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Biomedical subjects

K Rogers

Publications and source records attributed to K Rogers.

At least 55 records · Page 3Linked to original sources

Prevalence of anal human papillomavirus infection and intraepithelial neoplasia in renal allograft recipients.

A study was performed to test the hypothesis that renal allograft recipients are at high risk of developing anal human papillomavirus (HPV) infection and anal intraepithelial neoplasia (AIN). A total of 133 renal allograft recipients and 145 control patients underwent anoscopy and biopsy. A polymerase chain reaction was used to detect HPV16 DNA in biopsy samples. A histological diagnosis of anal HPV infection or AIN was made in 32 allograft recipients (HPV infection, five; AIN I, 20; AIN II, three; AIN III, three; AIN III and anal cancer, one). One subject with AIN was detected in the control group. HPV16 DNA was detected in 47 and 12.4 per cent of anal biopsies in the allograft and control groups respectively. Renal allograft recipients are at high risk of developing anal HPV infection and neoplasia (P < 0.05). Further studies are required to determine whether screening anal examination is required in organ allograft recipients.

Adult↗

Treatment of anal intraepithelial neoplasia.

The natural history and malignant potential of anal intraepithelial neoplasia (AIN) remain uncertain, making management decisions about such lesions difficult. The management of 70 patients with AIN is described. The majority of lesions encountered were low grade (AIN I and II; 43 of 70) and required no treatment, but eight invasive anal cancers associated with high-grade AIN occurred over the 4-year study period. Three were a result of apparent progression of high-grade lesions; three more invasive lesions were found in areas of AIN III on histological examination. Surgical excision was used to treat 27 patients with AIN III. Treatment of extensive lesions involving the perianal and anal canal epithelium circumferentially in six patients involved excision of the whole of this epithelium and application of split skin grafts.

Adult↗

Determinants of birth weight in Vietnamese detainees in Hong Kong.

Five hundred and fifty singleton pregnancies amongst Vietnamese Boat People delivering between January and December 1993 were studied post-natally. Multiple regression analysis showed no direct effect of ethnic origin on birth weight. When analyses were repeated on the two main ethnic subgroups we found that, amongst Anamese patients, both gestation at delivery and birth weight independently increased with longer duration of stay in Hong Kong. This relationship was not seen in Vietnamese patients of Chinese ethnic origin. Possible reasons for these different relationships are discussed.

Adult↗

The effects of hypothermic and normothermic cardiopulmonary bypass on glyceryl trinitrate activity.

Glyceryl trinitrate (GTN) is used to control arterial blood pressure during cardiopulmonary bypass (CPB) procedures, but its effects are often decreased during the period of extracorporeal support. The plasma and urine concentrations of GTN and glyceryl-1,2-dinitrate (1,2-GDN) and glyceryl-1,3-dinitrate (1,3-GDN) for male and female patients who received GTN during hypothermic CPB, and male and female patients who were given GTN during normothermic CPB, were measured by gas-liquid chromatography. During hypothermic CPB, the male and female subjects experienced significant decreases in GTN clearance (P < 0.05), 66% and 52%, respectively. Neither the males nor the females who underwent normothermic CPB experienced any significant change in GTN clearance. These results suggest that the lower core temperature during hypothermic CPB may decrease the biotransformation of GTN to GDNs and nitric oxide, thereby resulting in less dilation of blood vessels. Furthermore, the males in the hypothermic CPB group had significantly greater urinary concentrations of 1,3-GDN and 1,2-GDN than the females (P < 0.05), and the normothermic CPB males had a significantly greater urinary concentration of 1,2-GDN than the females in that group. The normothermic CPB males also had significantly higher plasma concentration of GTN at two time points, and 1,3-GDN at one time point, than the females. These data suggest that there may be a gender difference in GTN biotransformation.

Aged↗

Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer.

OBJECTIVE: To test the hypothesis that women with invasive vulvar cancer are at high risk of developing human papillomavirus (HPV)-associated anal squamous neoplasia. METHODS: Forty women (median age 54.5 years; range 25-86) who were being treated or had been treated for invasive vulvar cancer and who had not had radiotherapy to the pelvis or anogenital region underwent anal microendoscopy and biopsy. A second group of 80 women who were similar in age to the study group and had no history of anogenital HPV infection or neoplasia formed the control group. The polymerase chain reaction was used to detect HPV 16 DNA in the vulvar and anal tissue samples from 33 patients in the study group and in the anal biopsies of all controls. RESULTS: A histologic diagnosis of anal HPV infection or squamous neoplasia was made in 19 of 40 biopsies (47.5%) in the study group. These diagnoses consisted of one HPV, two anal squamous intraepithelial lesions (SIL) grade I, 15 and SIL grade III (four of which were associated with invasive anal cancers), and one invasive cancer in the absence of anal SIL. Human papillomavirus 16 DNA was detected in 16 of 33 (48.5%) of anal and 25 of 33 (75%) of vulvar biopsies. In addition, HPV 16 was detected in both the anal and vulvar samples in 13 of 16 cases (81%) of anal SIL III and invasive anal squamous cancer. No evidence of anal SIL was found in the controls, and HPV 16 DNA was identified in only 11 (13.7%) of the anal biopsies in this group. CONCLUSIONS: This study provides further evidence for the etiologic relation between genital and anal squamous neoplasia. Furthermore, it shows that women with vulvar cancer are at high risk of having or developing HPV-associated anal neoplasia, particularly in younger patients (P = .0006; 95% confidence interval 12-34). Routine anal examination should be performed in patients with invasive vulvar cancer.

Anal Canal↗

Randomized trial of laser scalpel for modified radical mastectomy.

The efficacy of a contact neodymium yttrium-aluminium-garnet laser scalpel was assessed during breast surgery. Forty consecutive women undergoing modified radical mastectomy were randomized to operation performed with a conventional or laser scalpel. The laser scalpel was associated with a significant reduction in mean operative blood loss (149 versus 421 ml; 95 per cent confidence interval of difference 176-368 ml, P < 0.001), but the mean operating time was longer (105 versus 80 min; 95 per cent confidence interval of difference 16-34 min, P < 0.001). No significant differences were found in the volume of postoperative wound drainage, incidence of axillary seroma, postoperative pain score or time to return of shoulder mobility. Use of a laser scalpel in breast surgery cannot be recommended.

Adult↗

Detection of tumour necrosis factor alpha and interleukin-1 beta in the rheumatoid osteoarthritic cartilage-pannus junction by immunohistochemical methods.

During inflammation the rheumatoid synovial membrane is invaded by a number of different cell types. When activated most of these cells produce cytokines including tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta). These cytokines are believed to stimulate production of degradative enzymes and disturb the equilibrium between such enzymes and their inhibitors resulting in tissue damage. In this study we investigated the localisation of TNF alpha and IL-1 beta at the cartilage-pannus junction (CPJ). Here, cytokines are well placed to influence the integrity of articular cartilage. Tissue was derived from advanced rheumatoid (RA) and, as a comparison, osteoarthritic (OA) joints at the time of replacement surgery (arthroplasty). Antibody staining of fixed serial sections of tissue localised cells that were associated with IL-1 beta and TNF alpha. Cell markers for macrophages and endothelial cells were included to provide positive identification of the cytokine-associated cells. Analysis of these sections revealed that both TNF alpha and IL-1 beta were associated with macrophages, particularly those in the synovium overlying cartilage (pannus) and endothelial cells. Positive staining was seen at the CPJ in RA and in similarly located tissue in OA. The similar distribution of cytokines in OA was unexpected even if the overall numbers of tissue and infiltrating cells in the CPJ were different in the two diseases. This highlights the possible role played by endogenous inhibitors [1, 2] in influencing the degree of cytokine activity necessary to explain the different pathogenic mechanisms in RA and OA.

Adult↗

The identification of informative parameters in the flow cytometric analysis of breast carcinoma.

DNA ploidy and the measurement of proliferation or S-phase fraction are both of prognostic significance in breast cancer, yet clinical use is minimal in the U.K. Immunohistochemistry is, however, used to aid diagnosis, so a panel of antibodies were analysed by flow cytometry to assess their predictive value for prognosis, tumour stage and grade. Of 10 parameters tested on 202 breast tumour samples, tumour cell proliferation and DNA ploidy were the two most informative; cytokeratin staining, natural killer and B-cell infiltration also proved to be of value but there was no prognostic value in measuring tumour infiltrating monocytes, helper/suppressor T-cell ratios, tumour cell reactivity with carcinoembryonic antigen or human milk fat globulin antibodies. For each of the informative parameters, scores numerically weighted towards a poorer prognosis were derived which when combined, correlated with tumour grade, stage and prognosis. Such data interpretation is objective, and can be transposed to other human tumours.

Adolescent↗

C-myc oncogene expression in anal squamous neoplasia.

AIMS: To determine the pattern of c-myc oncogene expression in anal squamous neoplasia and to determine if this could be used as a marker of disease progression. METHODS: The presence and localisation of the c-myc gene product p62 in archival specimens of anal squamous epithelium, normal and neoplastic, was examined using immunohistochemical staining with the monoclonal antibody Myc1-6E10. Ten normal and epithelia, 10 anal intraepithelial neoplasia (AIN) III, and 31 anal squamous cancers were examined. RESULTS: There was a noticeable difference between the staining characteristics of invasive tumours, normal anal epithelium, and AIN III. Intense, diffuse, mixed nuclear and cytoplasmic (n = 14) and exclusively nuclear (n = 8) staining in 22 of 31 (71%) of invasive anal tumours was observed. All positively staining tumours were well differentiated histologically, while the negatively staining nine of 31 (29%) were poorly differentiated (n = 7) and moderately well differentiated (n = 2). In six positively staining tumour sections adjacent areas of AIN III and non-dysplastic anal epithelium had staining characteristics similar to those of the invasive component. Staining in both normal anal epithelium (4/10) and AIN III specimens obtained from patients without a history of invasive disease (8/10) was less intense, focal in distribution, and exclusively nuclear. No difference in staining characteristics could be detected in these two groups. CONCLUSIONS: The results of this study suggest that c-myc oncogene expression is implicated in the pathogenesis of anal squamous neoplasia, and that immunohistochemical staining for c-myc protein may be helpful in identifying those AIN III lesions most likely to progress to invasive tumours.

Anal Canal↗

Immunohistochemical analysis of p53 expression in anal squamous neoplasia.

AIMS: To determine the pattern of expression of the p53 tumour suppressor gene product in anal squamous neoplasia, and to determine if this could be used as a marker of disease progression. The association between p53 expression and human papillomavirus (HPV) 16 DNA status of the anal lesions was also investigated. METHODS: The presence and localisation of the p53 protein in formalin fixed, paraffin wax embedded specimens of anal squamous epithelium (normal and neoplastic) was examined using immunohistochemical staining with a panel of two monoclonal antibodies (DO-1, DO-7) and one polyclonal antibody (CM-1). Thirty nine normal anal epithelia, 14 anal intraepithelial neoplasia (AIN) grade 1, seven AIN 2, and 20 AIN 3 specimens were obtained from patients without demonstrable invasive disease; twelve AIN 3 specimens adjacent to invasive disease and 34 anal squamous cancers were also examined. Genomic DNA from all 126 specimens was extracted and analysed for HPV 16 DNA using the polymerase chain reaction (PCR). RESULTS: Nuclear p53 was strongly expressed in 67% (23/34) of invasive anal squamous tumours, 75% (9/12) of AIN 3 specimens adjacent to invasive disease, and in 60% (12/20) of AIN 3 specimens obtained from patients without demonstrable invasive disease. Two of the patients in the latter group with positively staining specimens subsequently developed invasive tumours which had staining characteristics similar to those of the AIN 3 specimens. p53 protein was expressed in very low concentrations in low grade AIN and not at all in normal anal squamous epithelium. In those specimens which stained positively for p53, HPV 16 DNA sequences were detected in 69.5% (16/23) of invasive disease, 77.7% (7/9) of AIN 3 adjacent to invasive disease, 75% (9/12) of AIN 3 obtained from patients without demonstrable invasive disease, 33.3% (2/6) of AIN 2, and in 40% (2/5) of AIN 1. There was no significant correlation between p53 immunostaining and HPV 16 DNA status (p < 0.05). CONCLUSIONS: Aberrant expression of the p53 gene product is probably involved in the pathogenesis of anal squamous neoplasia. Long term follow up studies of all patients with AIN are required to determine if this could be used as a marker of likely disease progression from high grade AIN to invasive disease. There does not seem to be an association between the presence or absence of HPV 16 DNA sequences and mutant p53 proteins in anal squamous neoplasia.

Anus Neoplasms↗

The dynamics of prostaglandin metabolism in human fetal membranes and decidua around the time of parturition.

To address whether prostaglandins (PGs) produced in the amnion can gain access to the myometrium, we used three in vitro systems to determine the characteristics of PG secretion, metabolism, and transfer in amnion, chorion, and decidua around the time of parturition. PG metabolism, measured in explant cultures or cytosol preparations, occurs predominantly by the enzyme PG dehydrogenase, which was highest in chorion and was 2- to 3-fold more active for PGE2 than PGF2 alpha. The activity increased significantly around the time of labor onset. The activity of PG-9-ketoreductase, which interconverts the E and F series of PGs, was 2-3 orders of magnitude less than that of PG dehydrogenase. Using a dual chamber perfusion apparatus, we demonstrated that similar amounts of PGE2 were secreted from the fetal (amnion) and maternal (chorio-decidua) surfaces, and this ratio did not change with labor. Using radiolabeled PGE2, radioactivity traversed full thickness membranes at the rate of 4%/h. Only approximately 12% of the transferred radioactivity remained as intact PGE2, and very little conversion to PGF2 alpha was detected. No changes in transfer were detected around the onset of labor. We conclude that it is unlikely that PGE2 produced in the amnion acts directly on the myometrium.

Amnion↗

Inflammatory pseudotumour of the liver.

Inflammatory pseudotumours of the liver are uncommon, usually mistaken for malignant lesions and resected. This report describes the presentation of an inflammatory pseudotumour of the liver in a 28-year-old male which was demonstrated on C.T. scanning and diagnosed by percutaneous needle biopsy. This case was treated conservatively and spontaneously resolved within four months, emphasising the need to consider this lesion in the differential diagnosis of an intrahepatic mass.

Adult↗

Synthetase competition and tRNA context determine the in vivo identify of tRNA discriminator mutants.

The discriminator nucleotide (position 73) in tRNA has long been thought to play a role in tRNA identity as it is the only variable single-stranded nucleotide that is found near the site of aminoacylation. For this reason, a complete mutagenic analysis of the discriminator in three Escherichia coli amber suppressor tRNA backgrounds was undertaken; supE and supE-G1C72 glutamine tRNAs, gluA glutamate tRNA and supF tyrosine tRNA. The effect of mutation of the discriminator base on the identity of these tRNAs in vivo was assayed by N-terminal protein sequencing of E. coli dihydrofolate reductase, which is the product of suppression by the mutated amber suppressors, and confirmed by amino acid specific suppression experiments. In addition, suppressor efficiency assays were used to estimate the efficiency of aminoacylation in vivo. Our results indicate that the supE glutamine tRNA context can tolerate multiple mutations (including mutation of the discriminator and first base-pair) and still remain predominantly glutamine-accepting. Discriminator mutants of gluA glutamate tRNA exhibit increased and altered specificity probably due to the reduced ability of other synthetases to compete with glutamyl-tRNA synthetase. In the course of these experiments, a glutamate-specific mutant amber suppressor, gluA-A73, was created. Finally, in the case of supF tyrosine tRNA, the discriminator is an important identity element with partial to complete loss of tyrosine specificity resulting from mutation at this position. It is clear from these experiments that it may not be possible to assign a specific role in tRNA identity to the discriminator. The identity of a tRNA in vivo is determined by competition among aminoacyl-tRNA synthetases, which is in turn modulated by the nucleotide substitution as well as the tRNA context.

Amino Acids↗

Anal intraepithelial neoplasia: part of a multifocal disease process.

Invasive carcinomas of the anogenital epithelium share a common aetiological factor--human papillomavirus (HPV) type 16. Although genital intraepithelial neoplasia may be multifocal, there have been no studies of the prevalence of anal intraepithelial neoplasia in women with intraepithelial neoplasia of the genital tract. We tested the hypothesis that women with high-grade cervical intraepithelial neoplasia are at higher risk of disease in the anus than are control women of similar age with no history of anogenital neoplasia. 29 (19%) of 152 women with cervical intraepithelial neoplasia grade III had histological evidence of anal intraepithelial neoplasia. Of the 29 patients, 11 had grade III anal lesions; 2 of those women had concomitant invasive anal squamous-cell carcinomas. Only 7% (8/115) women with high-grade lesions of the cervix alone had evidence of anal intraepithelial neoplasia; by contrast, 57% (21/37) of those with more than one focus of intraepithelial neoplasia (cervix plus vulva, vagina, or both) had anal lesions. HPV 16 DNA was identified in 18 (51%) of 35 anal biopsy samples in the study group. No evidence of anal intraepithelial neoplasia was found in the control group (50 women), although 2 patients had grade I cervical lesions. HPV 16 DNA was identified in 12 (24%) of biopsy samples from the cervix and 7 (14%) from the anus in the control group; all 7 women with anal HPV 16 had concomitant cervical infection. The role of anal examination in the assessment of women with any focus of genital intraepithelial neoplasia requires further investigation.

Adult↗

Effect of tissue pressure on contact laser insults.

The effect of variations in tissue pressure transmitted through contact laser probes during tissue ablation has been investigated. Weights of 10 and 50 g were transmitted through the tip of the probes onto the gastric and colorectal wall. At all laser energies the depth of tissue vaporization was significantly greater at the higher tissue pressure with perforation of the viscus occurring at laser energies above 10 J. The lateral zones of thermal tissue necrosis were not influenced by tissue pressure. Deformation of the wall of the viscus under the pressure of the probe was identified as a sign of excessive tissue pressure likely to result in perforation of any tissue of similar thickness to the normal gastric or colorectal wall.

Humans↗

Preliminary evaluation of a new high power diode laser.

A high-powered semiconductor diode laser (805 nm) has recently been developed for medical use. The laser-tissue interactions of this wavelength have been compared with Nd:YAG (1064 nm). When used in the contact mode, the extent of tissue vaporization and zones of thermal necrosis produced by these two lasers were similar. The diode laser was also an effective and haemostatic laser scalpel. This compact laser unit has potential advantages over existing Nd:YAG lasers.

Animals↗