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Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients.

BACKGROUND: The aim of this study was to determine the visualization rate, identification rate, and clinical implications of biopsy of sentinel nodes in the internal mammary chain (IMC) in patients with breast cancer. METHODS: From January 1999 to December 2002, 691 sentinel node procedures were performed. Preoperative lymphoscintigraphy was performed after injection of (99m)Tc-labeled nanocolloid into the tumor (.2 mL; 115 MBq; 3.1 mCi). The sentinel node was surgically identified with the aid of patent blue dye and a gamma ray detection probe. RESULTS: The sentinel node in the IMC could be harvested in 130 (87%) of the 150 patients in whom it was visualized on the images and contained metastases in 22 (17%) of these 130 cases. In nine patients (7%), the IMC sentinel node was tumor positive, whereas the axilla was tumor-free. Stage migration was seen in all patients with a tumor-positive IMC sentinel node (17%). There was a change of management in 38 (29%) of the 130 patients: institution or omission of radiotherapy to the IMC, adjuvant systemic therapy, or omission of an axillary lymph node dissection. CONCLUSIONS: Pursuit of IMC sentinel nodes improves the staging of patients with breast cancer and enables treatment to be better adjusted to the needs of the individual patient.

Adult↗

Hunting for disease genes in multi-functional diseases.

Disease genes may be identified through functional, positional, and candidate gene approaches. Although extensive and often labor-intensive studies such as family linkage analysis, functional investigation of gene products and genome database searches are usually involved, thousands of human disease genes, especially for monogenic diseases with Mendelian transmission, have been identified. However, in diseases caused by more than one gene, or by a combination of genetic and environmental factors, identification of the genes is even more difficult. Common examples include atherosclerosis, cancer, Alzheimer's disease, asthma, diabetes, glaucoma, and age-related macular degeneration. There have been conflicting reports on the roles of associated genes. Even with population-based case-control studies and new statistical methods such as the sib-ship disequilibrium test and the discordant alleles test, there is no agreement on whether alpha2-macroglobulin (A2M) is a gene for Alzheimer's disease. Another example is the inconsistent association between age-related macular degeneration and ATP-binding cassette transporter (ABCR). Ethnic variation causes further complications. In our investigation of LDL-receptor variants in familial hypercholesterolemia, and the trabecular meshwork inducible glucocorticoid response protein, or myocillin (TIGR-MYOC) mutation pattern in primary open angle glaucoma, we did find dissimilar results in Chinese compared to Caucasians. New information from the Human Genome Project and advancements in technologies will aid the search for and confirm identification of disease genes despite such challenges.

ATP-Binding Cassette Transporters↗

The hunt for new genes and polymorphisms that can control the response to drugs.

There has been a great increase in the knowledge of understanding the genetic basis for individual variation in response to drugs. The study of variation in gene structure (polymorphism) can now predict the likely metabolic behavior in an individual for a number of drugs. This review documents the different strategies that can be used to find new genes and polymorphisms within these genes. Candidate genes can be used in case-control studies or studies where the parents of the person having an adverse effect from the drug are used as controls. New genes are being discovered in the drug development process and the technological development in molecular biology is expected to greatly enhance knowledge of the genes that regulate drug metabolism.

Animals↗

Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT).

OBJECTIVE: To examine the prevalence of thyroid disease and dysfunction including thyroid autoimmunity in Norway. MATERIALS AND METHODS: All inhabitants 20 years and older (94009) in Nord-Trondelag were invited to participate in a health survey with a questionnaire and blood samples. RESULTS: The prevalence of former diagnosed hyperthyroidism was 2.5% in females and 0.6% in males, hypothyroidism 4.8% and 0.9%, and goitre 2.9% and 0.4% respectively. In both sexes the prevalence increased with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.80 and 0.49-5.70 for females and 1. 50 and 0.56-4.60 for males. The TSH values increased with age. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb) (>200U/ml), the 97.5 percentiles dropped to 3.60 mU/l and 3. 40 mU/l respectively. The prevalence of pathological TSH values in females and males were TSH >/=10mU/l 0.90% and 0.37%; TSH 4.1-9. 9mU/l 5.1% and 3.7%; and TSH</=0.05mU/l 0.45% and 0.20% respectively. The prevalence of positive TPOAb (>200U/ml) was 13.9% in females and 2.8% in males. In females the lowest percentage (7.9%) of positive TPOAb was seen with TSH 0.2-1.9mU/l and increased both with lower and higher levels of TSH. The percentage of males with positive TPOAb was lower than in females in all TSH groups except for those with TSH>10mU/l (85% TPOAb positive). CONCLUSIONS: In spite of a high prevalence of recognised thyroid disease in the population a considerable number of inhabitants have undiagnosed thyroid dysfunction and also positive TPOAb.

Adult↗

Hunting for immune response regulatory genes: vaccination studies in infant twins.

The contribution of twin studies towards unraveling the complex mechanisms of multifactorial diseases is increasingly recognized. Recent twin studies using infant vaccination as a model for infectious diseases have confirmed the importance of host genetic factors as major regulators of the immune response. A combination of twin-based family studies and population-based association studies should lead to the identification of the specific genes involved. These genes and their products have the potential to be developed as targets for novel therapeutic and prophylactic agents against infectious diseases.

BCG Vaccine↗

Hunting for differentially expressed genes.

Differentially expressed genes are usually identified by comparing steady-state mRNA concentrations. Several methods have been used for this purpose, including differential hybridization, cDNA subtraction, differential display and, more recently, DNA chips. Subtractive hybridization has significantly improved after the polymerase chain reaction was incorporated into the original method and many new protocols have been established. Recently, the availability of the wellknown coding sequences for some organisms has greatly facilitated gene expression analysis using high-density microarrays. Here, we describe some of these modifications and discuss the benefits and drawbacks of the various methods corresponding to the main advances in this field.

Gene Expression↗

Republicans accused of witch-hunt against climate-change scientists.

Some of America's leading scientists have accused Republican politicians of intimidating climate-change experts by placing them under unprecedented scrutiny. A far-reaching inquiry into the careers of three of the U.S.'s most senior climate specialists has been launched by Joe Barton, chairman of the House of Representatives committee on energy and commerce. He has demanded details of all their sources of funding, methods, and everything they have ever published. The inquiry has sent shockwaves through the U.S. scientific establishment, already under pressure from the Bush administration, which links funding to policy objectives.

Climate↗