A prospective study was performed in 202 patients with 219 fibroadenomas, diagnosed by a combination of clinical examination, ultrasonography and fine-needle aspiration cytology. Patients were given the choice of excision or conservative management with regular monitoring by ultrasonography. Sixteen patients with 18 fibroadenomas opted for excision and all 18 lesions were histologically confirmed as fibroadenomas. A further 152 patients with 163 fibroadenomas were observed for a minimum period of 2 years; 13 fibroadenomas increased significantly in size (all 13 were excised and confirmed histologically as fibroadenomas), 19 decreased significantly in size, 42 resolved and the remaining 89 showed no change in size. Conservative management of fibroadenomas in patients under the age of 40 is safe and acceptable to the majority of women.

Adult↗

PubMed1995

Calcifying disorders of the skin.

Calcium is vital to many biologic processes. In skin, it has a profound effect on keratinocyte proliferation, differentiation, and cell-cell adhesion. Serum calcium is tightly regulated by parathyroid hormone and 1,25(OH)2D3. Despite this careful regulation, calcification and ossification of cutaneous and subcutaneous tissues may occur. Cutaneous calcification may be divided into four major categories: dystrophic, metastatic, idiopathic, and iatrogenic. Dystrophic calcification occurs as a result of local tissue injury or abnormalities. Metastatic calcification results from abnormal calcium and/or phosphate metabolism. Virtually any process that calcifies may secondarily ossify. Primary ossification may rarely occur.

Calcinosis↗

PubMed1995

An improved HPLC assay for the assessment of liver slice metabolic viability using 7-ethoxycoumarin.

The use of precision-cut liver slices constitutes a new in vitro metabolism technique for the study of coupled phase I and phase II biotransformations. This technique has the advantage of being easily amenable to studies with human tissue. As a means of characterizing the metabolic viability of diverse liver samples, a standard substrate capable of undergoing oxidative and conjugative pathways of metabolism would be desirable. An assay based on 7-ethoxycoumarin was developed whereby the metabolites--7-hydroxycoumarin, 7-hydroxycoumarin sulfate, and 7-hydroxycoumarin glucuronide--could be quantitated using a single HPLC analytical method. This required the synthesis of metabolite standards. 7-Hydroxycoumarin glucuronide was prepared by coupling 7-hydroxycoumarin with methyl 2,3,4-tri-O-acetyl-1-bromo-1-alpha-D- glucopyranuronate, under phase transfer conditions, to give the protected conjugate that was then hydrolyzed to give the glucuronide as the sodium salt. Assignment of configuration at the anomeric center was based on analysis of the simulated 1H and gated 13C NMR spectra, in addition to enzymatic hydrolysis. The sulfate conjugate was prepared by treatment of 7-hydroxycoumarin with Bu4N+ HSO4-/dicyclohexylcarbodiimide/pyridine. 7-Ethoxycoumarin, 7-hydroxycoumarin, and the glucuronide and sulfate conjugates were resolved by HPLC on a C8 Hypersil BDS column using ion-pairing conditions. Incubation of 7-ethoxycoumarin with rat or human liver slices in Krebs-Henseleit buffer resulted in the formation of these metabolites that were readily quantitated in the media with UV detection at 320 nm, using external standard curves. Although the sulfate was seen as the major metabolite in rats, the glucuronide predominated in human tissue. Two different human livers were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Ultrasonography as a method of measuring breast tumour size and monitoring response to primary systemic treatment.

Accurate measurement of change in tumour size is a prerequisite for the use of response-based regimens of primary systemic therapy for breast cancer. This study evaluated the accuracy of clinical assessment, mammography and ultrasonography in measuring tumour size and in monitoring response to treatment. Size was determined during the week preceding surgery and actual size measured from resected specimens. Sequential measurements were performed in 35 patients undergoing primary systemic treatment. There was moderate correlation between pathological and clinical size (n = 51, r2 = 0.68, P < 0.0001). Close correlation with pathological tumour size was observed for mammographic (n = 45, r2 = 0.84, P < 0.0001) and ultrasonographic (n = 52, r2 = 0.89, P < 0.0001) tumour size. Response was correctly evaluated by clinical assessment in 31 of 35 patients, by mammography in 20 of 35 and by ultrasonography in 31 of 35. Actual tumour size can be measured accurately by available imaging techniques but ultrasonography is the most practical and accurate method for monitoring response.

Adolescent↗

PubMed1994

Colour Doppler studies of axillary node metastases in breast carcinoma.

Colour Doppler scans were carried out on 80 patients with breast carcinoma. Both the tumour and the lower axilla were scanned in all 80 patients. Seventy-five patients subsequently underwent axillary lymph node dissection and histological examination. The sensitivity of colour Doppler scanning for axillary node involvement was 70%, with a specificity of 98% and a positive predictive value of 96%.

Adult↗

PubMed1994

The efficacy of double reading mammograms in breast screening.

The effect of double reporting the screening mammograms of 31,146 women attending as part of the UK National Health Service Breast Screening Programme was analysed. Ninety per cent had their mammograms read by two of three experienced radiologists. Overall 1846 (5.9%) women were recalled for further assessment. Two hundred and sixty-one patients (0.8%) underwent surgical intervention resulting in the detection of 191 cancers (6.1/1000 women screened). The benign-to-malignant ratio was 1:3.6 (PPV 73.2%). Of the invasive cancers detected 72% had no histological evidence of axillary lymph node metastases. Twenty-one of the 191 cancers detected (10.4%) were missed by one of the two reporters. Six of these were invasive cancers < or = 1 cm in diameter. Comparison of those lesions detected by both readers to those detected by only one, showed readers were more likely to detect those lesions appearing as an opacity (65% vs 38%), but less likely to detect significant microcalcification (15% vs 33%). The difference between the two groups when taken as a whole, however, failed to reach statistical significance (chi 2 = 6.76, d.f. = 3, P = 0.08). In summary, double reporting resulted in an increase in sensitivity of 10%. However, there was a decrease in specificity of 1.8% with 569 women being recalled unnecessarily for assessment and biopsy of 13 benign lesions. The estimated resultant additional financial cost was 13773 pounds.

Aged↗

PubMed1994

Color Doppler signals in breast diseases.

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Breast Neoplasms↗

PubMed1992

The cost of institutional care in Alzheimer's disease: nursing home and hospital use in a prospective cohort.

OBJECTIVE: To assess the nursing home and hospital use of patients with Alzheimer's Type Dementia. DESIGN: A prospective cohort study of 126 patients entered into an Alzheimer's disease registry after diagnosis at a university hospital clinic between 1980 and 1982. Only four patients were in nursing homes at enrollment. MEASUREMENTS AND MAIN RESULTS: Data regarding nursing home use came from the registry and the individual nursing homes themselves. Hospital-use data were obtained using Medicare claims files. Follow-up was obtained on 123 patients (98%). Eighty-five (69%) had died by July 1, 1989. Three-quarters of the cohort (92) eventually resided in nursing homes. The median nursing home length of stay was 2.75 years (mean 2.95, 95% CI = 2.5, 3.4), over 10 times the national median length of stay for all diagnoses. Based on prevailing rates in the region, nursing home charges for the cohort were estimated to be between $4.3 and $6.4 million ($35,000-$52,000 per patient). During the 5-year period 1983-1988, 69 patients filed Part A (hospital) claims to Medicare for 76 admissions and 616 inpatient days. Part A Medicare reimbursement for the cohort totaled $460,000 over 5 years ($3,700 per patient), an expenditure comparable to what a random Medicare cohort might incur. CONCLUSIONS: The combination of a high rate of nursing home entry and lengthy stays makes long-term care the largest determinant of the cost of care in Alzheimer's disease. While Alzheimer's Type Dementia undoubtedly has profound indirect costs, this study demonstrates that the direct institutional costs alone are considerable.

Aged↗

PubMed1990

Survival of outpatients with Alzheimer-type dementia.

OBJECTIVE: To study the clinical course of Alzheimer-type dementia and those factors that might predict or influence the length of survival. DESIGN: A prospective cohort study. PARTICIPANTS: One hundred and twenty-six patients diagnosed with Alzheimer-type dementia were selected from among 200 consecutive outpatients evaluated for suspected dementia from 1980 to 1982. All 126 patients had at least 6 years of follow-up. SETTING: All patients were initially seen as outpatients at a university hospital. MEASUREMENTS AND MAIN RESULTS: Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model. The mean age at symptom onset was 73.9 years and at enrollment in the study, 77.6 years. The median survival from time of enrollment in the study was 5.3 years (range, 0.2 to 7.2+ years) and from symptom onset, 9.3 years (range, 1.8 to 16+ years). Dementia severity, as measured by the Mini-Mental State Examination (MMSE), was strongly associated with survival (P less than 0.001); the median survival of patients with scores of 18 or below was 3 years less than that of patients with scores above 18 (relative risk, 2.7; 95% CI, 1.6 to 4.4). Comorbid conditions and symptom duration were not related to survival. A multivariate analysis of age at symptom onset and of historical features showed that the combination of wandering and falling (relative risk, 2.1; 95% CI, 0.9 to 5.2) and the presence of behavioral problems (relative risk, 1.4; 95% CI, 0.7 to 2.9) at the time of evaluation appeared to adversely affect survival. CONCLUSIONS: Length of survival in patients with Alzheimer-type dementia is highly variable; severity of disease (not duration), the combination of wandering and falling, and behavioral problems are associated with shorter survival. Our findings, if confirmed, may provide prognostic information for families and professionals and suggest areas in which interventions to improve survival might be focused.

Accidental Falls↗

PubMed1988

Substitution of a transposed premolar for a congenitally absent lateral incisor.

The purpose of this report is to review the orthodontic treatment of a patient with bilateral transposition of maxillary canines and first premolars in addition to congenital absence of a maxillary lateral incisor. This unique combination of factors led to substitution of the maxillary left first premolar for the left lateral incisor. The occlusal fit, gingival form, and esthetic appearance of premolar/lateral incisor substitution are discussed.

Adolescent↗

PubMed1987

Unusual clinical presentations of bilateral renal artery aneurysms in a child. The value of ultrasound in diagnosis.

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Aneurysm↗

PubMed1987

Structural alterations that differentially affect the mutagenic and antitrichomonal activities of 5-nitroimidazoles.

Two approaches have been used to develop nonmutagenic 5-nitroimidazoles. Both approaches are based on knowledge of the likely mechanisms by which this class of compounds cause mutagenicity. The first approach involved incorporating readily oxidizable gallate derivatives into the molecule. In one case, a very weakly mutagenic active antitrichomonal agent was obtained. The second approach involved incorporating a substituent at the C4 position of the ring. This generally resulted in a large reduction in mutagenicity and a lowering of antitrichomonal activity in vitro. In certain cases, however, mutagenicity was dramatically reduced while moderate antitrichomonal activity was retained. For example, 1,2-dimethyl-4-(2-hydroxyethyl)-5-nitroimidazole (5) showed good antitrichomonal activity in vitro (ED50 = 2 micrograms/kg) while possessing only 4% of the mutagenicity of metronidazole.

Animals↗

PubMed1986

The metabolic activation of ronidazole [(1-methyl-5-nitroimidazole-2-yl)-methyl carbamate] to reactive metabolites by mammalian, cecal bacterial and T. foetus enzymes.

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Animals↗

PubMed1986

Studies on the mechanism of activation and the mutagenicity of ronidazole, a 5-nitroimidazole.

Substantial evidence implicates the obligatory nucleophilic attack by water at C4 for the elimination of the carbamate and subsequent immobilization by electrophilic attack on protein thiols. Consequently, the strong correlation between the structural requirements for protein alkylation and for mutagenicity in TA100 suggests a possible role of nucleophilic addition at C4 or at the 2-methylene carbon for the expression of mutagenicity. Further studies directed at evaluating this possibility are currently in progress.

Alkylation↗