Combining lisinopril and l-arginine slows disease progression and reduces endothelin-1 in passive Heymann nephritis

BACKGROUND: Despite angiotensin-converting enzyme (ACE) inhibition is a very powerful therapy, it may not be uniformly renoprotective in patients with proteinuric nephropathies who might refer late in the course of the disease. In accelerated passive Heymann nephritis (PHN), a severe rat model of human membranous nephropathy, with proteinuria and increased urinary excretion of endothelin-1 (ET-1), early treatment with an ACE inhibition limited proteinuria as well as the exuberant formation of renal ET-1, while late treatment reduced urinary proteins not to a significant extent. Since biologic effects and production of ET-1 within the kidney are counteracted by nitric oxide, we studied the effect of combining lisinopril and l-arginine, the natural precursor of nitric oxide, starting late in the disease. METHODS: Uninephrectomized PHN rats were divided in four groups (N = 10) and daily given orally: vehicle; 1.25 g/L l-arginine; 40 mg/L lisinopril; and l-arginine + lisinopril. Treatments started at 2 months, when rats had massive proteinuria, until 9 months. Six normal rats served as control. RESULTS: Increase in systolic blood pressure was significantly limited by l-arginine. Lisinopril alone and the combination were more effective. Renal function impairment was not affected by l-arginine, partially ameliorated by ACE inhibitor and normalized by the combined therapy. In rats given l-arginine, proteinuria levels were similar to vehicle. ACE inhibitor kept proteinuria at values comparable to pretreatment and numerically lower than vehicle. Addition of l-arginine to lisinopril was more effective, with values significantly lower than vehicle. Glomerular and tubular changes were limited by the ACE inhibitor and further ameliorated by the combined therapy. Exaggerated urinary ET-1 of PHN was reduced by 23% and 40% after l-arginine and lisinopril, respectively, and by 62% with the combination. Defective urinary excretion of cyclic guanosine monophosphate (cGMP) was partially restored by lisinopril, while normalized by the combined therapy. CONCLUSION: Combining l-arginine with ACE inhibitors would represent a novel strategy for patients with severe nephropathy not completely responsive to ACE inhibition. Restoring the nitric oxide/ET-1 balance could be of benefit in halting renal disease progression.     

Acupotomy versus sodium hyaluronate for treatment of knee osteoarthritis in rabbits

Objective

To investigate the possible advantages of acupotomy over sodium hyaluronate injection for the treatment of knee osteoarthritis (KOA).

Which cystography in the diagnosis and grading of vesicoureteral reflux?

The gold standard procedure for the evaluation of vesicoureteral reflux (VUR) is the radiographic voiding cystourethrography (VCUG); direct radionuclide voiding cystography (DRVC) is an alternative method for detecting VUR. A new imaging procedure, voiding urosonography (VUS) with contrast medium, has recently been introduced. We have carried out a comparative study of these three techniques in 157 patients (aged 6 weeks–4.7 years). VUS showed the presence of VUR in 91 of 311 renal units; VCUG detected reflux in 64 of 233 renal units, and the DRVC in 23 of 78 renal units. VCUG and VUS were compared in 118 patients, and both procedures showed the same grade of reflux in 56 refluxing units (kappa value 0.92); in six cases the reflux grade was greater at VUS than at VCUG. Seven cases of reflux detected by VUS were not identified on VCUG. VCUG did not show a grade of VUR that was higher than in VUS in any patient. In the identification of 4°–5° grade reflux, the sensitivity of VUS reached 100%. VUS and DRVC were found to be equally effective in the detection of VUR (kappa value 0.85). In conclusion, we found that VUS is a useful method for the diagnosis and grading of patients with VUR.     

Preoperative administration of controlled-release oxycodone as a transition opioid for total intravenous anaesthesia in pain control after laparoscopic cholecystectomy

Background  The complexity of pain from laparoscopic cholecystectomy and the need for treating incident pain provide rationale for multipharmacological analgesia. We investigated the preoperative administration of controlled-release (CR) oxycodone as transition opioid from remifentanil infusion for pain after laparoscopic cholecystectomy. Methods  Fifty consecutive patients undergoing laparoscopic cholecystectomy were randomly, double-blindly assigned to treatment group (n = 25, CR oxycodone: 1 h before surgery and 12 h after the first administration) or to the control group (n = 25, placebo: administered at the same intervals). General anaesthesia was maintained with propofol and remifentanil target-controlled infusions (TCIs). All patients received ketorolac 30 mg i.v. Tramadol i.v. was administered for patient-controlled analgesia (PCA) postoperatively. Numerical rating scale for pain at rest and at movement (NRSr and NRSi), tramadol consumption, times to readiness to surgery and awakening, times to modified Aldrete’s and modified Post-Anesthetic Discharge Scoring System (PADSS) >9 and side effects were evaluated. Results  All NRSr and NRSi and tramadol consumption were significantly lower in the treatment group. The oxycodone group showed higher modified Aldrete’s scores at each time and reached a PADSS >9 faster. Side effects and postoperative nausea and vomiting episodes were comparable. Conclusions  We demonstrated the success of a multipharmacological treatment including opioid premedication with CR oxycodone used as transition opioid for TCI remifentanil infusion; the treatment group showed lower pain scores and rescue analgesic consumption, shorter time to discharge from recovery room and from surgical ward, and the same incidence of side effects, comparably to controls. Sources of financial support for the work: University of Parma, viale Gramsci 14, 43100 Parma PR, Italy.     

The use of fibrin sealant to prevent major complications following laparoscopic gastric bypass: results of a multicenter, randomized trial

Background

Published interim results have shown that fibrin sealant (Tissucol^®/Tisseel^® Baxter AG, Vienna, Austria) may be effective in preventing anastomotic leaks and internal hernias following laparoscopic Roux-en-Y gastric bypass (LRYGBP). We report the final results of a multicenter, randomized clinical trial evaluating the use of fibrin sealant in LRYGBP.

Methods

Between January 2004 and December 2005, 340 patients aged 21–65 years with a body mass index (BMI) of 40–59 kg/m² undergoing LRYGBP were randomized (1:1) to two treatment groups: fibrin sealant group (applied to gastrojejunal and jejunojejunal anastomoses and over mesenteric openings), and control group (no fibrin sealant; suture of the mesenteric openings). Operative time, early and late complications, reinterventions, time to oral diet initiation, and length of stay were assessed.

Results

Overall, 320 patients were included into the study: 160 in the control group and 160 in the fibrin sealant group. All patients completed follow-up assessments at 6 and 12 months, and 60.9% completed assessments at 24 months. There were no significant differences between groups with respect to demographics, operative time, oral diet initiation, hospital stay, and BMI reduction at 6, 12, and 24 months. The incidence of anastomotic leak was numerically, but not significantly, greater in the control group. The overall reintervention rate for specific early complications (<30 days) was significantly higher in the control group (p = 0.016). No deaths or conversions to open laparotomy occurred.

Conclusion

The use of fibrin sealant in laparoscopic RYGBP may be beneficial in reducing the reintervention rate for major perioperative (<30 days) complications. Larger studies are needed.     

Pathological features of Gleason score 6 prostate cancers in the low and intermediate range of prostate‐specific antigen level: is there a difference?

OBJECTIVE

To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate‐specific antigen level (4–10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.

PATIENTS AND METHODS

In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0–10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.

RESULTS

Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.

CONCLUSIONS

These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.     

The "sclerodermic hand": a radiological and clinical study

ObjectiveTo assess the clinical and radiographic features of hand involvement in patients with systemic sclerosis (SSc).MethodsForty-one unselected Sardinian SSc patients (32 women, 9 men; mean age 58.9, range 31–81 years; mean disease duration 11.8 years, range 1–36 years) were evaluated in this observational cross-sectional study. Twenty-six patients had diffuse scleroderma (dSSc) and 15 limited scleroderma (lSSc). Radiological examination of the hands was performed and the films were read by two independent rheumatologists blinded to the diagnosis using a classification system of four predefined radiological patterns (normal/minimal changes, articular degenerative, articular inflammatory and periarticular pattern). Correlations between radiological pattern, clinical and serological features were assessed.ResultsThe skeletal and articular involvement of the hand was frequent in SSc, being clinically evident in 30/41 (73%) and radiologically in 33/41 (80%) of patients. The periarticular pattern (defined as the occurrence of bone resorption of ungueal tufts, soft tissue calcifications and/or flexion deformities) was the most frequent pattern detected (14/41, 34.1%) and finger flexion contractures and bone resorptions were significantly associated with interstitial lung disease, reduced FVC, oesophagus involvement and prostacycline therapy. Calcinosis (29.2%) was found to be associated with erosions, suggesting a pathogenic link. An inflammatory pattern was also radiologically frequent (8/41, 19.5%), but erosions, with the exception of those localized at distal interphalangeal joints, were demonstrated mainly in patients with clinical picture of rheumatoid arthritis overlapped with SSc. We found no significant differences in terms of radiographic findings between lSSc and dSSc with the exception of calcinosis, which was more frequent in patients with lSSc.ConclusionThis cross-sectional study confirms that the skeletal and articular involvement of the hand is frequent in SSc.     

Febrile urinary tract infection in children: ampicillin and trimethoprim insufficient as empirical mono-therapy

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in defined groups of children (total number 694) with urinary tract infection (UTI) regarding age, first UTI (FUTI) or recurrent UTI (RUTI), renal abnormalities or vesico-ureteric reflux (VUR) in order to optimize empirical antibiotic therapy and prophylaxis. In patients aged between 1 month and 24 months with a first febrile UTI (FUTI; n = 205) the leading pathogen was Escherichia coli (E. coli) (83.4%). In comparison with patients with FUTI, those with RUTI (n = 24) had more Enterococcus and Enterobacter infections and higher resistance rates of E. coli against trimethoprim (TMP), trimethoprim/sulfamethoxazole (SXT) or ampicillin (AMP). Boys with ultrasound-detected renal abnormalities (n = 71) showed 14.2% Pseudomonas and 59.1% E. coli infections versus girls (n = 48) (2.1% Pseudomonas and 93.7% E. coli). Of 390 patients who underwent voiding cysto-urethrography, 31.5% had VUR. Of them, 45.5% received antimicrobial prophylaxis with SXT (n = 30) or cefazolin (n = 26). There was no difference between girls (n = 242) and boys (n = 148) regarding the frequency of VUR and pathogens. There were more TMP- and SXT-resistant E. coli cultures from patients with VUR (37.8%) than from those without VUR (25.8%). Treatment with TMP, SXT and AMP alone appeared to be insufficient in many cases because of high resistance rates of E. coli and other uropathogens.     

Using reagent-supported thromboelastometry (ROTEM((R))) to monitor haemostatic changes in congenital heart surgery employing deep hypothermic circulatory arrest

Objective: Cardiac surgery employing cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) can induce coagulation disturbances and bleeding complications that may be especially severe in infants. A better understanding of the coagulopathy and a quick method for its evaluation would be helpful in the management of patients exposed to CPB and DHCA. This study aimed to monitor coagulation defects in congenital heart surgery using rotational thromboelastometry (ROTEM((R))), standard coagulation tests and platelet flow cytometry. Methods: The study comprised 10 infants undergoing surgery for congenital heart disease on CPB and DHCA. Blood was sampled at skin incision, after heparinisation during CPB (directly pre- and directly post-DHCA) and after protamine administration post-CPB. ROTEM((R)) using different reagents including a heparinase-containing assay to evaluate coagulation during heparinisation, APTT and INR, and flow cytometry to evaluate platelet activation were performed. Results: During CPB, the ROTEM((R)) indicated CPB-induced clotting factor depletion and platelet dysfunction that persisted after CPB and heparin neutralisation. ROTEM((R)) results were available within 15min and therefore much faster than standard tests. ROTEM((R))-guided specific blood product treatment resulted in satisfactory coagulatory function. The highest degree of platelet activation was found directly after DHCA. Conclusions: A major benefit of ROTEM((R)) is the quick detection of a developing coagulopathy already during CPB. ROTEM((R)) guides quick and specific blood product treatment after CPB, which may decrease bleeding complications in cardiac surgery. The finding of maximal platelet activation directly after DHCA suggests that not only CPB but also hypothermia activates platelets in vivo, thereby contributing to platelet dysfunction.     

Laparoscopic common bile duct exploration

OBJECTIVE: To describe the technique of laparoscopic common bile duct exploration (LCBDE) with high clearance rates, low morbidity, and mortality rates. SUMMARY BACKGROUND DATA: LCBDE is well accepted by patients because treatment is obtained during the same anesthesia. If one stage therapy for gallstones and common bile duct stones provides success rates equivalent to those of the sequential approach, with lower costs, this should be considered the standard of care. METHODS: From September 1991 to March 2007, 5201 laparoscopic cholecystectomies were performed at S?o José Avaí Hospital. LCBDE was carried out in 481 patients (9.25%). RESULTS: Of 481 LCBDE, 225 (46.78%) were managed using a transcystic approach and 183 (38.05%) with choledochotomy (114 with transcystic choledochotomy and 69 with longitudinal opening of the common bile duct). Successful laparoscopic stone clearance was achieved in 468 (97.3%). An elective postsurgical endoscopic sphincterotomy were done on the 13 (2.70%) patients not cleared laparoscopically. Seven patients had unexpected retained stones. CONCLUSIONS: LCBDE during laparoscopic cholecystectomy solves 2 problems during the same anesthesia with high success rates and may be employed successfully.