Key hormone involved in appetite control

The hormone, called ghrelin, has been found to be involved in weight regulation or reduced caloric intake.

RESEARCHERS AT Oregon Health and Science University (OHSU) have identified a key hormone involved in appetite control and demonstrated its effect on the brain.

Scientists have presently shown that the hormone, called ghrelin, activates specialized neurons in the hypothalamus involved in weight regulation.

The research involved scientists at several collaborating institutions, including: Yale Medical School, Baylor College of Medicine, the University of Alberta and Lilly Research Laboratories.

The results are printed in Neuron. Researchers believe this information could be used to develop drugs aimed at stimulating appetite in patients who have undergone extreme weight loss due to illness, a condition known as cachexia.

These pharmaceuticals could also assist children who are developing at a slower than normal rate.

Conversely, drugs aimed at limiting production of the hormone might be developed to reduce appetite for those battling severe obesity.

"Ghrelin is a hormone produced in the stomach with the natural ability to stimulate feeding when introduced to specialized weight regulation brain cells called neuropeptide Y neurons.

In fact, past research has shown that when ghrelin levels are increased in mice for an extended period, the mice gain weight," said Michael Cowley, an assistant scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center .

"In both mice and humans, ghrelin levels increase naturally in response to weight loss or reduced caloric intake. As expected, the hormone diminishes in response to food intake. In other words, it's believed to be part of the body's natural signalling system which informs the brain when it's time to eat."

To pinpoint and witness the effects of ghrelin in the brain, the researchers used a fluorescent protein to highlight certain neurons, making the brain cells distinguishable from other surrounding neurons.

They then used tiny electrodes to record cell activity in response to ghrelin.

The research team also located a new source for ghrelin production in the body. The site is located in a section of the hypothalamus that had no previously known function and that is near the brain region affected by the hormone.

The research further shows that there are two sites where increased appetite may be generated, the stomach and the brain.

Quartz — a common mineral in teeth

A GROUP of mineralogists led by scientists Valentina Katkova from the Komi Institute of Geology has studied more than 200 second and milk teeth.

The scientists wanted to find out, what minerals our teeth contain. The scientists made tooth sections and examined them under microscope. X-ray-structure analysis and microprobe analysis were also made.

The scientists found that our teeth contain a large collection of various minerals.

The human body is quite a favourable environment for forming of minerals. In most of the organs and tissues apatite takes the first place, in teeth quartz is found more often — in each of the second teeth. In nature quartz looks very much like glass and forms beautiful large oblong crystals.

In the teeth the scientists found only tiny (less than 1 mm in diameter) round grains, yet they were real quartz crystals, mostly white or transparent, sometimes black or pink, according to a press release from the Komi Institute of Geology.

Quartz usually is formed in teeth, affected by caries, but in one healthy but defective cutting tooth the scientists found half a hundred crystals. It seems that quartz is formed from tooth fillings (almost everybody has them), because they are based on powdered quartz. Fillings also support apatite growth, which occurs a bit less often than quartz.

Apatit is a very useful mineral, because it contains much phosphor. It is not yet known why human teeth contain it. It is usually found in the dentine root canal in the form of corals or spike-shaped crystals. What medics call a `denticle' turned out to be a sort of apatite.

Denticles are small round particles on pulp and canal walls, and they are formed as a tooth reaction to microbe infection.

Besides quartz and apatite, human teeth contain other minerals as well.

In the cement whewellite, a sort of calcium compound, sometimes is found, in the pulp camera of one tooth, affected by parodontosis, the scientists found opal.

Feldspar grains, native iron, aragonite, siderite, acanthite, hematite and graphite also were discovered.

Tiny rhombic crystals of whitlockite, calcium phosphate, were found at the patches of destructed enamel. Dentine and pulp also produce organic minerals — glass-like spheres and cylinders of hydrocarbon composition.

Polymetallic compounds are formed deep inside the teeth covered with a metal crowns, including elements such as chromium, iron, zinc, tin, nickel and bismuth. Sometimes the amount of bismuth reaches nearly around 85 per cent of the inclusion mass.

Healthy teeth may contain certain elements such as aluminium, iron, tin and lead and sometimes even microparticles of native gold, silver and rare-earth metals.

Much to the surprise of the scientists, one milk-tooth had a cluster of crystals, half-composed of aluminium.

Babies' DNA stay with the mother

MANY WOMEN carry around their offspring's DNA for the rest of their lives, say Italian researchers.

These can trigger life-threatening diseases, says a report in New Scientist.

Cells from a foetus are known to exist in the mother's body for decades after childbirth.

But now researchers have found foetal DNA in women after 60 years after childbirth.

Foetal cells have been blamed for autoimmune diseases such as scleroderma, a rare and sometimes fatal condition.

They think that the foetal cells mount an immune response against the mother's own cells, although the details remain a mystery.

The research also casts doubt on plans to test for inherited diseases in foetuses by looking for foetal cells in the mother's blood.

If the mother has already had one child, it would be difficult to tell which baby's DNA you are looking at, adds the team.

Vaccine Against HPV-16 and, Possibly, Cervical Cancer

from Journal Watch
Physician-authored summaries and commentary
from the publishers of the New England Journal
of Medicine

Posted 01/21/2003


Summary

Cervical cancer is the second-ranking cause of cancer deaths in women worldwide. Almost all cases of cervical cancer are associated with human papillomavirus (HPV) infection, particularly HPV-16, which is present in nearly 50% of cases.

In an industry-funded study, a U.S. multicenter team randomized 2392 young women to receive 3 doses of an intramuscular vaccine that contained HPV-16 virus-like particles (not live virus) or placebo. Sixty-four percent of the women did not have evidence of HPV-16 infection at study entry: After a median follow-up of 17.4 months, significantly more cases of persistent HPV-16 infection were found in the placebo group than in the vaccine group (3.8 cases/100 woman-years vs. 0 cases). All 9 cases of HPV-16-related cervical intraepithelial neoplasia occurred in the placebo group. Among women who were infected with HPV-16 at study entry, rates of persistent HPV-16 infection were 6.3 and 0.6 cases/100 woman-years in the placebo and vaccine groups, respectively. No serious vaccine-related adverse events were reported, and symptoms that might have indicated adverse reactions were no more common in the vaccine group than in the placebo group.
Comment

The results of this large, well-designed study provide convincing evidence that this new vaccine can protect nearly perfectly against persistent HPV-16 infection and the preneoplastic conditions caused by such infection. This vaccine, or better yet, one that would protect against additional cancer-associated HPVs, might prove to be the most important intervention yet against cervical cancer.

— Anthony L. Komaroff, MD
Source

Koutsky LA et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002 Nov 21; 347:1645-51.

Crum CP. The beginning of the end for cervical cancer? N Engl J Med 2002 Nov 21; 347:1703-5.

Vaccine Against HPV-16 and, Possibly, Cervical Cancer

from Journal Watch
Physician-authored summaries and commentary
from the publishers of the New England Journal
of Medicine

Posted 01/21/2003


Summary

Cervical cancer is the second-ranking cause of cancer deaths in women worldwide. Almost all cases of cervical cancer are associated with human papillomavirus (HPV) infection, particularly HPV-16, which is present in nearly 50% of cases.

In an industry-funded study, a U.S. multicenter team randomized 2392 young women to receive 3 doses of an intramuscular vaccine that contained HPV-16 virus-like particles (not live virus) or placebo. Sixty-four percent of the women did not have evidence of HPV-16 infection at study entry: After a median follow-up of 17.4 months, significantly more cases of persistent HPV-16 infection were found in the placebo group than in the vaccine group (3.8 cases/100 woman-years vs. 0 cases). All 9 cases of HPV-16-related cervical intraepithelial neoplasia occurred in the placebo group. Among women who were infected with HPV-16 at study entry, rates of persistent HPV-16 infection were 6.3 and 0.6 cases/100 woman-years in the placebo and vaccine groups, respectively. No serious vaccine-related adverse events were reported, and symptoms that might have indicated adverse reactions were no more common in the vaccine group than in the placebo group.
Comment

The results of this large, well-designed study provide convincing evidence that this new vaccine can protect nearly perfectly against persistent HPV-16 infection and the preneoplastic conditions caused by such infection. This vaccine, or better yet, one that would protect against additional cancer-associated HPVs, might prove to be the most important intervention yet against cervical cancer.

— Anthony L. Komaroff, MD
Source

Koutsky LA et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002 Nov 21; 347:1645-51.

Crum CP. The beginning of the end for cervical cancer? N Engl J Med 2002 Nov 21; 347:1703-5.

Ginseng Boosts Memory Function After Stroke

Laurie Barclay, MD

Feb. 14, 2003 — Ginseng may help improve memory in patients with mild dementia following a stroke, according to the results of a randomized pilot study reported at the American Stroke Association's 28th International Stroke Conference. However, larger, controlled trials are needed to evaluate safety and efficacy.

"Chinese ginseng has been used for centuries in China to treat disease and aging," lead author Jinzhou Tian, MD, from Beijing University in China, says in a news release. "However, the effects of Chinese ginseng compound on mild and moderate dementia after stroke in humans have not been reported until now."

Chinese ginseng strikingly improves learning and memory following transient cerebral ischemia in rats. It increases the activity of brain acetylcholine and choline acetyltransferase in aged mice, while reducing the activity of acetylcholinesterase in the cerebral cortex and hippocampus.

In this randomized, double-blind, controlled clinical trial, 40 patients with mild and moderate dementia after ischemic stroke (26 men and 14 women) received one tablet of compound Chinese ginseng (n = 25) or one 40-mg tablet of almitrine + raubasine (n = 15), three times daily for 12 weeks. The ginseng compound was extracted from Chinese ginseng roots, leaves, and panax notoginseng. The combination of almitrine and raubasine is thought to increase oxygenation in brain tissue.

After treatment with Chinese ginseng, mean scores on the HVLT and total memory scores increased significantly (P < .05 and P < .001, respectively). Improvements in episodic memory function assessing immediate and delayed story recall, delayed word recall, verbal learning and verbal recognition, and visual recognition were greater in the ginseng group than in the almitrine + raubasine group.

"There is currently great interest in studying herbs used in traditional forms of medicines, and the problem of dementia after stroke is a significant one," says Robert J. Adams, MD, chairman of the Stroke Council of the American Heart Association. "This work showing that ginseng may improve memory after stroke needs to be further studied, with larger sample sizes. A placebo-controlled study would also be the next step. At this time, a recommendation to use this herb for memory enhancement would be premature."

28th International Stroke Conference: Abstract P327. Presented Feb. 14, 2003.

Reviewed by Gary D. Vogin, MD

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Beware High Serum Digoxin Concentrations

Laurie Barclay, MD

Feb. 18, 2003 — It's time to change the therapeutic window of digoxin to 0.5 to 0.8 ng/mL for men with heart failure, according to the results of a post-hoc analysis published in the Feb. 19 issue of The Journal of the American Medical Association.

"The Digitalis Investigation Group (DIG) reported that digoxin provided no overall mortality benefit and only a modest reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function," write Saif S. Rathore, MPH, from Yale University in New Haven, Connecticut, and colleagues. "The clinical outcomes associated with digoxin therapy at different serum concentrations in the DIG trial have not been assessed."

This post-hoc analysis evaluated data from 3,782 men enrolled in the DIG trial from August 1991 to December 1995 who had a left ventricular ejection fraction of 45% or less. At one month, serum digoxin concentration (SDC) in men randomized to digoxin therapy was 0.5 to 0.8 ng/mL in 572 men, 0.9 to 1.1 ng/mL in 322 men, and 1.2 ng/mL or greater in 277 men; 2,611 men were randomized to placebo.

All-cause mortality at a mean follow-up of 37 months was 29.9% for SDC 0.5 to 0.8 ng/mL, 38.8% for SDC 0.9 to 1.1 ng/mL, and 48.0% for SDC 1.2 ng/ml or greater (P = .006 for trend). Compared with men receiving placebo, men with SDC 0.5 to 0.8 ng/mL had a 6.3% lower mortality rate (95% confidence interval [CI], 2.1 - 10.5%), but men with SDC 1.2 ng/mL or higher had an 11.8% higher mortality rate (95% CI, 5.7% - 18.0%).

After multivariable adjustment, SDC was still linked to mortality risk. Hazard ratio was 0.80 for SDC 0.5 to 0.8 (95% CI, 0.68 - 0.94), 0.89 for SDC 0.9 to 1.1 ng/mL (95% CI, 0.74 - 1.08), and 1.16 for SDC 1.2 ng/mL or greater (95% CI, 0.96 - 1.39).

"Given that no study has demonstrated any substantive clinical benefit for higher SDCs, prudent practice would support an SDC of 0.5 to 0.8 ng/mL as a revised therapeutic range," the authors write. "Only a randomized controlled trial can confirm this recommendation; however, we believe our data provide sufficient grounds for consideration of lower target SDCs for men with stable heart failure and left ventricular dysfunction."

JAMA. 2003;289:871-878

Reviewed by Gary D. Vogin, MD

New Web Site Highlights Medical Errors, Patient Safety Lessons: A Newsmaker Interview With Carolyn M. Clancy, MD
Near-miss cases provide a forum in which healthcare professionals can learn about error prevention without blame, sponsors hope.
Medscape Medical News 2003

http://www.webmm.ahrq.gov/

Work Hours More Important Than Money in Specialty Selection


By Keith Mulvihill

NEW YORK (Reuters Health) Feb 17 - When choosing a specialty, new physicians are more likely to base their decision on the amount of vacation time and schedule regularity than on income, new study findings show.

The results of the study suggest that efforts to increase the number of primary care physicians should consider other factors such as work schedule and vacation time, the researchers say.

"There seems to be general agreement that the US health care system has too few primary care physicians and too many specialists," lead author James Thornton, from Eastern Michigan University in Ypsilanti, told Reuters Health.

"Some have cited this as a factor contributing to high and rising medical care spending, as well as compromising the overall quality of care," he added.

But, if the objective of health care policy is to increase the number of primary care physicians and decrease the number of specialists, Thornton points out that information is needed to help understand the factors that influence specialty choice.

Together with co-author Fred Esposto, Thornton evaluated the factors that influence specialty selection for medical residents by analyzing national data published by the American Medical Association. The findings are reported in the January issue of Health Economics.

The findings indicate "that new physicians are more likely to choose specialties for which they expect to make higher future earnings, everything else [being] the same," Thornton noted.

However, earnings were not the most important factor that guided specialty choice, he added. "Annual vacation time, weekly hours worked, and regularity of work schedule have a bigger effect on specialty choice than income."

"New physicians are very attracted to specialties for which they expect to have more annual vacation time, a regular work schedule, and, for primary care specialties, fewer hours worked in a typical week," Thornton said.

If the goal is to persuade more doctors to become primary care physicians, the findings suggest that work hour incentives rather than income benefits are more likely to achieve this objective, he noted.

Thornton believes that offering work hour incentives is feasible in the current medical care system where an increasing number of physicians are no longer self-employed, but are instead affiliated with large medical organizations.

Health Econ 2003;12:61-73.

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January 31, 2003
How Common Is Diastolic Dysfunction?

from Journal Watch
Physician-authored summaries and commentary
from the publishers of the New England Journal
of Medicine

Posted 02/20/2003


Summary

Diastolic dysfunction increasingly is recognized as an important cause of congestive heart failure (CHF). In this study, Mayo Clinic researchers surveyed a random sample of 2042 adults (age, 45 or older) in Minnesota to determine the prevalence of diastolic dysfunction. All subjects underwent Doppler echocardiography.

Twenty-one percent of subjects had mild diastolic dysfunction, and 7% had moderate-to-severe diastolic dysfunction; only a quarter of those with moderate-to-severe diastolic dysfunction had reduced ejection fractions (Comment

Diastolic dysfunction is common in a general adult population and often is "preclinical" (i.e., present in people not yet diagnosed with clinical CHF). Moreover, although diastolic and systolic dysfunction can coexist, most patients with diastolic dysfunction have normal ejection fractions; indeed, diastolic dysfunction predicts mortality independent of ejection fraction. According to the authors, clinical trials are in progress to determine how treatment modifies the course of diastolic heart failure.

Accreditation Body Sets Medical Residents' Work Time Limit at 80 Hours a Week


CHICAGO (Reuters) Feb 19 - Medical residents in the US--who work marathon shifts and 120-hour weeks that critics say lead to medical mistakes--cannot work more than an average of 80 hours a week, a body that accredits medical residency programs said on Tuesday.

Under new rules approved by the nonprofit Accreditation Council for Graduate Medical Education, medical residents must also get one day off out of seven and a 10-hour rest between being on call and working a shift. The rules, which schools must follow to be certified, take effect July 1.

The vote by the council's board of directors means the standards "go from being a should, to a must" in order to pass muster with the accrediting body, said Julie Jacob, a spokeswoman for the group.

Medical residents and the consumer group Public Citizen prefer federal standards, saying a private group lacks the strength to enforce the rules. But the government rejected a petition to a federal agency on that front last year.

The Committee on Interns and Residents, a union that represents 12,000 residents in the United States, said the move "is going in the right direction, but the weakness is enforceability," according to executive director Mark Levy.

The union is working to enact tougher laws on the state level, using a New York law as a model.

Critics say medical residents are now overworked, clocking an average 120 hours per week, a situation they argue leads to medical errors and deaths.

By making the standards mandatory, the accrediting group and the American Medical Association hope to head off federal legislation on residents' hours.

Certification with the council is voluntary, but many medical colleges seek it for recognition, state board certification, and to qualify for federal Medicare funding.

The group accredits about 7800 medical residency programs involving about 100,000 trainees.

Being a Doctor Means Having to Say You're Sorry

Laurie Barclay, MD

Feb. 25, 2003 — Neither doctors nor patients get the proper emotional support after being involved in a medical error, according to the results of a focus group analysis reported in the Feb. 26 issue of The Journal of the American Medical Association. The investigators suggest that doctors should make more of an effort to apologize to their patients, in addition to providing them with appropriate information regarding the nature and cause of the error.

"Health care institutions nationwide are developing ambitious programs to prevent medical errors," write Thomas G. Gallagher, MD, from the University of Washington School of Medicine in Seattle, and colleagues. "Yet, despite our best efforts, medical errors will inevitably occur."

Factors preventing full disclosure of medical errors to patients by physicians may include fear of a malpractice suit, concern about professional reputation, and feeling awkward or uncomfortable.

Of 13 focus groups held between April and June 2002, six involved only patients, four groups involved only physicians, and three groups included both patients and physicians. Of the 52 patients, 71% were female and 88% were white; average age was 60 years. Of the 46 academic and community physicians, 83% were male and 78% were white, and they had been in practice for an average of 16 years.

After reviewing transcripts of focus group discussions concerning a hypothetical medical error, the authors discovered that both patients and physicians had unmet needs regarding communication about errors. Patients wanted information about all harmful errors, including what happened, why it happened, how to improve the outcome, and how to prevent recurrences. Physicians agreed that harmful errors should be disclosed but were guarded in what they told patients about errors.

Although patients wanted an apology and other emotional support from physicians following errors, physicians were concerned that an apology might create legal liability. Physicians were also distraught over errors but did not know where to seek emotional support.

"The current response to medical errors may meet neither patients' desire for information about errors nor the needs of patients and physicians for emotional support following an error," the authors write. "Physicians should strive to meet patients' desire for an apology and for information on the nature, cause, and prevention of errors. Institutions should also address the emotional needs of practitioners who are involved in medical errors."

JAMA. 2003;289:1001-1007

Reviewed by Gary D. Vogin, MD