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Ronald H Clements

Publications and source records attributed to Ronald H Clements.

7 recordsLinked to original sources

Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity.

Intestinal macrophages, which are thought to orchestrate mucosal inflammatory responses, have received little investigative attention compared with macrophages from other tissues. Here we show that human intestinal macrophages do not express innate response receptors, including the receptors for LPS (CD14), Fcalpha (CD89), Fcgamma (CD64, CD32, CD16), CR3 (CD11b/CD18), and CR4 (CD11c/CD18); the growth factor receptors IL-2 (CD25) and IL-3 (CD123); and the integrin LFA-1 (CD11a/CD18). Moreover, resident intestinal macrophages also do not produce proinflammatory cytokines, including IL-1, IL-6, IL-10, IL-12, RANTES, TGF-beta, and TNF-alpha, in response to an array of inflammatory stimuli but retain avid phagocytic and bacteriocidal activity. Thus, intestinal macrophages are markedly distinct in phenotype and function from blood monocytes, although intestinal macrophages are derived from blood monocytes. To explain this paradox, we show that intestinal stromal cell-derived products downregulate both monocyte receptor expression and, via TGF-beta, cytokine production but not phagocytic or bacteriocidal activity, eliciting the phenotype and functional profile of intestinal macrophages. These findings indicate a mechanism in which blood monocytes recruited to the intestinal mucosa retain avid scavenger and host defense functions but acquire profound "inflammatory anergy," thereby promoting the absence of inflammation characteristic of normal intestinal mucosa despite the close proximity of immunostimulatory bacteria.

Antigens, Surface↗

Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4-12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2-6.5; P = .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3-19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6-11.6; P = .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity.

Adult↗

Beriberi after gastric bypass surgery in adolescence.

We report three cases of dry beriberi in adolescents who underwent gastric bypass surgery for clinically severe obesity. The key to successful treatment of this problem lies in prompt recognition and thiamine supplementation.

Adolescent↗

Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus.

Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these patients through an incompletely understood mechanism. Gastrointestinal hormonal changes have been suggested as an explanation for resolution of DM II. Preoperatively, 20 MO patients with DM-II were evaluated for demographics and fasting levels of the following: glucose, insulin, C-peptide, glucagon, cortisol, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb. Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12 weeks and compared with the preoperative result using Student t test with significance, P = 0.05. Results are expressed as mean +/- SD. Twenty patients (5 male and 15 female), age 40.3 +/- 7.9 years, weight 146.3 +/- 34.0 kg, height 158.7 +/- 18.7 cm, and BMI 52.7 +/- 8.8, were enrolled in this IRB-approved protocol. Weight and BMI decreased progressively (117.5 +/- 26.9 kg and 47.0 +/- 7.4, P = 0.01, respectively) during the study but reached significance only at 12 weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY. Insulin and cortisol both approached, but never achieved, significant changes over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C-peptide both decreased significantly. Glucagon remained essentially unchanged over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may play a role in the correction of DM-II after gastric bypass.

Adult↗

Gastrointestinal symptoms are more intense in morbidly obese patients and are improved with laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Currently there are few reports comparing gastrointestinal (GI) symptoms in the morbidly obese versus control subjects or the effect of laparoscopic Roux-en-Y gastric bypass (LRYGBP) on such symptoms. METHODS: A previously validated, 19-point GI symptom questionnaire was administered prospectively to each patient undergoing LRYGBP, and the questionnaire was re-administered 6 months postoperatively. Six symptom clusters (abdominal pain, irritable bowel [IBS], reflux, gastroesophageal reflux disease [GERD], sleep disturbances, and dysphagia) were compared in the following manner using Students t-test: 1) Control vs. Preop, 2) Control vs Postop, and 3) Preop vs Postop. Results are expressed as mean +/- standard deviation, significance P=0.05. RESULTS: 43 patients (40 female and 3 male, age 37.3 +/- 8.6, BMI 47.8 +/- 4.9) completed the questionnaire preoperatively, and 36 patients (34 female, 2 male, BMI 31.6 +/- 5.3) completed the questionnaire 6 months postoperatively, for a response-rate of 84%. Abdominal pain, IBS, reflux, GERD and sleep disturbance symptoms were significantly worse in preop versus controls. Dysphagia was not different. Postop vs preop scores revealed abdominal pain, IBS, GERD, reflux, and sleep disturbance symptoms to be improved significantly. Dysphagia was not significantly different. Only dysphagia was worse when comparing postoperative to controls. No other symptom cluster was significantly different in controls vs postoperative. CONCLUSIONS: Morbidly obese patients experience more intense GI symptoms than control subjects, and many of these symptoms return to control levels 6 months after LRYGBP. Dysphagia is equivalent to control subjects preoperatively but increases significantly after LRYGBP. This data suggests another quality-of-life improvement (relief of GI symptoms) for morbidly obese patients. Further follow-up is needed to document the long-term reduction of GI symptoms.

Adult↗

Reflux esophagitis.

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Comment↗

Gastrointestinal symptomatic outcome after laparoscopic Roux-en-Y gastric bypass.

Laparoscopic Roux-en-Y (RY) gastric bypass is an effective treatment for morbid obesity. However, little information is available regarding the gastrointestinal symptomatic outcome after laparoscopic RY gastric bypass for morbid obesity. The purpose of this study is to identify changes occurring in gastrointestinal symptoms after laparoscopic RY gastric bypass. A previously validated, 19-point gastrointestinal symptom questionnaire was administered prospectively to each patient seen for surgical consultation to treat morbid obesity. Patients rated the degree to which each symptom affected their lives on a 0 to 100 mm Liekert scale with 0 indicating absence of a symptom, 33 indicating the symptom was present occasionally, 67 indicating the symptom occurred frequently, and 100 indicating the symptom was continuous. The same survey was readministered 6 months postoperatively. The mean of each symptom (preoperative vs. postoperative value) was compared using Student's t test with significance at P<0.05. Forty-three preoperative patients (age 37.3+/-8.6 years; body mass index 47.8+/-4.9) and thirty-five, 6 months' postoperative patients (81% follow-up; body mass index 31.6+/-5.3) completed the questionnaire. The result for each symptom is expressed as mean+/-standard deviation of preoperative vs. postoperative scores. Significantly different symptoms include the following: abdominal pain 23.3+/-26.4 vs. 8.6+/-13.5, P=0.003; heartburn 34.0+/-26.6 vs. 8.0+/-14.0, P=0.0001; acid regurgitation 28.1+/-24.0 vs. 10.7+/-21.0, P=0.001; gnawing in epigastrium 19.3+/-22.7 vs. 7.5+/-16.0, P=0.01; abdominal distention 38.2+/-31.5 vs. 11.1+/-19.2, P=0.0001; eructation 27.7+/-24.4 vs. 15.5+/-16.9, P=0.01; increased flatus 40.2+/-25.7 vs. 25.2+/-25.3, P=0.005; decreased stools 5.4+/-16.8 vs. 17.4+/-20.0, P=0.0005; increased stools 23.9+/-26.7 vs. 6.5+/-11.7, P=0.0005; loose stools 29.7+/-26.5 vs. 17.5+/-20.0, P=0.03; urgent defecation 34.3+/-26.5 vs. 14.3+/-19.3, P=0.0009; difficulty falling asleep 44.1+/-38.4 vs. 27.5+/-32.9, P=0.05; insomnia 42.4+/-36.2 vs. 21.6+/-30.5, P=0.008; and rested on awakening 65.1+/-33.8 vs. 30.5+/-28.8, P=0.0001. Symptoms that did not significantly change included the following: nausea/vomiting 17.2+/-22.7 vs. 22.1+/-19.9, P=0.33; borborygmus 28.8+/-25.2 vs. 26.8+/-29.7, P=0.75; hard stools 10.3+/-22.9 vs. 7.1+/-18.6, P=0.56; incomplete evacuation of stool 17.2+/-22.8 vs. 13.4+/-21.7, P=0.45; and dysphagia 10.9+/-15.6 vs. 17.7+/-28.4, P=0.18. Laparoscopic RY gastric bypass significantly improves many gastrointestinal symptoms experienced by morbidly obese patients without adversely affecting any of the measured parameters. This information is useful in preoperative counseling to assure patients of overall symptomatic improvement after this operation in addition to significant weight loss and improvement of comorbid conditions.

Adult↗