Improved glucose tolerance in acyl CoA:diacylglycerol acyltransferase 1-null mice is dependent on diet

Background  

Mice that lack acyl CoA:diacylglycerol acyltransferase (Dgat1 ^-/- mice) are reported to have a reduced body fat content and improved glucose tolerance and insulin sensitivity. Studies so far have focussed on male null mice fed a high fat diet and there are few data on heterozygotes. We compared male and female Dgat1 ^-/-, Dgat1 ^+/- and Dgat1 ^+/+ C57Bl/6 mice fed on either standard chow or a high fat diet.     

Fontan conversion with arrhythmia surgery.

OBJECTIVE: Hemodynamic abnormalities and refractory atrial arrhythmias in patients late after the Fontan operation result in significant morbidity and mortality. We reviewed our experience with Fontan conversion and concomitant arrhythmia surgery. METHODS: Between January 1996 and February 2004, 16 patients underwent Fontan conversion and arrhythmia surgery. Mean age at the initial Fontan operation was 5.1+/-3.5 (range: 2-15) years and mean age at Fontan conversion was 17.0+/-5.8 (range: 6-30). The initial Fontan operations were atriopulmonary connections in 14 patients, extracardiac lateral tunnel in 1, and intracardiac lateral tunnel in 1. The types of arrhythmia included atrial flutter in 10 patients and atrial fibrillation in 3. Fontan conversion operation was performed with intracardiac lateral tunnel in 5 patients and extracardiac conduit in 11. Arrhythmia surgery included isthmus cryoablation in 10 patients and right-sided maze in 3. RESULTS: There has been no mortality. At Fontan conversion operation, 7 patients required permanent pacemaker. All patients have improved to New York Heart Association class I or II. With a mean follow-up of 26.9+/-30.6 (range:1-87) months, 16 patients had sinus rhythm, 2 patients had transient atrial flutter which was well controlled, and 2 patients required permanent pacemaker during follow-up. CONCLUSIONS: Fontan conversion with concomitant arrhythmia surgery and permanent pacemaker placement is safe, improves New York Heart Association functional class, and has a low incidence of recurrent arrhythmias. In most patients, concomitant permanent pacemakers are needed.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Hepatic artery injection of I-131-labeled lipiodol. Part I. Biodistribution study results in patients with hepatocellular carcinoma and liver metastases

Biodistribution of iodine-131-labeled Lipiodol Ultra-Fluide (I-131 LUF) injected into the hepatic artery was studied scintigraphically in 47 patients with hepatocellular carcinoma (n = 23), hepatic metastases (n = 14), or normal livers (n = 10). The investigation was extremely well tolerated. I-131 LUF concentrated mainly in the liver (L) and the lungs (l), with L/L + l activity ratios greater than 75% for all three groups of patients. I-131 LUF distribution was homogeneous in normal livers and heterogeneous in cirrhotic livers. I-131 LUF concentrated in the tumor with a tumorous (T) to nontumorous (NT) activity ratio (T/NT) of 4.3 +/- 3.6 for hepatocellular carcinoma and 2.4 +/- 0.7 for hepatic metastases. The effective half-life of I-131 LUF is more than 4.5 days for the three groups. It was eliminated mainly through the urine. Clearance from tumor is slower than from normal liver, as shown by the increase in T/NT at day 18. Biodistribution did not change in patients who had a second injection, which indicates that there is no saturation phenomenon. The results of this study suggest that LUF may be considered as a potential carrier vehicle for therapeutic agents.     

Urea rebound and delivered Kt/V determination with a continuous urea sensor

BACKGROUND: The recent introduction of urea sensors for dialysis monitoring has made possible new approaches to urea kinetic modelling. In this study we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V corrected for double-pool urea kinetics (Kt/Vdp) can be accurately determined using an on-line sensor providing a continuous measure of blood water urea. A modification of the Smye constant volume double-pool theory led to the following equations for Ceq and Kt/Vdp [formula: see text] where Cpre is the blood concentration measured at the start of dialysis, t is the length of the dialysis session (in min) and S(ex) is the constant slope of the blood urea logarithm concentration decline following development of the intercompartmental urea concentration gradient in the first 30-60 min of dialysis. METHODS: These equations were tested in 11 patients undergoing 165-240 min of paired filtration dialysis with continuous monitoring of blood urea concentration. Cpre was determined as the plateau concentration during a preliminary period of 15-20 min of slow isolated ultrafiltration. S(ex) was accurately determined from linear regression applied to the urea sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and Kt/Vdp determined from the above equations compared closely to values determined from 25-40 min of urea rebound monitoring with the urea sensor: 10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/- 0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed into on-line urea monitors to provide current and extrapolated values of Ceq and Kt/Vdp from about the first hour of dialysis.      

Expression of cadherins and CD44 isoforms in ovarian endometrial cysts

We evaluated the immunohistochemical expression of cadherins and CD44 variants in 20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20 ovarian carcinomas, and the serological and cystic fluid concentrations of soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20 cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas, immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44 H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A difference in immunostaining for E-cadherin was found between endometriomas and cystadenomas (P < 0.001) and for N- cadherin between endometriomas and carcinomas (P < 0.001). A difference in CD44H immunostaining was observed between endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian tumours and carcinomas. No difference in serum concentrations of soluble E- cadherins and CD44 standard was found between the four groups of tumours. Cystic fluid concentrations of E-cadherin were lower in endometriomas than in borderline tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44 standard cystic fluid were found in endometriomas than in other ovarian cysts. Endometriomas and borderline tumours share alterations of cadherins and CD44 isoforms which may help in the understanding of the aggressive and invasive potentials of endometriotic cells.      

Pulmonary damage by Vibrio vulnificus cytolysin.

Vibrio vulnificus is an estuarine bacterium that causes septicemia and serious wound infection. Cytolysin produced by V. vulnificus has been incriminated as one of the important virulence determinants of bacterial infection. Cytolysin (8 hemolytic units) given intravenously to mice via their tail veins caused severe hemoconcentration and lethality. Cytolysin treatment greatly increased pulmonary wet weight and vascular permeability as measured by (125)I-labeled albumin leakage without affecting those factors of other organs significantly. Blood neutrophils were markedly decreased in number after cytolysin injection, with a concomitant increase in the level of pulmonary myeloperoxidase activity, indicating that cytolysin-induced neutropenia might be due to pulmonary sequestration of neutrophils. By microscopic examination, severe perivascular edema and neutrophil infiltration were evident in lung tissues. These results suggest that increased vascular permeability and neutrophil sequestration in the lungs are important factors in lethal activity by cytolysin.     

Differentiation of human bone marrow cells into T lymphocytes by in vitro incubation with thymic extracts

Extracts of human or calf thymus influence differentiation of human bone marrow cells in vitro. Incubation of a putative stem cell fraction of human marrow with extracts of thymus for a period of 2 hr led to the appearance of lymphocytes with surface antigens recognized by a highly specific anti-T-cell antiserum. To a lesser degree, development of lymphocytes having the capacity to form rosettes with sheep erythrocytes was observed. Treatment of the so-called stem cell fraction with thymic extracts did not yield cells responsive to mitogenic influences of phyto-haemagglutinin or allogeneic cells. This model should permit further analyses of immunodeficiency diseases and provide a useful technique for purification and analysis of thymus extracts active with human haematopoietic cells.     

Ankylosing spondylitis susceptibility loci defined by genome-search meta-analysis

In genome scans of ankylosing spondylitis (AS), with the exception of the HLA loci, linkage has not been easy to replicate across studies. We applied the genome-search meta-analysis (GSMA) method to genome scans of AS and spondyloarthropathy (SpA) to assess evidence for linkage across studies. Three AS genome scans and one SpA scan including 430 families with 1,048 affected individuals were used. All four original genome scans mainly analyzed Caucasian families. Seven bins had both Psumrnk and Pord<0.05, suggesting these bins most likely contain AS-linked loci; bin 6.2, 6.1, 6.3, 16.3, 19.2, 17.1, and 16.4. The GSMA produced significant genome-wide evidence for linkage on chromosome 6p22.3–6p21.1 (Psumrnk=0.000003), including the HLA locus. In addition to the HLA-B27 locus, strong linkage evidence was found on chromosome 6p25.3–6p22.3 (Psumrnk=0.0013) and 6p21.1–6p15 (Psumrnk=0.043). In the GSMA of four genome scans including one SpA study, the bin 9.4 (9q21.32–9q33.1) was newly found for linkage (Psumrnk=0.043, Pord=0.013). This GSMA added the evidence of the HLA loci as the greatest susceptibility factor to AS and showed evidences of chromosome 6, 16q, 19, 17p, and 9q as non-HLA susceptibility loci.