Nebraska Right To Life Committee Endorses Gov. Heineman, Does Not Endorse Other Republican Candidates Opposed To Abortion Rights
The Nebraska Right to Life Political Action Committee earlier this week announced that it is endorsing Gov. Dave Heineman (R), who opposes abortion rights, to remain governor and is not endorsing his Republican opponents Dave Nabity and Tom Osborne, who also oppose abortion rights, for the May 9 primary, the Lincoln Journal-Star reports. Heineman in 2005 became governor after former Gov. Mike Johanns (R) was named U.S. agriculture secretary. NRL Executive Director Julie Schmit-Albin said that while Nabity and Osborne both oppose abortion rights, the group rewards incumbents with endorsements for actions they take while in office. She added that abortion-rights opponents “got more action in 15 months from Heineman than we did out of Johanns in six years.” Nabity said he would sign a bill similar to South Dakota’s law banning abortion except to save a pregnant woman’s life, adding, “I had hoped that [NRL] would be less political than to try to posture for political influence.” Osborne said, “I believe my voting record is 100% pro-life,” (Hicks, Lincoln Journal-Star, 3/22). The endorsements were made after the NRL PAC board met on March 11 (NRL PAC release, 3/20).
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Nevada Man Wants Surgery For His 100 Pound Scrotum
The rare but incredible case of Wesley Warren Jr. puts our daily burdens into perspective as the Nevada resident says he needs around a million dollars to pay for an operation to remove his 100 pound scrotum.
He has a hugely enlarged scrotum, the sack that protects the testicles and its size and weight causes him discomfort, pain and makes it incredibly difficult to get out and about.
“It’s not easy to get around… It makes me stay
in most of the time.”
Warren told the Las Vegas Review-Journal of his 100-pound scrotum.
Warren says the problems started in 2008 when he rolled over in bed and caught his scrotum with his leg, causing him a terrible pain. As the pain subsided his scrotum swelled to the size of a football and has been getting larger since.
Doctors say that Warren’s condition is extremely rare and although more common in tropical Africa and Asia, in these cases the problem is usually put down to a mosquito spread parasitic infection where thread like worms block the lymphatic drainage and fluids collect, that cause huge swelling known as lymphedema.
However physicians that have examined Warren’s case say there is no sign of this kind of infection and living close to downtown Las Vegas he’s hardly at risk of these kinds of tropical diseases.
Initially, he sought basic medical treatment, being given antibiotics for what doctors thought was a local infection. Slowly the swelling became so large he could no longer work, so he signed on for disability benefits. In 2010 he tried medical treatment again at the University Medical Center in Las Vegas. Doctors classified and reclassified his condition as scrotal elephantiasis, scrotal lymphedema or scrotal edema, a condition characterized by an excess of watery fluid collecting in tissues of the body.
Doctors at UMC thought they might be unable to save Warren’s penis and testicles, which was a shock to him :
“Basically, he was telling me there was a good chance that I would be castrated and have to go to the bathroom through a tube for the rest of my life … I really would like to have a relationship with a woman. I should be in the prime of my life right now.”
Doctors at UCLA were more hopeful, but then money issues kicked in; even if Nevada Medicaid would cover an out of state procedure, they wouldn’t pay enough for what looks to be a seven figure operation.
Warren said after he came back from LA :
“I really don’t think people know what I have … It’s not something people have seen before, I’m sure of that. I doubt if they can even imagine it.”
Rupert Shepherd
Story Of Lymphatic System Expands To Include Chapter On Valve Formation
A century after the valves that link the lymphatic and blood systems were first described, St. Jude Children’s Research Hospital scientists have detailed how those valves form and identified a gene that is critical to the process.
The gene is Prox1. Earlier work led by Guillermo Oliver, Ph.D., a member of the St. Jude Department of Genetics, showed Prox1 was essential for formation and maintenance of the entire lymphatic vasculature. The lymphatic vasculature is the network of vessels and ducts that help maintain the body’s fluid balance and serves as a highway along which everything from cancer cells to disease-fighting immune components moves. Oliver is senior author of the new study, which appeared in the October 15 edition of the scientific journal Genes & Development.
The new research suggests that Prox1 is also essential for proper formation of the one-way valves that control movement of fluid and nutrients from the lymphatic system into the blood stream. Researchers found evidence that the Prox1 protein also has a role in formation of the venous valves.
“Understanding how valves form is crucial to efforts to develop treatments for valve defects that affect both children and adults,” said the paper’s first author, R. Sathish Srinivasan, Ph.D., a research associate in the St. Jude Department of Genetics. Those defects are linked to a variety of problems including lymphedema and deep vein thrombosis, which are blood clots that form deep in veins and have the potential for causing life-threatening complications. Lymphedema is the painful and sometimes disfiguring swelling that can occur when lymph flow is disrupted.
For more than a decade, the lymphatic system has been a focus of Oliver’s laboratory. The laboratory’s contributions through the years include evidence that leaky lymphatic vessels might contribute to obesity. Oliver and his colleagues also demonstrated how the lymphatic system forms from Prox1-producing cells destined to become lymphatic endothelial cells (LECs) when they leave the developing veins and migrate throughout the body.
The investigators also showed the Coup-TFII gene is essential to the process. The Coup-TFII protein binds to the promoter region of the Prox1 gene. The binding switches on production of the Prox1 protein that is required to create and maintain the lymphatic system.
The newer research builds on that earlier work from Oliver’s laboratory. The latest study focused on the lymphovenous valves. These valves are found at just two locations in the body, on either side of the chest just under the clavicle bone where the lymphatic vessels intersect with the subclavian and internal jugular veins.
Working in mice, investigators discovered that these lymphovenous valves form from a newly identified subtype of endothelial cell found in developing veins. Like the LECs that form the lymphatic system, the newly identified endothelial cells make Prox1. But while the LECs leave the veins and migrate throughout the body, these endothelial cells stay put to form the lymphovenous valves.
Researchers demonstrated the process requires two copies of the Prox1 gene. That ensures adequate levels of the Coup-TFII-Prox1 complex and with it enough Prox1 to build and maintain the lymphatic system. Mice engineered to carry a single copy of Prox1 either did not survive or were born without lymphovenous and venous valves.
“If you have only one copy of Prox1 you are going to have a reduction in the Coup-TFII Prox1 complex and so a dramatic reduction in the number of cells available to build the lymphatic system. That explains the defects we see,” Srinivasan said.
New Research Finding Presented At American Society Of Hematology Annual Meeting
Researchers from Seidman Cancer Center at University Hospitals (UH) Case Medical Center and Case Western Reserve University School of Medicine presented new research findings in 25 presentations at the 53rd Annual Meeting of the American Society of Hematology (ASH) at the San Diego Convention Center.
“The breadth and depth of this innovative cancer research presented at ASH is truly outstanding,” says Stan Gerson, MD, Director of the Seidman Cancer Center at UH Case Medical Center and the Case Comprehensive Cancer Center at Case Western Reserve University. “Our faculty members are making tremendous advances in hematology and oncology which is reflected in their being chosen for oral and poster presentations.”
Speaking at the ASH “Scientific Symposium on Lymphoid Neoplasia” in a session titled “Autophagy and Metabolism in Lymphoid Malignancies,” Clark Distelhorst, MD, provided a synthesis of the latest research indicating that autophagy occurs in lymphoid malignancies and may be a novel therapeutic target for lymphoma and other lymphoid neoplasia. His research suggests that targeting autophagy (a process through which cells eat parts of themselves to generate sufficient energy to stay alive) may be a useful adjunct to the longstanding use of glucocorticoids, such as prednisone, to kill cancer cells.
His session outlined the growing body of evidence that treatments aimed at inducing autophagy have great promise in treating lymphoid malignancies. In his session, Dr. Distelhorst presented important data explaining how glucocorticoids starve tumor cells of glucose and thus induce autophagy. Researchers at UH Case Medical Center and Case Western Reserve University identified the Dexamethasone-induced Gene 2 (dig2) that encodes a protein mediator of autophagy.
“This new cancer-fighting strategy lays the groundwork for further development of autophagy inhibitors to enhance the glucocorticoids properties,” says Dr. Distelhorst, who is vice-chair of the ASH subcommittee on Lymphoid Neoplasia. “This is a major step forward in our research efforts to develop new therapies for lymphoid malignancies.”
Dr. Distelhorst’s session was Saturday, December 10, 4 p.m. – 5:30 p.m. in Room 6A. (San Diego Convention Center). ashnfex/ash/2011/webprogram/Paper35836.html
In a poster presentation (Abstract# 1907), Jeffery Auletta, MD, Kenneth Cooke, MD, and colleagues presented significant findings that mesenchymal stem cells (MSCs) effectively treat graft-versus-host disease (GvHD) while not interfering with bone marrow transplant’s efficacy in treating leukemia.
MSCs are non-hematopoietic (not blood-forming cells) adult stem cells found in the bone marrow and were discovered at UH Seidman Cancer Center and Case Western Reserve University. They maintain hematopoietic stem cell (blood-forming cells) development and also differentiate into fat cells, bone cells and cartilage cells. MSCs have been shown to suppress immune responses ex vivo (outside the body in cell culture conditions).
Due to these properties, MSCs have been used to treat GvHD in bone marrow transplant (BMT) patients. However, how MSC immunomodulation works in vivo (inside the body) has not been well studied, and, in fact, could potentially promote leukemia/lymphoma recurrence in transplant patients. That is, the benefit of BMT is that the donor graft kills residual leukemia in the transplant recipient (host), a process called graft-versus-leukemia (GvL).
“We used a pre-clinical mouse model of BMT to study how human MSCs mediate in vivo immune effects,” says Dr. Auletta. “Our results show for the first time using an animal model that human MSCs simultaneously attenuate GvHD, but spare GvL activity.”
UCSB Researchers Discover The Processes Leading To Acute Myeloid Leukemia
Researchers at UC Santa Barbara have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. The findings are published in a recent paper in the Journal of Biological Chemistry.
The UCSB research team described how a certain mutation in DNA disrupts cellular function in patients with acute myeloid leukemia (AML). The researchers were prompted to study this process by another research team’s discovery that AML patients have a mutation in a certain enzyme, which was reported in the New England Journal of Medicine. The enzyme is a protein called DNMT3A, which leads to changes in how the DNA of AML patients is methylated, or “tagged.” Norbert Reich, professor in the Department of Chemistry and Biochemistry at UCSB, was already studying that particular enzyme with his research group, so they began to study the disease process of AML at the cellular level.
Reich explained that tagging is a way of reading DNA at the cellular level. This falls within an area of study called epigenetics, a process that occurs “on top” of genetics. Each person has approximately 200 types of cells, all with the same DNA, and these must be controlled in different ways. “There is an enzyme – a protein – that tags DNA and controls which of the genes in your cells, your DNA, gets turned on and off,” said Reich. “So you have 20,000 genes, and you have to control them differently in your brain than in your liver.”
Reich explained that there is current interest in this broader field of epigenetics as a direction for the treatment of cancer. “There’s definitely the idea that this may be a new way of developing therapeutics, because you don’t have to kill the cancer cell,” said Reich. “Almost every cancer therapy that’s out there works on the principle that a cancer cell needs to be killed.”
With epigenetics, instead of only having DNA sequence coding for certain genes, there is an epigenetic process, with another layer of information on top of the genetic process. In this case, that information is the tagging by the methyl groups.
“If you really think about it, this is part of the answer as to how your cells can be so different and yet they all have the same DNA,” said Reich. “You have the same genome in every one of your cells, but you do not have the same epigenome, which is basically the methylation pattern, the tagging pattern. That is different in every type of your cells. And the way this relates back to cancer, with leukemia, in those patients, the tagging is messed up. The patterns are not correct. Our big contribution to that is we’ve explained how the mutations in the enzyme could lead to that disruption of the tagging pattern.”
The UCSB group developed a test to demonstrate that the mutant enzymes in AML can only work on DNA for short distances. As a result, the precise methylation patterns of a healthy cell are disturbed, resulting in genes being turned on at the wrong place and time, which in turn can initiate the growth of cancerous cells.
The team found that the mutation AML patients have causes a certain complex of four proteins to be disrupted. “The surprise was that the disruption doesn’t stop the enzyme from being active; it doesn’t stop the enzyme from tagging the DNA,” said Reich. “Instead, it stops the way it can do it. Instead of going to your DNA and tagging an entire region of chromosome, it goes there, does one thing, and leaves. That process, that change, is what we see in the AML patients. So we think we have a molecular explanation for this disease.”
Reich said that the currently prescribed drug Vidaza works by affecting the same enzyme that is mutated in AML. There is interest in the pharmaceutical industry in developing other therapeutics to target the enzymes responsible for tagging the DNA. These epigenetic inhibitors would reprogram rather than kill the cell.
Traditional cancer therapies use radiation and chemotherapy to remove or kill cancer cells. “The problem with that is that cancer cells are often very subtly different from normal cells,” said Reich. “So you have one of the most difficult therapeutic challenges known to man, which is to distinguish between two human cells – one that’s cancerous and one that’s not. Instead of killing the cell, the notion is that if you could just reprogram the cell, then it goes back to being normal. You intercept the cancer development. This is still an aspiration; it hasn’t been achieved really, but that’s what attracts people to the field of epigenetic-based therapies, because of the prospect of not having to kill cells.”
Celeste Holz-Schietinger and Douglas Matje, both graduate students working in the Reich lab, are the first and second authors of the paper.
View drug information on Vidaza.
Highlighting A Rare Subset Of Diseases Involving The Lymphatic System
A clinically challenging and under-studied subset of diseases affecting the lymphatic system and grouped under the disease spectrum lymphangiomatosis and Gorham’s disease is the focus of a special issue of Lymphatic Research and Biology, a peer-reviewed journal published by Mary Ann Liebert, Inc.. The issue is available free online.*
Guest Editor, and Journal Associate Editor Francine Blei MD, MBA, St. Luke’s Roosevelt Hospital, NY, has compiled a collection of articles that highlight the complex characteristics of these diseases, which can be localized, affect multiple sites, or be systemic, may be congenital or acquired, and may cause symptoms that range from mild to severe to life-threatening. The articles focus on current knowledge, ongoing research, and how these diseases differ from other lymphatic disorders.
“This disease spectrum affects a patient population that is small in number, but the effects of the disease(s) are devastating,” says Stanley G. Rockson, MD, Editor-in-Chief of Lymphatic Research and Biology and Allan and Tina Neill Professor of Lymphatic Research and Medicine, Stanford University School of Medicine, CA. The collection of articles in this special issue, “highlights the current state of knowledge (and ignorance) in this paradoxically neglected area of lymphatic health and disease.”
Neovacs Announces The Publication Of A PNAS Article On Anti-IFN
Neovacs, a biotech company pioneering the development of anti-cytokine and anti-viral regulation protein therapeutic vaccines, today announced the publication of an article on anti-IFN?± kinoid active immunization in the March 11th edition of the prestigious journal PNAS (the Proceedings of the National Academy of Sciences of the USA). The integral press release is available by clicking on this link (PDF).
In an article entitled “IFN?± kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model”, Prof. Daniel Zagury MD and colleagues demonstrate the efficacy of an anti-IFN?± kinoid active immunization approach in a mouse model of systemic lupus erythematosus (SLE, also referred to simply as “lupus”). Lupus is a frequent, life-threatening, chronic auto-immune disease which strikes up to 3 million people in the seven major developed countries (source: Datamonitor, 2007). Lupus can be fatal. The cause is not known but type I IFNs (IFN?± and ??) have recently been described as key agents in the etiopathogenic process.
In the PNAS article, Zagury et al. report that an IFN?±-derived immunogen called IFN?± kinoid (a heterocomplex of IFN?± and keyhole limpet hemocyanin) delayed and/or prevented the manifestations of lupus (including proteinuria, histological lesions and death triggered by IFN?± Adv challenge) in NZB/W mice. The IFN?± kinoid acted by triggering a strong IgG antibody immune response targeted specifically against IFN?±. Importantly, no cellular immune response against IFN?± was observed, as demonstrated by the lack of T cell proliferation after stimulation of splenocytes from immunized mice by the cytokine.
About Neovacs
Neovacs is acknowledged as a pioneer in the development of novel therapeutic vaccines against human cytokines (kinoids) and immunosuppressive viral proteins (toxoids). Neovacs’ key investors are Truffle Capital, Novartis Venture Fund and OTC Asset Management. Neovacs’ most advanced program (the TNF?± kinoid) is currently being tested in a Phase I/II clinical study in patients suffering from Crohn’s Disease.
Source
Neovacs
Vitamin D Deficiency Among Systemic Lupus Erythematosis Patients
Researchers have just found that vitamin D levels among systemic lupus erythematosis (SLE) patients directly relates to the severity of the disease and the development of the autoimmune disease. The study found that people with low levels of vitamin D are more prone to develop SLE than those with higher levels.
They also noticed that a destructive inflammatory marker was more apparent in vitamin D deficient SLE patients than those with high levels.
The study was published by Dr. Lauren Ritterhouse and her team from the University of Oklahoma Health Sciences Center. Their paper was the first of it’s kind to conclude that vitamin D deficiency among SLE patients should be treated.
Dr. Ritterhouse said that their finding:
“..strongly suggests that repletion with vitamin D
should be considered.”
Healthy control patients were observed to see if vitamin D levels related to SLE development, some of the patients had low vitamin D levels and others had high levels.
The researchers found evidence of early lupus development among healthy controls who had deficient levels of vitamin D, no evidence was found to suggest the same for patients with sufficient levels.
This means that those with lower levels of the vitamin are more at risk to develop lupus.
They also observed that a marker of destructive inflammation was far more widespread among patients who had a deficiency in their levels of vitamin D than those with normal levels.
So does that mean that very high levels of vitamin D is good for SLE patients? It seems so, as the data they gathered showed that the inflammatory marker was least apparent among patients with the very highest levels of vitamin D.
Treatment for SLE has progressed immensely over the years and, thanks to its modern advancements, patients have seen not only increased life expectancy, but less pain in general.
Repletion with vitamin D should be carried out among SLE patients to prevent their suffering from becoming any worse. Thanks to the research carried out at the University of Oklahoma, it is evident that such a course of treatment is necessary.
Joseph
(Source: John J. Cannel M.D.)
Statins Disappoint In Atherosclerosis Progression In Children With Lupus
According to the American College of Rheumatology (ACR) 322,000 adult Americans are affected by systemic lupus erythematosus (SLE) with approximately 5,000 to 10,000 children in the U.S. affected by lupus (Lehman 1996), although exact figures for pediatric SLE cases remain difficult to establish. One of the long-term complications of SLE in both adult and pediatric patients is accelerated atherosclerosis, a build-up of plaque in the arterial wall leading to heart attack and stroke.
Although Atorvastatin therapy was established as being ineffective in reducing atherosclerosis progression in children and adolescents with SLE, results of a trial revealed in Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the ACR, that statin therapy showed a positive trend towards effective treatment in people with more severe SLE who were not included in the Apple trial (Atherosclerosis Prevention in Pediatric Lupus Erythematosus trial).
According to medical evidence, SLE patients tend to have an eight-times higher risk of developing premature coronary heart disease than the general population. Compared to healthy pre-menopausal women, those with lupus have a 50-times higher potential risk of suffering a heart attack.
Lead researcher Dr. Laura Schanberg with the Department of Pediatrics at Duke University Medical Center in Durham, North Carolina states:
“The prognosis for pediatric lupus patients has significantly improved over the last few decades, however diagnosis at an earlier age subjects these patients to greater cardiovascular risk from systemic disease activity and treatment side effects over a longer time period.”
Earlier studies established that compared to adults, children with SLE have more severe organ damage, longer exposure to illness and potentially toxic treatments.
Although the prevalence of atherosclerosis in pediatric SLE is unknown, scientists have reported precursors of the disease, such as thickening of artery walls measured by carotid intima-media thickening (CIMT). In adults with SLE it has been shown that statins reduce atherosclerosis progression, however, this has not yet been investigated in pediatric SLE patients.
The APPLE Trial was a randomized, multi-center trial (21 North American sites) conducted in 221 SLE patients aged between 10 and 21 years to examine atorvastatin, commercially known as Lipitor®. Researchers randomized the participants, with 113 participants receiving atorvastatin therapy and 108 participants receiving either 10 or 20 mg of placebo daily depending on weight over a 36-month study period. The effectiveness of the therapy was determined by progression of CIMT measured by ultrasound.
Co-lead investigator of the Apple Trial, Dr. Christy Sandborg from the Stanford University School of Medicine in California summarized:
“Our results demonstrate no significant effect on progression of atherosclerosis in children and adolescents with SLE who were treated with atorvastatin use over the 3-year period. Further study of subgroups of SLE patients that may benefit from statin therapy is warranted.”
Although atorvastatin proved ineffective in reducing progression of atherosclerosis in this study population, it was determined to be safe and well tolerated.
Dr. Angelo Ravelli from the Universit? degli Studi di Genova and Istituto di Ricovero e Cura a Carattere Scientifico in Italy wrote in a related editorial also published this week in Arthritis & Rheumatism, that:
“Although the APPLE Trial found atorvastatin to be ineffective in pediatric SLE patients with low to moderate disease activity, a trend toward positive effect was detected. This indicates that while statin therapy may not be necessary in all SLE patients, preventative statin therapy may benefit those with more severe disease activity.”
At present, post-hoc subgroup analyses of the APPLE Trial are underway that may reveal those patient groups who could benefit from atorvastatin therapy.
Petra Rattue
A Simpler System Would Make It Easier For Clinicians To Treat Kidney Problems In Lupus Patients
The current classification system for kidney complications in patients with lupus is too detailed, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The results should make it easier for physicians to classify and treat kidney problems in patients with the disease.
People with the autoimmune disease systemic lupus erythematosus (lupus) can experience a number of medical complications, including lupus nephritis, an inflammatory kidney disorder. Lupus nephritis affects approximately 3 out of every 10,000 people, and it can be serious and lead to kidney failure.
Classifying the severity of patients’ lupus nephritis can help physicians choose appropriate therapies. The World Health Organization created a classification system that divided cases into six classes based on severity, and in 2003, the International Society of Nephrology and the Renal Pathology Society proposed some revisions. One of the most important changes subdivided class IV (when 50% or more of the kidney is diseased) into a segmental form and a global form depending on exactly how much of the kidney is affected.
This new classification of class IV lupus nephritis resulted from a study of 86 patients that suggested a difference in health outcomes, such as kidney failure, between those with segmental and global forms of the disease.
After the new classification system was published, various studies came to contradictory conclusions about differences in the health outcomes of patients in the two class IV groups. To provide some insight, Jo Berden, MD, PhD, Catharina Haring, MD (Radboud University Nijmegen Medical Center, in Nijmegen, The Netherlands), and their colleagues searched the medical literature and analyzed all of the studies and clinical trials that used the 2003 International Society of Nephrology and Renal Pathology Society classification of lupus nephritis in adult patients.
In the eight studies included in the final analysis, the incidence of kidney failure varied between 0% and 67%. The analysis did not support a significant difference in kidney outcomes between the segmental and global subclasses.
The results suggest the current classification system is too detailed. “This research is important because it could make the categorization of lupus nephritis easier and more comprehensive,” said Dr. Berden.