Liver transplantation: Issues for the next 20 years

The growing numbers of potential transplant recipients on waiting lists is increasingly disproportionate to the supply of cadaveric donor organs. The hope for the next 20 years is that supply will satisfy demand. This requires both a reduction in indications for the procedure and an increase in the transplants performed. A multi-pronged approach is needed to increase cadaveric organ donation, generating enthusiasm for donation among both the general public and hospital staff. Accurate assessment of marginal grafts with stringent criteria known to predict graft function will diminish wastage of organs. Methods of rehabilitating marginal grafts during extracorporeal perfusion will increase organ availability. Supply of non-heart beating donors can be greatly expanded and protocols developed with ethical consent to optimize their initial function despite warm ischemia. Splitting livers that fulfill selection criteria, thus providing for two recipients, should be universally applied with acceptable incentives to those units who do not directly benefit. A proportion of recipients, though not those transplanted for autoimmune disease, will be spared the side-effects of immunosuppression thanks to immune tolerance. Protocols for close monitoring of those patients for rejection during treatment withdrawal must be carefully observed. In addition to gene therapy, it is highly likely that hepatocyte transplantation will replace orthotopic grafting in patients without cirrhosis, especially for inherited metabolic diseases. It is much more difficult to envisage that heterologous stem cell transplantation or xenotransplantation will have clinical impact in the next 20 years, although research in those areas has obvious long-term potential.     

COMPARATIVE EVALUATION OF NO-SCALPEL VASECTOMY AND STANDARD INCISIONAL VASECTOMY

No-scalpel vasectomy employs a refined method of dissection and delivery of the vas deferens. We compared no-scalpel vasectomy with standard incisional vasectomy in 176 patients over a 33 month period. The haemorrhage rate was 1.08 per cent for no-scalpel vasectomy compared with 11.9 per cent for standard vasectomy (p < 0.005). The infection rate was 3.26 per cent for no-scalpel vasectomy as against 14.28 per cent for standard vasectomy (p < 0.01). There was a 37.5 per cent reduction in operating time and a substantial reduction in pain during and after the procedure when no-scalpel vasectomy was performed and also there was no failure of vasectomy. No-scalpel vasectomy is a satisfactory alternative to standard vasectomy with fewer complications and increased patient acceptability.KEYWORDS: Male sterilization, Vasectomy     

Growth monitoring: testing the new guidelines

OBJECTIVE: To assess the impact of recent guidelines from the UK joint working party of child health surveillance recommending that all children be measured at age 5 and again between 7 and 9 years of age to determine how many normal school age children are likely to be referred for specialist assessment. METHODS: The longitudinal data of 486 children measured by school nurses in a community setting were examined and compared with measurements made in a research setting by a single, skilled observer. MAIN OUTCOME MEASURES: Number of children identified as having abnormal stature (< 0.4th or > 99.6th centile) and abnormal growth rate height standard deviation score (HSDS) change > 0.67). RESULTS: The community survey identified seven (1.4%) children as having abnormal stature (four short, three tall), 11 (2.3%) were identified as "slow growing", and nine (1.9%) increased their HSDS by more than 0.67. These results were comparable to data collected in ideal research conditions. CONCLUSIONS: Following the recommendations would not result in an excess number of inappropriate referrals. However, this study highlights several unresolved issues such as interobserver variability and time interval between measurements. A large scale prospective study should be considered to establish realistic and cost-effective criteria before implementation of a national screening programme.     

Cytokeratin phenotypes at the dento-gingival junction in relative health and inflammation, in smokers and non-smokers

OBJECTIVES: The cells of the junctional epithelium (JE) provide and maintain the epithelial attachment, and remain morphologically and phenotypically distinct from oral sulcular (OSE) and external oral epithelia (EOE), from which they may be regenerated de novo. Expression of cytokeratins (CK) in human epithelia has been shown to be highly site-specific, implying a functional role. The aims of this study were to differentiate between the cyto-keratin profiles of JE, OSE, EOE and pocket epithelia (PE) in health and disease, in smokers and non-smokers.
MATERIALS AND METHODS: The cytokeratin profiles of 40 samples of healthy and clinically inflamed human gingival tissue taken from 15 smokers and 25 non-smokers were studied by immunocytochemistry. Cryostat sections of fresh frozen gingival tissues were stained with a panel of monoclonal antibodies (mAb) and visualised by a biotin-Streptavidin-peroxidase complex technique.
RESULTS: JE and PE expressed an identical range of cytokeratins irrespective of the inflammatory or smoking status, with the exception of CK4 expression, which tended to be increased in smokers. The OSE and EOE expressed non-cornifying and cornifying differentiation cytokeratins respectively, but in the presence of inflammation, both these epithelia showed increased expression of CK19 at a basal level in association with expression of one or more of the simple cytokeratins. JE/PE expressed CK17 in external layers only, approximating the tooth surface. All epithelia expressed CK6,16 the markers of high cell turnover.
CONCLUSIONS: CK19 was a consistent differentiation marker for JE and PE.Expression of CK8,18 was enhanced by inflammation. CK4 expression increased in association with smoking. Markers of differentiation were not always co-expressed equally within a pair. Pairs were not always completely mutually exclusive with frequent co-localisation.     

Multivariate Analysis of Clinical Factors in Restenosis after Coronary Stenting

Ojbective To find the independent predictors for restenosis after coronary stenting. Methods Quantitative angiography was performed on 60 cases (67 successfully dilated lesions) after angio-plasty over 6-months follow-up, and both univariate and multivariate logistic regression analysis were done to i-dentify the correlations of restenosis with clinical factors. Results The total restenosis rate was 31. 3% (21 of 67 lesions), and according to univariate analysis the patients who underwent coronary stenting≥ 3. 5mm had a lower rate of restenosis ( P < 0. 01). Collateral circulation to the obstruction site, high maximal inflation pressure, smoking and the less minimal lumen diameter after PTCA made the rate of restenosis higherower ( P < 0. 05) . Multivariate logistic regression analysis showed that coronary stenting ≥3. 5mm had a low rate of restenosis, but high maximal inflation pressure and smoking made the restenosis rate higher. Conclusion Coronary stent size, maximal inflation pressure and. smokin     

Patel S,Turner PR,Stubberfield C,Barry E,Rohlff CR,Stamps A,McKenzie E,Young K,Tyson K,Terrett J,Box G,Eccles S,Page MJ. Hyaluronidase gene profiling and role of HYAL‐1 overexpression in an orthotopic model of prostate cancer. International Journal of Cancer 2002;97(4): 416–424.

The original article to which this Erratum refers was published in International Journal of Cancer; 2002; 97(4) 416–422.     

Modulation of gastrointestinal function by MuDelta,a mixed μ opioid receptor agonist/ μ opioid receptor antagonist

BACKGROUND & PURPOSE

Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound (‘MuDelta’), could normalize GI motility without constipation.

EXPERIMENTAL APPROACH

MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified.

KEY RESULTS

δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model.

CONCLUSIONS AND IMPLICATIONS

MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.