Protective role of collaterals in patients with coronary artery occlusion

We reviewed the clinical, hemodynamic and angiographic data of 105 patients with right coronary artery occlusion and of 82 patients with left anterior descending coronary artery occlusion, subdivided into 3 groups by the presence and quality of collaterals to the occluded coronary (absent, poor or good collaterals). We found that patients with right coronary artery occlusion and good collaterals had a lower frequency of diaphragmatic myocardial infarction (60%) than patients with absent collaterals (100%) (P < 0.01). In addition, in patients with old diaphragmatic myocardial infarction, both poor and good collaterals were associated with a lower frequency of severe asynergy of the diaphragmatic left ventricular segments at left ventriculography (54% and 14%, respectively), compared to patients with no collaterals to the right coronary artery (92%, P < 0.02 vs. poor collaterals, P < 0.001 vs. good collaterals). In contrast, in patients with left anterior descending coronary artery occlusion, the presence of either poor or good collaterals to the left anterior descending coronary artery was not associated with a lower frequency of old anterior myocardial infarction, or, in patients with old anterior myocardial infarction, with a less severe asynergy of the anterior left ventricular segments.Our results suggest that collaterals are effective in protecting the diaphragmatic left ventricular wall in patients with right coronary artery occlusion, but not the anterior left ventricular wall in patients with left anterior descending coronary artery occlusion.     

Differential effect of weight loss on insulin resistance in surgically treated obese patients

PURPOSE: To compare the effects of equivalent weight loss induced by two bariatric surgical techniques on insulin action in severely obese patients. METHODS: Eighteen nondiabetic patients with severe obesity (mean [+/- SD] body mass index: 53.5 +/- 9.0 kg/m(2)) and 20 sex- and age-matched lean subjects (body mass index: 23.8 +/- 3.0 kg/m(2)) underwent metabolic studies, including measurement of insulin sensitivity by the insulin clamp technique. Patients then underwent either vertical banded gastroplasty with Roux-en-Y gastric bypass, or biliopancreatic diversion, and were restudied at 5 to 6 months and again at 16 to 24 months postsurgery. RESULTS: At baseline, patients were hyperinsulinemic (194 +/- 47 pmol/L vs. 55 +/- 25 pmol/L, P < 0.0001), hypertriglyceridemic (1.56 +/- 0.30 mmol/L vs. 0.78 +/- 0.32 mmol/L, P < 0.0001), and profoundly insulin resistant (insulin-mediated glucose disposal: 20.8 +/- 4.4 micromol/min/kg fat-free mass vs. 52.0 +/- 10.1 micromol/min/kg, P < 0.0001) as compared with controls. Weight loss by the two procedures was equivalent in both amount (averaging -53 kg) and time course. In the gastric bypass group, insulin sensitivity improved (23.8 +/- 6.0 micromol/min/kg at 5 months and 33.7 +/- 11.3 micromol/min/kg at 16 months, P < 0.01 vs. baseline and controls). In contrast, in the biliopancreatic diversion group, insulin sensitivity was normalized already at 6 months (52.5 +/- 12.4 micromol/min/kg, P = 0.72 vs. controls) and increased further at 24 months (68.7 +/- 9.5 micromol/min/kg, P < 0.01 vs. controls) despite a persistent obese phenotype (body mass index: 33.2 +/- 8.0 kg/m(2)). CONCLUSION: In surgically treated obese patients, insulin sensitivity improves in proportion to weight loss with use of predominantly restrictive procedures (gastric bypass), but is reversed completely by predominantly malabsorptive approaches (biliopancreatic diversion) long before normalization of body weight. Selective nutrient absorption and gut hormones may interact with one another in the genesis of the metabolic abnormalities of obesity.     

Clinical review: Growth hormone and cardiovascular risk factors

The aim of this article is to review the lessons on the relationship between GH and the principal metabolic cardiovascular risk factors that we learned from studies of GH deficiency (GHD) in the adult. The lesson that "organic" GHD has taught us is that primary impairment in the GH/IGF-I axis may lead to a high-risk cardiovascular profile that is partially reversible during GH replacement. Waiting for the definitive demonstration that GH substitution may reduce cardiovascular mortality in these patients, we find that data so far reported are encouraging and indicate in the beneficial cardiovascular effects of GH one of the major factors supporting this type of treatment in hypopituitary GHD adults. Moreover, enough evidence from GHD studies has been produced to suggest a physiological role for the GH/IGF-I axis in the control and regulation of several metabolic cardiovascular risk factors.     

Long-term follow-up after endoscopic biliary stent placement for bile duct strictures from laparoscopic cholecystectomy

BACKGROUND/AIMS: The outcome of endoscopic biliary stent insertion for postoperative bile duct stenosis was retrospectively evaluated. METHODOLOGY: Fifty-seven patients with biliary stenosis from laparoscopic cholecystectomy were included from February 1992 to January 2000. One to three stents were inserted for an average of 12.4 months, with stent exchange every 3 months to avoid cholangitis caused by clogging. RESULTS: Successful stent insertion was achieved in 43/57 (75.4%) patients. Stent insertion failed in 10 patients with complete and in 4 patients with incomplete biliary obstruction. Early complications occurred in 4 patients. Late complications occurred in 5/43 patients. Five patients experienced recurrence of stenosis. CONCLUSIONS: Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis.     

Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells

Adiponectin limits the development of liver fibrosis and activates adenosine monophosphate-activated protein kinase (AMPK). AMPK is a sensor of the cellular energy status, but its possible modulation of the fibrogenic properties of hepatic stellate cells (HSCs) has not been established. In this study, we investigated the role of AMPK activation in the biology of activated human HSCs. A time-dependent activation of AMPK was observed in response to a number of stimuli, including globular adiponectin, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), or metformin. All these compounds significantly inhibited platelet-derived growth factor (PDGF)-stimulated proliferation and migration of human HSCs and reduced the secretion of monocyte chemoattractant protein-1. In addition, AICAR limited the secretion of type I procollagen. Knockdown of AMPK by gene silencing increased the mitogenic effects of PDGF, confirming the negative modulation exerted by this pathway on HSCs. AMPK activation did not reduce PDGF-dependent activation of extracellular signal-regulated kinase (ERK) or Akt at early time points, whereas a marked inhibition was observed 24 hours after addition of PDGF, reflecting a block in cell cycle progression. In contrast, AICAR blocked short-term phosphorylation of ribosomal S6 kinase (p70(S6K)) and 4E binding protein-1 (4EBP1), 2 downstream effectors of the mammalian target of rapamycin (mTOR) pathway, by PDGF. The ability of interleukin-a (IL-1) to activate nuclear factor kappa B (NF-kappaB) was also reduced by AICAR. CONCLUSION: Activation of AMPK negatively modulates the activated phenotype of HSCs.     

Rehabilitation of Fecal Incontinence After Sphincter-Saving Surgery for Rectal Cancer: Encouraging Results

Purpose  Some patients, having undergone sphincter-saving operations for rectal cancer, may suffer from fecal incontinence. This study was designed to evaluate the results of rehabilitative treatment in patients with fecal incontinence after sphincter-saving operations and to identify the negative factors that influence therapeutic success. Methods  Between January 2000 and June 2007, 88 incontinent patients (54 women; age range, 47–73 years; 69 had received a low anterior rectal resection; 19 a straight coloanal anastomosis) were included in the study. After a preliminary clinical evaluation, including the Wexner Incontinence Scale score, anorectal manometry was performed. All 88 patients underwent rehabilitative treatment according to the “multimodal rehabilitative program” for fecal incontinence. At the end of program, all 88 patients were reassessed by means of a clinical evaluation and anorectal manometry; their results were compared with the clinical and manometric data from ten healthy control subjects. Postrehabilitative Wexner Incontinence Scale scores were used for an arbitrary schedule of patients divided into three classes: Class I, good (score ≤3); Class II, fair (score >3 to ≤6); Class III, poor (score >6). Results  After rehabilitation, there was a significant improvement in the overall mean Wexner Incontinence Scale score (P < 0.03) for both surgical operation types (low anterior rectal resection: P < 0.05; coloanal anastomosis: P < 0.02). Only 21 patients (23.8 percent) were symptom-free, and 37 (42 percent) were considered Class III. A significant postrehabilitative direct correlation was found between: 1) Wexner Incontinence Scale score and degree of genital relaxation (rρ _s 0.78; P < 0.001); 2) Wexner Incontinence Scale score and irradiation (rρ _s 0.72; P < 0.01); and 3) Wexner Incontinence Scale score and pelvic (rρ _s 0.65; P < 0.01) or anal surgery (rρ _s 0.68; P < 0.01). No significant differences were found between prerehabilitative and postrehabilitative anal pressures in low anterior rectal resection and coloanal anastomosis patients. Conclusions  After rehabilitation, some patients become symptom-free, many patients show an improvement in the Wexner Incontinence Scale score, and others exhibit the highest grades of fecal incontinence. Genital relaxation, radiotherapy, and previous pelvic, and/or anal surgery are impeding factors to rehabilitative success.     

The UDCA dosage deficit: a fate shared with CDCA

Ursodeoxycholic acid (UDCA) is used both as the treatment of choice in many cholestatic syndromes and as complementary therapy in many liver diseases. However, few dose-finding studies exist, and none has evaluated the efficacy and long-term safety of UDCA therapy in primary biliary cirrhosis (PBC). There is an open debate about UDCA's impact on the natural history of PBC, and no universal evidence of benefits on the major endpoint exists. This is perhaps due to a UDCA dosage deficit. Most clinical trials on PBC therapy have used conservative dosages of UDCA similar to those of chenodeoxycholic acid (CDCA) used for dissolution of gallstones. It may be necessary to re-evaluate the dosage of UDCA that provides the most effective treatment.     

Worrisome Trend of New Multiple Mechanisms of Linezolid Resistance in Staphylococcal Clones Diffused in Italy

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).     

Differential Immunohistochemical Expression of Syndecan-1 and Tumor Necrosis Factor Alpha in Colonic Mucosa of Patients with Crohn’s Disease

Tumor necrosis factor alpha (TNFα) in intestinal mucosa plays a key role in the inflammation characterizing Crohn’s disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFα and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFα and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFα and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFα in CD. In conclusion, TNFα and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFα.