Wireless high-frequency dorsal root ganglion stimulation for chronic low back pain: A pilot study.

OBJECTIVE: Evaluation of the efficacy of a wireless high-frequency stimulator placed over selected DRG of exiting nerve roots for the treatment of chronic low back pain. DESIGN: Feasibility. SUBJECTS: Six subjects with chronic, intractable back pain refractory to standard medical treatment. METHODS: Four stimulators (Freedom-4A) provided by Stimwave Technologies, were implanted over the DRG exiting nerve roots, bilaterally at both the T9 and L2 vertebral levels. Subjects were asked to evaluate stimulation independently with the devices turned on at T9 and subsequently L2 for each of 2 weeks. Subjects were then monitored for 8 weeks with the preferred stimulator. Pain reduction with the Visual Analog Scale (VAS), functionality with the Oswestry Disability Index (ODI), Patient Global Impression of Change (PGIC) and medication usage were evaluated. RESULTS: Four subjects preferred T9 stimulation with only one subject preferring stimulation at L2. One subject dropped out of the study before conclusion of the 4-week evaluation and is not included in this report. Average pain levels (n = 5) at 12-week post-implantation decreased with 61% for back pain and 56% for leg pain with a significant reduction in pain medication, including a 100% reduction in opioid pain medications. The average reduction in disability was 12%. Subjects reported an average impression of change of 6 (1 = no change, 7 = great deal better). CONCLUSIONS: Wireless high-frequency stimulation of the DRG is a viable option to treat chronic low back pain. Preliminary results show a subject preference for stimulation at the T9 vertebral level.

[Current Situation of Antibiotic Prophylaxis in Obesity and Metabolic Surgery - Data Analysis from the Study for Quality Assurance in Operative Treatment of Obesity in Germany]. / Aktueller Stand der Antibiotikaprophylaxe in der Adipositas- und metabolischen Chirurgie - Datenanalyse aus der Studie zur Qualitätskontrolle der operativen Therapie der Adipositas in Deutschland.

BACKGROUND: Since January 2005, the situation of metabolic and obesity surgery in Germany has been constantly evaluated by the German Bariatric Surgery Registry (GBSR). Data registration is performed using an internet online database with prospective data collection. All registered data were analysed in cooperation with the Institute of Quality Assurance at the Otto-von-Guericke University Magdeburg. METHODS: Data collection includes primary and revision/redo-procedures. A main focus of the current study is the analysis of data regarding the perioperative management, in particular, administration of antibiotics. RESULTS: Since 2005 a significant increase of primary bariatric procedures has been reported. For evaluation of the antibiotic regimen 12 296 primary operations including 684 balloons (BIB), 2950 gastric bandings (GB), 5115 Roux-en-Y-gastric bypasses (RYGBP), 120 Scopinaro's biliopancreatic diversions (BPD), 164 duodenal switches (DS), 3125 sleeve gastrectomies (SG) and 138 other procedures were analysed. In total 77.3 % of the patients with primary procedures received perioperative antibiotics. Patients without concomitant comorbidities received antibiotics significantly less often compared to those with comorbidities. Wound infection rates were comparable for patients who underwent either gastric banding or sleeve gastrectomy. CONCLUSION: Surgery has been accepted step by step as a treatment for morbid obesity and its comorbidities in Germany during the last few years. There is only little experience in the literature regarding antibiotic therapy as well as prophylaxis in bariatric surgery. Based on the results of the current study we recommend rather the selective than the routine use of antibiotics depending on different parameters, e.g., operative time, preoperative BMI and concomitant comorbidities.

[Comment on Gender-Specific Aspects in Obesity and Metabolic Surgery--Analysis of Data from the German Bariatric Surgery Registry]. / Kommentar zu genderspezifischen Aspekten in der Adipositas- und metabolischen Chirurgie--Daten der Qualitätssicherungsstudie für operative Therapie der Adipositas.

BACKGROUND: The current situation in obesity and metabolic surgery since January 2005 has been investigated with the help of the quality assurance study on surgical therapy for obesity = German Bariatric Surgery Registry (GBSR). The data were acquired and analysed in cooperation with the Institute for Quality Assurance in Surgical Medicine at the Otto-von-Guericke University. METHODS: Data acquisition was done with the help of an online database. On a voluntary basis, all obesity and metabolic surgical interventions since 2005 have been recorded. In addition to the surgical data, the findings of the yearly follow-up investigations were recorded. RESULTS: Since 2005 there have been 1,263 gastric balloon procedures, 11,840 sleeve gastrectomies, 13,722 Roux-en-Y gastric bypasses and 3999 gastric banding operations. The average age of the male patients in all interventions was significantly higher. The average BMI of female patients who received a gastric banding or a gastric balloon procedure was significantly lower than that of the male patients. Men exhibited a higher incidence of comorbidities than women. CONCLUSION: The number of obesity and metabolic surgical interventions in Germany is continuously increasing. The results of the study on surgical therapy for obesity (GBSR) reveal significant differences in the gender-specific incidence of preoperative comorbidities. postoperative complications and mortality. Further studies on gender-specific aspects are necessary in order to optimise patient selection and reduce the incidence of postoperative complications.

Bariatric surgery in adolescents and young adults--safety and effectiveness in a cohort of 345 patients.

OBJECTIVE: To examine the safety and effectiveness of adolescent bariatric surgery and to improve treatment recommendations for this age group. DESIGN: Prospective longitudinal registry. Since January 2005, patients undergoing bariatric surgery in Germany are enlisted in an online registry called 'study for quality assurance in obesity surgeries'. SUBJECTS: Adolescents and young adults up to the age of 21 years, operated from January 2005 to December 2010. MEASUREMENTS: Weight, BMI, comorbidities, complication rates. RESULTS: N=345 primary procedures were recorded by 58 hospitals. N=51 patients were under the age of 18 years. Follow-up information was available for 48% (n=167) of patients, with an average observation period of 544±412 days (median: 388 days). The most common surgical techniques were gastric banding (n=118, 34.2%), gastric bypass (n=116, 33.6%) and sleeve gastrectomy (n=78, 22.6%). Short-term complications (intra-operative; general postoperative; specific postoperative) were slightly lower for gastric banding (0.8%; 2.5%; 0.8%) than for gastric bypass (2.6%; 5.2%; 1.7%) or sleeve gastrectomy (0%; 9.0%; 7.7%). In accordance with published findings, weight and BMI reduction were lower for gastric banding (-28 kg; -9.5 kg m(-2)) compared to gastric bypass (-50 kg; -16.4 kg m(-2)) P< 0.001 or sleeve gastrectomy (-46 kg; -15.4 kg m(-2)) P< 0.001. Outcomes did not differ between the <18 and ≥18-year-old patients. CONCLUSION: Like in adults, bariatric surgery has low short-term complication rates and results in sustained weight loss in adolescents. However, the missing long-term observations prohibit a final conclusion about lasting effectiveness and safety. Clinical trials with structured follow-up programs and mechanisms to ascertain patient adherences are needed.

[Interdisciplinary European guidelines on metabolic and bariatric surgery]. / Interdisciplinární Evropská doporucení metabolické a bariatrické chirurgie.

In 2012, an outstanding expert panel derived from IFSO-EC (International Federation for the Surgery of Obesity - European Chapter) and EASO (European Association for the Study of Obesity), composed by key representatives of both Societies including past and present presidents together with EASOs OMTF (Obesity Management Task Force) chair, agreed to devote the joint Medico-Surgical Workshop of both institutions to the topic of metabolic surgery as a pre-satellite of the 2013 European Congress on Obesity (ECO) to be held in Liverpool given the extraordinarily advancement made specifically in this field during the past years. It was further agreed to revise and update the 2008 Interdisciplinary European Guidelines on Surgery of Severe Obesity produced in cooperation of both Societies by focusing in particular on the evidence gathered in relation to the effects on diabetes during this lustrum and the subsequent changes that have taken place in patient eligibility criteria. The expert panel composition allowed the coverage of key disciplines in the comprehensive management of obesity and obesity-associated diseases, aimed specifically at updating the clinical guidelines to reflect current knowledge, expertise and evidence-based data on metabolic and bariatric surgery.

[New data on quality assurance in bariatric surgery in Germany]. / Aktuelle Daten der Qualitätssicherungsstudie für operative Therapie der Adipositas in Deutschland.

BACKGROUND: Since January 1st 2005, the situation of bariatric surgery has been examined in Germany. All data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University of Magdeburg. METHODS: The voluntary data registration occurs in an internet online data bank. All primary bariatric procedures as well as re- and redo-procedures are documented. Follow-up data were collected once a year. Participation in the quality assurance study is obligatory for certificated centres. RESULTS: Since 2005 13,879 bariatric procedures have been performed at 83 hospitals. The number of primary procedures has increased from 596 in 2005 to 11,835 in 2010. Revisional surgery has been performed in 1,438 patients since 2005. Sleeve gastrectomy (SG) is the major procedure with 1,564 operations in 2010. The mean BMI was 48.8 kg/m². The incidence of comorbidities was 84.8%. CONCLUSION: Bariatric surgery has become more accepted in Germany. Beside the Roux-en-Y gastric bypass, sleeve gastrectomy is the most frequently performed operation. BMI and incidence of comorbidities are still high in comparison with literature values. Due to the lack of evidence, more randomised studies are necessary to standardise operative techniques and evaluate patient selection criteria. Quality assurance studies support a detailed analysis of these parameters.

Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2.

In the studies reported here, we have analyzed the production and consumption of T cell growth factor, more recently termed interleukin 2 (IL-2), as well as some cell-mediated immune functions, in murine strains [MRL, BXSB, NZB, and (NZB x NZWF1] manifesting systemic lupus erythematosus (SLE)-like syndromes. Young (4-6 wk) or old (4-8 mo) autoimmune or normal mice were studied and compared with regard to the following T cell functions in vitro after stimulation with concanavalin A (Con A): (a) mitogenic response; (b) IL-2 levels in culture supernates; and (c) the ability to respond to and adsorb IL-2. In addition, proliferative activity in the allogeneic mixed leukocyte culture and frequency of alloreactive cytotoxic T lymphocyte precursors (CTLp) were analyzed in some of these strains. Reduced Con A-induced mitogenic responses and IL-2 production appeared at 3-6 wk of age in the early, severe SLE developing strains MRL-Mp-lpr/lpr (MRL/l) and male BXSB and progressed thereafter. Similar defects appeared at a later stage in MRL/Mp-+/+ and (NZB x NZW)F1 hybrid mice, which develop late disease. Detailed analysis of cells from the enlarged lymph nodes and spleens of older MRL/l mice demonstrated that such cells: (a) responded poorly to Con A or allogeneic stimulator cells, even in the presence of exogenous IL-2; (b) did not suppress IL-2 production by normal spleen cells; (c) were relatively incapable of adsorbing or inactivating IL-2; and (d) had a markedly reduced anti-H-2b CTLp frequency in the mesenteric lymph nodes but a normal one in spleen. These results indicate that the proliferating Thy-1.2+, Lyt-1+ T cells in MRL/l mice are defective in their responses to mitogenic stimuli, in IL-2 production, and in expression of acceptor sites for IL-2. The relevance of these defects to the MRL/l disease as well as to the role of IL-2 in autoimmunity in general remains to be determined.

Surgical treatment of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease.

BACKGROUND: Overweight and obesity are the most significant risk factors for the development of hepatic steatosis, non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD) in children and adults. Both have been increasingly implicated in the genesis of hepatic fibrosis and cirrhosis. However, no consensus exists about whether weight reduction may reverse this process. METHODS: To assess the effect of obesity surgery on the histological evolution of NASH, diagnosed in 284 morbidly obese patients by routine liver biopsy ('first' biopsy) performed during bariatric surgery, we performed a 'second' biopsy after 18.6 +/- 8.3 months in 116 patients (109 female, 7 male). 68 patients underwent Roux-en-Y gastric bypass, 38 adjustable gastric banding and 16 biliopancreatic diversion with duodenal switch (BPD-DS). The second biopsy was taken during CHE (102) and relaparoscopy for suspected complications and revisional surgeries (12). All primary and secondary surgical procedures were done laparoscopically without intraoperative or postoperative major complications. All comorbidities were recorded pre- und postoperatively. RESULTS: From the first to the second biopsy, BMI decreased from 55.2 +/- 8.3 to 30.5 +/- 6.6 kg/m(2), arterial hypertension decreased from 65 to 43%, and type 2 diabetes decreased from 42 to 2%. On the first biopsy, non-alcoholic fatty liver disease (NAFLD) type 3 was observed in 186 patients (65.5%) and type 4 in 82 (28.9%). The second biopsy revealed complete regression of NAFLD in 89 patients (82.8%) and only 16 (13.8%) still had NAFLD type 1 (mild steatosis without inflammation). These two patients with NAFLD type 3 had adjustable gastric banding with insufficient weight loss (EWL <50%) in history. Complete regression of necroinflammatory activity was observed in 108 patients (93.1%). Among the 12 patients presenting fibrosis in the first biopsy, complete remission was observed in 10 and improvement in 2. Two patients with ascites during BPD-DS showed complete remission within 9-15 months. Two continued to show the same degree of fibrosis without evidence of disease activity. No worsening of steatosis, necroinflammatory activity or fibrosis was observed in any of the patients, and none progressed to cirrhosis. CONCLUSION: Obesity surgery improves steatosis, necroinflammatory activity and hepatic fibrosis in patients with morbid obesity and NASH. The improvement of all obesity-related comorbidities can be confirmed.

A nationwide survey on bariatric surgery in Germany--results 2005-2007.

BACKGROUND: Most studies on bariatric surgery outcomes are performed as clinical trials or reflect the clinical experience in single centers. The status of bariatric surgery in Germany has been examined since January 1st, 2005 with the cooperation of clinics and hospitals at the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University of Magdeburg (Germany). METHODS: In this prospective multicenter observational study, the data obtained for all primary bariatric procedures, including all repeated operations, performed on consecutive patients with morbid obesity at participating hospitals from 2005 to 2007 were prospectively collected using an Internet online data registry. In particular, perioperative characteristics, such as the spectrum of diagnostic measurements, type of surgical procedures, and short- and long-term outcomes, were investigated. RESULTS: During the study period, 629 surgical procedures were performed at 21 hospitals in 2005, 828 procedures at 32 hospitals in 2006, and 1,666 procedures at 35 hospitals in 2007. In 2005 and 2006, gastric banding was the most frequently performed operation, followed by the Roux-en-Y gastric bypass (RYGBP). In 2007, a RYGBP was carried out in 42.1% of all bariatric procedures. Among all patients, 74.4% were female. The mean body mass index (BMI) was 48.5 kg/m(2) in 2005, 48.4 kg/m(2) in 2006, and 48.0 kg/m(2) in 2007. Follow-up data after 12 months were available for 63.8% of the patients in 2005 and 2006; these data showed greater reduction of BMI after malabsorptive rather than restrictive bariatric procedures. The mortality was 0.1% (30 days) and 0.16% (overall). CONCLUSION: As indicated by the worldwide trend, there is an ongoing change from restrictive bariatric procedures to malabsorptive procedures and sleeve gastrectomy. Although the BMIs of German patients undergoing bariatric surgery appear to be substantially higher than those of patients from most other countries, there were no differences in intraoperative and short-term complications or in overall outcomes during follow-up when compared with published studies.

Results of sleeve gastrectomy-data from a nationwide survey on bariatric surgery in Germany.

BACKGROUND: Beginning January 1, 2005, the status and outcomes of bariatric surgery were examined in Germany. Data are registered in cooperation with the An-Institute of quality assurance in surgery at the Otto-von-Guericke-University Magdeburg. The objective of this study was to examine the morbidity and mortality rates secondary to sleeve gastrectomy (SG) in Germany since 2006. METHODS: Data collection occurred prospectively in an online data bank. All primary bariatric procedures performed were recorded as were all re-operations in patients that had already undergone a primary operation. Specific data compiled on the sleeve gastrectomy procedure were evaluated with a focus on operative details and complication rates. RESULTS: The total study cohort contains 3,122 patients. From January 2006 to December 2007, 144 sleeve gastrectomy procedures were performed in the 17 hospitals participating in the study. The mean body mass index (BMI) of all patients was 48.8 kg/m(2). The BMI of patients undergoing SG was 54.5 kg/m(2). In total, 73.8% of the patients were female and 26.2% of the patients were male. There were no significant differences between patients undergoing SG. The general complication rate after SG was 14.1%, and the surgical complication rate was 9.4%. The postoperative mortality rate was 1.4%. CONCLUSIONS: The complication rate during the first 2 years after SG in Germany is similar to that published in the literature. In order to improve the quality of bariatric surgery, an evaluation of data from a German multicenter trial is necessary to evaluate the position of SG in the bariatric algorithm.

Evidence of thromboembolism prophylaxis in bariatric surgery-results of a quality assurance trial in bariatric surgery in Germany from 2005 to 2007 and review of the literature.

BACKGROUND: Since January 1st, 2005, the current situation for bariatric surgery has been examined by means of a voluntary quality assurance study in Germany with a multicenter design in which 38 hospitals and surgical departments participated. The data are registered in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University of Magdeburg (Germany). METHODS: Data describing peri-interventional characteristics were prospectively documented in an internet online data registry. All primary bariatric procedures performed since January 1st, 2005, were registered. In addition, reoperations in patients who had previously undergone primary surgical intervention were included. As a representative excerpt from the overall prospective multicenter observational study on obesity surgery, data on the type, regimen, and time course of deep venous thrombosis (DVT) prophylaxis were documented. From the number and spectrum of complications, the incidences of clinically manifest DVT or pulmonary embolism (PE) were derived during the in-hospital course and follow-up in conjunction with the type of surgical procedure and body mass index (BMI). RESULTS: Overall, 3,122 bariatric procedures were performed at 38 German hospitals between January 2005 and December 2007. These procedures were subdivided into 2,869 primary operations and 253 revisions (sex ratio, male to female = 25.6:74.4%). The average BMI of all patients was 48.5 kg/m(2) in 2005, 48.4 kg/m(2) in 2006, and 48.0 kg/m(2) in 2007. In 2005 and 2006, gastric banding (GB) was the most commonly performed operation, followed by Roux-en-Y gastric bypass (RYGBP). In 2007, RYGBP was carried out in 42.1% of all bariatric procedures. Interestingly, the incidence of deep venous thrombosis (DVT) was only 0.06%, whereas PE occurred in 0.06% of patients only after hospital discharge. The DVT prophylaxis protocol used has been changed for the last 2 years: the majority of patients with a BMI above 50 kg/m(2) received low-molecular-weight heparin twice a day. CONCLUSION: In Germany, a trend from GB to sleeve gastrectomy (SG) and malabsorptive approach has been evaluated. This trend is associated with differences of the DVT prophylaxis regimen in the profile of bariatric surgical patients depending on BMI and the type of bariatric procedure. Despite the low incidence of DVT and pulmonary embolism (PE) detected, there is a lack of evidence on a reasonable regimen for sufficient DVT prophylaxis in bariatric surgery; instead, there are only recommendations from the guidelines and statements of a specific medical society. Therefore, prospective studies are necessary to determine the optimal DVT prophylaxis for bariatric surgical patients as well as obese patients undergoing surgery.

Electrical activity of the hypothalamus effects of intraventricular catecholamines.

The injection of epinephrine into the third ventricle of the rat brain causes a biphasic elevation and depression in the integrated multiple-unit electrical activity of the median eminence. Activity in the arcuate nucleus decreases after the injection of the catecholamines. These changes in the integrated multiple-unit electrical activity may be related to the secretion of hormones by the anterior pituitary gland.

Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis.

By genetically targeting tumorigenesis to specific hypothalamic neurons in transgenic mice using the promoter region of the gonadotropin-releasing hormone (GnRH) gene to express the SV40 T-antigen oncogene, we have produced neuronal tumors and developed clonal, differentiated, neurosecretory cell lines. These cells extend neurites, express the endogenous mouse GnRH mRNA, release GnRH in response to depolarization, have regulatable fast Na+ channels found in neurons, and express neuronal, but not glial, cell markers. These immortalized cells will provide an invaluable model system for study of hypothalamic neurosecretory neurons that regulate reproduction. Significantly, their derivation demonstrates the feasibility of immortalizing differentiated neurons by targeting tumorigenesis in transgenic mice to specific neurons of the CNS.

Dissociation of dopamine from its receptor as a signal in the pleiotropic hypothalamic regulation of prolactin secretion.

We have reviewed the literature, which supports an important role for dopamine withdrawal in the regulation of PRL secretion. Concentrations of dopamine in the hypophyseal portal circulation are sufficient to occupy the majority of dopamine receptors (1) and tonically suppress PRL secretion (20-26). Brief escapes from dopaminergic regulation associated with the secretion of PRL have been observed (37-41). Therefore, dopamine regulates secretion of PRL both by occupancy of, as well as dissociation from, specific D2 dopamine receptors. The rapid off rate from its receptor (2) is consistent with signals transmitted through brief decreases in dopamine concentration. The removal of dopamine for 10 min results in increases in intracellular cAMP and presumably activation of protein kinase A (39, 138) as well as activation of phospholipase C (137, 138) and protein kinase C (136). The removal of dopamine results directly in the release of PRL (37-41). Furthermore, the brief removal of dopamine results in the long-term potentiation of the PRL-releasing action of TRH (38-40). The potentiating action of dopamine withdrawal appears to be mediated by the activation of protein kinase A since pretreatment with VIP, a hormone that signals via protein kinase A, also potentiates the action of TRH (39). TRH stimulates PRL release via Ca2+/protein kinase C (177-184). The potentiating action of dopamine removal is selective for the Ca2+/protein kinase C pathway since dopamine removal does not potentiate the PRL-secreting action of VIP (38, 87, 92). The action of TRH is potentiated up to 30 min after the return of dopamine and the suppression of PRL to basal levels (38). In Fig. 10, dopamine dissociation from its receptor or VIP association to its receptor are shown separated by a broken line to indicate that by the time the potentiation of the action of TRH is tested, either dopamine is again occupying its receptor or VIP is no longer present. Therefore, the effect of protein kinase A activation is remembered by the lactotroph. We hypothesize that the responsiveness of the cell to TRH is potentiated by the phosphorylation of proteins by protein kinase A. Two potential substrates for protein kinase A are voltage-dependent Ca2+ channels and protein phosphatase inhibitors that would prolong the action of protein kinase C. When TRH occupies its receptor, intracellular Ca2+ levels are increased first from intracellular stores and subsequently by extracellular Ca2+ influx (187-189). Intracellular Ca2+ is mobilized by increased levels of IP3(128). Extracellular Ca2+ enters the lactotroph via voltage-dependent Ca2+ channels (189, 190).(ABSTRACT TRUNCATED AT 400 WORDS)

[Obesity - principles of surgical therapy]. / Adipositas - chirurgische Therapieprinzipen.

The prevalence of obesity and the number of surgeries for morbid obesity are increasing worldwide. Conservative therapy is largely ineffective in producing maintenance of weight loss in morbidly obese patients, and surgery is therefore increasingly considered as the only available option for these patients. Until approximately 15 years ago, many patients and physicians regarded bariatric surgery as dangerous because it required a large laparotomy and was associated with a relatively high risk of complications. Since laparoscopic techniques have become available, however, the number of patients referred for surgery has been increasing steadily. The principles of standard procedures are independent of access, whether open or laparoscopic. The pathophysiologic mechanisms are restriction, malabsorption, or a combination of both. New findings in the field of endocrine and humoral regulations have shown that surgical procedures can induce complex changes in the regulation of enterohormones. These mechanisms are the basis for metabolic effects, especially in cases of diabetes mellitus type 2. Obesity surgery is known to be the most effective and longest-lasting treatment for morbid obesity and many related conditions, but mounting evidence now suggests that it may also be among the most effective treatments for metabolic diseases and conditions such as type 2 diabetes, hypertension, high cholesterol, nonalcoholic fatty liver disease, and obstructive sleep apnea. Surgery for severe obesity goes far beyond weight loss; benefits include improved quality of life and extended life expectancy.

[Evidence of the Mini-/One-anastomosis-gastric-Bypass for being a standard procedure in obesity and metabolic surgery]. / Was macht den Mini­/One-anastomosis-gastric-Bypass zu einem Standardverfahren? ­ Evidenz zur Einschlingenrekonstruktion.

BACKGROUND: The Mini gastric bypass/One anastomosis gastric bypass (MGB/OAGB) was the third most commonly performed procedure in Germany, with 13.9% of all obesity and metabolic procedures in 2017 (StuDoQ|MBE). OBJECTIVE: This article reviews the currently published evidence for MGB/OAGB and the historical evidence on one anastomosis reconstruction. MATERIAL AND METHODS: A systematic literature search was performed in MEDLINE via PubMed and in Clinicaltrials.gov. from inception to 13 March 2018. A total of 35 studies met the inclusion criteria: 19 retrospective studies, 8 retrospective comparative trials, 2 systematic reviews, 3 systematic reviews and meta-analyses and 3 randomized clinical trials. A total of eight randomized clinical trials regarding MGB/OAGB are currently registered at Clinicaltrials.gov. RESULTS: In this study 35 eligible studies were included reporting data on >15,000 patients. The 30-day mortality rate ranged from 0-0.9% and severe complications needing intervention ranged from 0.8-7%, whereas perioperative morbidity ranged from 3.2-10.8%. The use of MGB/OAGB induced substantial weight loss with a total weight loss of 31-38% after 1 year and 23-32% after 5 years. Moreover, it showed a resolution or improvement in all major obesity-related diseases. Studies evaluating endpoints, such as end organ damage in diabetes, reduction of cardiovascular events and extending survival are missing and are available only for the Roux-en Y gastric bypass. CONCLUSION: This systematic review confirms the advantages of MGB/OAGB regarding weight loss and the antidiabetic effect in the short-term in comparison to Roux-en Y gastric bypass and sleeve gastrectomy. The role of bile reflux as a possible risk factor for neoplastic lesions in the long-term remains a point of discussion. The results of the registered randomized controlled trials will provide a better evidence in the future.

Frequency of intrinsic pulsatile gonadotropin-releasing hormone secretion is regulated by the expression of cyclic nucleotide-gated channels in GT1 cells.

Cultures of endogenous GnRH neurons and the GT1 GnRH neuronal cell line release GnRH in pulses (intrinsic pulsatile release) with an interpulse frequency similar to that seen in castrated animals. In both GT1 cells and transgenic rats, lowering cAMP levels by expression of a phosphodiesterase decreased the frequency of intrinsic GnRH pulsatility. We asked whether the cyclic nucleotide-gated cation (CNG) channels expressed in GT1 cells participated in cAMP modulation of intrinsic GnRH pulsatility. Because expression of the CNGA2 subunit is essential for formation of functional CNG channels, we developed an adenovirus (Ad) vector expressing a short interference RNA (siRNA) to the CNGA2 subunit (Ad-CNG-siRNA) or as an infection control, to the coding region of luciferase (Ad-Luc-siRNA). Infection with the Ad-CNG-siRNA of COS cells transfected with a CNGA2 expression vector significantly inhibited CNGA2 protein levels by 74% by Western blot. Infection of GT1-1 cells with Ad-CNG-siRNA resulted in a 68% decrease in the levels of CNGA2 mRNA, a 44% decrease in protein levels, and a clear decrease in immunostaining with an antibody to CNGA2. Infection of GT1-1 cells with Ad-CNG-siRNA decreased spontaneous Ca2+ oscillations compared with Ad-Luc-siRNA-infected or uninfected cells by 71%. Furthermore infection with Ad-CNG-siRNA resulted in a 2-fold increase in the interpulse interval in GnRH secretion (49.4+/-9.1 min) compared with uninfected cells (25.9+/-2.5 min) or Ad-Luc-siRNA (29.3+/-2.8 min)-infected cells. These data provide the first direct evidence that the CNG channel is a downstream signaling molecule in the regulation of the frequency of intrinsic GnRH pulsatility by cAMP.

Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2.

Granulocyte-macrophage colony-stimulating activity (GM-CSA) can be produced by a variety of normal cell types including mononuclear phagocytes, activated T lymphocytes, endothelial cells, and fibroblasts. Recent evidence shows that a major role of the monocyte-macrophage is the recruitment of environmental cells, i.e., fibroblasts, to produce GM-CSA. In this study we have identified interleukin 1 (IL-1) as a monokine that stimulates fibroblasts to produce and release GM-CSA and prostaglandin E2 (PGE2). Both purified human monocyte-derived IL-1 and human recombinant IL-1 (10(-10) M) can be substituted for monocyte-conditioned medium in stimulating fibroblast GM-CSA and PGE2 production. Both forms of IL-1 stimulate fibroblasts to produce GM-CSA and PGE2 in a dose-dependent fashion. The fibroblast-stimulating activity found in monocyte-conditioned medium was completely blocked by anti-IL-1. We conclude that monocytes produce IL-1, and that monocyte-derived IL-1 induces fibroblasts to produce GM-CSA and PGE2.