The effects of chronic treatment with the dihydropyridine, Bay K 8644, on hyperexcitability due to ethanol withdrawal, in vivo and in vitro.

1. The effects of chronic treatment with the dihydropyridine, Bay K 8644, were studied on the ethanol withdrawal syndrome, in vivo and in vitro. 2. Addition of racemic Bay K 8644 to the drinking mixture, throughout the chronic ethanol treatment, decreased the behavioural excitability seen during ethanol withdrawal in vivo. 3. All the signs of hyperexcitability in field potentials in the isolated hippocampal slice, caused by ethanol withdrawal, were decreased by the chronic administration of Bay K 8644. 4. These effects resembled those previously reported for chronic administration of calcium channel antagonists; racemic Bay K 8644 has both calcium channel activating and antagonist properties. 5. Measurement of brain levels of Bay K 8644 at the end of the chronic treatment showed that the compound reached micromolar concentrations during the treatment, but none could be detected in the tissues at the time of the above measurements. 6. It is possible that the results might be explained by predominance of the calcium channel antagonist properties of this compound, owing to the high central concentrations achieved during the treatment. Tolerance to the calcium channel activating properties of Bay K 8644 may also have occurred during the chronic treatment.     

How can the evaluation of genetic tests be enhanced? Lessons learned from the ACCE framework and evaluating genetic tests in the United Kingdom.

Advances in genetic technology are increasing the availability of genetic tests, not only for rare single gene disorders, but also for common diseases such as breast and colo-rectal cancer. Before there can be widespread uptake of these tests, they must be evaluated to confirm the benefits of their use. But how should genetic tests be evaluated, given the speed at which new tests are emerging? One highly influential approach is the analytic validity, clinical validity, clinical utility and ethical, legal and social issues (ACCE) framework, which has provided a benchmark for the evaluation of genetic tests. The approach has been adopted and adapted by the United Kingdom Genetic Testing Network, with the help of the Public Health Genetics Unit in Cambridge, to evaluate new genetic tests for use in the National Health Service. We discuss a number of conceptual, methodological, and practical issues concerning the evaluation of genetic tests, based on lessons learned from applying the ACCE framework and from the UK experience, and make a number of recommendations to further strengthen the evaluation of genetic tests.     

The role of bladder catheterization in total knee arthroplasty

The use of a urinary bladder catheter in the perioperative period for patients undergoing total knee arthroplasty is controversial. In the current study, two bladder management protocols were studied. One group of patients had an indwelling catheter inserted into the bladder before total knee arthroplasty. The other group of patients was observed and treated for urinary retention as necessary. From 1993 to 1998, 652 patients undergoing primary, unilateral total knee arthroplasty were randomized by surgeon into two groups: one group underwent preoperative insertion of an indwelling bladder catheter (306 patients), and one group (346 patients) had a catheter inserted postoperatively as necessary. Sixty-six percent (229 of 346) of these patients required catheterization (203 had indwelling catheters and 26 had intermittent straight catheters). A urinary tract infection developed in five patients (1.6%) in whom a catheter was inserted preoperatively. A urinary tract infection developed in six patients (1.7%) in whom a catheter was inserted if necessary. Five of these urinary tract infections developed in patients with delayed indwelling bladder catheters. A urinary tract infection did not develop in any patient in whom a straight catheter was inserted. There was no significant difference in the length of stay in the hospital between the two groups. The group in whom a catheter always was inserted generated $491 greater cost for total knee arthroplasty than patients in whom a catheter was inserted if necessary.     

TIPS for acute and chronic Budd-Chiari syndrome: a single-centre experience

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a technically challenging but feasible treatment for Budd-Chiari syndrome (BCS). However, information about the outcome, particularly in patients with liver failure, is scarce. We report our experience of TIPS for BCS. METHODS: Fifteen patients with BCS underwent TIPS. Eight had hepatic failure and seven underwent TIPS for BCS uncontrolled by medical treatment. RESULTS: Fourteen out of 15 had successful TIPS placement. Out of the eight hepatic failure patients, four died soon after TIPS: one liver rupture, one portal vein rupture, one liver failure and one pulmonary oedema. Another patient had a significant intrahepatic haematoma, which resolved with conservative management. TIPS was successfully placed in all of the seven patients with chronic BCS, in whom there was an average follow-up of 20 months. Ascites resolved and liver function improved in all. One patient died after 18 months from the original hepatic metastatic disease. Four patients have had evidence of TIPS dysfunction requiring three balloon dilatations and one restenting. No patient has required liver transplantation. CONCLUSIONS: TIPS should be the first line treatment for BCS uncontrolled by medical therapy. However, mortality in BCS with hepatic failure is high and liver transplantation could be a better option.     

Position statement on opportunistic genomic screening from the Association of Genetic Nurses and Counsellors (UK and Ireland)

The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening'' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.     

Your fate is in your hands? Handedness,digit ratio (2D:4D), and selection to a national talent development system

Over the past decade a small evidence base has highlighted the potential importance of seemingly innocuous variables related to one's hands, such as hand dominance and the relative length of the second and fourth digits (2D:4D ratio), to success in sport. This study compared 2D:4D digit ratio and handedness among handball players selected to advance in a national talent development system with those not selected. Participants included 480 youth handball players (240 females and 240 males) being considered as part of the talent selection programme for the German Youth National team. Hand dominance and digit ratio were compared to age-matched control data using standard t-tests. There was a greater proportion of left-handers compared to the normal population in males but not in females. There was also a lower digit ratio in both females and males. However, there were no differences between those selected for the next stage of talent development and those not selected on either handedness or digit ratio. These results add support for general effects for both digit ratio and handedness in elite handball; however, these factors seem inadequate to explain talent selection decisions at this level.     

Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer‐assisted digital image analysis (DIA) of Sirius Red‐stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively‐transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty‐two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 5–10). Portal hypertension (HVPG ≥ 6 < 10 mmHg) was present in 30 (69.8%), and HVPG ≥ 10 mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.75–23.25). Median Child–Pugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.3–12.4) versus 23% in stage 6 (IQR 17–33.7, P < 0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically‐significant portal hypertension (HVPG ≥ 10 mmHg, odds ratio: 1.085, confidence interval: 1.004–1.172, P = 0.040). A CPA of 14% was the best cut‐off value for clinically‐significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event‐free survival was significantly shorter in patients with CSPH or with a CPA value ≥ 14%, or with a combination of both. Conclusion: In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing “early” from “late” severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG ≥ 10 mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification.     

Simple and reproducible hepatectomy in the mouse using the clip technique

AIM: To investigate the reliability of massive hepatectomy models by using clip techniques.METHODS: We analyzed anatomical findings in 100 mice following massive hepatectomy induced by liver reduction > 70%. The impact of various factors in the different models was also analyzed, including learning curves, operative time, survival curves, and histopathological findings.RESULTS: According to anatomical results, models with 75%, 80%, and 90% hepatectomy produced massive hepatectomy. Learning curves and operative times were most optimal with the clip technique. Each hepatectomy performed using the clip technique produced a reasonable survival curve, and there were no differences in histopathological findings between the suture and clip techniques.CONCLUSION: Massive hepatectomy by the clip technique is simple and can provide reliable and relevant data.