Stability and morbidity of Le Fort I osteotomy with bioresorbable fixation: a randomized controlled trial.

A randomized controlled clinical trial was conducted to compare the use of bioresorbable and titanium mini-plates and screws in Le Fort I maxillary osteotomies for evaluation of clinical morbidity and stability. Forty patients requiring Le Fort I osteotomies were randomly assigned to two groups. One group underwent bioresorbable mini-plate fixation and the other titanium mini-plate fixation. Stability of the maxilla was determined by serial cephalometric analysis at 2 and 6 weeks and at 3, 6 and 12 months postoperatively. Subjective and objective assessment of clinical morbidity was made prospectively. There were no differences in complications between the two fixation materials. Maxillae with bioresorbable fixation were significantly more mobile at the second postoperative week. Bioresorbable plates were initially more easily palpable, but their palpability decreased with time. Titanium plates became significantly more palpable at the 1-year follow-up. There was no difference in neurosensory disturbance between groups. Patients with bioresorbable plate fixation showed significantly more upward displacement in anterior maxilla following impaction and posterior maxilla following downgrafting from the 2nd to 6th postoperative week. The horizontal and angular relapses in the two groups were comparable. Le Fort I osteotomy with bioresorbable fixation results in no greater morbidity than with titanium fixation up to 1 postoperative year.

Effects of cyclo (his-pro) plus zinc on glucose metabolism in genetically diabetic obese mice.

AIMS: The specific objective of this study was to determine acute and long-term effects of cyclo (his-pro) (CHP) plus zinc and l-histidine (CZH) treatment on glucose metabolism in genetically obese (ob/ob), type 2 diabetic mice. METHODS: Acute effects of 0.3 mg of CHP plus 10 mg of zinc and 0.5 mg of l-histidine/kg body weight (BW) on fed blood glucose concentrations and 3-h average of above fasting blood glucose concentrations (TAFGCs), an index of oral glucose tolerance test, in lean and ob/ob mice were determined. To evaluate long-term effects of CZH on TAFGCs, lean and ob/ob mice were treated with drinking water containing increasing doses of CHP (0, 0.5, 1.0 or 1.5 mg/l) plus 10 mg zinc and 0.5 mg of l-histidine/l for 3 weeks. During the treatment period, fed blood glucose concentrations, BW and food and water intake were determined. At the end of the treatment, fasting blood glucose concentrations, TAFGC and fed plasma insulin concentrations were determined. RESULTS: Blood glucose concentrations significantly decreased when CZH was administered acutely via gastric gavage in food-deprived ob/ob mice. Similarly, 1.0 mg/l CHP treatment of mice with fixed amounts of 10 mg zinc and 0.5 mg l-histidine/l was optimal to decrease fed blood glucose and plasma insulin concentrations during a 3-week treatment period in ob/ob mice. TAFGC values in these mice also improved most significantly with the same combination of CHP, zinc and l-histidine used to test for fed blood glucose and plasma insulin levels. Fasting blood glucose concentrations and BW gains also decreased in ob/ob mice treated with 1.0 mg of CHP/l plus the same amount of zinc and l-histidine used in the above experiments. No effects of CZH treatment in lean mice were observed. CONCLUSIONS: CZH is effective in decreasing blood glucose concentrations in genetically obese (ob/ob), type 2 diabetic mice. These data support our working hypothesis that CZH may be an important anti-hyperglycaemic agent.

Effects of arachidonic acid plus zinc on glucose disposal in genetically diabetic (ob/ob) mice.

AIM: The present study is designed to determine whether arachidonic acid (AA) plus zinc improves clinical signs of diabetes in genetically diabetic ob/ob mice. METHODS: In the first study, effects of acute administration of AA plus zinc on glucose disposal were determined in ob/ob and lean mice (n = 6 each). In the second study, ob/ob and lean mice were treated with increasing doses of AA plus zinc for 2 weeks (n = 5 each). Postprandial and fasting blood glucose concentrations, three-hour-area-average above fasting glucose concentration (TAFGC), water and food intake, body weight and plasma insulin concentrations were measured. RESULTS: Acute administration of AA plus zinc significantly increased glucose disposal in ob/ob mice. In the second study, postprandial and fasting blood glucose concentrations, TAFGC, and water and food intake in ob/ob mice treated with AA plus zinc for 2 weeks were significantly decreased compared with those in mice given no AA. Plasma insulin concentrations in both lean and ob/ob mice were not changed by AA treatment in drinking water. CONCLUSIONS: AA plus zinc in drinking water is effective in decreasing blood glucose levels in obese mice. These results indicate that use of these compounds should be considered as a dietary supplement to control hyperglycaemia in patients with type II diabetes.

Biexponential model for predicting weight loss after gastric surgery for obesity.

BACKGROUND: Following gastric restrictive surgery, morbidly obese patients rarely achieve their ideal body weight defined by Metropolitan Life tables. The final body weight will depend on the initial body composition because there will be greater weight loss from fat than lean body mass. The purpose of this study was to develop a mathematical model that accurately estimates the rate and extent of weight loss following gastric bypass surgery. METHODS: Patients underwent gastric bypass followed by intensive medical therapy and serial bioelectrical impedance analysis (BIA) body composition measurements. Differential equations were derived to model weight loss. RESULTS: Weight loss in the fat and lean body compartments followed monoexponential decay kinetics with differing rate constants. Total body weight loss (W(T)) at time t was W(T) = k(f)(k(f) - k(l)) (W(f(o))e(-k(f)t) + W(l(o))e(-k(l)t)), where W(fo) and W(lo) are the initial fat and lean body masses determined by BIA and k(f) and k(l) are the rate constants for the fat and lean compartments, respectively. Following surgically induced weight loss, k(f) = 7.61 +/- 1.27 x 10(-2), and k(l) = -0.93 +/- 0.13 x 10(-2), with the ratio of residual sum of the squares to the total sum of the squares of 98.8%. CONCLUSION: Accurate prediction of weight loss depends on the initial fat and lean compartment mass since each of these loses weight at a different rate and to a different extent. When these effects are accounted for, the total body weight loss can be accurately predicted for any given time following surgery.

Liquid meal replacements and glycemic control in obese type 2 diabetes patients.

OBJECTIVE: Although weight management is an important component in the treatment of type 2 diabetes, there has been concern about the use of liquid meal replacements (MRs) in treating obese patients with type 2 diabetes because of the sugar content of the MRs. The goal of this study was to evaluate the safety and feasibility of using MRs for weight loss in obese patients with type 2 diabetes. RESEARCH METHODS AND PROCEDURES: Seventy-five subjects with type 2 diabetes, treated only with oral agents, were recruited for this 12-week clinical study. Subjects were randomized into three groups using either a MR containing lactose, fructose, and sucrose, a MR in which fructose and sucrose were replaced with oligosaccharides (sugar-free Slim-Fast), or an exchange diet plan (EDP) using the proportion of macronutrients recommended by the American Diabetes Association. RESULTS: Fifty-seven patients (41 MR and 16 EDP) finished the study. None developed serious adverse effects, including major hypoglycemic reactions. Weight losses in the MR 1 and MR 2 groups were comparable (6.4% and 6.7%, respectively) and greater than the weight loss in the EDP group (4.9%). Fasting glucose level was significantly reduced in the MR group compared with the EDP group (p = 0.012). There was a significant reduction in the MR group in total cholesterol and low-density lipoprotein cholesterol that was not seen in the EDP group. DISCUSSION: We have shown that liquid MRs are a safe and effective weight loss tool for obese subjects with type 2 diabetes, and can result in improvements in body weight, glucose, insulin, hemoglobin A1c and lipid levels.

Insulin-leptin-visceral fat relation during weight loss.

INTRODUCTION: The relation between insulin-leptin-visceral fat axis during weight loss has not been studied previously. AIMS: To evaluate the insulin, leptin, and abdominal adiposity relation during weight loss in patients with upper body obesity. METHODOLOGY: Twenty volunteers (7 men, 13 women) with mean age 50.6+/-6.3 (SD) and upper body obesity (weight 105.4+/-12.3 kg, BMI 35.9+/-2.5 kg/m2) were recruited. Participants were enrolled in a one-arm clinical study using a calorie-deficient diet and an escalating dose regimen of sibutramine, starting with 5 mg daily and increasing in 5-mg increments to 20 mg per day. Body weight, insulin, leptin, glucose, lipids, abdominal computed tomography (CT), and total body electrical conductance (TOBEC) were measured serially at weeks 0, 4, 8, 12, and 24. RESULTS: Eighteen patients completed the 6-month study: one man and one woman discontinued because of adverse events. With diet and sibutramine, body weight was significantly and continuously reduced throughout the 6-month study. There was a 16.0% (p = 0.0001) reduction in body weight (p < 0.001) and 22.5% (p = 0.0001) decrease in total body fat mass. Abdominal CT scans showed a 28.3% (p = 0.0001) reduction in total abdominal fat, a 26.0% (p = 0.0001) reduction in subcutaneous fat (p < 0.001), and a 31.0% (p = 0.0003) reduction in visceral fat (p < 0.001). There was a 32.0% (p = 0.0008) reduction in leptin levels and 37.9% (p = 0.0001) reduction in insulin levels between baseline and week 4, but no further significant reduction in leptin and insulin levels was observed for the duration of the study. There was a significant correlation between insulin and leptin concentrations throughout the study (p = 0.0001). Leptin was presented as a function of insulin measured at the same time. Significant associations between visceral abdominal fat, subcutaneous fat, and leptin were also observed. CONCLUSION: In this study, we found that leptin and insulin were related in weight loss. The data suggest that insulin may act as a strong regulator of leptin secretion during weight loss and that circulating leptin levels can be predicted by insulin level. Using sibutramine in conjunction with hypocaloric diet reduced body weight and decreased fat mass significantly. Visceral and subcutaneous abdominal fat depots were shown to decrease. Whether sibutramine exerts any selective reduction of visceral abdominal fat as opposed to total body fat mass will require further clinical investigation.

Stimulation of intestinal mucosal afferent nerves increases superior mesenteric artery and decreases mesenteric adipose tissue blood flow.

We tested the hypothesis that stimulation of intestinal mucosal afferent nerves produces an increase in superior mesenteric artery (SMA) but a decrease in mesenteric adipose tissue (MAT) blood flow. In anesthetized rats, blood flow in the SMA (pulsed Doppler flowmetry) and MAT (hydrogen gas clearance) was measured simultaneously before and after administration of 0.9% saline, 640 microM capsaicin, or 5% dextrose into the intestinal lumen. The changes in the SMA were 3.8 +/- 3.0, 15.9 +/- 4.0, and 18.8 +/- 7.6%; and those in the MAT, 4.7 +/- 4.0, -11.5 +/- 3.4, and -0.07 +/- 3.4% of baseline, respectively. The data indicate that exposure of the intestinal lumen to an afferent nerve stimulant or nutrient induced a dichotomous pattern of blood flow changes, an increase in the SMA and a reduction in MAT. The capsaicin-sensitive afferent nerves may be instrumental in mediating these energy responses.

Synergistic antidiabetic activities of zinc, cyclo (his-pro), and arachidonic acid.

Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cyclo (his-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE alone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors.

The role of complementary medicine in the treatment of prostate cancer.

Complementary and alternative medicine (CAM) has recently attracted national attention in the United States because of its widespread use and associated cost. CAM covers a broad spectrum of healing philosophies and approaches. Despite its widespread use, little is known about its safety, efficacy, cost effectiveness, and mechanism of action. The role of CAM in the management of prostate cancer is becoming more apparent with its rise in use among patients who are suffering from prostate cancer. This trend is patient-driven and reflects the change in values perceived by patients toward conventional medical treatment. In this review, several complementary therapies that can be used for prevention and treatment of prostate cancer are discussed. These therapies were selected because they are supported by scientific evidence. The popularity of CAM continues to grow and CAM is here to stay. Health care professionals can no longer afford to ignore or to treat CAM as an entity outside of conventional science. To acknowledge and to monitor its use among our patients may in the future help evaluate the safety and efficacy of CAM. Our current challenge is to move the field of CAM forward scientifically and systematically with wisdom and reasoning.

Reduced length of stay by implementation of a clinical pathway for bariatric surgery in an academic health care center.

Bariatric surgery is being performed in increasing numbers in an era when reimbursements are being reduced. Academic health centers bear the responsibility for training surgeons to perform these operations yet must keep costs to a minimum and retain high quality. The UCLA Bariatric Surgery Program developed a clinical pathway for the pre- and postoperative management for gastric bypass patients to achieve these goals. Medical records for 182 consecutive gastric bypass patients were retrospectively reviewed before implementation of the pathway (Group I) during the fiscal year of 1998/1999. Data on average length of stay, average intensive care unit length of stay, average standard variable cost, percentage readmission rate, and percentage return to the operating room were collected. This information was compared with the data collected prospectively from 182 patients after implementation of the pathway in July of 1999 (Group II) during the fiscal year of 1999/2000. Hospital cost per admission was reduced by 40 per cent in Group II compared with Group I (P < 0.02). The average length of stay was reduced from 4.05 days in Group I to 3.17 days in Group II (P < 0.033). Overall readmission rate was decreased from 4.2 per cent in Group I to 3.2 per cent in Group II (P < 0.05). There were no differences in morbidities between both groups. The pathway reduced costs by reducing the hospital length of stay, intensive care unit utilization, and readmission rates. Quality was maintained as evidenced by a similar pattern of postoperative morbidities yet readmission rates were reduced. Our results indicate that implementation of a clinical pathway for bariatric surgery reduces cost and improves quality of care in an academic institution.

Reduced epinephrine-stimulated lipolytic activity in male golden-mantled ground squirrel during hibernation: an in situ microdialysis study.

We studied lipolytic activities in vivo in golden mantle ground squirrels during pre-hibernation and hibernation using microdialysis technique. Microdialysis probes were inserted into the abdominal subcutaneous adipose tissues. Baseline lipolysis were assessed by measuring glycerol concentration. Epinephrine-stimulated lipolysis was also examined. Eight squirrels (four male, four female) were studied in each of the two stages. Basal glycerol concentrations were lower in the hibernating state than in the pre-hibernation state in male squirrels (P < 0.05). Epinephrine application induced glycerol release in male and female squirrels (P < 0.001) in both stages. Male squirrels demonstrated a reduced epinephrine-stimulated glycerol release in the hibernating state, which was not observed in female squirrels.

Sympathetic modulation of lipolysis in subcutaneous adipose tissue: effects of gender and energy restriction.

To investigate the differences in the regulation of lipolysis between male and female obese subjects in vivo, we used an in situ microdialysis technique before and after 3 weeks of energy restriction. Using this method, we examined glycerol, glucose, and lactate responses after 5 minutes of epinephrine stimulation in the adipose tissues. Glycerol releases after the perfusion of phentolamine, orciprenaline, and propranolol were also studied. Sixteen subjects were studied (8 men, 8 women, 35 to 45 years of age, body mass index 38 to 50 kg/m2). In women, epinephrine provoked a greater glycerol release than in men in both abdominal and femoral regions (P < .05). In men and women there was a significant decrease in the concentration of glucose and a significant increase in lactate concentration after epinephrine stimulation (P < .001). After 3 weeks of energy restriction, glycerol release after epinephrine stimulation was greater in both sexes than that observed before energy restriction (P < .05). Both phentolamine and orciprenaline stimulated the release of glycerol (P < .01); phentolamine had a higher effect in women, while propranolol had no effect on glycerol release in both sexes. In summary, we have demonstrated that epinephrine provoked a greater lipolytic response in obese women in both abdominal and femoral adipose tissues. The lipolytic response was further enhanced after 3 weeks of energy restriction in each gender. The decrease in glucose concentration suggests that glucose may be reutilized for synthesis into new triacylglycerol. Knowledge about the sensitivity to lipolytic agents in subcutaneous adipose tissue may provide potential new approaches for modulating the lipolytic responses of subcutaneous adipose tissue differently in men and women.

Nutrition and prostate cancer.

Scientific evidence suggests that differences in the diet may, in large part, account for the variability of prostate cancer rates around the world. Epidemiologic studies and animal experiments have yielded compelling results to warrant clinical intervention studies on nutrition from scientists who work on the prevention and treatment of prostate cancer. This article reviews the most recent evidence as to possible mechanisms of action of various dietary constituents, and explores evidence of various nutritional strategies for the prevention of prostate cancer progression.

Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement.

BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo-controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population.

Blood pressure and plasma norepinephrine responses to dexfenfluramine in obese postmenopausal women.

Dexfenfluramine has been shown to reduce body weight and lower blood pressure in obese individuals. However. it is not clear whether the blood pressure-lowering effect is due to dexfenfluramine or to the loss of weight. This project was designed to study the effect of a 5-d treatment of dexfenfluramine on blood pressure changes in obese postmenopausal women. Twenty women aged 51-60 y matched for body mass index [BMI (in kg/m2) of 34.5-50.1] were assigned to either the dexfenfluramine group (15 mg orally twice a day for 5 d) or the control group. All subjects were instructed about an isoenergetic diet. Twenty-four-hour ambulatory blood pressure, plasma catecholamines, glucose, insulin, and lipids were measured at the beginning and repeated at the conclusion of the study. On day 5 the mean systolic (SBP) and mean diastolic blood pressures (DBP) in the dexfenfluramine group were lower than those of the control group (SBP: 114+/-7 mm Hg in the dexfenfluramine group compared with 124+/-12 mm Hg in the control group, P < 0.05; DBP: 70+/-9 mm Hg in the dexfenfluramine group compared with 76+/-10 mm Hg in the control group, P < 0.05). The mean plasma norepinephrine concentration was lower in the dexfenfluramine group than in the control group (1.60+/-0.5 compared with 2.41+/-0.5 nmol/L, respectively, P < 0.05). No differences were noted in epinephrine, glucose, insulin. and lipid concentrations between the two groups. We showed that a 5-d treatment of dexfenfluramine decreases blood pressure and reduces heart rate in obese postmenopausal women. Our data suggest that these effects are results of the direct action of dexfenfluramine.

Is the quality of diabetes care better in a diabetes clinic or in a general medicine clinic?

OBJECTIVE: To compare the quality of ambulatory diabetes care delivered by physicians in the diabetes clinic versus the general medicine clinic of a university-affiliated Veterans Administration medical center. RESEARCH DESIGN AND METHODS: This is a retrospective study that involved the review of medical records against predetermined process-of-care criteria. A total of 112 patients with diabetes were randomly selected, of whom 56 were cared for in the general medicine clinic and 56 in the diabetes clinic. The following main outcome measures were examined: 1) the compliance with individual criteria; and 2) the proportion of patient visits in each clinic receiving minimally acceptable quality, defined as a blood pressure measurement, a record of type of hypoglycemic medication, a glycated hemoglobin measurement within the past year, a urinalysis within the past year, an ophthalmologist or optometrist eye examination within the past year or scheduled in the next six months, a record of change in therapeutic management, and a scheduled return visit. RESULTS: The diabetes clinic performed significantly better than the general medicine clinic on the following criteria: a record of a patient's self-monitoring of blood glucose levels; a foot examination; a comprehensive eye examination; a glycated hemoglobin measurement; and a referral for diabetic education. The proportion of patient visits meeting the minimally acceptable levels of quality was better in the diabetes clinic than the general medicine clinic (73 vs. 52%, P = 0.02). CONCLUSIONS: Patients cared for by physicians in the diabetes clinic receive better quality of diabetes care than do patients cared for by physicians in the general medical clinic. If patient care is to be shifted from specialists to generalists, additional attention needs to be paid to ensure that generalists have the knowledge and system resources necessary to deliver an acceptable quality of diabetes care.

Antitumor actions of interferon-gamma and interleukin-1 beta on human papillary thyroid carcinoma cell lines.

To test the hypothesis that interferon-gamma (IFN gamma) and interleukin-1 beta (IL-1 beta) possess antitumor activity on human papillary thyroid carcinoma cells, we studied the in vitro effects of IFN gamma and IL-1 beta on the proliferation and invasiveness of two human PTC cell lines, TPC-1 (TP) and NPA (NP) cells. TP and NP cells were treated with various concentrations of IFN gamma and IL-1 beta alone and in combination. Cell proliferation was assessed by [3H]thymidine incorporation and cell number measurement. Tumor cell invasion was assessed by the ability of cells to penetrate through a Matrigel membrane. Both IFN gamma and IL-1 beta inhibited [3H]thymidine incorporation into TP cells in a dose-dependent manner and decreased TP cell number. In NP cells, treatment with IFN gamma and IL-1 beta also decreased [3H]thymidine incorporation and cell number. The inhibitory effects of IFN gamma and IL-1 beta on tumor cell proliferation were additive in both cell lines. In the invasion experiments, IFN gamma and IL-1 beta reduced the invasiveness of TP and NP cells. Again, the inhibitory effects of IFN gamma and IL-1 beta on tumor cell invasion were additive in both cell lines. In summary, the results showed that both IFN gamma and IL-1 beta are potent inhibitors of the proliferation and invasiveness of TP and NP cells. The additive effects of IFN gamma and IL-1 beta are evidence that they act through different pathways. Our findings suggest that IFN gamma and IL-1 beta are two of the anticancer factors that act to suppress the proliferation and reduce the invasive potential of human papillary thyroid carcinoma cells.