Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased AI was significantly associated with increased bcl-2 expression (p

Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele

Is screening for Factor V Leiden and Prothrombin G20210A Mutations in Renal Transplantation worthwhile? Results of a large single-center U.K. study

This single center study is the largest series of renal transplant recipients and donors screened for the commonest prothrombotic genotypes. A total of 562 transplant recipients and 457 kidney donors were genotyped for the factor V Leiden and prothrombin G20210A mutations. The prevalence of heterozygous factor V Leiden was 3.4% and 2.6% and prothrombin G20210A was 2.0% and 1.1% in recipients and donors, respectively, similar frequencies to that of the general U.K. population. The 30-day and 1-year graft survival rates in recipients with thrombophilic mutations were 93% and 93%, compared with 88% and 82% in patients without these mutations (log-rank P =0.34). Thrombophilia in recipients (odds ratio 0.55; confidence interval 0.06-2.29; P =0.56) or in donors (odds ratio 1.53; confidence interval 0.27-5.74; P =0.46) did not correlate with graft loss at 30 days after transplantation. In contrast to recent reports, this study did not demonstrate an association between thrombophilia and renal allograft loss, and routine screening is not recommended.

Antisense Bcl-2 Oligonucleotide Uptake in Human Transitional Cell Carcinoma.

Objectives; Antisense oligonucleotides (AO) downregulate Bcl-2 protein expression in various tumours if good target cell uptake is achieved. In this study, uptake of FITC labelled AO (FITC-AO) directed at Bcl-2 was examined in; (1) the RT4 bladder tumour cell line (2) normal pig urothelium and (3) human superficial bladder tumours. Methods; In the RT4 cell line, uptake of FITC-AO, FITC-scrambled and FITC-sense oligonucleotides were quantified by flow cytometry at 4h intervals over 24h. Uptake of FITC-AO was assessed in normal pig urothelium by flow cytometry after FITC-AO was infused for 1h. Uptake of FITC AO was assessed in samples from 14 human superficial bladder tumours which were maintained in an ex vivo model. In samples from 6 tumours, uptake at 4h was assessed using fluorescence microscopy. In samples from 8 separate tumours uptake every 4h within the first 24h incubation period was assessed by flow cytometry. Results; In the RT4 cell line the FITC-AO, FITC-scrambled and FITC-sense oligonucleotide uptake was similar. Disaggregated cells from the normal urothelium of the three pigs exhibited 33%, 46%, 51% of cells staining positively for FITC-AO as determined by flow cytometry. All 6 tumour samples had detectable intracellular FITC-AO by fluorescence microscopy at 4h. In the 8 tumours ,examined over the 24h incubation period, there was a range of percentages of positively staining cells. However, most tumours had a monotonic increase in intracellular fluorescence intensity that plateaued 16h post infusion. Conclusion; Antisense Bcl-2 oligonucleotides were readily taken up by superficial bladder cancer cells but the heterogenous uptake in tumour samples needs to be considered when assessing the bioavailability of these drugs.

Intensity-modulated radiotherapy reduces lung irradiation in patients with carcinoma of the oesophagus.

The 2-year survival rate after conventional radiotherapy for carcinoma of the oesophagus is around 10–20% [8]. Concomitant chemoradiation schedules have produced survival figures of 25–30% at 5 years, and this is now considered standard treatment [1]. Conformal radiotherapy techniques offer the potential to deliver higher doses of radiation to oesophageal tumours [5], and this may improve local tumour control. However, concerns regarding late normal tissue damage to the lung parenchyma and spinal cord remain a concern. Intensitymodulated radiotherapy (IMRT) allows complex dose distributions to be produced, and can reduce the dose to radiosensitive organs close to the tumour [2]. The present study was designed to investigate the impact of beam intensity modulation on treatment planning for carcinoma of the oesophagus, by comparing a standard three-dimensional conformal radiotherapy (3DCRT) technique to an IMRT technique using the same number and orientation of treatment fields.

Are gatekeepers to renal services referring patients equitably?

Objective: Patients with chronic kidney disease (CKD) benefit from specialist interventions to retard progression of renal failure and prevent cardiovascular events. Certain patient groups have poor access to specialist renal services when dialysis is required. This study used a population-based laboratory database to investigate access to and timeliness of referral to renal specialists relatively early in the course of the disease.

Methods: All tests for serum creatinine and haemoglobin (Hb) A1c in Northern Ireland in a two-year period (2001 and 2002) were retrieved for 345,441 adults. Of these, 16,856 patients had at least one serum creatinine level above 150 µmol/L in 2001 not deemed to be due to acute renal failure (crude prevalence 1.42%). This cohort was followed until the end of 2002 and the differences in the time to referral to a specialist were assessed using Cox's proportional hazards regression.

Results: Diabetic patients, older patients and those living in deprived areas were significantly more likely to have serum creatinine testing, compared with non-diabetic, younger and those living in more affluent areas. Delays in referral to renal specialists for patients with raised serum creatinine levels were significantly shorter among diabetic patients, women, younger individuals, those living in rural areas, those living close to renal centres and those living in deprived areas. Overall, only 19% of diabetic patients and 6% of non-diabetic patients who had CKD had seen a renal specialist within 12 months of their index creatinine test.

Conclusion: Contrary to other diseases, disadvantaged patients do not seem to be under-investigated for renal disease compared with their more affluent neighbours and are generally referred earlier for specialist assessment. However, the absolute rate of timely specialist assessment is low. Recent changes in referral criteria for CKD will result in more referrals and will have serious resource implications. Opportunities for health gain among patients with declining renal function are being missed, particularly among the old and those living furthest from specialist centres.