Published: September 12, 1992

Dr. George Crile Jr., the Cleveland surgeon who angered the medical establishment by insisting that some radical procedures for breast cancer and other diseases met the surgeon’s needs rather than the patient’s, died yesterday at the Cleveland Clinic Foundation. He was 84 years old and lived in Cleveland Heights.

He died of lung cancer, the clinic said.

Dr. Crile’s battle against unnecessary surgery affected the lives of uncounted people in this country, but particularly women stricken with breast cancers.

The controversy of two decades ago swirled around Dr. Crile’s campaign against radical mastectomy — removal of the entire breast and of surrounding lymph notes and major chest muscle — which was routinely performed on breast cancer patients for a century. Instead, he preferred to combat the cancer with a simple mastectomy or, in early stages, with a lumpectomy, in which the tumor and a minimal amount of surrounding tissue is removed by a local incision. Simpler and Safer

This conservative approach was far more common in Europe at the time, and many doctors were concerned when Dr. Crile championed it here. He aroused anger with intimations that some surgeons performed heroics of the scalpel for professional glory, reveling in their skill, or even for the large fees they could command.

Earlier, Dr. Crile had pursued his policy of keeping intrusive surgery to a minimum while specializing in diseases of the thyroid. Among the alternatives he advanced were treatments with new radioactive iodines able to control certain types of thyroid cancer.

His research made surgery simpler and safer. And he brought a simmering medical debate out into the open by encouraging patients to demand information so they might make informed decisions rather than be treated like children who would not understand.

Dr. Bernadine Healy, director of the National Institutes of Health, said yesterday that Dr. Crile was an “unsung hero” who had been the object of “ridicule and scorn” by his peers and had touched millions of American women in an “extraordinarily positive way.” Now, an Accepted Wisdom

“Now lumpectomy is a mainstream and humane treatment for women,” she said in a statement from Bethesda, Md.

Dr. Crile, known as Barney to distinguish him from his illustrious father, who helped found the Cleveland Clinic, spent decades searching for nonsurgical solutions to medical problems. His aversion to routinely performed radical mastectomy is now shared by most doctors.

“I came home from World War II convinced that operations in many fields of surgery were either too radical, or not even necessary,” he once said. “Universal acceptance of a procedure does not necessarily make it right.”

Dr. Crile, who was associated with the Cleveland Clinic for over half a century, retired as head of the department of general surgery in 1968 but continued as senior consultant and, since 1972, as emeritus consultant. In addition to working in his office, he remained a writer, compulsive diarist, world traveler, diver and film maker.

George Washington Crile Jr. was born in Cleveland on Nov. 3, 1907. His father was a distinguished surgeon of the respiratory system who contributed to the study of surgical shock. He also developed the nerve-block anesthesia and was an early user of blood transfusion. A founding partner, he was known at the Cleveland Clinic Foundation as “the Chief.”

Following in his father’s footsteps, the son graduated from Yale University and earned an M.D. summa cum laude at Harvard Medical School in 1929. After his residency at the Cleveland Clinic, he joined the surgical staff in 1937.

He served in the United States Navy in World War II with a team of enlistees from the clinic. Wartime research on ruptured appendixes showed them to be less life-threatening than commonly believed. That suggested that unsupervised emergency appendectomies aboard submarines, while courageous, could do more harm than good.

From that experience grew his impulse to take up the cudgels against orthodoxy. His work with thyroid cancers convinced him that less intrusive alternatives often could take the place of surgery, and his approach succeeded in reducing the need for it.

“With fewer thyroid operations to do,” he recalled, “I looked about for other fruitful fields.” He focused on breast cancer treatments that disfigured thousands of women every year. Sparking a Patients’ Revolt

Originally a firm believer in radical mastectomy, he was influenced by Dr. Reginald Murley, a Scottish physician who combined partial mastectomy with radiation treatment. Dr. Robert S. Dinsmorea, who then headed the surgical staff in Cleveland, was similarly persuaded. Dr. Crile performed his last radical mastectomy in 1954.

He published his first paper on the subject in 1961 to demonstrate that survival rates for lumpectomy or simple mastectomy were comparable to those for radical mastectomy. Doubtful colleagues asserted that this was only because he limited his treatments to women in the early stages of the disease.

But within years, more and more women revolted against the way their surgeons treated them as “cases” in the doctor-knows-best tradition. And a growing number of surgeons began to agree with them and Dr. Crile.

Dr. Crile’s books included “What Women Should Know About the Breast Cancer Controversy” (Macmillan, 1973) and “Surgery, Your Choices, Your Alternatives” (Delacorte, 1978).

Four months ago, the Cleveland Clinic named a new building in honor of the father and the son.

Dr. Crile lost his first wife, the former Jane Halle, to cancer in 1963. He is survived by his second wife, the former Helga Sandburg, daughter of the poet Carl Sandburg; three daughters, Ann Crile Esselstyn of Cleveland, Joan Foster of Atlanta, Ga., and Susan Crile of Manhattan, a son, George Crile 3d of Manhattan, a CBS News producer for “60 Minutes”; a sister, Margaret Garretson of Cleveland; 12 grandchildren and one great-grandchild.



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Published: October 16, 2007

An explosion of new research is vastly changing scientists’ understanding of diabetes and giving new clues about how to attack it.

The fifth leading killer of Americans, with 73,000 deaths a year, diabetes is a disease in which the body’s failure to regulate glucose, or blood sugar, can lead to serious and even fatal complications. Until very recently, the regulation of glucose — how much sugar is present in a person’s blood, how much is taken up by cells for fuel, and how much is released from energy stores — was regarded as a conversation between a few key players: the pancreas, the liver, muscle and fat.

Now, however, the party is proving to be much louder and more complex than anyone had shown before.

New research suggests that a hormone from the skeleton, of all places, may influence how the body handles sugar. Mounting evidence also demonstrates that signals from the immune system, the brain and the gut play critical roles in controlling glucose and lipid metabolism. (The findings are mainly relevant to Type 2 diabetes, the more common kind, which comes on in adulthood.)

Focusing on the cross-talk between more different organs, cells and molecules represents a “very important change in our paradigm” for understanding how the body handles glucose, said Dr. C. Ronald Kahn, a diabetes researcher and professor at Harvard Medical School.

The defining feature of diabetes is elevated blood sugar. But the reasons for abnormal sugar seem to “differ tremendously from person to person,” said Dr. Robert A. Rizza, a professor at the Mayo Clinic College of Medicine. Understanding exactly what signals are involved, he said, raises the hope of “providing the right care for each person each day, rather than giving everyone the same drug.”

Last summer, researchers at Columbia University Medical Center published startling results showing that a hormone released from bone may help regulate blood glucose.

When the lead researcher, Dr. Gerard Karsenty, first described the findings at a conference, the assembled scientists “were overwhelmed by the potential implications,” said Dr. Saul Malozowski, senior adviser for endocrine physiology research at the National Institute of Diabetes and Digestive and Kidney Diseases, who was not involved in the research. “It was coming from left field. People thought, ‘Oof, this is really new.’

“For the first time,” he went on, “we see that the skeleton is actually an endocrine organ,” producing hormones that act outside of bone.

In previous work, Dr. Karsenty had shown that leptin, a hormone produced by fat, is an important regulator of bone metabolism. In this work, he tested the idea that the conversation was a two-way street. “We hypothesized that if fat regulates bone, bone in essence must regulate fat,” he said.

Working with mice, he found that a previously known substance called osteocalcin, which is produced by bone, acted by signaling fat cells as well as the pancreas. The net effect is to improve how mice secrete and handle insulin, the hormone that helps the body move glucose from the bloodstream into cells of the muscle and liver, where it can be used for energy or stored for future use. Insulin is also important in regulating lipids.

In Type 2 diabetes, patients’ bodies no longer heed the hormone’s directives. Their cells are insulin-resistant, and blood glucose levels surge. Eventually, production of insulin in the pancreas declines as well.

Dr. Karsenty found that in mice prone to Type 2 diabetes, an increase in osteocalcin addressed the twin problems of insulin resistance and low insulin production. That is, it made the mice more sensitive to insulin and it increased their insulin production, thus bringing their blood sugar down. As a bonus, it also made obese mice less fat.

If osteocalcin works similarly in humans, it could turn out to be a “unique new treatment” for Type 2 diabetes, Dr. Malozowski said. (Most current diabetes drugs either raise insulin production or improve insulin sensitivity, but not both. Drugs that increase production tend to make insulin resistance worse.)

A deficiency in osteocalcin could also turn out to be a cause of Type 2 diabetes, Dr. Karsenty said. Another recent suspect in glucose regulation is the immune system. In 2003, researchers from two laboratories found that fat tissue from obese mice contained an abnormally large number of macrophages, immune cells that contribute to inflammation. The finding piqued the curiosity of researchers. “I remember reading the paper and thinking: ‘Wow, look at all those macrophages. What are they doing?’” said Dr. Jerrold M. Olefsky of the University of California, San Diego, School of Medicine.

Scientists have long suspected that inflammation was somehow related to insulin resistance, which precedes nearly all cases of Type 2 diabetes. In the early 1900s, diabetics were sometimes given high doses of aspirin, which is an anti-inflammatory, Dr. Olefsky said.

Only in the past few years has research into the relationship of obesity, inflammation and insulin resistance become “really hot,” said Dr. Alan R. Saltiel, director of the Life Sciences Institute at the University of Michigan.

Many researchers agree that obesity is accompanied by a state of chronic, low-grade inflammation in which some immune cells are activated, and that that may be a primary cause of insulin resistance. They also agree that the main type of cell responsible for the inflammation is the macrophage, Dr. Saltiel said.

But major questions remain, he said: “Why are these macrophages attracted to fat, liver and muscle in the first place? What are they doing? What are they secreting? What other immune cells are in there?”

New research also suggests that “not all macrophages are created equal,” added Dr. Saltiel. There appear to be “good ones and bad ones” competing in fat tissue, with potentially large consequences for inflammation and diabetes.

Meanwhile, the promise of anti-inflammatory compounds as treatment continues to attract attention. “Certain cellular anti-inflammatory proteins may now be important new targets for drug discovery for diabetes treatment,” Dr. Olefsky said. But damping down the immune system is also potentially risky, he noted, adding: “If you’re inhibiting the macrophage inflammatory pathway, that’s good for insulin resistance and diabetes. But it might not be so good for your susceptibility to infections.” A major goal is to develop a drug that quashes only the specific component of macrophage inflammation that leads to insulin resistance, without causing other side effects.

One class of current medications, called thiazolidinediones, may work in part by reducing inflammation, which may in turn improve insulin sensitivity. But an example from this class, the drug Avandia, was also found to increase the risk of heart attacks.

Another participant in the glucose conversation is the brain. Its role has long been suspected. More than a century ago, the French physiologist Claude Bernard suggested that the brain was important in blood sugar regulation. He punctured the brains of experimental animals in specific areas and managed to derange their blood sugar metabolism, making them diabetic.

But for years, virtually no one followed up on this finding, said Dr. Kahn, of Harvard.

People thought about glucose as a critical fuel for the brain, Dr. Kahn said, but did not explore the brain’s role in glucose regulation.

Only recently, with more advanced laboratory techniques, has this role been definitively established and expanded upon.

Today’s genetic techniques, said Dr. Rizza, at the Mayo Clinic, are what have “really driven the process.”

For instance, once scientists developed the ability to manipulate mice so that they lacked particular receptors in specific tissues, they could show that mice without insulin receptors in the brain could not regulate glucose properly and went on to develop diabetes, said Dr. Kahn, whose laboratory published this groundbreaking work in 2000.

Other researchers have shown that free fatty acids, as well as the hormone leptin, produced by fat tissue, signal directly to a part of the brain called the hypothalamus, which also regulates appetite, temperature and sex drive.

And several recent papers suggest that direct signaling by glucose itself to neurons in the hypothalamus is also crucial to normal blood sugar regulation in mice.

“If the brain is getting the message that you have adequate amounts of these hormones and nutrients, it will constrain glucose production by the liver and keep blood glucose relatively low,” said Dr. Michael W. Schwartz, a professor at the University of Washington. But if the brain senses inadequate amounts, he continued, it will “activate responses that cause the liver to make more glucose, and new evidence suggests that this contributes to diabetes and impaired glucose metabolism.”

The brain, therefore, appears to be listening to — and weighing and making sense of — a chorus of signals from insulin, leptin, free fatty acids and glucose itself. In response, it appears to send signals to liver and muscle cells by way of several nerves, though additional mechanisms are probably involved. The gut also seems to chime in, said Dr. Rizza, adding that for him, this aspect of sugar regulation came as “the biggest gee whiz of all.”

“Food comes in through the gut, so of course you should look there” for molecules involved in glucose regulation, he said. “But few people realized this until very recently.”

Hormones from the small intestine called incretins turn out to talk directly with the brain and pancreas in ways that help reduce blood sugar and cause animals and people to eat less and lose weight, Dr. Rizza said.

Numerous molecules that mimic incretins or prevent them from being degraded are in clinical trials. Two such drugs have been approved by the Food and Drug Administration: Byetta, an incretin mimic, from Amylin Pharmaceuticals and Eli Lilly; and Januvia, from Merck, which inhibits the destruction of the incretin GLP1. (Dr. Rizza is an adviser to Merck but says all consulting fees go to the Mayo Clinic for education and research.)

Still, it can be hard to predict how different drugs will interact in the body. And many promising candidates will turn out to have side effects — chattering helpfully with one organ, but problematically with another.

“The picture is becoming more and more complicated,” Dr. Saltiel said. “And let’s face it, it was pretty complicated before.”


九月 24, 2007


What is amblyopia?

The brain and the eye work together to produce vision. Light enters the eye and is changed into nerve signals that travel along the optic nerve to the brain. Amblyopia is the medical term used when the vision in one of the eyes is reduced because the eye and the brain are not working together properly. The eye itself looks normal, but it is not being used normally because the brain is favoring the other eye. This condition is also sometimes called lazy eye.

How common is amblyopia?

Amblyopia is the most common cause of visual impairment in childhood. The condition affects approximately 2 to 3 out of every 100 children. Unless it is successfully treated in early childhood, amblyopia usually persists into adulthood, and is the most common cause of monocular (one eye) visual impairment among children and young and middle-aged adults.

What causes amblyopia?

Amblyopia may be caused by any condition that affects normal visual development or use of the eyes. Amblyopia can be caused by strabismus, an imbalance in the positioning of the two eyes. Strabismus can cause the eyes to cross in (esotropia) or turn out (exotropia). Sometimes amblyopia is caused when one eye is more nearsighted, farsighted, or astigmatic than the other eye. Occasionally, amblyopia is caused by other eye conditions such as cataract.

How is amblyopia treated in children?

Treating amblyopia involves making the child use the eye with the reduced vision (weaker eye). Currently, there are two ways used to do this:

1. Atropine

A drop of a drug called atropine is placed in the stronger eye once a day to temporarily blur the vision so that the child will prefer to use the eye with amblyopia. Treatment with atropine also stimulates vision in the weaker eye and helps the part of the brain that manages vision develop more completely.

2. Patching

An opaque, adhesive patch is worn over the stronger eye for weeks to months. This therapy forces the child to use the eye with amblyopia. Patching stimulates vision in the weaker eye and helps the part of the brain that manages vision develop more completely.

Previously, eye care professionals often thought that treating amblyopia in older children would be of little benefit. However, surprising results from a nationwide clinical trial show that many children age seven through 17 with amblyopia may benefit from treatments that are more commonly used on younger children. This study shows that age alone should not be used as a factor to decide whether or not to treat a child for amblyopia.

Can amblyopia be treated in adults?

Studies are very limited at this time and scientists don’t know what the success rate might be for treating amblyopia in adults. During the first six to nine years of life, the visual system develops very rapidly. Complicated connections between the eye and the brain are created during that period of growth and development. Scientists are exploring whether treatment for amblyopia in adults can improve vision.



nucifera: 我的小妹患有懒惰眼,所以上网寻找了解相关资料。