The 80/20 Rule

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

The book has an extensive glossary, that explains the meaning and relevance of medical terms appearing throughout the chapters. The glossary can be read as a stand-along document. Here is an example of one term, "Pareto's Principle", excerpted from the glossary.

Pareto’s principle - Also known as the 80/20 rule, Pareto’s principle holds that a small number of items account for the vast majority of observations. For example, a small number of rich people account for the majority of wealth. Just two countries, India plus China, account for 37% of the world population. Within most countries, a small number of provinces or geographic areas contain the majority of the population of a country (e.g., east and west coastlines of the U.S.). A small number of books, compared with the total number of published books, account for the majority of book sales.

Likewise, a small number of diseases account for the bulk of human morbidity and mortality. For example, two common types of cancer, basal cell carcinoma of skin and squamous cell carcinoma of skin, account for about 1 million new cases of cancer each year in the U.S. This is approximately the sum total for all other types of cancer combined. We see a similar phenomenon when we count causes of death. About 2.6 million people die each year in the U.S. [98]. The top two causes of death account for 1,171,652 deaths (596,339 deaths from heart disease and 575,313 deaths from cancer [99]), or about 45% of all U.S. deaths. All of the remaining deaths are accounted for by more than 7000 conditions.

Sets of data that follow Pareto’s principle are often said to follow a Zipf distribution, or a power law distribution. These types of distributions are not tractable by standard statistical descriptors because they do not produce a symmetric bell-shaped curve. Simple measurements such as average and standard deviation have virtually no practical meaning when applied to Zipf distributions. Furthermore, the Gaussian distribution does not apply, and none of the statistical inferences built upon an assumption of a Gaussian distribution will hold on data sets that observe Pareto’s principle.

I urge you to read more about my book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: 80/20 rule, common disease, data analysis, glossary, orphan disease, orphan drugs, rare disease, statistics

Hamartoma Syndromes

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

The book has an extensive glossary, that explains the meaning and relevance of medical terms appearing throughout the chapters. The glossary can be read as a stand-along document. Here is an example of one term, "hamartoma", excerpted from the glossary.

Hamartoma - Hamartomas are benign tumors that occupy a peculiar zone lying between neoplasia (i.e., a clonal expansion of an abnormal cell) and hyperplasia (i.e., the localized overgrowth of a tissue). Some hamartomas are composed of tissues derived from several embryonic lineages (e.g., ectodermal tissues mixed with mesenchymal tissue). This is almost never the case in cancers, which are clonally derived neoplasms wherein every cell is derived from a single embryonic lineage. Tuberous sclerosis is an inherited hamartoma syndrome. The pathognomonic lesion in tuberous sclerosis is the brain tuber, from which the syndrome takes its name. Tubers of the brain consist of localized but poorly demarcated malformations of neuronal and glial cells. Like other hamartoma syndromes, the germline mutation in tuberous sclerosis produces benign hamartomas as well as carcinomas, indicating that hamartomas and cancers are biologically related. Hamartomas and cancers associated with tuberous sclerosis include cortical tubers of brain, retinal astrocytoma, cardiac rhabdomyoma, lymphangiomyomatosis (very rarely), facial angiofibroma, white ash leaf-shaped macules, subcutaneous nodules, cafe-au-lait spots, subungual fibromata, myocardial rhabdomyoma, multiple bilateral renal angiomyolipoma, ependymoma, renal carcinoma, subependymal giant cell astrocytoma [62].

Another genetic condition associated with hamartomas is Cowden syndrome, also known as multiple hamartoma syndrome. Cowden syndrome is associated with a loss of function mutation in PTEN, a tumor suppressor gene. Features that may be encountered are macrocephaly, intestinal hamartomatous polyps, benign hamartomatous skin tumors (multiple trichilemmomas, papillomatous papules, and acral keratoses), dysplastic gangliocytoma of the cerebellum, and a predisposition to cancers of the breast, thyroid and endometrium.

I urge you to read more about my book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, genetic disease, orphan disease, orphan drugs, types of cancer, tumor biology, rare cancers, hyperplasia, tissue overgrowth, carcinogenesis, glossary

Mosaic Variegated Aneuploidy Syndrome-1

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

The book has an extensive glossary, that explains the meaning and relevance of medical terms appearing throughout the chapters. The glossary can be read as a stand-along document. Here is an example of one term, "aneuploidy", excerpted from the glossary.

Aneuploidy - The presence of an abnormal number of chromosomes (for the species) in a cell. Most cancers contain aneuploid cells; an observation that holds true for virtually every poorly differentiated cancer. Aneuploidy is seen less often in benign tumors and well-differentiated tumors. Aneuploidy is also found in epithelial precancers and other growing lesions that can sometimes regress spontaneously (e.g., keratoacanthoma). These observations have prompted speculation that chromosomal instability and the acquisition of aneuploidy is an underlying cause of the cancer phenotype (i.e., tumor growth, invasion into surrounding tissues, and metastases).

Such causal associations invite skepticism, particularly in the realm of cancer biology, as virtually every cellular process and constituent of cancer cells has been shown to deviate from the norm. Nonetheless, there is good reason to suspect that aneuploidy is at least a factor in tumor development, as mutations that cause aneuploidy are associated with a heightened risk of cancer (e.g., Brca1 gene mutations [13] and mutations of mitotic checkpoint genes [14]). Cancer researchers have warned that aneuploidy, by itself, may not cause cancer [15]. Aneuploidy may need to be accompanied by other factors associated with genetic instability, such as the accumulation of DNA damage, specific cancer-causing mutations, epigenomic and cytogenetic abnormalities, and reduced cell death [15].

As usual, a rare disease helps to clarify the role of aneuploidy in carcinogenesis. Mosaic variegated aneuploidy syndrome-1 (MVA1) is caused by a homozygous or compound heterozygous mutation in the BUB1B gene, which encodes a key protein in the mitotic spindle check point. This disease is characterized by widespread aneuploidy in more than 25% of the cells of the body, and a heightened risk of developing childhood cancers (e.g., rhabdomyosarcoma, Wilms tumor, and leukemia). Because the underlying cause of mosaic variegated aneuploidy syndrome-1 is a gene that produces aneuploidy, and because such aneuploidy is an early event (i.e., congenital) that precedes the development of cancer and that is found in the developed cancer cells, then it is reasonable to infer that aneuploidy is closely associated with events that lead to cancer. See Mutator phenotype, Carcinogenesis, Cytogenetics, and Karyotype.

I urge you to read more about my book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, orphan disease, orphan drugs, types of cancer, cancer types, tumor types, tumor biology, rare cancers, common cancers, aneuploidy, cytogenetics, euploidy, carcinogenesis, glossary