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Biomedical subjects

D Jenkins

Publications and source records attributed to D Jenkins.

At least 217 records · Page 12Linked to original sources

Quantitative DNA analysis of low grade cervical intraepithelial neoplasia and human papillomavirus infection by static and flow cytometry.

Quantitative deoxyribonucleic acid (DNA) analysis of cervical biopsy specimens from 26 women with cytological, colposcopic, and histological evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia grade I, reactive atypia, or human papillomavirus infection alone or in combination was performed in a comparative evaluation of Feulgen microspectrophotometry, the fast interval processor image analysis system, and flow cytometry. The fast interval processor image analysis system showed a distinct advantage over the other methods, being faster and allowing the operator to see the cells that were selected for measurement. The three methods of measurement together showed that the DNA content of at least 2% of the cells measured exceeded 5C (C being the haploid amount of DNA in a normal cell and 2C representing the diploid complement of a normal cell) in all cases of cervical intraepithelial neoplasia grade I and reactive atypia and in 87% of those reported as showing human papillomavirus infection alone. In contrast, the DNA content of cervical biopsy specimens from the transformation zone of 11 normal controls did not exceed 4C. This study shows the value of using a DNA threshold--that is, the "5C exceeding rate"--to distinguish between normal and neoplastic appearances of the cervix. These results support the view that cervical infection by human papillomavirus is a true precursor of neoplasia.

Aneuploidy↗

A new fixed cryosection technique for the simultaneous immunocytochemical demonstration of T6 and S100 antigens.

A formalin-calcium fixation method of preparing cryosections is described, which allows demonstration of Langerhans' cells by S100 antigen staining on frozen sections. The number of Langerhans' cells given by T6 antigen staining is also higher in formalin-calcium fixed frozen sections than acetone fixed frozen sections. The preparation is suitable for dual demonstration of the two antigens on the same section enabling a more accurate numerical evaluation of Langerhans' cell populations in the normal cervical epithelium.

Adult↗

Continuous 5-fluorouracil infusion in refractory carcinoma of the breast.

UNLABELLED: Twenty-five patients with refractory, metastatic carcinoma of the breast were treated with continuous ambulatory 5-fluorouracil (5 FU) infusion (200 to 300 mg/m2/day) through a chronic indwelling central venous catheter. All patients had had extensive previous treatment, including hormonal therapy in 20/25 patients (80%), radiation therapy in 18/25 patients (72%), and an average of 4.6 previous chemotherapy drugs per patient (range 1-10). Twenty-three of 25 patients (92%) had had previous bolus 5 FU. Seventeen of 25 patients (68%) had two or more metastatic sites of involvement and 17/25 patients (68%) had visceral involvement. RESULTS: complete remission-1/25 (4%), partial remission-7/25 (28%), stable disease-6/25 (24%), and progressive disease-11/25 (44%), for an overall response rate of 8/25 (32%). Median duration of response was 6 months. Toxicities included hand-foot syndrome, mucositis, diarrhea, and nausea and vomiting, and required treatment interruption and/or dose attenuation in 9/25 patients (36%). No myelosuppression or serious catheter-related problems were seen. We conclude that continuous 5 FU infusion is a potentially effective salvage treatment that may provide meaningful palliation in some patients with carcinoma of the breast, in spite of extensive previous treatment.

Adult↗

Single oral dose pharmacokinetics of bisoprolol 10 mg in liver disease.

The pharmacokinetic profile of an oral single dose of the new cardioselective beta-blocking agent, bisoprolol, was studied in patients with moderate and severe liver disease (Pugh group B and C, respectively) and normal subjects. In patients with liver disease a significant increase in the drug elimination half-life, mean residence time, area under the curve, and time to reach maximum plasma concentration (Tmax) was observed with a significant reduction in the oral clearance compared with the control population. There was significant positive correlation between the Pugh Score (an objective measurement of hepatic dysfunction) and the volume of distribution. The drug was well tolerated although a rise in blood urea and creatinine of over 50% was observed in 4 of 9 patients with severe liver disease. In conclusion, the delayed absorption in these patients results in lower plasma concentrations and indicates that dose adjustment is not necessary but it is recommended that the upper limit for the daily dose should be set at 10 mg; this also applies under chronic dosing of bisoprolol.

Administration, Oral↗

Subpopulations of Langerhans' cells in cervical neoplasia.

Multiple markers were used to count Langerhans' cells in the cervix. In the normal cervix, thymocyte antigen (T6) and adenosine triphosphatase (ATPase) demonstrated the largest population of Langerhans' cells. MHC Class II positive cells were equivalent to 60%, and S100 positive cells were equivalent to 35% of T6 or ATPase positive cells. Whereas Langerhans' cells demonstrated by T6, ATPase, and MHC Class II antigen were evenly distributed throughout the epithelium, the S100 positive cells were seen predominantly near lymphocytic aggregates and capillaries. In human papillomavirus infection and cervical intraepithelial neoplasia the numbers of T6, ATPase, or MHC Class II positive Langerhans' cells were reduced by 60% but the S100 positive cells were almost completely depleted. These findings suggested that there were different subpopulations of Langerhans' cells in the cervical epithelium. The depletion of Langerhans' cells, particularly the selective depletion of the S100 positive subpopulation, might cause a localized immunodeficiency that impairs immune surveillance and the cell-mediated immune response to human papillomavirus infection and cervical intraepithelial neoplasia.

Adult↗

Lymphocyte phenotypes in cervical intraepithelial neoplasia and human papillomavirus infection.

Lymphocyte phenotypes in cervical mucosa were studied using a panel of monoclonal antibodies. T lymphocytes were predominant both within the epithelium and in the subepithelial stroma. In the normal cervix, both the T4+ (helper/inducer) and T8+ (suppressor/cytotoxic) subsets were present in a ratio similar to that in the peripheral circulation. In human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) there was depletion of intraepithelial lymphocytes, especially of T4+ subset, with reversal of the ratio of T4+ to T8+ subsets to less than one. In contrast, there was no significant reduction in the number of lymphocytes in the subepithelial stroma. Tac+ (antigen primed and clonal expanding) lymphocytes were absent both within the epithelium and in the subepithelial stroma. These findings support our suggestion that there is a localized immunodeficiency in HPV infection and CIN. The aetiological and therapeutic implications are discussed.

Adolescent↗

Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia.

Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and E11 which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb E11 positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb E11 positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti-virus mechanism or non-specific phagocytosis.

Adult↗

Natural killer cells in cervical intraepithelial neoplasia and human papillomavirus infection.

A semiquantitative immunocytochemical study of natural killer (NK) cells in cervical mucosa was performed by the immunoperoxidase technique using anti-Leu-7 and anti-Leu-11 monoclonal antibodies. NK cells were present in two of the five normal controls and five of six specimens showing human papillomavirus (HPV) infection. Of the 12 CIN studied, six were positive for both Leu-7 and Leu-11 staining and three were positive for Leu-11 alone. NK cells were found predominantly in the subepithelial stroma. The frequency and pattern of distribution of these cells were similar in all grades of CIN. The number of NK cells present was usually small but the degree of infiltration by Leu-11 positive cells was pronounced in two HPV infections and in one CIN 1. NK cells may have a role in surveillance against HPV infection and the development and progression of CIN.

Adult↗

Management of squamous atypia (borderline nuclear abnormalities): repeat cytology or colposcopy?

A prospective cytological, colposcopic and histological study was conducted in 44 women with cervical cytology showing borderline nuclear abnormalities insufficient for the diagnosis of dyskaryosis. Atypical squamous epithelium was found on colposcopy in 41 patients and cervical intraepithelial neoplasia (CIN) was diagnosed on histology in 33 patients (75%) including 10 with CIN 3. Repeat cytology obtained under colposcopic vision was negative in 12 (33.4%) patients with CIN. The high prevalence of CIN in smears showing only borderline nuclear abnormalities and the high false negative rate of repeat cytology indicate that colposcopy should be the first line of management for these patients.

Adult↗

Multiple listerial liver abscesses.

Hepatic involvement in listeriosis is uncommon in adults. Cases previously reported include three presenting as acute hepatitis and three of listerial liver abscesses found at necropsy. We report a case of multiple listerial liver abscesses. We believe this to be the first time this diagnosis has been made in a living patient.

Aged↗

Routine papillomavirus antigen staining of cervical punch biopsy specimens.

Immunocytochemical staining for papillomavirus antigen was carried out on 1147 consecutive cervical punch biopsy specimens over 12 months. Of 876 cases with cervical intraepithelial neoplasia (CIN) 351, were antigen positive and of 49 cases with histological evidence of human papillomavirus (HPV) infection but no CIN, 14 were positive. There were 204 cases reported to be normal on routine histological examination and 12 cases reported to show features suggestive but not diagnostic of HPV infection. Of the normal group, 24 (12%) were antigen positive and of the equivocal group, two were positive. In 122 of the normal or equivocal groups cytological examination was repeated at the time of colposcopy, and dyskaryosis was reported in 36. In only four cases was disease shown by HPV antigen staining when there was no diagnostic histological or cytological abnormality. HPV antigen staining assists in the recognition of the range of histological changes associated with productive HPV infection but is an insensitive test and has only limited value in supplementing histological and cytological examinations as a diagnostic aid in routine colposcopic pathology.

Antigens, Viral↗

Quantitative deoxyribonucleic acid analysis of patients with mild cervical atypia: a potentially malignant lesion?

Quantitative deoxyribonucleic acid (DNA) analysis of cervical biopsy material from 32 women with cytologic, colposcopic, and histologic evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia I, reactive atypia, or human papillomavirus infection was carried out using flow cytometry and Feulgen microspectrophotometry. Evidence of aneuploidy, ie, neoplastic transformation, was demonstrated in all cases of cervical intraepithelial neoplasia I and 68% of cases with human papillomavirus-induced atypia. These results support the growing impression that human papillomavirus-induced cervical atypia should be regarded as a true precursor of cervical neoplasia, and emphasize the necessity to refer patients with mild atypia for definitive diagnosis and management.

Carcinoma in Situ↗

T-lymphocyte populations in normal and coeliac small intestinal mucosa defined by monoclonal antibodies.

Counts of T-lymphocytes within surface and crypt epithelium and lamina propria of normal and coeliac small intestinal mucosa using an immunoperoxidase method are described and related statistically to changes in mucosal structure determined by quantitative histology. The use of multiple pan-T-lymphocyte and subset antibodies allowed comparison of marker patterns in normal and abnormal mucosa. Total numbers of surface epithelial T-lymphocytes and subtypes were not found to be increased in coeliac disease, but there was an increase in density per unit length of epithelium. Distinctive changes in expression of Leu 1, Leu 2, and Leu 5 by the surface epithelial T-lymphocytes suggest that, although their total numbers are not increased, these cells are not passively crowded but have an active role, possibly as committed cytotoxic lymphocytes. Natural killer cells do not appear to be a major population in normal or coeliac small intestinal mucosa.

Adolescent↗

Histological and immunocytochemical study of cervical intraepithelial neoplasia (CIN) with associated HPV 6 and HPV 16 infections.

Histological and immunocytochemical features of cervical intraepithelial neoplasia (CIN) associated with HPV 6 and HPV 16, either singly or in combination, were studied in 48 cases. Features of HPV infection (koilocytosis, binucleation, multinucleation, giant irregular nuclei and individual cell dyskeratosis) were present in high prevalence in both HPV 6 and HPV 16 associated CIN. Abnormal mitoses seemed to be a good indicator of CIN and were present in about 50% of cases of CIN associated with either HPV 6 or HPV 16 infection. This finding provides no support for the view held by some investigators that associated HPV 16 infection can be predicted by the presence of abnormal mitoses. Expression of HPV antigen was shown in about 40% of cases with a slight, but not significantly, higher prevalence in cases of combined HPV 6 and HPV 16 infection. Conventional histology and immunocytochemistry could not distinguish CIN associated with HPV 6 from CIN associated with HPV 16 infection.

Antigens, Viral↗