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Special report on the official positions of the International Society for Clinical Densitometry.

The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. Following an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Absorptiometry, Photon↗

The colorectal microRNAome.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. These studies suggest that the human genome contains many more miRNAs than currently identified and provide an approach for the large-scale experimental cloning of novel human miRNAs in human tissues.

Base Sequence↗

Recent insights in programmed electrical stimulation for the management of sustained ventricular arrhythmias.

After more than 20 years of clinical use, programmed electrical stimulation for induction of cardiac arrhythmias remains an important clinical and research tool. The procedure continues to undergo refinement but is not without controversy regarding its accuracy in predicting drug efficacy as determined by serial testing for suppression of ventricular tachyarrhythmias. Recent work has streamlined technical aspects of the procedure itself and promises to improve the selection of patients likely to benefit from such studies. Despite these advances, however, recent publications from the Electrophysiologic Study Versus Electrocardiographic Monitoring trial raise fundamental questions about the ability of any current strategy to predict the efficacy of antiarrhythmic drugs for the prevention of ventricular arrhythmias.

Anti-Arrhythmia Agents↗

Official positions of the international society for clinical densitometry.

The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. After an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD Position Development Conferences and presents selected Official Positions of general interest.

Absorptiometry, Photon↗

Initial evaluation of the early aberration reporting system--Florida.

INTRODUCTION: In recent years, many syndromic surveillance systems have been deployed around the United States for the early detection of biologic terrorism-related and naturally occurring outbreaks. These systems and the associated aberration detection methods need to be evaluated. OBJECTIVE: This study evaluated several detection methods of the Early Aberration Reporting System (EARS) under serially correlated syndromic data and to demonstrated the need for calibrating these methods. METHODS: In an initial evaluation of the Syndromic Tracking and Reporting System in Hillsborough County, Florida, serially correlated syndromic data were simulated using statistical models in conjunction with real syndromic data. The detection methods were tested against two patterns of simulated outbreaks. They were compared using a conditional average run length and a receiver operating characteristic curve under defined patterns of detection. RESULTS: Increasing serial correlation inflates the false alarm rate and elevates sensitivity. Among the detection methods in EARS, C2 and P-chart have the best overall receiver operating characteristic curve within the context of the simulations. C2 is least affected by the serial correlation, the outbreak type, and the defined patterns of detection signal. CONCLUSION: Evaluation of the detection methods needs to be adaptable to the constantly changing nature of syndromic surveillance. Deployment of EARS and other methods requires adjusting the false alarm rate and sensitivity in accordance with the syndromic data, the operating resources, and the objectives of the local system. For timely detection, C2 is superior to other methods, including C3, under the simulation conditions. P-chart is the most sensitive when the serial correlation is negligible.

Algorithms↗

Effect of deep hypothermia and circulatory arrest on cerebral blood flow and metabolism.

The primary goal of monitoring cerebral blood flow and metabolism is to improve our understanding of the association with cardiopulmonary bypass and deep hypothermic circulatory arrest so that effective brain protection strategies can be developed and employed. A review of our cerebral blood flow/cardiopulmonary bypass database, presently totaling 275 neonates and infants, for the purposes of this publication, reveals certain trends and some conclusions that can be drawn. Deep hypothermic circulatory arrest continues to be a factor in the delayed recovery of cerebral blood flow and metabolism in these patients. Examining flow and metabolism serially in the postoperative period shows that in the majority of patients, flow, metabolism and autoregulation return to normal within 24 hours after operation. Some patients' cerebral oxygen metabolism is unable to exert a protective response of increasing extraction in the setting of low cerebral blood flow. We have also observed that in the setting of low cardiac output after cardiac repair, cerebral blood flow is low. It is therefore likely that low cardiac output and pressure-passive cerebral blood flow potentiate brain ischemia after cardiopulmonary bypass and operation in some patients. We have also examined in our series of 275 patients selective neuroprotection strategies for their potential for improving recovery of cerebral blood flow and cerebral metabolism. Duration of cooling on cardiopulmonary bypass correlates directly with suppression of metabolism due to hypothermia. Low-flow cardiopulmonary bypass instead of deep hypothermic circulatory arrest, and topical brain cooling with ice during deep hypothermic circulatory arrest, improve cerebral blood flow and cerebral metabolic recovery.

Brain Ischemia↗

Condition and type of housing as an indicator of potential environmental lead exposure and pediatric blood lead levels.

Environmental evaluations in a prospective behavioral study of children with blood lead levels up to about 50 micrograms/dl were performed by an intensive environmental survey and by exterior visual evaluation of housing quality. Serial blood lead values for infants in the study were compared to exterior housing type and quality, which itself was also compared with results of the intensive environmental evaluation. Five housing condition and type categories were defined: public housing; private housing (satisfactory, deteriorated, and dilapidated); and rehabilitated private housing. In this interim report on the first subset of available data, the housing categories were found to differ in paint and environment dust lead levels, with public and rehabilitated housing having lowest values. Blood lead concentrations of children differed across housing categories as early as 6 months of age, with children residing in public housing having lowest levels, followed by those in rehabilitated housing. The spread in mean blood lead concentrations among the housing quality categories increased with increasing age of the children. Housing category accounted for over one-half of the blood lead variability in 18-month-old children.

Dust↗

Correlations of patch test reactivity and the repeated open application test (ROAT)/provocative use test (PUT).

The clinical relevance of patch test reactions is often difficult to determine. Use tests have been developed to further evaluate the significance of patch test results. We review studies that have defined correlations between the threshold concentrations at patch testing and the outcome of use tests for particular chemical allergens. Results of patch testing with serial dilutions of colophony, cinnamic aldehyde, and isoeugenol have shown concordance with the outcome of use tests. On the other hand, poor correlations between patch test reactivity and the use test were demonstrated in another study on isoeugenol and on studies on hydroxycitronellal, formaldehyde and chromium. These studies shed light on some factors that may influence the outcome of use tests. Individual factors such as patch test sensitivity, regional variations in reactivity and percutaneous penetration appear to play significant roles. Exposure dose, length of time of exposure, and other factors yet to be determined also affect degree of reactivity. Because patients with low thresholds in serial dilution patch testing are known to react to lower concentrations of products at use testing, results of these studies may be used to help identify subjects with a high risk of developing clinical disease. From the public health standpoint, data obtained may be used as a guide in limiting exposure concentrations in consumer products.

Acrolein↗

Pharmacokinetics of methylprednisolone in elderly and young healthy males.

OBJECTIVE: To characterize and compare the pharmacokinetics of a single intravenous dose of methylprednisolone in elderly and young healthy males. DESIGN: A randomized, parallel pharmacokinetic trial. SETTING: A public university-affiliated hospital. SUBJECTS: Seven healthy, elderly white males (aged 69 to 82 years) and five healthy, young white males (aged 24 to 37 years) who gave informed consent and fulfilled all screening criteria. MEASUREMENTS: Serial blood samples were obtained over a 24-hour study period after intravenous administration of a 10-mg dose of methylprednisolone. Serum methylprednisolone concentrations were determined by high performance liquid chromatography and utilized to determine the pharmacokinetic parameters. RESULTS: Methylprednisolone serum concentrations declined in a linear manner in both groups. However, 4 hours after the dose, the mean serum concentration of methylprednisolone was 50.9 +/- 15.1 ng/mL in the elderly group and 37.6 +/- 7.5 (P = 0.07) ng/mL in the young group. The clearance of methylprednisolone was 237 +/- 62 mL/h/kg, with a volume of distribution of 1.10 +/- 0.07 L/kg, for the elderly group, whereas the young males had a mean drug clearance of 359 +/- 90 mL/h/kg (P < 0.05) and a mean volume of distribution of 1.28 +/- 0.34 L/kg. The half-life of methylprednisolone ranged from 1.90 to 5.40 hours in the elderly group; the range was 1.99 to 3.31 hour (P = 0.016) in the young group. CONCLUSION: A slower methylprednisolone clearance was noted in the elderly group compared with the young counterparts. This pharmacokinetic alteration seen in healthy elderly subjects may contribute to the increased incidence of adverse effects from chronic glucocorticoid therapy that has been observed among elderly patients.

Adult↗

Identification of astrocytoma associated genes including cell surface markers.

BACKGROUND: Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. METHODS: We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas 1. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie 2, and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. RESULTS: A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. CONCLUSIONS: This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes.

Adult↗

Psychotherapy of dysthymia.

OBJECTIVE: The author reviews empirical research on the psychotherapy of dysthymia. Dysthymia, a prevalent mood disorder, has been shown frequently to respond to antidepressant medication. The need for a treatment for dysthymic subjects unable or unwilling to take, or unresponsive to, medication still remains. METHODS: Studies were located by computerized search and the author's knowledge of the literature. All reports of studies on psychotherapy outcome for dysthymic patients, except studies of late-life chronic major depression, were included. RESULTS: Psychotherapy research on dysthymia has been confined to small, usually uncontrolled studies with varying methods and limited follow-up. Cognitive approaches have been most frequently studied; the results have not been dramatic but do suggest that some dysthymic patients respond to brief cognitive therapies. Preliminary results of an ongoing study of interpersonal psychotherapy are promising. CONCLUSIONS: Given the public health importance of dysthymia and the availability of treatments, the time is ripe for clinical trials of antidysthymic psychotherapy. The author proposes the following guidelines for such trials: time-limited, manual-based psychotherapy, interpersonal focus, serial design, continuation and maintenance treatment, combined treatments, and follow-up assessments.

Adult↗

High-throughput discovery of germ-cell-specific genes.

As a specialized cell population that plays the unique role of transmitting genetic information to subsequent generations, germ cells have been intensively studied to unravel their unique physiology from the specification of primordial germ cells to the fateful reunion of gametes during fertilization. For their differential expression, germ-cell-specific genes are the keys to understanding these unique features. In the last decade, the emerging methodologies designed for large-scale and high-throughput analysis have created an ever-increasing amount of data. Among these methodologies, expressed sequence tag libraries, serial analysis of gene expression, and microarrays provide valuable expression data that can be further analyzed. Using the mouse as a model system, we describe a strategy starting from the quick identification of germ-cell-specific genes using public domain expression data to the functional characterization of the identified genes using targeted gene disruption. This strategy should accelerate the process to fill in the missing pieces of the germ cell physiology puzzle and the construction of genetic networks to help us to understand the etiology of infertility. Furthermore, these identified germ-cell-specific genes may lead to the development of new contraceptives targeted specifically to germ cells.

Animals↗

The journals crisis: redirecting the blame.

Publishers and librarians are the usual culprits blamed for the "journals crisis", typically defined as an ever-tightening spiral of increasing serial prices and decreasing number of subscribers. An alternative viewpoint is expressed in this article-the author community bears the brunt of the blame for this situation. The glut of published articles, the surplus of journals, and the growing publication rate per academic chemist drive the crisis. Therefore, any global publication paradigm change must originate from within the author community.

Journal Article↗

Effect of exercise on cardiovascular ageing.

Ageing of the cardiovascular system presents several costly public health problems, loss of quality of life, dependency, and other various health hazards. Large declines of 0-24% per decade in cardiovascular function have been cited in the literature but no long-term longitudinal studies have been reported. Serially measured cardiovascular function was performed on 12 normal men, aged 44-79 years, at 0, 10, 15, 20 and 25 years. Over the same time period, daily exercise training data were reported monthly including mode, frequency, intensity, and duration. Although seven men developed some form of pathological disease, the total group's cardiovascular function remained 60% greater than the average of ten investigations. The overall decline in cardiovascular function (Vo2 max) was 13%, or 5% per decade, 45.4 ml.min-1.kg-1 to 39.5 ml.min-1.kg-1. In summary, cardiovascular function was one-half, or 0.24 ml.min-1.kg-1.year-1 of the 0.45 ml.min-1.kg-1.year-1 reported to be the average decline for ageing cited in the literature.

Aged↗

Molecular phenotype of zebrafish ovarian follicle by serial analysis of gene expression and proteomic profiling, and comparison with the transcriptomes of other animals.

BACKGROUND: The ability of an oocyte to develop into a viable embryo depends on the accumulation of specific maternal information and molecules, such as RNAs and proteins. A serial analysis of gene expression (SAGE) was carried out in parallel with proteomic analysis on fully-grown ovarian follicles from zebrafish (Danio rerio). The data obtained were compared with ovary/follicle/egg molecular phenotypes of other animals, published or available in public sequence databases. RESULTS: Sequencing of 27,486 SAGE tags identified 11,399 different ones, including 3,329 tags with an occurrence superior to one. Fifty-eight genes were expressed at over 0.15% of the total population and represented 17.34% of the mRNA population identified. The three most expressed transcripts were a rhamnose-binding lectin, beta-actin 2, and a transcribed locus similar to the H2B histone family. Comparison with the large-scale expressed sequence tags sequencing approach revealed highly expressed transcripts that were not previously known to be expressed at high levels in fish ovaries, like the short-sized polarized metallothionein 2 transcript. A higher sensitivity for the detection of transcripts with a characterized maternal genetic contribution was also demonstrated compared to large-scale sequencing of cDNA libraries. Ferritin heavy polypeptide 1, heat shock protein 90-beta, lactate dehydrogenase B4, beta-actin isoforms, tubulin beta 2, ATP synthase subunit 9, together with 40 S ribosomal protein S27a, were common highly-expressed transcripts of vertebrate ovary/unfertilized egg. Comparison of transcriptome and proteome data revealed that transcript levels provide little predictive value with respect to the extent of protein abundance. All the proteins identified by proteomic analysis of fully-grown zebrafish follicles had at least one transcript counterpart, with two exceptions: eosinophil chemotactic cytokine and nothepsin. CONCLUSION: This study provides a complete sequence data set of maternal mRNA stored in zebrafish germ cells at the end of oogenesis. This catalogue contains highly-expressed transcripts that are part of a vertebrate ovarian expressed gene signature. Comparison of transcriptome and proteome data identified downregulated transcripts or proteins potentially incorporated in the oocyte by endocytosis. The molecular phenotype described provides groundwork for future experimental approaches aimed at identifying functionally important stored maternal transcripts and proteins involved in oogenesis and early stages of embryo development.

Animals↗

A randomized trial of a serialized self-help smoking cessation program for pregnant women in an HMO.

We report the results of a population-based randomized clinical trial that tested the effectiveness of a prenatal self-help smoking cessation program. The intervention consisted predominantly of printed materials received through the mail. The population (n = 242) consisted of a socioeconomically and ethnically diverse group of pregnant women enrolled in a large health maintenance organization (HMO) who reported they were smoking at the time of their first prenatal visit. Biochemical confirmation of continuous abstinence achieved prior to the 20th completed week of pregnancy and lasting through delivery revealed 22.2 per cent of the women in the eight-week serialized program quit versus 8.6 per cent of controls with usual care. The adjusted odds ratio was 2.80 (95 per cent CI = 1.17, 6.69). We conclude that a low-cost prenatal self-help intervention can significantly affect the public health problem of smoking during pregnancy and its associated risks for maternal and child health.

Adolescent↗

Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer.

Difficulties in the detection, diagnosis, and treatment of ovarian cancer result in an overall low survival rate of women with this disease. A better understanding of the pathways involved in ovarian tumorigenesis will likely provide new targets for early and effective intervention. Here, we have used serial analysis of gene expression (SAGE) to generate global gene expression profiles from various ovarian cell lines and tissues, including primary cancers, ovarian surface epithelia cells, and cystadenoma cells. The profiles were used to compare overall patterns of gene expression and to identify differentially expressed genes. We have sequenced a total of 385,000 tags, yielding >56,000 genes expressed in 10 different libraries derived from ovarian tissues. In general, ovarian cancer cell lines showed relatively high levels of similarity to libraries from other cancer cell lines, regardless of the tissue of origin (ovarian or colon), indicating that these lines had lost many of their tissue-specific expression patterns. In contrast, immortalized ovarian surface epithelia and ovarian cystadenoma cells showed much higher similarity to primary ovarian carcinomas than to primary colon carcinomas. Primary tissue specimens therefore appeared to be a better model for gene expression analyses. Using the expression profiles described above and stringent selection criteria, we have identified a number of genes highly differentially expressed between nontransformed ovarian epithelia and ovarian carcinomas. Some of the genes identified are already known to be overexpressed in ovarian cancer, but several represent novel candidates. Many of the genes up-regulated in ovarian cancer represent surface or secreted proteins such as claudin-3 and -4, HE4, mucin-1, epithelial cellular adhesion molecule, and mesothelin. Interestingly, both apolipoprotein E (ApoE) and ApoJ, two proteins involved in lipid homeostasis, are among the genes highly up-regulated in ovarian cancer. Selected serial analysis of gene expression results were further validated through immunohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in archival material. These experiments provided additional evidence of the relevance of our findings in vivo. The publicly available expression data reported here should stimulate and aid further research in the field of ovarian cancer.

Cell Transformation, Neoplastic↗

[A general roentgenographic procedure with high reliability and minimum radiation exposure].

Needs for exposure procedures in dental radiography with improved reliability and radiation hygiene, that can be applied with a minimum of time, have been documented. This publication presents a systematic approach to reliable dental radiography using beam guiding instruments which may meet such requirements. It can provide accurate radiographs in endodontic, periodontic and general practice and is adaptable to more time consuming special purpose radiography, including "serial identical" exposures and exposures of handicapped or anaesthetized patients.

Humans↗