Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones.

CONTEXT: In obese patients with type 2 diabetes (T2DM), Roux-en-Y-gastric-bypass (RYGB) and sleeve gastrectomy (SLG) improve glycemic control. OBJECTIVE: The objective of this study was to investigate the mechanisms of surgery-induced T2DM improvement and role of gastrointestinal hormones. PATIENTS, SETTING, AND INTERVENTION: In 35 patients with T2DM, we performed a mixed-meal test before and 15 days and 1 year after surgery (23 RYGB and 12 SLG). MAIN OUTCOME MEASURES: Insulin sensitivity, ß-cell function, and amylin, ghrelin, PYY, pancreatic polypeptide (PP), glucagon, and glucagon-like peptide-1 (GLP-1) responses to the meal were measured. RESULTS: T2DM remission occurred in 13 patients undergoing RYGB and in 7 patients undergoing SLG. Similarly in the RYGB and SLG groups, ß-cell glucose sensitivity improved both early and long term (P < .005), whereas insulin sensitivity improved long term only (P < .006), in proportion to body mass index changes (P < .001). Early after RYGB, glucagon and GLP-1 responses to the meal increased, whereas the PP response decreased. At 1 year, PYY was increased, and PP, amylin, ghrelin, and GLP-1 were reduced. After SLG, hormonal responses were similar to those with RYGB except that PP was increased, whereas amylin was unchanged. In remitters, fasting GLP-1 was higher (P = .04), but its meal response was flat compared with that of nonremitters; postsurgery, however, the GLP-1 response was higher. Other hormone responses were similar between the 2 groups. In logistic regression, presurgery ß-cell glucose sensitivity (positive, P < .0001) and meal-stimulated GLP-1 response (negative, P = .004) were the only predictors of remission. CONCLUSIONS: RYGB and SLG have a similar impact on diabetes remission, of which baseline ß-cell glucose sensitivity and a restored GLP-1 response are the chief determinants. Other hormonal responses are the consequences of the altered gastrointestinal anatomy.

The role of beta-cell function and insulin sensitivity in the remission of type 2 diabetes after gastric bypass surgery.

CONTEXT: Bariatric surgery can induce remission in a high proportion of severely obese patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: Our objective was to investigate predictors and mechanisms of surgery-induced diabetes remission. PATIENTS AND SETTING: Forty-three morbidly obese subjects (body mass index = 45.6 ± 5.0 kg/m(2)), 32 with T2DM and 11 nondiabetic [normal glucose tolerance (NGT)], participated at a clinical research center. INTERVENTION: Patients underwent Roux-en-Y gastric bypass. MAIN OUTCOME MEASURES: Diabetes remission and ß-cell function were evaluated. RESULTS: Subjects were tested before and 45 d and 1 yr after surgery. Weight decreased similarly in T2DM and NGT (-39 kg at 1 yr, P < 0.0001). Insulin sensitivity improved in both groups in proportion to the changes in body mass index but remained lower in T2DM than NGT (386 ± 91 vs. 479 ± 89 ml/min · m(2), P < 0.01). Based on glycosylated hemoglobin and oral glucose testing, diabetes had remitted in nine patients at 45 d and in an additional 16 at 1 yr. In T2DM, ß-cell glucose sensitivity increased early after surgery but was no further improved and still abnormal at 1 yr [median, 48 (coefficient interval, 53) pmol/min · m(2) · mm vs. median, 100 (coefficient interval, 68) of NGT, P < 0.001]. Baseline ß-cell glucose sensitivity was progressively worse in early remitters, late remitters, and nonremitters (median, 54[coefficient interval, 50] vs. median, 22[coefficient interval, 26] vs. median, 4[coefficient interval, 10] pmol/min · m(2) · mm) and, by logistic regression, was the only predictor of failure [odds ratio for bottom tertile = 7.9 (95% confidence interval = 1.2-51.9); P = 0.03]. CONCLUSIONS: In morbid obesity, Roux-en-Y gastric bypass causes rapid and profound metabolic adaptations; insulin sensitivity improves in proportion to the weight loss, and ß-cell glucose sensitivity increases independently of weight loss. Over a period of 1 yr after surgery, diabetes remission depends on the starting degree of ß-cell dysfunction.

[Clinical-diagnostic and therapeutic considerations in a rare case of mesenteric cyst]. / Considerazioni clinico-diagnostiche e terapeutiche su un raro caso di cisti mesenterica.

The authors report a rare case of mesenteric cyst in a 36 years old woman. These cysts have a pathogenesis that primarily may be ectopic lymphatic tissue and their most common site is in the small bowel mesentery, especially of the ileum. In the case reported the cyst was located in the right mesocolon. Mesenteric cysts can appear as chronic abdominal pain, a painless abdominal mass, or acute abdomen. Diagnostic aids include abdominal computed tomography and sonography, that usually make diagnosis of mesenteric cyst. Treatment of choice is enucleation; resection of the adjacent bowel may occasionally be necessary.

[Efficacy of continuous intercostal analgesia versus epidural analgesia on post-thoracotomy pain]. / Efficacia del blocco analgesico intercostale continuo versus l'analgesia epidurale nel dolore post-toracotomico.

The authors compare the efficacy of epidural morphine analgesia with continuous intercostal extrapleural block using bupivacaine 0.5% after thoracotomy. They affirm that antalgic treatment in thoracotomised patients is the most important factor in preventing the onset of major complications that may negatively influence the results of surgery. The efficacy of the analgesic techniques examined was evaluated using El-Baz's visual analogic scale of pain, through the analysis of spirometric values and on the incidence of postoperative complications. The authors demonstrate that the extrapleural continuous nerve block is a reliable method of post-thoracotomic analgesia.

[CT-guided FNA in the diagnosis of lung opacities. Our experience]. / La FNA-CT guidata nella diagnosi delle opacità polmonari. Nostra esperienza.

Between January 1989 and December 1994 we accomplished 130 CT-guided transthoracic fine needle aspirations (FNA) in 120 patients. Ten patients underwent a second FNA because of the negativity and doubts of the first. Diagnosis was targeted in 114 (95%) patients and 89% showed cytological evidence of malignancy. FNA-CT guided is reliable in the diagnosis of lung cancer, but less accurate in excluding diagnosis of malignancy. In our experience FNA had an accuracy with regard to lung cancer, of 92%. Sensitivity and specificity were respectively 93.8% and 100%. There were 6 false negative and 9 very negative. All patients should have bronchoscopy rather than FNA as the initial diagnostic procedure and perform it only in the absence of endobronchial lesions and malignant cells obtained with cytologic sputum or fiber bronchoscopy. In our experience 91 patients have lung cancer and thoracotomy was performed in 21% with confirm of diagnosis. FNA offers several advantages over other diagnostic procedures used in the evaluation of patients with intra-thoracic nodules and masses. The uses of small needles (20-22 gauge) and CT-guide has practically eliminated the risk of major haemorrhage. Deep and superficial lesions of the lung may be approached safely with FNA-CT guided and complications are no fatalities. Pneumothorax occurred in our experience in 5 cases and no occurred a chest drainage.

Diverse properties of external and internal forms of yeast invertase derived from the same gene.

It has been shown by genetic analysis that the external and internal invertases from Saccharomyces cerevisiae share a common structural gene [Taussig, R., & Carlson, M. (1983) Nucleic Acids Res. 11, 1943-1954]. However, the only amino acid composition of these two forms of invertase reported to date has revealed extensive differences [Gascon, S., Neumann, N.P., & Lampen, J.O. (1968) J. Biol. Chem. 243, 1573-1577]. We have found from amino acid analyses of both enzymes and sodium dodecyl sulfate-polyacrylamide gel analysis of their cyanogen bromide peptides that they are most likely identical in their amino acid sequence. However, the invertases exhibit dramatically different physical properties, particularly in their stability. The most striking difference was in their renaturation following guanidine treatment where it was shown that inactivated external invertase could be renatured completely. Endo-beta-N-acetylglucosaminidase H treated external invertase was restored to 40% of its original activity while internal invertase remained completely inactive. The observed differences may be attributed to the presence and absence of the oligosaccharide moiety in the external and internal invertases, respectively.

Complete amino acid sequence of an allosteric enzyme, T2 bacteriophage deoxycytidylate deaminase.

The amino acid sequence of deoxycytidylate deaminase isolated from T2 phage-infected Escherichia coli has been determined. The enzyme is a hexamer, consisting of identical polypeptide subunits, each composed of 188 amino acids with a calculated Mr = 20,560. The primary structure was established by automatic Edman degradation of the intact carboxymethylated protein and of peptides derived from the protein by cleavage with cyanogen bromide, trypsin, chymotrypsin, the Staphylococcus aureus V8 protease, and 2-(2-nitrophenylsulfenyl)-3-methyl-3-bromoindolenine. Knowledge of the primary structure of deoxycytidylate deaminase should aid in determining the allosteric binding site of the negative effector, dTTP, recently reported (Maley, F., and Maley, G.F. (1982) J. Biol. Chem. 257, 11876-11878), and eventually that of the enzyme's positive regulator, dCTP, as well as its substrate. The deaminase has been crystallized through the use of polyethylene glycol; a scanning electron micrograph is presented.

The primary structure of Lactobacillus casei thymidylate synthetase. II. The complete amino acid sequence of the active site peptide, CNBr 4.

The 102 amino acid residues of CNBr 4, the largest of 5 cyanogen bromide peptides from the Lactobacillus casei thymidylate synthetase were completely sequenced by means of limited tryptic, tryptic, chymotryptic, and staphylococcal protease peptides. CNBr 4 contains both of the cysteines in an enzyme subunit, with the 5-fluorodeoxyuridylate-reactive cysteine at residue 198 and the other at residue 244.

The primary structure of Lactobacillus casei thymidylate synthetase. I. The isolation of cyanogen bromide peptides 1 through 5 and the complete amino acid sequence of CNBr 1, 2, 3, and 5.

Thymidylate synthetase from Lactobacillus casei was S-carboxymethylated and degraded by treatment with cyanogen bromide. Although the protein contains 6 methionine residues, only 5 cyanogen bromide peptides were obtained due to the presence of 1 methionine on the NH2 terminus and another adjacent to a threonine residue which was resistant to cleavage. The peptides were isolated by differential extraction, first with ammonium acetate, then pyridine acetate, and finally the residue was solubilized with 50% acetic acid. Each peptide was further purified to homogeneity by Bio-Gel chromatography. The size of the peptides from the amino to carboxyl end of the enzyme subunit was CNBr 1, 4,100; CNBr 2, 10,300; CNBr 3, 8,100; CNBr 4, 11,800; CNBr 5, 2,200. The sum of the amino acid residues of the peptides is equal to the sum of the residues in an enzyme subunit, indicating that all of the CNBr peptides have been isolated. The CNBr-resistant methionine was located in CNBr 2 and the 5-fluoro-2'-deoxyuridine 5'-monophosphate binding site in CNBr 4. The holoenzyme molecular weight, based on the residue weights of the amino acids in the two equivalent subunits, is equal to 73,176. The complete sequence of each of the CNBr peptides, except for CNBr 4, which is presented in the following paper, is described.