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Biomedical subjects

F Sharp

Publications and source records attributed to F Sharp.

At least 19 recordsLinked to original sources
PubMed2000

Relation between tissue structure and imposed electrical current flow in cervical neoplasia.

BACKGROUND: When an electrical potential is applied to human tissue, the pattern of the resulting current flow is determined by the shapes, arrangements, and internal structure of the tissue cells. By measurement of the electrical current patterns over a range of frequencies, and use of an inverse modelling procedure, electrical variables describing the tissue structure can be calculated. We used this method to develop a screening technique for the detection of cervical precancers. METHODS: We used a pencil probe (diameter 5 mm) to measure electrical impedance spectra from eight points on the cervix in 124 women with abnormal cervical smears. Variables that should be sensitive to the expected tissue changes were calculated. These were compared with the colposcopic results. FINDINGS: The measured electrical impedance changes were those predicted on the basis of the expected tissue structures. Measurements made on normal squamous tissues were well separated from those made on precancerous tissues. We constructed receiver-operating-characteristic curves, comparing measurements made on normal tissue and that showing cervical intraepithelial neoplasia grade 2/3; the area under the curve was 0.951. These groups of women could be separated with a sensitivity of 0.92 and a specificity of 0.92. INTERPRETATION: Characteristics of the electrical impedance spectra of tissues can be explained by changes in cell arrangements (layering) and in the size of the nuclei. This relation opens the way to deriving tissue structure from electrical impedance spectral measurements. We show that this approach can be used to give good separation of normal and precancerous cervical tissues.

Biopsy↗
PubMed1999

The significance of Erb-b2 immunostaining in cervical cancer.

OBJECTIVE: The aim of this study was to assess the relationship between survival and erb-b2 immunohistochemical staining in patients with early stage cervical carcinoma. METHODS: Archival specimens for 126 patients with stage IB/IIA cervical carcinoma treated with radical hysterectomy and bilateral pelvic node dissection (RH-BPND) were retrieved and submitted to immunohistochemistry for ERBB2 expression. The association between positive results and poor survival was assessed in a multivariate analysis. RESULTS: Erb-b2 immunostaining was significantly associated with poor survival (P = 0.0284) but less so than parametrial extension (P = 0.0014) and nodal disease (P = 0.0106). Tumor type (squamous/adenosquamous/adenocarcinoma) and the status of surgical margins were not significantly associated with survival. CONCLUSIONS: These results supported further investigations of ERBB2 expression as a marker of high-risk disease in patients treated with RH-BPND.

Adenocarcinoma↗
PubMed1999

Outcome after surgical resection for high-grade anal intraepithelial neoplasia (Bowen's disease).

BACKGROUND: High-grade anal intraepithelial neoplasia (Bowen's disease) may predispose to anal carcinoma. Treatment options include surgical resection but effectiveness remains uncertain. This paper reports long-term follow-up of patients with high-grade anal intraepithelial neoplasia treated by surgical resection. METHODS: Between 1989 and 1996, 46 patients were identified with high-grade anal intraepithelial neoplasia. Thirty-four underwent local excision of all macroscopically abnormal disease and the resulting defect was left open, closed primarily or skin grafted. Regular follow-up subsequently included anoscopy and biopsy of any suspicious lesions. RESULTS: Median follow-up was 41 (range 12-104) months. Total excision was difficult; 19 patients had histological evidence of incomplete excision at the time of initial resection. Some 12 of 19 had histo-logically proven recurrent high-grade intraepithelial neoplasia within 1 year. Even with microscopically complete excision two of 15 patients subsequently developed recurrent high-grade intraepithelial neoplasia at 6 and 32 months after operation. No patient developed carcinoma but five had complica-tions of anal stenosis or faecal incontinence. CONCLUSION: Although no definite recommendations can be made for the treatment of high-grade anal intraepithelial neoplasia, these results illustrate some potential drawbacks of surgical excision with a high potential for incomplete excision and persistent disease, even after complete excision in some patients, and a high morbidity rate.

Anus Neoplasms↗
PubMed1997

Skin appendage involvement in anal intraepithelial neoplasia.

BACKGROUND: High-grade anal intraepithelial neoplasia (AIN III) may be premalignant. Surgical excision of large areas of anal epithelium carries significant morbidity. Ablation treatments may carry less morbidity; however, the depth of ablation is uncertain and failure to ablate dysplasia in hair shafts and other skin appendages may lead to early recurrence. METHODS: This study assesses morphometric aspects of skin appendages in perianal skin and anal canal mucosa in tissues from 30 patients with AIN III. Both normal and dysplastic epithelium was assessed in each patient. The depth to which AIN III involved skin appendages was measured using computerized image analysis. RESULTS: Both the perianal epidermis and anal canal mucosa affected by AIN III were significantly thicker than normal. Nineteen of 30 patients with AIN III had skin appendage involvement. Some 57 per cent of hair follicles (79 of 138), 16 per cent of sebaceous glands (11 of 69) and 25 per cent of sweat glands (24 of 96) observed beneath an abnormal epithelium had evidence of AIN. The median depth of AIN involvement of the hair follicle was 1.14 (range 0.44-1.67) mm, sebaceous glands 1.44 (range 0.96-1.90) mm, and sweat glands 0.94 (range 0.50-2.20) mm. These figures do not take into account tissue shrinkage due to histological processing. CONCLUSION: AIN III involvement of epithelial appendages is a significant problem. For disease eradication, tissue destruction or removal to a depth of at least 2.2 mm below the adjacent basement membrane is required. Surgical excision of high-grade AIN remains the treatment of choice.

Adult↗
PubMed1995

Positron emission tomography: 2-deoxy-2-[18F]-fluoro-D-glucose uptake in locally advanced breast cancers.

Fifteen patients with locally advanced breast cancers were studied using the radiopharmaceutical 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) with positron emission tomography (PET). Five patients were sequentially imaged before and after two pulses of chemotherapy. In 14 of 15 tumours increased uptake of FDG was observed which correlated with the clinical site of the tumour. The PET images were compared with the mammographic and ultrasonomammographic appearances of the tumours in selected patients. In two patients with normal mammograms PET imaging detected the tumour and in a further four patients, with suspicious but not conclusively malignant mammographic changes, a well-defined area of increased FDG uptake was demonstrated by PET. In all five sequentially imaged tumours, following chemotherapy, there was a decrease of the FDG tumour: normal breast uptake ratio. In four patients who completed a full chemotherapeutic course this change preceded a pathological response of their tumours. These findings suggest that this technique may be of benefit in imaging carcinomas in the breasts of pre-menopausal women which may appear dense on mammography and moreover, that sequential imaging may have a role in the prediction, at an early stage, of the response of locally advanced carcinomas to chemotherapy.

Adult↗
PubMed1994

Drugs acting at the strychnine-insensitive glycine receptor do not induce HSP-70 protein in the cingulate cortex.

The potential for compounds acting at the strychnine-insensitive glycine receptor to injure neurons was examined using induction of a 70 kDa heat shock protein (HSP-70) as a marker. HSP-70 was consistently detected in retrosplenial and cingulate cortices after MK-801 but not glycine drug treatment. Elsewhere in the cortex, mild diffuse HSP-70 immunoreactivity was detected following 7-chlorokynurenic acid. Following HA-966, intense hippocampal HSP-70 immunoreactivity was observed. These findings indicate that even after very high doses, drugs acting at the strychnine-insensitive glycine receptor are less likely to injure cingulate cortical neurons than other classes of NMDA antagonists.

Amino Acids↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

Preliminary observations of holmium:YAG laser tissue interaction using human uterus.

Preliminary observations of a pulsed Ho:YAG laser on human uterine tissue in-vitro are presented. The tissue effect on the uterine myometrium was demonstrated using fresh uteri which had been subjected to laser energy. The laser crater and surrounding zone of thermal necrosis (ZTN) was quantified. Measurements demonstrated a consistent narrow ZTN (0.8-1.8 mm) irrespective of power or pulse frequency used. The percentage forward transmission of laser energy through 1 mm of myometrium was investigated using a pyroelectric detector and found to be 0.41%. Finally, a visible and measureable photoacoustic component to the Ho:YAG laser was demonstrated using a water bath and needle hydrophone.

Biophysical Phenomena↗
PubMed1992

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↗
PubMed1992

Artificial sapphire contact probes in Nd:YAG endometrial ablation: a quantitative in vitro and in vivo study.

Artificial sapphire contact probes offer theoretical advantages in Nd:YAG endometrial ablation. To examine this, an in vitro and in vivo study of laser-tissue interaction was performed. In vitro, a linear correlation was found between applied energy and total depth of effect, that is, photovaporization and photocoagulation. Using a Round (MTR 1.5) contact probe, an applied energy of 30 joules gave a depth of myometrial effect of 3.3 mm. In vivo, there was a significant reduction in tissue effect (p less than 0.001) compared to in vitro. Difficulty of manipulation of the contact laser probe within the uterus also caused a significant reduction (p less than 0.001) in depth of tissue ablation achieved on the posterior uterine wall compared with that achievable at the uterine fundus, but this may be counteracted by increasing applied energy.

Endometrium↗
PubMed1992

In-vivo studies of uterine electrosurgery.

OBJECTIVE: To study the effects of electrosurgery on the living human uterus. DESIGN: Prospective observational study. SUBJECTS: Nine women with recurrent refractory dysfunctional uterine bleeding, listed for hysterectomy. INTERVENTION: Experimental endometrial resection on patients immediately prior to hysterectomy. MAIN OUTCOME MEASURES: The influence of power output, duration of exposure and repetition of consecutive surgical applications on the size of the zone of thermal necrosis in uterine tissue. RESULTS: Resection of the endometrium was associated with a narrow zone of thermal necrosis of between 0.69 and 0.76 mm which was not dependent on power output. Duration of exposure, however, was directly related to tissue necrosis (1.44 vs 1.88 mm for 1s and 5s, respectively). Coagulation by pin-point desiccation caused a zone of thermal necrosis of 3.30-3.77 mm that was independent of either power or duration of exposure to electrical energy. Thermal transmission through the uterus in situ, during electrosurgery was minimal, the maximum recorded rise in temperature from the baseline was 0.4 degrees C. The differences between the in vitro and in vivo effects of electrosurgery are highlighted and the possible reasons for these differences explored. CONCLUSIONS: The potential for unwanted thermally-induced damage to the uterus is small.

Electrosurgery↗
PubMed1992

Nucleolar organiser regions (AgNORS) in anal intraepithelial neoplasia and invasive anal squamous cell carcinoma.

AIM: To evaluate the usefulness of counting nucleolar organiser region associated proteins (AgNORs) in the management of anal squamous neoplasia. METHOD: Using a silver staining technique for NOR associated proteins, 32 routinely processed paraffin wax embedded sections of anal epithelium were assessed. These consisted of normal anal epithelium (n = 9), anal intraepithelial neoplasia (AIN) grades I (n = 5), and III (n = 13), and invasive squamous neoplasia of the anus (n = 5). RESULTS: The median AgNOR counts for every 100 cells are as follows: normal anal epithelium 2.15 (95% CI 1.89-3.94); AIN I 3.21 (95% CI 2.89-7.14); AIN III 4.32 (95% CI 4.00-8.10); and invasive squamous cell carcinoma of the anus 5.51 (95% CI 2.48-10.62). There were significant differences between AgNOR counts in anal cancer and normal epithelium (p < 0.05; Mann-Whitney U test)), AIN III and normal anal epithelium (p < 0.005), and AIN III and AIN I (p < 0.05). No significant differences were observed between AIN I and normal anal epithelium, anal cancer and AIN I, and anal cancer and AIN III. There was a considerable degree of overlap among the different groups. CONCLUSIONS: Despite the strong association between AgNOR values and degree of dysplasia, the variability within pathological grade may preclude the adoption of this technique on its own as a prognostic indicator. It may, however, be useful in conjunction with other markers of neoplastic growth such as c-myc oncogene amplification or overexpression as a marker of disease progression in AIN and invasive anal squamous cell cancer.

Anus Neoplasms↗