Preliminary observations of holmium:YAG laser tissue interaction using human uterus.

Preliminary observations of a pulsed Ho:YAG laser on human uterine tissue in-vitro are presented. The tissue effect on the uterine myometrium was demonstrated using fresh uteri which had been subjected to laser energy. The laser crater and surrounding zone of thermal necrosis (ZTN) was quantified. Measurements demonstrated a consistent narrow ZTN (0.8-1.8 mm) irrespective of power or pulse frequency used. The percentage forward transmission of laser energy through 1 mm of myometrium was investigated using a pyroelectric detector and found to be 0.41%. Finally, a visible and measureable photoacoustic component to the Ho:YAG laser was demonstrated using a water bath and needle hydrophone.     

Over-expression of p53 nuclear oncoprotein in colorectal adenomas.

p53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53 protein is undetectable by standard immunohistochemical staining and the over-expression found in neoplastic cells correlates with the presence of point mutations of evolutionary conserved regions of the p53 gene. We examined the expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17 tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19 moderate, 6 severe), 11 moderately differentiated adenocarcinomas (6 Duke's A, 4 Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1 which recognises p53 protein in conventionally fixed and processed histological material. We found that 15 out of 36 colorectal adenomas showed p53 immunoreactivity, although in 4 positive cases (26%) the staining was very focal (less than 0.1% positive cells). More than 80% of severely dysplastic adenomas showed strong p53 immunoreactivity and this over-expression was correlated with increased cell proliferative rate as detected by the proliferating-cell-nuclear-antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%) colorectal adenocarcinomas as previously shown. Our data suggest that the p53 gene mutation, with the subsequent over-expression of the protein, occurs in colorectal adenomas and may therefore be a fundamental genetic event underlying the dysplasia and loss of proliferative control that are characteristic of adenomas with malignant potential.     

A descriptive study of the decline in cervical screening coverage rates in the North East and Yorkshire and the Humber regions of the UK from 1995 to 2005

Since the mid-1990s, there has been a steady decline in coverage rates for cervical screening in the target age group (25-64 years) across England. This article describes the rate of decline from 1995 to 2005 in the old health authority areas of the North East and the Yorkshire and the Humber (NEYH) regions in relation to age group, deprivation, ethnicity and religion. The results show that the rate of decline is faster in these northern regions than that in England as a whole, with a very strong correlation between age and rate of change of coverage rates. Younger age groups experience the fastest rate of decline, and those over 55 years show an increase in coverage rates. There is an association between the deprivation of the old health authority areas and the rate of change of coverage rates, with weaker evidence that areas with high proportions of Black or Mixed ethnicity may have a faster decline. However, the rate of decline is not associated with other ethnic groups or religions. Therefore, interventions could be targeted at younger women and those who live in deprived areas to prevent the widening of inequalities.     

Acute clostridial enteritis--or pig-bel?

Acute postprandial gastric dilatation and associated clostridial enteritis necroticans is a well recognised but unusual clinical condition. Non-pathological overeating, gastric distension, and clostridial enteritis, termed pig-bel, has been reported in Papua, New Guinea. A similar condition (Darmbrand) was reported from Germany after the second world war, but it is not a condition seen in our society today. Gastric dilatation alone may be seen in individuals with anorexia nervosa, who may occasionally indulge in episodes of overeating (bulimia). We wish to report a case of gastric dilatation associated with a fulminating enteritis, and discuss the similarities with enteritis necroticans (pig-bel).     

Gout in solid organ transplantation: a challenging clinical problem

Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor.Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined.Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with renal failure, solid organ transplant or tophaceous/polyarticular gout. Monitoring for hepatotoxicty is essential for patients taking benzbromarone.Physicians should carefully consider therapeutic options for the management of hypertension and hyperlipidaemia, which are common in transplant recipients. While loop and thiazide diuretics increase serum urate, amlodipine and losartan have the same antihypertensive effect with the additional benefit of lowering serum urate. Atorvastatin, but not simvastatin, may lower uric acid, and while fenofibrate may reduce serum urate it has been associated with a decline in renal function.Gout in solid organ transplantation is an increasing and challenging clinical problem; it impacts adversely on patients' quality of life. Recognition and, if possible, alleviation of risk factors, prompt treatment of acute attacks and early introduction of hypouricaemic therapy with careful monitoring are the keys to successful management.     

IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis

The interleukin (IL)-17/IL-23 axis is an important pro-inflammatory pathway in rheumatoid arthritis (RA). IL-23 maintains CD4(+) T-helper 17 (Th(17)) cells, whereas IL-12 negates IL-17A production by promoting Th(1)-cell differentiation. We sought evidence for any effect of polymorphisms within the interleukin-23 receptor (IL-23R), IL-12 or IL-21 genes on serum cytokine concentrations in 81 patients with RA. Serum cytokines were measured using bead-based multiplex assays. Targeted cytokines were detected in up to 66% of samples. A subgroup of 48 patients had detectable serum IL-17A. Within this subgroup, patients, homozygous for the IL-23R rs11209026 major allele had significantly higher serum IL-17A concentrations compared with patients with the minor allele (394.51 ± 529.72 pg ml(-1) vs 176.11 ± 277.32 pg ml(-1); P = 0.017). There was no significant difference in any of the cytokine concentrations examined in patients positive for the minor allele vs homozygosity for the major allele of IL-12B rs3213337, IL-12Bpro rs17860508 and IL-21 rs6822844. Our results suggest the IL-23R Arg381Gln substitution may influence serum IL-17A concentrations. In patients with the 381Gln allele higher IL-23 concentrations may be needed to produce similar IL-17A concentrations to those in patients with the 381Arg allele. This suggests altered IL-23R function in patients with the minor allele and warrants further functional studies.     

Quantification of cellular autofluorescence of human skin using multiphoton tomography and fluorescence lifetime imaging in two spectral detection channels

We explore the diagnostic potential of imaging endogenous fluorophores using two photon microscopy and fluorescence lifetime imaging (FLIM) in human skin with two spectral detection channels. Freshly excised benign dysplastic nevi (DN) and malignant nodular Basal Cell Carcinomas (nBCCs) were excited at 760 nm. The resulting fluorescence signal was binned manually on a cell by cell basis. This improved the reliability of fitting using a double exponential decay model and allowed the fluorescence signatures from different cell populations within the tissue to be identified and studied. We also performed a direct comparison between different diagnostic groups. A statistically significant difference between the median mean fluorescence lifetime of 2.79 ns versus 2.52 ns (blue channel, 300-500 nm) and 2.08 ns versus 1.33 ns (green channel, 500-640 nm) was found between nBCCs and DN respectively, using the Mann-Whitney U test (p < 0.01). Further differences in the distribution of fluorescence lifetime parameters and inter-patient variability are also discussed.