Prospective Randomized Clinical Trial Comparing Intradermal, Intraparenchymal, and Subareolar Injection Routes for Sentinel Lymph Node Mapping and Biopsy in Breast Cancer

Background Multiple injection routes, including intradermal (ID), intraparenchymal (IP), and subareolar (SA), are used for ^99mTc-sulfur colloid administration for sentinel lymph node (SLN) mapping and biopsy in breast cancer. The aim of this study was to compare localization by ID, IP, and SA injection routes based on preoperative lymphoscintigraphy and intraoperative identification.Methods Four hundred prospectively randomized breast cancers underwent SLN mapping and biopsy.Results Preoperative lymphoscintigraphy demonstrated localization to the axilla in 126/133 (95%) ID, 82/132 (62%) IP, and 96/133 (72%) SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.081 IP vs. SA), with a mean duration of preoperative lymphoscintigraphy of 139 ± 18 minutes. Mean time to first localization when localization was demonstrated on preoperative lymphoscintigraphy was 8 ± 14 minutes for ID, 53 ± 49 for IP, and 22 ± 29 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.003 IP vs. SA). Intraoperative identification of a SLN at the time of SLN biopsy was successful in 133/133 (100%) ID, 121/134 (90%) IP, and 126/133 (95%) SA (P < 0.001 ID vs IP; P = 0.014 ID vs. SA; P = 0.168 IP vs. SA), with a mean time from injection of ^99mTc-sulfur colloid to start of SLN biopsy of 288 ± 71 minutes. Mean intraoperative time to harvest the first SLN was 9 ± 4 minutes for ID, 13 ± 6 for IP, and 12 ± 6 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.410 IP vs. SA).Conclusions The ID injection route demonstrated a significantly greater frequency of localization, decreased time to first localization on preoperative lymphoscintigraphy, and decreased time to harvest the first SLN. This represents the first prospective randomized clinical trial to confirm superiority of the ID route for administration of ^99mTc-sulfur colloid during SLN mapping and biopsy in breast cancer.     

Gastroesophageal Reflux in Patients with Morbid Obesity: A Role of Obstructive Sleep Apnea Syndrome?

Background  Obesity is a risk factor for gastroesophageal reflux disease (GERD) and for obstructive sleep apnea (OSA). Our aim was to evaluate in morbidly obese patients the prevalence of OSA and GERD and their possible relationship. Methods  Morbidly obese patients [body mass index (BMI) >40 or >35 kg/m² in association with comorbidities] selected for bariatric surgery were prospectively included. Every patient underwent a 24-h pH monitoring, esophageal manometry, and nocturnal polysomnographic recording. Results  Sixty-eight patients [59 women and 9 men, age 39.1 ± 11.1 years; BMI 46.5 ± 6.4 kg/m² (mean ± SD)] were included. Fifty-six percent of patients had an abnormal Demester score, 44% had abnormal time spent at pH <4, and 80.9% had OSA [apnea hypopnea index (AHI) >10] and 39.7% had both conditions. The lower esophageal sphincter (LES) pressure was lower in patients with GERD (11.6 ± 3.4 vs 13.4 ± 3.6 mm Hg, respectively; P = 0.039). There was a relationship between AHI and BMI (r = 0.337; P = 0.005). Patients with OSA were older (40.5 ± 10.9 vs 33.5 ± 10.4 years; P = 0.039). GERD tended to be more frequent in patients with OSA (49.1% vs 23.1%, respectively; P = 0.089). There was no significant relationship between pH-metric data and AHI in either the 24-h total recording time or the nocturnal recording time. In multivariate analysis, GERD was significantly associated with a low LES pressure (P = 0.031) and with OSA (P = 0.045) but not with gender, age, and BMI. Conclusion  In this population of morbidly obese patients, OSA and GERD were frequent, associated in about 40% of patients. GERD was significantly associated with LES hypotonia and OSA independently of BMI.     

Lymphoseek: A Molecular Imaging Agent for Melanoma Sentinel Lymph Node Mapping

Background Lymphoseek is a molecular imaging agent specifically designed for sentinel lymph node mapping. We conducted a phase I clinical trial in which Lymphoseek was compared with filtered [^99mTc]sulfur colloid (fTcSC) for melanoma sentinel lymph node detection. Methods Twenty-four patients (33–81 years) with melanoma participated in this study. Four groups of six patients received an intradermal administration (.5 mCi) of 1.0, 5.0, or 10.0 nmol of ^99mTc-labeled Lymphoseek or filtered [^99mTc]sulfur colloid. The injection site clearance was monitored by nuclear imaging for 3 hours. Lymph nodes obtained by gamma-guided biopsy (4.0–8.7 hours after injection) were assayed for radioactivity. Clinical chemistry values were monitored (before injection, before surgery, and 4 and 24 hours), and whole-body scans were acquired at 1 and 12 hours after injection. Results Lymphoseek exhibited a significantly (P < .001) faster injection site clearance at all dose levels. The mean Lymphoseek clearance half-time was 2.17 ± .96 hours (n = 18) compared with 14.7 ± 6.3 hours for fTcSC (n = 6). The mean sentinel lymph node uptakes of Lymphoseek (.73% ± .94%) and fTcSC (.85% ± 1.19%) were statistically equivalent (P = .68). Lymphoseek exhibited a lower mean number of sentinel lymph nodes per basin (1.6) than fTcSC (1.9). No adverse events were observed, nor were any clinically significant alterations in laboratory parameters. Radiation absorbed doses were lower than filtered [^99mTc]sulfur colloid. Conclusions The molecular imaging agent Lymphoseek demonstrated faster injection site clearance and equivalent primary sentinel node uptake when compared with filtered [^99mTc]sulfur colloid.     

Is Lean Body Mass Decreased after Obesity Treatment by Adjustable Gastric Banding?

Background There is concern that surgically-induced weight loss in obese subjects is associated with a disproportionate decrease in lean body mass (LBM) and in skeletal muscle mass (SMM), a major constituent of LBM. To address this issue, 1) we measured total and regional body composition following gastric banding in a group of obese subjects, and 2) we compared these data to those of a non-surgical control group of similar age and body size. Methods Body composition was assessed by dualenergy X-ray absorptiometry (DEXA) before and after laparoscopic adjustable silicone gastric banding (LAGB) in 32 women (after 1 year: age 43.7 ± 8.4 years, BMI 36.4 ± 5.9 kg/m², mean ± SD), and in 117 control women (age 44.5 ± 7.5 years; BMI 36.7 ± 5.5 kg/m²) referred for non-surgical weight management, prior to weight loss. SMM was estimated using a published equation based on LBM of the extremities (appendicular LBM). Results 1 year after LAGB, body weight loss (−23.7 ± 11.6 kg, P < 10⁻⁶) was mainly due to decreased fat mass (−21.2 ± 11.2 kg, P < 10⁻⁶), and total LBM was modestly, although significantly, decreased (−2.1 ± 4.2 kg, P = 0.01). Appendicular LBM (−0.7 ± 2.7 kg) and total SMM (−0.9 ± 3.0 kg) were not significantly modified. None of the body composition variables was significantly decreased in weight-reduced subjects compared to the control group, especially appendicular LBM and total SMM. Conclusions Results provide no evidence for a decrease in appendicular LBM and total SMM with weight loss following LAGB. Follow-up of these obese patients revealed a very favorable pattern of change in total and regional body composition, with preservation of muscle mass.     

Muscle mass deficits are associated with bone mineral density in men with idiopathic vertebral fracture

Introduction and hypothesis The causes of idiopathic vertebral fractures (IVF) in men are poorly understood. We hypothesised that in IVF, areal bone mineral density (aBMD) deficits would be associated with reduced muscle mass. Methods In this case-control study, 48 men (61.5 ± 12.1 years old) presenting with symptomatic IVF were compared with 48 healthy controls matched for age (±5 years) and stature (±5 cm). The aBMD and soft-tissue body composition were determined by dual energy X-ray absorptiometry (DXA). Muscle mass was defined as the ratio of appendicular lean mass to the square of height (ALMI). Sex hormones, IGF-I and its binding protein IGFBP-3 were measured by immunoassay. Results ALMI was significantly lower in IVF patients (8.27 ± 0.90 vs 8.65 ± 0.88 kg/m², t = 2.193, df = 47, P = 0.033 by paired sample t-test). Hierarchical regression analysis revealed that for IVF patients, ALMI explained the greatest proportion of variance in BMD at the lumbar spine, femoral neck and total hip (R ² _change = 16.4–22.7%, P = 0.012–0.002) and only IGFBP-3 explained variance in ALMI (R ² _change = 19.9%, P = 0.006). Conclusions In men with IVF, ALMI was reduced and associated with IGFBP-3. ALMI was identified as a novel factor that explained a greater proportion of variance in BMD than either fat mass or serum biochemistry. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Relationship between Obstructive Sleep Apnea and Liver Abnormalities in Morbidly Obese Patients: A Prospective Study

Background Morbid obesity is a risk factor of nonalcoholic steatohepatitis (NASH). Obstructive sleep apnea (OSA) could also be an independent risk factor for elevated liver enzymes and NASH. The relationships between liver injuries and OSA in morbidly obese patients requiring bariatric surgery were studied prospectively. Methods Every consecutive morbidly obese patient (BMI ≥40 kg/m² or ≥35 kg/m² with severe comorbidities) requiring bariatric surgery was included between January 2003 and October 2004. Polygraphic recording, serum aminotransferases (ALT, AST), γ-glutamyltransferase (GGT) and liver biopsy were systematically performed. OSA was present when the apnea–hypopnea index (AHI) was >10/h. Results 62 patients (54 F; age 38.5 ± 11.0 (SD) yrs; BMI 47.8 ± 8.4 kg/m²) were included. Liver enzymes (AST, ALT or GGT) were increased in 46.6%. NASH was present in 34.4% and OSA in 84.7%. Patients with OSA were significantly older (P = 0.015) and had a higher BMI (P = 0.003). In multivariate analysis, risk factors for elevated liver enzymes were the presence of OSA and male sex.The presence of NASH was similar in patients with or without OSA (32.7% vs 44.4% of patients, P = 0.76). Conclusion In this cohort of morbidly obese patients requiring bariatric surgery, one-third of patients had NASH, a prevalence similar to previous studies. OSA was found to be a risk factor for elevated liver enzymes but not for NASH.     

Gastroesophageal Reflux Disease in Morbid Obesity: The Effect of Roux-en-Y Gastric Bypass

Background  Gastroesophageal reflux disease (GERD) is a common condition in obesity. The impact of Roux-en-Y gastric bypass (RYGBP) on GERD is poorly known. We studied the effect of the RYGBP on GERD in patients with morbid obesity (MO). Methods  Twenty consecutive patients with MO (BMI > 40 kg/m²) were studied before and 6 months after RYGBP. GERD symptoms were evaluated with Carlsson–Dent questionnaire (CDQ). All the patients underwent esophageal manometry and ambulatory 24-h pH-metry. Chi-square test was used to compare categorical variables, and Wilcoxon test was used for numerical variables. A p value under 0.05 was considered significant. Results  There were 16 women (80%) and 4 men (20%) with mean age 38.9 ± 6.9 years included in this study. BMI was 48.5 ± 6.2 kg/m² and 33.2 ± 4.5 kg/m² before and after RYGBP, respectively. Mean weight reduction was 42.5 ± 9.7 kg (p < 0.001). Reflux symptoms measured by CDQ and esophageal acid exposure improved significantly after RYGBP. The percentage of time of pH < 4 was 10.7 ± 6.7 before and 1.6 ± 1.2 after the surgical procedure (p < 0.001). LES basal pressure before and after the RYGBP was 18 ± 11 and 20.1 ± 5.6 mmHg (p = 0.372), and the esophageal body amplitude was 104.2 ± 47.2 and 75.1 ± 36.2 mmHg, respectively (p = 0.005). Conclusion  RYGBP improves GERD symptoms and reduces esophageal acid exposure in patients with MO.     

Sleeve Gastrectomy — A Restrictive Procedure?

Background Diet and surgically-induced weight loss have been shown to lead to alterations in motor and sensory function of the stomach.We investigated the clinical outcome and gastric emptying of solid foods in morbidly obese (MO) patients following sleeve gastrectomy (SG). Methods We studied 23 MO patients [(7 males, 16 females), mean age 38.9 ± 11.0 years (range 20–64 years), mean weight 135.1 ± 19.0 kg (range 97–167 kg), mean BMI 47.2 ± 4.8 kg/m2 (range 39.6–56.0 kg/m2)] who each underwent a sleeve gastrectomy (SG) for weight reduction. At the monthly follow-up visits, variations in weight and BMI changes, postoperative meal size and frequency, and presence of gastrointestinal symptoms were recorded. 11 patients underwent scintigraphic measurement of the gastric emptying of a solid meal pre- and 6 months postoperatively. Results A significant reduction in patients’ weight was evidenced at 6 and 12 months postoperatively [98.6 ± 11.8 kg and 87.0 ± 10.7 kg respectively (P = 0.001)]. BMI decreased to 35.2 ± 4.3 kg/m² at 6 months and to 31.1 ± 4.5 kg/m² at 12 months, respectively (P = 0.001). Although meal size was drastically reduced, meal frequency increased postoperatively in 12 patients (52.2%). Only 5 patients (21.8%) reported occasional vomiting after meals following SG. The gastric emptying half-time (T1/2) accelerated (47.6 ± 23.2 vs. 94.3 ± 15.4, P < 0.01) and the T-lag phase duration decreased (9.5 ± 2 min vs. 19.2 ± 2 min, P < 0.05) postoperatively. The percentage of the meal emptied from the stomach 90 min after consumption increased significantly after SG (75.4 ± 14.9% vs. 49.2 ± 8.7%, P < 0.01). Conclusions This study indicates that following SG, the stomach empties its contents rapidly into the small intestine and symptoms of vomiting after eating (characteristic of restrictive procedures) are either absent or very mild. Therefore, the term ‘restrictive’ is possibly ill-advised for this new bariatric operation. It remains for other mechanisms of energy intake reduction, such as intestinal distension and satiety signals through gut hormones to be investigated, to comprehensively explain precisely how this ‘food limiting’ procedure results in weight loss.     

Iron deficiency in children with early chronic kidney disease

Iron deficiency (ID) contributes to the development of anemia in patients with chronic kidney disease (CKD). The frequency of ID in children with early CKD has not previously been reported. This was a retrospective chart review of children with CKD stages 2 and 3 followed at the CKD clinic of Children’s Hospital of Michigan. ID was defined as low ferritin and transferrin saturation <20%. Patients on iron supplements were considered as iron-deficient cases. There were 50 patients included in the study (72% male) with a mean age of 10.31 (±5.21). The mean glomerular filtration rate (GFR) was 55.4 ml/min/1.73 m² (±14.61). ID was present in 42% of patients, out of whom almost half (42.9%) presented with anemia. Females had a higher frequency of ID (64.3%). The frequency of ID with anemia increased from 4.3% to 29.6%, (p = 0.03) in stage 2 to stage 3 CKD, respectively. The frequency of ID without anemia also increased with progression of CKD from stage 2 to stage 3, however, the difference was not statistically significant. ID is frequent in patients with early CKD. Monitoring of iron tests and treatment of ID is important in this population of patients.     

Abnormal cell calcium concentrations in cultured bone cells obtained from femurs of obese and noninsulin-dependent diabetic rats

Summary Cytoplasmic free calcium concentration [Ca²⁺]i was quantified in cultured bone cells with osteoblastic characteristics. The cells were obtained from femurs of obese (fa/fa) Wistar-Kyoto rats, from nonobese, noninsulin-dependent diabetic (NIDD) Sprague Dawley rats, and from their appropriate controls. [Ca²⁺]i was also determined in bone cells obtained fromin vivo insulin-treated NIDD rats. Obese (Wistar Kyoto) rats had increased body weight (313±13 vs. 249±4 g;P<0.01), decreased femur weights (0.68±0.05 vs. 0.89±0.05 g;P<0.05), similar glucose levels (148±5 vs. 139±3 mg/dl), and higher plasma insulin levels (6.0±0.5 vs. 0.7±0.1 ng/ml;P<0.01) when compared with their nonobese [(fa/+); (+/+)] littermates. Nonobese, NIDD rats, compared with their appropriate controls (nondiabetic Sprague Dawley rats) had higher plasma glucose levels (235±32 vs. 145±3 mg/dl;P<0.01) but their plasma insulins, body weights, and femur weights were similar to controls (0.7±0.1 vs 0.6±0.1 ng/ml; 302±4 vs. 318±14 g; 0.97±0.4 vs. 0.98±0.04 g, respectively). Long-term (4 weeks) daily insulin treatment (2 u/100 g) of the NIDD rats increased their plasma insulin (1.9 ng/ml;P<0.05) and body weight (369±13 g;P<0.05) but did not change their plasma glucose levels (225±5 mg/dl), or femur weights (0.98±0.4 g). [Ca²⁺]i in bone cells derived from the femurs of obese animals was higher than in cells derived from their nonobese littermates (156±22 vs. 71±13 nM;P<0.01). In bone cells from NIDD rats, [Ca²⁺]i was lower compared with controls (146±22 vs. 229±19 nM;P<0.001). Insulin treatment of the diabetic animals augmented the decrease in [Ca²⁺]i in their bone cells (68±11 nM;P<0.005 compared with nontreated rats). These data reveal that [Ca²⁺]i in cultured bone cells from obese nondiabetic and nonobese NIDD rats differs from that of their controls. Compared with their controls, the changes in [Ca²⁺]i in bone cells from the NIDD and obese animals were in opposite directions. Whether the underlying mechanisms for the changes in cell [Ca²⁺]i in nondiabetic obese and nonobese NIDD animals differ, and whether the changes in [Ca²⁺]i observed in the cultured cells reflect thein vivo condition in bone cells of these animals are questions that await further investigations.     

Effect of raloxifene on clinical fractures in Asian women with postmenopausal osteoporosis

Osteoporosis is becoming a major public health problem in Asian countries, with a rapid increase in osteoporotic fractures projected as urbanization increases, particularly in China. The purpose of this post hoc analysis was to assess the effects of 12 months of treatment with raloxifene on the incidence of clinical fractures in postmenopausal Asian women, compared to a placebo, by combining two independently designed studies (one Japanese study and one Chinese study). A total of 488 women, 284 in Japan and 204 in China were included in the analysis. Baseline characteristics (mean ± SD) for the Japanese and Chinese women were: age, 64.8 ± 6.3 years and 65.3 ± 6.0 years; body mass index, 21.8 ± 2.8 kg/m² and 23.0 ± 2.9 kg/m²; and prevalent vertebral fractures, 26.4% and 13.7%, respectively. In both studies, the clinical vertebral and nonvertebral fractures were confirmed by radiographs or clinical reports at a central research facility. From the two combined studies, the incidence of new clinical vertebral fractures was significantly lower in the raloxifene 60 mg/day (RLX60) group (0 out of 194, P = 0.01) and in the pooled raloxifene group (those taking 60 mg/day and those taking 120 mg/day) (0 out of 289, P = 0.002), compared with the placebo group (7 out of 199, 3.5%). The pooled raloxifene group, as well as the RLX60 group, also had a significantly lower incidence of any new clinical fracture (P = 0.001 and P = 0.01, respectively) compared to the placebo group. In conclusion, raloxifene treatment at 60 mg/day for 1 year resulted in a significant reduction in the risk of new clinical vertebral fractures and any new clinical fracture in postmenopausal Asian women with osteoporosis.     

Analysis of Safety and Efficacy of Intragastric Balloon in Extremely Obese Patients

Background  The implantation of an intragastric balloon constitutes a short-term effective non-surgical intervention to lose weight. The aim of this study was to evaluate retrospectively the clinical outcome and safety of gastric balloon therapy (GBT) in extremely obese patients. Methods  One hundred and nine super- and super-super-obese patients, 64 males and 45 females, mean age 39.1 ± 8.4 years, mean body mass index (BMI) 68.8 ± 8.9 kg/m², who underwent GBT for weight loss, were studied retrospectively. GBT was assessed in massively obese patients concerning tolerance, weight loss, number of comorbidities and complications. Results  A significant reduction in patients’ weight and BMI was evident after GBT. Regarding safety, no major complications occurred. Minor complications at balloon placement and removal occurred in one (0.9%) and three patients (2.8%) respectively. Mean duration of GBT was 177.6 ± 56.8 days. After GBT, the mean weight loss was 26.3 ± 15.2 kg (p < 0.001) and the mean BMI reduction was 8.7 ± 5.1 kg/m² (p < 0.001) representing a mean percentage of excess BMI lost (%EBL) of 19.7 ± 10.2. The highest BMI loss was observed in patients with BMI > 80 kg/m². A noteworthy improvement of comorbidities in 56.8% of the patients was also noted. Of the 109 patients, 69 received subsequent bariatric surgery. All the procedures were performed laparoscopically. Ten patients, with a mean BMI of 68.6 ± 10.6 kg/m² after the removal of the first BIB, received a second BIB resulting in a non-significant weight and BMI loss of 6.3 ± 9.4 kg and 1.8 ± 2.9 kg/m², respectively. Conclusions  Our study indicates the safety and efficacy of GBT in extremely obese patients particularly as a first step before a definitive anti-obesity operation. GBT appears to be a safe, tolerable, and potentially effective procedure for the initial treatment of morbid obesity.     

Renal hemodynamic changes and renal functional reserve in children with type I diabetes mellitus

Increased glomerular filtration rate (GFR) has been implicated in the development of diabetic nephropathy. Large normal interindividual variations of GFR hamper the diagnosis of renal hemodynamic alterations. We examined renal functional reserve (RFR) in children with type 1 diabetes mellitus to assess whether hyperfiltration occurs. The renal hemodynamic response following dopamine infusion was examined in 51 normoalbuminuric diabetic children (7.7 ± 3.6 years) with a mean duration of diabetes of 6.2 years and compared them with 34 controls. Mean baseline GFR in diabetic children did not differ from the control population (130.7 ± 22.9 vs. 124.8 ± 25 ml/min per 1.73 m²), whereas renal plasma flow was significantly lower (463.7 ± 103.9 vs. 587.2 ± 105 ml/min per 1.73 m², p < 0.001), and filtration fraction was increased (29 ± 8 vs. 21 ± 2%, p < 0.001), compared with controls. The mean RFR was lower (p < 0.001) than in control subjects (−0.77 ± 23 vs. 21 ± 8 ml/min per 1.73 m²). This study documents an increased filtration fraction and reduced or absent RFR in children with type 1 diabetes mellitus in the stage before apparent nephropathy. GFR values were within normal range. Although the reduced RFR and increased filtration fraction indicate the presence of hemodynamic changes, their relevance to the development of hyperfiltration and subsequent diabetic nephropathy remains unknown.     

High Prevalence of Small Intestinal Bacterial Overgrowth in Patients with Morbid Obesity: A Contributor to Severe Hepatic Steatosis

Background With the increasing prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become a major cause of liver diseases. Small intestinal bacterial overgrowth (SIBO) could be related to NAFLD. Our aim was to determine the prevalence of SIBO and its relationship with liver lesions in morbidly obese patients. Methods A glucose hydrogen (H₂) breath test (positive if fasting breath H₂ concentration > 20 ppm and/or an increase of > 10 ppm over baseline within the first 2 h) was performed in obese patients referred for bariatric surgery (body mass index [BMI] >  40 kg/m² or >  35 in association with comorbidities) and in healthy non-obese subjects. In obese patients, a surgical liver biopsy was performed. Results One hundred and forty-six patients (129 women, age [mean±SE]: 40.7 ± 11.4 years) were prospectively included in the study. The mean BMI was 46.1±6.4 kg/m². A liver biopsy was available in 137 patients and a breath test in 136. The frequency of positive breath tests was higher in obese patients (24/136, 17.1%) than in healthy subjects (1/40, 2.5%; P=0.031). In the univariate analysis, SIBO was not associated with clinical variables, but tended to be associated with more frequent severe hepatic steatosis (26.3 vs. 10.3%, P=0.127), whereas the frequency of sinusoidal or portal fibrosis, lobular necrosis and non-alcoholic steatohepatitis (NASH) were not different. In the multivariate analysis, SIBO (P=0.005) and the presence of a metabolic syndrome (P=0.006) were independent factors of severe hepatic steatosis. Conclusion In morbidly obese patients, bacterial overgrowth prevalence is higher than in healthy subjects and is associated with severe hepatic steatosis.     

Cyclosporine-A-induced nephrotoxicity in children with minimal-change nephrotic syndrome: long-term treatment up to 10 years

The impact of cyclosporine A (CsA) therapy in patients with steroid-dependent nephrotic-syndrome (SDNS) on long-term renal function is controversial. Data beyond 5 years are rare. Long-term renal function was evaluated in children with SDNS with and without CsA therapy, especially beyond 5 years. Twenty children were treated with CsA (study group) for a mean of 5.4 ± 2.2 years (ten patients for 5–11 years). Glomerular filtration rate (GFR) was calculated before and after 3 and 12 months and at latest follow-up of therapy. Fifteen children with cyclophosphamide-treated SDNS without CsA served as controls. In the study group, GFR decreased within 12 months from 136 ± 19 to 120 ± 31, to 114 ± 14 ml/min per 1.73 m² at latest follow-up (p < 0.0001). Patients with CsA > 5 years had a GFR of 111 ± 14 ml/min per 1.73 m² at latest follow-up without a GFR below 90 ml/min per 1.73 m². No CsA toxicity was found in biopsies. In the control group, GFR dropped within 3 months, from 137 ± 27 to 130 ± 24, to 126 ± 19 ml/min per 1.73 m² at latest follow-up (p = 0.1). Patients with and without nephrotoxic CsA therapy showed a drop in GFR. In CsA-treated patients, GFR was about 12% lower at latest follow-up compared with patients without nephrotoxic therapy but always remained within normal range. CsA seems to be safe, even in long-term treatment for more than 5 years.     

Mammoscintigraphy with Tc-99m sestamibi in the evaluation of benign and malignant breast disease

Ninety-eight women and 3 men (age range, 16–88 years; mean 46 years) with 103 lesions underwent technetium-99m methoxyisobutylisonitrile (^99mTc-sestamibi, ^99mTc-MIBI) breast scintigraphy prior to biopsy to assess the value of this technique for the detection of breast carcinomas and for their differentiation from benign breast masses. Scans of 29 patients were ^99mTc-sestamibi-positive and 72 were ^99mTc-sestamibi-negative. Scintimammographic findings were true positive in 21 (72%) biopsy confirmed carcinomas and true negative in 65 (89%) benign lesions. ^99mTc-sestamibi scans were false-negative in 7 cases of breast cancer: 4 infiltrating ductal carcinomas and 3 infiltrating ductal with an intraductal component. There were 8 false positive scans which included 4 fibroadenomas, 2 papillomas and 2 areas of chronic inflammation. The mean size of the ^99mTc-sestamibi-positive carcinomas was 2.9 ± 1.2 cm, which contrasts to the size of ^99mTc-sestamibi-negative breast malignancies, which averaged 1.8 ± 0.6 cm (P < 0.0005). The sensitivity of using ^99mTc-sestamibi for detection of breast carcinoma was 75% and its specificity 89%. The positive and negative predictive values were 88% and 93% respectively. Interobserver agreement between the 2 independent and blinded nuclear medicine physicians was 98%. Size of tumor is a critical factor in the detection of sestamibi uptake. ^99mTc-sestamibi can help in the investigation of breast masses.     

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.     

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.