(DH) Combined Stats Press Notice – Inpatient And Outpatient Waiting Figures, NHS Cancelled Operations, NHS Critical Care Beds, UK
The following statistics were released today by the Department of Health:
NHS inpatient and outpatient waiting times figures, 31 January 2009
The key points from the latest release are:
Inpatient Waiting times
- The number of patients, for whom English commissioners are responsible, waiting over the 26 weeks standard for inpatient admission at the end of January 2009 was 106 (compared to the total of 576,000).
- The number of patients, for whom English commissioners are responsible, waiting over 13 weeks at the end of January 2009 was 45,500, an increase of 6,000 (15.2%) from December 2008, but a fall of 7,500 (14.2%) from January 2008.
Outpatient Waiting times
- The number of patients, for whom English commissioners are responsible, waiting over the 13 weeks standard for a first outpatient appointment following GP referral at the end of January 2009 was 305 (compared to the total of 810,000). Of these 305, 38 were English residents waiting for appointments in Welsh hospitals.
- The number of patients, for whom English commissioners are responsible, waiting over 8 weeks at the end of January 2009 was 45,600, a decrease of 1,300 (2.8%) from December 2008, but a rise of 15,600 (52.1%) from January 2008.
Full release available as a separate press notice, released at 09:30 27th
February 2009
Additional tables are available here.
NHS cancelled operations, quarter ending 31 December 2008
The key points from the latest release are:
- During the quarter ending 31 December 2008, 16,100 operations were cancelled at the last minute for non-clinical reasons. In the same period in 2007, there were 15,700 cancelled operations.
- Cancelled operations during the quarter represented 1.0% of all elective activity, compared to 1.0% in the same period in 2007.
- Of these cancellations, 665 (4.1%) of patients were not treated within 28 days of a cancellation. In the same period in 2007, 720 (4.6%) of patients were not treated within 28 days.
Full tables are available here.
NHS inpatient and outpatient waiting: elective admission events occurring during the quarter ending 31 December 2008
The key points from the latest release are:
Inpatient Events
- The number of decisions to admit has increased by 154,000 (14.6%) since the equivalent quarter last year. Similarly, the number of admissions from the list has increased by 97,000 (9.8%) since the equivalent quarter last year.
Outpatient Referrals and attendances
- First attendances at consultant outpatient clinics have increased by 294,000 (8.5%) to 3.7 million and total attendances increased by 815,000 (7.5%) to 11.6 million compared to the equivalent quarter of 2007-08.
- Did not attend (DNA) rates have decreased this quarter compared to the equivalent quarter of 2007-08. This quarter, the percentage of patients who did not attend for their first outpatient attendance is 8.8% a fall of 0.3% against the equivalent quarter of 2007-08.
- The number of GP referrals made has increased by 245,000 (10.7%) against the same period last year. The number of other referrals made has increased by 112,000 (8.3%) against Q3 2007-08.
Full tables are available here.
NHS Critical care beds, January 2009 census
The key points from the latest release are:
- The overall number of open and staffed adult critical care beds was 3,637. This represents 139 (4.0%) more beds than at 15 July 2008, and 164 (4.7%) more beds than one year ago.
- 2,666 (73.3%) of the beds were in general critical care with the remaining 971 (26.7%) in specialist critical care units/wards such as cardiothoracic, neurological, liver, spinal injury or burns units.
- 2.030 (55.8%) of the beds were being used for intensive care (level 3) and 1,607 (44.2%) were being used for high dependency (level 2) care on the census day.
Full tables are available here.
Department of Health, UK
New Urgent Care Centres Could Swamp GP Practices With Unresolved Cases, UK
Government plans to replace Accident & Emergency (A&E) departments with new urgent care centres managed by General Practitioners (GPs) and nurses could inundate practices with unresolved cases, according to new figures obtained by the journal Pulse.
It has emerged this week that one of the first urgent care centres in the UK has sent up to 40% of its patients back to their GP.
The new centres are being set up as a gateway to emergency and urgent care – in an attempt to free up A&E departments. However, GPs say the plan lacks an evidence base is a repeat of the errors made with walk-in centres.
The College of Emergency Medicine recently said that it had ’serious concerns’ about the centres, saying they were being imposed for reasons of cost and without evidence of ‘clinical or financial benefits’.
The urgent care centre in Hemel Hempstead – which saw 6,309 patients in its first three months of opening – predicts it will eventually treat 65% of patients currently visiting A&E. However, according to discharge figures, 38% of patients are being told to get in touch with their own GP, with just 27% discharged, 17% were referred to hospital, while 7% were referred to A&E.
Herts Urgent Care – which runs the centre, says the venture is a success. It is the first of eight centres planned for Hertfordshire as part of the Government’s nationwide rollout – being driven by SHAs in the wake of Lord Darzi’s Next Stage Review.
However, Dr Peter Graves, CEO of Beds & Herts LMC, said the policy had been forced upon them without appropriate consultation. “We wish they had used walk-in-centres as a model for whether these would work or not. We had some disastrous stories – they led to serious financial deficits for PCTs, and sent people back to GPs for stuff they said they would deal with.”
A spokeswoman for Hertfordshire PCTs said: ‘This is not new work for GPs and these patients would have been referred to their GP for follow up had they been treated originally at a traditional A&E department.’
Click here to read the full story in Pulse
About PulseToday
PulseToday is the GP’s website in the UK providing general practice news, clinical education and practice information to GPs and primary care staff.
You can register on this site to get access to further information by visiting:
www.pulsetoday.co.uk/subscribemenu.asp
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
GP Practices Losing Patients And Staff To Local Polyclinic, Bradford, England
The first GP-led health centre in the United Kingdom to open is already taking not only patients but also staff from nearby practices, according to the medical journal Pulse.
Even though the polyclinic is situated in an under-doctored area of Bradford, nearly half of those registered there come from neighbouring practices. One local GP practice has already lost two practice nurses who were offered a ’significant pay rise’ by the polyclinic.
Fear has grown among General Practitioners (GPs) that the new centres will undermine practices after a recent report by the Health Services Management centre warned they would have to take up approximately 20% of GPs’ patients to avoid becoming white elephants.
The Hillside Bridge Healthcare Centre in Bradford registered 198 new patients in its first sixty days of operation – 86 of them came from other local practices, 77 came from practices slightly further away, while 35 were previously unregistered patients.
According to Sarah Rhodes, Practice Manager, Avicenna Medical Practice, and chair of the local practice managers association, two nurse practitioners and approximately 20 patients had defected to the new centre since it opened. “The main impact is staff moving down there because they pay more than the general practices do. We’ve lost both of our nurse practitioners. We’re having to advertise and we’re currently having to use locums.”
The centre, which also provides out-of-hours services in the area, is run by non-profit organisation Local Care Direct. Alan Whitaker, Communications & Community Relations Manager, Local Care Direct, said “Local Care Direct is not aggressively seeking to register patients already with other local practices. Patients are at liberty to register wherever they like to find the service which best suits their needs. We have advertised externally for nursing staff at different levels to fulfill different roles at different locations and do not actively seek to influence staff to leave other practices.”
Click here to view the full article online in Pulse.
About PulseToday
PulseToday is the GP’s website in the UK providing general practice news, clinical education and practice information to GPs and primary care staff.
You can register on this site to get access to further information by visiting:
www.pulsetoday.co.uk/subscribemenu.asp
Written by – Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Greater Risk Of Death In Patients With GI Bleeding Admitted On The Weekend
Studies examine patients with upper GI hemorrhage and GI hemorrhage due to peptic ulcer disease
Previous studies have raised questions regarding differences in quality of care for patients hospitalized on a weekend compared to weekdays. In fact, a growing body of health services research has demonstrated an association between admission to hospitals on the weekend and increased mortality. This “weekend effect” has been attributed to reduced hospital staffing and access to specific intensive treatments and procedures.
Two recent studies published in Clinical Gastroenterology and Hepatology further our understanding of this weekend effect. Clinical Gastroenterology and Hepatology is the official journal of the American Gastroenterological Association (AGA) Institute.
Higher Mortality Reported among Upper GI Bleeding Patients Admitted on the Weekends
Patients with non-variceal upper gastrointestinal hemorrhage (NVUGIH) admitted on the weekend had higher mortality and lower rates of early endoscopy, reports a new study in Clinical Gastroenterology and Hepatology. In addition, patients with acute variceal hemorrhage (AVH) admitted to non-teaching hospitals also had lower utilization of early endoscopy but no difference in survival (hospitals were considered to be teaching hospitals if they had an AMA-approved residency program, were a member of the Council of Teaching Hospitals or had a full time equivalent interns and residents-to-patients ratio of 0.25 or higher).
“Although previous studies have demonstrated differences in outcomes between weekend and weekday admissions, there has been limited analysis focusing on patients with GI bleeding, a common medical emergency that carries significant disease and death,” said Ashwin N. Ananthakrishnan, MD, MPH, of the Medical College of Wisconsin and lead author of the study. “The most important finding of our study is the higher mortality among NVUGIH patients admitted on weekends. This finding underscores the need for research into identifying the reasons for the weekend effect and to institute appropriate interventions.”
Acute NVUGIH accounts for a majority of upper GI bleeding, while AVH, often complicating cirrhosis and portal hypertension, forms the other large category.
In this cross-sectional study using the Nationwide Inpatient Sample 2004, a total of 28,820 discharges with AVH and 391,119 discharges with NVUGIH were identified through appropriate ICD-9-CM codes. Admissions were considered to be weekend admissions if they were admitted between midnight on Friday through midnight on Sunday.
On analysis, NVUGIH patients admitted on weekends had 22 percent higher adjusted in-hospital mortality and were 36 percent less likely to undergo early endoscopy within one day of hospitalization. There was one excess death for every 143 patients admitted on a weekend. Weekend admission was not predictive of in-hospital mortality in patients with AVH, but was associated with lower likelihood of early endoscopy in non-teaching hospitals. Early endoscopy was associated with significantly shorter hospital stays (NVUGIH: – 1.08 days, AVH: – 2.35 days) and lower hospitalization charges (NVUGIH: -$1,958, AVH – $8,870).
Weekend Patients with Peptic Ulcer-Related UGIB Have Increased Risk of Death
Patients admitted to the hospital on the weekend for peptic ulcer-related hemorrhage have higher mortality and more frequently undergo surgery. Although wait times for endoscopy are prolonged in patients hospitalized on the weekend, this delay does not appear to mediate the weekend effect for mortality, reports another new study also published in Clinical Gastroenterology and Hepatology.
“In addition to increased mortality and higher rates of surgical intervention, patients hospitalized on the weekend experienced greater hospital charges and length of stay than those admitted during weekdays,” said Robert P. Myers, MD, of the University of Calgary and lead author of the study. “Future studies should explore alternative processes of care that may mediate these effects, as upper gastrointestinal bleeding represents a considerable clinical and economic burden.”
The annual prevalence of upper gastrointestinal bleeding (UGIB) is approximately 170 per 100,000 people and cost is estimated at approximately $750 million. Peptic ulcer disease accounts for 50 to 70 percent of UGIB cases.
Data were extracted from the 1993-2005 U.S. Nationwide Inpatient Sample to identify patients hospitalized for UGIB due to peptic ulceration. Differences in in-hospital mortality between patients admitted on weekends and weekdays were evaluated using logistic regression models, adjusting for patient and clinical factors, including the timing of upper endoscopy.
Between 1993 and 2005, there were 237,412 admissions to 3,166 hospitals for peptic ulcer-related UGIB. Compared with patients admitted on a weekday, those admitted on the weekend had an increased risk of death (3.4 percent versus 3.0 percent), higher rates of surgical intervention (3.4 percent versus 3.1 percent), prolonged hospital stays and increased hospital charges. Although patients hospitalized on the weekend tended to be slightly sicker than patients hospitalized on a weekday (e.g., more likely to be admitted urgently and to have clotting disorders), the observed differences persisted despite adjustment for these patient and hospital-related factors.
Patients admitted on the weekend had a longer mean time to endoscopy (2.21 ± 0.01 versus 2.06 ± 0.01 days) and were less likely to undergo endoscopy on the day of admission (30 percent versus 34 percent). After adjusting for the timing of endoscopy, weekend admission remained an independent predictor of increased mortality.
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Article adapted by Medical News Today from original press release.
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About the AGA Institute
The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is one of the oldest medical-specialty societies in the U.S. Comprised of two non-profit organizations – the AGA and the AGA Institute – our more than 17,000 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, while the AGA Institute, a 501(c3) organization, runs the organization’s practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization’s annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. For more information, please visit http://www.gastro.org.
About Clinical Gastroenterology and Hepatology
The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org.
Source: Alissa Cruz
American Gastroenterological Association
Study Shows Potential For Resolving Type 2 Diabetes With Bariatric Surgery – 90% Of All Diabetics Overweight Or Obese
As the incidence of obesity-induced type 2 diabetes mellitus continues to increase worldwide, medical research indicates that surgery to reduce obesity can completely eliminate all manifestations of diabetes. In a study published in the March 2009 issue of The American Journal of Medicine, investigators analyzed 621 studies from 1990 to April of 2006, which showed that 78.1% of diabetic patients had complete resolution and diabetes was improved or resolved in 86.6% of patients as the result of bariatric surgery. The primary risk factor for type 2 diabetes is obesity, and 90% of all patients with type 2 diabetes are overweight or obese.
The dataset included 135,246 patients where 3188 patients reported resolution of the clinical and laboratory manifestations of type 2 diabetes. Nineteen studies with 11,175 patients reported both weight loss and diabetes resolution outcomes separately for the 4070 diabetic patients in those studies. Clinical findings were substantiated by the laboratory parameters of serum insulin, HbA1c, and glucose.
Researchers observed a progressive relationship of diabetes resolution and weight loss as a function of the operation performed: laparoscopic adjustable gastric banding, gastroplasty, gastric bypass, and biliopancreatic diversion/duodenal switch (BPD/DS). Gastric banding yielded 56.7% resolution, gastroplasty 79.7%, gastric bypass 80.3% and BPD/DS 95.1%. After more than 2 year post-operative, the corresponding resolutions were 58.3%, 77.5%, 70.9%, and 95.9%. In addition, the percent excess weight loss was 46.2%, 55.5%, 59.7% and 63.6%, for the type of surgery performed, respectively.
Writing in the article, Henry Buchwald, MD, PhD, Department of Surgery, University of Minnesota, states, “This systematic review and meta-analysis demonstrate that bariatric surgery has a powerful treatment effect in morbidly obese persons with type 2 diabetes; 82% of patients had resolution of the clinical and laboratory manifestations of diabetes in the first 2 years after surgery, and 62% remained free of diabetes more than 2 years after surgery (80% and 75% for the total group). Randomized clinical trials comparing surgery and medical therapies for type 2 diabetes are urgently needed. Considering the potential benefits for millions of people, such trials should assess the risk/benefit ratio of surgery in less obese (BMI 30-35 kg/m2) populations, as well as in the morbidly obese (BMI>35 kg/m2) population.”
The article is :” Weight and Type 2 Diabetes after Bariatric Surgery: Systematic Review and Meta-analysis” by Henry Buchwald, MD, PhD, Rhonda Estok, RN, BSN, Kyle Fahrbach, PhD, Deirdre Banel, BA, Michael D. Jensen, MD, Walter J. Pories, MD, John P. Bantle, MD, and Isabella Sledge, MD, MPH. It appears in The American Journal of Medicine, Volume 122, Issue 3 (March 2009) published by Elsevier.
About The American Journal Of Medicine
The American Journal of Medicine , known as the “Green Journal,” is one of the oldest and most prestigious general internal medicine journals published in the United States. It is ranked 11th out of 100 General and Internal Medicine titles according to the 2007 Journal Citation Reports© published by Thomson Reuters.
AJM, the official journal of The Association of Professors of Medicine, a group comprised of chairs of departments of internal medicine at 125-plus U.S. medical schools, publishes peer-reviewed, original scientific studies that have direct clinical significance. The information contained in this article in The American Journal of Medicine is not a substitute for medical advice or treatment, and the Journal recommends consultation with your physician or healthcare professional. AJM is published by Elsevier
About Elsevier
Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier’s 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect , MD Consult, Scopus, bibliographic databases, and online reference works.
Elsevier is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc, a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier’s ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).
Elsevier
Obese Children Should Have Gastric Bands To Manage Diabetes Says UK Expert
A UK expert is recommending, on the basis of a study, that obese children from the age of 15
onwards who have weight-related diabetes should have gastric bands fitted to make their stomachs much smaller so they lose weight. This should be
a last resort because there are serious health risks, and should only be considered when all other methods, such as diet and exercise, have
failed.
Weight loss is a recognized way of controlling diabetes, but recent research shows children find it difficult to stick to a strict diet and exercise
programme.
The Daily Telegraph reported today, Monday 2 March, that Professor Julian Shield of Bristol University and Bristol Royal Hospital for Children, who
did a weight loss study of 73 teenagers with type 2 diabetes and found they had increased rather than reduced their weight over 12 months, told the
press on Sunday that:
“We have reached the point where it is necessary because of the significant threat of mortality and the morbidity of this disease. There needs to be a
formal scientific trial of this method in adolescents.”
He said the children they see with type 2 diabetes find it very hard to lose weight by other means and they have all the health problems they see in adults
with diabetes.
“They are suffering high blood sugars, they are hypertensive and they have high blood fats. Their health is seriously at risk,” said Shield.
A gastric band is an inflatable silicone ring that a surgeon fits around the top of the stomach. The idea is that with a smaller stomach the person can’t
eat as much. It costs the NHS about 2,500 pounds per procedure. The fatality rate is less than one per cent but up to 10 per cent of patients can have
serious complications.
According to a report in the Daily Mail, Shield said that diabetic adults can lose 60 to 70 per cent of their excess weight with gastric banding, which he
recommended in preference to gastric bypass surgery because it has fewer potential complications. He said research from the US suggested gastric
banding was effective in 90 per cent of cases of adolescents aged 18 and 19.
In the UK doctors have tended to use diet and exercise to help obese diabetic children lose weight, but Shield said this was “tinkering around the
edges” and gastric banding was a potential cure for these patients.
Cases of type 2 diabetes have been rising steeply in Britain in line with obesity, although typically a disease of middle age, it is now happening in all
age groups. 17 per cent of British children are now obese, about 900,000 in total, said Shield, and about 1,400 of them have type 2 diabetes, at a rate
of 100 new cases a year.
A representative of the National Obesity Forum told the Daily Mail that he supported Shield’s suggestion.
GP Dr David Haslam told the paper that:
“The epidemic of obesity has reached a desperate place when we are talking about a 15-year-old having surgery but that is the situation we are in,
because having type 2 diabetes will knock at least 20 years off their lives.”
Gastric banding has been available through the NHS for children under 18 since 2006, but it is only used in very rare cases.
Click here for
NHS information on Obesity Treatment.
Sources: Daily Mail, Daily Telegraph.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Researchers Piggyback To Safer Reprogrammed Stem Cells
Austin Smith and his research team at the Centre for Stem Cell Research in Cambridge have just published in the journal Development (http://dev.biologists.org/) a new and safer way of generating pluripotent stem cells – the stem cells that can give rise to every tissue of the body.
Rapid developments in stem cell research in recent years have provided a way for stem cell scientists to convert specialised cells, such as skin cells, into stem cells that can form numerous cell types of the body. Research into the creation of these ‘reprogrammed’ cells – so-called induced pluripotent stem (iPS) cells – is of vital importance because it could lead to new ways of creating human stem cells from adult tissues for the study and treatment of disease. But there is one key problem with the techniques currently used to generate such stem cells: they rely on potentially harmful viruses to deliver the reprogramming factors that change specialised cells into iPS cells.
Now Austin Smith and his team report in the journal Development an approach that avoids the use of such viruses. They successfully persuaded partly specialised mouse cells, called Epi-stem cells, to reprogram into iPS cells using a single reprogramming factor called Klf4. Instead of relying on viruses to introduce Klf4 into the Epi-stem cells, they turned to a special type of DNA, called a transposable element, which can insert itself into an organism’s DNA and carry a cargo with it, in this case Klf4. The transposable element Smith and colleagues used in their study is called Piggybac, which delivered a single copy of Klf4 into the Epi-stem cells, causing them to reprogram into iPS cells. The researchers then used an enzyme to cut the Klf4 out of Piggybac. In doing so, they discovered that the iPS cells could maintain themselves using their own Klf4 gene, which had been switched on during the reprogramming process. Once the Piggybac Klf4 is removed, they report, iPS cells can go on to create normal mice when introduced into newly developing mouse embryos and can give rise to the offspring of these mice by contributing to their reproductive cells. This is the most stringent test of the normality of iPS cells. As Professor Smith explains below, this is a significant advance in the field.
“The paper we’ve published in Development , together with two other publications in Nature’, says Professor Smith, ‘ is a significant technical development in the field as together these papers present a more reliable and precise method for generating iPS cells. The method allows for greater control over the genetic modification process and this is fully reversible once reprogramming is complete. Therefore, the final iPS cells carry no potentially damaging foreign DNA. Our findings published in Development show that this approach produces perfectly reprogrammed mouse cells. The Nature papers show that it can also work in human cells. These studies provide a new tool to help advance basic research into reprogramming and pave the way to the creation of human iPS cells suitable for biomedical applications.”
Notes:
Development is a leading journal in the field of development biology and is published by the not-for-profit publisher, the Company of Biologists (http://www.biologists.com/).
The Centre for Stem Cell Research (http://www.cscr.cam.ac.uk/) is funded by the Wellcome Trust and Medical Research Council and is part of the University of Cambridge, UK.
Source: Jane Alfred
The Company of Biologists
Self-Digestion As A Means Of Survival
In times of starvation, cells tighten their belts: they start to digest their own proteins and cellular organs. The process – known as autophagy – takes place in special organelles called autophagosomes. It is a strategy that simple yeast cells have developed as a means of survival when times get tough, and in the course of evolution, it has become a kind of self-cleaning process. In mammalian cells, autophagosomes are also responsible for getting rid of misfolded proteins, damaged organelles or disease-causing bacteria.
If this process malfunctions, it can result in infectious diseases, as well as cancer, Parkinson’s or Alzheimer’s disease. Biochemists at Frankfurt’s Goethe University, working together with scientists from the University of Tromsø in Norway, the Weizmann Institute in Israel and the Tokyo Metropolitan Institute in Japan have just come up with an explanation as to how autophagosomes know exactly which proteins and organelles they should degrade.
“Although autophagy has been known for more than 30 years, it is astonishing that no-one thought of looking for the receptors that make this process so selective” explains Prof. Ivan Dikic from the Institute of Biochemistry II and the Cluster of Excellence ‘Macromolecular Complexes’ in Frankfurt. He had a head start in this field, since over several years, he and his group have researched and now published their work on another self-cleaning process in the cell: the degradation of small proteins in the proteasome, which acts as a kind of molecular shredder.
“We know that the molecules which are destined to be discarded are marked with the small protein ubiquitin and this is recognised by a receptor located at the gateway to the proteasome. It was natural to suggest a similar recognition mechanism for protein degradation by autophagosomes”, says Dikic.
Unlike the proteasome, which is a complex molecular machine, autophagosomes simply consist of a double membrane that floats around in the cytoplasm. Not unlike white blood cells, they can engulf larger proteins or even whole cell organelles. But since they have no enzymes with which they can digest their own cargo, they fuse with lysosomes. When a Yoshinori Ohsumi’s group in Japan reported that they had discovered ubiquitin-like proteins (ATG8) on the outer surface of the autophagosome and gone on to prove that they were specific for autophagy, Dikic and his colleague Dr. Vladimir Kirkin immediately began their search for potential autophagy receptors that might bind to the family of ATG8 proteins.
The team of international scientists report in the current issue of the renowned journal “Molecular Cell”, that by employing methods from cell biology, biochemistry and mouse genetics, they have been able to identify a further protein, in addition to the known p62/SQSTM1 protein, that may act as a receptor. This is the protein NBR1, which has long been associated with cancer. Both proteins have a similar chain-like structure. At one end they bind to the ubiquitin that marks the protein aggregates and organelles that are to be degraded. Next to the ubiquitin-binding site is a domain that binds to the ATG8 proteins found at the autophagosomal membrane. Here, the protein waste can dock onto the autophagosome and can then be wrapped up in the membrane.
Vladimir Kirkin, who is now at Merck Serono in Darmstadt, is continuing these investigations with the long-term aim of developing new drugs. Dikic and his group are now concentrating on mitochondria – which are implicated in oxidative stress in cells – hoping to locate the receptors for autophagy on these important organelles.
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Article adapted by Medical News Today from original press release.
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http://www.cell.com/molecular-cell/abstract/S1097-2765(09)00064-1
http://www.biochem2.de
Source: Ivan Dikic
Goethe University Frankfurt
Stem Cell Breakthrough: Pluripotency Without Using Viruses
Scientists from Canada and the UK have found a new way to create stem cells without using viruses to introduce genetic material into the nuclei
to make the cells pluripotent, instead they insert four genes that reprogram the cells then remove them later. The researchers said their work could lead
to possible cures for a range of degenerative diseases that destroy tissue, such as spinal cord injury, macular degeneration, diabetes and Parkinson’s
disease.
The researchers in Canada were from the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto, Ontario and the Department of
Molecular Genetics at the University of Toronto, and the researchers in the UK were from the The Wellcome Trust Sanger Institute in Hinxton,
Cambridgeshire, and the MRC Centre for Regenerative Medicine at the Institute for Stem Cell Research in the University of Edinburgh. The study is
published in an advanced online 1 March issue of Nature.
The researchers found that introducing just four genes that act as transcription factors, called c-Myc, Klf4, Oct4 and Sox2 was enough to reprogram
cells from adult tissue into pluripotent cells.
The pluripotent cells resembled embryonic stem cells in that they acquired the potential to differentiate into a wide range of adult cell types.
The current method for achieving this relies on using viruses (such as retroviruses, lentiviruses and adenoviruses) and plasmids (small pieces of DNA
that self-replicate like viruses inside host cells) that introduce genetic material to induce pluripotency.
Retroviruses and lentiviruses bring with them the risk that they will damage host cell DNA and unleash uncontrolled cell growth, rather like cancer,
and while the other two, lentiviruses and plasmids don’t, they have limited reprogramming potential.
So given these disadvantages, finding a new way to induce pluripotency without disrupting healthy genes is a real breakthrough in adult stem cell
science, diminishing reliance on embryonic stem cells, which is controversial because it involves the destruction of embryos.
Senior author Dr Andras Nagy, who is a Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, an Investigator at the
McEwen Centre for Regenerative Medicine, and Canada Research Chair in Stem Cells and Regeneration, said:
“We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable.”
“This new method of generating stem cells does not require embryos as starting points and could be used to generate cells from many adult tissues
such as a patient’s own skin cells,” he added.
Nagy and colleagues used a new “wrapping” method to deliver the four transcription factor genes into the adult cells to reprogram then into stem cells.
They wrote that this method, which is called “piggyBac (PB) transposition” is “host-factor independent, and has recently been demonstrated to be
functional in various human and mouse cell lines”.
In this study the researchers were able to show successful and efficient reprogramming of mouse and human fibroblasts taken from embryonic stem
cell lines, but there is no reason in principle why this could not happen to fibroblasts taken from adult tissue.
The stable pluripotent cells they created displayed all the characteristic markers of pluripotency and succeeded in a “series of rigorous differentiation
assays”.
Nagy and colleagues also showed it was possible to remove the PB wrapping seamlessly from established pluripotent cell lines, which gives scientists
an important tool for research.
They concluded that:
“We anticipate that the unique properties of this virus-independent simplification of iPS [induced pluripotent stem] cell production will accelerate this field further towards full
exploration of the reprogramming process and future cell-based therapies.”
An important step in the study took place in the lab of co-author Dr Keisuke Kaji from the Medical Research Council (MRC) Centre for Regenerative
Medicine at the University of Edinburgh. That work is the subject of a separate study in the same issue of the journal.
Kaji told the press that:
“I was very excited when I found stem cell-like cells in my culture dishes. Nobody, including me, thought it was really possible.”
“It is a step towards the practical use of reprogrammed cells in medicine,” Kaji added.
In 2005 Nagy created Canada’s first embryonic stem cell lines from embryos no longer needed by couples undergoing fertility treatment.
The Canadian Stem Cell Network and the Juvenile Diabetes Research Foundation (United States) paid for the research.
“piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells.”
Knut Woltjen, Iacovos P. Michael, Paria Mohseni, Ridham Desai, Maria Mileikovsky, Riikka Hämäläinen, Rebecca Cowling, Wei Wang, Pentao Liu,
Marina Gertsenstein, Keisuke Kaji, Hoon-Ki Sung & Andras Nagy.
Nature Advance Online Publication, 1 March 2009.
doi:10.1038/nature07863
Click here for
Abstract.
“Virus-free induction of pluripotency and subsequent excision of reprogramming factors.”
Keisuke Kaji, Katherine Norrby, Agnieszka Paca, Maria Mileikovsky, Paria Mohseni & Knut Woltjen.
NatureAdvance Online Publication, 1 March 2009.
doi:10.1038/nature07864
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Abstract.
Sources: Journal abstract, Samuel Lunenfeld Research Institute press statement.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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Synchronous Bilateral Percutaneous Nephrostolithotomy: Analysis Of Clinical Outcomes, Cost And Surgeon Reimbursement
UroToday.com – For those patients presenting with bilateral bulky renal stone disease (i.e. >1.5 cm staghorn calculi) planned bilateral simultaneous percutaneous nephrolithotomy (SB-PCNL) is safe and efficacious.
The researchers at University of Texas Southwestern demonstrated this in a retrospective review of 15 patients treated with SB-PCNL in 34 renal units and compared them to 62 patients who underwent a unilateral PCNL procedure for staghorn calculi during the same time period. The staged bilateral PCNL costs were calculated from the unilateral PCNL patient group.
One quarter of the SB-PCNL patients and 40% of the unilateral PCNL patients had a staghorn calculus. A second look nephroscopy was performed on 66% of the SB-PCNL patients for a stone-free rate of 87%; and 39% of unilateral PCNL patients required a second look procedure to render them stone-free. Complication rates were similar for the two groups; 27% for SB-PCNL and 23-30% for the staged unilateral PCNL.
Compared to staged bilateral PCNL, the SB-PCNL was associated with shorter overall anesthesia/room time and lower overall and component costs. In addition, the SB-PCNL reduced by half the length of stay compared to the staged bilateral PCNL.
While all of these reductions result in cost savings of between $4,000 and $5,000 for the SB-PCNL, the physician reimbursement is 11% to 46% less for this approach compared to the staged bilateral PCNL. It would seem appropriate for third party payors to reevaluate reimbursement policies in support of what urologists have come to recognize is best for the patient.
Bagrodia A, Raman JD, Bensalah K, Pearle MS, Lotan Y
J Urol. 2009 Jan;181(1):149-53.
doi:10.1016/j.juro.2008.09.011
Written by UroToday.com Contributing Editor Elspeth M. McDougall, MD, FRCSC, MHPE
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