Spinal hyperbaric ropivacaine-fentanyl for day-surgery

BACKGROUND: Adequate intraoperative analgesia combined with faster mobilization might be achieved by replacing hyperbaric ropivacaine partly with fentanyl. METHODS: Sixty spinal anesthesia patients were randomized into 2 groups of either fentanyl 20 microg mixed with hyperbaric ropivacaine 10 mg (group FR10) or hyperbaric ropivacaine 15 mg (group R15). Forty-five patients underwent inguinal hernia repair and 15 patients had lower extremity surgery. Sensory block was tested by pinprick, and motor block was tested by use of a modified Bromage scale at 5-minute intervals for 30 minutes, 15-minute intervals for 60 minutes, and at 30-minute intervals until full recovery. RESULTS: The groups did not differ significantly regarding success (27 of 30 [group FR10] and 29 of 30 [group R15]), median onset time (10 [5 to 25] v 10 [5 to 20] minutes) or median duration of T10 sensory block (55 [20 to 115] v 80 [5 to 170] minutes), respectively. Recovery from spinal block was significantly quicker in group FR10 than in group R15, recorded in ability to walk (2.5 hours v 3 hours [P=.017]), full motor recovery (1 hour v 1.5 hour [ P <.001]), and sensory recovery to S1 (2.5 hours v 3.3 hours [ P=.026]). Pruritus occurred in 18 (60%) of group FR10 v 0 of group R15 patients ( P <.001). This symptom was mild in all except 1 patient, who received ondansetron 8 mg IV. In the OR, the groups did not differ hemodynamically: 9 (30%) of the group FR10 and 10 (33%) of the group R15 patients, respectively, required medication for hypotension and/or bradycardia. Full motor block (Bromage 3) developed less frequently (P <.001) in group FR10 patients than in group R15 patients (1 [3%] v 14 [47%]), and the group FR10 patients recovered faster in a median time of 60 v 90 minutes (P <.001). In both groups, sensory and motor blocks were more extensive on the operative side compared with the nonoperative side ( P <.001). CONCLUSION: Faster mobilization but equal onset and duration of analgesia were achieved with intrathecal hyperbaric ropivacaine 10 mg plus fentanyl 20 microg as compared with hyperbaric ropivacaine 15 mg.     

Sterol parameters as markers of liver function in primary biliary cirrhosis before and after liver transplantation

Serum cholesterol reflects poorly cholesterol metabolism. From serum noncholesterol sterols cholestanol, campesterol, and sitosterol are surrogate markers of cholesterol absorption, but reflect also cholestasis, while those of lathosterol reflect cholesterol synthesis and hepatic parenchymal function. We investigated these sterols at end-stage of primary biliary cirrhosis (PBC) - prior to liver transplantation and shortly after transplantation in 67 patients to show their role as index of cholestasis and parenchymal liver function. Median preoperative values of cholestanol were increased 7.6 times, those of plant sterols 1.6-3.7 times above and the campesterol/sitosterol ratio was decreased twice below our control values, respective lathosterol levels being mainly subnormal. After transplantation, the proportions to cholesterol of the absorption markers decreased, and those of synthesis markers and the ratios of campesterol/sitosterol increased significantly. Thus, surrogate sterol markers of cholesterol absorption and synthesis in serum are also good clinical markers of chronic cholestasis and degree of hepatic parenchymal cell function in PBC. Postoperative improvement of serum sterol profile indicate clinically good function of the liver graft.     

Volumetric MR-guided high-intensity focused ultrasound versus uterine artery embolisation for treatment of symptomatic uterine fibroids: comparison of symptom improvement and reintervention rates

Purpose

To compare the effectiveness of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) with that of uterine artery embolisation (UAE) for treatment of uterine fibroids.

Methods

Between January 2010 and January 2013, 51 women with symptomatic uterine fibroids underwent MR-HIFU. Follow-up and MR imaging were compared to 68 women treated with UAE, who fulfilled eligibility criteria for MR-HIFU – e.g., size (≤ 12 cm) and number (≤ 5) of fibroids. We compared median symptom severity (tSSS), total health-realted quality of life (HRQoL) scores, and reintervention rates. The adjusted effect on symptom relief and HRQoL improvement was calculated using multivariable linear regression. Cox regression was applied to calculate the adjusted risk of reintervention between both treatments.

Results

Median tSSS improved significantly from baseline to three-month follow-up (P?P?P?P?=?0.002) times higher risk of reintervention within 12 months (18/51 vs. 3/68).

Conclusion

Both MR-HIFU and UAE result in significant symptom relief related to uterine fibroids. However, MR-HIFU is associated with a higher risk of reintervention.

Key Points

? This study compared outcomes between volumetric MR-HIFU and UAE for uterine fibroids. ? Both MR-HIFU and UAE result in significant symptom relief and quality of life improvement. ? UAE had a stronger positive effect on the clinical outcomes. ? Reintervention rate after MR-HIFU ablation was significantly higher than after UAE.     

Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation

There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.     

Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.     

Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. METHODS: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. RESULTS: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (chi 2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA. CONCLUSIONS: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. CLINICAL RELEVANCE: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.     

FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells

Migration of developing germ cells from the basal to the adluminal compartment of the seminiferous epithelium requires extensive tissue restructuring, resulting in the production of reactive oxygen species. Sertoli cells are involved in this process. Glutathione (GSH), produced by Sertoli cells, has an essential role in cell protection against oxidative stress. Intracellular GSH content is maintained by de novo synthesis, involving glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, and by recycling from oxidized GSH, catalysed by glutathione reductase (GR). To assess whether follicle-stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) modulate GSH production in Sertoli cells by regulating the expression of GCLC, GCLM and/or GR, we performed in vitro studies using rat Sertoli cells in primary culture. FSH and bFGF stimulation increased Sertoli cell GSH levels after 24 h incubation. The simultaneous addition of FSH and bFGF did not produce any further effect. GCLM expression was upregulated by FSH and bFGF 6 h. At 24 h, only the FSH-mediated effect was still observed. FSH and bFGF also upregulated GR expression. In conclusion, our results show that FSH and bFGF increase GSH levels in Sertoli cells through stimulation of the de novo synthesis and recycling by upregulating GCLM and GR expression respectively. Therefore, protection of germ cells against oxidative stress seems to be regulated by hormones and germ cell-released growth factors capable of influencing the production of Sertoli cell GSH.     

High revision rates after laparoscopic vertical banded gastroplasty

BACKGROUND: To evaluate, in a surgical department at a university hospital in Stockholm, Sweden, the long-term results after laparoscopic vertical banded gastroplasty (VBG), with special emphasis on revisional surgery. Few studies are available with long-term results after laparoscopic VBG. Some short-term studies have shown results similar to gastric banding. METHODS: All consecutive patients who underwent attempted laparoscopic VBG between 1995 and 2005 were followed up regarding weight loss and the need for revisional surgery. Follow-up was from the date of surgery to the end of the observational period (December 2006). RESULTS: In 486 patients, laparoscopic VBG was attempted. Of the 486 cases, 64 were converted to open surgery. Conversions were common in the first patients, with a conversion rate of 4% during the last 100 patients. The mean body mass index at surgery was 42.4 kg/m2. The median follow-up was 3 years (range 0-11). All patients lost weight. A total of 104 patients (21%) required revisional surgery 114 times during the follow-up period, with food intolerance/vomiting and insufficient weight loss the most common reasons. Of the 104 patients, 31 underwent repeat VBG, of whom 10 needed a secondary revisional procedure, and 49 required conversion to gastric bypass, of whom none have required additional revisional surgery. CONCLUSION: Laparoscopic VBG is associated with high revisional rates. In the case of failed VBG, repeat VBG seems to be a poor option and conversion to gastric bypass yields better results. We have abandoned VBG as a surgical option in the treatment of obesity.     

Value of albumin dialysis therapy in severe liver insufficiency

A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patients own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.