Gastrointestinal function and eating behavior after gastric bypass and duodenal switch

BackgroundDuodenal switch provides greater weight loss than gastric bypass in severely obese patients; however, comparative data on the changes in gastrointestinal symptoms, bowel function, eating behavior, dietary intake, and psychosocial functioning are limited.MethodsThe setting for the present study was 2 university hospitals in Norway and Sweden. Participants with a body mass index of 50–60 kg/m² were randomly assigned to gastric bypass (n = 31) or duodenal switch (n = 29) and followed up for 2 years. Of the 60 patients, 97% completed the study. Their mean weight decreased by 31.2% after gastric bypass and 44.8% after duodenal switch. At inclusion and 1 and 2 years of follow-up, the participants completed the Gastrointestinal Symptom Rating Scale, a bowel function questionnaire, the Three-Factor Eating Questionnaire-R21, a 4-day food record, and the Obesity-related Problems scale.ResultsCompared with the gastric bypass group, the duodenal switch group reported more symptoms of diarrhea (P = .0002), a greater mean number of daytime defecations (P = .007), and more anal leakage of stool (50% versus 18% of participants, respectively; P = .015) after 2 years. The scores for uncontrolled and emotional eating were significantly and similarly reduced after both operations. The mean total caloric intake and intake of fat and carbohydrates were significantly reduced in both groups. Protein intake was significantly reduced only after gastric bypass (P = .008, between-group comparison). Psychosocial function was significantly improved after both operations (P = .23, between the 2 groups).ConclusionGastrointestinal side effects and anal leakage of stool were more pronounced after duodenal switch than after gastric bypass. Both procedures led to reduced uncontrolled and emotional eating, reduced caloric intake, and improved psychosocial functioning.     

Ki67 and 4F2 antigen expression as well as DNA synthesis predict survival at relapse/tumour progression in low-grade B-cell lymphoma

Previous work has shown that parameters of cell activation studied on lymphoma biopsies can be used to discriminate between low-grade and high-grade non-Hodgkin's lymphomas and to predict prognosis in the low-grade malignancy group alone. We have now examined expression of several activation antigens and indicators of DNA synthesis in 29 patients with low-grade malignant B-cell lymphomas at the time of primary diagnosis and later at relapse and/or tumour progression. At both times, the level of 4F2 antigen expression examined by flow cytometry on cells in suspension as well as the number of Ki67 antigen-positive cells examined by immunohistochemistry were predictive of patient survival. DNA synthesis estimated by (3H-TdR) thymidine incorporation was of prognostic value at the second biopsy only. These parameters were more sensitive than histological demonstration of morphological transformation in secondary high-grade lymphomas in identifying high-risk patients at repeated biopsy. We propose that Ki67 or 4F2 expression or a marker of DNA synthesis (such as 3H-TdR incorporation or labelling index) should be evaluated when repeated biopsies are performed, in order to select patients for whom aggressive chemotherapy may be considered.     

Vecuronium and danger of vagal induced cardiac arrest during laparotomy: A case report and literature review

Key words  vecuronium - bradycardia - cardiac arrest     

Action of opioid agonist-antagonist drugs on the pupil and nociceptive responses in mice

Opioid derivatives with mixed agonist-antagonist activities are becoming increasingly more popular in analgesia. We tested the mydriatic and analgesic activity of morphine in mice in comparison with similar effects of three agonist-antagonist agents: buprenorphine, butorphanol and nalbuphine. We also examined the antagonistic action of these three drugs by evaluating the analgesia and mydriasis in animals pretreated with morphine.The analgesic effect was assayed using the hot plate method while the pupillary responses were measured with a binocular operating microscope.Morphine produced dose-dependent mydriasis and analgesia in mice. The morphine-type agent buprenorphine and two nalorphine-type agonist-antagonists, butorphanol and nalbuphine, caused agonistic mydriatic and analgesic effects, usually less effective then morphine. Buprenorphine proved to have higher agonist activity than butorphanol and nalbuphine. The difference between butorphanol and nalbuphine was not statistically significant.A correlation between the mydriatic and the analgesic activity, known to exist among opioid derivatives with agonist activity only, was also demonstrated in the three investigated agonist-antagonist agents.Morphine-induced mydriasis and analgesia were reversed by all three agonist-antagonist drugs, but buprenorphine is a significantly weak antagonist in comparison with butorphanol and nalbuphine. An antagonistic property (antimydriatic and antianalgesic effects after pretreatment with morphine) of both nalorphine-type investigated drugs was not statistically significant, except for the antianalgesic effect of nalbuphine in doses 1 and 3mg·kg^–1, which was higher in comparison with butorphanol.(Stav A, Rabinowitz R, Korczyn AD: Action of opioid agonist-antagonist drugs on the pupil and nociceptive responses in mice. J Anesth 6: 439–445, 1992)     

The metalloproteinase inhibitor TIMP-2 is down-regulated by androgens in LNCaP prostate carcinoma cells

Tissue inhibitors of metalloproteinases (TIMPs) have been shown to perform several biological functions in tumor promotion, principally by their action of inhibiting matrix metalloproteinases (MMPs) at different steps of the metastatic process. In particular, TIMP-2 is involved in a functional complex with the membrane-type 1 (MT1) MMP to convert the secreted MMP-2 progelatinase into the fully active proteolytic enzyme. We used the human, androgen-sensitive prostate carcinoma cell line LNCaP in coculture with the human osteosarcoma cell line OHS to experimentally address the possibility of androgen-dependent regulatory effects on the functional MT1-MMP/TIMP-2/MMP-2 complex upon interaction between prostate carcinoma and osteoblastic cells in metastasis of prostate cancer to bone. In the LNCaP cells a gradual, time-dependent decline in TIMP-2 mRNA expression was observed in the presence of the synthetic androgen analogue R1881 (100 nM), reaching ∼25% of the control level after 48 h of incubation. Consistent with this, the accumulation of secreted TIMP-2 in media from R1881-treated cells was significantly inhibited already after 3 h. Neither MMP-2 gelatinolytic activity nor expression of MT1-MMP was detected in LNCaP cells. In contrast, the OHS cells showed membrane-associated MT1-MMP expression as well as MMP-2 secretion. However, R1881 treatment of the LNCaP/OHS coculture model did not seem to change the overall proteolytic activity of the MT1-MMP/TIMP-2/MMP-2 complex. Hormonal control of TIMP-2 expression in prostate carcinoma cells has not been previously reported, but whether such regulation has any functional role in the development of osteoblastic metastases in prostate cancer is still unclear. This revised version was published online in July 2006 with corrections to the Cover Date.     

BMP-6 inhibits growth of mature human B cells; induction of Smad phosphorylation and upregulation of Id1

Background

Follicular dendritic cells (FDCs) play a central role in controlling B-cell response maturation, isotype switching and the maintenance of B-cell memory. These functions are based on prolonged preservation of antigen and its presentation in its native form by FDCs. However, when entrapping entire pathogens, FDCs can turn into dangerous long-term reservoirs that may preserve viruses or prions in highly infectious form. Despite various efforts, the ontogeny of FDCs has remained elusive. They have been proposed to derive either from bone marrow stromal cells, myeloid cells or local mesenchymal precursors. Still, differentiating FDCs from their precursors in vitro may allow addressing many unsolved issues associated with the (patho-) biology of these important antigen-presenting cells. The aim of our study was to demonstrate that FDC-like cells can be deduced from monocytes, and to develop a protocol in order to quantitatively generate them in vitro.

Results

Employing highly purified human monocytes as a starter population, low concentrations of Il-4 (25 U/ml) and GM-CSF (3 U/ml) in combination with Dexamethasone (Dex) (0.5 μM) in serum-free medium trigger the differentiation into FDC-like cells. After transient de-novo membrane expression of alkaline phosphatase (AP), such cells highly up-regulate surface expression of complement receptor I (CD35). Co-expression of CD68 confirms the monocytic origin of both, AP^pos and CD35^pos cells. The common leukocyte antigen CD45 is strongly down-regulated. Successive stimulation with TNF-α up-regulates adhesion molecules ICAM-1 (CD54) and VCAM (CD106). Importantly, both, AP^pos as well as AP^neg FDC-like cells, heterotypically cluster with and emperipolese B cells and exhibit the FDC characteristic ability to entrap functionally preserved antigen for prolonged times. Identical characteristics are found in monocytes which were highly expanded in vitro by higher doses of GM-CSF (25 U/ml) in the absence of Dex and Il-4 before employing the above differentiation cocktail.

Conclusion

In this work we provide evidence that FDC-like cells can be derived from monocytes in vitro. Monocyte-derived FDC-like cells quantitatively produced offer a broad utility covering basic research as well as clinical application.     

Is the brain water channel aquaporin‐4 a pathogenetic factor in idiopathic intracranial hypertension? Results from a combined clinical and genetic study in a Norwegian cohort

Purpose: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown aetiology. Patients with IIH usually suffer from headache and visual disturbances. High intracranial pressure despite normal ventricle size and negative MRI indicate perturbed water flux across cellular membranes, which is provided by the brain water channel aquaporin‐4 (AQP4). IIH could be associated with malfunctioning intracerebral water homeostasis and cerebrospinal fluid (CSF) reabsorption based on functional or regulatory alterations of AQP4. Methods: Clinical data, blood and CSF samples were collected from 28 patients with IIH. Clinical characteristics were assessed, and a genetic association study was performed by sequencing the AQP4 gene on chromosome 18. Genetic data were compared with 52 healthy controls and matched by age, sex and ethnicity. Chi‐square test and linear discriminant analysis (LDA) were used in the search of a genotype–phenotype association. Results: While the majority of patients responded to medical treatment, four required shunt application. All, except one, had a good visual outcome. The 24 AQP4 gene SNPs showed no association with IIH. Full cross‐validation of the LDA modelling resulted in only 55.1% correct classification of the cases and controls, with a corresponding estimated p‐value 0.37. Conclusions: Our genetic case–control study did not indicate an association between AQP4 gene variants and IIH. However, the theory of an etiopathogenic link between IIH and AQP4 is tempting, and discussed in this article. Association studies with large sample size are difficult to perform owing is the rarity of the condition.