The use of transversely tubularized bowel segment for segmental ureteral replacement

The aim of the present study was to evaluate the results of the use of a new technique, i.e. transversely tubularized bowel segment (TTBS) for segmental ureteral replacement in pigs. Eight pigs had segmental left ureteral replacement with the TTBS technique, via midline incision in 5 and flank incision in 3. The right ureters were left untouched and used as controls. The pigs were evaluated by excretory urography approximately 3 months after surgery and then sacrificed thereafter, harvesting the kidneys, ureters, and the bladders en bloc for macroscopic and histologic examination. Three pigs died in the early postoperative period. The remaining 5 pigs were followed for 82-112 days. Postoperative intravenous urograms revealed moderate ureterohydronephrosis in 2, mild ureteral dilation in 1, and normal upper tracts in 2. The 2 pigs with moderate ureterohydronephrosis had had midline incisions, and examination after having sacrificed these pigs revealed many intestinal adhesions to the anastomotic region. Easy catheterization of each left ureter through ileal ureteral segment and histologic examination thereafter demonstrated that all ileal ureteral segments including anastomotic sites were patent. Adjacent to the junctional area, metaplastic transitional epithelium covered atrophic villi and in some regions crypts as well. Ureteral replacement by the TTBS technique seems to be a safe and effective surgical treatment option in segmental ureteral defects in short term. However, long-term follow-up studies are needed.     

Caudal ropivacaine and neostigmine in pediatric surgery

BACKGROUND: Neostigmine has been added to local anesthetics for different nerve blocks. This study was conducted to evaluate effects of neostigmine when added to ropivacaine for caudal anesthesia. METHODS: We studied children, aged 1-5 yr, undergoing inguinal hernia and hypospadias surgery. After standard induction of anesthesia, Group I received 0.2% ropivacaine 0.5 ml/kg and Group II received 0.2% ropivacaine 0.5 ml/kg with 2 microg/kg neostigmine via the caudal route. Heart rate, mean arterial pressure, and pulse oximetry were recorded before induction, after induction, and then every 10 min after caudal anesthesia. Hemodynamic, Toddler-Preschooler Postoperative Pain Scale pain score, and sedation score values were recorded 30 min after extubation and at hours 2, 4, 6, 12, and 24. A pain score greater than 3/10 resulted in administration of rectal paracetamol. RESULTS: There were no differences between the groups in demographic and hemodynamic data, duration of surgery and anesthesia, time to extubation, or sedation scores. The pain scores were significantly lower in Group II at 6 and 12 h (P < 0.05). Time to first analgesic requirement was statistically prolonged in Group II (19.2 +/- 5.5h) when compared with Group I (7.1 +/- 5.7 h) (P < 0.05). Total analgesic consumption was statistically larger in Group I (174 +/- 96 mg) when compared with Group II (80 +/- 85.5 mg) (P < 0.05). The incidence of vomiting (3 patients in Group II and 1 patient in Group I) was not statistically significantly different. CONCLUSIONS: The authors found that a single caudal injection of neostigmine when added to ropivacaine offers an advantage over ropivacaine alone for postoperative pain relief in children undergoing genitourinary surgery.     

Intravenous magnesium sulfate prophylaxis for atrial fibrillation after coronary artery bypass surgery

OBJECTIVE: Atrial fibrillation is a rhythm disorder commonly seen early after coronary artery bypass grafting, and it increases morbidity. METHODS: To investigate the effectiveness of magnesium sulfate in the prophylaxis of atrial fibrillation, we conducted a prospective, randomized, placebo-controlled clinical study on 200 consecutive patients in whom we performed elective and initial coronary artery bypass grafting operations. In each group 50% of patients underwent beating-heart operations. In the treatment group 100 patients (76 men and 24 women; mean age, 57.63 +/- 9.68 years) received 24.34 mEq (3 g) of magnesium sulfate in 100 mL of saline solution that was administered over 2 hours (50 mL/h) preoperatively, perioperatively, and at postoperative days 0, 1, 2, and 3. In the control group 100 patients (74 men and 26 women; mean age, 59.96 +/- 9.29 years) received only 100 mL of saline solution according to the same administration schedule as the treatment group. RESULTS: Atrial fibrillation developed in 15 patients from the treatment group and in 16 patients from the control group. The arrhythmia developed after 37.87 +/- 12.76 and 45.26 +/- 15.27 hours in the treatment and control groups, respectively. Although a significant relationship was found between low magnesium sulfate levels and increased incidence of atrial fibrillation (P <.05), when the incidence of postoperative atrial fibrillation is concerned, no significant difference was found between the 2 groups (P >.05). Also, no significant difference was found between operations with cardiopulmonary bypass and beating-heart operations in terms of atrial fibrillation incidence (P >.05). However, atrial fibrillation extended the duration of hospital stay in both groups (P <.05). CONCLUSION: Our findings indicate that magnesium sulfate infusion alone is not sufficient for the prophylaxis of atrial fibrillation.     

Allelic variants of cytochromes P450 2C modify the risk for acute myocardial infarction

SUMMARY: Cytochromes P450 (CYP) 2C8 and 2C9 are polymorphic enzymes responsible for the biosynthesis of vasoactive substances from arachidonic acid including endothelium-derived hyperpolarizing factor. Inter-individual differences in the action of these substances might be important in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI) and hypertension. This study describes the relationship between genetic variants of CYP2C8 and CYP2C9, and morbidity in myocardial infarction in a large Swedish patient material. The study included 1172 AMI patients and 1503 control subjects (matched by age, sex and residential area) who participated in the Stockholm Heart Epidemiology Program (SHEEP). Genotyping was performed by allelic discrimination using a 5'-nuclease assay for the CYP2C8 and CYP2C9 variants. To estimate associations to AMI risks, odds ratios (OR) with 95% confidence intervals (CI) were calculated. The frequencies of CYP2C8*1, 2C8*3, 2C9*1, 2C9*2 and 2C9*3 variants in the control group were 0.91, 0.095, 0.83, 0.11 and 0.065, respectively. The risk of AMI in the female individuals carrying the *2 or *3 variant alleles of CYP2C9 and that of all individuals carrying the *3 variant of CYP2C8 was higher [OR (95% CI): 1.3 (1.0-1.9), P = 0.09; 1.5 (1.0-2.2), P = 0.06 and 1.2 (1.0-1.5), P = 0.07, respectively] compared to the groups with CYP2C8*1 and CYP2C9*1. Possession of rare genetic variants of the CYP2C8 and CYP2C9 genes in females is associated with a modest increase in risk of AMI. This might be related to genetic differences in the formation of endogenous vasoregulating eicosanoids.     

A double-orifice atrioventricular valve case: intraoperative transesophageal echocardiography in diagnosis and treatment

We describe a 45-yr-old woman with an intermediate type atrioventricular septal defect associated with a double-orifice left atrioventricular valve (DOLAV). We diagnosed this exceptional anomaly by intraoperative transesophageal echocardiography (TEE) during surgery that was scheduled for only a primum type atrial septal defect (ASD) repair. Preoperative transthoracic echocardiography and angiography revealed the ASD but could not demonstrate the DOLAV. We were able to repair this rare and challenging abnormality successfully under the guidance of TEE imaging during the operation. TEE provides valuable information about both anatomy and functional aspect of the valvular structures. Besides its proven role in cardiac surgery, intraoperative use of TEE also serves as a useful tool for diagnosis of such unexpected and potentially missed abnormalities.     

Failure strength of bioabsorbable interference screws: effects of in vivo degradation for 12 weeks

We investigated the effect of in vivo degradation for 6-12 weeks on the fixation strength of polylactide bioabsorbable interference screws. Ten bioabsorbable interference screws were used to fix the patellar tendon autograft in ten live sheep knees, which were equally divided into two groups and killed in the 6th or 12th week. The control group consisted of four cadaveric knees. Following the killing of the animals the screws were retrieved and reused to fix patellar tendon grafts in cadaveric sheep knees. Tendon pull-out tests were performed for the partially degraded screws, for the control group, and for the reused screws of the control group. Macroscopic and microscopic examinations of the 6- and 12-week specimens were performed. Tendons pulled-out with an average force of 357+/-30 N in the cadaveric control group on the first use and with 465+/-118 N on the second use. The partially degraded screws failed with a mean load of 399+/-119 N in the 6-week group, and 12-week screws at 447+/-72 N. No macroscopic sign of degradation was observed on the retrieved screws. Histological examination of the 6 week specimens showed necrotic changes in the tendon around screw contact areas. Healing with granulation tissue was present in the same area in the 12th week. Foreign body reaction or an excessive inflammatory reaction was not observed. In vivo degradation of poly- l-lactide interference screws for 12 weeks thus causes neither a loss in the fixation strength of the screws nor an obvious inflammatory reaction.     

Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes

Several-fold differences have been observed among patients in the biotransformation of cyclophosphamide. The aim of this study was to investigate the contribution of CYP2C9 and CYP2C19 and their polymorphisms to the variability of cyclophosphamide activation. The formation of 4-hydroxycyclophosphamide was studied in microsomes from a total of 32 different genotyped human livers, as well as in yeast microsomes expressing different genetic variants of CYP2C9 and CYP2C19. The kinetic data obtained in the yeast system revealed that the intrinsic clearance (V(max)/K(m)) of cyclophosphamide by CYP2C9.2 and CYP2C9.3 samples was approximately threefold lower than that by CYP2C9.1. However, in liver microsomes, there were no statistically significant differences in the intrinsic clearance of 4-hydroxycyclophosphamide formation between the group of seven CYP2C9*1/*1 livers and the remaining nine with one or two variant CYP2C9 alleles ( P>0.7). We found a statistically significant correlation ( r(s)=0.65, P=0.003) between 4-hydroxylation of cyclophosphamide and 5'-hydroxylation of R-omeprazole, a measure of CYP2C19 activity in human liver microsomes ( n=19). No correlation was found between 4-hydroxylation of cyclophosphamide and the formation rate of hydroxycelecoxib, mainly catalysed by CYP2C9 ( r(s)=0.17, P=0.55, n=32). In conclusion, based on the correlation with the formation of R-5'-hydroxyomeprazole, CYP2C19 may partly contribute to the bioactivation of cyclophosphamide in human liver microsomes, while the role of CYP2C9 appears minor.     

CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers

OBJECTIVE: This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. METHODS: Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C9*2 and *3 was carried out with PCR-RFLP. RESULTS: The frequencies of CYP2C9*1, *2, and *3 alleles were 0.74 (95%CI: 0.68-0.80), 0.16 (95%CI: 0.11-0.21) and 0.10 (95%CI: 0.06-0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3'-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C9*1/*3 (0.83+/-0.4, n=14, 95% CI for the difference: 0.02-0.4) and CYP2C9*2/*3 (1.10+/-0.5, n=4, 95% CI for the difference: 0.16-0.8) genotypes compared to CYP2C9*1/*1 (0.62+/-0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C9*3 variant. CONCLUSIONS: The frequencies of CYP2C9*1, *2, and *3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C9*3 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied