Non-invasive monitoring of kidney allograft rejection through IDO metabolism evaluation

The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma (IFN-gamma) and via tryptophan depletion, suppresses adaptive T cell-mediated immunity in inflammation, host immune defense, and maternal tolerance. Its role in solid organ transplantation is still unclear. Therefore, we investigated the usefulness of IDO-mediated tryptophan catabolism in the evaluation of kidney allograft rejection. Blood, urine, and tissue samples were collected from 34 renal transplant patients without rejection and from nine patients with biopsy-confirmed episodes of acute rejection (n=12). Concentrations of kynurenine and tryptophan in serum and urine were analyzed by high-pressure liquid chromatography. Kynurenine to tryptophan ratio (kyn/trp) was calculated to estimate IDO activity. Immunostaining for IDO was performed on renal biopsies. Neopterin was assessed using radioimmunoassay. Kyn/trp and neopterin were detectable at low levels in serum of healthy volunteers and were increased in non-rejecting allograft recipients. Serum levels of kyn/trp were higher in recipients with rejection compared to non-rejectors as early as by day 1 post-surgery. Rejection episodes occurring within 13+/-5.9 days after transplantation were accompanied by elevated kyn/trp in serum (114+/-44.5 micromol/mmol, P=0.001) and urine (126+/-65.9 micromol/mmol, P=0.02) compared to levels during stable graft function. Kyn/trp correlated significantly with neopterin suggesting an IFN-gamma-induced increase in IDO activity. Immunostaining showed upregulation of IDO in rejection biopsies, localized in tubular-epithelial cells. Non-rejected grafts displayed no IDO expression. Acute rejection is associated with simultaneously increased serum and urinary kyn/trp in patients after kidney transplantation. Thus, IDO activity might offer a novel non-invasive means of immunomonitoring of renal allografts.     

Bone modeling in gallium nitrate-treated rats

Summary Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorptionin vitro. This study investigated the effects of chronic GaN administration on bone, kidney, and parathyroid gland activity of growing rats. Experimental animals received GaN (1.75 mg elemental gallium i.p. QOD×8, Ga⁺), and controls received the solvent (Ga⁻). In the bone of Ga⁺ rats the number of osteoclasts was increased (Ga⁺: 70.4±2.31 osteoclasts/mm²; Ga⁻: 46.5±1.61 osteoclasts/mm²,P<0.001), and apposition rate and osteoid width were unchanged. Ga was concentrated in bone (2.4 μmol/g cortical bone) and detected by electron microprobe on the surface of a few trabeculae. Alkaline (Alp) and acid (Acp) phosphatase activities were higher in Ga⁺ than in Ga⁻ calvaria (Ga⁺: Alp 223±23.4 U/mg prot, Ga⁻: Alp 145±13.3 U/mg prot,P<0.02; Ga⁺: Acp 69.5±4.7 U/mg prot, Ga⁻: 57.5±2.8 U/mg prot,P<0.05). Serum iPTH was increased (Ga⁺: 112.9±17.6 pg/ml, Ga⁻: 41.4±7.4 pg/ml,P<0.01), serum calcium was reduced (Ga⁺: 2.4±0.02 mmol/l, Ga⁻: 2.6±0.03 mmol/l,P<0.001); calciuria remained comparable to controls. Relative to the hypocalcemia this suggests renal loss of Ca. The calcemic response to hPTH 1-34 (i.v. 50 μ/kg) was decreased 2 hours after injection of the hormone (ΔCa: TPTX Ga⁺: 0.11±0.04 mmol/l, Ga⁻: 0.33 ±0.03 mmol/lP<0.01). In conclusion, Ga, at the dosage used, does not inhibit the activity of osteoblasts in rats and does not interfere with mineralization but increases the number of osteoclasts through stimulation of parathyroid gland activity, induced by a fall in serum calcium. The hypocalcemia seems to be related to skeletal resistance to PTH and to increased renal calcium loss.     

Normalization of Insulin Sensitivity in the Obese Patient after Stable Weight Reduction with Bilio-Pancreatic Diversion

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven eX-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (O)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCi ratio with respect to the normal controls (O vs N: 0.01164 ± 0.00039 vs 0.02392 ± 0.0039, p < 0.05). IVGTT, AUCs: significant differences were found in each case: N vs X: 0.0591 ± 0.0075 vs 0.1402 ± 0.0399, p < 0.05; N vs O: 0.0591 ± 0.0075 vs 0.0223 ± 0.0031, p < 0.01; X vs O: 0.1402 ± 0.0399 vs 0.0223 ± 0.0031, p < 0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 ± 0.00288 vs 0.00905 ± 0.00135 per min, p < 0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs O: 12.04 × 10⁻⁵ ± 2.61 × 10⁻⁵ vs 3.29 × 10⁻⁵ ± 0.61 × 10⁻⁵, p < 0.066; X vs O: 16.42 × 10⁻⁵ ± 4.23 × 10⁻⁵ vs 3.29 × 10⁻⁵ ± 0.61 × 10⁻⁵ per min per pM, p < 0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.     

The Effect of Surgical Weight Reduction on Functional Status in Morbidly Obese Patients with Low Back Pain

Background: Although low back (LBP) pain is not a lifethreatening disease, it is a source of significant discomfort and disability and accounts for work absences. It has been shown previously that morbid obesity is associated with increased frequency of LBP and that surgical weight loss improves the symptomatology. However, there are no studies to quantitatively assess the exact degree of functional disability caused by severe obesity and the degree of improvement of LBP that follows weight loss from bariatric surgery. Methods: 29 morbidly obese candidates for bariatric surgery with LBP, weight 132.5±27 (mean±SD) kg and BMI 47.2±8.8 kg/m² were examined for their functional status using psychometric instruments specifically designed to objectively assess the patients' complaints. The preoperative scores were measured by a) visual analogue scales (VAS1, VAS2, VAS3), b) Roland-Morris disability questionnaire, c) Oswestry LBP disability questionnaire, and d) Waddell disability index, and were compared with the scores obtained by the same instruments 2 years after vertical banded gastroplasty. Results: The postoperative weight (92.3±19 kg) and BMI (32.9±6.3 kg/m²) of the 29 patients were significantly reduced (P<0.001). The improved functional disability scores were statistically significant: a) VAS1 1.59±1.86 (mean±SD) vs 0.32±0.64, P<0.001; b) VAS2 5.5±1.97 vs 2.14±1.88, P<0.001; c) VAS3 0.77±1.11 vs 0.09±0.29, P=0.006, d) Roland-Morris 7.89±5.11 vs 1.89±2.13, P<0.001; e) Oswestry 21.22±15.63 vs 5.61±7.51, P<0.001; f) Waddell 2.81±1.37 vs 0.56±0.72, P<0.001. Conclusions: Surgical weight loss significantly improves the degree of functional disability of morbidly obese patients suffering from LBP.     

Differences in Salivary Habituation to a Taste Stimulus in Bariatric Surgery Candidates and Normal-Weight Controls

Background  Previous studies show that slower habituation to taste stimuli is associated with reduced rates of satiation and greater energy intake. This study compared rates of salivary habituation to gustatory presentations of lemon juice in 34 severely obese bariatric surgery candidates [48.8 ± 7.9 years, 85% female, body mass index (BMI) = 47.4 ± 7.5 kg/m²] and 18 normal-weight controls (48.4 ± 9.5 years, 88.9% female, BMI = 22.7 ± 1.2 kg/m²). Methods  Parotid saliva was collected from cotton rolls positioned in the oral cavity during two baseline water trials and ten lemon juice trials. Data were condensed into trial blocks, representing mean values for the two baseline water trials and each of five pairs of lemon juice trials (i.e., blocks 1–5). Salivary change across lemon juice trials was calculated by subtracting values for blocks 1 through 5 from baseline. Results  A significant interaction of group (bariatric surgery candidates/normal-weight controls) by blocked trials [F (4, 200) = 3.0; p < 0.05] indicated that the groups differed in their pattern of salivary responding, with bariatric surgery candidates’ salivation (grams) failing to decrease significantly over the five blocked trials (−0.47 ± 0.18, p = 0.12), unlike that of the normal-weight controls (−1.30 ± 0.25, p < 0.001). Conclusion  These findings suggest that severely obese participants’ rate of salivary habituation to a taste stimulus is delayed compared to normal-weight controls. This provides support that satiation in bariatric surgery candidates is impaired, possibly leading to increased energy intake and positive energy balance.     

Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg⁻¹·min⁻¹ increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg⁻¹·min⁻¹ showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg⁻¹·min⁻¹, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice.     

Right Ventricular Systolic Function Is Not Depressed In Morbid Obesity

Background: The increased pulmonary blood volume associated with the increased total blood volume in morbidly obese patients increases pulmonary artery pressure and pulmonary vascular resistance, resulting in increased right ventricular (RV) afterload. Thus, the morbidly obese may develop RV dysfunction owing to the increased RV afterload. We examined this possibility by assessing RV contractile function in morbidly obese patients, using RV end-systolic pressure-volume relationship and RV systolic time intervals. Methods: Included were 25 morbidly obese patients undergoing gastric bypass surgery under general anesthesia. Pulmonary artery pressure and RV end-systolic volume were measured with a thermodilution pulmonary artery catheter. Pulmonary arterial dicrotic notch pressure was used as an estimate of RV end-systolic pressure. Two data points were used to define RV end-systolic pressure-volume relationship. RV systolic time intervals were determined by simultaneous graphic display of the electrocardiograph, phonocardiograph, and pulmonary artery pressure curve, and were expressed as a pre-ejection period/RV ejection time ratio. Results: The mean slope of right ventricular end-systolic pressure-volume relationship line was 0.54 ± 0.13 and mean pulmonary vascular resistance 274 ± 80 dyne·sec·cm⁻⁵·m⁻². The mean pre-ejection period/RV ejection time ratio was 0.4 ± 0.11. There was an inverse correlation between the pre-ejection/RV ejection time ratio and the slope of RV end-systolic pressure-volume relationship line (R²=0.658, P<0.0001). Conclusion: Our data indicate that RV function is not depressed in morbid obesity despite increased RV afterload.     

Red Blood Cell Aggregation and Deformability among Patients Qualified for Bariatric Surgery

Background The study presents red blood cell (RBC) aggregability and deformability among obese patients qualified for bariatric surgery and its correlation with plasma lipid concentration. Methods We studied 40 morbidly obese patients who were qualified for bariatric surgery: mean age was 43.5 ± 11.3 years, and mean body mass index (BMI) was 48.9 ± 7.7 kg/m².The RBC deformability and aggregation parameters: aggregation index (AI), syllectogram amplitude (AMP) and aggregation half-time (t_1/2) were measured by Laser-assisted Optical Rotational Cell Analyser - LORCA. Results Elongation index of RBC was significantly lower in obese patients than in the control group (P < 0.001) in 3.16–60.03 Pa shear stresses. Correlations between elongation index and triglyceride levels ranged between 0.42 to 0.44 (P < 0.05). AI was significantly higher in the obese patients (P < 0.001), t_1/2 and the AMP were decreased (P < 0.001) compared to the control group. The RBC aggregation index correlated positively with total cholesterol level (r = 0.61, P < 0.05), non-HDL cholesterol level (r = 0.54, P < 0.05) and BMI (r = 0.48, P < 0.05). Negative correlation presented t_1/2 with total cholesterol (r = −0.64, P < 0.05), non-HDL cholesterol (r = −0.51, P < 0.05) and BMI (r= −0.59, P < 0.05). Conclusion Obesity is associated with RBC rheological disturbances expressed by a decrease in RBC deformability, increased total aggregation extent and the alteration of kinetics of RBC aggregation. These results may suggest the necessity of introducing treatment forms to correct erythrocyte rheological properties, which may improve the blood-flow condition in the microcirculation and prevent postoperative complications after bariatric surgery.     

Effects of Laparoscopic Pneumoperitoneum and Changes in Position on Arterial Pulse Pressure Wave-Form: Comparison Between Morbidly Obese and Normal-Weight Patients

Background: Laparoscopic adjustable gastric banding (LAGB) is commonly indicated in morbidly obese patients. There is controversy regarding the hemodynamic effects of pneumoperitoneum (PNP) in obese patients. PNP and changes in body posture have complex effects on venous return that may be detected by respiratory changes in the arterial pressure waveform. The aim of this study was to compare pneumoperitoneum-induced and reverse Trendelenburg (RT) changes in arterial pulse pressure in obese and normal-weight patients. Methods: 15 morbidly obese patients undergoing LAGB were compared to 15 normal-weight patients undergoing laparoscopic surgery. Arterial pressure was non-invasively recorded using an arterial tonometer. Respiratory changes in pulse pressure (ΔPp) were recorded in the supine position without and with PNP, and in RT position with pneumoperitoneum. Results: PNP increased ΔPp values in normal weight (P<0.001), but not in obese patients. RT position increased ΔPp values in obese patients, but did not cause additional changes in normal-weight patients. Conclusions: Unlike normal-weight patients, PNP in the supine position has minimal effect on the arterial pulse-pressure wave-form in obese patients. This observation may reflect physiological differences in total blood volume and loading conditions of the heart between morbidly obese and normal-weight patients, which affect venous return during PNP. Differences in abdominal vascular zone conditions between obese and normal weight-patients may explain these results.     

Gallbladder Pathology in Morbid Obesity

Background: Obese patients are at increased risk for biliary disease. The prevalence and type of gallbladder pathology in morbidly obese patients was evaluated, and compared with a non-obese control group. Methods: A consecutive series of obese patients (n=478) who had undergone bariatric surgery with concurrent routine cholecystectomy and a consecutive group of organ donors (n=481) were compared. Gallbladder pathology was defined as: cholelithiasis, cholecystitis, cholesterolosis, or normal pathology. Results: Mean age of obese patients and of donors was 42 ± 9 and 43 ± 17 years respectively and mean BMI was 52 ± 10 and 27 ± 7 kg/m² respectively, P<0.05. There were more females in the obesity group (88% vs 47%, P<0.0001). 31% of obese patients and 7% of controls had a previous cholecystectomy (P<0.0001). 21% of the obese and 72% of the controls had normal gallbladder pathology (P<0.0001). Overall, obese patients had a higher incidence of cholelithiasis (25% vs 5%, P<0.0001), cholecystitis (50% vs 17%, P<0.0001), and cholesterolosis (38% vs 6%, P<0.0001) compared with controls. Obese patients with BMI <50 were more likely than those with BMI ≥50 to have normal gallbladder pathology (27% vs 14%, P<0.001). Female patients were more likely to have undergone previous cholecystectomy than males in both the obese group (34% vs 11%, P<0.001) and the control group (12% vs 2%, P<0.0001). Normal pathology was more common in male patients (80% vs 63%, P<0.0001) and patients <50 years (76% vs 66%, P<0.05) in the control group. Conclusions: Obese patients have an increased incidence of benign gallbladder disease than a group of controls, and the relative risk appears to be positively correlated with the level of increase in the BMI. Obesity appears to change the effect of age and gender on gallbladder pathology.     

Relationship between the Upper Airway and Obstructive Sleep Apnea-Hypopnea Syndrome in Morbidly Obese Women

Background The authors studied changes in the upper airway in morbidly obese women and the relationship to sleep apnea-hypopnea syndrome (OSAS). Methods Patients underwent a cardiorespiratory polygraphic study, respiratory function test (spirometry, plethysmography, maximum inspiratory pressures and arterial blood gas analysis), and computed tomographic studies of the upper airway. Results 40 morbidly obese women being evaluated for bariatric surgery (mean age 39.6 ± 9.6 years old, BMI 48.7 ± 5.6 kg/m²) were studied. 37 women had OSAS, and 14 had severe OSAS. Results on respiratory function tests were normal. BMI and weight had a positive correlation with apnea-hypopnea index (AHI), apnea index (AI), desaturation index (DI), lowest oxygen saturation and CT90. Uvula diameter had a negative correlation with FEV₁, FVC, VC IN and a positive correlation with TLC. Retropharynx soft tissue at the retropalatal level had a negative correlation with FEV₁, FVC and VC IN. The oropharynx area at maximal inspiration (total lung capacity) obtained a negative correlation with the AHI (r = −0.423, P = 0.044), AI (r = −0.484, P = 0.042) and DI (r = −0.484, P = 0.019). Conclusions Prevalence of OSAS in morbidly obese women is very high. Our results show the significant correlation between BMI and AHI in morbidly obese women. Uvula diameter and retropharynx soft tissue are the upper airway parameters with higher relationship with pulmonary function. A reduction in the cross-sectional area of the airway at the level of the oropharynx could be related to the severity of OSAS in morbidly obese women.     

Increased Serum Amyloid A Concentrations in Morbid Obesity Decrease after Gastric Bypass

Background: Obesity is considered a state of low-grade chronic inflammation, which may favor the development of cardiovascular diseases. Serum amyloid A (SAA) is an acute phase protein synthesized in response to infection, inflammation, injury, and stress. The aim of the present study was to compare the circulating concentrations of SAA and the mRNA expression in omental adipose tissue between lean and obese individuals and to analyze the effect of weight loss after gastric bypass. Methods: 16 lean volunteers (BMI 20.5 ± 0.6 kg/m²) and 24 obese patients (BMI 47.0 ± 1.2 kg/m²) were included in the study. Serum concentrations of SAA were measured by ELISA. In addition, the concentrations of SAA in 18 morbidly obese patients (7 male/11 female; BMI 44.6 ± 1.9 kg/m²) were measured before and after weight loss following Roux-en-Y gastric bypass (RYGBP). SAA expression in omental adipose tissue was quantified by RT-PCR in biopsies from obese patients undergoing RYGBP and from age-matched lean individuals subjected to Nissen fundoplication. Results: Obese patients exhibited significantly increased circulating SAA concentrations (6.6 ± 0.5 vs 39.3 ± 9.1 μg/ml; P<0.01) compared to lean subjects. A significant positive correlation was found between logSAA and body fat (r=0.631, P<0.0001). Obese patients showed significantly increased (P<0.05) mRNA expression of SAA in omental adipose tissue compared to lean subjects. Weight loss significantly decreased SAA concentrations after RYGBP (final BMI 28.5 ± 0.9 kg/m², P<0.0001 vs initial) from 47.5 ± 14.5 to 15.7 ± 2.9 μg/ml (P<0.05). Conclusion: It can be concluded that serum SAA and mRNA expression of SAA in omental adipose tissue are increased in obese patients contributing to the obesity-associated cardiovascular disease risk. Moreover, weight loss reduces SAA concentrations, which may contribute to the beneficial effects accompanying weight reduction.     

One-Year Changes in Energy Expenditure and Serum Leptin Following Adjustable Gastric Banding in Obese Women

Background: Weight loss is associated with a decrease in both energy expenditure and circulating leptin levels. Whether this holds true when the influence of body composition on energy expenditure and leptin is taken into account remains controversial. The aim of the study was to assess changes in resting metabolic rate (RMR) and serum leptin adjusted for body composition during surgically induced weight loss. Methods: In 36 women (age 42.7±8.7 years; BMI 47.2±8.5 kg/m²; mean±SD) undergoing laparoscopic adjustable gastric banding (LAGB) for morbid obesity, we measured RMR (by indirect calorimetry), body composition (by dual-energy X-ray absorptiometry) and serum leptin (by immunoradiometry), immediately before and 1 year after surgery. Results: 1 year after LAGB, there were significant decreases in body weight (−23.7±11.6 kg, P<0.001), fat mass (FM: −20.9±11.3 kg, P<0.0001), lean body mass (LBM: −3±5.3 kg, P=0.005), RMR (−298±309 kcal/day, P<0.0001), serum leptin (−24.0±18.4 ng/ml, P<0.0001), RMR/LBM ratio (−3.9±5.8 kcal/kg LBM/day, P<0.01) and leptin/FM ratio (−0.21±0.29 ng/kg FM/ml, P<0.001). RMR values after surgery were correctly predicted by the regression equation relating RMR to LBM and FM at baseline, whereas this was not the case for serum leptin (in relation to FM). Conclusions: Changes in RMR 1 year after LAGB were explained by changes in body composition whereas changes in serum leptin were not. The data provide no evidence for a metabolic adaptation of RMR with weight loss, but suggest that serum leptin is decreased beyond expected values based on body composition, a factor that may favor weight regain after surgically induced weight loss.     

Gastric Emptying of Solids and Semi-solids in Morbidly Obese and Non-obese Subjects: An Assessment Using the <Superscript>13</Superscript>C-Octanoic Acid and <Superscript>13</Superscript>C-Acetic Acid Breath Tests

Background It has been suggested that obesity is associated with an altered rate of gastric emptying. The objective of the present study was to determine whether the rates of solid and semi-solid gastric emptying differ between morbidly obese patients and lean subjects. Methods The Gastric-emptying time (GET) of solid and semi-solid meals were compared between lean healthy subjects and morbidly obese patients enrolled in two previously published studies. GET of solid and semi-solid meals was measured using the ¹³C-octanoic acid breath test and ¹³C-acetic acid breath test, respectively, in 24 lean and 14 morbidly obese individuals of both sexes. Student t-test was used to compare the mean data between the lean and morbidly obese groups. The influence of sex, gender, BMI and morbid obesity on the GET of solid meals was verified by linear regression analysis. Results Mean t(1/2) values of solid GET (± standard deviation) were 203.6 ±  76.0 min and 143.5 ± 19.1 min for lean and obese subjects, respectively (P = 0.0010). Mean t(lag) values of solid GET were 127.3 ± 42.7 min and 98.4 ± 13.0 min for lean and obese subjects, respectively (P = 0.0044). No significant difference in semi-solid GET was observed between the lean and morbidly obese groups. Conclusion The present study demonstrated a significantly enhanced gastric emptying of the solid meal test in morbidly obese patients when compared to lean subjects. This finding is compatible with the hypothesis that rapid gastric emptying in morbidly obese subjects increases caloric intake due to a more rapid loss of satiety.     

A randomized study of the effects of perioperative i.v. lidocaine on hemodynamic and hormonal responses for cesarean section

Purpose  Intravenous infusion of lidocaine attenuates the stress response to surgery. We aimed to evaluate the effects of perioperative lidocaine on the hemodynamic and hormonal responses for cesarean delivery. Methods  After the gaining of ethical approval, 90 patients scheduled for elective cesarean delivery were randomly allocated to receive either lidocaine 1.5 mg·kg⁻¹ i.v. bolus 30 min before induction, followed by an infusion of 1.5 mg·kg⁻¹·h⁻¹ until 1 h after surgery (n = 45), or saline placebo (n = 45). Anesthesia was maintained with 50% nitrous oxide in oxygen with 0.7% isoflurane. Hemodynamic variables, plasma cortisol, maternal and neonatal lidocaine concentrations, Apgar scores at 1 and 5 min, neonatal acid-base status, and the neurologic and adaptive capacity score (NACS) were recorded. Results  After induction, patients receiving lidocaine had a smaller increase in heart rate and mean arterial blood pressure (P < 0.02) and lower plasma cortisol concentrations (31.1 ± 9.91 vs 45.6 ± 8.43 μg·dL⁻¹; P < 0.001). There were no differences between the two groups in Apgar scores, NACS, or neonatal acid-base status. After delivery, maternal and umbilical venous concentrations and umbilical vein-to-maternal vein ratios of lidocaine were 2.05 ± 0.42 μg·mL⁻ and 1.06 ± 0.31 μg·mL⁻¹, and 0.52 ± 0.07, respectively. Conclusion  Perioperative lidocaine is safe and effective in attenuating the maternal stress response to surgery for cesarean delivery.     

Gastro-Esophageal Reflux and Esophageal Motility Disorders in Morbidly Obese Patients before and after Bariatric Surgery

Background Obesity is a predisposing factor to gastro- esophageal reflux disease (GERD), but esophageal function remains poorly studied in morbidly obese patients and could be modified by bariatric surgery. Methods Every morbidly obese patient (BMI ≥40 kg/m² or ≥35 in association with co-morbidity) was prospectively included with an evaluation of GERD symptoms, endoscopy, 24-hour pH monitoring and esophageal manometry before and after adjustable gastric banding (AGB) or Roux-en-Y gastric bypass (RYGBP). Results Before surgery, 100 patients were included (84 F, age 38.4 ± 10.9 years, BMI 45.1 ± 6.02 kg/m2), of whom 73% reported GERD symptoms. Endoscopy evidenced hiatus hernia in 39.4% and esophagitis in 6.4%. The DeMeester score was pathological in 53.3%; 69% of patients had lower esophageal sphincter (LES) pressure <15 mmHg and 7 had esophageal dyskinesia. BMI was significantly related to the DeMeester score (P = 0.018) but not to LES tone or esophageal dyskinesia. Postoperative data were available in 27 patients (AGB n = 12/60, RYGBP n = 15/36). The DeMeester score (normal <14.72) was significantly decreased after RYGBP (24.8 ± 13.7 before vs 5.8 ± 4.9 after; P < 0.001) but tended to increase after AGB (11.5 ± 5.1 before vs 51.7 ± 70.7 after; P = 0.09), with severe dyskinesia in 2 cases. Conclusion: GERD and LES incompetence are highly prevalent in morbidly obese patients. Preliminary postoperative data show different effects of RYGBP and AGB on esophageal function, with worsening of pH-metric data with occasional severe dyskinesia after AGB.     

Net Fluxes Over Working Thigh of Hormones,Growth Factors and Biomarkers of Bone Metabolism During Short Lasting Dynamic Exercise

The purpose of this study was to evaluate the responses of hormones, growth factors, and biomarkers involved in bone and muscle metabolism during exercise and in recovery. One leg knee-extension exercise and concomitant sampling from the artery and vein were performed. In 12 healthy individuals (6 men and 6 women; age 21–36 years) blood was drawn from the femoral artery and vein at rest, after 10 minutes warm-up, after 15 minutes work at 61% of peak one leg VO₂, and after 5 minutes work at peak one leg VO₂, as well as 5, 30, and 60 minutes in recovery. Blood flow in the femoral vein was measured using the thermodilution technique. Arteriovenous differences were measured over working thigh for growth hormone (GH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGF BP3), parathyroid hormone (PTH) and bone biomarkers, i.e., the carboxyterminal propeptide of type I procollagen (PICP), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), osteocalcin, and bone-specific alkaline phosphatase (b-ALP). There was an uptake of GH (3.1 ± 1.2 mU · min⁻¹, P < 0.001; mean ± SE) over thigh during exercise and a release of IGF-I at the end of exercise (60 ± 36 μg · min⁻¹; P < 0.01). PICP was also released after the maximal exercise (23 ± 12 μg · min⁻¹; P < 0.01) as well as ICTP (0.5 ± 0.3 μg · min⁻¹; P < 0.05) and b-ALP (0.2 ± 0.1 μkat · min⁻¹; P < 0.05). Osteocalcin, IGF BP3, and PTH revealed no clearcut pattern. In the present study, exercise induces endocrine changes which point to anabolic effects on muscle and bone tissue. Received: 12 February 1996 / Accepted: 6 June 1996     

Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia

Purpose This study was performed in order to assess the effects of olprinone, a phosphodiesterase III inhibitor, on hepatic oxygen delivery (DO₂H), oxygen consumption (VO₂H), and mitochondrial oxidation in the liver of a porcine endotoxemia model. Methods Fourteen pigs received continuous infusion of endotoxin via the portal vein for 240 min. From t = 150 to t = 240 min, animals were randomly divided into two groups to receive saline (control [CONT]; n = 7), or olprinone (OLP; n = 7) via the central vein. Results In the OLP group, prior to olprinone treatment at 150 min, endotoxin induced significant decreases in the cardiac index (CI; from 120 ± 31 to 65 ± 13 ml·kg⁻¹·min⁻¹; P < 0.01) and DO₂H (from 3.58 ± 0.81 to 1.55 ± 0.49 ml·kg⁻¹·min⁻¹; P < 0.01), while VO₂H was maintained. After administration of olprinone (from t = 150 to t = 240 min), CI was unchanged, while DO₂H increased from 1.55 ± 0.49 to 1.93 ± 0.38 ml·kg⁻¹·min⁻¹ (P < 0.01) and VO₂H increased from 0.42 ± 0.28 to 0.69 ± 0.38 ml·kg⁻¹·min⁻¹ (P < 0.01). At t = 240 min, the oxidation level of cytochrome aa3 was significantly higher in the OLP group than in the CONT group (OLP, 66.2 ± 19.3% vs CONT, 26.4 ± 17.3%; P < 0.01). Conclusion Our data for this porcine endotoxemia model suggest that olprinone may have beneficial therapeutic effects in restoring not only systemic and hepatic circulation but also mitochondrial oxidation in the liver.     

Sodium transport and bone mineral density in hypercalciuria with thiazide treatment

Erythrocyte sodium-potassium (Na⁺/K⁺) -ATPase and sodium-lithium (Na⁺/Li⁺) countertransport activities were measured in 18 children (aged 9.6 years, range 6–16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na⁺/K⁺-ATPase activity than 23 age-matched healthy controls (mean±SEM 2,156±110 μmol P/l erythrocyte per hour vs. 3,165±175, P<0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90±0.07 mmol/mmol versus 0.51±0.06 respectively, P<0.01. The corresponding iPTH levels were 5.9±0.6 pmol/l and 5.1±0.7, P<0.05. The Na ⁺ /K ⁺ -ATPase activity increased significantly (2,769±169 μmol P/l erythrocyte per hour vs. 2,156±110 in the control period, P<0.01) and the Na ⁺ /Li ⁺ countertransport decreased (268±28 μmol Li/l erythrocyte per hour vs. 328 ⁺ 26 in the control period, P<0.03). The bone mineral density Z score rose from –1.3±0.26 to –0.8±0.22 (P<0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na ⁺ /K ⁺ -ATPase and Na ⁺ /Li ⁺ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density. Received March 3, 1997; received in revised form and accepted July 7, 1997