Metabolic gene profile in early human fetal heart development.

The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol receptor and gamma-aminobutyric acid (GABA) receptor transcripts were detected, and have not been described previously in human fetal heart during this period. For the first time global gene expression of heart has been described in human samples to create a database of normal development to understand and compare with known abnormal fetal heart development.

Differential changes in gene expression in human brain during late first trimester and early second trimester of pregnancy.

OBJECTIVE: This study aimed to describe brain development during the first (B1) and second trimester (B3) in human fetuses. DESIGN: Ten brains from 10 to 18 weeks of gestational age (GA) were collected, and the RNA was used for transcriptome analysis (Affymetrix 1.0 ST microarray chip). Differences in brain development within 10 to 18 GA were investigated by dividing the sample into 10 to 12 (B1), 13 to 15(B2) and 16 to 18(B3) weeks. A fold change of 2 or above, with a false discovery rate of 5%, was used as cut-off to determine differential gene expression for individual genes. Quantitative real-time PCR was used to confirm differences. Tests for enrichment procedures (using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were then used to identify functional groups of mRNA. RESULTS: At 10 to 12 weeks, brains showed neuronal migration to be upregulated. From 10 to 18 weeks, brains showed genes coding for neuronal migration, differentiation and connectivity upregulated. ALDH1A1 and NPY genes, marker of spinal cord and striatum, were upregulated in B1 and B3 brains, respectively. Also, SLITRK6-HAS2 and CRYAB-PCDH18 genes for ear and eye sensory input were upregulated in B1. CONCLUSIONS: For the first time, brain global gene expression was described in human samples. Period B1 was dominated by genes coding for neuronal migration, differentiation, programmed cell death and sensory organs. B3 was dominated by neuronal proliferation, branching and myelination. Creating such a database will allow comparison with abnormals in future studies.

Silicone breast implants: lessons from a saga.

In the following eleven lessons learned from the silicone breast implant saga in the United States are listed. Some Lessons From The Saga Of Silicone Breast Implants In The U.S. 1. The intrinsic differences between science and the law mean that there will continue to be tension at the interface between the two. 2. Weak scientific evidence makes for weak scientific, clinical and legal judgments. 3. Health policy can influence the weighing of evidence as did the FDA ban on gel filled silicone breast implants in 1992. 4. As the probative value of scientific evidence decreases (that is, the quality and relevance of the evidence) the courts have increasing difficulty in evaluation. 5. Weak scientific evidence along with poor legal judgments can distort clinical understanding and result in harm to patients. 6. Widely publicized speculation and litigation can obscure less dramatic but frequent and serious complications. 7. Clinicans, toxicologists, industry and regulators should maintain surveillance of medical devices, in representative groups if not in all recipients of the devices. 8. The precise identity and composition of each medical device implanted into a person should be recorded both by the manufacturer and in the health care record. 9. The factual basis for informed consent should be vetted by a disinterested party. 10. Patients, clinicians and industry all have a strong interest in assuring the safety of medical devices through regulation. 11. The criteria and process for evaluating the admissibility of scientific evidence in legal proceedings have been improved but universal adoption of the improvements has not been accomplished and further changes may be necessary.

Health care reform continues: themes for academic medicine.

The challenge for U.S. academic medicine in this decade is to redesign itself to serve its classic functions--teaching, research, and special service to patients--while filling the needs of what is evolving into a comprehensive integrated system of health care. First, in the absence of federally legislated comprehensive health care reform, the health care community must develop a consensus on the purposes, scope, and content of health care to bring some reason and order to the short-term, market-driven incrementalism that governs today's health care. Specifically, the author proposes that the issues of health care be defined in a broad social context, that the gap between public health and medicine be lessened, and that perspectives of public health and health promotion and disease prevention be more effectively incorporated into medical education. Second, there is an urgent need for new approaches to funding and financial management of teaching, research, and patient care in academic health centers to counter the erosion of traditional sources of support. Third, to sustain generalist physician practices of high quality, a conceptual basis for generalism must be defined in affirmative functional terms, and the generalist's frame of reference and intellectual tools and processes must be formulated. Last, many forces are now acting to reduce the intellectual content of medical practice and teaching. Academic medicine--in teaching and in research--must nurture and promote the intellectual content and standards of all aspects of medicine to sustain the quality of clinical practice over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Contributions of aerospace medicine to clinical medicine.

The contributions of aerospace medicine to clinical medicine far exceed the aggregate of the clinical applications of individual technologies which originated in aerospace medicine, important though these be. Contributions of aerospace medicine to clinical medicine will be discussed in seven categories: The raising of issues, questions, and need for systems for protection or support for man before such issues and needs were recognized by clinicians to be important or feasible; Contributing to the manpower pool of able clinical investigators through recruitment and special training in research; Providing fundamental insights into specific biologic processes of clinical significance; The recruitment of disciplines not previously involved extensively in addressing biologic problems and the creation or strengthening of hybrid disciplines such as bionics and bioengineering; Pioneering emphasis on safety, prevention and environmental health now being incorporated into clinical medicine; The development of specific research technologies which have been used to address an array of clinical problems; Specific technologies of clinical significance to which aerospace medicine has contributed, including systems for air transport of patients, many components of modern systems for patient monitoring, components of circulatory and ventillatory support systems, hypoxia warning systems, prevention of toxic exposure and treatment of toxic injury, prevention and treatment of burns, restraint systems, artificial organs, the application of models to clinical practice, and the ordering and automating of information processing.

Antepartum diagnosis of fetal intracranial hemorrhage by ultrasound.

Presented is a patient with acute onset of preeclampsia and abruptio placenta at approximately 26 weeks' gestation. Ultrasonography demonstrated evidence of in utero fetal intracranial hemorrhage, which was confirmed at autopsy. The implication of this finding is discussed.