Breastfeeding following bariatric surgery among obese women with and without diabetes mellitus.

BACKGROUND: Information on exclusive breastfeeding (BF) and BF initiation following bariatric surgery (BS) among obese women with diabetes mellitus (DM) and without DM (non-DM) is limited. METHODS: Retrospective cohort study. Obesity was defined by BMI (kg/m2) as grade 1 (30-34.9), grade 2 (35-39.9) or grade 3 (≥40). The 65 women in the DM group (40 women with gestational, 19 with Type 2 and 6 with Type 1) was similar to 84 with non-DM in BS type: Roux-en-Y (51 vs 55%), sleeve gastrectomy (32 vs 35%), laparoscopic gastric banding (17 vs 7%) and gastro-duodenal anastomosis (0 vs 4%). RESULTS: Women with DM were older (35 vs 33y), of advanced age (54 vs 27%), with higher prevalence of grade 3 obesity (66 vs 46%), chronic hypertension (31 vs 10%), delivery of late-preterm infants (23 vs 10%) and neonatal hypoglycemia (25 vs 12%). Although infant feeding intention was similar: BF (66 vs 79%), partial BF (9 vs 7%) or formula (25 vs 14%), at discharge women with DM had lower exclusive BF (29 vs 41%) and BF initiation rates (68 vs 76%) than those with non-DM. Women with grade 3 obesity (52% were DM) differed from those with grades 1-2 (34% were DM) in exclusive BF (27 vs 52%), and BF initiation rates (66 vs 86%). CONCLUSION: After BS, women with DM, especially those with grade 3 obesity, had higher rates of chronic hypertension and preeclampsia and lower rates of exclusive BF and BF initiation than those who had DM but had less severe obesity.

Neuropharmacology of purinergic receptors in human submucous plexus: Involvement of P2X1, P2X2, P2X3 channels, P2Y and A3 metabotropic receptors in neurotransmission.

RATIONALE: The role of purinergic signaling in human ENS is not well understood. We sought to further characterize the neuropharmacology of purinergic receptors in human ENS and test the hypothesis that endogenous purines are critical regulators of neurotransmission. EXPERIMENTAL APPROACH: LSCM-Fluo-4/(Ca(2+))-imaging of postsynaptic Ca(2+) transients (PSCaTs) was used as a reporter of synaptic transmission evoked by fiber tract electrical stimulation in human SMP surgical preparations. Pharmacological analysis of purinergic signaling was done in 1,556 neurons (identified by HuC/D-immunoreactivity) in 235 ganglia from 107 patients; P2XR-immunoreactivity was evaluated in 19 patients. Real-time MSORT (Di-8-ANEPPS) imaging tested effects of adenosine on fast excitatory synaptic potentials (fEPSPs). RESULTS: Synaptic transmission is sensitive to pharmacological manipulations that alter accumulation of extracellular purines: Apyrase blocks PSCaTs in a majority of neurons. An ecto-NTPDase-inhibitor 6-N,N-diethyl-D-ß,γ-dibromomethyleneATP or adenosine deaminase augments PSCaTs. Blockade of reuptake/deamination of eADO inhibits PSCaTs. Adenosine inhibits fEPSPs and PSCaTs (IC50 = 25 µM), sensitive to MRS1220-antagonism (A3AR). A P2Y agonist ADPßS inhibits PSCaTs (IC50 = 111 nM) in neurons without stimulatory ADPbS responses (EC50 = 960 nM). ATP or a P2X1,2,2/3 (α,ß-MeATP) agonist evokes fast, slow, biphasic Ca(2+) transients or Ca(2+) oscillations (ATP,EC50 = 400 mM). PSCaTs are sensitive to P2X1 antagonist NF279. Low (20 nM) or high (5 µM) concentrations of P2X antagonist TNP-ATP block PSCaTs in different neurons; proportions of neurons with P2XR-immunoreactivity follow the order P2X2 > P2X1 >> P2X3; P2X1 + P2X2 and P2X3 + P2X2 are co-localized. RT-PCR identified mRNA-transcripts for P2X1-7, P2Y1,2,12-14R. CONCLUSIONS: Purines are critical regulators of neurotransmission in human ENS. Purinergic signaling involves P2X1, P2X2, P2X3 channels, P2X1 + P2X2 co-localization and inhibitory P2Y or A3 receptors. These are potential novel therapeutic targets for neurogastroenterology.

Effect of bariatric surgery on normal and abnormal renal function.

BACKGROUND: Obesity has been associated with hypertension, diabetes mellitus, and metabolic syndrome, risk factors for chronic kidney disease. In addition, obesity has been found to have an independent, negative effect on renal function and the progression of renal insufficiency. METHODS: The serum creatinine (CR) in 813 patients who had undergone obesity surgery from 2003 to 2009 at a large academic medical center and had been followed up for ≥24 months was retrospectively monitored. Renal function, as measured by the CR level, was assessed at baseline and at 6, 12, and ≥24 months of follow-up. The groups were stratified by the baseline CR as follows: normal (CR <1.3 mg/dL), mild impairment (CR 1.3-1.6 mg/dL), and moderate impairment (CR >1.6 mg/dL). RESULTS: Of the 813 patients, 757 had a CR <1.3 mg/dL at baseline. Of those 757 patients, 97.6% had maintained a CR of <1.3 mg/dL, 1.3% had a CR of 1.3-1.6 mg/dL, 1.1% had a CR of >1.6 mg/dL (n = 757) at 6 months of follow-up. At 1 year of follow-up, 99% had maintained a CR of <1.3 mg/dL and 1% had a CR of >1.3% (n = 509). At 2 years of follow-up, 100% had a CR value of <1.3 mg/dL (n = 388). Of the remaining 56 patients, 71.4% had been classified as having mild impairment (CR 1.3-1.6 mg/dL) and 28.5% as having moderate impairment (CR >1.6 mg/dL) before weight loss surgery. Examination of the CR values at ≥2 years after weight loss surgery demonstrated that 76.7% had a normal CR level, 12.5% had mild impairment, and 10.7% had moderate impairment. CONCLUSION: Bariatric surgery does not have a negative effect on renal function as measured by the CR, whether CR at baseline is <1.3 or ≥1.3 mg/dL when monitored for ≥24 months. For those with impaired renal function and a CR ≥1.3 mg/dL, improvement in CR was seen in 76.7% at ≥2 years postoperatively, at a point at which the weight loss velocity, hydration, and nutritional status have stabilized. The weight loss associated with bariatric surgery could potentially have a positive effect on renal function at ≥24 months, such as was found in the present study by a stable or reduced CR level. The etiology for this might be a direct effect of weight loss on impaired renal function or an indirect effect by reducing the rates of co-morbidities, such as diabetes mellitus and hypertension, both risk factors for renal disease. Additional prospective studies, including weight-matched controls, are needed.

Dual purinergic synaptic transmission in the human enteric nervous system.

Based on findings in rodents, we sought to test the hypothesis that purinergic modulation of synaptic transmission occurs in the human intestine. Time series analysis of intraneuronal free Ca(2+) levels in submucosal plexus (SMP) from Roux-en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca(2+) imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca(2+) response. Short-circuit current (I(sc) = chloride secretion) was recorded in mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation was used to study I(sc) responses. Ca(2+) imaging was done in 1,222 neurons responding to high-K(+) depolarization from 61 surgical cases. FTS evoked synaptic Ca(2+) responses in 62% of recorded neurons. FTS caused frequency-dependent Ca(2+) responses (0.1-100 Hz). FTS Ca(2+) responses were inhibited by Omega-conotoxin (70%), hexamethonium (50%), TTX, high Mg(2+)/low Ca(2+) (< or = 100%), or capsaicin (25%). A P2Y(1) receptor (P2Y(1)R) antagonist, MRS-2179 or PLC inhibitor U-73122, blocked FTS responses (75-90%). P2Y(1)R-immunoreactivity occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective adenosine A(3) receptor (AdoA(3)R) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency-dependent inhibition of FTS Ca(2+) responses (IC(50) = 8.5 x 10(-8) M). The AdoA(3)R antagonist MRS-1220 augmented such Ca(2+) responses; 2-Cl-IBMECA competed with MRS-1220. Knockdown of AdoA(1)R with 8-cyclopentyl-3-N-(3-{[3-(4-fluorosulphonyl)benzoyl]-oxy}-propyl)-1-N-propyl-xanthine did not prevent 2-Cl-IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension I(sc) responses. The SMP from Roux-en-Y patients is a suitable model to study synaptic transmission in human enteric nervous system (huENS). The P2Y(1)/Galphaq/PLC/inositol 1,3,5-trisphosphate/Ca(2+) signaling pathway, N-type Ca(2+) channels, nicotinic receptors, and extrinsic nerves contribute to neurotransmission in huENS. Inhibitory AdoA(3)R inhibit nucleotide or cholinergic transmission in the huENS.

Neurogastroenterology of tegaserod (HTF 919) in the submucosal division of the guinea-pig and human enteric nervous system.

Actions of the 5-HT(4) serotonergic receptor partial agonist, tegaserod, were investigated on mucosal secretion in the guinea-pig and human small intestine and on electrophysiological behaviour of secretomotor neurons in the guinea-pig small intestinal submucosal plexus. Expression of 5-HT(4) receptor protein and immunohistochemical localization of the 5-HT(4) receptor in the submucosal plexus in relation to expression and localization of choline acetyltransferase and the vesicular acetylcholine (ACh) transporter were determined for the enteric nervous system of human and guinea-pig small intestine. Immunoreactivity for the 5-HT(4) receptor was expressed as ring-like fluorescence surrounding the perimeter of the neuronal cell bodies and co-localized with the vesicular ACh transporter. Exposure of mucosal/submucosal preparations to tegaserod in Ussing chambers evoked increases in mucosal secretion reflected by stimulation of short-circuit current. Stimulation of secretion had a relative high EC(50) of 28.1 +/- 1.3 mumol L(-1), was resistant to neural blockade and appeared to be a direct action on the secretory epithelium. Tegaserod acted at presynaptic 5-HT(4) receptors to facilitate the release of ACh at nicotinic synapses on secretomotor neurons in the submucosal plexus. The 5-HT(2B) receptor subtype was not involved in actions at nicotinic synapses or stimulation of secretion.

Heating and humidifying of carbon dioxide during pneumoperitoneum is not indicated: a prospective randomized trial.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum usually is created by a compressed gas source. This exposes the patient to cool dry gas delivered at room temperature (21 degrees C) with 0% relative humidity. Various delivery methods are available for humidifying and heating CO2 gas. This study was designed to determine the effects of heating and humidifying gas for the intraabdominal environment. METHODS: For this study, 44 patients undergoing laparoscopic Roux-en-Y gastric bypass were randomly assigned to one of four arms in a prospective, randomized, single-blinded fashion: raw CO2 (group 1), heated CO2 (group 2), humidified CO2 (group 3), and heated and humidified CO2 (group 4). A commercially available CO2 heater-humidifier was used. Core temperatures, intraabdominal humidity, perioperative data, and postoperative outcomes were monitored. Peritoneal biopsies were taken in each group at the beginning and end of the case. Biopsies were subjected staining protocols designed to identify structural damage and macrophage activity. Postoperative narcotic use, pain scale scores, recovery room time, and length of hospital stay were recorded. One-way analysis of variance (ANOVA) and the nonparametric Kruskal-Wallis test were used to compare the groups. RESULTS: Demographics, volume of CO2 used, intraabdominal humidity, bladder temperatures, lens fogging, and operative times were not significantly different between the groups. Core temperatures were stable, and intraabdominal humidity measurements approached 100% for all the patients over the entire procedure. Total narcotic dosage and pain scale scores were not statistically different. Recovery room times and length of hospital stay were similar in all the groups. Only one biopsy in the heated-humidified group showed an increase in macrophage activity. CONCLUSIONS: The intraabdominal environment in terms of temperature and humidity was similar in all the groups. There was no significant difference in the intraoperative body temperatures or the postoperative variable measured. No histologic changes were identified. Heating or humidifying of CO2 is not justified for patients undergoing laparoscopic bariatric surgery.

Endoscopic management of stomal stenosis after Roux-en-Y gastric bypass.

BACKGROUND: In the United States, Roux-en-Y gastric bypass has evolved into the procedure of choice for clinically severe obesity. Stomal stenosis resulting in gastric outlet obstruction is a recognized complication. Endoscopic balloon dilation is often used to treat this condition. To evaluate the safety and efficacy of endoscopic management of stomal stenosis we evaluated our treatment methods and outcomes. METHODS: The records of all patients undergoing Roux-en-Y gastric bypass from 1 July 2000 to 30 June 2002 were studied. Stenosis was defined as signs and symptoms of obstruction with inability to cannulate the gastrojejunostomy using an 8.5-mm diagnostic endoscope. Charts were reviewed and demographic data, operative course, symptoms, and outcomes were recorded. RESULTS: A total of 562 patients underwent Roux-en-Y gastric bypass for obesity during the study period. Of these, 38 patients underwent endoscopic balloon dilation for stomal stenosis, for a stenosis rate of 6.8%. The average time from surgery to initial dilation was 7.7 weeks (range 3 to 24). The average number of dilations required was 2.1 (range one to six). The mean initial balloon size was 13 mm and the mean final balloon size was 16 mm. Two patients failed endoscopic dilation and proceeded to surgery, including one patient who developed pneumomediastinum and pneumothorax after dilation. All patients were relieved of their gastric outlet obstruction. The success rate for endoscopic balloon dilation was 95% with a 3% complication rate. CONCLUSIONS: In our experience, the rate of gastrojejunostomy stenosis following Roux-en-Y gastric bypass is 6.8%. Endoscopic balloon dilation is a safe and effective therapy for stomal stenosis with a high success rate. It should be considered an appropriate intervention with a low risk for reoperation.

Robotic resection of pancreatic neuroendocrine tumor.

Computer-assisted surgical devices, or "surgical robots," have recently been approved for general surgical use. The device allows the surgeon remote control of multi-articulated instrument arms with a three-dimensional view. Here we report the first known case of pancreatic resection with use of a computer-assisted, or robotic, surgical device. A 46-year old woman presented with back pain and a complex cystic mass in the tail of the pancreas. The daVinci surgical robot was used to remove the lesion en bloc with the tail of the pancreas and spleen. The patient did well and returned to full activity promptly. In summary, robotic technology may enhance advanced laparoscopic procedures. Pancreatic resection is feasible, and future experience will determine the true benefits of this technique.

Computer-enhanced robotic telesurgery. Initial experience in foregut surgery.

BACKGROUND: A new type of computer-enhanced telemanipulator device for "robotic" laparoscopic surgery was recently approved. We prospectively evaluated the initial patients undergoing procedures with this new device at our institution. METHODS: Patient demographics, operative indications, port placement, operative time, robot time, complications, and hospital stay were recorded. Follow-up evaluation was appropriate for the individual procedure. RESULTS: Initially, 35 cases were managed. There were 22 anti-reflux procedures, 9 Heller myotomies, 1 pyloroplasty, 1 distal pancreatectomy with splenectomy, 1 esophagectomy with intrathoracic anastomosis, and 1 diagnostic laparoscopy. The operative times ranged from 88 to 458 min. The robot use times were between 16 and 185 min. There were no device-related complications. CONCLUSIONS: Computer-enhanced robotic telesurgery is a safe and effective treatment method for a variety of diseases of the proximal gastrointestinal tract. Further study is needed to determine the benefits of this approach as compared with current technology.

Computer-assisted robotic heller myotomy: initial case report.

PURPOSE: Our objective was to determine the efficacy of computer-assisted robotic laparoscopic Heller myotomy. METHODS: A 76-year-old woman with a significant history of achalasia was evaluated for laparoscopic Heller myotomy. The daVinci surgical system was used throughout the procedure. RESULTS: Computer assistance allowed scaling of hand motions from a range of 2:1 to 5:1. Successful dissection of the esophageal musculature was accomplished, and a Toupet-type fundoplication was performed. The patient was discharged from the hospital the day after surgery with five port incisions, each <1 cm. CONCLUSIONS: Telemanipulator computer-assisted surgical devices may have applications in procedures that require advanced and finely tuned motions, such as Heller myotomy. The benefits of extra magnification and three-dimensional imaging can help prevent esophageal perforation and identify residual circular muscle fibers.

Long term evaluation of septic arthritis in hemophilic patients.

Before 1983, septic arthritis was rare in patients with hemophilia. With the advent of human immunodeficiency virus infection in the hemophilia population, many centers noted an increasing incidence of patients with septic arthritis. Fifteen septic joints in 10 patients with severe hemophilia were documented. Eight patients were human immunodeficiency virus positive, 1 was human immunodeficiency virus negative, and 1 was not tested. The diagnosis was delayed in 5 patients because the symptoms are similar to an acute hemarthrosis. An elevated temperature was common. The white blood cell count was elevated in only 1/3 of the infections, being modified by human immunodeficiency virus infection. Associated risk factors included infected angioaccess catheters (2), pneumonia (2), and generalized sepsis (1). All but 1 joint responded to appropriate antibiotics and either repeated aspiration or arthrotomy. However, 6 patients died of acquired immunodeficiency syndrome from 2 to 109 months after infection. Three patients are alive 29, 86, and 96 months, respectively, after infection.

Immunologic aspects of scleroderma.

Recent investigations of immunologic events in systemic sclerosis focus on the identification of which immune system cells are participating in the disease process, what antigens are stimulating the T and B cells, which cytokines are involved, and which cell adhesion molecules promote cell-cell and cell-extracellular matrix interactions. Increased numbers of gamma/delta and activated CD4+ T cells are present in involved skin of line-200 chickens, an animal model of systemic sclerosis. CD4+ T cells from patients with systemic sclerosis are stimulated by human type I collagen, and immunoglobulins from some patients with systemic sclerosis bind retroviral proteins, the terminal galactosyl (alpha 1-3)-galactose disaccharide of laminin, or a 138 amino acid region of the PM-Scl antigen. The development of an anticentromere antibody response in patients with systemic sclerosis appears to require the presence of a polar amino acid at position 26 in the antigen-binding cleft of the HLA-DQB1 molecule. Interleukin-2, interleukin-4, interleukin-6, and transforming growth factor-beta have been implicated as cytokines that may be involved in the pathogenesis of systemic sclerosis. Increased expression of intercellular adhesion molecule 1 (ICAM-1) on systemic sclerosis fibroblasts is responsible for increased binding of T cells to those fibroblasts through ICAM-1/lymphocyte function-associated antigen 1 interactions. beta 1 and beta 2 integrins, ICAM-1, and endothelial leukocyte adhesion molecule 1 all may be involved in the homing of lymphocytes to involved skin in patients with systemic sclerosis.

Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis.

OBJECTIVE: To determine the clinical and serologic risk factors for digital ischemic events in patients with systemic sclerosis (SSc). METHODS: Retrospective review of clinical and laboratory data and review of current clinical status of 98 patients with SSc, seen between 1985 and 1990. RESULTS: Amputation of 1 or more digits due to ischemia occurred in 20.4% of the patients; 9.2% had multiple digit loss. Sclerodactyly alone and anticentromere antibody (ACA) were associated with loss of 1 or more digits. Age, smoking status, duration of disease, or duration of Raynaud's phenomenon were not predictive for loss of digits. CONCLUSION: Patients with limited SSc who are positive for ACA have an increased risk of major peripheral vascular occlusive disease.

Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha, and interferon-gamma levels in sera from patients with scleroderma.

OBJECTIVE: To determine whether interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-4, interferon-gamma (IFN gamma), IL-6, and tumor necrosis factor alpha (TNF alpha) are detected more frequently in sera from scleroderma patients than in sera from controls. METHODS: Serum concentrations of these cytokines were measured in 78 scleroderma patients and 73 controls, using enzyme-linked immunosorbent assay, radioimmunoassay, and bioassay techniques. RESULTS: IL-2, IL-4, and IL-6 were each detected more frequently in sera from scleroderma patients than in sera from controls. TNF alpha and IL-1 alpha were found with equal frequency in patient and control sera. IL-1 beta and IFN gamma were not detected in any sera. CONCLUSION: IL-2, IL-4, and IL-6 may be among the cytokines that contribute to the disease process in scleroderma patients. To our knowledge, this is the first report of elevated serum IL-4 levels in human disease.

Spontaneous and clastogen induced chromosomal breakage in scleroderma.

Spontaneous and clastogen induced chromosomal damage was evaluated in lymphocytes of 10 patients with scleroderma and 21 controls. Peripheral blood lymphocytes from patients with scleroderma not only had elevated rates of spontaneous chromosomal damage (p = 0.002), but also bleomycin induced (p = 0.041), streptonigrin induced (p = 0.035), and 4-nitroquinoline-1-oxide induced (p = 0.032) chromosomal breakage. Our findings suggest that scleroderma lymphocytes may have a generalized susceptibility to DNA damage caused by free radicals.

Vertebral osteomyelitis caused by Nocardia asteroides: report and review of the literature.

A 65-year-old man with 9 months of radicular lower back pain was admitted for treatment of presumed malignancy of the lumbar spine. Lumbar radiographs showed destruction of the L4-L5 endplates and obliteration of the disc space, which was more compatible with an infectious process. After 2 different closed biopsy specimens failed to reveal an etiologic organism, N. asteroides was cultured from an open biopsy sample of the affected vertebrae. This and 8 other cases in the English literature of vertebral osteomyelitis caused by N. asteroides are reviewed.

Musculoskeletal syndromes associated with acne.

The acne conglobata (AC)-, acne fulminans (AF)-, and isotretinoin-associated musculoskeletal syndromes are three distinct clinical entities. The AC-associated musculoskeletal syndrome occurs primarily in black men over the age of 22, who develop sacroilitis with or without a peripheral arthropathy. In contrast, the AF-associated musculoskeletal syndrome is found almost exclusively in white male teenagers. Fever, weight loss, and arthralgias are prominent components of this syndrome. A unique feature of the AF-associated musculoskeletal syndrome is osteolytic lesions that occur most frequently in the clavicle, sternum, long bones, and ilium. The isotretinoin-associated musculoskeletal syndrome occurs with equal frequency in male and female acne patients. Mild, transient myalgias and arthralgias are very common and do not require discontinuation of isotretinoin therapy. Asymptomatic, small, hyperostotic lesions of the spine occur in approximately 10% of acne patients with the isotretinoin-associated musculoskeletal syndrome.

Increased expression of intercellular adhesion molecule 1 on the fibroblasts of scleroderma patients.

The surface expression of intercellular adhesion molecule 1 (ICAM-1) and class I and class II major histocompatibility complex molecules on cultured dermal fibroblasts from 7 scleroderma patients and 6 control donors was compared. Scleroderma fibroblast lines contained 41.0 +/- 3.0% (mean +/- SEM) cells with high levels of ICAM-1 expression (ICAM-1-high), whereas 26.9 +/- 1.5% of control fibroblasts were ICAM-1-high (P = 0.0003). There were no differences in the expression of class I and class II molecules. ICAM-1-high and ICAM-1-low fibroblasts produced equal amounts of total protein and procollagen. The increase in the number of ICAM-1-high fibroblasts in scleroderma patients may facilitate T cell activation and lymphokine production, and thus indirectly contribute to the fibrotic process.

Function of autoreactive T cells in immune responses.

We have constructed a model (Fig. 2) to explain the activation and regulation of autoreactive T cells by antigen. Antigen priming appears to be important for both antigen-specific and autoreactive T cells. Once activated, these T cells have the capacity to stimulate B cells to produce antibody in a very similar manner. It is possible that these two types of T cells work in concert to maintain an active immune response. Under circumstances where antigen-specific T-cell help may be limiting, autoreactive T cells may function to enhance B-cell responses. In addition, antigen appears to activate the regulatory mechanisms that are important for down-regulating the B-cell antibody response. Carrier-specific T-suppressor cells are antigen-specific in their activation but can be antigen-nonspecific in their effector function. In this way the regulatory mechanism driven by antigen can function to inactivate the antigen-specific and the autoreactive T-cell activation of B cells.