Surgical site infection surveillance in breast implants surgery

The results of long-term follow-up of surgical site infection (SSI) after aesthetical breast surgery are reported. 205 consecutive patients operated from 1/2000 to 3/2002 were followed for at least one year. Postoperative incidents were observed in 26 (12.7%) patients, including SSI in six (2.9%) patients. After surgery, the mean time to SSI was 113 days, with only two cases in the first postoperative month. In all SSI cases, no antibiotic prophylaxis had been given. The causative role of infectious agents in breast implant capsule occurrence is under investigation.     

Epidemiological investigation of a Serratia liquefaciens outbreak in a neurosurgery department

Between February 2001 and March 2003, 17 patients from the neurosurgery department of the University Hospital of Rangueil (Toulouse, Southern France) developed Serratia liquefaciens infections. Due to the atypical antibiotype displayed by the clinical isolates (i.e. gentamicin resistance), an outbreak was suspected. Molecular analysis carried out by pulsed-field gel electrophoresis demonstrated a genetic link for all patients. Furthermore, the patient who introduced the epidemic Serratia strain was also identified and shown to be related to the two epidemic peaks observed during the outbreak period. Investigation failed to reveal a reservoir among the antiseptics and soaps, or among the mechanical ventilators used. However, when the colonization of patients was investigated, positive carriage was observed and could be considered as a potential risk for the spread of the epidemic strain. Due to the delay between antibiotherapy and S. liquefaciens colonization, a selection effect had to be considered. Finally, implementation of hygiene measures was accompanied by control of the outbreak.     

Extracorporeal circulation as an additional method for cerebral protection in simultaneous carotid endarterectomy and coronary artery surgical revascularization

Surgical management of patients with concomitant carotid and coronary artery stenosis remains controversial. Our policy was always to perform at the same time carotid endarterectomy (CE) and coronary artery bypass grafting (CABG), but it was also considered that extracorporeal circulation (ECC), because of full heparinization, hemodilution, pulsatile flow, and hypothermia could provide better cerebral protection during CE. Retrospective data of 124 patients undergoing simultaneous CE and CABGs between January 1994 and December 2001 were reviewed. CE was performed prior to ECC in 65 patients (Group 1-mean age: 70.4 years; sex ratio: 49 male/16 female) and under ECC, prior to CABGs in 59 patients (Group 2-mean age: 69.9 years; sex ratio: 46 male/13 female). Overall hospital mortality was 7.3% (9/124): cardiac-related in 5 patients, or due to septicemia (1 patient), or ARD syndrome (1 patient), or stroke in two others. Univariate analysis demonstrated overweight, unstable angina, and emergency to be significant risk factors. Bilateral carotid stenosis was a significant risk factor of neurologic event when CE was performed prior to ECC (p < 0.05). In Group 1, mortality was 9.2% (6/65), and the incidence of neurologic events was 10.7% (7/65), and was responsible for two of the early deaths in patients with bilateral carotid stenosis. In Group 2, mortality was 5.1% (3/59) but never related to CE, while the neurologic morbidity was 1.7% (1 transient ischemic attack). It is concluded that (1) hospital mortality in patients undergoing simultaneous CE and CABGs was mainly cardiac-related. (2) The combined approach of both localizations appears to be mandatory, when carotid stenosis, even asymptomatic, was hemodynamically significant, or with ulcerative lesions likely to be responsible for embolism. (3) CE, first performed under ECC, appears to be a safe procedure, combining, in terms of cerebral protection, the benefits previously called up. This approach is all the more interesting when carotid stenosis is bilateral; hypothermia < or = 28 degrees C during the carotid clamping time is obviously the optimal method for cerebral protection when ipsilateral or contralateral supply is reduced, or even absent.     

Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes

To understand better the defects in the proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells in primary culture. When compared with cells from control subjects, myotubes established from patients with type 2 diabetes presented the same defects as those previously evidenced in vivo in muscle biopsies, including defective stimulation of phosphatidylinositol (PI) 3-kinase activity, decreased association of PI 3-kinase with insulin receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation during insulin stimulation. In contrast to IRS-1, the signaling through IRS-2 was not altered. Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes. Concomitantly, there was a higher basal mitogen-activated protein kinase (MAPK) activity in these cells, and inhibition of the MAPKs with PD98059 strongly reduced the level of serine 636 phosphorylation. These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells.     

Acute effect of the dual angiotensin-converting enzyme and neutral endopeptidase 24-11 inhibitor mixanpril on insulin sensitivity in obese Zucker rat

The aim of this study was to determine whether acute dual angiotensin-converting enzyme (ACE)/neutral endopeptidase 24-11 (NEP) inhibition could improve whole body insulin-mediated glucose disposal (IMGD) more than ACE inhibition alone and whether this effect was mediated by the kinin-nitric oxide (NO) pathway activation. We therefore compared in anaesthetized obese (fa/fa) Zucker rats (ZOs) the effects of captopril (2 mg kg(-1), i.v.+2 mg kg(-1) h(-1)), retrothiorphan (25 mg kg(-1), i.v. +25 mg kg(-1) h(-1)), a selective NEP inhibitor, and mixanpril (25 mg kg(-1), i.v. +25 mg kg(-1) h(-1)), a dual ACE/NEP inhibitor, on IMGD using hyperinsulinaemic euglycaemic clamp technique. The role of the kinin-NO pathway in the effects of mixanpril was tested using a bradykinin B2 receptor antagonist (Hoe-140, 300 microg kg(-1)) and a NO-synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME, 10 mg kg(-1) i.v. +10 mg kg(-1) h(-1)) as pretreatments. Insulin sensitivity index (ISI) was lower in ZO controls than in lean littermates. Increases in ISI were observed in captopril- and retrothiorphan-treated ZOs. In mixanpril-treated ZOs, ISI was further increased, compared to captopril- and retrothiorphan-treated ZOs. In ZOs, Hoe-140 and L-NAME alone did not significantly alter and slightly reduced the ISI respectively. Hoe-140 and L-NAME markedly inhibited the ISI improvement induced by mixanpril. These results show that in obese insulin-resistant Zucker rats, under acute conditions, NEP or ACE inhibition can improve IMGD and that dual ACE/NEP inhibition improves IMGD more effectively than does either single inhibition. This effect is linked to an increased activation of the kinin-NO pathway.     

Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and APN) inhibitor prodrugs

Prodrugs of phosphinic dual inhibitors of the enkephalin degrading enzymes, neutral endopeptidase (NEP) and aminopeptidase N (APN), corresponding to the formula H(3)N(+)CH(R(1))P(O)(OR)CH(2)CH(CH(2)Bip)CONHCH(CH(3))COOCH(2)Ph, with R(1) = CH(3) or Ph and R being a benzyl ester, a S-acyl-2-thioethyl derivative, or an acyloxyalkyl group, were synthesized to improve the poor central bioavailability of their precursors. As expected, these compounds (50 mg/kg, iv or ip) induced long lasting ( approximately 2 h) antinociceptive responses in the hot plate test in mice with a ceiling effect varying between 25 and 42% of analgesia. A very rapid hydrolysis of the carboxylate ester contrasting with a slow deprotection of the phosphinate group (t(1/2) approximately 1 h) was observed in serum while 80% of free drug was obtained after 1 h incubation with brain membranes. These results account for the long duration of action observed with these prodrugs.     

Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect

Recent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Delta9-tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant-like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism. This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Delta9-tetrahydrocannabinol increased the release of Met-enkephalin-like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo [3H]diprenorphine binding to opioid receptors in total mouse brain. The repetitive pretreatment during 3 weeks of Delta9-tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone-induced withdrawal syndrome. However, this repetitive administration of Delta9-tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm. Taken together, these behavioural and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.