection and then a DST using 1 or 2 mg of dexamethasone. With the common 1-mg DST, 24-hour urinary cortisol levels in nonsuppressors and suppressors did not differ. With the 2-mg DST, however, nonsuppressors had significantly higher urinary cortisol levels than suppressors, and all nonsuppressors had urinary cortisol levels above the normal range. Thus, the 1-mg DST may not identify the heuristically important subgroup of psychiatric patients who have a pathophysiologically meaningful alteration in pituitary-adrenal regulation.