Researchers at the University of Pennsylvania School of Medicine have discovered how low-oxygen conditions can worsen chronic kidney disease (CKD). The key player is a protein called hypoxia-inducible-factor (HIF-1) that, as its name suggests, is active when the kidney does not get enough oxygen, a condition known as hypoxia. The findings appear in a December issue of the Journal of Clinical Investigation.

CKD afflicts 20 million Americans who have hypertension, atherosclerosis, diabetes, and other conditions. The kidney has less oxygen reserves than other organs to start, and CKD is associated with less capillary blood flow, reducing oxygenation even further. As CKD progresses, kidneys become full of fibrous tissue and cannot filter wastes out of blood or regulate body salt. Eventually kidney dialysis, a form of renal replacement therapy, may be needed to carry out these processes. Ultimately, the clinical goal is to optimize treatment to halt or delay the progression of CKD by better understanding its molecular underpinnings.

“Fibrosis worsens when the kidney becomes hypoxic,” states lead author Volker Haase, MD, Assistant Professor of Medicine, Renal Electrolyte and Hypertension Division. “We found that HIF-1 is more stable when oxygen is in short supply and that HIF-1 causes kidney epithelial cells to regress to a less-differentiated cell type. This transition is driven by HIF-1, a protein that turns on many genes that promote the synthesis of fibrous connective tissue, thus interfering with the kidney’s normal filtering function,” says Haase.

The study was conducted using mice that had been engineered to turn off expression of HIF-1О± (a critical subunit of HIF-1) in their kidneys. One kidney from each mouse was put under oxygen stress by obstructing the ureter, and the other kidney served as a control. As long as HIF-1a was silenced, fibrosis was reduced in the oxygen-deprived kidney. This demonstrated that HIF-1 promoted the fibrotic process under reduced oxygen conditions.

Kidney biopsies from patients with diabetes who also suffer from CKD were tested for HIF-1О± levels. Normal kidneys had almost no HIF-1О±, whereas kidneys from diabetics had moderate to high expression of HIF-1О±. “This observation, along with increased expression of the genes controlled by HIF-1 in diseased kidneys in mice, shows that HIF-1 is the molecular link between hypoxia and CKD in humans as well as rodents,” says Haase.

The next step is to test other models of CKD and identify additional molecular targets of HIF-1 that can promote fibrosis. “We also hope to study the inflammatory response to hypoxia in the diseased kidney,” concludes Haase. “We already know that some pro-inflammatory proteins are stimulated by hypoxia.”

Some day, it may be possible to use HIF-1 and HIF-regulated genes as molecular markers to identify those patients that are at high risk for rapid progression of CKD requiring dialysis.

This study was carried out by D. F. Higgins PhD, N. Shrimanker BA and Y. Akai, MD- PhD of the University of Pennsylvania; K. Kimura MD, Y. Akai MD, Y. Saito MD and M. Iwano MD of Nara Medical University, Japan; W. M. Bernhardt MD, B. Hohenstein MD and K-U. Eckardt MD of Friedrich-Alexander University, Germany; R. S. Johnson PhD of UCSD; M. Kretzler MD of University of Michigan; and C. D. Cohen MD of University of Munich, Germany. This research was supported by the National Institutes of Health, the University of Pennsylvania Research Foundation, the Penn Center for Molecular Studies in Digestive and Liver Disease, the Ministry of Education and Science of Japan, the American Heart Association and the Deutsche Forschungsgemeinschaft.

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System.

Penn’s School of Medicine is currently ranked #3 in the nation in U.S. News & World Report’s survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation’s first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn.edu

A new study has shown that the use of statins in people aged 60 and over increases the risk of developing Type 2 diabetes by nine per cent. The researchers, however, stressed the risk is low, especially when compared with the beneficial effect that statins have on reducing heart problems.

Life-saving statins

These are the conclusions of a University of Glasgow study involving 91,000 people, published in the medical journal, The Lancet.

Credited with saving thousands of lives each year, statins are currently prescribed only to those at significant risk of a heart attack or stroke. However in recent years, many doctors have been urging that everyone over 50 should receive them.

Risk heavily outweighed by benefits

Stressing that the increased risk only applied to those aged over 60, Director of Research at Diabetes UK, Dr. Iain Frame, said:

“This small increased risk is heavily outweighed by the benefits of statins in those at high risk of heart problems. This research, therefore, should on no account be taken as a reason for those over 60 at high risk of heart disease to stop taking statins.”

Source
Diabetes UK

Neurosurgery researchers at UC Davis Health System have used a new, leading-edge stem cell therapy to promote the growth of bone tissue following the removal of cervical discs — the cushions between the bones in the neck — to relieve chronic, debilitating pain.

The procedure was performed by associate professors of neurosurgery Kee Kim and Rudolph Schrot. It used bone marrow-derived adult stem cells to promote the growth of the bone tissue essential for spinal fusion following surgery, as part of a nationwide, multicenter clinical trial of the therapy.

Removal of the cervical disc relieves pain by eliminating friction between the vertebrae and/or nerve compression. Spinal fusion is used following surgery for degenerative disc disease, where the cushioning cartilage has worn away, leaving bone to rub against bone and herniated discs, where the discs pinch or compress nerves.

“We hope that this investigational procedure eventually will help those who undergo spinal fusion in the back as well as in the neck,” said Kim, who also is chief of spinal neurosurgery at UC Davis. “And the knowledge gained about stem cells also will be applied in the near future to treat without surgery those suffering from back pain.”

Millions of Americans are affected by spine diseases, with approximately 40 percent of all spinal fusion surgery performed for cervical spinal fusion. Some 230,000 patients are candidates for spinal fusion, with the numbers of potential patients increasing by 2 to 3 percent each year as the nation’s population ages.

“This is an exciting clinical trial to test the ability of the bone-forming stem cells from healthy donors to help patients with spinal disease,” said Jan Nolta, director of the UC Davis Institute for Regenerative Cures.

“For the past 50 years, bone marrow-derived stem cells have been used to rebuild patients’ blood-forming systems. We know that subsets of stem cells from the marrow also can robustly build bone. Their use now to promote vertebral fusion is a new and extremely promising area of clinical study,” she said.

The stem cell procedure at UC Davis took place early in August. The patient was a 53-year-old male from the Sacramento region with degenerative disc disease.

In the surgery, called an anterior cervical discectomy, a cervical disc or multiple discs are removed via an incision in the front of the neck. The investigational stem cell therapy then is applied to promote fusion of the vertebrae across the space created by the disc removal.

The stem cells are derived from a healthy single adult donor’s bone marrow, and thus are very homogenous, Kim said. They are grown in culture to high concentration with minimal chance for rejection by the recipient, he said.

Adequate spinal fusion fails to occur in 8 to 35 percent or more of patients, and persistent pain occurs in up to 60 percent of patients with fusion failure, which often necessitates additional surgery.

“A lack of effective new bone growth after spine fusion surgery can be a significant problem, especially in surgeries involving multiple spinal segments,” said Schrot, co-principal investigator for the study. “This new technology may help patients grow new bone, and it avoids harvesting a bone graft from the patient’s own hip or using bone from a deceased donor.”

Current methods of promoting spinal fusion include implanting bone tissue from the patient’s hip or a cadaver to encourage bone regrowth as well as implanting bone growth-inducing proteins. However, the Food and Drug Administration has not approved the use of bone morphogenetic proteins for cervical spinal fusion. Their use has been associated with life-threatening complications, particularly in the neck.

The leading-edge stem cell procedure is part of a prospective, randomized, single-blinded controlled study to evaluate the safety and preliminary efficacy of an investigational therapy: modified bone marrow-derived stem cells combined with the use of a delivery device as an alternative to promote and maintain spinal fusion.

The study includes 10 investigational centers nationwide. The UC Davis Department of Neurological Surgery anticipates enrolling up to 10 study participants who will be treated with the stem cell therapy and followed for 36 months after their surgeries. A total of 24 participants will be enrolled nationwide.

The study is one of several clinical trials under way in the UC Davis Spine Center and led by Kim. He anticipates launching a clinical trial soon to study the safety of injecting stem cells into disc tissue to repair degenerated discs.

The current study is sponsored by Mesoblast, Ltd., of Melbourne, Australia, which is developing adult universal-donor stem cell products built upon the discovery of adult-derived mesenchymal precursor cells. Kim and Schrot will not be compensated for their participation in the study.

Did you know that there are more dog owners than cat owners in America, but more cats than dogs in those homes? According to the 2007 “U.S. Pet Ownership and Demographic Sourcebook” (Sourcebook) published by the American Veterinary Medical Association (AVMA) there are 43 million dog owning households compared with 37.5 million cat owning households, but 81.7 million cats compared to 72 million dogs. Not surprisingly, women were the primary caregivers to most of them. About 64% of pet-owning households owned more than one pet, and all pet owners spent a total of $24.5 billion on veterinary care in 2006. These are just a few of the fascinating facts offered up about owners, pets, and veterinary medicine in the latest edition of the Sourcebook, which is published every five years.

“Veterinarians aren’t the only ones who will find this data interesting. People involved in every aspect of the pet industry, veterinary medicine and the general public will find facts and figures in this study that interest them. In fact, the data is considered so important that even the U.S. Census Bureau cites our statistics,” said Dr. Gregory S. Hammer, president of the AVMA.

“The Sourcebook is the most complete source of data and analysis on pet populations, veterinary care and spending on veterinary care, and pet owner demographics. The data used in the development of the book is drawn from responses from nearly 48,000 U.S. households-a much larger sample than that used by other pet studies,” explained Allison Shepherd, senior manager of market research with the AVMA.

The “U.S. Pet Ownership and Demographic Sourcebook” is available from the AVMA for $189 ($174 in a downloadable PDF) for AVMA members and $279 ($264 in downloadable PDF) for the non-members. The study can be ordered calling (800) 248-2862 at or here.

American Veterinary Medical Association

Emerging Healthcare Solutions, Inc. (PinkSheets:EHSI) announced that its newly acquired biotechnology division Celulas Genetica will submit an international patent application for the Rutherford Procedure, a revolutionary new stem-cell treatment for liver disease.

Celulas Genetica has engaged a patent specialist to file the Patent Cooperation Treaty (PTC) application with a receiving office in China. The biotech company licensed the procedure from a Chinese firm, BBFITCL, and plans to conduct the treatment’s clinical trials in China, as well.

“We believe that the Rutherford Procedure could very well revolutionize the treatment of liver disease worldwide,” said EHSI President and CEO Cindy Morrissey. “Filing a PTC application is a necessary step to protect the value of this crucial asset.”

The Rutherford Procedure is a groundbreaking organ regeneration treatment intended to utilize proton-beam technology to destroy diseased organ tissue for regeneration using adult stem cells. Celulas Genetica is currently exploring the possibility of working with a Chinese proton therapy facility to develop the new treatment for use around the globe.

Morrissey announced earlier this week that she plans to travel to China soon to meet with stem-cell researchers and potentially help open a Celulas Genetica business office there. Extending its reach into the R&D hotbed of China would build on EHSI’s rapidly expanding global footprint: Celulas Genetica is headquartered in Panama, and EHSI opened business offices in Poland and Germany last month.

Last week, EHSI announced its acquisition of a Rotary Cell Culture System, or bioreactor, developed using revolutionary NASA research in the field of microgravity. Cell cultures, including stem cells, grown inside the bioreactor look and function much closer to human cells grown within the body than cell cultures grown in Petri dishes. During the Rutherford Procedure, proton therapy will be used to destroy scar-tissue cells in the liver using high-energy proton beams, a non-invasive treatment proven to minimize damage to healthy tissues and to eliminate the side effects (including nausea) of traditional radiation therapy.

As the scar tissue is systematically destroyed by the proton therapy, a catheter will deliver the patient’s own cultured stem cells directly to his or her liver through the bloodstream. As more and more diseased tissue is destroyed, these cultured stem cells could help regenerate the patient’s damaged, cirrhotic liver into a healthy, functioning organ once more.

EHSI invests in technology developed to compete in the stem-cell research industry alongside Amgen Inc. (NASDAQ:AMGN), Acorda Therapeutics, Inc. (NASDAQ:ACOR), Celgene Corp. (NASDAQ:CELG) and Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN).

Source:

Emerging Healthcare Solutions, Inc.

Voiding dysfunction and urinary incontinence in children is common. While these issues can significantly affect quality of life, children are also at an increased risk of urinary tract infections (UTIs), urgency issues and constipation later in life. In two articles on pediatric voiding dysfunction, Pamela Ellsworth and Anthony Caldamone present techniques to evaluate and manage pediatric patients with these issues.

Behavioral, pharmacologic, minimally invasive and surgical therapies are explored, as well as symptom management. Patient education is key, say the authors, and nurses can be a guiding force for children throughout the health care process.

“Pediatric Voiding Dysfunction: Current Evaluation and Management; Pediatric Voiding Dysfunction: A Case Study”
Pamela Ellsworth, MD, FAAP, FACS, and Anthony Caldamone, MD, FAAP, FACS
Urologic Nursing; August 2008

About the Society of Urologic Nurses and Associates (SUNA)

The Society of Urologic Nurses and Associates is a professional organization committed to excellence in clinical practice and research through education of its members, patients, family and community. Our vision is to be the nursing authority in the management of persons with urological healthcare concerns.

Society of Urologic Nurses and Associates

Only one in 40 11-year-olds meets the national target of an hour of physical exercise a day, say researchers. A University of Bath study found that 95 per cent of boys and 99.6 per cent of girls fell short of this time. The Archives of Disease in Childhood study follows a warning that the NHS must do more to counter obesity.

The researchers monitored the physical activity levels of more than 5,500 11-year-olds in the South West of England over seven consecutive days between January 2003 and January 2005. The children were part of the Avon Longitudinal Study of Parents and Children (ALSPAC), which has tracked the health of more than 14,000 children since birth.

The researchers were particularly interested in total levels of physical activity and the amount of moderate to vigorous exercise the kids were taking daily.

“It’s a worrying fact that children and young people lead an increasingly sedentary lifestyle and lack physical activity,” said Libby Dowling, Care Advisor at Diabetes UK.

“This, in conjunction with diets that are high in fat, salt and sugar, is directly linked to rising levels of obesity and the increase of Type 2 diabetes in younger people.

“If we don’t put the emphasis back on exercise and healthy lifestyle, children and young people in the UK may face a lifetime of ill health.”

diabetes

Patients on with an underactive thyroid taking medication require smaller amounts as they get older, if treatment levels are not adjusted their excessive doses considerably raise the likelihood of bone fractures, Canadian researchers revealed in the BMJ (British Medical Journal). The authors stress that patients need regular dose monitoring to check whether their treatments need altering.

Levothyroxine, a synthetic form of the thyroid hormone, thyroxine, is commonly prescribed for hypothyroidism (underactive thyroid gland).

The majority of patients with an underactive thyroid are diagnosed before they are old. When we age we need less thyroxine. In many cases patients’ doses are not being reduced when they enter old age, leading to a higher risk of hyperthyroidism (thyroid hormone levels are too high). Hyperthyroidism raises the risk of fracture, especially among older females.

The authors explain that prior studies that looked at a possible link between levothyroxine and bone fractures have produced conflitcting results. Lorraine L Lipscombe, from the Women’s College Research Institute, Canada, and team decided to find out what effect levothyroxine doses might have on the risk of fractures among elderly patients.

They gathered data from a population-based study from Ontario involving 213,511 individuals aged at least 70 years – they had all been prescribed levothyroxine at least once between 1 April 2002 and 31 March 2007. They identified fractures from hospital records – each case was matched to five individuals who had not had a fracture yet (controls).

They identified both the cases and controls as current users, recent past users (had stopped the medication 15 to 180 days before the study began), or remote users (had stopped the medication at least 180 days before the study began) of levothyroxine.

During the study period 10.4% (22,236) of patients had at least one fracture.

They found that the risk of a fracture was considerably higher among the current and past levothyroxine use patients, compared to the remote use ones. Current users on medium and high levothyroxine doses had a much higher fracture risk than those on low doses, the authors added.

There was a clear link between hip and other bone fractures and higher levels of dosage among males and females, even after other fracture risk factors were taken into account.

The researchers concluded:

“Our findings provide evidence that levothyroxine treatment may increase the risk of fragility fractures in older people even at conventional dosages, suggesting that closer monitoring and modification of treatment targets may be warranted in this vulnerable population.”
Accompanying Editorial
Professor Graham Leese at Ninewells Hospital in Dundee warns thyroxine requirements may be much lower than expected among elderly patients.

Even though we have known about the risk of bone fractures linked to excessive thyroid hormone, the amount of funding in this area continues to be too low.

He wrote:

“With the prevalence of treated hypothyroidism increasing, and the annual economic burden of fractures in the United Kingdom currently estimated at €5.8bn (ВЈ5.1bn; $8.4bn), such research warrants a higher priority.”

“Levothyroxine dose and risk of fractures in older adults: nested case-control study”
Marci R Turner, medical resident, Ximena Camacho, analyst, Hadas D Fischer, epidemiologist, Peter C Austin, senior scientist, Geoff M Anderson, professor, Paula A Rochon, Lorraine L Lipscombe
BMJ 2011; 342:d2238

In the year that saw the UK top the European league table for obesity in women, a
new survey shows that GPs still believe that they are losing the fight against
obesity.1

According to the survey of 202 GPs conducted by Taylor Nelson, 60 per cent said
that they encourage the majority of obese patients to lose weight.1 However, over
half reported feeling that their efforts were unsuccessful.1 Worryingly, just 1 per
cent felt they were completely successful in supporting their patients’ weight loss
attempts.1

Lack of patient motivation and unchanging behaviour driving failure

The survey highlighted that over half of the GPs surveyed attributed lack of
motivation of the patient to change their behaviour as the key factor limiting their
ability to support patients to lose weight.1 Overall behavioural factors including
lack of exercise, eating unhealthy foods and overeating were identified as key
barriers and were consistently ranked as more significant than non-behavioural
factors, such as lack of nutritional knowledge and or insufficient ongoing support
from healthcare professionals for patients.1

Behavioural change at the core of weight-loss success

Although 93 per cent of the GPs surveyed recognised behavioural change as ‘very
important’ in helping patients to lose weight successfully, only 19 per cent reported
providing behavioural change support to all patients attempting to lose weight.
In December 2006, the National Institute of Health and Clinical Excellence (NICE)
issued guidance on the treatment of obesity which emphasised the role that
behavioural change should play in obesity management.2

The GPs surveyed cited lack of resources and funding as reasons for not
providing patients with this behavioural change support.1

Dr Colin Waine, Chairman of the National Obesity Forum, commented: “These
findings highlight that GPs are playing an active role in the fight against obesity,
and are well aware of the hurdles that obese patients face when trying to lose
weight. Primary care organisations need to utilise all the resources and support
available in order to maximise efforts and help people to change their behaviour.
There is good evidence that web-based support services are extremely effective in
helping to keep patients motivated between GP visits and encourage weight loss.”

Behavioural change support: change for life

To help GPs tackle obesity and support their patients, Abbott has developed an
online resource. Change for life offers healthcare professionals advice on setting
up special obesity services, including information on crucial resources, running
patient group sessions and protocol for running one-to-one support sessions. The
service is also available to their patients to track their progress. For more
information, log on and register at changeforlifeonline.

Clinical evidence supports combination approach

The survey also highlighted that 47 per cent of GPs said that they believed a
combination behavioural change and other weight loss methods is the most
successful way of helping their patients to lose weight.1 Clinical trials have shown
that treating patients with pharmacotherapy can help to achieve and sustain
significant weight loss when provided in conjunction with support to encourage
behavioural change.3

References

1. Survey of 202 UK-based general practitioners conducted by independent
market research firm, Taylor Nelson, on behalf of Abbott.
2. National Institute of Clinical Excellence, Obesity Guidelines, December 2006,
Please click here.
3. Wadden, T.A. et al. New England Journal of Medicine 2005; 353(20):2111-20.

About the survey

The survey was conducted on the internet by Taylor Nelson on behalf of Abbott. The sample included 202 GPs from practices across the UK.

Changing behaviour for long-term weight loss

The change for life coaching programme helps
people to identify their specific eating behaviours and the physical, emotional and
lifestyle issues that contribute to them. Change for life was developed by a team
of qualified medical experts and can be accessed 24 hours a day. As well as stepby-
step guidance and education, change for life provides several unique online
tools to help people to change their behaviour, lose weight and keep it off. There
are three section of the site: a general public area available to everyone, an area
available only to patients taking pharmacotherapy to aid weight loss, and a further
section of the site provided to assist healthcare professionals in helping their
obese and overweight patients to lose weight.

changeforlifeonline

About Abbott

Abbott is a global, broad-based health care company devoted to the discovery,
development, manufacture and marketing of pharmaceuticals and medical
products, including nutritionals, devices and diagnostics. The company employs
65,000 people and markets its products in more than 130 countries

Elderly patients are often critical about consultations with their doctor. Hierarchical structures, time pressure and traditions in the health care sector make these patients and their relatives passive when facing the doctor and his or her position of power. This is shown in a thesis from the Sahlgrenska Academy, University of Gothenburg, Sweden.

The study is based on interviews with 20 elderly patients and their relatives in Gothenburg, Sweden, and about an equal number of doctors.

‘We cannot disregard that the ability of doctors to communicate with elderly patients and their relatives could be improved, and that this shortcoming may explain why this group of patients feel insecure in meeting with the doctor. They don’t feel at home in the health care system and sometimes have problems understanding the doctor,’ says Sandra Pennbrant, nurse and the author of the thesis.

A good relationship between the doctor and the patient leads to reduced apprehension and increased faith in the health care system. This kind of relationship requires, among other things, that the doctor and the patient discuss the situation and that the doctor listens to what the patient has to say before deciding on a treatment plan.

‘Elderly patients and their relatives tend to have a critical view of meetings with the doctor. Doctors and patients have the same understanding of how good relations can be created, but it seems that doctors have a hard time accomplishing it in real life,’ says Pennbrant.

The interviewed doctors feel it is difficult to create good relationships when meeting with elderly patients and that this is mainly because the patient often only stays in hospital for a short time.

Pennbrant concludes that the health care sector needs to become a learning organisation where the medical personnel are trained to prevent misunderstandings in their meeting with elderly patients and their relatives.

‘Doctors need to learn to acknowledge the questions elderly patients may have and consider their medical conditions and personalities in communication and when building relations. Relatives should also participate in this meeting, so that they feel their work is supported and appreciated,’ says Pennbrant.

Thesis for the Degree of Doctor of Philosophy at the Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, publicly defended 2009-10-23
Title of the thesis: How elderly patients, relatives and doctors experience their meeting – A sociocultural study in a hospital setting
Link to thesis: hdl.handle/2077/21198

Source:
Elin Lindström Claessen

University of Gothenburg