August 25, 2011 | 1:38 am

Crohn’s Disease:  An interview with Ron Bahar, MD

Posted by Norman Lavin, M.D, PhD., UCLA Medical School

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Ron Bahar, MD is a board-certified pediatric gastroenterologist and Assistant Clinical Professor of Pediatrics at The UCLA David Geffen School of Medicine.  He is a native of Lincoln, Nebraska.  He completed his undergraduate studies at the University of Wisconsin-Madison, and medical school at the University of Nebraska College of Medicine.  He then moved to Los Angeles to complete pediatric residency and pediatric gastroenterology fellowship training at UCLA.  He was an attending physician at UCLA for three years before opening a private practice in Encino in 2000.  His areas of interest include inflammatory bowel disease and irritable bowel syndrome in children.

Dr. Lavin:  What is Crohn’s Disease?

Ron Bahar: Crohn’s disease is a chronic inflammatory bowel disorder which can involve the entirety of the gut, from lips to anus.  In addition, other organs, including skin in the form of erythema nodusom (red nodules), joints in the form of arthritis, and kidney disease in the form of stones, are commonly concurrently affected. 

Dr. L.: How do patients with Crohn’s disease present, and how is the diagnosis confirmed?

R.B.: Crohn’s disease most commonly presents in patients in their second and third decades of life, but also occurs in children.  Symptoms typically include abdominal pain, diarrhea, rectal bleeding, poor appetite, weight loss, and oral ulcers.  With regard specifically to children, individuals frequently display poor linear growth (short stature) and poor weight gain, along with failure of the development of secondary sexual characteristics (delayed puberty). 

Patients are usually referred from their generalist (pediatrician or internist) to a pediatric or adult gastroenterologist.  Based on history and physical examination, along with screening blood and stool studies, which commonly show evidence of anemia, inflammation, low blood protein, and white blood cells in the stool, the diagnosis is often strongly suspected.  However, Crohn’s disease cannot be confirmed without diagnostic upper gastrointestinal endoscopy, colonoscopy and biopsy.  If the diagnosis is still equivocal, or if the extent of the disease in the small intestine has not adequately been quantified, wireless capsule endoscopy (pill camera) can then be employed. 

Dr. L.:  Discuss the incidence, prevalence, genetics, and immunology of Crohn’s disease:

R.B.: The incidence (the number of new cases in the population) is approximately 5 per 100,000 in the United States.  The prevalence (the total number of patients in the population) has been estimated at between 26 and nearly 200 per 100,000 in this population.  The incidence of Crohn’s disease amongst Ashkenazi Jews is 2-8 times that of the general population, and also affects Sephardic Jews more than the general population, but not as frequently as the Ashkenazi families.  The relative risk of Crohn’s in siblings of an individual with the disease is 17 to 35 times that of this same group.  It is slightly more common in males than in females.

In 2001, the mutations in the gene NOD2/CARD15 (which encodes for a protein seen in white blood cells and plays a role in the regulation of the immune response) was determined to be associated with a significant increased risk of severe, penetrating disease in patients with Crohn’s disease.  Various additional gene mutations have since been implicated as well. 

The body’s antibody reactivity to microbes, such as brewer’s yeast and E. coli bacteria, has also been associated with an increased risk for more serious manifestations of Crohn’s disease.  Through this research, physicians can now specifically target therapy based on individual genetic and immunological profiles.

Dr. L.:  Discuss the treatment of Crohn’s disease:

R.B.: Crohn’s disease is not curable.  However, advancements in medical therapy over the last several decades have made it more “livable” than ever, and patients generally lead entirely “normal” lives.  Medications used in the treatment of Crohn’s disease in both FDA-approved and off-label fashions are divided into broad categories.  They include 5-ASAs (sulfasalazine derivatives), anti-inflammatory steroids, immune-system modulators such as 6-mercaptopurine and methotrexate, and biologic agents (antibodies) such as Remicade and Humira.  In addition, liquid dietary formula typically delivered via tube feeding as a sole source of nutrition is now used as an alternative to traditional medical therapy in selected patients. 

For patients with intractable Crohn’s disease, surgery is an option.  The most common of these procedures is removal of the end of the small intestine called the terminal ileum. 

To find a pediatric gastroenterologist who is a member of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, please refer to the following link:
http://www.naspghan.org/aspModules/PublicLocateDoctor/PublicLocateDoctor.asp

For support group information for patients with Crohn’s disease, visit the Crohn’s and Colitis Foundation of America’s official website at:
http://www.ccfa.org/

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August 11, 2011 | 12:51 pm

Jews, industrial pipe cleaners, and osteoporosis

Posted by Norman Lavin, M.D, PhD., UCLA Medical School

Chances are that you or a family member are taking a medication to reverse or improve Osteoporosis – a condition of poor bone density. The most common class of treatment is the Biphosphonates for which Fosamax is a prime example.  The purpose of this article is not to discuss the clinical uses of this drug, but rather to review the history of Biphosphonate development by several Jewish scientists and physicians.  I will specifically focus on “The Stumble” effect – that moment when a basic observation is recognized for its greater relevance, as with Alexander Fleming’s work with Penicillium molds or the story of Isaac Newton and the apple.

“Stumble” is not meant to imply a lack of awareness but, to the contrary, the sudden insight of a connection between apparently unrelated concepts.  In this context, the story of the clinical uses of Biphosphonates may be more akin to a serendipitous revelation – the enlightening discovery of something important that was not deliberately sought.

In 1897 in Germany, two Jews – Baeyer and Hofmann - first synthesized Biphosphonates for medical use, but for 63 years this compound sat idle on chemists’ shelves receiving scant attention.  In the 1930’s, phosphates were recognized as crystal inhibiting substances.

A few years later, L. Rothstein accidently added phosphate to an irrigation system which prevented blockage by inhibiting crystal formation which led to derivatives for scale prevention.  In 1960, it was used for water softening and prevention of deposits in plumbing.  Procter and Gamble then bought it for detergent research.

Three more Jews working in Berne, Switzerland demonstrated that soft tissue calcifications could be prevented by the intravenous injection of polyphosphates. The major clinical break through, however, occurred in 1968 when a child with severe calcification of his respiratory muscles leading to inability to breathe was treated with Etidronate (a bisphosphonate) and surprisingly recovered. This led to the use of this class of drugs in the treatment of metabolic bone disease.  The child survived and grew into adulthood – testimony to a fortuitous juxtaposition of basic science, clinical skill, and recognition of potential benefit – in other word, an informed “Stumble”.

Is what has been said so far a contradiction?  Biphosphonates inhibit calcification and inhibit bone resorption, therefore, how can they increase bone density? Paradoxically, these medications have two distinct biologic effects.  At high doses, there is inhibition of calcification, whereas at lower doses, there is inhibition of bone resorption.  This latter effect proves beneficial in osteoporosis which led to a new understanding of bone formation:  bone requires reshaping for optimal mechanical function.  This process is initiated by recruiting ‘cleaning’ cells (osteoclasts) which leads to bone resorption followed by ‘building’ cells (osteoblasts) that lead to new bone synthesis.  Biphosphonates exert their major biologic action on bone resorption through inhibition of osteoclasts.

The history of the Biphosphonates – from detergents to pipe cleaners to pharmaceutical agents – demonstrates with remarkable clarity that the application of these associations requires perseverance and sound scientific judgment.  At the same time, we are witness to Jewish researchers and scientists and physicians who unknown to each other are now inextricably linked in helping prevent fractures, deformities and in some cases- death.

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