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Biomedical subjects

M A Duggan

Publications and source records attributed to M A Duggan.

At least 37 records · Page 2Linked to original sources

Absence of human papilloma virus DNA in oropharyngeal spindle-cell squamous carcinomas.

The presence of human papilloma virus (HPV) DNA in verrucous carcinomas and some squamous-cell carcinomas (SCC) of the oropharynx suggests a role for the virus in their pathogenesis. Spindle-cell squamous carcinoma is an uncommon variant of oropharyngeal SCC. Its association with the HPV has not been reported. In situ and dot blot hybridization, using biotinylated probes to HPV 6, 11, 16, 18, 31, 33, and 35, failed to detect HPV DNA in nine studied cases of spindle-cell squamous carcinoma, as did polymerase chain reaction amplification, using a general HPV primer and type specific primers for HPV 6, 11, 16, 18, 31, and 33. Similar to previous studies, all patients were tobacco users, many were alcohol abusers, and six had a remote history of irradiation to the area. These factors, rather than the HPV, appear to have a more significant role in the development of this specific neoplasm.

Adult↗

A paired comparison of dot blot hybridization and PCR amplification for HPV testing of cervical scrapes interpreted as CIN 1.

The rate of Human Papillomavirus (HPV) detection in CIN 1 lesions is quite variable for several reasons. Amongst these, the sensitivity level of the HPV detection system probably ranks supreme. The prevalence of HPV DNA in cervical scrape samples from 234 patients referred for colposcopic investigation of a CIN 1 lesion was compared using dot blot hybridization (DBH) and polymerase chain reaction (PCR) amplification. Both methods were performed on the same patient sample so that determinants of HPV positivity other than the detection system could be controlled. Probes and primers to HPV 6, 11, 16, 18, 31, 33, and 35, and consensus HPV primers were used. The overall HPV positivity rate was 24% using DBH and 70% using PCR. Identified types by DBH and PCR respectively were; HPV 6/11: 1% and 2%, HPV 16/18: 16% and 41%, and HPV 31/33/35: 7% and 14%. PCR detected unidentified types in 13%. Since PCR resulted in a 2.9 times higher HPV DNA detection rate, the choice of detection system has a major impact on the HPV status of cervical smears interpreted as CIN 1.

Cervix Uteri↗

Adenocarcinoma in situ of the endocervix: human papillomavirus determination by dot blot hybridization and polymerase chain reaction amplification.

The frequency of human papillomavirus (HPV) in series of endocervical adenocarcinoma in situ (AIS) ranges from 6 to 100%. Some of this variability can be attributed to small study numbers and such technical considerations as the sensitivity of the hybridization method employed. Consequently, the role of the HPV in AIS oncogenesis is unclear. The frequency and relative distribution of HPV DNA types 6, 11, 16, 18, 31, 33, and 35 in 37 cases of AIS were determined and correlated with clinical variables. All cases were first typed by dot blot hybridization (DBH), and those found to be HPV negative were subsequently typed by polymerase chain reaction amplification with DBH enhancement (PCR/DBH). The HPV DNA positivity rate was 27% by DBH alone and 52% by PCR/DBH amplification. Combining the results of both methods, the overall HPV positivity rate was 66%: HPV 18 in 15 cases (43%), HPV 16 in eight cases (23%). The HPV status did not correlate with any clinical variable. This study showed that the sensitivity of the hybridization method is principally accountable for the variable frequency of HPV in AIS. The identification of only high-risk oncogenic HPV types in two-thirds of the cases suggests a significant role for the virus in AIS oncogenesis; HPV status, however, does not delineate a clinical profile.

Adenocarcinoma↗

The human papillomavirus status of 114 endocervical adenocarcinoma cases by dot blot hybridization.

The reported rate of human papillomavirus (HPV) positivity in cases of endocervical adenocarcinoma averages 38% (range, 0% to 100%) and, in contrast to cervical squamous cell carcinoma, HPV type 18 rather than type 16 is the predominant type. The HPV positivity rate and distribution of types (status) in 114 endocervical adenocarcinoma cases (37 in situ and 77 invasive) were determined by dot blot hybridization using biotinylated probes to HPV types 6, 11, 16, 18, 31, 33, and 35. Human papillomavirus DNA was present in 27% of in situ and in 44% of invasive adenocarcinomas, and in nearly all histologic subtypes of invasive adenocarcinoma. Human papillomavirus status was not predictive of tumor grade, volume, depth of invasion, lymph-vascular space involvement, age at presentation, or year of diagnosis. Type of HPV might influence the histologic subtype of invasive adenocarcinoma, as HPV type 16 predominated in the adenosquamous carcinomas while HPV type 18 was more frequently found in all other subtypes. Since only types 16, 18, and 33 were identified, an oncogenic role for HPV in endocervical carcinogenesis was supported.

Adenocarcinoma↗

Estrogen and progesterone receptor, human papillomavirus, and DNA ploidy analysis in invasive carcinoma of the cervix in pregnancy.

From 1980 to 1991, 13 patients had pregnancy-associated invasive carcinoma of the cervix: four carcinomas were stage IA; eight were stage IB; and one was stage IVB. Gestational ages range from 8 weeks to 3 months postpartum. Two patients are dead of disease and a third is alive with metastases. Results of immunoenzyme studies for estrogen receptors (ER) were variably positive in all except one tumor, whereas results of studies for progesterone receptors (PR) were uniformly negative. Thus, these hormone receptor studies are unlikely to be of prognostic significance. Six tumors contained human papillomavirus (HPV) DNA by in situ or dot blot hybridization (three, HPV 16; two, HPV 18; one, HPV 31/33/35). Thus, neither ER nor PR expression appears to be related to the infecting HPV type. Using flow cytometry, three tumors were determined to be aneuploid and a fourth, tetraploid. To correlate HPV or DNA flow cytometry data with prognosis will require study of larger numbers of patients from multiple centres.

Carcinoma↗

Age is prognostic variable in cervical squamous cell carcinoma.

A clinico-pathologic review was performed on all younger (under 35 years) and older (55 years or over) women with a diagnosis of cervical squamous cell carcinoma assessed at the Tom Baker Cancer Centre from 1980 to 1985 to determine the effect of age at diagnosis on survival. 45 younger women were identified: 32 were Stage IB; 10, Stage II; and 3, Stage III. 64 older women were identified: 16 were Stage IB; 30, Stage II; 14, Stage III; and 4, Stage IV. For Stage IB women, 40.6% of younger patients developed persistent or recurrent disease and all except one are dead; only one (6.2%) older woman's tumour recurred and she is alive with disease. Younger women had a poorer disease-free survival not only for Stage IB disease (p = 0.014) but also in Stages II and III (p = 0.020). In this study age at diagnosis was an independent prognostic variable with younger women having a poorer disease-free and overall survival.

Adult↗

Verrucous carcinoma of the genital tract: is it a distinct entity?

Between 1974 and 1985, 16 patients (7 men, 9 women) with a diagnosis of genital verrucous carcinoma were identified from the cancer registry of the Tom Baker Cancer Centre in Calgary. All the men had lesions on the penis. In the women, five lesions were on the vulva, four were on the cervix and two were on the vagina (two women each had two involved sites). The histologic slides from the surgically excised specimens were reviewed, and, by applying strict criteria, all cases could be reclassified as giant condyloma (five cases), intraepithelial neoplasia with or without condylomatous features (eight cases) or invasive squamous cell carcinoma (five cases). The authors believe that, in genital lesions associated with the human papillomavirus, a diagnosis of verrucous carcinoma is nonspecific and may lead to inappropriate clinical management.

Adult↗

Fibroadenoma of the breast: diagnostic pitfalls of fine-needle aspiration.

On fine-needle aspiration (FNA), fibroadenomas have a characteristic cytological appearance, although occasional cases are misinterpreted as carcinomas and vice versa. In a review of 521 breast aspirates correlated with the subsequent histology, six of 87 fibroadenomas (7%) were malignant or suspicious of malignancy on FNA (false positives). Following cytological review, four were still suspicious of malignancy because of cellular dyscohesion and prominent nucleoli, while two were fibroadenomas. On FNA, four of 145 carcinomas (3%) were diagnosed as fibroadenomas (false negatives). On review, three were malignant or suspicious of malignancy, while one was consistent with a fibroadenoma. Three false negative diagnoses were due to underappreciation of single malignant cells present between epithelial groupings typical of a fibroadenoma, while one was due to undersampling of the carcinoma. Cytologically, some fibroadenomas are sufficiently atypical that histological confirmation is necessary to exclude a malignancy. Misinterpreting carcinomas as fibroadenomas could be avoided by careful study of the morphology of isolated cells.

Adenofibroma↗

Morphometric analysis of nucleolar organizer regions in benign and malignant peritoneal effusions using backscattered electron microscopy.

Nucleolar organizer regions are loops of DNA associated with silver-stainable proteins (AgNORs). In general, malignant cells have more and larger AgNORs than benign cells. An inconsistent argyrophilic method and difficulties in objectively evaluating AgNORs account for some of the reluctance to utilize AgNOR staining as a diagnostic tool to differentiate benign and malignant lesions. Sections from paraffin-embedded cell blocks of 10 cases of benign and malignant peritoneal effusions were stained with a modified AgNOR method. Backscattered electron imaging in the scanning electron microscope, together with image analysis, was used to evaluate more objectively a number of AgNOR parameters and to determine which measurement was the most reliable discriminant of the two types of fluids. One hundred nuclei per case were identified and imaged. In contrast to benign nuclei, AgNORs in malignant nuclei were more numerous (P less than 0.0001) and larger (P less than 0.0001). A cut-off mean AgNOR area of 1.1 microns 2 (P less than 0.0001) correctly categorized all malignant (greater than 1.1 microns 2) and benign (less than or equal to 1.1 micron 2) cases. This system's objectivity and specificity could be used to enhance the cytological interpretation of effusions, where the separation of reactive mesothelial cells and malignant cells is extremely difficult.

Adenocarcinoma↗

Vascular proliferation of the thyroid. A complication of fine-needle aspiration.

Fine-needle aspiration (FNA) of the thyroid has a low morbidity rate, with hematoma formation being the most commonly encountered complication. We describe two cases of exuberant vascular proliferation within the thyroid gland, one resembling a cavernous hemangioma and the other with similar changes but with areas of papillary endothelial hyperplasia. Both lesions occurred in patients with a recent history of FNA prior to the thyroidectomy procedure. The vascular proliferation was interpreted as organizational changes in a hematoma secondary to the FNA. These cases, in conjunction with a recent case of Masson's vegetant intravascular hemangioendothelioma complicating thyroid FNA, expand the literature on vascular proliferations that may develop subsequent to thyroid FNA.

Biopsy, Needle↗

Human papillomavirus DNA in anal carcinomas. Comparison of in situ and dot blot hybridization.

Because the sensitivities of individual hybridization techniques differ considerably, their role in accounting for the published frequencies of human papillomavirus (HPV) DNA in anal squamous cell carcinomas, ranging from 0 to 61%, must be investigated. With the use of biotinylated probes to HPV 6, 11, 16, 18, and 33, three hybridization techniques were performed on the same paraffin-embedded tissue blocks selected from 13 cases of anal squamous cell carcinoma. HPV DNA was detected in 0%, 62%, and 85% of cases with the use of in situ hybridization with horseradish peroxidase, in situ hybridization with alkaline phosphatase, and dot blot hybridization, respectively. By dot blot hybridization, 69% had HPV 16/6 and 15% had HPV 6/11. An HPV DNA frequency range of 0-85% in the same group of tumors with the use of three hybridization techniques indicates the influential role of the method on HPV DNA prevalences. HPV DNA was identified regardless of patient gender or type of squamous cell carcinoma. The presence of HPV 16 in 82% of the positive cases in supportive evidence of the carcinogenic role of the HPV in anal squamous cell carcinoma.

Adult↗

Human papillomavirus type 16 associated with oral squamous carcinoma in a cardiac transplant recipient.

Human papillomavirus type 16 (HPV 16) has been associated with a variety of squamous carcinomas, particularly those involving the anogenital tract. The authors report the development of an oropharyngeal carcinoma in a 43-year-old man approximately 20 months after cardiac transplantation while he was on a maintenance regimen of cyclosporine A and prednisone. The carcinoma was resistant to treatment, and he died of complications related to metastatic disease 3 years posttransplantation. Molecular biologic studies using nonisotopic-labeled viral DNA probes were done. In situ hybridization demonstrated the presence of HPV 16 DNA in the tumor cells. DNA dot blot analysis confirmed the presence of multiple copies of HPV 16 DNA within the tumor cells and their absence from adjacent normal-appearing tissue. Southern blot analysis suggested that the HPV 16 DNA was integrated into the tumor cell genome. With increasing recognition of the carcinogenicity of HPV type 16 infection, a role for this virus in the development of squamous cell malignancies in immunosuppressed organ transplant recipients is likely to be noted with increasing frequency.

Adult↗

Nonisotopic human papillomavirus DNA typing of cervical smears obtained at the initial colposcopic examination.

To determine the prevalence of human papillomavirus (HPV) infection in 401 patients attending colposcopy for the first time, scraped cervical cells were investigated using dot blot hybridization and biotinylated DNA probes to HPV 6 and 11 (low-risk types) and 16, 18, and 33 (high-risk types). The HPV DNA was isolated from 52% of patients (low-risk types = 4%, high-risk types = 48%). Seventy-five percent had a cervical intraepithelial neoplasia (CIN)-condyloma. Low-risk types were infrequent (7%) and high-risk types (41%) predominant in condyloma/CIN I lesions when converse rates were expected. As CIN I lesions harboring high-risk types are at some risk of progressing to a higher grade dysplasia, colposcopic examination and treatment of this subgroup would seem justified. As expected, high-risk types were statistically associated with increasing grades of dysplasia. This hybridization method identified typeable HPV DNA in 60% of patients with a CIN-condyloma, and highlighted a unique HPV profile for this patient cohort.

Adolescent↗

Intestinal differentiation in ovarian mucinous tumours.

Fifty-five ovarian mucinous tumours, 22 benign, 16 borderline and 17 malignant, were examined for intestinal differentiation (ID). This was defined by the presence of one or more of endocrine, absorptive, goblet or Paneth cells, and identified by routine haematoxylin and eosin as well as histochemical and immunoperoxidase techniques. Twenty benign (91%), 14 borderline (88%) and all malignant tumours contained foci of ID. The frequency of ID was not significantly different between the mucinous tumour types (chi-squared test for independence). Follow-up was available on all patients with borderline tumours: 14 were stage Ia, including both cases without ID, and 2 were stage Ic at presentation. All are alive and free of disease at 9-39 months (median 15.5 months). We conclude that the presence of ID in borderline mucinous tumours is unlikely to be of prognostic significance, and that a subdivision of these tumours into müllerian and intestinal types is unnecessary.

Adolescent↗

A comparison of cervical scrapes for HPV typing by dot-blot hybridization obtained by wood and plastic spatulas.

A cross-over study was designed to determine whether the type of spatula used to collect cervical cells influences the ability of dot-blot hybridization to detect HPV DNA. Fifty-nine patients had a cervical scrape with a wood spatula first and a plastic spatula second: 60 were scraped in the inverse order. The order of sampling did not affect the HPV DNA positivity rate, which was nearly similar for both wood and plastic spatulas (30 and 32%, respectively). Wood spatulas collected more cells and greater than 1 x 10(5) cells more often than plastic spatulas (P = 0.001 and 0.06, respectively). Non-purple (negative) dots were more frequent in samples obtained by wood than by plastic spatulas (P = 0.001). The study showed that cervical cell collection by wood spatulas is preferred as they harvest more cells, thus optimizing the sensitivity of the hybridization method, and the spatulas are also more economical. Although they yielded more non-purple dots, a reduction in these dots by using plastic spatulas did not result in a significantly increased HPV positivity rate.

Cohort Studies↗

HPV DNA typing of adult-onset respiratory papillomatosis.

Respiratory papillomatosis is a recalcitrant, human papillomavirus-induced disorder of the upper airways. Using in situ hybridization and biotinylated deoxyribonucleic acid (DNA) probes, the type of human papillomavirus (HPV) in nine adults was determined both at presentation and during subsequent recurrences. Fifty-three biopsies obtained from seven men and two women over a 10-year period were examined for HPV 6, 11, 16 and 18. All patients had either type 6 or 11. One dual infection was found. Despite intensive therapy with lasers with or without alpha interferon, no elimination or change in viral type occurred. Despite identical histologies, the amount of HPV DNA present in a given patient's papillomata varied markedly. The results suggest that adult-onset respiratory papillomatosis is due to HPV 6 and/or HPV 11, and that its recurrent nature, despite therapy, is due to persistence of a viral reservoir.

Adult↗

Hepatolithiasis in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia is a rare, hereditary fibrovascular dysplasia. We report a case associated with hepatolithiasis. Hepatolithiasis, relatively common in East Asia, is rare in the West. The association of the two conditions has not been previously reported. In this case, vascular malformations in the liver gave rise to arteriovenous and arterioportal fistulas, causing arteriovenous shunting and protal hypertension, respectively. Abnormal blood flow is the proposed mechanism for the hepatic fibrosis and nodular regeneration. Hepatic fibrosis, by causing stenosis of large intrahepatic bile ducts, bile stasis, and secondary infection, is the hypothesized mechanism for calculus formation. Hepatolithiasis ultimately caused death from acute bacterial cholangitis and septicemia.

Cholestasis, Intrahepatic↗