Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Initial experience of the High-Density Grid catheter in patients undergoing catheter ablation for atrial fibrillation

Purpose

A significant proportion of patients undergoing catheter ablation for atrial fibrillation (AF) experience arrhythmia recurrence. This is mostly due to pulmonary vein reconnection (PVR). Whether mapping using High-Density Wave (HDW) technology is superior to standard bipolar (SB) configuration at detecting PVR is unknown. We aimed to evaluate the efficacy of HDW technology compared to SB mapping in identifying PVR.

Methods

High-Density (HD) multipolar Grid catheters were used to create left atrial geometries and voltage maps in 36 patients undergoing catheter ablation for AF (either due to recurrence of an atrial arrhythmia from previous AF ablation or de novo AF ablation). Nineteen SB maps were also created and compared. Ablation was performed until pulmonary vein isolation was achieved.

Results

Median time of mapping with HDW was 22.3 [IQR: 8.2] min. The number of points collected with HDW (13299.6±1362.8 vs 6952.8±841.9, p<0.001) and used (2337.3±158.0 vs 1727.5±163.8, p<0.001) was significantly higher compared to SB. Moreover, HDW was able to identify more sleeves (16 for right and 8 for left veins), where these were confirmed electrically silent by SB, with significantly increased PVR sleeve size as identified by HDW (p<0.001 for both right and left veins). Importantly, with the use of HDW, the ablation strategy changed in 23 patients (64% of targeted veins) with a significantly increased number of lesions required as compared to SB for right (p=0.005) and left veins (p=0.003).

Conclusion

HDW technology is superior to SB in detecting pulmonary vein reconnections. This could potentially result into a significant change in ablation strategy and possibly to increased success rate following pulmonary vein isolation.

     

Energy-dependent accumulation of norfloxacin and porin expression in clinical isolates of Klebsiella pneumoniae and relationship to extended-spectrum beta-lactamase production

The relationships between porin deficiency, active efflux of fluoroquinolones, and extended-spectrum beta-lactamase (ESBL) production were determined for 53 clinical isolates of Klebsiella pneumoniae. Thirty-two ESBL-positive strains (including 22 strains expressing porins and 10 strains lacking porins) and 21 ESBL-negative strains were evaluated. Active efflux of norfloxacin was defined as a >/=50% increase in the accumulation of norfloxacin in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) in comparison with the corresponding basal value in the absence of CCCP. The quinolone resistance-determining regions of both gyrA and parC from 13 strains, representing all isolates with different porin profiles and with or without active efflux, were determined. Porin loss was significantly more common among ESBL-positive strains (10 of 32 [31.2%]) than among ESBL-negative strains (0 of 2 [0%]) (P < 0.01). Active efflux was observed in 7 of 10 (70%) strains lacking porins and in 4 of 43 (9.3%) strains producing porins (P < 0.001). The 11 strains showing active efflux corresponded to 3 of 21 (14.3%) ESBL-negative strains and 8 of 32 (25.5%) ESBL-positive strains (P > 0.05). Basal values of norfloxacin accumulation were higher in strains lacking active efflux than in those that had this mechanism (P < 0.05). In the absence of topoisomerase changes, the contribution of either porin loss or active efflux to fluoroquinolone resistance in K. pneumoniae was negligible. It is concluded that among K. pneumoniae strains of clinical origin, porin loss was observed only in those producing ESBL, and that a significant number of porin-deficient strains also expressed active efflux of norfloxacin. In terms of fluoroquinolone resistance, both mechanisms are significant only in the presence of topoisomerase modifications.     

Tratamiento de la eventración subxifoidea: técnica de doble malla ajustada al defecto

Introduction

Subxiphoid incisional hernia has characteristics that differentiate it from the rest and make it a distinctive entity. The fact that it has its sac very near the rib cage and sternum determines the pressure in the margins. The repair, by open or by laparoscopic approach, has not demonstrated good results despite the generalised use of a prosthesis. They are uncommon, and have a significant comorbidity in patients (severe heart diseases, transplants, immunosuppressed), after surgery of the hepato-bilio-pancreatic area with transverse incisions, or very high mid-laparotomies for gastro-oesophageal surgery.

Material and methods

A new technique has been developed in our Unit, based on a double mesh and adapted to the anatomical and physiological characteristics of the region. The series consisted of 35 consecutive patients operated on between 2004 and 2010, following an agreed surgical and management protocol.

Results

There were no significant complications -the most frequent (17.4%) was a seroma- except one case of a wound infection due to skin ischaemia in one patient who had had multiple operations and a transplant. During the post-surgical follow up to the present (between 4 and 80 months), there has been no recurrence of the incisional hernia and no significant local discomfort has been reported.

Conclusions

The «adjusted double mesh» technique achieved good results in our hands, from the surgical point of view (reproducibility, recurrence), and for the patient, with minimal discomfort and recovery of quality of life.     

Infección de la prótesis en la reparación herniaria. Nuestra experiencia en 5 años

Introduction

Prosthesis infection is an infrequent but important complication in abdominal wall surgery. The aim of this study is to evaluate the incidence and risk factors for the infection of the prosthesis after hernia repair, as well as the treatment to apply.

Material and method

Between January 2002 and December 2006, we performed 1055 prosthetic hernia repairs: 761 inguinal hernias (72.1%), 74 umbilical hernias (7%) and 220 ventral hernias (20.9%). We prospectively analysed preoperative, intraoperative and postoperative variables, as well as the incidence of infection of surgical wound and of prosthesis. We used ASA classification for preoperative anaesthetic evaluation.

Results

The overall percentage of infection of the prosthesis was 1.3%. Infection was observed in 11 repairs with polypropylene mesh (PPL), in 4 with PTFE mesh, and one case in combined mesh. Risk factors of mesh infection were: obesity (p=0.002), diabetes (p=0.020), the type of repair (p=0.047), emergency surgery (p=0.001), the type and size of mesh (p=0.003; p=0.007) and time of surgery >180 min (p<0.001). Seven of the 11 patients with infection of PPL prosthesis were resolved with conservative treatment, whereas all the cases with PTFE infection or mixed mesh needed removal to solve the problem.

Conclusions

Several factors are involved in producing a prosthesis infection. Whereas antibiotic treatment and surgical drainage of the infection can be sufficient in most PPL mesh infection, PTFE prostheses need to be removed prematurely in order to halt the infection process.     

Are the antioxidant properties of carvedilol important for the protection of cardiac mitochondria?

The cellular role of mitochondria includes ATP generation and the modulation of cytosolic calcium signals, besides being the "crossroads" for several cell death pathways. The maintenance of optimal mitochondrial functioning during the disease process increases the chances for survival. For example, ischaemia followed by reperfusion is known to negatively affect mitochondrial function, namely by inducing a deleterious condition called mitochondrial permeability transition (MPT). The MPT is responsible for mitochondrial dysfunction and can ultimately lead to cell death. Therefore, it seems important to protect mitochondrial function in cardiac disease. Carvedilol, a beta-adrenergic receptor antagonist with antioxidant properties, has a positive impact on cardiac mitochondria during in vitro, ex-vivo and in vivo models of cardiac dysfunction. Particularly, carvedilol was shown to inhibit MPT in isolated heart mitochondria and protect mitochondria against the oxidative damage induced by the xanthine oxidase/hypoxanthine pro-oxidant system. The observation that carvedilol acts as an inhibitor of mitochondrial complex-I is also of importance, since this mitochondrial system was proposed as cause of the cardiotoxicity associated with the anti-neoplasic drug doxorubicin. This review points out the major findings concerning the positive impact of carvedilol on mitochondrial function and its use in the treatment of myocardial diseases where oxidative stress is known to be involved.