UroToday – The incontinent patient is evaluated in order to make a presumptive diagnosis so that treatment can be offered. The evaluation begins with a history and a physical examination. The history focuses on the description of the patient’s incontinence.

Although the history may define the patient’s problem it may be misleading. Urge incontinence may be triggered by activities such as coughing so that by history the patient would seem to have stress incontinence. A patient who only complains of urge may also have stress incontinence. Mixed incontinence is very common with at least 65% of patients with stress incontinence having associated urgency or urge incontinence. It may be impossible to determine by history alone which is the more significant problem. Assessing the patient’s bother and determining their expectations of treatment may further guide how aggressive one needs to be both with the evaluation and the presentation of treatment options.

The important parts of the physical exam are an examination of the abdomen and pelvis including a provocative stress test. If the test is done supine and there is no leakage it should be repeated standing, as this will increase the patient’s abdominal pressure. A urinalysis and a post-void residual (PVR) should be performed in all incontinent patients.

Incontinence questionnaires, voiding diaries, and pad weight tests can provide more objective data than the history alone. Upper tract imaging is indicated in the patient with a history of hematuria and in patients with suspected hydroureteronephrosis. Other imaging may be useful to further evaluate other suspected pelvic pathology. Urodynamics are performed to determine if the incontinence is due to bladder or urethral dysfunction or both, to assess if the patient has a storage or emptying problem and lastly in an effort to identify patients whose upper tracts are at risk due to high bladder storage pressures.

The most common abnormality of bladder function is detrusor over activity that causes urge incontinence. Detrusor over activity is defined as the inability to suppress involuntary detrusor contractions during filling.1 A cystometrogram may fail to demonstrate any detrusor over activity in a patient who has urge incontinence by history. Any patients with symptoms of urge incontinence by history should be presumed to have urge incontinence. The purpose of urodynamics is not to diagnose detrusor over activity but to examine compliance, to diagnose stress incontinence, to rule out obstruction as a cause of either overflow or urge incontinence and to insure that the patient has a reasonable, safe, bladder capacity.

The diagnosis of stress incontinence is best made with measurement of the abdominal pressure required to induce urinary loss, the Valsalva or abdominal leak point pressure and, or fluoroscopy. Stress incontinence is diagnosed if there is urethral loss of urine associated with an elevation of abdominal pressure. Valsalva leak point pressure (VLPP) is used to diagnose stress incontinence since it is abdominal pressure that is the expulsive force in stress incontinence. Measurement of the VLPP allows for quantification of the degree of urethral dysfunction. A normal urethra will not leak at any pressure. A mobile urethra will leak at high abdominal pressures (>120 cm H2O) and a poorly functioning intrinsic sphincter will leak at low pressures (

UroToday – Botulinum toxin (BTX) is used therapeutically for several disorders associated with excessive muscular contractions including focal dystonias. Recently BTX has been successfully used for the treatment of disorders of the gastrointestinal and urinary tracts. Nevertheless, controversy exists regarding safety of this treatment.
Several studies reported autonomic effects of BTX, particularly of BTX B used to treat cervical dystonia, including dry mouth, blurred vision, lightheadedness and constipation.(1,2,3)

In the present study intraprostatic injection of BTX A has been successfully used to reduce voiding dysfunction in 77 patients with Benign Prostatic Hyperplasia (BPH).

In another clinical experience, seven patients, all of whom reported no symptomatic improvement with BTX A treatment, have been treated using intraprostatic injection of BTX B (NeuroBloc, Elan, Ireland) with the same technique, in order to avoid the risk of resistance to BTX A and to obtain long-lasting results. The NeuroBloc equivalent was determined by multiplying by 50 the dose as Botox units, so 10000 U of BTX B were used.

Two months after injections, AUA score decreased from 23.6 В±1.7 to 12.3 В±2 points (P =0.00001), serum PSA from 4.1 В±0.6 to 2.0 В±0.8 ng per ml (P =0.0004), prostatic volume from 47.8 В±9.8 to 26.1 В±6.0 ml (P =0.0009), and residual volume from 76 В±26 to 47 В±7.6 ml (P =0.02). At the same time, mean peak urinary flow rate increased from 9.4 В±3.0 to 14.4 В±0.7 ml per second (P =0.002). Two of the seven patients (40%) experienced erectile dysfunction and dry mouth.

Furthermore, to investigate cardiovascular autonomic effects of BTX A, we have studied six patients, from 22 to 62 years old, without detectable cardiovascular or autonomic diseases, treated with 150 units (0.75 ml) of BTX A (Dysport, Ipsen SpA, Milan, Italy) for chronic anal fissure. We have utilized the Ewing protocol at baseline (before treatment) and repeated the tests within 96 hours and within 30 days after treatment with BTX. The Ewing protocol, including measurement of heart rate changes during deep breathing, Valsalva maneuver and standing up; blood-pressure measurement during handgrip and during standing up, have been developed to assess the autonomic control of cardiovascular system and to diagnose autonomic neuropathy. To class the severity of damage of ANS, a score (0 = normal response; 1 = borderline; 2 = abnormal) is given to each test. The final score can change from 0/10-1/10 (normal pattern), to 2/10-4/10 (borderline pattern), to 5/10-10/10 (abnormal pattern). None of the patients had worsening of test scores after toxin injections. In particular, before treatment a borderline pattern (2/10 score) was found in 4 patients. At 96-hour evaluation, a borderline pattern (2/10 score) was found in 1 patient. At 30 days evaluation, all patients who had previously reported abnormal score no longer had such scores, and a normal pattern (0/10) was found in all treated patients.

In these clinical trials BTX did not produce any serious cardiovascular adverse events. Besides, BTX B caused significant decrease of saliva production and erectile dysfunction in 40% of patients. According to our results, in a recent double blind randomized trial BTX A and B were compared in the treatment of 20 patients with cervical dystonia; patients treated with BTX B showed dry mouth and greater severity of chronic constipation in absence of severe autonomic dysfunctions in each group of patients. (3)

Although BTX B affects neuromuscular cholinergic synapses, its clinical effects on autonomic cholinergic synapses are considerably stronger, as reflected by the adverse events reported. It is unclear whether this reflects either a relatively higher affinity of BTX B, as compared to BTX A, for autonomic synapses, or the observation that doses of BTX B for production of neuromuscular effects in humans are several-fold higher than those of toxin A, such that at therapeutic neuromuscular doses, autonomic synapses are stimulated by BTX B. However, in our patients it seems conceivable that erectile dysfunction and dry mouth may represent, respectively, a local diffusion to autonomic targets and a systemic effect. Therefore, given its side effect profile, BTX B should be used carefully in patients with pre-existing autonomic dysfunction, other anticholinergic treatment, or conditions in which anticholinergics are contraindicated.

References:

1. Tintner R, Gross R, Winzer UF, Smalky KA, Jankovic J. Autonomic function after botulinum toxin type A or B: A double blind, randomized trial. Neurology 2005; 65: 765-767
2. Jankovich J. Treatment of cervical dystonia with botulinum toxin. Mov Disord 2004;19: S109-115
3. DresslerD, Benecke R. Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperidrosis. Eur Neurol 2003; 49: 34-38

Giuseppe Brisinda, MD, Federica Cadeddu, MD, and Giorgio Maria MD as part of Beyond the Abstract on UroToday

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice.

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Copyright © 2008 – UroToday

Corresponding Author
Giuseppe Brisinda
Department of Surgery
Catholic School of Medicine
University Hospital “Agostino Gemelli”
Largo Agostino Gemelli 8
00168 Rome (Italy)

View drug information on Botox.

The House Energy and Commerce Committee on Wednesday approved a number of health care-related bills, CQ Today reports. The committee approved:
A bill (HR 758) that would prohibit insurance companies from limiting hospital stays to less than 48 hours for patients who have had a mastectomy or breast-conserving surgery and less than 24 hours for patients who have had lymph node dissection for the treatment of cancer. The committee also approved an amendment that would prohibit insurers from discontinuing coverage if a plan member unintentionally failed to disclose information on an insurance application about an unrelated condition;

A measure (HR 1014) that would require new drug applications submitted to FDA to include specific data on the drug’s effect by gender, age and race. The measure also would create a campaign to educate women older than age 65 about cardiovascular health. An amendment to the bill would provide $204.4 million over five years to reauthorize a chronic disease risk factor screening program for uninsured and underinsured women ages 40 to 64;

Legislation (HR 1532) that would create a nationwide initiative to eradicate tuberculosis through new medications and public health programs;

A bill (HR 2583) that would provide $44.2 million from fiscal year 2010 to FY 2014 to establish a loan program for public and not-for-profit hospitals to create residency training programs for physicians. Under the bill, preference would be given to rural areas;

Legislation (HR 2994) that would encourage physicians and hospitals to improve pain management;

A measure (HR 5265) that would encourage research on muscular dystrophy treatment and increase data collection about the disease by government health agencies;

A bill (HR 6469) that would authorize a $5 million increase for the Organ Procurement and Transplantation Network to $7 million per year;

A bill (HR 6353) that would prohibit online pharmacies from dispensing prescriptions in most cases to patients who have not been seen in person by the prescribing physician;

Legislation (HR 5265) that would encourage research on muscular dystrophy treatment and increase data collection about the disease by government health agencies; and

A bill (S 1760) that would provide $120 million annually between FY 2008 and FY 2013 to reauthorize the Healthy Start program, which provides grants to communities with higher infant mortality rates (Teitelbaum/Armstrong, CQ Today, 9/17).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

A 30 percent increase in chronic kidney disease over the past decade has prompted the U.S. Renal Data System (USRDS) to issue for the first time a separate report documenting the magnitude of the disease, which affects an estimated 27 million Americans and accounts for more than 24 percent of Medicare costs. The USRDS is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). The USRDS 2008 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease, is online at usrds/.

“NIDDK’s annual analysis and publication of data on kidney disease in the United States is essential in quantifying public health trends, guiding funding priorities, and designing targeted kidney research programs,” said NIH Director Elias A. Zerhouni, M.D. “The major focus on chronic kidney disease in this year’s report acknowledges that this disorder is a growing public health issue deserving of wider public awareness and intensified scientific investigation.”

Using data from multiple sources, the USRDS has created a new handbook of information that can be used by researchers, government officials, health program planners, and others to develop research goals, assess public health needs, set program priorities, and inform policymakers and the public. USRDS research depends on collaborations with other agencies of the U.S. Department of Health and Human Services, especially the Centers for Medicare and Medicaid Services, the Health Resources and Services Administration, and the Centers for Disease Control and Prevention. Patient registries for other countries also contribute data for analyses.

Volume One of the report defines the disease burden of chronic kidney disease and examines cardiovascular and other related health problems, rates of adverse health events, preventive care, prescription medication therapies, delivery of care in the transition to end-stage renal disease, and the cost to Medicare and employer group health plans.

One of the major findings central to public health is that those with chronic kidney disease are more likely to die from cardiovascular disease than to reach end-stage kidney disease. However, cardiovascular risk factors can be detected and treated. This suggests that those transitioning from chronic to end-stage kidney disease merit more attention. Expenditures during the transition from chronic to end-stage kidney disease are considerable, ranging from $14,500 for Medicare patients to $29,000 for those covered by employer group health plans in the month of dialysis initiation.

“These latest data on kidney disease underscore the importance of the research we fund,” said NIDDK Director Griffin P. Rodgers, M.D. “With rising rates of chronic and end-stage kidney disease, we need to stimulate research that will help us discover new, effective therapies for these devastating disorders.”

Volume Two reports that the number of people with end-stage kidney disease is increasing in size and cost. The incidence of chronic kidney disease in 2006 was more than 100,000, or 360 per one million people, an increase of 3.4 percent over the 2005 incidence rate. There were more than half a million patients with end-stage kidney disease in 2006. Of these, 70 percent were on dialysis. An important step before a patient begins dialysis is the preparation of a vascular access, which is the site on the patient’s body where blood is removed and returned during dialysis.

The three types of vascular access for dialysis are arteriovenous (AV) fistula, an AV graft, and a venous catheter. Both the fistula and the graft involve connecting an artery to a vein, usually beneath the skin in a patient’s arm. The fistula is considered the best long-term vascular access for dialysis. The catheter is a tube inserted into a vein in the patient’s neck, chest, or leg near the groin. It is usually only used as a temporary access until a permanent fistula or graft can be developed. This volume reports that more than 80 percent of new dialysis patients started with a catheter, more than 50 percent of current dialysis patients had a fistula, and 30 percent had a graft. Click here for more information on vascular access.

Volume Two also reports that Medicare paid about $70,000 per dialysis patient. Patients with end-stage kidney disease accounted for a little more than 1 percent of the Medicare population and more than 7 percent of Medicare costs. Total cost for end-stage kidney disease was $33.6 billion. This number includes Medicare spending and all expenditures by other payers, such as employer group health plans.

In addition, more than 18,000 kidney transplants were performed in 2006, an increase of 3.5 percent over 2005. Use of deceased donor kidneys increased between 2003 and 2006 at a rate of about 6 percent to 7 percent. Use of living donors fell 3 percent during that period, but the use of living unrelated donors continues to increase relative to the total number of living donations, and now accounts for 45 percent of all living donor transplantations. Click here for more information on kidney transplantation.

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NIDDK conducts and supports research in diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic, and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. For more information about NIDDK and its programs, see niddk.nih.

The National Institutes of Health (NIH) – The Nation’s Medical Research Agency – includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.

Source: Arthur Stone

NIH/National Institute of Diabetes and Digestive and Kidney Diseases

For the first time, researchers at Brigham and Women’s Hospital (BWH) have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including bronchioles, alveoli and pulmonary vessels. This research is published in the May 12, 2011 issue of the New England Journal of Medicine.

“This research describes, for the first time, a true human lung stem cell. The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung,” said Piero Anversa, MD, director of the Center for Regenerative Medicine at Brigham and Women’s Hospital and corresponding author.

Using lung tissue from surgical samples, researchers identified and isolated the human lung stem cell and tested the functionality of the stem cell both in vitro and in vivo. Once the stem cell was isolated, researchers demonstrated in vitro that the cell was capable of dividing both into new stem cells and also into cells that would grow into various types of lung tissue. Next, researchers injected the stem cell into mice with damaged lungs. The injected stem cells differentiated into new bronchioles, alveoli and pulmonary vessel cells which not only formed new lung tissue, but also integrated structurally to the existing lung tissue in the mice.

The researchers define this cell as truly “stem” because it fulfills the three categories necessary to fall under stem cell categorization: first, the cell renews itself; second, it forms into many different types of lung cells; and third, it is transmissible, meaning that after a mouse was injected with the stem cells and responded by generating new tissue, researchers were then able to isolate the stem cell in the treated mouse, and use that cell in a new mouse with the same results.

“These are the critical first steps in developing clinical treatments for those with lung disease for which no therapies exist. Further research is needed, but we are excited about the impact this discovery could have on our ability to regenerate or recreate new lung tissues to replace damaged areas of the lungs,” said Joseph Loscalzo, MD, PhD, chair of the Department of Medicine at BWH and co-author.

This research was funded through grants from the National Institutes of Health (NIH).

Source:
Lori J. Shanks
Brigham and Women’s Hospital

EB Brands, of Yonkers, New York, is recalling three million fitness balls because they may burst while being used if they are overinflated, according to the US Consumer Product Safety Commission. EB Brands stresses that this is a voluntary recall.

According to EB Brands, 47 reports have so far come in of their fitness balls suddenly bursting while in use – reports include a fracture, and multiple bruises.
The EB Brands fitness balls being recalled are:

Bally Total Fitness
Everlast
Valeo
Body Fit Fitness Balls

EB Brands says this recall involves rubber fitness balls with diameter sizes of 55cm, 65cm and 75cm. They were sold with a pump and inflation instructions. They came in various colors and had the Bally Total Fitness, Everlast, or Valeo logo printed on them.

The balls were sold at retail outlets throughout the USA from May 2000 through to February 2009, and were sold for between $15 and $30. They were manufactured in China.
What you should do if you have one of these fitness balls
You should contact EB Brands and ask for a new copy of instructions which has updated details on how to safely inflate the ball. Contact EB Brands at (800) 624-5671 between 9 a.m. and 5 p.m. ET Monday through Friday.

New instructions on how to inflate the ball.

Lawmakers on Tuesday “explicitly ruled out” the possibility of enacting President Obama’s proposal to have private insurers cover the costs of combat-related injuries for veterans, the Washington Post reports (Scott Tyson, Washington Post, 3/18). Under the policy, which is included in Obama’s fiscal year 2010 budget proposal, the Department of Veterans Affairs would bill health insurers for treatment of injuries and conditions sustained as a result of veterans’ military service. Currently, VA covers those costs and bills health insurers only for treatment for conditions unrelated to veterans’ military service (Kaiser Daily Health Policy Report, 3/10). VA estimates the plan could save the agency $530 million annually in health care costs (Washington Post, 3/18).

The plan has received “little if any support on Capitol Hill,” the Washington Times reports. Senate Committee on Veterans’ Affairs Chair Daniel Akaka (D-Hawaii) said his panel would not develop or move legislation that would shift the cost of veterans’ health care away from VA to the private sector. Akaka said, “VA’s sacred duty is to care for veterans injured in honorable service to our nation, and the department should not turn to wounded warriors’ private insurance to pay for combat injures” (Lengell, Washington Times, 3/18). House Committee on Veterans’ Affairs Chair Bob Filner (D-Calif.) said that the proposal “to charge ‘third-party’ insurance companies for service-connected medical treatment will not be taken up. … (The) budget cannot be balanced on the backs (or legs, or kidneys or hearts) of our nation’s combat-wounded heroes” (Johnson, CQ Today, 3/17). Several other lawmakers have said the plan would be “dead on arrival” (Goldstein, Kansas City Star, 3/18).

Talks
Veterans groups have expressed concerns that the plan would cause insurers to increase premiums, and that veterans with severe injuries could reach their maximum coverage limits, leaving themselves and their families without any coverage benefits, the Times reports (Washington Times, 3/18). They also said that civilian employers could be disinclined to hire veterans because of concerns that they would drive up insurance rates. American Legion Commander David Rehbein said that during meetings with the groups on Tuesday, “It became apparent … that the president intends to move forward with this unreasonable plan.” He added that Obama “refused to hear arguments about the moral and government-avowed obligations that would be compromised by it.” More discussions between veterans groups and the administration will be held Thursday (CQ Today, 3/17).

White House Press Secretary Robert Gibbs said the administration has not made its “final … decision on third-party billing as it relates to service-related injuries.” He noted that Obama is seeking to increase VA discretionary spending by 11% as part of his budget. According to Gibbs, “This president takes very seriously the needs of our wounded warriors that have given so much to protect our freedom on battlefields throughout the world” (Washington Post, 3/18).

Opinion Pieces
Paul Rieckhoff, New York Post: Obama’s plan “forsakes a sacred promise to our veterans — the promise that we will care for them in return for their service,” Rieckhoff, executive director of Iraq and Afghanistan Veterans of America, writes in a New York Post opinion piece. He states that the Obama administration “may see this third-party-billing idea as a big cost-saver,” but “while we are all concerned about the economy, we cannot shift the burden to our veterans.” Rieckhoff concludes, “This country founded the VA to care for those who served and sacrificed, and we must ensure that it continues to fulfill that duty. The nation can’t go back on its commitment to its warriors and their families” (Rieckhoff, New York Post, 3/18).

David Rehbein, Wall Street Journal: Obama’s attempt to “unfairly generate $540 million on the backs of veterans” would “have an adverse impact on service-connected disabled veterans and their families,” Rehbein writes in a Journal opinion piece. He adds, “This plan is as unfair as it is unnecessary,” as “it is the president and Congress who send troops in harm’s way, not the CEO of BlueCross BlueShield.” The American Legion has “long advocated for Medicare to reimburse the VA for its treatment of Medicare-eligible veterans,” according to Rehbein. He continues, “Veterans pay into the Medicare system, yet they are unable to use Medicare benefits in the VA health system, which was created specifically for them,” adding, “We also believe that direct billing between two federal agencies will reduce the opportunities for waste, fraud and abuse that tend to occur when for-profit corporations enter the mix” (Rehbein, Wall Street Journal, 3/18).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

© 2009 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

In a disease like ALS – one that’s always fatal and that has a long history of research-resistant biology – finding a proof of principle in animal models is significant.

This week, Johns Hopkins researchers report that transplanting a new line of stem cell-like cells into rat models of the disease clearly shifts key signs of neurodegenerative disease in general and ALS in particular – slowing the animals’ neuron loss and extending life.

The new work supports the hypothesis that artificially outnumbering unhealthy cells with healthy ones in targeted parts of the spinal cord preserves limb strength and breathing and can increase survival.

An account of the work appears online this week in Nature Neuroscience.

Two parts of the study hold special interest: One is that the target area for the added cells – parts of the cervical spinal cord that control the diaphragm muscles largely responsible for breathing – reap the most benefit. Forty-seven percent more motor neurons survived there than in untreated model animals. Respiratory failure from diaphragm weakness is the usual cause of death in ALS, also called Lou Gehrig’s disease.

“While the added cells, in the long run, didn’t save all of the nerves to the diaphragm, they did maintain its nerve’s ability to function and stave off death significantly longer,” says neuroscientist Nicholas Maragakis, M.D., an associate professor of neurology at Johns Hopkins who led the research team.

“We intentionally targeted the motor neurons in this region,” he says, “since we knew that, as in ALS, their death results in respiratory decline.”

Also significant is that the transplanted cells, called glial restricted precursors (GRPs), address a well-known flaw in people with ALS and in its animal models. Both humans and models are stunted in their ability to clear away the neurotransmitter glutamate. And excess glutamate – common in ALS – overstimulates the motor neurons that spark muscle movement, causing death. The event, called excitotoxicity, also occurs in other neurological diseases.

So on a more basic level, the study adds clout to the principle – in live animals – that excitotoxicity is a major bad guy in ALS and that finding more effective ways to avoid or lessen it could help protect the nervous system.

In their research, the team transplanted some 900,000 glial restricted precursors overall to specific sites in the cervical spinal cord of each model rat in early stages of disease. The GRPs the scientists used began life as what’s called astrocyte progenitor cells from healthy rat spinal cord tissue. Following transplant, they transformed into mature, healthy astrocytes, found living alongside sick motor neurons.

Astrocytes are the most common cells in the central nervous system. Work at Johns Hopkins and elsewhere has shown their crucial role in keeping the CNS in healthy balance. Not only are the cells studded with transporter molecules that mop up glutamate; they also maintain proper ion levels and nutrient support of nerve cells.

The study showed that at least a third of the added GRPs “took root” after their transplantation. With time, almost 90 percent of the GRPs had differentiated into astrocytes. Unlike the model rats’ own astrocytes, the new ones continued to appear healthy. None of the GRPs damaged the spinal cord or formed tumors – a worry with some stem cell therapies.

Transplanting alternate GRPs – those that the team engineered to lack glutamate transporters – offered none of the protective properties.

“Our findings demonstrate that astrocyte replacement, by transplantation, is both possible and useful,” Maragakis explains. “This targeted cell delivery to the cervical spinal cord is a promising strategy to slow that loss of motor neurons in ALS. We hope at some point that these principles will translate to the clinic.”

Earlier research by U.S. scientists suggests that, while astrocytes go downhill in ALS, they may not be a primary cause of the disease. The idea is more that they’re involved in its progression. Diseased astrocytes, studies show, may make motor neurons more susceptible to death by excitotoxicity.

###

Amyotrophic lateral sclerosis (ALS) is a motor neuron disorder that affects roughly 30,000 people in this country. It’s characterized by a rapid decline in motor neurons, with death from respiratory failure typically occurring from two to five years after diagnosis.

Principal researchers in this study are members of the Robert Packard Center for ALS Research at Johns Hopkins, which funded the work along with grants from the ALS Association and the National Institutes of Health.

The research team included Angelo Lepore, Britta Rauck, Christine Dejea, Andrea Pardo and Jeffrey Rothstein, all of Johns Hopkins, and Mahendra Rao with the Invitrogen Corp., of Carlsbad, Calif.

On the Web: alscenter/

Source: Maryalice Yakutchik

Johns Hopkins Medical Institutions

March is designated National Kidney Month to mark the growing impact of kidney disease on public health. National Kidney Foundation data suggest that more than 26 million Americans have kidney disease, a 30 percent increase over the past decade.

Most people are born with two kidneys. They are bean-shaped, and about the size of a fist. Located on the left and right sides of the spine, just below the rib cage, their main job is to filter extra salt, water and wastes out of the blood and make urine. They also help control blood pressure and make hormones the body needs to stay healthy. Kidney disease occurs when the small blood vessels in the kidneys are damaged, making the kidneys unable to do their job. Waste then builds up in the blood, harming the body.

Early kidney disease has no symptoms. Most people don’t know they have it until their kidneys begin to fail. The only way to tell if you have kidney disease is through simple blood and urine tests. Primary risk factors include diabetes, heart disease, high blood pressure, family history and being over age 60. Secondary risks include obesity, autoimmune diseases, urinary tract infections and systemic infections.

Over the coming years, the rate of kidney disease in the United States is expected to rise because of high obesity rates, the link between obesity, diabetes and high blood pressure and the aging of the Baby Boom generation.

In addition to being one of the top kidney transplant centers in the nation, University of Alabama at Birmingham (UAB) researchers are working on groundbreaking research into chronic kidney disease and acute kidney injury, in an effort to expand the knowledge base in the development, treatment and outcomes for patients with chronic kidney disease and acute kidney injury. This includes:

– UAB is one of eight George M. O’Brien Kidney Research Centers in the country, as designated by the National Institutes of Health, putting UAB at the forefront in the development of new methods to treat and prevent kidney failure. Acute kidney injury, or acute kidney failure, is a rapid loss of renal function due to damage to the kidneys. It develops in 5 to 7 percent of medical-surgical patients, complicates the recovery of 15 to 25 percent of intensive care patients, and can double the length of a patient’s hospital stay. “Despite major advances in renal replacement therapy, the mortality of patients with acute kidney injury has not significantly decreased in the past 30 to 40 years,” said Anupam Agarwal, M.D., director of UAB’s nephrology division and principal investigator of the O’Brien Center grant. “With this center, we hope to gain a better understanding of the reasons acute kidney injury occurs, expand diagnostic abilities, and expand therapeutic and preventative approaches to treating the disease.”

– UAB is performing the largest investigation to understand why the rate of stroke death is significantly higher in the Southeast, and blacks are more likely to die from stroke than whites, the Reasons for Geographic and Racial Differences in Stroke (REGARDS), which is led by George Howard, D.Sc. An ancillary study of the REGARDS project, Renal REGARDS, is being carried out by UAB nephrologist David Warnock, M.D., and colleagues, to see if there are common factors that will associate the risk for developing stroke with the risks for kidney disease. “If you look at the number of strokes per year, per population base, there are about three times more incidents of stroke among blacks. The incidence and severity of kidney disease is clearly greater among blacks than whites in the same population base. Why is that? We are working to find out,” Warnock said. Study results already have shown several things. The most important efforts to date have identified the importance of family history of kidney disease, and the fact that more white subjects have less severe kidney disease than blacks, but blacks seem to have more severe kidney disease.

University of Alabama at Birmingham
701 20th St. S, AB 1320
Birmingham
AL 35294-0113
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uab.edu

A new study from the University of Washington reported obese children are at increased mortality risk in later years following primary liver transplantation (LT). Pediatric patients who are thin or severely thin, experience an early mortality risk within the first year post-LT. Details of the ten-year survival analysis are published in the November issue of Liver Transplantation, a peer-reviewed journal of the American Association for the Study of Liver Diseases (AASLD).

Childhood obesity is a serious public health concern worldwide. According to the World Health Organization (WHO), the prevalence of obesity has been increasing at an alarming rate, with 22 million children under the age of five worldwide who are overweight. In the U.S., the National Center for Health Statistics estimates that 17% of children between the ages of 2 and 19 years old are overweight or obese.

“Controversies exist regarding the mortality of patients undergoing liver transplantation at the extremes of body mass index (BMI), and in pediatric patients weight is typically the only factor considered in survival analysis,” explained lead study author AndrГ© Dick, M.D., from Seattle Children’s Hospital and the University of Washington. “Our study is the largest thus far to report on the impact of pre-transplant BMI on post liver transplant survival in the pediatric population.” Prior studies in adult populations have shown there to be a negative impact on post transplantation survival for LT patients with extreme BMIs.

For the present study, researchers reviewed data from the Organ Procurement and Transplantation Network (OPTN) and found that 7,942 patients less than 18 years of age (who had full BMI data) underwent primary liver transplantation between 1987 and 2007. Using the WHO BMI criteria, the authors categorized patients as severely thin, thin, normal weight, overweight, or obese. During the study period 61% of patients were at normal weight.

Results indicate that children who were thin or severely thin had a significantly lower survival (84%) at one year compared to the survival (89%) of children in the normal and overweight groups. Researchers found no significant difference in survival during the first year after transplantation for obese pediatric patients. However, by the twelfth year following LT, those in the obese group had significantly lower survival (72%) than the survival (77%) of normal weight or overweight pediatric patients.

The authors observed that obesity had a significantly negative impact on pediatric patient survival more than five years after LT. They speculate post metabolic syndrome (PTMS) could contribute to the late morbidity and mortality due to the time it takes to develop long-term obesity-related conditions such as diabetes, hypertension, and hyperlipidemia. Moreover, long-term use of immunosuppressive therapy following transplantation, which while improving patient survival, can exacerbate the effects of PTMS. “Further research is needed to determine the optimal immunosuppressive regimen that will lessen the effects of PTMS,” concluded Dr. Dick. “Pre- and post-transplant identification of malnourished or obese pediatric patients, along with optimization of their modifiable risk factors will help to best use scarce donor organs and maximize patient survival.”

Sources: Wiley – Blackwell, AlphaGalileo Foundation.