Ascites

The word ascites is of Greek origin (askos) and means bag or sac. Ascites describes the condition of pathologic fluid accumulation within the abdominal cavity. Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL depending on the phase of the menstrual cycle. This article focuses only on ascites associated with cirrhosis.

The accumulation of ascitic fluid represents a state of total-body sodium and water excess, but the event that initiates the unbalance is unclear. Three theories of ascites formation have been proposed.

The underfilling theory suggests that the primary abnormality is inappropriate sequestration of fluid within the splanchnic vascular bed due to portal hypertension and a consequent decrease in effective circulating blood volume. This activates the plasma renin, aldosterone, and sympathetic nervous system, resulting in renal sodium and water retention.

The overflow theory suggests that the primary abnormality is inappropriate renal retention of sodium and water in the absence of volume depletion. This theory was developed in accordance with the observation that patients with cirrhosis have intravascular hypervolemia rather than hypovolemia.

The most recent theory, the peripheral arterial vasodilation hypothesis, includes components of both of the other theories. It suggests that portal hypertension leads to vasodilation, which causes decreased effective arterial blood volume. As the natural history of the disease progresses, neurohumoral excitation increases, more renal sodium is retained, and plasma volume expands. This leads to overflow of fluid into the peritoneal cavity. According to the vasodilation theory, the underfilling theory is proposed to be operative early and the overflow theory is proposed to be operative late in the natural history of cirrhosis.

Although the sequence of events that occurs between the development of portal hypertension and renal sodium retention is not entirely clear, portal hypertension apparently leads to an increase in nitric oxide levels. Nitric oxide mediates splanchnic and peripheral vasodilation. Patients with ascites have greater hepatic artery nitric oxide synthase activity compared to patients without ascites.

Regardless of the initiating event, a number of factors contribute to the accumulation of fluid in the abdominal cavity. Elevated levels of epinephrine and norepinephrine are well-documented factors. Hypoalbuminemia and reduced plasma oncotic pressure favor the extravasation of fluid from the plasma to the peritoneal fluid, and, thus, ascites is infrequent in patients with cirrhosis unless both portal hypertension and hypoalbuminemia are present.

Ambulatory patients with an episode of cirrhotic ascites have a 3-year mortality rate of 50%. The development of refractory ascites carries a poor prognosis, with a 1-year survival rate of less than 50%.

Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL depending on the phase of the menstrual cycle.

Collagenous and Lymphocytic Colitis

Collagenous colitis (CC) was described concurrently in 1976 by Lindstrom and by Freeman. In 1980, Read described microscopic colitis, which is clinically indistinguishable from CC but is differentiated from it by colonic biopsy features. Later, the term lymphocytic colitis (LC) was proposed by Lazenby to replace the term microscopic colitis and to distinguish it from infectious colitis and inflammatory bowel disease (ulcerative colitis and Crohn disease). The term microscopic colitis is now used to describe both CC and LC, and these conditions should be considered in any patient with unexplained nonbloody diarrhea. Patients undergoing either sigmoidoscopy or colonoscopy for unexplained diarrhea who have normal endoscopic findings should have biopsy samples taken to diagnose or rule out either form of microscopic colitis.

LC and CC are relatively rare conditions that are diagnosed when a patient with chronic watery nonbloody diarrhea has an endoscopically or radiographically normal colon, but colonic biopsies show unique inflammatory changes. Because the mucosa is not ulcerated or otherwise disrupted, the diarrhea generally does not contain blood or pus.

• The characteristic feature of LC is an infiltration of lymphocytes into the colonic epithelium. CC shares this feature but additionally shows a distinctive thickening of the subepithelial collagen table. LC and CC have been suggested to represent different phases of a single pathophysiologic process, with LC possibly being a precursor or earlier phase of CC; however, this has not been proven.

• The diarrhea in CC is more likely due to the inflammatory process than to the subepithelial collagen layer, although this layer may serve as a cofactor in the role of a diffusion barrier.

• Increased levels of immunoreactive prostaglandin E2 in stool water may contribute to a secretory diarrhea.

• Some patients with CC and concurrent collagenous infiltration of the duodenum and/or the ileum have demonstrated altered small bowel dysfunction, demonstrated by reduced D-xylose absorption.

• Some individuals have bile acid malabsorption demonstrated by the Se-75-homotaurocholate (SeHCAT) test, in which a positive test result is shown by retention of less than 11% of the administered dose of radioactivity after 7 days.

• Some patients with CC may have increased mucosal secretion of vascular endothelial growth factor, a fibrosis-enhancing peptide.

United States

True incidence is not known. The disease has been increasingly diagnosed over the past 20 years, but it is still uncommon. A recently published population-based study found the incidence of microscopic colitis to increase significantly from 1.1 per 100,000 persons in the late 1980s to 19.6 per 100,000 persons by the end of 2001. Rates increased with age. Prevalence at the end of the study period was 103.0 per 100,000 persons (39.3 for CC and 63.7 for LC).

Morbidity is limited to the consequences of diarrhea and malabsorption, including metabolic abnormalities such as hypokalemia and dehydration, weight loss, fatigue, and vitamin deficiencies. This is not considered a life-threatening condition; however, profuse watery diarrhea may lead to severe dehydration and electrolyte abnormalities requiring intensive resuscitation.

LC affects similar numbers of men and women, while CC is up to 20 times more frequent in women than in men.

Both conditions are observed most commonly in people older than 40 years, with peak incidence in the sixth and seventh decades of life, and the incidence of both conditions increases with age. Isolated cases have been reported in younger populations, including children.

Hirschsprung Disease

Hirschsprung disease is a developmental disorder of the enteric nervous system and is characterized by an absence of ganglion cells in the distal colon resulting in a functional obstruction. Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung in 1886, the pathophysiology was not clearly determined until the middle of the 20th century when Whitehouse and Kernohan described the aganglionosis of the distal intestine as the cause of obstruction in their series of patients (Whitehouse, 1948). In 1949, Swenson described the first consistent definitive procedure for Hirschsprung disease, rectosigmoidectomy with coloanal anastomosis. Since then, other operations have been described, including the Duhamel and Soave techniques. More recently, advances in surgical technique, including minimally invasive procedures, and earlier diagnosis have resulted in decreased morbidity and mortality for patients with Hirschsprung disease.

Most cases are now diagnosed in the newborn period. Hirschsprung disease should be considered in any newborn who fails to pass meconium within 24-48 hours after birth. Although contrast enema is useful in establishing the diagnosis, full-thickness rectal biopsy remains the criterion standard. Once the diagnosis is confirmed, the basic treatment is to remove the poorly functioning aganglionic bowel and create an anastomosis to the distal rectum with the healthy innervated bowel (with or without an initial diversion).

Congenital aganglionosis of the distal bowel defines Hirschsprung disease. Aganglionosis begins with the anus, which is always involved, and continues proximally for a variable distance. Both the myenteric (Auerbach) and submucosal (Meissner) plexus are absent, resulting in reduced bowel peristalsis and function. The precise mechanism underlying the development of Hirschsprung disease is unknown.

Enteric ganglion cells are derived from the neural crest. During normal development, neuroblasts will be found in the small intestine by the 7th week of gestation and will reach the colon by the 12th week of gestation (Okamoto, 1967). One possible etiology for Hirschsprung disease is a defect in the migration of these neuroblasts down their path to the distal intestine. Alternatively, normal migration may occur with a failure of neuroblasts to survive, proliferate, or differentiate in the distal aganglionic segment. Abnormal distribution in affected intestine of components required for neuronal growth and development, such as fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors, may be responsible for this theory (Gaillard, 1982; Langer, 1994; Tosney, 1986).

Additionally, the observation that the smooth muscle cells of aganglionic colon are electrically inactive when undergoing electrophysiologic studies also points to a myogenic component in the development of Hirschsprung disease (Kubota, 2002). Finally, abnormalities in the interstitial cells of Cajal, pacemaker cells connecting enteric nerves and intestinal smooth muscle have also been postulated as an important contributing factor (Ward, 2001; Vanderwinden, 1996).

Three neuronal plexus innervate the intestine: the submucosal (ie, Meissner) plexus, the intermuscular (ie, Auerbach) plexus, and the smaller mucosal plexus. All of these plexus are finely integrated and involved in all aspects of bowel function, including absorption, secretion, motility, and blood flow.

Normal motility is primarily under the control of intrinsic neurons. Bowel function is adequate, despite a loss of extrinsic innervation. These ganglia control both contraction and relaxation of smooth muscle, with relaxation predominating. Extrinsic control is mainly through the cholinergic and adrenergic fibers. The cholinergic fibers cause contraction, and the adrenergic fibers mainly cause inhibition.

In patients with Hirschsprung disease, ganglion cells are absent, leading to a marked increase in extrinsic intestinal innervation. The innervation of both the cholinergic and adrenergic systems is 2-3 times that of normal innervation. The adrenergic (excitatory) system is thought to predominate over the cholinergic (inhibitory) system, leading to an increase in smooth muscle tone. With the loss of the intrinsic enteric inhibitory nerves, the increased tone is unopposed and leads to an imbalance of smooth muscle contractility, uncoordinated peristalsis, and a functional obstruction.

Ogilvie Syndrome

Ogilvie syndrome, or acute colonic pseudo-obstruction (ACPO), is a clinical disorder with the signs, symptoms, and radiographic appearance of an acute large bowel obstruction with no evidence of distal colonic obstruction. The colon may become massively dilated; if not decompressed, the patient risks perforation, peritonitis, and death.

In 1948, Sir Heneage Ogilvie described 2 patients with metastatic cancer and retroperitoneal spread to the celiac plexus. The patients also had signs and symptoms of colonic obstruction but with no evidence of organic obstruction to the intestinal flow. Ogilvie hypothesized that the etiology of their conditions was an imbalance in the autonomic nervous system with sympathetic deprivation to the colon leading to unopposed parasympathetic tone, regional contraction, and, thus, a functional obstruction.

In 1958, Dudley et al used the term pseudo-obstruction to describe the clinical appearance of a mechanical obstruction with no evidence of organic disease during laparotomy.

PATOFISIOLOGI

The pathophysiology of ACPO is not clearly understood. Research into the neurophysiology of the colon reveals that Ogilvie's hypothesis was close to the proposed current understanding. The parasympathetic nervous system is responsible for stimulating gut motility. The vagus nerve supplies the parasympathetic tone from the upper GI tract to the splenic flexure, and the sacral parasympathetic nerves (S2 to S5) supply the left colon and rectum. Sympathetic stimuli result in the inhibition of bowel motility and contraction of sphincters. The lower 6 thoracic segments supply the sympathetic tone to the right colon, while lumbar segments 1-3 supply the left colon.

Based on evidence from pharmacologic studies, metabolic abnormalities, retroperitoneal trauma, and various spinal blockade studies, an imbalance in the autonomic innervation appears to lead to a functional bowel obstruction. Unlike Ogilvie's hypothesis, some current evidence suggests that an interruption of the sacral parasympathetic nerves occurs, leading to an adynamic distal colon that is similar to Hirschsprung disease, except with normal ganglion cells observable on autopsy. Other research supports the belief that the sympathetic tone increases in these patients, who usually are very ill, leading to inhibition of colonic motility.

The cecum is the usual site of the largest dilatation in patients with ACPO and is thus prone to the greatest risk of perforation. The Laplace law indicates that the intraluminal pressure needed to stretch the wall of a hollow tube is inversely proportional to its diameter. The largest diameter in the colon is the cecum; therefore, the cecum requires the smallest amount of pressure to increase in size and to thus increase wall tension. As the wall tension of the colon increases, ischemia with longitudinal splitting of the serosa, herniation of the mucosa, and perforation can occur.

Buyer beware of psychiatric genetic tests

You can now buy a commercial genetic test that claims to assess your risk of developing bipolar disorder. Genetic tests for major depression and schizophrenia are also expected to reach the market soon. However, although the suspects are numerous, the genes responsible for most brain disorders remain unknown. So, when it comes to commercial genetic tests, we just don’t know enough to make the tests useful, reports the May issue of the Harvard Mental Health Letter.
One problem is that the genetics field is advancing so rapidly that it’s hard to keep up with developments, never mind figure out which ones are clinically relevant. Most experts also believe that psychiatric disorders develop because of the interplay between multiple genes, each exerting small effects. That makes finding the responsible genes harder. Further complicating matters, research has revealed that many healthy relatives of people with psychiatric disorders have risk genes. Whether a person develops an illness depends on unknown ways the risk genes interact with other genes and environmental factors.

Scientists have identified perhaps thousands of candidate genes that may contribute to psychiatric conditions. But experts continue to debate which genes are actually involved. Most candidate genes fail to hold up—meaning that the association between the gene and a given illness disappears when scientists try to replicate the results. One analysis estimated that 70% to 80% of candidate genes are false positives.

Dr. Michael Miller, editor in chief of the Harvard Mental Health Letter,notes that someday it may be possible to reliably assess risk for psychiatric disorders. But at this point, the technology—and the science—is still evolving.

On the prevention of myopia

I was astonished to read that still today one can question the development of myopia when working in dim light (1). The extra accomodation strain that it causes on the reading eye is indisputable. Suboptimal lighting, however, is only a minor factor in the development of myopia. The constant haste combined with vast close-work in the modern society maintain accomodation stress that often leads to accomodation spasm. Thus the present prevention of myopia is a global disgrace. It has been allowed to be continued unchanged for the past 100 years!

The old beliefs of myopia being inherited hinder the acceptance of the fact based on practical experience that this is not the case.

The most important way to counteract the development of myopia is if a child as early as possible would use reading glasses (+3.0, possibly as add to the plus-distant correction) in all close work. In the case that myopia already has developed it is of uttermost importance to avoid close work with distant correction. Bifocals with significant plus addition is the method of choice.

In year 1972 I published Tetralogia (2), which arosed severe resistance among my Finnish colleagues. Tetralogia deals with accommodation strain leading to accommodation spasm and pseudomyopia and the prevention of myopia. I have developed polyphasic fogging method for revealing the spasm of accomodation (3). I stressed also the clinical significance, which accommodation strain has to our organism as a whole (2,4).

From the year 1973 Donald S Rehm has handled the same theme. As the President of International Myopia Prevention Association he, in year 2005, wrote a petition to FDA, which became rejected (5). It is sad to see, that all the leading American Institutions have done everything in their power to hide this knowledge from the parents and to retain the business of minusglasses and the billions- bringing operative activity of healthy corneas. Quoting President Rehm if professionals “had any concern for the people of the world they could expose and end this tragedy almost overnight”.

For an ophthalmologist it is impossible to think that a professional on the eyebranch would not understand this much about the physiology of accommodation. Is this unconcernedness thus a question of conscious denying of the truth or is this all about the money?

Blood-Thinner No Help for Dialysis Treatment

TUESDAY, May 13 (HealthDay News) -- A major trial has dashed the hope that the clot-preventing drug Plavix could help in the delicate balancing act needed to establish a blood vessel suitable for dialysis for kidney patients.

Giving Plavix (clopidogrel) did reduce the risk that a blood clot would block the vessel created by combining a vein and an artery, a standard procedure for kidney dialysis. But adding the clot-preventing drug did not increase the number of fistulas, as they are called, that could be used for artificial kidney treatment over the long run, the study authors reported.

The study was done because "early thrombosis [blood clotting] is one of the major causes of fistula failure," said Dr. Laura M. Dember, an associate professor of medicine at Boston University, and lead author of the report.

"What we found was that despite the reduction in thrombosis that was clear enough, there was an equal proportion of fistula failure," Dember said. "What is ultimately important is the usability of the fistula for dialysis."

The researchers published their findings in the May 14 issue of the Journal of the American Medical Association.

About 470,000 Americans have kidney failure and are kept alive by dialysis, in which their blood is run through a machine that filters out impurities. The preferred technique for linking to the artificial kidney is to create a fistula, which has lower rates of thrombosis -- blockage -- and infection than alternatives such as synthetic artery-vein grafts. But many fistulas never mature enough to allow dialysis.

The multi-center trial included 877 people with total or partial kidney failure who underwent surgery to create a fistula. Half were given Plavix for six weeks after the surgery, while the other half were not.

Plavix did reduce the risk of blockage by 37 percent over the six-week period. Among the 866 people who were tested, 12.2 percent of those given Plavix had a blockage, compared to 19.5 percent of those not given the anti-clotting drug.

But Plavix therapy did not reduce the incidence of cases in which the fistula could not be used for dialysis, which was 61.8 percent in those getting the drug and 59.5 percent in those getting a placebo.

The rate of fistula failure was about 50 percent higher than anticipated, Dember said, and that might have an effect on future practice.

"There has been an increased emphasis on trying to create fistulas in as many patients as possible," she said. "So, the criteria have changed. We need to develop better methods for selecting suitable candidates for fistula creation."

The trial also indicated the direction that that research should take, Dember said.

"Our future efforts should be directed at understanding the basic mechanisms of fistula maturation," she said. "If we better understand those mechanisms, we should be able to identify maturity-enhancing interventions.

Dialysis patients with metabolic syndrome

St. Louis, Mo. – March 07, 2007 - A study of kidney dialysis patients found that nearly 70 percent had metabolic syndrome, a set of symptoms that is a predictor of cardiovascular disease, at the time they initiated maintenance dialysis. This information further illuminates the relationship between heart and kidney disease, as dialysis patients are already known to have an elevated risk of cardiovascular problems.

“Metabolic syndrome is a term we apply to anyone having three of the following five criteria: abdominal obesity, elevated triglyceride levels, low HDL cholesterol (also known as “good cholesterol”) levels, high blood pressure, or high blood glucose after fasting,” says study author Dr. Daniel Young. The study also showed that white, female and diabetic dialysis patients showed the highest incidence of metabolic syndrome.

Dr. Young sees potential to use metabolic syndrome as a medical diagnostic tool. “Checking new dialysis patients for these criteria may assist us in identifying the patients most vulnerable to cardiovascular disease in this population.” In addition, he suggests that additional research involving metabolic syndrome and the earlier stages of kidney disease may yield important insights into the diagnosis of kidney disease itself.

Mammography, Ultrasound Finds More Breast

TUESDAY, May 13 (HealthDay News) -- While undoubtedly lifesaving for many women, mammography is far from perfect. But, undergoing breast ultrasound in addition to standard mammography can find more cancers in high-risk women, particularly those with dense breast tissue, a new study found.

But, the study authors noted, ultrasound also significantly increases the rate of false-positive readings.

"In our study participants, half of the breast cancers were found using mammography alone. By adding ultrasound, we found 78 percent of the cancers," said the study's lead author, Dr. Wendie Berg, a radiologist at an outpatient center in Lutherville, Md., affiliated with Johns Hopkins Medical Center.

However, identifying those extra cancers came with a cost of significantly more false-positive readings.

"With mammography, a woman has about a one in 40 chance that a biopsy will turn out not to be cancer. With the addition of ultrasound, it's one in 10," Berg said.

Results of the study, which was funded by the Avon Foundation and the U.S. National Cancer Institute, were published in the May 14 issue of the Journal of the American Medical Association.

Each year, more than 180,000 American women are diagnosed with breast cancer, and almost 41,000 will lose their lives to the disease. Death rates from breast cancer have been declining, possible due to earlier detection and diagnosis, according to the American Cancer Society.

The new study included almost 3,000 women recruited from 21 centers. The average age was 55 years old, and all of the women had a higher-than-normal risk of breast cancer.

The women were randomly assigned to receive either mammography alone or mammography plus ultrasound performed by a physician.

Forty women were diagnosed with breast cancer within a year of their initial screening. Mammography alone uncovered 20 cancers, 50 percent, while the combination screening technique found 31 of the cancers, or about 78 percent, according to the study.

That means for every woman screened, mammography alone will find 7.6 cancers, mammography plus ultrasound will detect 11.8 cancers, and three cancers will be missed altogether, the researchers said.

The study found that ultrasound was a good complementary screening tool for mammography, because it found cancers that mammography might miss.

"Ultrasound performs best in cases for which mammography performs weakest, i.e., in breast areas with dense fibroglandular tissue," Dr. Christiane Kuhl, with the Department of Radiology at the University of Bonn in Germany, wrote in an accompanying editorial in the journal. Kuhl also noted that the drawbacks to ultrasound include the frequency of false-positives, the cost of the test, and a lack of evidence that the test affects mortality.

Berg noted that there aren't currently enough physicians or ultrasound technicians trained for ultrasound to be a viable, widely used screening tool right now, even just for high-risk women.

"On average, physicians can only perform three to five ultrasounds per hour," said Berg, compared to as many as 50 mammograms in an hour, according to the editorial.

Dr. Julia Smith, director of the Lynne Cohen Breast Cancer Preventative Care Program at the New York University Cancer Institute and Bellevue Hospital in New York City, said, "I already do ultrasounds on women at risk. As a complementary test, ultrasound can be a very useful test. Also, we know it's relatively inexpensive and safe."

Magnetic resonance imaging (MRI) may be more effective than either mammography or ultrasound, and it's fast becoming a popular tool for breast cancer screening, but, Smith said, the cost of MRI is prohibitive.

Given limited health-care resources, Kuhl wrote that "mammography will probably remain the basis for breast cancer screening for the foreseeable future."

Smith said what's most important is for women to talk with their doctors about their individual risk of breast cancer, and then decide which screening tests would be most appropriate.

cervical cancer

The results, published today in the prestigious international journal Lancet, show that while the vaccine provides effective protection against high grade cervical pre-cancerous lesions caused by human papillomavirus (HPV) types 16 and 18, it also demonstrated additional protection against infections from other strains of HPV that account for another 10 percent of cervical cancers.

The Perth component of the international study was conducted by the Vaccine Trials Group at the Telethon Institute for Child Health Research in collaboration with Princess Margaret Hospital and King Edward Memorial Hospital.

Report co-author Dr Rachel Skinner, who headed the Perth trial, said the results were very encouraging.

“We have found through this study that this vaccine is extremely effective in the prevention of pre-cancerous disease of the cervix due to infection with HPV types 16 and 18,” Dr Rachel Skinner said.

“However we now have evidence that Cervarix offers women broader protection by providing some protection against infections caused by HPV types 45 and 31. These types together with HPV types 16 and 18 account for 80 per cent of cases of cervical cancer worldwide.

“Not only will vaccinated women potentially benefit from a high level of protection against cervical cancer, they will also benefit from a reduction in abnormal Pap smears. However it is crucial that women who choose vaccination continue with regular Paps as the vaccine does not provide complete protection against cervical cancer.”

The international study is the single largest cervical cancer vaccine efficacy study with over 18,000 women aged 15-25 years involved from all corners of the globe, including Europe, Asia Pacific, Latin and North America and women from six centres throughout Australia.

The Therapeutic Goods Adminstration has now approved Cervarix for women aged 10-45 years, making it the first vaccine in Australia available for women over the age of 26 years.

Cellular atypia of the breast predictive of cancer

Several previous studies have shown that atypical hyperplasia (also called atypia) in breast tissue is a major risk factor for breast cancer. Women who have a breast biopsy and are diagnosed with atypia are considered at high risk. Many are counseled to consider preventive medications such as tamoxifen or other risk-reducing approaches. However, questions remained from prior research on whether a positive family history further increases risk in women with atypia and for how long the increased risk in women with atypia lasts.

“The most commonly used tool for risk prediction in women with atypia is the Gail model, which may predict inaccurately because our study shows that family history does not change risk significantly in women with atypia,” says Amy Degnim, M.D., a Mayo Clinic surgeon and study author. “Our findings indicate that women with atypia have a higher absolute risk for breast cancer than previously estimated. This risk is 25 percent over 25 years and is much higher in women with multiple areas of atypia and calcification.” The Gail model predicts risk by using age at onset of menses, age at birth of first child, number of previous breast biopsies, presence of atypia, and number of close relatives with breast cancer.

While the Mayo Clinic study found that family history did not further increase risk, age at diagnosis of atypia did affect risk, with younger women (under age 45) more than twice as likely to develop breast cancer compared to women diagnosed with atypia after 55. The number of areas of atypical hyperplasia was significant as well. With one area of atypia, breast cancer risk was 2.3-fold compared to the general population; this risk more than doubled when two sites were found and increased to nearly eightfold as sites increased to three or more. The group of women with the highest risk had three or more areas of atypia and calcification -- with a 10.4-fold risk over the general population.

“With the ability to stratify the risk of breast cancer in women with atypia, we can have more informed discussions with our patients regarding their personal risk,” says Dr. Degnim. “This will help us to have individualized discussions regarding how aggressively to pursue risk-reduction treatments.”

These findings resulted from reviewing the records of 331 women with atypia identified within the Mayo cohort of 9,376 women who had benign breast biopsies surgically obtained between 1967 and 1991. More than half (55.9 percent) of the women were over age 55 when diagnosed with atypia, and 42.9 percent had a family history of breast cancer. The majority (68.6 percent) of women showed calcification in the biopsy tissue, and 40 percent had multiple sites of atypical hyperplasia.

The American Cancer Society reports that more than 240,000 women will be diagnosed in the United States this year with breast cancer, and more than 40,000 will die from it. Dr. Degnim and her fellow researchers have been working to better understand the steps that precede breast cancer and which of them can be recognized in benign breast tissue. The current study contributes to Mayo’s emerging model that seeks to define every woman’s risk more precisely and to tailor screening and risk-reduction measures to women depending on their individual risks.

Health Tip: Treating an Ulcer

(HealthDay News) -- Ulcers are sores that occur in the lining of the digestive tract. They can be triggered by factors such as bacteria, medication or excess production of stomach acid.

If you have an ulcer, here are things you should discuss with your doctor to promote healing, courtesy of the American Academy of Family Physicians:

• Medications can help ulcers heal. Antibiotics are prescribed to thwart bacteria, and other medications may be taken to help reduce stomach acid.
• Avoid smoking.
• Don't take anti-inflammatory medications such as aspirin or ibuprofen.
• Avoid caffeine and alcohol in your diet. If you do have some, try to make sure it's after you've eaten a meal or snack.
• Don't eat foods that seem to aggravate your ulcer. Examples may include chocolate, coffee, certain herbs and spices, and some spicy foods.
• Eat several small meals throughout the day, rather than one big meal.

Physical Impairment Elderly

SATURDAY, May 3 (HealthDay News) -- Two new studies show that anticholinergics, a commonly prescribed group of drugs, may cause elderly people to "slow down" in their daily physical activities.

The two reports from researchers at Wake Forest University School of Medicine support findings released a few weeks ago that anticholinergic drugs -- which treat a variety of diseases and conditions, including acid reflux, Parkinson's disease and urinary incontinence -- may cause older people to lose their thinking skills more quickly than those who don't take the medicines.

Anticholinergic drugs work by stopping acetylcholine, a chemical that enhances communication between nerve cells in the brain, from binding to its receptors in nerve cells.

In the first Wake Forest study, older adults taking anticholinergics became more likely to walk more slowly and to need help in other daily activities.

"These results were true even in older adults who have normal memory and thinking abilities," study author Dr. Kaycee M. Sink said in a prepared statement. "For older adults taking a moderately anticholinergic medication, or two or more mildly anticholinergic medications, their function was similar to that of someone three to four years older."

Common anticholinergic medicines cited in the study included the blood pressure medication nifedipine (Adalat or Procardia), the stomach antacid ranitidine (Zantac) and the incontinence medication tolterodine (Detrol).

The findings, which involved more than 3,000 people, average age 78, were scheduled to be presented Saturday at the American Geriatrics Society annual meeting, in Washington, D.C.

In a separate Wake Forest study, published online in April in the Journal of the American Geriatrics Society, Sink found that older nursing home residents who took medicines for dementia along with anticholingerics for incontinence declined in function 50 percent faster than those only treated only for dementia.

"Over a year's time, the decline we observed would represent a resident going from requiring only limited assistance in an activity to being completely dependent, or from requiring only supervision to requiring extensive assistance in an activity," said Sink, an assistant professor of internal medicine-gerontology at Wake Forest.

The seniors in the second study had completed at least two consecutive prescriptions for cholinesterase inhibitors, a family of drugs used to treat dementia by increasing levels of acetylcholine. These include donepezil (brand name Aricept), galantamine (Razadyne), rivastigmine (Exelon) and tacrine (Cognex).

About 10 percent of those studied were also taking either oxybutynin or tolterodine, the two most commonly prescribed drugs for urinary incontinence.

"The two drugs are pharmacological opposites, which led us to hypothesize that the simultaneous treatment of dementia and incontinence could lead to reduced effectiveness of one or both drugs, Sink said.

As an estimated 33 percent of people with dementia also take a medicine to control incontinence, this finding is especially alarming.

The two studies suggest that physicians should carefully consider the implications when prescribing anticholingeric medications to older adults.

Familial Breast Cancer Risk Lasts a Lifetime for Sisters

TUESDAY, May 13 (HealthDay News) -- New research has found both bad news and good news on breast cancer risk.

The bad news is a risk factor you can't change: Women whose sisters were diagnosed with breast cancer face an increased risk of breast cancer throughout their lives, regardless of their sister's age at diagnosis, according to a study in the May 13 issue of the Journal of the National Cancer Institute (JNCI).

The good news comes from a risk factor you can do something about: Women who exercise are much less likely to develop breast cancer, according to two new research studies -- one from the same issue of JNCI, and the other from the 2008 online first edition of the British Journal of Sports Medicine.

The first study from JNCI compared the rate of breast cancer in nearly 24,000 sisters of women with breast cancer to the rate of cancer in nearly 1.8 million women with sisters who didn't have breast cancer. All of the women were from Sweden, and the data collection for the study spanned from 1958 to 2001.

The researchers found that women between the ages of 20 and 39 who had a sister who'd been diagnosed with breast cancer faced a sixfold higher risk of breast cancer than did women whose sisters didn't have breast cancer. The excess risk declined as the women aged but didn't disappear. Women who were older than 50 with a sister with breast cancer had about a twofold risk of developing the disease, according to the study. And, it didn't matter what age the sister was when she was diagnosed.

"After the diagnosis of breast cancer in a family, the other sisters -- especially the youngest -- have an increased risk of breast cancer that persists for 20 years," said one of the study's authors, Marie Reilly, a professor of biostatistics at the Karolinska Institute in Stockholm, Sweden. "This suggests that sisters of breast cancer patients, especially the young sisters, should be intensely screened, independent of the screening recommendations for women their age."

Dr. Julia Smith, director of the Lynne Cohen Breast Cancer Preventative Care Program at the New York University Cancer Institute and Bellevue Hospital in New York City, called the findings "interesting and troubling." She added, "Sisters have to worry about increased risk no matter when their sister was diagnosed."

The second study from JNCI relied on data from the Nurse's Health Study II and included information from almost 65,000 women who completed questionnaires about their physical activity from age 12 until age 35. During the six-year follow-up period, 550 women from that group were diagnosed with breast cancer.

Women who walked about 13 hours a week or ran 3.25 hours a week had a 23 percent reduced risk of developing premenopausal breast cancer than women who were less active. The incidence rates of breast cancer were 194 per 100,000 "person-years" for the least active women, compared to 136 cases per 100,000 "person-years" for the most active women.

"These results suggest that consistent physical activity during a woman's lifetime is associated with decreased breast cancer risk. Unlike many risk factors for breast cancer, physical activity is an exposure that can be modified," wrote the study's authors, who were led by Dr. Graham Colditz, of Washington University School of Medicine in St. Louis.

Smith said: "For many reasons, women should continue to exercise and try to be in shape." It makes sense that exercise might reduce breast cancer risk, she said, adding, "Women who are exercising regularly are decreasing body fat and estrogen."

The third study on breast cancer risk was an analysis of 62 other studies that looked at the impact of physical activity and breast cancer risk. This review, published online ahead of the print version of the British Journal of Sports Medicine, found that women who are physically active have a 25 percent decreased risk of breast cancer.

The researchers found that both recreational or on-the-job activity could reduce risk, and that moderate and vigorous exercise caused a similar reduction in risk. This review also found that activity performed after menopause was more effective in reducing risk.

Smith recommends that women exercise at least 20 minutes, three times a week, and preferably more. She said that during those 20 minutes of moderate to vigorous exercise, the heart rate should consistently be above baseline.

Smoking Heart Risks Quickly

TUESDAY, May 6 (HealthDay News) -- New research shows that women who quit smoking have a 47 percent lower risk of dying from coronary heart disease within five years of extinguishing their last cigarette.

The risks of dying from other conditions also decline after quitting, although the time frame varies depending on the disease.

"The harms of smoking are reversible and can decline to the level of nonsmokers," said study author Stacey Kenfield, whose report is in the May 7 issue of the Journal of the American Medical Association. "For some conditions like chronic obstructive pulmonary disease, it can take more than 20 years, but there is a rapid reduction for others."

"It's never too early to stop, and it's never too late to stop," added Kenfield, who is a postdoctoral research fellow in the department of epidemiology at the Harvard School of Public Health in Boston.

Smoking is still the leading preventable cause of death in the United States. Not only does tobacco smoke cause lung cancer, it is also implicated in heart disease, other cancers and respiratory diseases.

According to the World Health Organization, an estimated 3 million people in industrialized countries will have died as a result of tobacco use by 2030, and an additional 7 million people in developing countries face the same fate.

This research is a continued follow-up on the Nurses' Health Study, a large trial involving more than 100,000 women. Scientists now have 22 years of data on the participants.

Current smokers had almost triple the risk of overall death compared with women who had never smoked.

Current smokers also had a 63 percent increased risk for colon cancer compared with never-smokers, while former smokers had a 23 percent increased risk. There was no significant association between smoking and ovarian cancer.

And women who started smoking earlier in life were at a higher risk for overall mortality, of dying from respiratory disease and from any smoking-related disease.

However, a smoker's overall risk of dying returned to the level of a never-smoker 20 years after quitting. The overall risk declined 13 percent within the first five years of abstaining.

Most of the excess risk of dying from coronary heart disease vanished within five years of quitting.

For chronic obstructive pulmonary disease, the return to normal took more than 20 years, although there was a 13 percent reduction in the risk of death seen within five to 10 years after quitting.

And the risk for lung cancer didn't return to normal for 30 years after quitting, although there was a 21 percent reduction in risk within the first five years compared with women who continued to smoke.

Many previous studies on tobacco use had focused on men and on lung cancer, the authors stated. They also only looked at smoking status at the beginning of the study. "We got smoking information every two years, so we feel we have a more accurate estimate of current and past smoking," Kenfield said. "We saw increased risks for current smokers [than previous studies], and we think that's because we know who the current smokers are."

"This shows the power of quitting smoking," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "We've known this for a number of years, but the beauty of this study is it is a very large and well-studied group of people. When I tell people to quit smoking, I say the effect of the heart precedes that of the lungs. If you've smoked, you need to be cognizant that you're still at an increased risk of lung cancer."

Natural family planning method is as effective as contraceptive pill

The symptothermal method (STM) is a form of natural family planning (NFP) that enables couples to identify accurately the time of the woman’s fertile phase by measuring her temperature and observing cervical secretions. In the largest, prospective study of STM, the researchers found that if the couples then either abstained from sex or used a barrier method during the fertile period, the rate of unplanned pregnancies per year was 0.4% and 0.6% respectively. Out of all the 900 women who took part in the study, including those who had unprotected sex during their fertile period, 1.8 per 100 became unintentionally pregnant.

The lead author of the report, Petra Frank-Herrmann, assistant professor and managing director of the natural fertility section in the Department of Gynaecological Endocrinology at the University of Heidelberg, Germany, said: “For a contraceptive method to be rated as highly efficient as the hormonal pill, there should be less than one pregnancy per 100 women per year when the method is used correctly. The pregnancy rate for women who used the STM method correctly in our study was 0.4%, which can be interpreted as one pregnancy occurring per 250 women per year. Therefore, we maintain that the effectiveness of STM is comparable to the effectiveness of modern contraceptive methods such as oral contraceptives, and is an effective and acceptable method of family planning.”

A number of fertility awareness based (FAB) methods of family planning have been advocated over the years, but comparisons between different methods and studies of their effectiveness have been limited and hampered by problems such as differences in cultural backgrounds, different ways to measure the effectiveness of a FAB method, different ways of classifying unintended pregnancies and other methodological problems.

“To be able to make an informed choice when selecting a family planning method, couples need to know the efficacy of a method when used both perfectly and imperfectly,” said Prof Frank-Herrmann. “We believe that this is a significant prospective cohort study that clearly defines STM and perfect and imperfect use, and which defines intended and unintended pregnancies, classifying them according to the couples’ intentions before conception.”

The researchers selected data from a cohort of 900 women who were part of a much larger study of 1,599 women using STM, which was conducted by the German Natural Family Planning study centre between 1985 and 2005. The 900 women provided data on 17,638 cycles to Prof Frank-Herrmann and her colleagues.

STM identifies the beginning and end of a woman’s fertile period using two measurements (body temperature and cervical secretions) in order to have a double-check system. The first fertile day is when the woman first identifies either: 1) first appearance or change of appearance of cervical secretion, or 2) the sixth day of the cycle. After 12 cycles, this second guideline is replaced by a calculation that subtracts seven days from the earliest day to show a temperature rise in the preceding 12 cycles, in order to identify the first fertile day. The woman is then in her fertile period. The fertile phase ends after the woman has identified: 1) the evening of the third day after the cervical secretion peak day, and 2) the evening when the woman measures the third higher temperature reading, with all three being higher than the previous six readings and the last one being 0.2 degrees C higher than the previous six.

Prof Frank-Herrmann said: “The women or couples who want to learn the method have to buy a book, or attend an NFP course, or get some teaching by a qualified NFP teacher. Learning STM is usually no problem. There are precise rules that work. However, in contrast to the oral contraceptive pill or other family planning methods, STM needs more engagement and time to learn it.”

Every month the women in the study sent charts to the researchers that showed their cycles, their observations of temperature and cervical secretions, and that recorded their sexual behaviour and family planning intentions for the next cycle.

Of the 900 women, 322 used only STM and 509 women used STM with occasional barriers during the fertile time. Sixty-nine women did not document their sexual behaviour. Out of the women who documented their sexual behaviour and abstained from sex during their fertile period (“perfect use”) the unintended pregnancy rate was 0.4 per 100 women and 13 cycles [2], and 0.6 for women who used STM plus a barrier if they had sex during their fertile period. For cycles in which couples had unprotected sex during the fertile phase, the pregnancy rates rose to 7.5 per 100 women and 13 cycles. The drop-out rate from using STM for reasons such as dissatisfaction or difficulties with the method was 9.2 per 100 women and 13 cycles, and compared well with the drop-out rates from other methods of family planning, which can be as high as 30%, although direct comparisons are difficult due to methodological problems. “This demonstrates a fairly good acceptability for this particular FAB method,” said Prof Frank-Herrmann.

The authors were surprised by the relatively low rate of unintended pregnancies (7.5%) among women who had unprotected sex during their fertile period. “If people are trying for pregnancy you expect a pregnancy rate of 28% per cycle,” said Prof Frank-Herrmann. “Therefore, we think that some of the couples were practising conscious, intelligent risk-taking, and were having no unprotected sex during the few highly fertile days, but had unprotected intercourse on the days at the margins of the fertile time when the risk of pregnancy was lower.”

Some studies have suggested that women’s libido is higher during their fertile period, and this could be one of the reasons why NFP methods traditionally have had a reputation for being less effective than other methods of family planning. However, Prof Frank-Herrmann said: “There are studies that suggest that this is only the case for a small proportion of women, and that, in fact, women also identify other parts of their cycle with increased sexual desire. Most women who use FAB do not find this a problem. It’s possible that the increased libido may be one of the reasons that some of the couples in our study used a barrier, such as a condom, in the fertile phase.

“This is the first time that a large, prospective STM database has been established with sufficient detailed information on sexual behaviour. It enables the true method effectiveness for STM to be calculated and we found this was 0.4% per year when there was no intercourse during the fertile phase. The user-effectiveness of STM, in other words the total number of unintended pregnancies that were due to both method and user failure, was 1.8% after 13 cycles of use, and this compares very well with results from other European studies of FAB methods of family planning. The markedly good user-effectiveness rate may be explained partly by the motivation of the couples and their teachers who agreed to participate in the study,” she concluded.

Magnesium sulfate side effects nifedipine as tocolytic

Their findings suggest that, since the effectiveness of the two drugs appears similar, physicians should consider side effects more strongly when choosing which drug to prescribe.

Newborns whose mothers had received magnesium sulfate were also more likely to be admitted to the neonatal intensive care unit than those whose mothers had received the alternative treatment, although the data do not offer an explanation for this finding and more research needs to be conducted to rule out other causes. What is clear is that currently available treatments for preterm labor are far from perfect.

"There is no free lunch with any of these drugs," said Deirdre Lyell, MD, a specialist in high-risk obstetrics at the hospital's Johnson Center for Pregnancy and Newborn Services. "But magnesium sulfate has some particularly unpleasant side effects, including vomiting, lethargy and blurry vision. The alternative treatment, nifedipine, often leaves women feeling better."

Side effects are particularly important for women struggling with the risk of premature birth and the rapid medical decisions that might need to be made about the care of their newborn. Lyell, assistant professor of obstetrics and gynecology at the medical school, and Yasser El-Sayed, MD, associate professor of obstetrics and gynecology at the medical school, are the lead and senior authors respectively of the research, which will be published in the July issue of Obstetrics & Gynecology. The study is the largest multicenter trial that randomized the use of the preterm labor drugs to compare outcome.

Preterm labor is defined as labor before 37 weeks' gestation. Although it's not always possible to prevent premature birth, physicians strive to delay delivery for at least 48 hours. The extra time allows a doctor to arrange to transfer the woman to a medical facility experienced in treating premature infants and helps maximize the effectiveness of steroids used to help the fetus to prepare for the harsh outside world.

Magnesium sulfate, nifedipine and other preterm labor treatments, called tocolytics, are thought to work by relaxing overactive uterine muscles and halting ongoing cervical changes that may lead to delivery. But it's not been clear if one is better than the others. Force of habit has dictated the use of magnesium sulfate by many physicians in the absence of a compelling reason to choose an alternative.

Lyell and El-Sayed and their collaborators randomly assigned 192 patients at Packard Children's or Santa Clara Valley Medical Center who were in preterm labor to receive either magnesium sulfate, which is an intravenous treatment, or nifedipine, an oral treatment. They found that magnesium sulfate was more effective in achieving the study's primary outcome - preventing delivery for 48 hours with uterine quiescence. But there were no significant differences in the treatments' ability to delay delivery, in the gestational age of the newborn or in the birth weight of the infants. The researchers speculate that this seeming contradiction could be explained if nifedipine, rather than stopping a woman's contractions, simply renders them clinically ineffective.

However, two-thirds of the women who received magnesium sulfate experienced mild to severe side effects such as shortness of breath and fluid build-up in the lungs during the treatment. In contrast, one-third of the women who received nifedipine experienced side effects of the treatment, including headaches. Nifedipine is commonly used to treat high blood pressure and heart disease.

"The take-home message is that we saw no differences in relevant outcomes between the two groups," said Lyell, "but there was a significant difference in the side effects experienced by the women, and some of these were very serious."

Lyell and El-Sayed emphasized that magnesium sulfate is still an appropriate treatment for preterm labor. It continues to be used regularly both at Packard Children's and Santa Clara Valley Medical Center. But they believe it may be time for physicians to give more weight to expected side effects when considering what to try first.

"It's been my experience that women who have had magnesium sulfate remember it; they don't like it," said Lyell. "Those who receive nifedipine don't feel as bad. These drugs are prescribed under what are already very difficult circumstances for the patients, and side effects are very important to them."