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Biomedical subjects

S M Thomas

Publications and source records attributed to S M Thomas.

At least 19 recordsLinked to original sources
PubMed1997

Establishment of a human squamous cell carcinoma cell line of the upper aero-digestive tract.

A human squamous cell carcinoma (SCC) cell line has been established from the surgical specimen of an untreated, upper aero-digestive tract tumour, diagnosed as a squamous carcinoma, grade III, of the pyriform fossa. The tumour tissue was grown as a xenograft in an athymic nude mouse and was designated as NT-8. Histological examination of the surgical specimen and the nude mouse tumour showed that the two were identical. NT-8 was subsequently passed by subcutaneous injections into nude mice. After the 6th passage in nude mouse, the tumour was cultured in vitro where it grew as an epithelial cell line, with a typical cobblestone appearance. This cell line was designated as NT-8e. Both the primary tumour as well as xenograft and the cells in culture have retained several common morphological and biochemical characteristics. Immunological markers for epithelial cells including epithelial membrane antigen and cytokeratins were seen in all three, confirming the epithelial lineage. Characterization of the NT-8e cell line including growth parameters, anchorage-independent growth and tumorigenicity in nude mice, chromosome counts and DNA content by flow cytometry have been carried out.

Animals↗
PubMed1997

X-ray pelvimetry--which is the best technique?

AIM: To provide definitive data on the radiation doses given to both mother and fetus using different pelvimetry techniques at a number of centres. This data was combined with an assessment of image quality, to determine the optimum technique. PATIENTS AND METHODS: Multiple thermoluminescent dosimeters (TLDs) were used to measure patient and fetal doses inside an anthropomorphic phantom of a pregnant women at full term. Measurements were made at twenty hospitals that routinely perform pelvimetry using techniques including computed tomography (CT), conventional radiography, conventional radiography using an air-gap technique, and digital fluorography. To assess image quality the images obtained by the different techniques were reviewed by a panel of two radiologists and a senior radiographer. RESULTS: A wide range of absorbed doses and relative risks to mother and fetus was observed. The largest and smallest doses encountered in the study differed by a factor of approximately forty. CT pelvimetry was seen to give an average of 25% of the dose of conventional pelvimetry, and at some centres dose savings of over 90% would be possible by performing lateral CT scanograms in preference to plain film pelvimetry. However, a surprisingly wide variation in doses was observed between centres performing CT pelvimetry, and in some cases the potential dose saving would be small. An air-gap technique practised by one of the centres in the survey was found to give absorbed doses and relative risks comparable to average CT scanograms. A digital fluorography technique also gave a very low dose at one centre. However, a similar technique performed at another of the centres conferred little benefit over conventional pelvimetry. There was no observable correlation between the dose administered to the patient and image quality for any of the techniques, and CT and conventional pelvimetry both gave similar image quality. CONCLUSION: While CT deserves its reputation as a low dose technique for pelvimetry, in some cases there may be little dose saving over conventional techniques. The total mAs from the CT examination should be kept as low as possible. Low absorbed doses with good image quality may also be achieved without specialized equipment using an air gap technique. This method is highly recommended as an alternative to CT, for example if no CT scanner is available.

Female↗
PubMed1997

Intravascular contrast media: can we justify the continued use of ionic contrast agents?

Cost has been the major factor preventing the universal conversion to non-ionic contrast agents. We assessed the costs and potential benefits of making this change in our department. During a 10-month-period the use of all intravascular contrast agents and reaction rates were audited prospectively. One thousand three hundred and ninety-four examinations were included. A local protocol for the use of ionic and non-ionic contrast media was already in place, based on the Royal College of Radiologists Guidelines. For each patient the contrast agent used, risk factors, and presence or absence of a contrast reaction were recorded. Non-ionic contrast agent usage exceeded ionic by a factor of 10. Patients receiving ionic agents intravenously had a reaction rate of 16.8% compared with 2.7% for non-ionic contrast media. The use of ionic contrast media was subsequently suspended and the effect of this on overall costs assessed by retrospectively and prospectively analysing hospital expenditure on contrast agents. No increase in costs was found. The reasons for this are two-fold. Firstly in our institution the protocol in place and the nature of the workload resulted in relatively small volumes of ionic contrast media being used compared with non-ionic agents. Secondly, since our department is a bulk purchaser of non-ionic agents, substantial discounts could be negotiated. The benefits of non-ionic contrast media are well recognized and our experience suggests that cost may no longer be a barrier to conversion to these lower risk agents.

Contrast Media↗
PubMed1997

Changing cancer outcome: the role of LSUMC Minority-Based Clinical Community Oncology Program.

The National Cancer Institute has recognized the need for minority participation in clinical trials as a means to enhance cancer outcomes in minority populations and to validate the outcomes of clinical research. In 1994, Louisiana State University Medical Center in New Orleans was granted an award by the National Cancer Institute to establish a Minority-Based Clinical Community Oncology Program. This article outlines the Louisiana State University's Minority Based Clinical Community Oncology Program. During the initial funding period, the Program has established a regional network of cancer physicians and healthcare professionals to provide state-of-the-art cancer treatment and prevention trials to South Louisiana for indigent and minority populations who otherwise would have little access to this care. Because of the success of the Program in patient accrual to both cancer treatment and cancer prevention and control protocol trials, Louisiana State University Medical Center has applied for a continuation of funding for the Program for the next five years.

Clinical Trials as Topic↗
PubMed1997

Promoters of progression of diabetic nephropathy: the relative roles of blood glucose and blood pressure control.

BACKGROUND AND AIMS: Hyperglycaemia is a strong risk factor for the development of renal disease in insulin dependent diabetes mellitus but it is uncertain whether it contributes to the progression of incipient or established nephropathy. The rigorous treatment of blood pressure in recent years may help uncover the contribution of hyperglycaemia, if any, to the progression of renal failure. Our aim therefore, was to assess in a current cohort of insulin dependent diabetic patients with diabetic nephropathy the relative importance of glycaemic control and blood pressure on disease progression. METHODS: All insulin dependent diabetic patients with persistent albuminuria (> 300 mg/24 h) attending the diabetic clinic at Guy's Hospital between 1977 and 1993 were recruited. Serial measurements of blood pressure, HbA1 and GFR were performed every 6 months until end-stage renal disease or death. Only patients with at least 1 year of follow up were analysed. The mean follow up period was 8 years (range 1.5-15.5 years). Baseline and time dependent variables were related to the rate of change of GFR using weighted linear regression and stepwise multiple regression analysis. The impact of each variable on the change of GFR with time was adjusted for the effect of other potentially confounding variables by analysis of co-variance. RESULTS: Patients had well-controlled blood pressure throughout the observation period (mean arterial pressure 97 +/- 8 mmHg) and the average rate of decline of GFR was 4.32 +/- 4.08 ml/min/year. In univariate analysis baseline and mean HbA1 were linearly related to the rate of decline of GFR (baseline r5-0.565, P < 0.001; mean r-0.5107, P < 0.001) with those with a higher HbA1 having a faster rate of progression. In stepwise multivariate analysis both mean HbA1 mean diastolic blood pressure (P < 0.0001 and P = 0.019, respectively) was significantly and independently related with a faster rate of decline of GFR. CONCLUSIONS: Worse glycaemic control is associated with a faster rate of progression of diabetic nephropathy once blood pressure is controlled. Thus improvement of glycaemic control in patients where good blood pressure control has been achieved may potentially further delay the progression of nephropathy.

Adolescent↗
PubMed1996

A modified Luria-Delbrück fluctuation assay for estimating and comparing mutation rates.

We have investigated the accuracy with which mutation rates may be estimated using a modification of the Luria and Delbrück fluctuation experiment protocol. The modification involves growing a larger-than-usual culture, and plating out a small aliquot of it. Monte Carlo simulations of the experiments confirm that the modification leads to a decrease in the coefficient of variation of the estimated mutation rate where this is based on the median number of mutants detected in a number of cultures grown in parallel. If sets of experimental and control cultures are compared using the Mann-Whitney U-test, then fractional increases in mutation rate can be reliably detected using relatively small numbers of cultures. The modified protocols promise better estimates of mutation rates, offer a powerful test of differences in mutation rates, and are easier to implement in practice.

Computer Simulation↗
PubMed1996

Is the metacarpal index useful in the diagnosis of Marfan syndrome?

AIM: This study was undertaken to analyse the importance of the Metacarpal Index (MCI) in making the diagnosis of Marfan syndrome. PATIENTS AND METHODS: The characteristics of 42 patients with Marfan syndrome as defined by strict criteria were analysed. Fifty-one consecutive accident and emergency patients comprised the control group for the MCI measurements. RESULTS: Using MCI alone four (7.8%) of controls had an abnormal MCI, and seven (16.6%) of Marfan patients were normal. Thirty-two (76%) of Marfan patients had an abnormal MCI and three (13.4%) were equivocal. Using other skeletal parameters (upper segment to lower segment ratio, arm span 3 cm or more greater than height, or palate, pectus or scoliosis deformity) 40 (95%) of the Marfan group had an abnormality. Other parameters: 18 (43%) in the Marfan group gave a history of retinal detachment or ectopia lentis. Echocardiographic measurements showed aortic root dilatation in 29 (69%) and in 21 (50%) mitral valve prolapse was found; 37 (88%) had one or other cardiac abnormality. Using all parameters excluding MCI: All the patients would still have fulfilled the diagnostic criteria for the diagnosis of Marfan syndrome. CONCLUSION: The role of the MCI, a radiation dependent and time consuming measurement, is probably insignificant in diagnosis of the majority of Marfan patients. Combined with clinical measurements, an echocardiogram is probably the single most useful investigation, aiding both diagnosis and management.

Adult↗
PubMed1996

Ultrasound appearance of pseudomembranous colitis.

A case illustrating that ultrasound can be useful in the diagnosis of pseudomembranous colitis is reported. Diagnosis of pseudomembranous colitis is usually made from microbiological or histopathological investigations. The ultrasound appearance of grossly thickened bowel wall with luminal narrowing is non-specific, but in the correct clinical context should suggest the diagnosis of pseudomembranous colitis.

Enterocolitis, Pseudomembranous↗
PubMed1995

Specific and redundant roles of Src and Fyn in organizing the cytoskeleton.

Mouse embryos lacking Csk, a negative regulator of Src family kinases, exhibit defects in neurulation and die at mid-gestation. To determine the role of activated Src family kinases in the csk- phenotype, we have introduced mutations in the src and fyn genes into the csk- mutant background. Genetic analysis reveals that src, but not fyn, is partly epistatic to the csk gene. Biochemical analysis indicates that several cytoskeletal proteins are hyperphosphorylated on tyrosine residues in csk- cells. Regulation of cortactin and tensin hyperphosphorylation is Src-dependent, whereas focal adhesion kinase and paxillin hyperphosphorylation is partly dependent on both Src and Fyn. Furthermore, the src- mutation can restore the normal distribution of cortactin and partly correct filamentous actin organization in csk-cells. Thus, Src family kinases have both specific and overlapping functions in regulation of the cytoskeleton. The disturbance of these functions may be a molecular basis for the phenotype exhibited by csk- mutants.

Animals↗
PubMed1995

Superoxide dismutase activity in lymphoblastoid cells from motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients.

Point mutations in the gene encoding Cu,Zn superoxide dismutase (SOD1) are associated with autosomal dominant familial amyotrophic lateral sclerosis (FALS). We have measured Cu,Zn SOD activity in lymphoblastoid cells from affected and at risk FALS patients carrying mutations in the SOD1 gene, FALS patients without mutations in the SOD1 gene, individuals affected by the sporadic form of the disease (SALS), normal controls and individuals with other neurological abnormalities. The results show a significant decrease in Cu,Zn SOD activity in affected and at risk FALS individuals as compared to FALS patients without mutations, SALS individuals, normal and neurological controls. It is concluded that decreased SOD activity may contribute, together with other as yet unknown factors, to motor neurone demise.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Calcium influx induces neurite growth through a Src-Ras signaling cassette.

We find that calcium influx through voltage-dependent calcium channels causes extensive neurite outgrowth in PC12 cells. The calcium signal transduction pathway promoting neurite outgrowth causes the rapid activation of protein tyrosine kinases, which include Src. Protein tyrosine phosphorylation results in the formation of an Shc/Grb2 complex, leading to Ras activation, MAP kinase activation, and the subsequent induction of the immediate early gene NGFI-A. Protein tyrosine phosphorylation, gene induction, and neurite outgrowth are inhibited by the expression of dominant negative forms of both Src and Ras, indicating a requirement for both proto-oncoproteins in calcium signaling. Our results suggest that a signaling cassette which includes Src and Ras is likely to underlie a broad range of calcium of actions in the nervous system.

Adaptor Proteins, Signal Transducing↗
PubMed1995

The role of thyroid fine needle aspiration (FNA) cytology in a District General Hospital setting.

The pilot study was undertaken to evaluate the role of FNA cytology in the clinical management of patients with thyroid swelling, in a District General Hospital (DGH) setting. One hundred and eleven patients were investigated over a period of 3 years, with a total of 142 fine needle aspirations. Statistical analysis showed a sensitivity of 71%, a specificity of 91% and a false negative rate of 2.7%. These results compare very favourably with other institutions. This study therefore shows that thyroid nodule FNA cytology can be performed in a DGH with a high standard of diagnostic accuracy, the results of which play a key role in patient management.

Biopsy, Needle↗