Aging and aggregate costs of medical care: conceptual and policy issues.

The conventional wisdom says that because the cost of health care for the aged is more than that of the young at any time, there is a positive relationship between the aging or higher life expectancy of the population and aggregate health care spending. It is difficult, however, to find evidence to support this argument. We present a simple framework that shows how aging of the population may not necessarily increase the total cost of medical care over time or be observed across nations.

C8orf4 is a transforming growth factor B induced transcript downregulated in metastatic colon cancer.

Transforming growth factor (TGF) beta mediates a tumor suppressor pathway in human colon epithelial cells. We were interested in identifying and characterizing novel genes regulated by the TGF beta pathway in the colon. We employed expression microarrays to identify transcripts induced by TGF beta in Vaco 330, a colon adenoma cell line.

Single-stage adenosine tilt testing in patients with unexplained syncope.

Introduction: We previously have shown that a 3-minute single-stage adenosine tilt test has a diagnostic yield comparable to a two-stage protocol consisting of a 30-minute drug-free tilt followed by a 15-minute isoproterenol tilt. In this study, we sought to further define the clinical utility of adenosine tilt testing in patients with unexplained syncope by prospectively evaluating test specificity and determining predictors of a positive test response.

Methods And Results: The specificity of single-stage adenosine tilt testing was determined using 30 control subjects.

Mutational analysis of the tyrosine phosphatome in colorectal cancers.

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity.

Three classes of genes mutated in colorectal cancers with chromosomal instability.

Although most colorectal cancers are chromosomally unstable, the basis for this instability has not been defined. To determine whether genes shown to cause chromosomal instability in model systems were mutated in colorectal cancers, we identified their human homologues and determined their sequence in a panel of colorectal cancers. We found 19 somatic mutations in five genes representing three distinct instability pathways.

The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter.

The orphan cotransport protein expressed by the SLC5A8 gene has been shown to play a role in controlling the growth of colon cancers, and the silencing of this gene is a common and early event in human colon neoplasia. We expressed this protein in Xenopus laevis oocytes and have found that it transports small monocarboxylic acids. The electrogenic activity of the cotransporter, which we have named SMCT (sodium monocarboxylate transporter), was dependent on external Na(+) and was compatible with a 3 : 1 stoichiometry between Na(+) and monocarboxylates.

Macular perimetry in low vision.

Background: Detection of residual visual function is critical for vision rehabilitation. Macular perimetry may provide essential information in this regard. In the presence of reduced vision, fixation maintenance is paramount for perimetric test validation.

Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer.

Aberrant WNT pathway signaling is an early progression event in 90% of colorectal cancers. It occurs through mutations mainly of APC and less often of CTNNB1 (encoding beta-catenin) or AXIN2 (encoding axin-2, also known as conductin). These mutations allow ligand-independent WNT signaling that culminates in abnormal accumulation of free beta-catenin in the nucleus.

Lighting up and slimming down: the effects of body weight and cigarette prices on adolescent smoking initiation.

This paper examines the influence of body weight, body image, and cigarette prices in determining adolescent smoking initiation. Adolescents who desire to lose weight may initiate smoking as a method of appetite control. Such behavior may undermine the goals of tobacco control policies that seek to prevent smoking initiation.

The effects of daylight and daylight saving time on US pedestrian fatalities and motor vehicle occupant fatalities.

This paper analyzes the effects of daylight and daylight saving time (DST) on pedestrian and motor vehicle occupant fatalities in the United States. Multivariate analyses of county level data from the Fatality Analysis Reporting System for 2-week periods in 1998 and 1999 are used. Results show that full year daylight saving time would reduce pedestrian fatalities by 171 per year, or by 13% of all pedestrian fatalities in the 5:00-10.

Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo.

The slope of the action potential duration (APD) restitution curve may be a significant determinant of the propensity to develop ventricular fibrillation, with steeper slopes associated with a more arrhythmogenic substrate. We hypothesized that one mechanism by which beta-blockers reduce sudden cardiac death is by flattening the APD restitution curve. Therefore, we investigated whether infusion of esmolol modulates the APD restitution curve in vivo.

Continued epidemic of bladder cancer in workers exposed to ortho-toluidine in a chemical factory.

Ortho-toluidine (o-toluidine), an aromatic amine, is classified by the International Agency for Research on Cancer as a probable human carcinogen. A cohort study published in 1991 reported a 6.5-fold excess incidence of bladder cancer in a chemical plant that used o-toluidine.

An update on electrical cardioversion of atrial fibrillation.

Atrial fibrillation is the most frequently encountered sustained arrhythmia in clinical practice. Electrical cardioversion of atrial fibrillation using damped sine wave shocks has been a mainstay of therapy for nearly 4 decades; its limitation remains a failure rate that approaches 20%. Although several alternatives have been proposed, including delivering 720 J shocks using dual monophasic defibrillators, ibutilide pretreatment and internal cardioversion, each of these approaches has significant limitations, which preclude its routine use.

Manipulation of nonsense mediated decay identifies gene mutations in colon cancer Cells with microsatellite instability.

Cancer cells showing microsatellite instability (MSI) demonstrate a high frequency of acquired frameshift mutations that result in the generation of nonsense mutations. RNA transcripts carrying these nonsense mutations are usually targeted for degradation through the nonsense mediated decay (NMD) pathway. Blocking this pathway with drugs such as emitine, results in the 'stabilization' of these mutant transcripts, which can now be detected on cDNA arrays.

PRL-3 expression in metastatic cancers.

Purpose: Expression of the PRL-3 tyrosine phosphatase is elevated in liver metastases derived from colorectal cancer (CRC). We sought to determine the cellular basis of this elevation and assess the expression of PRL-3 in metastatic lesions derived from cancers of the colon and other tissues.

Experimental Design: We developed modifications of in situ hybridization methods that facilitated the study of paraffin-embedded sections.

A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2.

Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in approximately 20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative.

Pharmacogenetic considerations in diseases of cardiac ion channels.

Phenotypic variation within a species arises from differences in genetic makeup between individuals. This inherent diversity empowers the species as a whole to explore and expand into new environmental niches and also to survive new stressors within an ever-changing environment. Paradoxically, one class of stressors currently challenging the human population is therapeutic drugs: medications designed to combat disease are often associated with a host of nonspecific side effects.

Integrated pest management in an urban community: a successful partnership for prevention.

Pesticides, applied in large quantities in urban communities to control cockroaches, pose potential threats to health, especially to children, who have proportionately greater exposures and unique, developmentally determined vulnerabilities. Integrated pest management (IPM) relies on nonchemical tools--cleaning of food residues, removal of potential nutrients, and sealing cracks and crevices. Least toxic pesticides are used sparingly.

Use of a continuous local anesthetic infusion for pain management after median sternotomy.

Background: The use of large doses of opioid analgesics to treat pain after cardiac surgery can prolong the time to tracheal extubation and interfere with recovery of bowel and bladder function in the postoperative period. Therefore, the authors investigated the efficacy of a continuous infusion of bupivacaine 0.25% or 0.

Globalization and the transfer of hazardous industry: asbestos in Mexico, 1979-2000.

This study quantified asbestos use in Mexico in the past decade and evaluated available data on mortality due to malignant mesothelioma in Mexico between 1979 and 2000. Mortality data were analyzed from secondary databases of the Mexican Social Security System and the Ministry of Health. Data on the import and export of asbestos in Mexico were obtained from the Ministry of Trade and Industrial Development of Mexico.

Endocardial detection of repolarization alternans.

Repolarization alternans (RPA) is prognostic of sudden cardiac death and is thought to be mechanistically linked to the initiation of ventricular tachyarrhythmias. Thus, implantable cardiac device detection of RPA may be therapeutically valuable. Because alternans detection is currently limited to surface electrocardiograms, we investigated whether RPA could be measured using a single right-ventricular endocardial lead in humans.