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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 73 records · Page 4Linked to original sources
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

Inhibitors of sterol synthesis. Submicromolar 14 alpha-ethyl-5 alpha-cholest-7-ene-3 beta, 15 alpha-diol causes a major modification of the sterol composition of CHO-K1 cells and a marked change in cell morphology.

Incubation of Chinese hamster ovary cells (CHO-K1) with 14 alpha-ethyl-5 alpha-cholest-7-ene-3 beta,15 alpha-diol (0.1 microM) in lipid-deficient medium led to a major change in cellular sterol composition, which was characterized by a very marked accumulation of C30 sterols (lanosterol and 24,25-dihydrolanosterol). The accumulation of C30 sterols was associated with a striking change in cell morphology. The change in cell shape (elongation) was similar to that described previously (A. W. Hsie and T. T. Puck, 1971. Proc. Natl. Acad. Sci. USA. 68: 358-361; and confirmed herein) for CHO-K1 cells incubated in the presence of dibutyryl cAMP (1 mM). This change in morphology, induced by dibutyryl cAMP, was not accompanied by a change in cellular sterol composition. The cell elongation and accumulation of C30 sterols, induced by the 14 alpha-ethyl diol, were prevented by the addition of cholesterol (10 microM or 100 microM) and were reversed by removal of the 14 alpha-ethyl diol from the incubation medium. Incubation of the cells with the 14 alpha-ethyl diol had no effect on the levels of cAMP under the conditions studied. Incubation of the cells with miconazole (10 microM) or with lanosterol (10 microM) was also associated with the accumulation of C30 sterols and an elongation of the cells. 24,25-Dihydrolanosterol (10 microM) also induced similar changes in cellular morphology. The results presented herein demonstrate that marked changes in the sterol composition of CHO-K1 cells can be effected by incubation of the cells with 14 alpha-ethyl-5 alpha-cholest-7-ene-3 beta, 15 alpha-diol, miconazole, or lanosterol. In addition, the findings reported herein indicate an important role of sterols in the control of the shape of these cells.

Animals↗
PubMed1994

Pathogenesis of human strongyloidiasis: autopsy and quantitative parasitological analysis.

The distribution of pathologic lesions and the parasite burden of major organs were studied in seven patients with disseminated strongyloidiasis who were autopsied at the University of Texas Medical Branch (Galveston, TX). All patients were immunosuppressed and had additional bacterial, viral, and fungal infections; six patients had received cortisone therapy and one patient had AIDS. High Strongyloides burdens were noted in untreated patients or in those with a short period of treatment. The proximal small intestine and the lungs showed the heaviest parasite burden, with large numbers of filariform larvae found in both locations. The lungs showed persistence of larvae in all patients, in the absence of intestinal or extraintestinal infection; this suggests that the respiratory cycle may be more resistant to therapy than the intestinal cycle. In the intestines, filariform larvae were seen at all levels, but higher burdens were seen in the upper as compared to lower small intestine, and larvae were more concentrated in the proximal jejunum than in the duodenum. Autoinfection (i.e., filariform larval penetration) occurred more prominently in the distal small and proximal large intestine than in the distal colon. Most filariform larvae were found in the intestinal lymphatics and were highly concentrated in mesenteric and retroperitoneal lymph nodes; conversely, larvae were not found in the spleen and were found in very low density in the liver. These findings, in concert, suggest that during autoinfection in humans, the Stronglyloides larvae transverse lymphatics to the thoracic duct, then pursue a lymphohematogenous dissemination to the lungs where they penetrate the air spaces and ascend through the airways to reach the gut.

AIDS-Related Opportunistic Infections↗
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

Non-alimentary aspects of the irritable bowel syndrome.

The irritable bowel syndrome (IBS) is characterized by alimentary and non-alimentary symptoms; the aim of this study was to assess the clinical value and discriminant function of non-alimentary symptoms in the irritable bowel syndrome. Alimentary and non-alimentary symptoms, estimated daily dietary fibre intakes, ability to express personal feelings, anxiety and depression ratings, and life events and difficulties inventories were compared in 128 hospital out-patients with IBS and 113 age and sex matched control subjects not seeking health care, randomly recruited from the community. Alimentary symptoms correlated closely with those non-alimentary symptoms often associated with the hyperventilation syndromes, difficulties in expressing personal feelings and anxiety, and depression ratings. Life events and difficulties, and estimated daily dietary fibre intakes did not differ significantly between patients and controls. With the exception of abdominal bloating, no significant gender differences were observed in IBS symptoms in either the IBS or control groups. The irritable bowel syndrome is one facet of a more general condition of illness behaviour which includes the hyperventilation syndrome and an inassertiveness in expressing personal feelings. Though non-alimentary symptoms did not improve diagnostic accuracy beyond that achieved by a combination of alimentary symptoms, their recognition provides alternative approaches to the management of refractory IBS.

Adult↗
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

Delay in fixation does not affect the immunoreactivity of proliferating cell nuclear antigen (PCNA).

The effect of delayed fixation on the immunoreactivity of proliferating cell nuclear antigen (PCNA) was investigated using eight breast carcinomas. Topologically shuffled samples of each tumour were immersed in fixative at times of 0.5, 1, 2, 4, 6, 18, and 24 h after surgical removal. In addition to a PCNA index (percentage of positive cells per 1200 tumour cells), a semi-quantitative PCNA grading system was used, based on estimates of more than or less than 50 per cent of positive tumour cells at each time interval. The PCNA index of six tumours increased by a mean of 10 per cent with a fixation delay of 24 h. The PCNA grade of all eight tumours showed no change with delayed fixation.

Antigens, Neoplasm↗
PubMed1992

Reassessment of the rate of fixative diffusion.

The diffusion of fixatives is slow. Early work using plasma gels and animal tissues showed the distance penetrated by a fixative to be a simple function of the fixation time but this relation has not been established in human tissues. The rates of diffusion into whole human spleens were measured for three primary fixatives over periods ranging from one to 25 days. A positive correlation was demonstrated between penetration distance (mm) and fixation time (hours). The diffusion rates were slower than those in previous studies. These results have possible implications for the handling of surgical specimens.

Diffusion↗
PubMed1992

Assessment of specimen fixation in a surgical pathology service.

The quality of specimen fixation was examined within a routine diagnostic histopathology service. For each specimen the adequacy of fixation was assessed and the transit time between operating theatre and the laboratory was measured. Preliminary fixation was found to be inadequate in 25% of specimens and some form of manipulation to assist fixation was required in 36% of specimens. The mean transit time was 22 (SD 10.7) hours. Specimen fixation and transport are additional factors to consider in quality assurance of histopathology.

England↗