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Biomedical subjects

M R Novelli

Publications and source records attributed to M R Novelli.

12 recordsLinked to original sources
PubMed2006

Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett's oesophagus.

BACKGROUND AND AIMS: Endoscopic surveillance of Barrett's oesophagus currently relies on multiple random biopsies. This approach is time consuming, has a poor diagnostic yield, and significant interobserver variability. Elastic scattering spectroscopy is a real time in vivo optical technique which detects changes in the physical properties of cells. The aim of this study was to assess the potential for elastic scattering to detect high grade dysplasia or cancer within Barrett's oesophagus. METHODS: Elastic scattering spectroscopy measurements collected in vivo were matched with histological specimens taken from identical sites within Barrett's oesophagus. All biopsies were reviewed by three gastrointestinal pathologists and defined as either "low risk" (non-dysplastic or low grade dysplasia) or "high risk" (high grade dysplasia or cancer). Two different statistical approaches (leave one out and block validation) were used to validate the model. RESULTS: A total of 181 matched biopsy sites from 81 patients, where histopathological consensus was reached, were analysed. There was good pathologist agreement in differentiating high grade dysplasia and cancer from other pathology (kappa = 0.72). Elastic scattering spectroscopy detected high risk sites with 92% sensitivity and 60% specificity and differentiated high risk sites from inflammation with a sensitivity and specificity of 79%. If used to target biopsies during endoscopy, the number of low risk biopsies taken would decrease by 60% with minimal loss of accuracy. A negative spectroscopy result would exclude high grade dysplasia or cancer with an accuracy of >99.5%. CONCLUSIONS: These preliminary results show that elastic scattering spectroscopy has the potential to target conventional biopsies in Barrett's surveillance saving significant endoscopist and pathologist time with consequent financial savings. This technique now requires validation in prospective studies.

Adenocarcinoma↗
PubMed2002

Haemorrhage into chronic plaque psoriasis as a consequence of disseminated intravascular coagulation.

We describe a patient with chronic plaque psoriasis who developed haemorrhage into pre-existing lesions during an episode of disseminated intravascular coagulation secondary to sepsis. Disseminated intravascular coagulation is a complex disorder characterized by widespread intravascular deposition of fibrin with consumption of coagulation factors and platelets and occurs as a consequence of many disorders that release procoagulant material into the circulation or cause widespread endothelial damage or platelet aggregation. As both disseminated intravascular coagulation and psoriasis occur relatively frequently in the general population we were surprised to find no previous reports of this phenomenon in the literature.

Chronic Disease↗
PubMed1999

Tumor burden and clonality in multiple intestinal neoplasia mouse/normal mouse aggregation chimeras.

Aggregation chimeras were formed between C57BL/6 mice heterozygous for the Apc(min) (Min) mutation and wild-type SWR mice, that differ in their Pla2g2a status, a modifier of Apc(min), and also in their resistance to intestinal polyp formation. Variation in the dolichos biflorus agglutinin-staining patterns of the intestines of these mouse strains was used to determine the chimeric composition of the intestine in individual mice and to examine the clonal composition of adenomas. Macroscopic adenoma numbers in chimeric mice were compared with the expected adenoma numbers based on the percentage of C57BL/6J-Apc(min/+) epithelium in individual mice. These results unexpectedly show that there was no apparent inhibitory effect of the SWR-derived (Pla2g2a wild-type) tissue on adenoma formation in the C57BL/6J-Apc(min/+) epithelium. This suggests that the main genetic modifiers of the Min phenotype act at a cellular or crypt-restricted level with no discernable systemic effect. All adenomas were seen to contain C57BL/6J-Apc(min/+)-derived epithelium, confirming that the germ-line mutation of the mApc gene is necessary to initiate tumorigenesis in this model system, and that the mApc gene acts in a cell autonomous fashion.

Adenoma↗
PubMed1998

Helical CT pneumocolon to assess colonic tumors: radiologic-pathologic correlation.

OBJECTIVE: The objective of this study was to determine the accuracy of helical CT pneumocolon in the staging of colonic carcinomas. SUBJECTS AND METHODS: Fifty-two patients (27 men, 25 women; age range, 40-88 years old; mean age, 67 years old) with known or strongly suspected colonic disorders underwent CT pneumocolon. After bowel cleansing, administration of smooth muscle relaxant, and rectal air insufflation, CT pneumocolon was performed with 5-mm collimation, 2.5-mm reconstruction interval, and a pitch of 1.5. Two contrast administration protocols were used. Twelve patients received 100 ml of i.v. contrast material that was injected at 3 ml/sec; scan delay was 45 sec. The other 40 patients received 150 ml of contrast material at 5 ml/sec; scan delay was 25 sec. Images were prospectively evaluated. All patients had pathologic confirmation: 46 patients had resections and six patients had endoscopic biopsies. RESULTS: Diagnostic images were obtained in 47 of 52 patients. In the 47 patients, there were 38 colonic carcinomas (one synchronous), nine diverticular strictures, eight polyps, one ischemic stricture, and one normal study. Thirty of 38 carcinomas were correctly staged by CT. Sensitivity and specificity for serosal infiltration were 100% (35/35 carcinomas) and 33% (one of three carcinomas), respectively; sensitivity and specificity for lymph node involvement were 56% (nine of 16 carcinomas) and 95% (21/22 carcinomas), respectively. Four polyps that were smaller than 5 mm in diameter were not revealed by CT. Twelve of 14 benign lesions were correctly diagnosed and two were believed to be malignant. No malignant lesion was misdiagnosed. CONCLUSION: CT pneumocolon gave an overall staging accuracy of 79% in 38 carcinomas.

Adult↗
PubMed1997

Genomic and cDNA sequence analysis of the cell matrix adhesion regulator gene.

The cell matrix adhesion regulator (CMAR) gene has been suggested to be a signal transduction molecule influencing cell adhesion to collagen and, through this, possibly involved in tumor suppression. The originally reported CMAR cDNA was 464 bp long with a tyrosine phosphorylation site at the extreme 3' end, which mutagenesis studies had shown to be central to the function of this gene. Since the discovery of a 4-bp insertion polymorphism within the originally reported coding region, further sequence information has been obtained. The cDNA has been extended 5' by approximately 2 kb revealing a 559-bp region showing strong homology to the proposed 5' untranslated sequence of a murine protein kinase receptor family member, variant in kinase (vik). CMAR genomic sequencing has shown the presence of an intron, the intron/exon boundary lying within this region of homology. An RNA transcript for CMAR of approximately 2.5 kb has also been identified. The data suggest complex mechanisms for control of expression of two closely associated genes, CMAR and the vik- associated sequence.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1996

The mutation rate and cancer.

The selection of advantageous mutations underlies tumorigenesis. The growth of a tumor is therefore a form of evolution at the somatic level, in which the population is comprised of individual cells within the tumor. Models of tumorigenesis have considered the relative importance of mutation and selection. We show that selection is more important than an increased mutation rate in the growth of a tumor. Some cancers may acquire a "mutator phenotype," probably leading to faster growth, but mutator phenotypes are not necessary for carcinogenesis.

Biological Evolution↗
PubMed1996

Polyclonal origin of colonic adenomas in an XO/XY patient with FAP.

It is widely accepted that tumors are monoclonal in origin, arising from a mutation or series of mutations in a single cell and its descendants. The clonal origin of colonic adenomas and uninvolved intestinal mucosa from an XO/XY mosaic individual with familial adenomatous polyposis (FAP) was examined directly by in situ hybridization with Y chromosome probes. In this patient, the crypts of the small and large intestine were clonal, but at least 76 percent of the microadenomas were polyclonal in origin.

Adenomatous Polyposis Coli↗
PubMed1996

Clinico-pathological features and p53 expression in left-sided sporadic colorectal cancers with and without microsatellite instability.

Defects in mismatch repair (MMR) can result in the development of a 'mutator phenotype', manifest as an increase in DNA replication errors (RERs). Patients with hereditary non-polyposis colorectal cancer (HNPCC) have germline mutations in MMR genes. These patients develop carcinomas of the colon and other specific sites at a significantly earlier age than patients with sporadic carcinomas. RERs are found in the cancers from patients with HNPCC and have been demonstrated in 10-20 per cent of sporadic colorectal cancers (CRCs). Loss of MMR may simply accelerate tumour development, but it is also possible that these tumours follow a different carcinogenetic pathway from tumours with intact MMR. In particular, it has been suggested that p53 mutations occur less often in RER-positive (RER+) sporadic colorectal cancers. In this study, the clinico-pathological features and frequency of p53 overexpression in 17 left-sided RER+ CRCs were compared with 35 left-sided RER- CRCs. No differences were found in the age and tumour stage at presentation, mucinous differentiation, or Jass prognostic grouping between these two types of CRC. Thirteen out of 17 (76 per cent) RER+ and 19/35 (54 per cent) RER- tumours showed overexpression of p53, a non-significant difference (chi 2 test). Although some previous studies have suggested differences in the clinico-pathological features and p53 expression of RER+ and RER- right-sided CRCs, our results show that these differences do not exist in left-sided cancers.

Aged↗
PubMed1993

Orofacial myiasis.

Oral myiasis is rare, particularly in western developed countries. This case report describes the presentation of oral myiasis as an enlarged submandibular lymph node associated with a buccal mass, in a Caucasian male who had recently returned from the Gambia. It highlights the need for increased clinical awareness when dealing with patients who have recently travelled overseas.

Diagnosis, Differential↗
PubMed1992

Renal cell carcinoma: comparison of morphological and flow cytometric parameters of primary tumour and invasive tumour lying within the renal vein.

Histological assessment and DNA flow cytometry have been performed on 15 kidneys containing primary adenocarcinomas which had invaded the renal vein. Comparison of morphological variables showed that samples of the intravenous tumour were more commonly composed of granular cells (53 per cent) than were samples from the main tumour mass (16 per cent), and were also of higher nuclear grade. In 7 of 14 kidneys, DNA studies showed either a higher S-phase fraction (five cases) or DNA aneuploidy (two cases) in tumour cells lying within the renal vein. The mean S-phase fraction was also shown to increase in higher nuclear grades. Thus, both morphological and biological differences exist between invasive tumour cells lying within the renal vein and those in the main tumour. This is a useful model for the investigation of venous invasion and may give a better prediction of the metastatic potential of renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1990

Gastric dysplasia: inter-observer variation, sulphomucin staining and nucleolar organizer region counting.

Gastric dysplasia is regarded as a pre-neoplastic lesion and is generally believed to have higher potential for malignant transformation with increasing grade. To obtain consistency in diagnosis and management, reproducible diagnostic criteria are needed. We have used the classification system of the International Study Group on Gastric Cancer--ISGGC and investigated the interobserver variation in histological diagnosis. A Kappa statistic of 0.579, which reflects moderate agreement, was obtained for variation between two experienced pathologists. The prevalence of type III intestinal metaplasia was studied and found to occur in 55% of dysplastic areas, but in only 9% of hyperplastic areas (P less than 0.01). In addition, the correlation of mean nucleolar organizer region (AgNOR) counts with diagnostic categorization was investigated. A significant inter-observer variation was found between an experienced pathologist and a postgraduate student and only one of the observers obtained statistically significant separation of mean AgNOR counts between the categories of high-grade dysplasia, low-grade dysplasia, atypical hyperplasia, simple hyperplasia and normal.

Adult↗