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Biomedical subjects

I D Miller

Publications and source records attributed to I D Miller.

At least 19 recordsLinked to original sources
PubMed2000

Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy.

PURPOSE: To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION: [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.

Adult↗
PubMed1999

Psychological factors can predict the response to primary chemotherapy in patients with locally advanced breast cancer.

This study evaluated the possible value of psychological variables in predicting clinical and pathological response to primary chemotherapy. 96 women with newly diagnosed large, or locally advanced, breast cancer (T2 > 4 cm, T3, T4, N2 and M0) participated in a prospective, randomised trial to evaluate the effects of relaxation training with guided imagery and L-arginine on response to primary chemotherapy. Before the first of six cycles of primary chemotherapy, women were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Eysenck Personality Questionnaire (EPQ). The primary outcomes were clinical response (evaluated using standard International Union Against Cancer (UICC) criteria) and pathological response (graded by means of a previously published 5-point scale) following primary chemotherapy. Stepwise linear regressions were used to estimate the predictive value of age, menopausal status, clinical nodal status, tumour size at diagnosis, oestrogen receptor status, dietary supplementation (L-arginine versus placebo), personality (EPQ-L scores), mood (HADS scores) and a psychological intervention. HADS depression score was a significant independent predictor of pathological response to chemotherapy. HADS anxiety score was a significant independent predictor of clinical response. Because the original tumour size before chemotherapy (also a significant predictor of clinical and pathological responses) was taken into account in the analyses, the results cannot be explained in terms of psychobiological factors related to tumour size. This study supports the importance of psychological factors as independent predictors of response to primary chemotherapy in patients with breast cancer. If they can be replicated, these findings have major implications for the management of women with breast cancer. Psychological factors need to be assessed and evaluated in future trials of chemotherapy.

Adult↗
PubMed1999

Psychological, clinical and pathological effects of relaxation training and guided imagery during primary chemotherapy.

The diagnosis and treatment of breast cancer are stressful, and stress may be associated with a poorer response to chemotherapy. There is a need, therefore, to develop and evaluate interventions that might enhance quality of life and, possibly, improve treatment response. The effects of relaxation combined with guided imagery (visualizing host defences destroying tumour cells) on quality of life and response to primary chemotherapy, to date, have not been adequately evaluated. Ninety-six women with newly diagnosed large or locally advanced breast cancer (T2 > 4 cm, T3, T4, or TxN2 and M0) took part in a prospective, randomized controlled trial. Patients were randomized following diagnosis to a control condition (standard care) or to the experimental condition (standard care plus relaxation training and imagery). Psychometric tests to evaluate mood and quality of life were carried out before each of the six cycles of chemotherapy and 3 weeks after cycle 6: tests of personality and coping strategy were carried out prior to cycles one and six. Clinical response to chemotherapy was evaluated after six cycles of chemotherapy using standard UICC criteria and pathological response was assessed from the tissue removed at surgery. As hypothesized, patients in the experimental group were more relaxed and easy going during the study (Mood Rating Scale). Quality of life was better in the experimental group (Global Self-assessment and Rotterdam Symptom Checklist). The intervention also reduced emotional suppression (Courtauld Emotional Control Scale). The incidence of clinically significant mood disturbance was very low and the incidence in the two groups was similar. Finally, although the groups did not differ for clinical or pathological response to chemotherapy, imagery ratings were correlated with clinical response. These simple, inexpensive and beneficial interventions should be offered to patients wishing to improve quality of life during primary chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Immunohistochemical localization of cytochrome P450 CYP1B1 in breast cancer with monoclonal antibodies specific for CYP1B1.

Cytochrome P450 CYP1B1 is a recently identified member of the CYP1 P450 family. We have shown that this P450 displays increased expression in several types of human cancer, indicating that CYP1B1 is a potential tumor biomarker. In this study we developed monoclonal antibodies (MAbs) to CYP1B1 that are effective on formalin-fixed, paraffin-embedded tissue sections and investigated the presence of CYP1B1 in a series of primary breast cancers. The MAbs were generated using a synthetic peptide coupled to carrier protein as the immunogen. The MAbs specifically recognized CYP1B1 and did not recognize either CYP1A1 or CYP1A2, related CYP1 forms. The MAbs were tested by immunohistochemistry and were found to be effective on formalin-fixed, paraffin-embedded tissue sections. The majority of breast cancers showed positive immunoreactivity for CYP1B1, and in each case CYP1B1 was specifically localized to tumor cells. The presence of CYP1B1 in breast cancer cells is likely to contribute to their metabolism of estradiol because CYP1B1 is a specific estradiol hydroxylase. (J Histochem Cytochem 47:1457-1464, 1999)

Amino Acid Sequence↗
PubMed1998

Large-scale PACS implementation.

The transition to filmless radiology is a much more formidable task than making the request for proposal to purchase a (Picture Archiving and Communications System) PACS. The Department of Defense and the Veterans Administration have been pioneers in the transformation of medical diagnostic imaging to the electronic environment. Many civilian sites are expected to implement large-scale PACS in the next five to ten years. This presentation will related the empirical insights gleaned at our institution from a large-scale PACS implementation. Our PACS integration was introduced into a fully operational department (not a new hospital) in which work flow had to continue with minimal impact. Impediments to user acceptance will be addressed. The critical components of this enormous task will be discussed. The topics covered during this session will include issues such as phased implementation, DICOM (digital imaging and communications in medicine) standard-based interaction of devices, hospital information system (HIS)/radiology information system (RIS) interface, user approval, networking, workstation deployment and backup procedures. The presentation will make specific suggestions regarding the implementation team, operating instructions, quality control (QC), training and education. The concept of identifying key functional areas is relevant to transitioning the facility to be entirely on line. Special attention must be paid to specific functional areas such as the operating rooms and trauma rooms where the clinical requirements may not match the PACS capabilities. The printing of films may be necessary for certain circumstances. The integration of teleradiology and remote clinics into a PACS is a salient topic with respect to the overall role of the radiologists providing rapid consultation. A Web-based server allows a clinician to review images and reports on a desk-top (personal) computer and thus reduce the number of dedicated PACS review workstations. This session will focus on effective strategies for a seamless transition. Critical issues involve maintaining a good working relationship with the vendor, cultivating personnel readiness and instituting well-defined support systems. Success depends on the ability to integrate the institutional directives, user expectations and available technologies. A team approach is mandatory for success.

Computer Communication Networks↗
PubMed1998

Staging of the axilla in breast cancer: accurate in vivo assessment using positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

OBJECTIVE: To evaluate the ability of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) to determine noninvasively axillary lymph node status in patients with breast cancer. BACKGROUND: The presence of axillary lymph node metastasis is the most important prognostic factor in women with breast cancer. It signifies the presence of occult metastatic disease and indicates the need for adjuvant therapy. The only reliable way in which this important prognostic information may be obtained is by performing axillary dissection, which may be associated with significant complications and delay in discharge from the hospital. PET with 18F-FDG can visualize primary cancers in the breast and metastatic tumor deposits. METHODS: Fifty patients with untreated breast cancer had clinical examination of their axilla performed (graded as positive or negative), followed by PET of the axilla and midthorax. PET data were analyzed blindly and graded as positive or negative, depending on the presence or absence of axillary nodal metastases. Cytopathologic assessment of the axillary nodes was carried out within 1 week of PET, by fine-needle aspiration cytology in 5 patients and axillary dissection in 45; the excised specimens were examined by a single pathologist. RESULTS: The overall sensitivity of PET in 50 patients was 90% and the specificity was 97%. Clinical examination of the same patients had an overall sensitivity of 57% and a specificity of 90%. In the 24 patients with locally advanced breast cancer (T3, T4, TxN2), PET had a sensitivity of 93% and a specificity of 100%. In T1 tumors (seven patients), the sensitivity and specificity were 100%. PET had a high predictive value (>90%) and accuracy (94%) in staging the axilla. CONCLUSIONS: PET is a sensitive and specific method of staging the axilla in patients with breast cancer. It may obviate the need for axillary surgery in women with small primary tumors, define the women likely to benefit from axillary dissection, or allow radiotherapy to be substituted for surgery, particularly in post-menopausal women.

Adult↗
PubMed1997

p53 protein expression in a population-based series of primary vulval squamous cell carcinoma and immediate adjacent field change.

OBJECTIVES: Our aim was to study correlations between survival, disease recurrence, and p53 protein expression in a well defined population-based series of vulval squamous cell carcinoma and immediate adjacent epithelial skin changes. METHODS: One hundred fifteen vulval squamous cell carcinoma were studied. Epithelial skin changes immediately adjacent to tumor were classified into nonneoplastic epithelial disorders (NNED) or vulval intraepithelial neoplasia (VIN). Archival specimens containing primary tumor and immediate adjacent skin were immunostained with a mouse monoclonal antibody to p53 protein. RESULTS: p53 overexpression, defined as greater than 10% nuclear epithelial staining, was observed in 68% of tumors. Tumor immunostaining did not correlate with actuarial survival or disease-free interval. p53 overexpression was associated with a nonsignificant trend toward shorter disease-free interval in those tumors with nodal metastatic disease at diagnosis (P = 0.07). The only clinicopathological variable found to correlate with p53 expression was tumor grade (P = 0.002). Immediate adjacent abnormal skin changes were associated with p53 overexpression in 32% of cases. Adjacent normal skin did not immunostain for p53, p53 overexpression was most likely to occur in adjacent epithelial changes incorporating both NNED and high grade VIN (P = 0.005). Patterns of epithelial p53 overexpression in adjacent abnormal skin were either basal or full thickness. Full thickness epithelial p53 overexpression was most likely to occur in those disorders containing VIN (P < 0.0001). Positive immunostaining of adjacent skin abnormalities did not predict local tumor recurrence. CONCLUSIONS: This study demonstrates that although vulval squamous tumor p53 expression is not of prognostic significance, distinct immunostaining patterns can be observed in immediate adjacent skin. Vulval epithelial skin disorders displaying histological features of both NNED and VIN III may contain a profile of underlying molecular change which is of significance in subsequent tumor development.

Adult↗
PubMed1997

Pancreatic tissue in a lateral cervical cyst attached to the thyroid gland--a presumed foregut remnant.

AIM: To report the previously undescribed occurrence of a lateral neck cyst, attached to the thyroid gland, containing pancreatic tissue. METHODS AND RESULTS: A 41-year-old man presented with a recurrent cystic lesion of the thyroid. At thyroidectomy cystic masses containing mucinous material were present in the neck, and there was a nodular lesion attached to the lower pole of the thyroid. Histological examination of the latter lesion revealed an epithelial lined cyst, with pancreatic tissue (exocrine and endocrine) in addition to fat, fibrous tissue, muscle and cartilage in the wall. CONCLUSIONS: The possible origin of this structure is discussed, with the conclusion being that it most likely represents a foregut remnant.

Adult↗
PubMed1996

Male breast cancer: clinico-pathological features, immunocytochemical characteristics and prognosis.

A series of 30 cases of male breast cancer in the North-East of Scotland is reviewed. The aims of the study were to document clinico-pathological and immunocytochemical features (available for 25) of these patients and to establish which factors could predict prognosis. Tumours were studied for the expression of oestrogen receptors (ERs), the oestrogen-dependent proteins pS2 and cathepsin D, the oncoprotein products of c-erb-B2 and the p53 tumour-suppressor-gene derived protein. Clinico-pathological features documented were in agreement with those reported by other authors. The overall 5-year survival was 53%. Tumour grade and lymph-node status influenced prognosis. In this series, 64% of the tumours expressed ERs, 50% pS2, 46% cathepsin D, 42% the c-erb-B2 transmembrane oncoprotein and 54% p53. In contrast to female breast cancer, the presence of either substantial amounts of ERs or the oestrogen-dependent protein pS2 correlated with poorer prognosis in males. This correlation has not previously been documented.

Breast Neoplasms, Male↗
PubMed1996

A study of the value and prognostic significance of mucin staining in squamous cell carcinoma of the uterine cervix.

One hundred and eighty-one cases of squamous carcinoma of the uterine cervix, which had been retrieved from the archives of Aberdeen Royal Hospital, from 1974 to 1988, were stained with periodic acid-Schiff following diastase and alcian blue to ascertain the value and prognostic significance of demonstrating the presence of mucin. Each case was typed and graded on a representative haematoxylin and eosin section, while the age at diagnosis, stage and survival (within a minimum five year follow-up) was obtained from examination of hospital case notes and death certificates. The data was analysed by Cox regression which revealed that the demonstration of mucin, either by both stains or only one method, had no bearing on prognosis. On this basis, it is concluded that routine mucin staining of squamous carcinomas of the uterine cervix is not justified.

Biomarkers, Tumor↗
PubMed1994

Cervical carcinoma in the Grampian region (1980-1991): a population-based study of survival and cervical cytology history.

OBJECTIVES: To study survival in women treated for cervical carcinoma in Grampian region, to identify clinical and pathological prognostic factors, and to correlate survival with cytology history. DESIGN: A retrospective study of all cases of cervical carcinoma using a prospectively gathered database. Data validated by 1 in 10 randomised retrospective case note sampling. SETTING: Aberdeen Royal Infirmary. SUBJECTS: Three hundred and sixty-three women resident within Grampian diagnosed as having cervical carcinoma between 1980 and 1991, with five-year survival data on the 206 diagnosed by the end of 1986. MAIN OUTCOME MEASURE: Five-year survival rates. RESULTS: The mean annual incidence of cervical carcinoma in our population was 11.2 per 100,000 women, with an overall five-year survival of 67% in those under 40 years of age and 60% in those aged 40 years and over. On univariate analysis, survival was significantly adversely affected by tumour stage, grade and absence of previous smears. On multivariate analysis, the effect of previous smear history was lost, but stage and grade remained strong independent risk factors for survival. There was no significant difference in five-year survival by age or tumour type. CONCLUSIONS: The prognosis of cervical carcinoma in Grampian region was independently affected only by stage of disease and tumour grading and cervical smear history.

Adult↗
PubMed1993

Optical modelling of light distributions in skin tissue following laser irradiation.

A Monte-Carlo method is used to compute light distributions in a multilayer skin model for variable width finite beams. By means of a 4-layer skin model in which blood may be represented as a discrete layer, vascular lesions such as port wine stains may be studied. Light distributions and thermal profiles are simulated, representing the irradiation of a port wine stain using 577 nm and 585 nm wavelengths. Damage thresholds at 585 nm are found to substantially exceed those predicted at 577 nm, although the nature of the damage differs at the two wavelengths. Variations due to beam width are found to be unimportant if the diameter exceeds 1 mm. The predictions are compared with clinical results, and a novel 5-layer approach based on new optical parameters is adopted to account for discrepancies in epidermal temperature.

Hemangioma↗
PubMed1993

Intraosseous leiomyoma of the mandible: report of a case.

A rare case of intraosseous leiomyoma of the mandible is reported. This is the fourth recorded case involving the mandible. The literature is reviewed and the amenability of the lesion to simple local excision is highlighted.

Actins↗
PubMed1992

A population-based study of microinvasive disease of the cervix--a colposcopic and cytologic analysis.

A study of 61 cases of microinvasion of the cervix occurring in our population between 1980 and 1989 is reported. The mean age of the women was 39 years, compared with 30 years for cervical intraepithelial grade 3 (CIN III) and 47 years for frank invasion, respectively. Colposcopic suspicion of microinvasion was present in 31 cases, giving a sensitivity of colposcopic diagnosis of 50% and a specificity of 91%. In 21 cases (34%) there was no suspicion either cytologically or colposcopically of microinvasion. Colposcopy predicted microinvasion more accurately with increasing depth of invasion. In 28 women there had been previous smears within 10 years available for review. The time interval between the first abnormal smear and the histological diagnosis ranged from 1 month to 9.8 years (mean, 4 years).

Adult↗