Translational Medicine and the NCATS

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On 23 December, President Obama signed the bill creating (NCATS) the National Center for Advancing Translational Sciences. NCATS, a $576 million branch of (NIH) the National Institution of Health, opened its doors 4 January 2012 with 230 employees.

The mission of the National Center for Advancing Translational Sciences is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions
Congress created NCATS from other programs, most notably the Clinical and Translational Awards program (CTSA) while dissolving (NCRR) the National Center for Research Resources. CTSA funds basic research in 60 academic medical centers and will initially receive 80% of the NCATS budget. NCATS assembles: the Cures Acceleration Network, the National Human Genome Research Institute, the Rapid Access to Interventional Development, the Office of Rare Diseases Research and the NIH-FDA Regulatory Science Initiative under one roof -- from the laboratory to the clinic.
Congress was careful to stress diagnostic advancements with a lessor emphasis on bringing treatments to fruition, and this is a good thing. Translational medicine promises, more than anything, a better understanding of disease through the genome, proteinomics and diagnostics in particular.

More expensive treatments do not trump more accurate diagnosis. Fifteen percent of our diagnoses are wrong as it is and as many as sixty percent of autopsies find missed or wrong antemortem clinical information.  CAT scans do not replace autopsies, but the later are out of style. Translational medicine if well done, might improve the science of medicine as it is practiced as well as the understanding of diseaseand the discipline of patient care.

http://ncats.nih.gov/
    

Political Idiocy

Share | The current challenge for the medical profession seems no different than what Hippocrates faced 4,540 years ago when he proposed the scientific method for health care as opposed to the mythology, rituals and disingenuous quacks of the day.

When Rick Santorum suggests that we should stop funding anti-natal care because it might lead to abortion, one wonders if there can be any political solution to our current medical care problems much less complete disaster. We already score a third world ranking by infant mortality, perinatal mortality or longevity. Can any polarized political mythology possibly make it better? 

Plague, Yersinia pestis

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A draft genome of Yersinia pestis from victims of the Black Death maps the genome from the plague of 1347-8. Researchers obtained DNA from the teeth of plague victims buried in a mass grave in East Smithfield, (originally the Churchyard of the Holly Trinity) near the Tower of London. [1]

Alexander Yersin linked Y. pestis to bubonic plague in 1894. However, controversy and doubt exist over the identity of the plague organism in part because today’s plague does not match the virulence of the Black Death that ravaged Europe in the 1300s. The sequencing by an improved technique (molecular capture assay) apparently establishes that the organism of the Black Death is the same as today’s plague with minor differences.

The bubonic plague existed in Asia with appearances in the Middle East and the Justinian plague in Rome and Constantinople in 541-542. Hippocrates describes a plague in Athens in 430-426 BC. Sanskrit tablets describe plague in Asia as early as 600 BC. Jewish physicians even associated plague with rats in the Tara also about 600 BC. Neither ancient plague, nor modern plague, 19^th century to the present time manifested the virulence and devastation of the Black Death of 1347.

The diversity of today’s plague in China suggests that the Far East may have been the reservoir with appearances in Europe carried down the Silk Road and through the Mediterranean by rats aboard ship. The configuration of large Phoenician trading ships may have further enabled the spread[2]

Doubters question whether the plague prior to 1347 was even the same organism. One researcher suggests that the ancient plague in Athens was Salmonella.[3] A look to the history of clinical medicine could end the controversy at least from a practical standpoint. The clinical acumen of Hippocrates in 450 BC was sufficient to distinguish Typhoid from the plague as well as small pox, malaria and TB.[4] There may be historical confusion and laboratory doubt but the clinical picture of plague was and is so distinctive that physicians of that day should not have confused plague with other infections.

The issue of virulence in the case of the Black Death seems explainable by the minor differences in the genome then and now. It would be interesting to see which changes correlated with the change in virulence. With its rapid spread, Y. pestis had an ideal environment in which to evolve taking advantage of weaknesses in the host population. With that evolution, came increased virulence, which shortened the duration between onset and death. The shorter time of infectiousness inhibited the further spread of the epidemic. Thus, the epidemic faded away. Furthermore, the population at risk diminishes as those most susceptible to the infection die off leaving those with minor expositors and resulting mobilized immune systems -- and those with genetic resistance to the disease in the first place -- in greater numbers relative to the further spread of the disease.

One might further speculate that faced with a diminished population, it was to the organism's advantage to devolve into a less virulent form in order to give greater expositor to others and thus a greater chance of continuing its presence and preserving its DNA. I would suppose that process of devolving to be the mechanism of dormancy in China or elsewhere in East Asia.

I do not think that it would have been essential that Y. pestis devolve along the exact genetic lines that it used in achieving greater virulence. The change in strategy might explain the dichotomy in the sequencing of today’s Y. pestis DNA with that of ancient DNA. [5]

My epidemiology professor speculated that the Black Death Y. pestis achieved a level of virulence in which it spread pneumatically, thus the name pneumonic plague. One might further imagine that with a pneumonic form, the cyanosis would turn the victim black in death.

If indeed the above considerations proves relevant, it would not be surprising to find today's Y. pestis devolved to a less virulent form than the Black Death which so devastated Europe.


http://www.nature.com/nature/journal/v478/n7370/full/478465a.html

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[1] Kirstin Bos et al, Nature,478, 27Oct 2011, p 506

[2] conjecture

[3] Edward C. Holmes, Nature, 478, p465

[4] Hippocrates’ medical text

[5] Further conjecture, but clinically objective

Cloud Computing for Medical Record

http://blogs.ft.com/fttechhub/#axzz1dch1Vyjh                        

How will cloud computing accommodate confidentiality and permissions to use the data for data mining?
Assuming it can, the thing most needed is a linked database containing a complete and continuously updated list of every disease and syndrome known to man. Thus any provisional diagnosis or problem could in real time list every related entity (differential diagnosis) meeting the same of similar basic criteria. The inaccuracy of initial diagnosis remains an ongoing problem in US medicine, 15-17% missed or wrong diagnosis by current studies. A statistically derived differential diagnosis would go a long way towards inducing the clinician to look for possible error or deeper consideration. |

Extended Care

Share | For the geriatric generation a nursing home becomes a self fulfilling prophecy. The level of inactivity results in rapid loss of muscle mass, and CNS function. If the patients is not vegetative to start with, they soon will be. There is a clear connection between the physical demand and intellectual engagement of independent living/survival and CNS capacity. The same can be said for a care taker wherein the patient becomes dependent and bedridden.

I remember a family concerned over the old man burning himself up in his home. He had started two fires by accident, extinguishing both without help. The family was worried and felt guilt. They insisted on a nursing home. They placed him in one and then another facility. He hated them both. They sold his house. The old man was vegetative within the year. The loss of familiar surroundings and the demands of daily living amounted to an insurmountable loss for this old man. He was not alone.

Far too many seniors get put away at enormous cost -- and abandonment. This phenomena sadly occurs in America far more than in any other culture. Furthermore, the insurance industry enshrines the practice with advertising and nursing home coverage. Medicare furthers the concept as does the option of medicaid. The corruption of medicaid in this matter is a story in itself.

In other cultures the old man or woman is honored with respect engagement and ongoing responsibilities, far beyond the basic needs of living. The grand parent or great grand parent remains in the family as a stabilizing influence, baby sitter, house sitter, dog sitter, gofer, watchdog wood cutter, gardner and venerated source of wisdom. These demands preclude atrophy of both brain and body. There is no wonder why the life expectancy in the US is so much lower than in much of the rest of the world. According to a CIA study in 2010 America comes in 37th. We are number one in cost however.

FGM Female Genital Mutilation

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I am a physician outraged by the continuing genital mutilation of children in the US. Children born in the US are citizens of the US whether their parents are or not. Those children like it or not are protected by our laws and our customs not those of the immigrant. If the immigrant family obtains US citizenship, then that family has pledged allegiance to our flag and our laws. If citizenship is not the case, then such an illegal act of child abuse/assault justifies and demands immediate deportation.

I encountered only one of these cases of genital mutilation in my practice and that was enough. An adolescent Egyptian girl with dysuria had a large distended blader. I could not examine her without her aunt in the room. What we saw was unimaginable. Fortunately, the aunt was supportive. The patient had multiple urethroplasties with a fair outcome.  

We have a heavy burden of African and Middle East immigrants, most of who came here to escape violence in their own country. Committing more violence while here, is unacceptable. Some immigrants seek citizenship others not. In either case, justice prevails. The problem is the secretive nature of the act and the immigrants’ commitment to their own cultural tradition.

Eventually a physician will examine these children. The clear duty is to the child, not the family. The law demands that the physician report the crime to the police and child welfare.

 
Excuses given:
·         Custom and tradition: Communities that practice FGM maintain their customs and preserve their cultural identity by continuing the practice.
·         Women’s sexuality: In some societies, FGM espiers to control womens sexuality by reducing their sexual fulfillment.
·         Religion: While religious duty is commonly cited as a justification for the practice of FGM, it is important to note that FGM is a cultural, not religious, practice. In fact, while Jews, Christians, Muslims, and other indigenous religions in Africa, practice FGM, none of these religions requires it.

There is no room for dancing around some concept of other cultures or political correctness. The life altering and life threatening complications for these girls who have yet not a voice in the matter are far too great.

 At the request of HHS, the Centers for Disease Control and Prevention (CDC) undertook a study to determine the prevalence of FGM in the United States. Using data from the 1990 U.S. Census, along with country-specific prevalence data on FGM, the CDC estimated that in 1990, there were approximately 168,000 girls and women living in the United States with or at risk for FGM. This estimate has to be a gross under-estimate given that every female infant born to some of these communities is at risk. The United Kingdom estimated 200,000 in their country alone.

In my view, immigration has gotten too far ahead of cultural evolution.

    

Microscope

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ZEISS

I cannot imagine what it is  like to practice medicine without a microscope. Boy does that date me. Our clinic ran a lab, that is before small clinical labs were virtually eliminated by regulation. From my experience with hospital labs, it is a good idea to look over your urine, gram stains and blood smears. OK, things are more efficient now. You don't have time to stick your nose in the lab. The computer-screen images everything you need including x-rays. Sure, if you are in the Mayo Clinic. What about rural health. Wherever you go for an outdoor lifestyle there won't be that kind of support.

Enter super-microscopy, a field not yet adapted for small office use but what potential. With a small library of fluorescent dyes, one could diagnose a wide array of infectious and parasitic diseases. Who knows, with weather change, we could be looking for malaria.  Some fluoroscopy techniques yield super-microscopy imaging with traditional light microscopes and filters. This is not a costly thing.

Traditional light microscopes with wave lengths of between 350 and 750 nm become blurry right at the cell wall or edge of microbes, 200 nm. With fluorescent dyes that respond to a much narrower range of wavelength the image sharpens up to a resolution around 20 nm. That tenfold improvement in resolution is a real big deal for clinical use.

Commercial interests will work away from that goal of clinical use, however, because large scale clinic use of fluro-microscopy would threaten the high profit margins of hospital and commercial laboratories' revenue stream.

I wouldn't hang my shingle without one.