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Biomedical subjects

I S D Roberts

Publications and source records attributed to I S D Roberts.

9 recordsLinked to original sources
PubMed2006

Assessment of the Cardiff nephrectomy cut-up protocol with total blocking of the renal sinus: effect on tumour staging and practical issues.

AIM: To evaluate the effects on detection of vascular invasion and workload of a new standard dissection protocol for examining nephrectomy specimens for renal cell carcinoma. METHODS: Using 192 consecutive renal cell carcinoma nephrectomy specimens, the incidence of vascular invasion and number of tissue blocks per tumour were compared before and after introduction of the new protocol. RESULTS: The Cardiff protocol increased the percentage of tumours staged as T3b (renal sinus or hilar vein invasion) from 37.7% to 55.7% cases (p<0.001), with an increase from 9.1% to 21.7% of those staged as T3b due to renal sinus vein invasion alone (p<0.01). A small, but significant, permanent increase in workload was observed from an average of 11.7 to 13.4 blocks per case (p<0.001). CONCLUSIONS: This protocol is suitable for use in routine practice to evaluate pathological prognostic determinants important for clinical management, while causing only a small increase in workload.

Carcinoma, Renal Cell↗
PubMed2005

Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer.

Hypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. We investigated the hypoxia transcriptome in primary human bladder cancer using cDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated in 39 bladder tumour specimens (27 superficial and 12 invasive). We correlated array mRNA fold changes with carbonic anhydrase 9 (CA IX) staining of tumours as a surrogate marker of hypoxia. Of 6000 genes, 32 were hypoxia inducible in vitro more than two-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor mRNA was upregulated two-fold by hypoxia and 2-18-fold in 31 out of 39 tumours. Glucose transporter 1 was also upregulated on both arrays mRNA, and fold changes on the in vivo array significantly correlated with CA IX staining of tumours (P=0.008). However, insulin-like growth factor binding protein 3 mRNA was the most strongly differentially expressed gene in both arrays and this confirmed its upregulation in urine of bladder cancer patients (n=157, P<0.01). This study defines genes suitable for an in vivo hypoxia 'profile', shows the heterogeneity of the hypoxia response and describes new hypoxia-regulated genes.

Carbonic Anhydrases↗
PubMed2005

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma.

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, non-randomized dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10-150 mg ml(-1) in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml(-1). Urinary VEGF was affected by Suramin at doses above 50 mg ml(-1), corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml(-1) intravesically.

Administration, Intravesical↗
PubMed2003

The autopsy: complete or not complete?

Less invasive or non-invasive alternatives to the complete autopsy have been sought for some time, and a range of methods, ranging from needle sampling to endoscopy to magnetic resonance imaging, have been considered. Evaluations of these methods are few and far between, but generally confirm the predictable conclusion that incomplete autopsies provide incomplete information. It is not difficult to envisage a situation whereby pressure for non-invasive autopsies will allow them to become prevalent, whether properly evaluated or not. However, used appropriately, non-invasive or less invasive autopsies may be valuable tools capable of answering specific questions in situations where it is not possible to perform a complete autopsy.

Autopsy↗
PubMed2003

Accuracy of magnetic resonance imaging in determining cause of sudden death in adults: comparison with conventional autopsy.

AIM: To determine the accuracy and define the limitations of post mortem magnetic resonance imaging (MRI) in determining the cause of sudden death in adults. METHODS AND RESULTS: Sudden unexpected adult deaths in the community, reported to the Coroner (n = 10), excluding suspicious, violent or potentially drug-related deaths, were submitted to whole body MRI, followed by full invasive autopsy. The MRI scans were reported independently by four radiologists, blinded to the autopsy findings; two had previous experience of post mortem MRI. An abnormality that related to the cause of death as identified at autopsy, was identified by at least one radiologist in eight cases. These were pulmonary consolidation (autopsy finding pneumonia) (n = 1), pneumoperitoneum (autopsy finding perforated peptic ulcer) (n = 2), left ventricular failure (autopsy finding ischaemic heart disease) (n = 4), and disseminated bronchial carcinoma (n = 1). However, in only one case were all radiologists able to provide a confident cause of death (disseminated bronchial carcinoma). In two cases, in which death occurred 2-6 days and 3-6 days before MRI, early decomposition prevented interpretation of the images. Severe coronary artery atheroma was detected at autopsy in 7/10, but these lesions were not detected by MRI. Previous experience in reporting post mortem MRI, without autopsy comparison, did not result in more accurate interpretation of the images. CONCLUSIONS: This pilot study suggests that post mortem MRI can identify some abnormalities relating to the common causes of sudden death in adults, but there is a need for greater experience in correlating MRI with autopsy findings before a reliable cause of death can be made by MRI alone. Inability to image coronary artery lesions, differentiating thrombus from clot and pulmonary oedema from pneumonic exudates, are specific problems that may be corrected with greater experience and higher resolution scans.

Adult↗
PubMed2002

The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study.

Calcification and fibrointimal proliferation are associated with advanced complicated atherosclerosis in large arteries but may also occur in smaller vessels, resulting in ischaemic tissue necrosis. This study investigates whether the mechanisms of calcification and intimal fibrosis are similar in vessels of different sizes. The localization of osteopontin (OPN), matrix Gla protein (MGP), thrombospondin-1 (TSP-1), and cartilage oligomeric matrix protein (COMP) was investigated in three types of human vascular lesions: atherosclerosis, chronic vascular rejection (CVR) in renal allografts, and calcific uraemic arteriolopathy (calciphylaxis). These lesions were chosen as they affect different sized blood vessels and they exhibit a fibroproliferative intimal reaction, with or without calcification, resulting in luminal obliteration and ischaemic complications. OPN, MGP, TSP-1, and COMP were not detected in normal blood vessels. However, OPN and MGP were expressed at sites of calcification within atherosclerotic lesions and in microvessels in calciphylaxis, suggesting that calcification in different sized vessels may occur by a common mechanism. These proteins were not detected in areas of fibrointimal proliferation. In contrast, TSP-1 was localized primarily within the fibrous tissue of atherosclerotic lesions and was also expressed in the expanded fibrous intima of arteries showing CVR. COMP was localized primarily within the fibrous tissue under the lipid core of the majority of advanced atherosclerotic lesions. TSP-1 and COMP were also detected in areas of microcalcification in atherosclerotic lesions and TSP-1 was detected adjacent to areas of calcification in calciphylaxis. However, neither TSP-1 nor COMP was localized to calcific foci within these lesions. The localization of OPN, MGP, TSP-1, and COMP to pathological, but not normal arterial intima supports a pathogenetic role for these proteins in the development of vascular fibrosis and calcification. Modulation of their production and activity may offer a novel approach to the therapy of a number of vascular diseases.

Adult↗