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Cocaine vaccine early trial promising in treating addiction

Dipali Pathak
713-798-4710
pathak@bcm.edu

HOUSTON — (Oct. 5, 2009) — A cocaine vaccine that recruits the immune system to help block the drug’s euphoric effects proved effective in 38 percent of subjects who received the vaccine, said a Baylor College of Medicine researcher who led the study.

Q&A with Dr. Kosten

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Text-only Q&A

A consortium of researchers began the work when principal investigator Dr. Thomas R. Kosten, a professor at BCM, was on faculty at Yale University School of Medicine. Kosten and his team evaluated the safety and effectiveness of a novel cocaine vaccine that has been more than 15 years in development. The report appears in the current issue of Archives of General Psychiatry.

Plans to improve cocaine vaccine

“The concept works,” said Kosten, “There are lots of ways to engineer it after that to make it work better.”

He plans to continue work to improve the vaccine and find better ways to bolster the immune system against the effects of cocaine.

Kosten holds the Jay H. Waggoner Endowed Chair in the Menninger Department of Psychiatry and Behavioral Sciences at BCM. He is also the research director of the Veterans Affairs National Substance Use Disorders Quality Enhancement Research Initiative based at the Michael E. DeBakey Veterans Affairs Medical Center in Houston.

This study took place in one center, the Veterans Affairs Connecticut Healthcare System. Plans for a study of the vaccine in many sites are now under way.

Promising step

“The results of this study represent a promising step toward an effective medical treatment for cocaine addiction,” said Dr. Nora Volkow, director of the National Institute on Drug Abuse. “Provided that larger follow-up studies confirm its safety and efficacy, this vaccine would offer a valuable new approach to treating cocaine addiction, for which no FDA-approved medication is currently available.”

Kosten is quick to note that the vaccine is not a panacea, but the result shows that a vaccine can work in addictive disease, he said.

“The vaccine provokes the body to make antibodies. These antibodies bind to the cocaine, preventing it from leaving the bloodstream,” said Kosten.

The cocaine can be excreted in the liver or kidneys. An enzyme in the blood, cholinesterase, breaks down the cocaine. The fact that this enzyme continually breaks the drug down makes cocaine a better target for vaccines than other addictive drugs.

Effectiveness depends on level of antibody

In the study, 94 subjects who were on methadone were randomized to receive either the vaccine or an inactive medicine, a placebo. Neither they nor the physicians knew who received the vaccine until the study was over. Most subjects smoked crack cocaine. Over 12 weeks, the subject received five injections of either the vaccine or the placebo.

The vaccine’s effect depended on the level of antibody achieved. Those who reach high levels of antibodies are more likely to be able to stay cocaine-free.

“That’s the biggest problem with this vaccine. It is first generation and it does not create antibodies in everybody,” said Kosten. “Twenty-five percent of the people who get the vaccine do not make much antibody response.”

Relapse prevention medication

The vaccine can act as a preventive to relapse for those who want to stop taking the drug, Kosten said. It does not completely prevent cocaine cravings, but when the effect of the drug is blocked by the vaccine, people’s cravings will diminish.

“This is a relapse prevention medication. If you take cocaine, you won’t feel anything,” he said.

Others who took part in this research include Drs. Bridget A. Martell and James Poling and registered nurse Ellen Mitchell of Yale University School of Medicine and the Veterans Affairs Connecticut Hospital; and Drs. Frank M. Orson, Roger D. Rossen and Tracie Gardner of Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center in Houston.

Funding for this study came from the National Institute of Drug Abuse, the Veterans Affairs Mental Illness Research, Education and Clinic Center in New England, the Veterans Affairs Office of Research and Development/Cooperative Studies Program Career Development Award. Celtic Pharmaceuticals provided vaccine and paid travel fees for consultative services as well as providing a small amount of administrative funds for design and conduct of the study.

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Do All Good Doctors Shave the Head for Hair Transplant Surgery?

This hair loss question was answered by Dr. Glenn Charles of Florida who is a member of the Coalition of Independent Hair Restoration Physicians.  His professional answer is below.

Do all the good doctors require you shave your head before hair transplant surgery?

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The question is what is more important? Making the surgery easy for the doctor and staff or keeping the patient happy even though the surgery may take a little longer. When a hair transplant megasession of densely packed grafts are placed into an area that has existing hair, there is often the development of postoperative shock loss and significant thinning hair. This can be very upsetting to the patient. Some physicians may choose to require shaving prior to surgery to avoid the potential patient complaints. Interestingly enough I have heard that some doctors actually charge more if the patient does not shave.

Dr. Glenn Charles, D.O.

Bill Seemiller – aka Falceros
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Merkel cell originates from skin not neural crest

HOUSTON -- (October 2, 2009) -- Finding a treatment for a deadly type of skin cancer could be closer now that Merkel cells are found to originate from the skin, say researchers from Baylor College of Medicine in Houston and Case Western Reserve University School of Medicine in Cleveland, in a report that appears in the journal Developmental Biology.

diagram of a touch dome

In hairy skin, Merkel cell-neurite complexes cluster together and form touch domes. As shown in schematic, a sensory neuron (purple) contacts a cluster of mouse Merkel cells (green) in the skin at the epidermal-dermal interface.

"Our previous study showed direct evidence that Merkel cells are essential for detecting light touch," said Dr. Ellen Lumpkin, assistant professor of neuroscience, molecular physiology and biophysics and molecular and human genetics at BCM. "Our latest finding shows us more characteristics of these cells that will have implications in not only neuroscience research, but also dermatology since Merkel cells give rise to Merkel cell carcinoma."

Knowledge of origin helpful

Since the cell's first description in 1875, researchers have speculated whether they derived from skin cells or neural crest cells. Neural crest cells form, among other structures, most of the peripheral nervous system.

"Merkel cells have characteristics that make them more akin to neural crest cells, such as appearance and proteins they express," said Dr. Stephen Maricich, assistant professor of pediatrics, neurosciences and otolaryngology at CWRU SOM. "Not knowing exactly how they developed made treating Merkel cell carcinoma and other skin problems difficult." Merkel cells may be involved in other skin conditions such as psoriasis, added Maricich.

Knocking out Atho1

touch dome stained with FM1-43

Mice were injected with FM1-43, a fluorescent dye which labels sensory cells and neurons, 24 hr before imaging the touch domes. In wild-type mice (A), both the Merkel cells (triangle arrow heads) and the sensory nerve fiber (arrows) are visible. In the mice where Atoh1 has been deleted (B), no cells resembling Merkel cells are seen, confirming these mice lack Merkel cells. The nerve fiber is present and hyper-innervates the vacant touch dome. These data support epidermal origin of Merkel cells.

Using genetically-engineered mouse lines, researchers were able to delete Atoh 1, a gene essential to the formation of Merkel cells. When this was done in the neural crest, Merkel cells still developed. However, when this same process was completed in the skin, Merkel cells did not develop.

"Knocking out Atoh 1 in the neural crest line caused other problems despite Merkel cells being present. However, when Atoh 1 was knocked out in skin cells, only Merkel cells were missing with no other issues," said Maricich, who is lead author on the study. "This showed us that we had specifically targeted the Merkel cells and that Atoh 1 in skin cells was necessary to their development."

Fate mapping

touch dome stained with Merkel-cell specific markers

Immunostaining using Merkel-cell specific markers confirms Merkel cell loss in Atoh1 conditional knockout mice. As seen in the top panel, wild-type touch domes contain Merkel cells (Keratin8, green) and sensory nerve fibers (Neurofilament-200, red). In the bottom panel, Atoh1 conditional knockout touch domes have no Keratin-8 staining, confirming Merkel cell absence. However, as seen in the FM images, the nerve (red) hyper-innervates the vacant touch dome.

Researchers also fate mapped the cells, which supported their initial findings. Fate mapping is a technique used to trace the developmental fate of an embryo, showing which tissues the cells in each region will give rise to.

"The techniques used in this study will help neuroscientists to further explore the function of Merkel cells, including the behavioral consequences when only Merkel cells have been deleted," said Lumpkin, a study co-author.

Another aspect of future research, said Lumpkin, is understanding how these touch receptors affect the development of the brain.

Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Other researchers who contributed to this study include Dr. George R. Miesegaes, department of molecular and human genetics at BCM, now with the U.S. Food and Drug Administration, Center for Drug Evaluation and Research; and Kristin M. Morrison, department of pediatrics, Case Western Reserve University.

For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab or www.bcm.edu/news.

Images courtesy Aislyn Nelson and Dr. Ellen Lumpkin.

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New Surgical Instrument Revolutionizes FUE (Follicular Unit Extraction)

Hair Transplant Pysician Dr Alan FellerCoalition member Dr. Alan Feller recently released a new and revolutionary surgical tool designed to make the follicular unit extraction (FUE) procedure easier and more effective. Since FUE places forces on the hair follicles during extraction that could potentially damage the grafts, the development of this tool was designed to reduce these forces and create more viable and better quality grafts during hair transplant surgery.

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Noble social amoeba maintain diversity

HOUSTON -- (September 30, 2009) -- In the seemingly simple world of the social amoeba, some cheat, giving advantage to their genetic kin. Why, then, do they not take over the population?

One possibility, said collaborating researchers from Baylor College of Medicine and Rice University, are mutations that confer the ability to resist cheaters. They describe this population in a report that goes online today in the journal Nature.

"These resistant strains are 'noble' in that they do not take advantage of the other strains," said Anupama Khare, a graduate student in the laboratory of Dr. Gad Shaulsky at BCM and the paper's first author. "In fact, they even reduce the cheater's ability to cheat such strains."

The paper is the latest chapter in the story of the Dictyostelium discoideum or social amoeba that is being unraveled in the laboratories of Shaulsky, professor of molecular and human genetics at BCM, Dr. Adam Kuspa, chair of biochemistry and molecular biology at BCM and Dr. Joan E. Strassmann and Dr. David C. Queller, professors in the department of ecology and evolutionary biology at Rice University.

Stalks and spores

Social amoebae live as single-cell organisms in normal times. When starved, they form multi-cellular organisms made up of stalks and spores. At one point in this process, some of the cells "sacrifice" themselves and become the dead stalks that support a body of spores, made up of living cells that keep the population alive. This population can be genetically diverse, and a roughly equal proportion of cells from the different gene pools sacrifice themselves to become stalks. That means that the different gene types survive in equal proportions.

Yet some amoeba "cheat" and as a result, more of that particular genotype survives. If this strategy always worked, these "cheaters" would take over the population.

Cheater resistant

To test their hypothesis that some amoebas are cheater resistant, the researchers mixed a population of mutated cells with a cheater strain and allowed them to develop into stalks and spores as chimeras. They thought that the cheater cells would exploit most of the cells in the mutant population, and that a high proportion of any cells left would be resistant to cheating. After several generations, their hypothesis proved true. Further studies showed that these "noble" social amoebae not only resisted the cheaters, they also did not themselves cheat on other amoebae.

"In this study Anu has demonstrated so clearly and cleanly such a response to cheaters at the molecular level. It is also very interesting that these resisters are noble, in the sense that they themselves do not exploit their ancestor," said Strassmann.

"The active cheating in social amobae is more similar to animal sociality, and is therefore a good model system for exploring the complex evolutionary dynamics of genes affecting cooperation, cheating and cheater-resistance," the authors wrote.

"The ones we identified don't abolish cheating completely," said Khare.

"Think of them as the firebreaks that prevent the flames from spreading," said Shaulsky. "Or they are like the people resistant or vaccinated against the flu that prevent it from spreading."

Lorenzo Santorelli of both BCM and Rice also took part in this work.

Funding for this research came from the National Science Foundation and the Cullen Foundation.

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Hair Transplants for Women – Naturally Occurring Female Hairline Patterns

This insightful article was written by Dr. Bernard Nusbaum of Coral Gables, Florida.  Dr. Nusbaum is a member of the Coalition of Independent Hair Restoration Physicians

Hair transplantation for hairline reconstruction is gaining popularity among women with hair loss, thinning hair, high hairlines and those who have undergone cosmetic facial procedures which can alter the hairline, such as face and forehead lifts.  While male hairline patterns have been described in the medical literature, these parameters, when applied to women, do not achieve appropriate facial framing and a “feminine” look.

There is a general lack of   information describing natural hairline patterns in women.  Most descriptions only address the height of the hairline by evaluating vertical facial proportions. In order to develop guidelines for female hairline restoration design, we studied 360 female volunteers at an informal hair salon setting and determined the most common features necessary to achieve a feminine, natural look.  The average age of the subjects was 41 with a range of 16 to 70.  This type of extensive survey has never been done before and we hope that with greater awareness of what occurs in nature, hair restoration results in women will improve.  Below you will find the results.

A widow’s peak was present in 81%.  Peaks or mounds on the sides of the hairline were seen in 98% of the subjects.  86% had these side mounds on both sides and 12% had a mound on one side only.  Of those with mounds on both sides, 64% had a more prominent mound on the right.  Of those with one mound, 83% had the mound located on the right.  The average size of the widows peak and side mounds was determined.  Hairline cowlicks were present in 64%; 61% had one cowlick, 3% had two cowlicks and one subject had three cowlicks.  Of those with one cowlick (219 women), 70% had the cowlick on the left.  It is interesting that brain development and right or left “handedness” has been associated with cowlick position and direction.

The precise locations of the hairline structures were measured and averages were determined. The average height of the center hairline, as measured from the middle of both eyebrows was 5.4 cm.  Due to the large number of women studied, these averages are very accurate in determining the most common hairline shapes and locations.

The shape of the receding temples was concave triangular or concave oval in 87%.  99% of these women had fine hairs within the receding temples.

No correlation was found between age of the subjects and shape of the receding temples or height of the hairline, meaning that these features are most likely inherited and not age dependent.

Based on our findings, the following are proposed guidelines for designing the hairline in women via surgical hair replacement:

  1. Creation of a widow’s peak.
  2. Hairline 5.5 to 6 cm above the mid-eyebrow, taking into account the point at which the vertical forehead transitions to the horizontal frontal scalp.
  3. Creation of side peaks or mounds
  4. Concave triangular or concave oval temporal recessions with fine hairs within the recessions.

Since balding in men gets worse over time, receding hairline patterns are appropriate for male hairline restoration, while such patterns are inappropriate for female hair loss sufferers in achieving a “feminine”  look.

Due to geographic location, the women in this study may represent a particular ethnic background and ethnic differences may exist.

Bernard P. Nusbaum, M.D.

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Bill Seemiller – aka Falceros
Associate Publisher/Editor