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Biomedical subjects

S Woodhouse

Publications and source records attributed to S Woodhouse.

17 recordsLinked to original sources

Effects of radiotherapy on different histopathological types of rectal carcinoma.

BACKGROUND: Down staging by pre-operative chemoradiotherapy is currently considered part of the standard therapeutic approach to rectal carcinoma. The aim of this study was to assess the response to chemoradiotherapy of different histopathological types of rectal carcinoma with emphasis on the mucinous variant. METHOD: Between 1997 and 2002, 71 patients who received pre-operative chemoradiotherapy followed by surgery for rectal carcinoma were enrolled in the study. Staging of the rectal carcinoma was performed according to transrectal ultrasound findings (TN score) prior to the chemoradiotherapy. The chemoradiotherapy was followed by radical resection with mesorectal excision. All surgical specimens were examined by a single pathologist (MB). Pathological TN staging was assessed and tumour regression was graded according to a standard method (TRG1, complete response - TRG5 no response). Tumours were classified as mucinous or nonmucinous according to pre- and post-operative biopsy and specimen histopathological types. TN score change and TRG differences between groups were assessed. RESULTS: Tumour regression was seen after chemoradiotherapy in 94.4% of the patients, while in 5.6% of the patients no response was found. The change in TN score and TRG were correlated. Higher TRG was associated with a smaller decrease in TN staging. TRG was significantly lower in the nonmucinous compared to the mucinous group and the decrease in TN grade was significantly larger in the nonmucinous group. CONCLUSION: Mucinous carcinoma was associated with a lower response to pre-operative chemo-radiotherapy in this group of rectal carcinoma patients. Further studies are needed to determine its prognostic value.

Adenocarcinoma↗

Laboratory ascertainment of Cryptosporidium and local authority policies for investigating sporadic cases of cryptosporidiosis in two regions of the United Kingdom.

To discover laboratory ascertainment and reporting practice for cases of cryptosporidiosis in two health authority regions, we surveyed laboratories serving Wales and the North West of England for faecal screening policies and methods for detection of Cryptosporidium. Forty-eight of the 49 laboratories responded, of which 39 (81%) screen all stool specimens from symptomatic individuals for Cryptosporidium and 9 (19%) screen selected specimens. Although laboratory screening is more complete than has been reported in other regions, we identified discrepancies where patient age was used as a selection criterion, and we make suggestions to amend this. Forty-two (88%) responding laboratories report confirmed cases to the regional Communicable Disease Surveillance Centre (CDSC) and 45 (94%) report to the local authority environmental health department. We also surveyed local authorities in both regions for policy and practice concerning the investigation of reported cases of cryptosporidiosis in the same regions. All 59 local authorities responded, of which 57 (97%) investigate cases by completion of an exposure questionnaire as well as providing advice on the prevention of spread of infection. Variation in case ascertainment may influence perception of incidence, clusters and outbreaks of cases of cryptosporidiosis.

Animals↗

Risk of invasive meningococcal disease among school workers in Cheshire, United Kingdom.

We have demonstrated an increased risk of invasive meningococcal disease among school workers in Cheshire, United Kingdom, compared with other adults in that area (relative risk, 6.0; 95% confidence interval, 2.75--13.07). If this trend is observed elsewhere in the United Kingdom, it may have policy implications for the prevention of such disease in this group of individuals.

Adolescent↗

Loss of heterozygosity and HIV infection in patients with anal squamous-cell carcinoma.

PURPOSE: This study was designed to determine whether loss of heterozygosity and/or microsatellite instability correlate with HIV infection and tumor recurrence after chemoradiation therapy in patients with squamous-cell carcinoma of the anus. BACKGROUND: The molecular mechanisms leading to the progression of HIV-related squamous-cell carcinoma of the anus are poorly understood. In particular, genetic alterations responsible for resistance to chemoradiation have important clinical and functional implications. METHODS: In a case-control study, we analyzed normal and tumor DNA samples of four patients with squamous-cell carcinoma of the anus who were successfully treated with chemoradiotherapy and four patients with radio-resistant squamous-cell carcinoma of the anus who required abdominoperineal resection for local recurrence. To determine the presence of microsatellite instability, we used the reference panel of five pairs of microsatellite primers recommended for colorectal cancer specimens. These include the microsatellite markers BAT25, BAT26, D5S346 (APC), D2S123 (hMSH2), and D17S250 (P53). In addition, we used microsatellite markers for loss of heterozygosity analyses that were tightly linked to tumor suppressor genes. These included D3S1611 (hMLH1), D17S513 (P53), D18S46 and 18qTA (DCC/SMAD4), D5S107 (APC), and CA5 (hMSH2). RESULTS: There were two HIV-positive and two HIV-negative patients in each group. Three HIV-positive patients (one in the chemoradiotherapy group and two in the nonchemoradiotherapy group) demonstrated loss of heterozygosity. In the chemoradiotherapy group, one HIV-positive patient demonstrated loss of heterozygosity at the hMLH1 locus. In the nonchemoradiotherapy group, two HIV-positive patients exhibited a total of four instances of loss of heterozygosity. One tumor had loss of heterozygosity at hMSH2 and DCC/SMAD4; another tumor demonstrated loss of heterozygosity at hMSH2 and APC. Microsatellite instability-low was found in two HIV-positive patients. No instances of loss of heterozygosity and microsatellite instability were detected in HIV-negative patients. CONCLUSION: Loss of heterozygosity and microsatellite instability, which reflect inactivation of tumor-suppressor genes and genomic instability, occur with increased frequency in HIV-associated squamous-cell carcinoma. These data demonstrate for the first time evidence of loss of heterozygosity at the APC and DCC/SMAD4 gene loci in anal carcinoma. Although the findings presented here need to be expanded in a larger study, the recurrent loss of heterozygosity at D2S123, which was demonstrated in HIV-positive patients with radio-resistant squamous-cell carcinoma of the anus, is notable.

Adult↗

A lead cancer nurse role at Birmingham Children's Hospital National Health Service Trust.

This paper reports on an innovative scheme and course developed as part of a Lead Cancer Nurse role based at the Birmingham Children's Hospital NHS Trust, UK. In doing so issues are raised which may be helpful to others should they consider adopting a similar scheme and the possibilities of the scope of the role are highlighted.

Education, Nursing, Continuing↗

Effect of patient obesity on the accuracy of thallium-201 myocardial perfusion imaging.

The effects of patient habitus (e.g., breast attenuation in women and diaphragmatic attenuation in men) have long been recognized as factors that reduce the accuracy of myocardial perfusion imaging. Although it has long been assumed that patient obesity effects accuracy, this has never been formally evaluated. We studied the effects of patient obesity, defined as a body mass index (BMI) > or = 30, on 607 patients who underwent exercise thallium-201 single-photon emission computed tomography (SPECT). Because the effects of obesity are most likely mediated through increased photon attenuation and scatter, we also evaluated the effects of other markers of patient size: body surface area (BSA) and patient weight. Accuracy was determined by performing quantitative analysis and measuring the area under the receiver operating characteristic curve (AUC). Obesity was associated with significantly lower accuracy (AUC 0.86 +/- 0.03 vs 0.92 +/- 0.02, p <0.05) despite similar estimates of maximal coronary blood flow (as estimated by heart rate and rate-pressure product at peak exercise) and severity of coronary disease. There were no significant differences attributable to either patient weight or BSA. Weight and BSA correlated significantly with left ventricular chamber size whereas BMI did not. We conclude that the accuracy of quantitative SPECT thallium-201 is significantly reduced by patient obesity and that although BSA and weight are also associated with increased attenuation, they have no effect on accuracy, which is most likely due to the compensating effects of increased chamber size.

Body Mass Index↗

Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia.

PURPOSE: In recent studies, serotonin and several gut peptides have been shown to serve as regulators of colonic transit. Thus, the distribution, density, and intensity of cells secreting serotonin or certain gut peptides could be abnormal in patients with colonic inertia. The aim of this study was to evaluate the distribution, density, and staining intensity of enterochromaffin and serotonin cells in the colonic mucosa of patients with colonic inertia compared with a control group. METHODS: Between 1993 and 1998 tissue blocks from the right and left side of the colon were obtained in 19 consecutive patients (18 females; mean age, 43.7 +/- 11.5 years) who underwent subtotal colectomy for colonic inertia. The control group consisted of colonoscopic biopsies from the right and left colon of 15 patients (all females; mean age, 52.7 +/- 16.5 years) for indications other then constipation, inflammatory bowel diseases, or carcinoma. Immunocytochemical staining of enterochromaffin and serotonin cells were performed on 4 microm tissue sections with the primary rabbit antibody against chromogranin A or serotonin, and the biotinylated secondary antibody and enzyme-labeled-streptavidin. The average cell number per microscopic field (x200) was calculated and the proportion of cells with various staining distribution was expressed as the percentage of the entire positive cell population as low, moderate, and high intensity. Student's t-test and chi-squared test were used for statistical analysis, with significance level set at P < 0.05. RESULTS: The quantity of both enterochromaffin cells (16.8 +/- 10.2) and serotonin cells (12.1 +/- 6.4) in the mucosa of the left colon in patients with colonic inertia was significantly higher when compared with the right side of the colon (enterochromaffin cells, 9.4 +/- 6.0; serotonin cells, 7.8 +/- 3.6; P < 0.01). The percentage of both types of cells with low staining intensity was increased, whereas the cells with high and moderate staining intensity were decreased (P < 0.01) in the left colon as compared with the right. The number of enterochromaffin cells in left-sided colonic mucosa was significantly higher in the colonic inertia group than in the control group (16.8 +/- 10.1 vs. 10.4 +/- 6.0; P < 0.05). Moreover, the numbers of serotonin cells in both the right and left colon was also significantly higher in the colonic inertia group than in the control group (right, 7.8 +/- 3.6 vs. 4.1 +/- 2.4; left, 12.1 +/- 6.4 vs. 5.8 +/- 3.7; P < 0.01). In both sides of the colon, the percentage of enterochromaffin and serotonin cells with low staining was significantly higher, whereas percentage of those cells with high or moderate staining was significantly lower in the colonic inertia group than in the control group. In the colonic inertia group there was a significantly positive correlation between numbers of enterochromaffin and serotonin cells (right side, P < 0.01; left side, P < 0.05). CONCLUSION: In patients with colonic inertia, the number of both enterochromaffin and serotonin cells are significantly increased in the colonic mucosa, especially in the left colon. As indicated by staining distribution, enterochromaffin and serotonin cells contain significantly less hormone than do the same cells in the control group.

Adult↗

Atypical epithelial cells and specimen adequacy: current laboratory practices of participants in the college of American pathologists interlaboratory comparison program in cervicovaginal cytology.

CONTEXT: The Bethesda System for reporting cervical/vaginal cytologic diagnoses introduced terminology for atypical squamous and glandular cells and categories for specimen adequacy. OBJECTIVES: To analyze current laboratory reporting practices and compare trends to previous surveys. DESIGN: Questionnaire surveys were mailed to 2000 laboratories in 1996 and 1997. PARTICIPANTS: Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. MAIN OUTCOME MEASURES: Laboratory policies, criteria, and reporting rates for Bethesda System categories. RESULTS: The 1996 specimen adequacy survey had 1166 respondents, and 768 laboratories returned the 1997 questionnaire focusing on atypical squamous cells of undetermined significance (ASCUS) and glandular cells of undetermined significance (AGUS). Nearly all laboratories (92%) routinely reported specimen adequacy, an increase from the 66% rate in 1991. The median rate for unsatisfactory specimens was 0.5% (mean 0.95%), and the median rate for the satisfactory but limited category was 5.8% (mean 9.3%). The Bethesda criteria for designating a specimen unsatisfactory were used by more than 90% of laboratories. Nearly all laboratories (97%) used the term ASCUS in 1997, and more than 80% of laboratories used the Bethesda criteria for this category. Median reporting rates for epithelial abnormalities were as follows: ASCUS, 4.5%; AGUS, 0.3%; low-grade squamous intraepithelial lesion (SIL), 1.6%; and high-grade SIL, 0.5%. The median ASCUS/SIL ratio was 2.0, with 80% of laboratories reporting ratios between 0.64 and 4.23. The median ASCUS rate and ASCUS/SIL ratio were higher than 1993 survey results. Nearly all laboratories attempted follow-up studies on patients with abnormal cytology results, and midsized laboratories achieved the highest rates of follow-up. Median rates of abnormalities following an ASCUS or AGUS diagnosis were 20% and 15%, respectively. Laboratory respondents commonly used written recommendations in ASCUS/AGUS reports. CONCLUSIONS: Most laboratories that responded to the surveys had adopted Bethesda terminology and criteria for specimen adequacy and ASCUS/AGUS. Reporting rates for SIL and adequacy categories have remained stable, but median ASCUS rates and ASCUS/SIL ratios are higher than in 1993. The AGUS category is reported infrequently, but can be associated with significant pathology.

Clinical Laboratory Techniques↗

Sulfation of chondroitin sulfate in human articular cartilage. The effect of age, topographical position, and zone of cartilage on tissue composition.

The chondroitin ABC lyase digestion products of normal human femoral condyle articular cartilage and of purified aggrecan were analyzed for their mono- and nonsulfated disaccharide composition. Changes in the total tissue chemistry were most pronounced during the period from birth to 20 years of age, when the -[GlcAbeta,3GalNAc6]- disaccharide content increased from approximately 50% to 85% of the total disaccharide content and there was a concomitant decrease in the content of the 4-sulfated disaccharide. In general, the disaccharide content of the deeper layers of immature cartilage were richer in the 4-sulfated residue than the upper regions of the tissue. As the tissue aged and decreased in thickness, the disaccharide composition became more evenly 6-sulfated. The newly synthesized chondroitin sulfate chains had a similar composition to the endogenous chains and also underwent the same age and zonal changes. The monoclonal antisera 3B3(+) and 2B6(+) were used to immunolocalize the unsaturated 6- and 4-sulfated residues generated at the reducing termini of the chondroitin sulfate chains by digestion with chondroitin ABC lyase, and these analyses indicated that the sulfation pattern at this position did not necessarily reflect the internal disaccharide composition of the chains. In summary, the sulfation pattern of chondroitin sulfate disaccharides from human normal articular cartilage varies with the age of the specimen, the position (topography) on the joint surface, and the zone of cartilage analyzed. Furthermore, these changes in composition are a consequence of both extracellular, post-translational processing of the core protein of aggrecan and changes in the sulfotransferase activity of the chondrocyte.

Adolescent↗

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Adaptation, Psychological↗

Early changes in the sulfation of chondroitin in guinea-pig articular cartilage, a possible predictor of osteoarthritis.

Male Dunkin Hartley guinea-pigs have been shown to develop spontaneous osteoarthritis, in the knee joint, which is histologically apparent from the age of 3 months onwards. We have used capillary electrophoresis (CE) to examine subtle changes in the sulfation of chondroitin in guinea-pig articular and xiphisternal cartilage. An age-related increase in the 6:4 sulfation ratio of chondroitin was observed, with the medial tibial plateau developing more rapidly than the other joint surfaces. The observed sulfation patterns may be related to the onset of spontaneous osteoarthritis which, in the guinea-pig, develops initially on the medial tibial plateau. Chondroitin from patellar groove cartilage of animals between 3 and 12 months of age always had a significantly lower 6:4 sulfate ratio than the other joint surfaces.

Animals↗

Physician response to screening for hypercholesterolaemia in a coronary care unit.

Hypercholesterolaemia is a known risk factor for coronary artery disease. This study describes a retrospective analysis of 176 patients admitted to the Coronary Care Unit (CCU) in a six month period with an admission fasting serum cholesterol of greater than 5.5 millimoles per litre (mmols/L). The patient records were examined at least six months after hospital discharge to determine what action, if any, was instituted in response to their hypercholesterolaemia. One hundred and thirty-four (76%) patients had a discharge diagnosis of myocardial ischaemia or infarction. Of the 176 patients, 73 were referred to a dietitian, 31 were given dietary advice by a medical officer, 13 were commenced on lipid-lowering drugs with nine continuing lipid-lowering drugs and only 13 patients were referred to this hospital's lipid clinic. Sixty-nine (39%) received no response to their hypercholesterolaemia. It is likely that our experience is not unique and greater attention to CCU measured lipid results and risk factor modification should be instituted by physicians.

Adult↗

The pharmacology of N-methyl LTC4; a metabolically stable LTC4-mimetic.

N-methyl LTC4 (NMLTC4) a synthetic analogue of LTC4, has been shown not to be a substrate for gamma-glutamyl transpeptidase. NMLTC4 produced contractions of the guinea pig ileum and trachea with pD2 values of 7.7 +/- 0.12 (n = 6) and 8.1 +/- 0.1 (n = 6) respectively, compared with values of 9.0 +/- 0.1 (n = 5) and 8.0 +/- 0.2 (n = 6) for LTC4. The concentration-response curve to LTC4 and NMLTC4 on ileum was displaced to the right by FPL55712. The corresponding pA2 values were 6.3 +/- 0.3 (n = 10) for LTC4 and 5.7 +/- 0.2 (n = 6) for NMLTC4. In the presence of acivicin, a gamma-glutamyl transpeptidase inhibitor, the LTC4 concentration-response curve on trachea was displaced to the left, but the NMLTC4 curve was unaffected. The comparative potencies in the presence of acivicin on trachea indicate that LTC4 is approximately 6 times more potent than NMLTC4 whereas on ileum, in the presence of FPL55712 LTC4 is approximately 14 times more potent. In-vivo NMLTC4 is a weak bronchoconstrictor substance being 20-30 less potent than LTC4. However, unlike the in-vitro studies the bronchospasm was significantly reduced by pretreatment with LTD4 antagonists. NMLTC4 administered intravenously produced a pronounced hypertensive effect which appeared to be due to peripheral vasoconstriction.

Animals↗