: Health Hinge

Czerniecki’s extensive research,[6] supported in part by American Cancer Society and National Institute of Health grants, has already shown the safety and efficacy of delivering mature, peptide-pulsed dendritic cell vaccines in a variety of ways.[7] His research also has discovered alternate sentinel lymph node mapping possibilities [8] and opportunities to avoid axillary dissection.[9] He has discovered that immunohistochemical analysis improves the sensitivity of this procedure.[10] Currently the Rena Rowan Breast Center of the Abramson Cancer Center is seeking eligible patients[11] to continue clinical trials of Czerneicki’s alternative approach which focuses on the body’s immune system and uses the patient’s own cells to develop a vaccine that will attack the cancer cells to prevent the development of invasive breast cancer.[12]

This philanthropic organization was founded in 2008 by the Olympic figure skater, coach, inventor of the ice-skating term hydroblading, and choreographer Uschi Keszler who is herself a breast cancer survivor. The Pennies-in-Action fund recognizes, along with many experts, that vaccines rather than chemotherapy remain the most advantageous avenue for dealing with cancer.[3] It has consequently targeted as its initial project the breast cancer vaccine research of surgeon and researcher in endocrinology and oncology Brian Czerniecki, M.D., Ph.D. on the staff of the Abramson Cancer Center of the Hospital of the University of Pennsylvania. Czerniecki has had success in clinical trials [4] and a history of gaining patents on inventions that increase antigens against cancer.[5]

Uschi Keszler’s Pennies-in-Action Cancer Research Fund,[1] holding a pending 501(c)(3) non-profit foundation status, exists to support research for breast cancer curative programs, including preventative vaccines and other biological therapies [2] that do not damage the immune system.

Genetic information provides a unique type of knowledge about an individual and his/her family, fundamentally different than a typically laboratory test that provides a “snapshot” of an individual’s health status. The unique status of genetic information and inherited disease has a number of ramifications with regard to ethical, legal, and societal concerns.

There are a variety of career paths within the field of medical genetics, and naturally the training required for each area differs considerably. It should be noted that the information included in this section applies to the typical pathways in the United States and there may be differences in other countries. US Practitioners in clinical, counseling, or diagnostic subspecialties generally obtain board certification through the American Board of Medical Genetics.

Angiotensin receptor blockers in Marfan syndrome & Loeys-Dietz
Bone marrow transplantation
Gene therapy

In general, metabolic disorders arise from enzyme deficiencies that disrupt normal metabolic pathways. For instance, in the hypothetical example:

Compound “A” is metabolized to “B” by enzyme “X”, compound “B” is metabolized to “C” by enzyme “Y”, and compound “C” is metabolized to “D” by enzyme “Z”. If enzyme “Z” is missing, compound “D” will be missing, while compounds “A”, “B”, and “C” will build up. The pathogenesis of this particular condition could result from lack of compound “D”, if it is critical for some cellular function, or from toxicity due to excess “A”, “B”, and/or “C”. Treatment of the metabolic disorder could be achieved through dietary supplementation of compound “D” and dietary restriction of compounds “A”, “B”, and/or “C” or by treatment with a medication that promoted disposal of excess “A”, “B”, or “C”. Another approach that can be taken is enzyme replacement therapy, in which a patient is given an infusion of the missing enzyme.
Diet

Dietary restriction and supplementation are key measures taken in several well-known metabolic disorders, including galactosemia, phenylketonuria (PKU), maple syrup urine disease, organic acidurias and urea cycle disorders. Such restrictive diets can be difficult for the patient and family to maintain, and require close consultation with a nutritionist who has special experience in metabolic disorders. The composition of the diet will change depending on the caloric needs of the growing child and special attention is needed during a pregnancy if a woman is affected with one of these disorders.
Medication

Medical approaches include enhancement of residual enzyme activity (in cases where the enzyme is made but is not functioning properly), inhibition of other enzymes in the biochemical pathway to prevent buildup of a toxic compound, or diversion of a toxic compound to another form that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with homocystinuria to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of biotinidase, treatment with NTBC in Tyrosinemia to inhibit the production of succinylacetone which causes liver toxicity, and the use of sodium benzoate to decrease ammonia build-up in urea cycle disorders.
Enzyme replacement therapy

Certain lysosomal storage diseases are treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples include Gaucher disease, Fabry disease, Mucopolysaccharidoses and Glycogen storage disease type II. Such treatments are limited by the ability of the enzyme to reach the affected areas (the blood brain barrier prevents enzyme from reaching the brain, for example), and can sometimes be associated with allergic reactions. The long-term clinical effectiveness of enzyme replacement therapies vary widely among different disorders.

Each cell of the body contains the hereditary information (DNA) wrapped up in structures called chromosomes. Since genetic syndromes are typically the result of alterations of the chromosomes or genes, there is no treatment currently available that can correct the genetic alterations in every cell of the body. Therefore, there is currently no “cure” for genetic disorders. However, for many genetic syndromes there is treatment available to manage the symptoms. In some cases, particularly inborn errors of metabolism, the mechanism of disease is well understood and offers the potential for dietary and medical management to prevent or reduce the long-term complications. In other cases, infusion therapy is used to replace the missing enzyme. Current research is actively seeking to use gene therapy or other new medications to treat specific genetic disorders.

DNA sequencing is used to directly analyze the genomic DNA sequence of a particular gene. In general, only the parts of the gene that code for the expressed protein (exons) and small amounts of the flanking untranslated regions and introns are analyzed. Therefore, although these tests are highly specific and sensitive, they do not routinely identify all of the mutations that could cause disease.
DNA methylation analysis is used to diagnose certain genetic disorders that are caused by disruptions of epigenetic mechanisms such as genomic imprinting and uniparental disomy.
Southern blotting is an early technique basic on detection of fragments of DNA separated by size through gel electrophoresis and detected using radiolabeled probes. This test was routinely used to detect deletions or duplications in conditions such as Duchenne muscular dystrophy but is being replaced by high-resolution array comparative genomic hybridization techniques. Southern blotting is still useful in the diagnosis of disorders caused by trinucleotide repeats.
Short tandem repeats are unique markers that can be used to determine haplotypes and are used in identity testing for maternal cell contamination.

Biochemical studies are performed to screen for imbalances of metabolites in the bodily fluid, usually the blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Specific tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also employed under certain circumstances. In the US, the newborn screen incorporates biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients suspected to have a metabolic condition might undergo the following tests:
Quantitative amino acid analysis is typically performed using the ninhydrin reaction, followed by liquid chromatography to measure the amount of amino acid in the sample (either urine, plasma/serum, or CSF). Measurement of amino acids in plasma or serum is used in the evaluation of disorders of amino acid metabolism such as urea cycle disorders, maple syrup urine disease, and PKU. Measurement of amino acids in urine can be useful in the diagnosis of cystinuria or renal Fanconi syndrome as can be seen in cystinosis.
Urine organic acid analysis can be either performed using quantitative or qualitative methods, but in either case the test is used to detect the excretion of abnormal organic acids. These compounds are normally produced during bodily metabolism of amino acids and odd-chain fatty acids, but accumulate in patients with certain metabolic conditions.
The acylcarnitine combination profile detects compounds such as organic acids and fatty acids conjugated to carnitine. The test is used for detection of disorders involving fatty acid metabolism, including MCAD.
Pyruvate and lactate are byproducts of normal metabolism, particularly during anaerobic metabolism. These compounds normally accumulate during exercise or ischemia, but are also elevated in patients with disorders of pyruvate metabolism or mitochondrial disorders.
Ammonia is an end product of amino acid metabolism and is converted in the liver to urea through a series of enzymatic reactions termed the urea cycle. Elevated ammonia can therefore be detected in patients with urea cycle disorders, as well as other conditions involving liver failure.
Enzyme testing is performed for a wide range of metabolic disorders to confirm a diagnosis suspected based on screening tests.