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Dorothy R Pathak

Publications and source records attributed to Dorothy R Pathak.

7 recordsLinked to original sources
PubMed2005

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology.

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation.

Journal Article↗
PubMed2005

The effect of selected preparation variables on the radiochemical purity of 99mTc-sestamibi.

OBJECTIVE: Measurement of cardiac perfusion via agents such as 99mTc-sestamibi (Cardiolite; DuPont-Merck Pharmaceutical Co., Inc.) is widely used in clinical nuclear medicine for the diagnosis of coronary artery disease. The monograph for 99mTc-sestamibi recommends at least 90% radiochemical purity (RCP) for clinical use. Various factors may influence the RCP of certain reagent kits. Some of these include the amount of activity added to the reagent kit, the generator ingrowth time, the generator manufacturer, the age of the eluate, and the age of the formulated kit. A D-optimal design with a 20-experiment run was devised to study the effects of these variables either alone or in combination on the RCP of 99mTc-sestamibi. METHODS: The RCP was assessed by Baker-Flex thin-layer and high-performance liquid chromatographic methods, immediately and 6 h after reconstitution of the 99mTc-sestamibi. RESULTS: The results showed that 4 of the 5 variables studied were statistically significant predictors of the RCP. The age of the formulated kit did not influence the RCP. CONCLUSION: For any combination of these 4 variables, the mean RCP remained greater than or equal to 90%, that is, within the recommended range of RCP for clinical use at radioactivity levels ranging from 5,550 MBq to 37,000 MBq.

Chromatography↗
PubMed2004

Glucosinolate derivatives in stored fermented cabbage.

The research focused on the glucosinolate (GLS) breakdown products formed during the fermentation of cabbage. A relationship between the contents of degradation products in fermented cabbage and native GLS in raw cabbage was investigated. The effect of fermented cabbage storage on the contents of individual compounds was also assayed. Ascorbigen formed from one of the degradation products of glucobrassicin (indole GLS) was found to be a dominating compound in fermented cabbage. Irrespective of the time of fermented cabbage storage, the content of ascorbigen reached approximately 14 micromol/100 g. Neither the content of isothiocyanates, the major degradation products of aliphatic GLS, nor that of cyanides exceeded 2.5 microM. Storage of cabbage caused periodical increases and decreases in the contents of cyanides and consequent declines in the contents of isothiocyanates. The highest relative contents (expressed as a percentage of the native GLS content) of degradation products--ranging from >70 to 96%--were reported for the products of glucoraphanin degradation, whereas the lowest-- <5% --were reported for the products of sinigrin degradation.

Ascorbic Acid↗
PubMed2003

Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations.

BACKGROUND: It has been suggested that BRCA-associated breast carcinoma may often lack a detectable preinvasive phase. To investigate this hypothesis, the authors compared the prevalence of histopathologic lesions in prophylactic mastectomy (PM) specimens from women with BRCA mutations and in mastectomy specimens obtained at autopsy from an age and race-matched comparison group without a known cancer predisposition. METHODS: All specimens from women with a deleterious BRCA1 or BRCA2 mutation who participated in an ongoing follow-up study and underwent PM at Memorial Sloan-Kettering Cancer Center between November 1, 1987 and May 31, 2001 were reviewed. For each case, breast tissue from two age and race-matched women without a known cancer predisposition was also reviewed. The prevalence of benign, premalignant, and cancerous lesions was compared. RESULTS: Mastectomy specimens from 24 cases and 48 comparison subjects were reviewed. Ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH), and atypical lobular hyperplasia (ALH) were all more common in PM specimens from women with BRCA mutations than in those from the comparison group. The odds ratio for the detection of any high-risk lesion (DCIS, lobular carcinoma in situ, ADH, or ALH) in specimens from BRCA mutation carriers was 12.7 (95% confidence interval, 3.1-52.4; P < 0.001). CONCLUSIONS: Lesions associated with an increased risk of subsequent malignancy are more common in PM specimens from women with BRCA mutations than in breast tissue obtained at autopsy from unaffected women without a known predisposition. This finding suggests that hereditary breast carcinoma has a preinvasive phase that may be detectable with aggressive surveillance.

Adult↗
PubMed2003

Development of a clinical decision rule for triage of women with palpable breast masses.

BACKGROUND AND OBJECTIVE: Given the large numbers of open breast biopsies performed in women who have benign breast masses, we developed a clinical decision rule (CDR), called BREASTAID, to triage women into open biopsy or follow-up. METHODS: A prospective cohort design was used to obtain data on 452 palpable breast masses evaluated at a referral clinic. Breast cancer was defined as ductal carcinoma in situ or invasive cancer at open biopsy. Separate logistic regression models were developed at three logical stages of the clinical workup. Bayes' theorem was applied in a stepwise fashion to revise model probabilities to generate a final probability of cancer. Receiver operator characteristics curves were generated to determine the optimum cut-point. Results derived from the CDR were compared with actual clinical practice. RESULTS: A total of 452 masses in 380 women were included. Clinical practice resulted in 180 masses (39.8%) undergoing open biopsy, 41 (22.8%) of which were cancers. Age, history of breast cancer in the mother, mass size, mammography findings, and fine needle aspiration biopsy results were included in the final models. When applied to the derivation dataset, BREASTAID successfully identified 40 of 41 cancer masses (sensitivity 97.6%, 95% confidence interval [CI] 94.1-99.9), and 350 of 411 noncancer masses (specificity 85.2%, 95% CI 81.8-88.5). BREASTAID would have reduced the number of biopsies performed on the 411 benign masses from 139 to 61. CONCLUSIONS: This study demonstrated that a CDR based on routinely collected clinical variables has the potential to accurately triage women with palpable breast masses. Further validation of the rule is required before its clinical use can be considered.

Adult↗
PubMed2003

BREASTAID: Clinical results from early development of a clinical decision rule for palpable solid breast masses.

OBJECTIVE: To develop a clinical decision rule (entitled BREASTAID) that will predict the probability of malignancy in women with palpable solid breast masses. SUMMARY BACKGROUND DATA: Currently, 80% of open breast biopsies are benign, resulting in excessive economic, psychologic, and physical morbidity. METHODS: A total of 452 solid breast masses were evaluated in a surgical breast clinic between November 1994 and February 1998. Breast cancer status was defined histologically as ductal carcinoma in situ or invasive cancer. Noncancer status included benign histology, mass resolution, or stability at 12-month follow-up. Data were collected on risk factors, clinical breast examination, mammography, and cytology results. Three multiple logistic regression models were used to generate the probability of cancer at 3 logical steps in the workup; Bayes' theorem was applied in a stepwise fashion to generate a final probability of cancer. RESULTS: A model incorporating only clinical breast examination and mammography resulted in an excessive number of either missed cases or biopsies compared with one that included cytology. Using a cut-point of 4%, this latter BREASTAID model had 97.6% sensitivity and 85.1% specificity. Compared with triple diagnosis, BREASTAID would have reduced the open biopsy rate from 39.8% (180 of 452) to 22.3% (101 of 452), improving the diagnostic yield from 22.7% to 40.6%. CONCLUSIONS: This study convincingly demonstrates that at minimum, clinical, radiologic, and cytologic evaluations are required to accurately evaluate a solid breast mass. BREASTAID has the potential to minimize the number of open biopsies performed while allowing safe triage to follow-up. Before widespread application, further validation studies are required.

Bayes Theorem↗