Discovering patterns in microarray data.

The human genome is a complex system characterized by gene interactions and nonlinear behaviors. Complex systems cannot be viewed as the aggregate of their isolated pieces but must be studied as an integrated whole. Microarray technologies offer the opportunity to see the entire biological system as it existed at one moment in time.

Adherence to prescription medications among medical professionals.

Background: We evaluated adherence to medication usage by health care professionals to estimate the expected upper limit of adherence among the general population.

Methods: In a self-administered survey, physicians and nurses were asked about their use of prescribed medications for acute and chronic illnesses. The settings were a teaching hospital, employee health service, medical college, and educational conferences.

Clinical and laboratory evaluation of all-trans retinoic acid modulation of chemotherapy in patients with acute myelogenous leukaemia.

All-trans retinoic acid (ATRA) is synergistic with chemotherapy in leukaemia cell lines. We treated 53 patients with newly diagnosed acute myelogenous leukaemia (AML) with high-dose cytarabine-based chemotherapy followed by ATRA. Peripheral blood and bone marrow samples were obtained to study the effect of in vitro exposure to ATRA and to measure apoptosis and bcl-2.

Artificial neural networks applied to survival prediction in breast cancer.

In this study, we evaluated the accuracy of a neural network in predicting 5-, 10- and 15-year breast-cancer-specific survival. A series of 951 breast cancer patients was divided into a training set of 651 and a validation set of 300 patients. Eight variables were entered as input to the network: tumor size, axillary nodal status, histological type, mitotic count, nuclear pleomorphism, tubule formation, tumor necrosis and age.

Methylenetetrahydrofolate reductase thermolabile variant and oral clefts.

Folic acid can prevent neural tube defects; in some cases the mechanism is probably a correction of a metabolic defect caused by thermolabile methylenetetrahydrofolate reductase (MTHFR) found in increased frequency in cases. It is less clear whether folic acid can prevent oral clefts, in part because it is not known whether thermolabile MTHFR is more common in those with oral clefts. This study examined the prevalence of the mutation (677 C-->T) that causes thermolabile MTHFR in subjects with oral clefts from a national Irish support group, and an anonymous control group randomly selected from a neonatal screening program covering all births in Ireland.

The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother.

Recent reports have implicated the "thermolabile" (T) variant of methylenetetrahydrofolate reductase (MTHFR) in the causation of folate-dependent neural tube defects (NTDs). We report herein the largest genetic study of NTD cases (n=271) and families (n=218) to date, establishing that, in Ireland, the "TT" genotype is found in 18.8% of cases versus 8.

Effect of variation in the apo A-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II. EARS Group.

The aims of the study were to investigate associations of the apolipoprotein (apo) A-IV polymorphisms Thr347Ser and Gln360His with anthropomorphic measurements and fasting and postprandial lipids in subjects participating in the European Atherosclerosis Research Study II (EARS II). The allelic frequencies of Ser347 and His360 were 0.185 and 0.

Fiberoptic bronchoscopy in coronary care unit patients: indications, safety, and clinical implications.

Study Objectives: To evaluate the indications, safety, therapeutic impact, and outcome of fiberoptic bronchoscopy (FOB) in coronary care unit (CCU) patients.

Design: Retrospective review of all CCU patients undergoing FOB during a 6-year period.

Setting: Tertiary care university hospital.

Specimen banks for cancer prognostic factor research.

Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues.

Low blood folates in NTD pregnancies are only partly explained by thermolabile 5,10-methylenetetrahydrofolate reductase: low folate status alone may be the critical factor.

Thermolabile 5,10-methylenetetrahydrofolate reductase (MTHFR) is the first folate-related variant to be associated with an increased risk of neural tube defects (NTDs). The variant causes high plasma homocysteine levels and reduced red cell folate (RCF) levels, both of which have also been linked to an increased risk of NTDs. We examined the relationship between folate status and presence of the common mutation MTHFR C677T in 82 NTD-affected and 260 control mothers.

Predicting response to adjuvant and radiation therapy in patients with early stage breast carcinoma.

Background: Screening and surveillance is increasing the detection of early stage breast carcinoma. The ability to predict accurately the response to adjuvant therapy (chemotherapy or tamoxifen therapy) or postlumpectomy radiation therapy in these patients can be vital to their survival, because this prediction determines the best postsurgical therapy for each patient.

Methods: This study evaluated data from 226 patients with TNM Stage I and early Stage II breast carcinoma and included the variables p53 and c-erbB-2 (HER-2/neu).

Artificial neural networks improve the accuracy of cancer survival prediction.

Background: The TNM staging system originated as a response to the need for an accurate, consistent, universal cancer outcome prediction system. Since the TNM staging system was introduced in the 1950s, new prognostic factors have been identified and new methods for integrating prognostic factors have been developed. This study compares the prediction accuracy of the TNM staging system with that of artificial neural network statistical models.

Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously.

Background: Prompt recognition of the reversal of respiratory failure may permit earlier discontinuation of mechanical ventilation, without harm to the patient.

Methods: We conducted a randomized, controlled trial in 300 adult patients receiving mechanical ventilation in medical and coronary intensive care units. In the intervention group, patients underwent daily screening of respiratory function by physicians, respiratory therapists, and nurses to identify those possibly capable of breathing spontaneously; successful tests were followed by two-hour trials of spontaneous breathing in those who met the criteria.

Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women.

Hyperinsulinemia, a manifestation of insulin resistance, precursor of non-insulin dependent diabetes mellitus (NIDDM) and the hallmark of Syndrome X was assessed in 27 obese post-menopausal women. Insulin-like growth factor binding protein-1 (IGFBP-1), which had been shown previously to correlate inversely with insulin in animal and human studies, was evaluated as a diagnostic marker for abnormal glucose stimulated area under the curve (AUC) insulin (defined a priori as > or = 100 microU/ml). We performed analysis of variance and logistic regression to assess IGFBP-1 and other study covariates, including body mass index, blood pressure, lipids and measures of glucose and insulin in hyperinsulinemic vs.

A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects.

It is now well-established that folic acid, taken peri-conceptionally, can reduce the risk of neural tube defects (NTDs). Recent work has demonstrated that an abnormality of homocysteine metabolism is a critical factor. The gene for 5,10 methylenetetrahydrofolate reductase, an enzyme important in homocysteine metabolism, was studied in relation to NTDs.

Artificial neural networks for cancer research: outcome prediction.

The use of artificial neural networks in biological and medical research has increased tremendously in the last few years. Artificial neural networks are being used in cancer research for image processing, the analysis of laboratory data for breast cancer diagnosis, the discovery of chemotherapeutic agents, and for cancer outcome prediction. A neural network generalizes from the input data to patterns inherent in the data, and its uses these patterns to make predictions or to classify.

Increasing the power of surrogate endpoint biomarkers: the aggregation of predictive factors.

A variable that predicts an outcome with sufficient accuracy is called a predictive factor. Predictive factors can be divided into three types based on the outcomes to be predicted and on the accuracy with which they can be predicted. These three types include risk factors, where the main outcome of interest is incidence and the predictive accuracy is less than 100%; diagnostic factors, where the main outcome of interest is also incidence but the predictive accuracy is almost 100%; and prognostic factors, where the main outcome of interest is death and the predictive accuracy is variable.

The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials.

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened.