Biomedical subjects
K Malone
Publications and source records attributed to K Malone.
Mouse models of human cancer web-based resources.
The Mouse Models of Human Cancers Consortium (MMHCC) is a collaborative program designed to derive and characterize mouse models of human malignancies. To enhance information and resource exchange among the MMHCC investigators and other cancer research scientists, the NCI Center for Bioinformatics (NCICB, http://ncicb.nci.nih.gov/) has developed web-based resources that are freely available to the cancer research community. These resources include a website (http://emice.nci.nih.gov) and databases for cancer models (http://cancermodels.nci.nih.gov) and cancer images (http://cancerimages.nci.nih.gov).
Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.
Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.
Comparison of a 6-hour and 9-hour protocol for evaluation of moderate-to-low risk chest pain patients in an emergency department diagnostic unit.
OBJECTIVE: To compare the 30-day outcomes of patients enrolled in a 6-hour and 9-hour emergency department (ED)-based chest pain centre (CPC) protocol. METHODS: All patients with the chief complaint of chest pain, who were older than 25 years, or with cocaine usage within 96 hours of initial presentation, were eligible for enrolment. Exclusion criteria included acute ST-segment elevation or depression >1 mm in 2 contiguous leads, history of coronary artery disease (CAD), haemodynamic instability or clinical syndromes consistent with unstable angina. Outcomes included ED disposition and cardiac events at 30 days (defined as acute myocardial infarction (AMI), percutaneous trans-luminal coronary angiography (PTCA), coronary artery bypass graft surgery (CABG),ventricular tachycardia or fibrillation (VT/VF) arrest, congestive heart failure (CHF) admission or cardiac-related death). The 9-hour protocol consisted of ST-segment monitoring,serial CK-MB draws at 0, 3,6 and 9 hours as well as a graded exercise test (GXT) prior to ED disposition. The 6-hour protocol eliminated the 9-hour serum marker determination, included cardiac Troponin-I (cTn-I) and allowed a GXT, 3 hours earlier. Follow-up was obtained by medical record review, phone contact, letter and also review of national and state death registries. RESULTS: The 9-hour protocol (October 1991-December 1997) included 2,133 patients and the 6-hour protocol (January 1998- August 1998) had 184 patients enrolled. The 6-hour protocol was not different from the 9-hour one in terms of percentage admissions (9-hour: 310, 14.5%; 6-hour: 33, 17.9%; p=0.213), Coronary Care Unit admission (9-hour: 59, 2.8%; 6-hour: 5, 2.7%; p=0.303) or 30-day cardiac events (9-hour: 38, 1.9%; 6-hour: 2, 1.3%; p=0.605). CONCLUSION: The 6-hour CPC strategy is an effective and safe evaluation method for patients at low to moderate risk for acute coronary syndromes.
Serotonin syndrome during treatment with paroxetine and risperidone.
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Identifying and mapping novel retinal-expressed ESTs from humans.
PURPOSE: The goal of this study was to develop efficient methods to identify tissue-specific expressed sequence tags (ESTs) and to map their locations in the human genome. Through a combination of database analysis and laboratory investigation, unique retina-specific ESTs were identified and mapped as candidate genes for inherited retinal diseases. METHODS: DNA sequences from retina-specific EST clusters were obtained from the TIGR Human Gene Index Database. Further processing of the EST sequence data was necessary to ensure that each EST cluster represented a novel, non-redundant mapping candidate. Processing involved screening for homologies to known genes and proteins using BLAST, excluding known human gene sequences and repeat sequences, and developing primers for PCR amplification of the gene encoding each cDNA cluster from genomic DNA. The EST clusters were mapped using the GeneBridge 4.0 Radiation Hybrid Mapping Panel with standard PCR conditions. RESULTS: A total of 83 retinal-expressed EST clusters were examined as potential novel, non-redundant mapping candidates. Fifty-five clusters were mapped successfully and their locations compared to the locations of known retinal disease genes. Fourteen EST clusters localize to candidate regions for inherited retinal diseases. CONCLUSIONS: This pilot study developed methodology for mapping uniquely expressed retinal ESTs and for identifying potential candidate genes for inherited retinal disorders. Despite the overall success, several complicating factors contributed to the high failure rate (33%) for mapping EST-clustered sequences. These include redundancy in the sequence data, widely dispersed sequences, ambiguous nucleotides within the sequences, the possibility of amplifying through introns and the presence of repetitive elements within the sequence. However, the combination of database analysis and laboratory mapping is a powerful method for identification of candidate genes for inherited diseases.
Participation in breast cancer risk counseling among women with a family history.
Recent scientific breakthroughs in the genetics of breast cancer may have had effects on women's perceptions of risk and subsequent worry about breast cancer. Here, we present the rates of interest in counseling among women identified from diverse sources, their levels of cancer worry and perceived risk, and predictors of their agreement to participate in breast cancer risk counseling. Women were identified through breast cancer cases and through media offers. They completed a telephone survey and were ultimately either entered or not entered into a counseling trial. Overall, almost half (46%) of cases who were approached responded to the contact letter asking for information about potentially interested relatives. A total of 588 women responded to the brief media solicitations over a 15-week period. Participants recruited from media contacts reported slightly but significantly higher levels of worry about getting cancer, compared to case-recruited participants. Cancer worry negatively and significantly predicted entry into the counseling project. The results presented here may have implications for recruiting women in the general population with a family history of breast cancer for counseling about their risk for the disease.
Characteristics of women who use perineal powders.
OBJECTIVE: To examine demographic and behavioral factors related to perineal application of powders. METHODS: Controls from three case-control studies (N = 1206) were asked identical questions about the use of genital powders by direct perineal application. The relationship of perineal powder application with demographic factors, reproductive factors, body mass index (BMI), douching, and alcohol and tobacco use was assessed. Data were analyzed by multiple logistic regression. RESULTS: Women who douched (prevalence odds ratio [prevalence OR] 2.0, 95% confidence interval [CI] 1.0, 3.9), drank alcohol (prevalence OR 1.8, 95% CI 1.2, 2.8), smoked cigarettes (prevalence OR 1.3, 95% CI 1.0, 1.8), or were in the highest BMI quartile were more likely to engage in perineal use of powder (prevalence OR 1.6, 95% CI 1.1, 2.6). There appeared to be a close response relationship between the number of perineal applications of powder and BMI (P < .002). CONCLUSION: Body mass index might confound the relationship between perineal powder application and the development of ovarian cancer. Other factors, such as alcohol and tobacco use and douching, are related to perineal use of powder and may represent similar behavioral characteristics.
Plasma tryptophan levels and prolactin response to fenfluramine in healthy volunteers.
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Standards and practice guidelines as the foundation for clinical practice.
The structure and organization of health care delivery are in the midst of rapid change. Health care providers from a variety of disciplines are being challenged to define their practice and the expected patient outcomes resulting from their processes of care delivery. Standards and clinical practice guidelines are important tools for enhancing the quality of health care delivery and for documenting care. The article describes a process for developing standards and clinical practice guidelines and presents an organizational scheme for them. Based on recommendations from diverse national groups, a format for practice guidelines is presented, and a system for implementation and ongoing evaluation is recommended.
Response to "an alternative material for silicone casting" by james m. Sabo.
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Casting in sport.
Attempts by sports medicine professionals to return high school athletes with hand and wrist injuries to competition quickly and safely have been the source of confusion and debate on many playing fields around the country. In addition to the differing views regarding the appropriateness of playing cast usage in high school football, a debate exists among sports medicine professionals as to which material is best suited for playing cast construction. Materials used in playing cast construction should be hard enough to provide sufficient stabilization to the injured area and include adequate padding to absorb blunt impact forces. The purpose of the biomechanical portion of this investigation was to attempt to determine the most appropriate materials for use in constructing playing casts for the hand and wrist by assessing different materials for: 1) hardness using a Shore durometer, and 2) ability to absorb impact using a force platform. Results revealed that RTV11 and Scotchcast were the "least hard" of the underlying casting materials and that Temper Stick foam greatly increased the ability of RTV11 to absorb impact. Assessment of the mechanical properties of playing cast materials and review of current developments in high school football rules are used to aid practitioners in choosing the most appropriate materials for playing cast construction.
Non-fatal deliberate self-poisoning in Dublin's north inner city--an overview.
It is almost three decades since a survey of attempted suicide in Dublin City Hospitals was published. In 1962, 159 cases in the City of Dublin and Borough of Dun Laoghaire were studied and reported. Over a six month period (November 1989-April 1990) 147 cases of deliberate self-poisoning were admitted to the Mater Hospital, Dublin, of which 100 case notes were appropriate for examination. In 1973, a six month survey of attempted suicide was carried out at the Mater Hospital, Dublin where 38 patients were admitted following non-fatal deliberate self-poisoning. In our study, the female to male ratio was 2:1, 50% of cases took more than one drug type,, benzodiazepines being the most commonly ingested compound. Alarmingly over a quarter (28%) of females under 25 had overdosed on paracetamol either alone or in conjunction with other compounds. Alcohol was consumed in 46% of all cases. 40% of cases involved a past history of deliberate self-poisoning and 60% had a past history of psychiatric intervention. Our survey outlines current trends in deliberate self-poisoning in Dublin's North Inner City. We have compared our 1990 survey to the similar survey conducted by our unit seventeen years ago. Several characteristics remain unaltered. The number of overdoses has almost trebled. We have noted a sharp rise in unemployment, alcohol abuse and psychiatric history among female overdoses. We have noted the disturbing introduction of paracetamol overdose particularly among young females (25%). Finally we have documented the introduction of overdosing amongst the homeless population which did not exist in the 1973 survey, but which accounts for 12% of our survey.(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of lymphocytic infiltrates in C4 mouse mammary tumors.
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Characterization of lymphocytic infiltrates in normal, preneoplastic, and neoplastic mouse mammary tissues.
Lymphocytic infiltrates were isolated from normal, preneoplastic, and neoplastic mouse mammary tissues. The surface markers on the infiltrating lymphocytes were characterized by immunofluorescent staining and flow cytometry. Preneoplastic and neoplastic tissues contained 10- to 20-fold more in situ lymphocytes than did the normal pregnant gland. Most of these lympocytes were T-cells. Relative to the T-cells in normal gland, the T-cells in C4 preneoplastic hyperplastic alveolar nodules and their spontaneous tumors have shifted in favor of the killer-suppressor subpopulation. This shift of T-cell subpopulations was a localized phenomenon and was not seen in the lymph nodes of hyperplastic alveolar nodules and tumor bearing mice. C4 lesion infiltrating cells also contained a subpopulation of lymphocytes that expressed 5- to 6-fold more LFA-1 antigen (lymphocyte function associated antigen-1) than did normal lymph node cells. The infiltrating lymphocytes of mammary tumors from cloned cell lines, on the contrary, had the same staining profile as did the lymphocytes from normal gland. Since most studies with human breast cancer infiltrates have demonstrated increased killer/suppressor T-cells and the presence of activated lymphocytes (J. Hurlimann and P. Saraga, Int. J. Cancer, 35: 753-762, 1985; H.L. Whitwell, H.P.A. Hughes, M. Moore, and A. Ahmed, Br. J. Cancer, 49: 161-172, 1984; and J.A. Ledbetter, R.V. Rouse, H. Spedding Micklem, and L. Herzenberg, J. Exp. Med., 152: 280-295, 1980) the C4 hyperplastic alveolar nodules and spontaneous tumor system may be a more relevant model for studying breast cancer infiltrates.
Outcomes of family-centered residential treatment.
This article describes a family-centered residential treatment model and presents results from a quasiexperimental study examining its effectiveness in achieving permanency outcomes for children. Greater postdischarge stability was achieved for participants in the family-centered program than in the agency's standard residential treatment service. Implications for child welfare policy and practice are highlighted.