Necrotizing Fasciitis Research Paper
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A special virus-leukemia program was initiated under a special appropriation, included in the FY appropriation signed into law on September A reorganization of the DHEW provided for an expansion of the secretary's office with the creation of three new assistant secretaries, including an assistant secretary for health and scientific affairs. Philip R. Lee was appointed to the new position of assistant secretary for health and scientific affairs on November 2.
Robert Q. Marston was appointed NIH associate director for regional medical programs and chief of the division. At a White House meeting June 27, the NIH director and institute directors discussed with the President how the benefits of research findings in health could be brought more rapidly to all the people. A Division of Environmental Health Sciences was established in NIH November 1 to conduct, foster and coordinate research on the biological, chemical, and physical effects of environmental agents. Paul Kotin, scientific director for etiology, NCI, was named director of the new division. An advisory committee to the NIH director was appointed on November 9 to provide advice on the further development of NIH research and related programs. NIMH's Division of Clinical, Behavioral and Biological Research, within the mental health Intramural Research Program, comprising activities conducted in the Clinical Center and other NIH facilities, continued here under an agreement for joint administration between the two companion bureaus.
The program includes the entire range of chemical effects on living organisms. On September 26, the deed for Establishment of the John E. Under a reorganization of health activities announced on April 1, NIH assumed status as a new operating agency within the department, with the NIH director reporting directly to the assistant secretary for health and scientific Affairs. A proposed facility to house the biomedical communications network was designated the Lister Hill National Center for Biomedical Communications by passage of P. Established by the DHEW secretary on August 9, the Center for Population Research conducts a contract and grant program in population and reproduction research.
The center was designated by the President as the primary Federal agency responsible for population research and training. On August 16 the National Eye Institute was created to build an enlarged program based on blindness research formerly conducted in the National Institute of Neurological Diseases and Blindness. Marshall W. Nirenberg, chief of NIH's Laboratory of Biochemical Genetics, for discovering the key to deciphering the genetic code.
On October 24 the President signed into law P. Roger O. Merlin K. The bureau continues to use NIH facilities and buildings. A bureau-level organization was established for the National Cancer Institute on July Christian B. Charles C. It also established a President's Biomedical Research Panel. Baruch Blumberg, Institute for Cancer Research. Gajdusek was honored for his research on kuru and Dr. Blumberg for his work on the Australia antigen at the National Institute of Arthritis and Metabolic Diseases On July 13, Dr.
Julius B. Richmond took the oath of office as DHEW assistant secretary for health and Surgeon General, becoming the first person to hold both offices simultaneously. Hans J. A protocol of cooperation in the exchange of information on medicine and public health between the United States and China was signed on June 22 in Beijing's historic Great Hall. On June 30 Dr. Fredrickson stepped down as NIH director. Thomas E. Malone was appointed acting director. Magnuson was involved in support of biomedical research at NIH since James B. David S. Hogness, Stanford University, gave the first lecture, October Roscoe O. Robert C. Gallo, NCI.
On January 18, Building 1 was officially named the James A. Shannon Building in honor of the former NIH director NCI dedicated its R. The building houses the institute's information programs that serve health professionals and scientists. Gallo, Jr. NIH and Howard Hughes Medical Institute launched a multimillion dollar cooperative program in August to help increase the vigor of American biomedical research and continue the flow of new doctors into research areas.
Also created was the National Center for Nursing Research. NIH scheduled monthly events, hosted by individual components throughout the year, to commemorate its th anniversary. Fifty-six promising science students — one from each state and U. On July 23 President Reagan named a member Commission on the Human Immunodeficiency Virus Epidemic, which held its first meeting following the announcement. Recognizing the importance of computerized information processing methods for the conduct of biomedical research, Congress establishes the National Center for Biotechnology Information NCBI as a division of the National Library of Medicine on November 4.
Whitehead, founder of the Whitehead Institute of Biomedical Research. On May 22, NIH conducted its first gene transfer in humans. A cancer patient was infused with tumor-infiltrating lymphocytes TIL that had been altered by insertion of a gene. This allowed scientists to track the special cancer-fighting cells in the body to increase the understanding of TIL therapy. The President and Mrs. Bush attended the ceremonies. The Recombinant DNA Advisory Committee approved the first experiments involving transfer of human genes for therapeutic purposes on July The treatment was initiated on September 14 in a 4-year-old girl with adenosine deaminase deficiency. It was announced in September that the gene that caused osteoarthritis was isolated by scientists supported by the National Institute of Arthritis and Musculoskeletal Diseases.
The Office of Research on Women's Health was established to strengthen NIH's efforts to improve the prevention, diagnosis and treatment of illness in women and to enhance research related to diseases and conditions that affect women. On January 29, NIH scientists treated the first cancer patients with human gene therapy. Two patients received transfusions of special cancer-killing cells removed from their own tumors and armed in the laboratory with a gene capable of producing a potent antitumor toxin, tumor necrosis factor. She was the first woman appointed to this post. In August the National Center for Human Genome Research announced the start of a new, unified effort to develop a "framework" map of the human genome — expected to take 2 to 3 years to complete.
About 3, women will be enrolled at each center to investigate women's most common causes of death and disability. NHLBI scientists for the first time successfully transferred a normal cystic fibrosis gene into the cells lining a CF patient's lungs. Martin Rodbell, NIEHS, shared the Nobel Prize in physiology or medicine for research on G proteins, key components of the communication system that regulates cellular activity.
NLM unveiled the "Visible Man," a detailed atlas of human anatomy created from thousands of images of a human body collected by radiographic and photographic techniques. The first multicenter trial of bone marrow transplantation in children with sickle cell disease demonstrated that the procedure can provide a cure for young patients that have a matched sibling, according to NHLBI-supported scientists. Results from the NIH-supported Dietary and Systolic Hypertension trial indicated that blood pressure can be swiftly and significantly lowered through a diet low in fat and high in vegetables, fruits, and low-fat dairy foods.
Results from an NIH trial showed that a low-dose diuretic cuts by half the chance that an older person with high systolic blood pressure will develop heart failure. In those who had already had a heart attack, their chance of developing heart failure dropped by 80 percent. A team led by NIH-funded scientists determined the complete genome sequence of the E. This accomplishment gives researchers a powerful new tool for understanding fundamental questions of biological evolution and function. Hatfield attended the groundbreaking ceremonies for the new Clinical Center, which will be called the Mark O. Hatfield Clinical Research Center.
NICHD's new zebrafish facility opened. Zebrafish have become the mainstay of developmental biologists for studying the development of the vascular system and central nervous system, as well as the functional genomics of the zebrafish. A large prevention trial conducted by NCI showed that long-term use of a moderate-dose vitamin E supplement substantially reduced prostate cancer incidence and deaths in male smokers.
Results from a NCI-sponsored clinical trial showed that women at high risk of developing breast cancer who took the drug tamoxifen had 49 percent fewer cases of breast cancer than those who didn't. Tamoxifen was hailed as the first drug to prevent breast cancer in women at high risk for the disease. Between and , the rate of Sudden Infant Death Syndrome SIDS dropped by 38 percent, much of that likely being due to a 66 percent decrease during the same period in the number of U. The complete sequence of two bacteria that are among the major causes of sexually transmitted diseases worldwide — Treponema pallidum, responsible for syphilis, and Chlamydia trachomatis, responsible for chlamydial infections — were obtained by two separate teams of scientists supported by NIAID and others.
Senator John Glenn and six other astronauts spent nine days in space aboard NASA's Space Shuttle Discovery conducting about 83 scientific projects, the most research-intensive space journey yet. An international team funded by NHGRI and others obtained the complete sequence of the million-base genome of the roundworm, Caenorhabditis elegans. This marks the first time that scientists have spelled out the instructions for a complete animal which, like humans, has a nervous system, digests food, reproduces, and gets old, making it a very important organism in which to carry out studies that parallel human biology. Hatfield Clinical Research Center on the north face of Building Underlying vitamin D deficiency in postmenopausal women is associated with increased risk of hip fracture, according to a study supported by NIA and NCRR.
A meta-analysis study, led by an NICHD researcher, found that pregnant women infected with HIV could reduce the risk of transmitting the virus to their infants by about 50 percent if they deliver by cesarean section before they go into labor and before their membranes rupture. NIH Director Dr. The Council will provide advice and recommendations to, and consult with, the NIH Director regarding matters related to medical research, NIH's policies and programs, and public participation in NIH's activities.
COPR was chartered in November Earlier, Dr. Varmus named Dr. Gary Nabel as the director of the new VRC, which currently exists as a "center without walls". A joint Uganda — U. A single-oral dose of the antiretroviral drug nevirapine given to the HIV-infected mother while in labor and another to her baby within three days of birth reduced the transmission rate by half compared with a similar short course of AZT.
Women with preeclampsia, a potentially fatal complication of pregnancy, were found to have an imbalance of two key chemical compounds that control blood pressure, prostacyclin and thromboxane, months before their symptoms appeared, according to NICHD scientists. NIH announced its plan to establish a repository called PubMed Central for free electronic distribution of primary research reports in the life sciences. The new site would be integrated with NLM's widely used bibliographic site PubMed and is intended to be one of several repositories in an international system first proposed by NIH director Dr.
Harold Varmus. PubMed Central would begin receiving, storing and distributing content — including peer — reviewed articles, preprints, and other screened reports from existing journals, new journals, and reputable scientific organizations — in January Children born to mothers with untreated hypothyroidism during pregnancy were found to score lower on IQ tests than children of healthy mothers suggesting that early detection and treatment of hypothyroidism in pregnant women may be a critical part of prenatal care, according to a study funded by NICHD and others.
A research effort led by NIAID scientists produced the first high-resolution genetic map of Plasmodium falciparum, the deadliest malaria parasite, which is responsible for the death of more than two million people annually. Scientists supported by NHGRI along with groups in England and Japan completed the first sequence of a human chromosome, chromosome Genes on chromosome 22 have been implicated in immune system function, congenital heart disease, and several cancers including leukemia. After leading NIH for 6 years, Dr. Scientists funded by NIDCR and NIAMS, along with an NCI scientist discovered that leptin, the product of the obesity gene, acts as a bone inhibitor by telling the brain to slow down the rate of bone formation, showing for the first time that the brain has a central role in controlling bone formation and density.
A team including NCI scientists and grantees used microarray technology to show that the most common form of non-Hodgkin's lymphoma NHL , diffuse large B-cell lymphoma, is actually two distinct diseases, thus explaining why 40 percent of patients with this NHL can be cured through chemotherapy while others succumb to the disease. This is the first demonstration of a technology that promises to revolutionize cancer diagnosis as well as many other areas of research. David Platt Rall. NIH launched the first phase of a consumer-friendly database, ClinicalTrials. John's wort could significantly compromise the effectiveness of a protease inhibitor often used to treat those infected with HIV. An NIAID study showed that a nasal spray flu vaccine not only protected young children against the three strains of influenza for which the vaccine was designed to provide protection but also a flu strain not covered by the vaccine.
It also protected the children against flu-related middle-ear infections. Scientists supported by NHGRI and DOE along with the private company Celera completely sequenced the genome of the fruitfly Drosophila melanogaster, which is used to study a host of biological questions related to aging, development, learning, memory and more. An NHLBI-supported clinical trial showed that lowering the amount of salt for those who ate a "usual" American diet as well as those following the DASH diet — rich in vegetables, fruits and low-fat dairy foods and low in saturated fat, total fat and cholesterol — lowered blood pressure correspondingly for both those with and without hypertension, including African Americans.
The information from this project has been completely, immediately, and freely released to the world with no restrictions on its use. Researchers supported by NIGMS demonstrated that a simple and inexpensive change in basic surgical procedures — giving patients more oxygen during and immediately after surgery — can cut the rate of wound infections in half, thus saving millions of dollars in hospital costs by helping to prevent post-surgical wound infection, nausea and vomiting.
A team of scientists funded by NIAID determined the complete sequence of the genome of the bacterium — Vibrio cholerae — that causes cholera. By comparing the sequence of this strain with that of harmless strains of E. The new approach uses microarray gene chip technology to analyze the activity of more than genes at once. This advance should ultimately help physicians diagnose the cause of a woman's breast cancer and guide decisions about the most effective treatments. The new cells at least partially restored the heart's ability to pump blood. NIAID grantees completed sequencing the genome of Streptococcus pyogenes, a bacterium that causes a wide variety of human diseases including strep throat, scarlet fever, pneumonia, toxic shock syndrome, blood "poisoning," acute rheumatic fever, rheumatic heart disease, and the flesh-eating disease known as necrotizing fasciitis.
This information should aid scientists in developing new ways to prevent and treat these diseases. Seemingly the most effective typhoid vaccine ever developed, it is also virtually free of side effects. About 16 million people worldwide develop typhoid each year, and , die from it, mainly in developing countries without adequate sewage and sanitation. CML is a disease in which too many white blood cells are made in the bone marrow, the spongy tissue inside the large bones in the body. NCI funded the lion's share of the basic research that led to the discovery and development by Novartis of Gleevec, the first anti-cancer drug specifically developed to target the molecular problem that causes a particular type of cancer.
NHGRI scientists and others developed a method that combined microarray gene chip technology with a form of artificial intelligence. This enabled them to tell the difference between four childhood cancers that often look alike — neuroblastoma, Ewing's sarcoma, non-Hodgkin lymphoma Burkitt's lymphoma and rhabdomyosarcoma. Because the treatments for these tumors are quite different, an accurate diagnosis can be critical for a child's survival. This study should help lead to the discovery of genes that are altered in these tumors and ultimately to the development of effective new treatments.
This finding opens up the possibility of repairing heart muscle damage after a heart attack. Animal studies by NIDA researchers found that craving for cocaine seems to increase, rather than decrease, in the days and months after drug use has stopped. This phenomenon helps explain why addiction is a chronic, relapsing disease. People at high risk for type 2 diabetes can sharply lower their chances of getting the disease by losing weight 5 percent to 7 percent of their body weight and by getting 30 minutes of walking or other moderate exercise every day, according to the findings of a clinical trial sponsored by NIDDK. On August 9, President Bush announced that Federal funds could be used to support research using existing lines of human embryonic stem cells that meet certain criteria.
NIH then developed a registry of the known human embryonic stem cell lines so researchers could identify in their applications for funding which sources of stem cells they plan to use. An NEI-sponsored clinical trial showed that people at high risk of developing advanced stages of age-related macular degeneration AMD significantly lowered that risk by taking a high-dose combination of zinc and the antioxidants vitamin C, vitamin E and beta-carotene. These nutrients are the first effective treatment to slow the progression of AMD, a leading cause of visual impairment and blindness in Americans 65 years of age and older. NCRR-supported scientists were part of a team that cloned the world's first "knockout" pigs — ones with a particular gene removed.
The gene they removed was for a molecule on the surface of the pig cells that the human immune system recognizes and attacks, leading to the failure of transplanted tissues or organs. A team of NICHD and other scientists developed the first vaccine against Staphylococcus aureus, a major cause of infection and death among hospital patients. The findings, in a group of participants in NHLBI's long-running Framingham Study, are the first to tie homocysteine levels measured several years before with a later diagnosis of AD and the other dementias, providing some of the most powerful evidence yet of an association between high plasma homocysteine and later significant memory loss. NIAID released its Counter-Bioterrorism Research Agenda, a document describing an accelerated research plan for the most threatening agents of bioterrorism.
The agenda outlines the research NIAID will undertake to help protect civilian populations from diseases such as smallpox, anthrax and plague should those who wish to do harm unleash them intentionally. The success of this study puts us one step closer to the goal of having enough vaccine for every American if needed to respond to a potential outbreak. The international Mouse Genome Sequencing Consortium, jointly funded by NHGRI and several NIH institutes along with the Wellcome Trust in the United Kingdom, announced that it had assembled and deposited into public databases an advanced draft sequence of the mouse genome, the genetic blueprint for the most important animal model in biomedical research.
The sequence is freely available on the Internet. Roderic I. Researchers used whole-genome sequencing technology and computational methods to genetically compare two important isolates of the anthrax bacterium: the well-known Ames strain and an isolate from the Florida anthrax attacks. These techniques will enable researchers to more accurately trace the origin of individual bacterial strains, determine if those strains have been genetically modified, and assess differences in their ability to cause disease or resist antibiotics. NHLBI stopped early a major clinical trial of the risks and benefits of combined estrogen and progestin in healthy menopausal women due to an increased risk of invasive breast cancer.
The large trial, a component of the Women's Health Initiative WHI , also found increases in coronary heart disease, stroke, and pulmonary embolism in study participants on estrogen plus progestin compared to women taking placebo pills. There were some benefits of estrogen plus progestin, including fewer cases of hip fractures and colon cancer, but on balance the harm was greater than the benefit. NIH licensed a new technology that allows physicians and researchers to make detailed, three-dimensional maps of nerve pathways in the brain, heart muscle fibers, and other soft tissues. A new approach to cancer treatment that replaces a patient's immune system with cancer-fighting cells can lead to tumor shrinkage.
NCI researchers demonstrated that immune cells, activated in the laboratory against patients' tumors and then administered to those patients, could attack cancer cells in the body. The experimental technique, known as adoptive transfer, has shown promising results in patients with metastatic melanoma who have not responded to standard treatment. NIAID-supported researchers proved conclusively that the malaria-causing parasite Plasmodium falciparum became resistant to the anti-malarial drug chloroquine through mutations in a single parasite gene.
This finding has potentially important implications for malaria treatment and control. An international research consortium of NHGRI, other NIH components, and other countries launched a public-private effort to create the next generation map of the human genome. Called the International HapMap Project, this new venture is aimed at speeding the discovery of genes related to common illnesses such as asthma, cancer, diabetes and heart disease.
The international effort to sequence the three billion DNA letters is considered by many to be one of the most ambitious scientific undertakings of all time. The first draft of the human sequence was completed in June Researchers have now produced a "finished" sequence, which covers about 99 percent of the human genome's gene-containing regions, and has been sequenced to an accuracy of All of the sequence data have been deposited into public databases and made freely available to scientists around the world, with no restrictions on their use or redistribution.
The complete genetic blueprint of Bacillus anthracis — the microbe that gained notoriety during the anthrax mail attacks — has been completed by NIAID-funded researchers. This bacterium, which can cause potentially fatal inhalational anthrax, differs very little from a common soil bacterium related to it. Scientists hope that the genetic differences between these two may reveal valuable clues to its vulnerabilities. NHLBI published new clinical practice guidelines for the prevention, detection, and treatment of high blood pressure — a major risk factor for heart disease and the chief risk factor for stroke and heart failure. The guidelines define a new blood pressure category called "prehypertension" that includes about 22 percent of American adults, or about 45 million people.
Americans' lifetime risk of developing hypertension is greater than previously thought, according to the new guidelines. Medications and lifestyle changes are both crucial parts of treatment. Researchers supported by NIMH found a gene called 5-HTT that influences whether people become depressed when faced with major life stresses such as relationship problems, financial difficulties and illness. The gene by itself does not cause depression, but it does affect how likely people are to get depressed when faced with major life stresses. Another study led by NIAAA researchers found that this same gene affects drinking habits in college students.
These studies are major contributions toward understanding how a person's response to their environment is influenced by their genetic makeup. A team led by NIDCR and NICHD researchers discovered that "baby" teeth, the temporary teeth that children begin losing around their sixth birthday, contain a rich supply of stem cells in their dental pulp. The cells, named SHED, remain alive inside the tooth for a short time after it falls out of a child's mouth. This easily accessible source of stem cells could be readily harvested for research. Scientists hope they can learn to manipulate them to repair damaged teeth, induce the regeneration of bone, and treat neural injury or disease.
After an egg is fertilized, a specialized protein called L-selectin on the embryo surface binds to carbohydrates on the uterine wall. Scientists think that this interaction slows the embryo down to a complete stop so it can then attach to the wall of the uterus. The finding may lead to insights into infertility and early pregnancy loss. An international research team funded by NINR found that filters made from old cotton saris cut the number of cholera cases in rural Bangladesh villages almost in half. Other inexpensive cloth should work just as well in other parts of the world where cholera is endemic. Cholera is a waterborne disease that causes severe diarrhea and vomiting, killing thousands of people around the world every year.
This simple preventive measure has the potential to make a significant impact on a global health problem. NIH director Dr. Elias Zerhouni names five new institute directors: Dr. President George W. Bush visits NIH on Feb. Construction begins on a new Perimeter Security System including a fence around the Bethesda campus. Construction begins on the Bldg. Zerhouni announces the NIH Roadmap for Medical Research, a comprehensive plan whose purpose is to identify the major scientific opportunities and gaps in medical research that no single institute or center at NIH could tackle alone.
NIH opens the Mark O. It is the world's largest facility dedicated to clinical research. The ,square-foot addition welcomed occupants of its research wings in fall , and was to admit its first patients in early January The NIH Roadmap for Medical Research, a coordinated effort to speed the results of bench research to the patient bedside, marks its first anniversary, which includes the award of 9 grants to the inaugural class of winners of the NIH Director's Pioneer Awards. Elias Zerhouni announces an NIH proposal to enhance public access to taxpayer-supported research by creating an online, searchable archive of all NIH-funded publications within 6 months of their appearance in journals.
NIH proposes enhancements to its rules governing potential conflicts of interest on the part of employees, thereby resolving public and congressional concerns about the outside activities of NIH staff. The ultimate goal of the Blueprint is to accelerate neuroscience research to reduce the burden of nervous system disorders and maintain a healthy nervous system throughout life. COPR advocates building trust through community partnerships, building relationships with patients, building partnerships with community providers and building trust in both scientists and NIH scientific research. An international clinical trial concluded that women should consider taking letrozole after 5 years of tamoxifen treatment to continue to reduce the risk of recurrence of breast cancer.
This advance in breast cancer treatment will improve the outlook for many thousands of women. NCI supported the U. As of July , about 10 million American women were taking some form of hormone therapy, including approximately 6. A large, multi-center prevention study of estrogen-alone hormone therapy in healthy, postmenopausal women without a uterus, was stopped in February after researchers found that estrogen-alone had no effect on coronary heart disease risk, but increased the risk of stroke. The study, part of the NHLBI-sponsored Women's Health Initiative WHI , also found that estrogen-alone therapy significantly increased the risk of deep vein thrombosis, had no significant effect on the risk of breast or colorectal cancer, and reduced the risk of hip and other fractures.
In addition, among older women in the study, estrogen-alone therapy did not prevent cognitive decline. The International Human Genome Sequencing Consortium, led in the United States by the National Human Genome Research Institute and the Department of Energy, published its scientific description of the finished human genome sequence, reducing the estimated number of human protein-coding genes from 35, to only 20,,, a surprisingly low number for our species. Adding to a developing body of research examining a possible link between diabetes and cognitive decline, a long-term study supported by NIA found that diabetes mellitus was linked to a 65 percent increased risk of developing Alzheimer's disease AD. These results are among the first to examine how certain cognitive systems, including memory for words and events, the speed of processing information, and the ability to recognize spatial patterns, decline in people with diabetes, while others do not.
Further research, some currently under way, will tell researchers whether therapies for diabetes may in fact play a role in lowering risk of AD or cognitive decline. From language to literature, from music to mathematics, a single protein, known as mBDNF, appears central to the formation of the long-term memories needed to learn these and all other disciplines. Most of what we accomplish as human beings depends on what we learn. This discovery, led by scientists at NICHD, brings the possibility of studying this protein system in people with learning and memory disorders and perhaps designing new medications that might help to compensate for these problems. Continuing studies will reveal whether the same applies to those with type 2 diabetes, the more prevalent form of the disease.
A pilot project involves a few types of cancer chosen for their value in helping to determine the feasibility of a possible larger-scale project. The project will develop and test the complex science and technology framework needed to systematically identify and characterize genomic changes associated with cancer. Because of selective breeding over the past few centuries, modern dog breeds are a model of genetic diversity, from 6-pound Chihuahuas to pound Great Danes, from high-energy Jack Russell Terriers to mild-mannered basset hounds, and from the herding instincts of Shetland sheepdogs to pointers pointing. However, selective breeding has also caused many dog breeds to be predisposed to genetic disorders including heart disease, cancer and blindness.
In combination with the human genome, the dog genome sequence will help researchers identify genetic contributors to several diseases. The Duchess of Cornwall's interest in osteoporosis — her mother and grandmother died as a result of the disease — spurred the visit. Bush made his fourth visit to NIH in less than 3 years on November 1 to announce the government's pandemic influenza preparations and response.
His previous visit, on January 26, was for a minute town hall-style meeting to emcee a discussion with five citizens on the topic "Strengthening Health Care. NIH launched a new state-of-the-art way for applicants to submit their grant applications electronically. Beginning with the receipt date of Dec. NIH plans to transition all of its competing grant programs from paper to electronic by May The International HapMap Consortium, a public-private effort to chart patterns of genetic variation in the world's population, published the human haplotype map, or HapMap. With more than 1 million markers of genetic variation, the HapMap is a comprehensive catalog of human genetic variation showing "neighborhoods" of correlated genetic variation, or haplotypes, across the entire human genome.
Researchers will be able to identify genetic contributions to common diseases far more efficiently using HapMap data than with traditional approaches. NIH launched a major new program, the Institutional Clinical and Translational Science Awards CTSAs program, to encourage the development of clinical and translational science, so that new treatments can be developed more efficiently and delivered more quickly to patients.
Credit likely goes to clinical strategies proven in the s to significantly delay or prevent kidney failure: angiotensin-converting enzyme inhibitors ACE-inhibitors and angiotensin receptor blockers ARBs , which lower protein in the urine and are thought to directly prevent injury to the kidneys' blood vessels; and careful control of diabetes and blood pressure. The nation's leading cancer organizations reported in October that Americans' risk of dying from cancer continues to decline and that the rate of new cancers is holding steady. Observed cancer death rates from all cancers combined dropped 1. Key NIH Roadmap accomplishments include:. Elias Zerhouni convened the first in a series of emergency meetings at which clinical directors, nursing and administrative leaders rapidly hammered out ways NIH could help.
In partnership with the American Association of Medical Colleges, NIH created and activated a telemedicine brain trust for specialty medical consultations over a telephone hotline. An advance team and medical team numbering about 50 people deployed temporarily to a field hospital in Mississippi. In addition, the Clinical Center made beds of "surge capacity" available for patients who might need to be transferred from the affected areas, such as young cancer patients who would need specialized services. The Chimpanzee Sequencing and Analysis Consortium, which is supported in part by NHGRI, described its landmark analysis comparing the genome of the chimp Pan troglodytes with that of humans Homo sapiens.
The chimp sequence draft represents the first non-human primate genome. Zerhouni announced the latest and final regulations to prevent conflicts of interest at NIH on August In the works since interim final regulations were published in February of , the new revised standards became effective on August 31, when they appeared in the Federal Register. The researchers found that antiviral treatment is a critical component of a multi-pronged approach. An international group of researchers working in more than 20 laboratories around the globe and funded in part by NIAID sequenced the genomes of three parasites that cause deadly insect-borne diseases: African sleeping sickness, leishmaniasis and Chagas disease.
Knowing the full genetic make-up of the three parasites might lead to better ways to treat or prevent the diseases they cause. They also had no effect on the most common cancers in women or on total cancers. The PSI aims to figure out the three-dimensional shapes of proteins, with the long-term goal of being able to predict most protein structures from their DNA sequences. More than 1, protein structures were solved in the PSI's first phase, which was dedicated to figuring out how to process proteins and determine their three-dimensional structures more efficiently. NHGRI announced 13 more organisms that the Large-Scale Sequencing Research Network will target, including 9 mammals, as part of its ongoing effort to produce genomic data that will expand biological knowledge and improve human health.
The Edmond J. Safra Family Lodge opened its doors to guests on Wednesday, June 1. This new addition to the NIH campus offers a temporary residence for families and loved ones of adult patients who are receiving care at the NIH Clinical Center. Project Bioshield, which was signed into law on July 21, gives federal agencies new tools to accelerate research on medical countermeasures to safeguard Americans against chemical, biological, radiological or nuclear attack.
Researchers funded by NIH were asked to begin voluntarily submitting their manuscripts on May 2, to the National Library of Medicine's PubMed Central upon acceptance for publication. The public will also have greater access to published material about the medical research their tax dollars support. The large study, with 33, participants, concluded that diuretics should be the first therapy for most patients with high blood pressure. Three independent research teams supported by NEI found a gene, called complement factor H CFH , that affects a person's risk of developing age-related macular degeneration AMD , the leading cause of blindness in people over age One team, which included NIH's own researchers, found that people with this variant of the CFH gene are more than seven times more likely to develop the disease.
The fashion show brought to life the Red Dress, the national symbol for women and heart disease awareness. NCI-funded research spanning nearly 2 decades helped lead to FDA approval for a vaccine to prevent cervical cancer, a disease that claims the lives of nearly 4, women each year in the United States. It is the first cancer vaccine approved by the FDA. NHLBI's nearly half-century commitment to exploring innovative mechanical approaches for treating damaged hearts led to the development of the first totally implanted artificial heart, approved by FDA in September The top royalty earner is the invention of a Taxol-coated stent, which helps more than half a million Americans each year avoid bypass surgery.
On May 2, NIH dedicated a new research facility for studying globally important infectious diseases. Bill Young Center for Biodefense and Emerging Infectious Diseases will house studies of naturally occurring infectious diseases, infectious agents that might be used for bioterrorism and potential vaccines. A multicenter research team, funded in part by NHGRI, completed the draft genome sequence of the rhesus macaque monkey and deposited the information into free public databases.
The macaque is the second non-human primate, after the chimpanzee, to have its genome sequenced. The genome sequence will facilitate research in neuroscience, behavioral biology, reproductive physiology, endocrinology, and cardiovascular studies. The network unites more than investigators at dozens of research centers nationwide to study more than 40 rare diseases, most of which are difficult to diagnose and treat because they are so poorly understood.
The new initiative will help move discoveries more quickly to patients. As part of the largest hypertension clinical trial conducted to date, researchers began a comprehensive outreach program to improve high blood pressure control nationwide. About physicians in 34 states and Washington, DC, have completed training to educate other physicians in their communities. Their goal is to help doctors and patients prevent and better treat high blood pressure. The drug misoprostol was shown to provide a safe, convenient, and inexpensive way to prevent postpartum hemorrhage, a major killer of women in developing countries. In a clinical study conducted in rural villages in India, women who received the drug after birth were less likely to have serious postpartum bleeding, and had significantly lower average blood loss, than women who received placebo.
Leading scientists and experts on women's health joined study participants for a 2-day conference at NIH. Attendees discussed the findings, public health impact, and future directions of the Women's Health Initiative — the largest and most comprehensive study of postmenopausal women's health ever conducted in the United States. The NIH Pathway to Independence Award program introduced a new opportunity for promising postdoctoral scientists to receive both mentored and independent research support from the same award.
Announced in January, the program answers a National Academy of Sciences call for new ways to help early-career scientific investigators progress from postdoctoral studies to running their own research programs. NIH created a plan for continuity of operations should a pandemic flu outbreak occur. The goal is to maintain critical operations and protect patients, visitors, and employees — as well as animals and ongoing research — in the event of widespread infectious disease or other emergencies. The first comprehensive analysis of an animal's reaction to the influenza virus provided new insights into this deadly flu, which disproportionately killed young people at the prime of life.
NIAID-funded scientists found that the virus triggers a hyperactive immune response that may be the key to its lethal effects. A deeper understanding of the virus will aid efforts to develop improved therapies against future influenza threats, including the H5N1 avian influenza virus. The U. Senate passed an amended version by unanimous consent on December 8. The House approved the Senate version by voice vote on December 9. The legislation — NIH's third omnibus reauthorization in history and first since — affirmed the importance of NIH and its vital role in advancing biomedical research to improve the health of the Nation.
Elias Zerhouni endorsed the conclusions of a National Academies report on women in science, which proposed that immediate, decisive action must be taken to maximize the potential of women scientists. The report found that women currently face barriers to hiring and promotion in research universities in many fields of science and engineering, which deprives the nation of an important source of talent and may reduce U. An imaging molecule known as FDDNP binds to abnormal proteins in the brain and shows promise for enabling early and reliable diagnosis of Alzheimer's disease. When administered to patients before a brain scan, the molecule helps to distinguish among people who are healthy, those with Alzheimer's disease, and those with mild cognitive impairment, which sometimes progresses to Alzheimer's disease.
NIEHS-supported researchers announced that they had successfully sequenced the DNA of 15 mouse strains most commonly used in biomedical research. More than 8. The new data will help researchers better understand complex genetic traits, such as why some individuals are more susceptible to certain diseases, and how environmental agents influence the development of disease. Bush visited NIH on January 17, touring a cancer research laboratory and participating in a discussion on cancer prevention. It was his fifth visit to the NIH campus in the past 4 years. The president praised the agency's work, touting the new vaccine against cervical cancer. An experimental vaccine — originally created and tested over the past 2 decades by NIAID scientists — appears safe and effective in preventing hepatitis E, a sometimes-deadly viral disease prevalent in developing countries.
NINDS launched the new Neurological Emergencies Treatment Trials NETT network, a nationwide clinical study that will look at emergency interventions for stroke, massive seizure, brain or spinal cord injury, and other major emergencies that affect the brain and nervous system. The long-term goal of the study, conducted in ambulances and hospitals across the country, is to improve medical care in the first minutes and hours after neurological emergencies occur. By modifying only 4 genes in human skin cells, researchers supported by NCRR and NIGMS found that they could "reprogram" the cells to give them the characteristics of embryonic stem cells.
This major advance could open doors to innovative therapies in the future, where people's own cells might be reprogrammed and used to repair their damaged tissues and organs. EUREKA, a new funding initiative to help researchers with original ideas, was launched by 5 institutes. EUREKA — exceptional, unconventional research enabling knowledge acceleration — awards seek to raise the profile of paradigm-shifting concepts that might otherwise get overlooked. A collaborative effort by 3 international research teams uncovered new clues about why some people develop type 2 diabetes and others don't. The NIH-funded research relied on a relatively new method, called a genome-wide association study GWAS , which rapidly and cost effectively analyzes and compares genetic differences between people with and without specific illnesses.
The scientists identified 4 new genetic risk factors for type 2 diabetes. Elias Zerhouni established an NIH-wide working group to address the issues that surround GWAS research, which holds tremendous promise for uncovering new and more effective methods for preventing, diagnosing, and treating disease. In addition, the appearance of large pronormoblasts suggested that she was infected with parvovirus B Excess viral DNA in her bone marrow confirmed that her illness was caused by persistent parvovirus B19 infection.
Serum immunoglobulin levels decreased beyond the lower normal limit, which indicated that her humoral immunity was impaired after rituximab-combined chemotherapy. Although she had been infected with parvovirus B19, she was re-infected and failed to control the viral expansion. High-titer immunoglobulin against parvovirus B19 was intravenously administrated and resulted in remarkable reticulocytosis and improvement of anemia. High-titer immunoglobulin, which contained a sufficient amount of neutralizing antibodies against parvovirus B19, likely inactivated most viruses in vivo. These investigators successfully eradicated the virus after 2 courses of high-dose therapy at 0. It is important to consider that parvovirus B19 infection is a possible cause of progressive anemia in B-cell lymphoma patients treated with rituximab-combined chemotherapy.
The authors proposed that the use of high-titer immunoglobulin against parvovirus B19 may enable such immunocompromised patients to eradicate the virus before sufficient immune system reconstruction. Perlmutter et al examined if plasma exchange or IVIG would be better than placebo sham IVIG in reducing severity of neuropsychiatric symptoms in children, exacerbations of tics and obsessive symptoms. Symptom severity was rated at baseline, and at 1 month and 12 months after treatment by use of standard assessment scales for OCD, tics, anxiety, depression, and global function.
A total of 30 children entered the study and 29 completed the trial. Ten received plasma exchange, 9 IVIG, and 10 placebo. The authors concluded that plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection-triggered OCD and tic disorders. They stated that further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies.
These were used at baseline and on weeks 2, 4, 6, 10, and 14 post-treatment, after which blinding was broken. The study was conducted from March through August These researchers observed no significant differences between both treatment groups regarding post-treatment changes in tic severity. Then, there was a Though this improvement was maintained over the following 8 weeks, no statistically significant differences between the IVIG and the placebo group with regard to improvements in obsessions and compulsions were detected at subsequent assessments. IVIG treatment was associated with significantly more side effects than placebo, most notably headache.
The authors concluded that based on the present results, IVIG can not be recommended in tic disorders. In an attempt to improve this outcome, in , they began to empirically treat affected patients with IVIG and corticosteroids. These investigators reviewed the clinical records and echocardiograms of 20 affected patients encountered in their institutions and treated with IVIG and corticosteroids from to All 20 were initially referred at a median gestational age of 23 weeks range of 18 to 38 weeks ; 19 mothers were anti-Ro antibody positive, 8 anti-La antibody positive, and 7 had clinical autoimmune disease.
During pregnancy, maternal IVIG was given in 9 and dexamethasone in Twelve underwent pacemaker implantation. Four with hydrops at presentation died perinatally, despite initial improvement in function in 3. At a median follow-up of 2. They stated that further studies prospective, multi-center randomized trials including the evaluation of maternal and neonatal titers before and after therapy are needed to determine the optimal dose and timing of IVIG administration. The updated search identified 1 new study; 10 studies of variable quality undertaken in 8 countries are included in this review.
The authors concluded that because of concerns about study quality, there is still insufficient evidence to support the routine administration of IVIG to prevent mortality in infants with suspected or subsequently proved neonatal infection. A large study of the effectiveness of IVIG in neonates with suspected infection has recently been completed. The results of that trial should establish the usefulness of IVIG for suspected infection in newborns. The INIS Collaborative Group stated that neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin.
Meta-analyses of trials of IVIG for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality. The primary outcome was death or major disability at the age of 2 years. There was no significant between-group difference in the rates of the primary outcome, which occurred in of 1, infants Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes.
In follow-up of 2-year-old infants, there were no significant differences in the rates of major or non-major disability or of adverse events. The authors concluded that therapy with IVIG had no effect on the outcomes of suspected or proven neonatal sepsis. These produce improvement within a few days after initiation, and so are useful for acute exacerbation including myasthenic crisis or in the peri-operative period.
High-dose prednisone has been more universally preferred for remission induction, but it acts more slowly than IVIG and PE, commonly only after a delay of several weeks. Slow tapering of steroids after a high-dose pulse offers a method of maintaining the state of remission. However, because of significant side effects, other immunosuppressants ISs are frequently added as "steroid-sparing agents". The currently available ISs exert their immunosuppressive effects by 3 mechanisms:. In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. Until now, the treatment of MG has been based primarily on experience rather than gold-standard evidence from randomized controlled trials.
It is hoped that well-organized studies and newer experimental trials will lead to improved treatments. When discontinuing immune globulin, it is advisable to do so during the spring months to minimize exposure to viral infections. We generally wait three or four months after discontinuation before performing immune testing. Alijotas-Reig stated that currently there are no reliable data regarding the actual treatment received by women with refractory obstetric APS OAPS. These researchers evaluated current clinical evidence and new trends in the treatment of refractory OAPS.
A non-systematic but comprehensive literature search using relevant keywords was made to identify relevant articles published in English from different computerized databases: PubMed Medline , Google Scholar electronic database search and The Cochrane Library, from January to March Studies on the treatment of poor obstetric outcomes in women with OAPS were included. Prospective randomized clinical trials, cohort studies, reviews, systematic reviews and meta-analysis were retrieved. A total of articles were finally selected for this review, including 17 randomized clinical trials and 4 meta-analyses. The majority of articles were non-randomized original papers and basic and clinical reviews. Unfortunately, well-designed studies regarding the usefulness of new drugs in refractory OAPS are scarce.
Hydroxychloroquine and low-dose prednisolone appear to be useful when added to standard therapy. Current data do not support the use of IVIG in this field. Also, UpToDate reviews on "Attention deficit hyperactivity disorder in children and adolescents: Treatment with medications" Krull, a , "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis" Krull, b , and "Adult attention deficit hyperactivity disorder" Searight and Burke, do NOT mention the use of IVIG as a therapeutic option. The investigators concluded that plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection triggered OCD and tic disorders.
The investigators stated that further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies. This 3- armed trial with 10 or less participants per arm has limited statistical power. Martino et al stated that despite their empirical use in community settings, there is still a lack of conclusive, evidence-based data regarding the usefulness of antibiotic and immuno-modulatory treatments in children with PANDAS.
Another study found no correlation between clinical exacerbations and changes in a variety of markers of brain autoimmunity, the proposed pathogenesis of PANDAS. Marconi et al stated that the use of treatment strategies, such as therapeutic plasmapheresis or IVIG, has been proposed to explain the autoimmune process responsible for the pathogenesis of PANDAS. Moreover, they stated that further research is still necessary in order to understand the role of streptococcal infection in the pathogenesis of PANDAS. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms?
Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy. IVIG is effective and should be offered in the long-term treatment of chronic inflammatory demyelinating polyneuropathy Level A. IVIG is probably effective and should be considered for treating moderate-to-severe myasthenia gravis and multifocal motor neuropathy Level B. IVIG is possibly effective and may be considered for treating non-responsive dermatomyositis in adults and Lambert-Eaton myasthenic syndrome Level C.
Evidence is insufficient to support or refute use of IVIG in the treatment of immunoglobulin M paraprotein-associated neuropathy, inclusion body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher syndrome, or in the routine treatment of post-polio syndrome or in children with GBS Level U. One review author extracted the data and 2 others checked these data.
For methodological reasons, no formal meta-analysis was performed. These researchers identified 7 RCTs. These trials differ in inclusion criteria, comparison with alternative treatment and outcomes. All these 3 smaller studies were under-powered. Adverse events due to IVIG were moderate fever, nausea, headache , self-limiting and subjectively less severe than with PE although, given the available data, no statistical comparison was possible. Other than where specific limitations were mentioned the trials were generally at low-risk of bias. A further, but under-powered, trial showed no significant difference between IVIG and oral methylprednisolone.
Despite the wide use of IVIG, consensus on its optimal use is deficient. The effectiveness of IVIG has been proven in Guillain-Barre syndrome level A , chronic inflammatory demyelinating polyradiculoneuropathy level A , multi-focal mononeuropathy level A , acute exacerbations of MG and short-term treatment of severe MG level A. As a second-line treatment, the use of IVIG is recommended in dermatomyositis in combination with prednisone level B and is considered as a treatment option in polymyositis level C.
As a 2nd- or even 3rd-line therapy, the use of IVIG should be considered in patients with RRMS if conventional immunomodulatory therapies are not tolerated level B and in relapses during pregnancy or post-partum period good clinical practice point. Finally, it appears that the use of IVIG has a beneficial effect also in stiff-person syndrome level A , some paraneoplastic neuropathies level B , and some acute-demyelinating diseases and childhood refractory epilepsy good practice point. In a Cochrane review, Lunn and Nobile-Orazio evaluated the effects of immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated demyelinating peripheral neuropathy. They also checked bibliographies and contacted authors and experts in the field.
These researchers included randomized or quasi-randomized controlled trials involving participants of any age treated with any type of immunotherapy for anti-myelin-associated glycoprotein antibody-associated demyelinating peripheral neuropathy with monoclonal gammopathy of undetermined significance and of any severity. The primary outcome measure was change in the Neuropathy Impairment Scale or Modified Rankin Scale at 6 months after randomization.
Secondary outcome measures were: Neuropathy Impairment Scale or the Modified Rankin Score at 12 months after randomization; meter walk time, subjective clinical scores and electrophysiological parameters at 6 and 12 months after randomization; IgM paraprotein levels and anti-myelin-associated glycoprotein antibody titers at 6 months after randomization; and adverse effects of treatments. The 2 authors independently selected studies; and 2 authors independently assessed the risk of bias in included studies. These investigators identified 7 eligible trials participants , which tested IVIG, alfa-interferon alfa-2a, PE, cyclophosphamide and steroids, and rituximab. Only 2 trials, of IVIG with 33 participants, including 20 with antibodies against myelin-associated glycoprotein , had comparable interventions and outcomes, but both were short-term trials.
There were no clinical or statistically significant benefits of the treatments used on the outcomes pre-defined for this review, but not all the predefined outcomes were used in every included trial. Intravenous immunoglobulin showed a statistical benefit in terms of improvement in Modified Rankin Scale at 2 weeks and meter walk time at 4 weeks. Cyclophosphamide failed to show any benefit in the trial's primary outcome, and showed a barely significant benefit in the primary outcome specified here, but some toxic adverse events were identified. A trial of rituximab was of poor methodological quality with a high risk of bias and a further larger study is awaited. Serious adverse events were few in the other trials. The authors concluded that there is inadequate reliable evidence from trials of immunotherapies in anti-myelin-associated glycoprotein paraproteinemic neuropathy to form an evidence base supporting any particular immunotherapy treatment.
There is very low quality evidence of benefit from rituximab. They stated that large, well-designed, randomized trials of at least 6 to 12 months duration are needed to evaluate existing or novel therapies, preferably employing unified, consistent, well-designed, responsive and valid outcome measures. Furthermore, in a review on "Intravenous immunoglobulin for treatment of neuromuscular disease", Ruzhansky and Brannagan stated that "Clinical trials in amyotrophic lateral sclerosis, inclusion body myositis, and anti—myelin-associated glycoprotein neuropathy have been negative".
Drulovic et al noted that Hashimoto's encephalopathy HE is a rare autoimmune syndrome characterized by various neuropsychiatric manifestations, responsive to steroid treatment and associated with Hashimoto's thyroiditis. There are only a few reports suggesting that IVIG might represent an effective treatment modality for the severe steroid-resistant HE cases. These investigators presented a patient with HE who developed a complete recovery after the IVIG therapy followed by a long-lasting remission. After detailed examinations, the diagnosis of HE was established.
Two years later, in June , new manifestations unsteadiness in gait, personality changes, seizures, and persistent headache gradually developed during a 6-month period. Response to steroids was unsatisfactory and partial, since headaches and personality changes had continuously worsened. Gradual improvement was noticed and a complete recovery developed over the following weeks. Up to March , during a 7-year follow-up period, remission persisted. The authors concluded that to their best knowledge, this was the first report of a long-lasting remission of HE after IVIG therapy. Therefore, this case further supported administration of IVIG, as a potentially beneficial treatment modality, in severe cases of HE that are completely or partially resistant to steroids.
Olmez et al shared their experience on clinical presentation and management of patients diagnosed with HE. These researchers identified 13 patients who met the criteria for the diagnosis of HE. The median age was 49 years range of 2 to 66 and all except 1 were women. Encephalopathy in the form of altered mental status, stroke-like symptoms or seizures, with prompt resolution of symptoms upon receiving steroids, was the commonest presentation, seen in 7 patients. The second commonest presentation was subacute progressive decrease in cognitive function, which reversed within days to weeks after steroid therapy, seen in 4 patients.
Electroencephalogram EEG was available in 12 patients and was abnormal in 8, showing non-specific cerebral dysfunction in all 8 and epileptiform activity in 3. Treatment consisted of steroids in the acute phase for 12 of 13 patients with rapid improvement in symptoms. Maintenance therapy was rituximab in 7 patients, IVIG in 7, azathioprine in 4, mycophenolate mofetil in 3, and methotrexate in 1 some patients received sequential therapy with different agents. There was complete or near complete resolution of symptoms in 12 of the 13 patients. The authors concluded that they presented a cohort of patients in whom central nervous system dysfunction was associated with elevated anti-thyroid antibodies and reversal of disease followed immunomodulatory therapies.
This was a small study and the findings were confounded by sequential therapies with different agents. He and colleagues reported the findings of a case of a year old man presented with unconsciousness, spasms and a previous misdiagnosis as viral encephalitis. Response to anti-viral and steroid therapy was unsatisfactory, but treatment with immunoglobulin combined with corticosteroid therapy achieved rapid and complete recovery. The authors concluded that any patient presenting with acute or subacute unexplained encephalopathy should be considered HE, even if the thyroid function is normal. Thyroid antibody testing should be performed because this may be the most important clue to diagnosis. As soon as the diagnosis is made, steroid therapy is the first choice.
If the steroid therapy does not lead to immediate improvement, IVIG is an effective alternative treatment. An UpToDate review on "Hashimoto's encephalopathy" Rubin, stated that "Clinical improvement with intravenous immunoglobulin, and plasmapheresis has been reported in individual cases". Since available evidence is based on single-case studies as well as small case-series studies, the role of IVIG for the treatment for autoimmune encephalopathy has yet to be established. In a Cochrane review, Wong et al assessed the safety and effectiveness of the use of IVIG antenatally to women with severe fetal red blood cell alloimmunization. These investigators searched the Cochrane Pregnancy and Childbirth Group trials register December 19, , and reference lists of articles.
Randomized trials assessing the antenatal use of IVIG administered at any dose, frequency or duration with a control group using any other, or no treatment in the management of fetal red blood cell alloimmunization were selected for analysis. Two review authors independently assessed the available evidence. There were no included studies. The authors concluded that no information is available from randomized trials to indicate whether the antenatal use of IVIG is effective in the management of fetal red blood cell alloimmunization. Several case series suggested a beneficial role in delaying the onset of fetal anemia requiring invasive intrauterine transfusion. An UpToDate review on "Epidemiology, pathogenesis, treatment, and prevention of enterovirus and parechovirus infections" Modlin, stated that "The therapeutic options for more serious infections are limited and none has been subjected to adequate evaluation by clinical trials.
Intravenous immune globulin IVIG has been administered to B-cell deficient patients with persistent meningoencephalitis, on a case by case basis, with mixed results". Joao stated that human B cell immune deficiencies are associated with increased susceptibility to viral and fungi infections, which are T cell immunity related infections. Also, some viral infections occurring in immune depressed patients such as cytomegalovirus CMV infections are recommended to be treated with IVIG in combination with anti-viral therapy.
This fact has no clear biological explanation but it has been shown to be successful. Recently, B cells and immunoglobulin were identified as essential elements driving T cell receptor TCR diversity generation. Idiotype peptides of B cell immunoglobulin may be the driving force for the antigen presenting function of B cells and other antigen presenting cells to influence the T cell repertoire. This seems to be another relevance of Jerne's idiotypic network and another function of immunoglobulin.
Since T cells function depends on the diversity of the TCR repertoire, means to increase the diversity of the T cell repertoire may improve T cell function in situations characterized by a contracted TCR repertoire e. The fact that immunoglobulin influences the composition of T cell repertoire by increasing its diversity allows a much wider application of this molecule in the clinical practice. The author presented a novel reasoning for the use of IVIG in humans, which should be explored. All the situations where immune reconstitution occurs are potentially a target for this therapeutically mechanism, aiming to improve the diversity of the reconstituted immune repertoires.
This new role of Ig molecule may help to explain several effects that IVIG have in the T cell compartment, such as modulation of the activation and function of effectors T cells. The idea that immunoglobulin is essential in the generation and maintenance of a diverse compartment of T cells, affecting T cell function via that mechanism suggests a promising approach to medical conditions involving immune reconstitution.
The primary end-point was to determine the cumulative incidence of CMV infection in patients who received prophylactic IVIG according to the algorithm intervention group and compare it with that of a sequentially assessed control group, to which prophylactic IVIG were not administered. The study included 79 patients 44 in the intervention and 35 in the control group. Gavhed et al stated that there is currently no well-accepted therapy for central nervous system Langerhans cell histiocytosis CNS-LCH , a neuroinflammatory disease clinically characterized by often progressive, neurological symptoms including ataxia, dysarthria, dysphagia, hyper-tonicity, intellectual impairment and behavioral abnormalities.
During the IVIG treatment, the neurological deterioration initially appeared to be haltered, but over time there was still some deterioration. Edeer-Karaca et al stated that common variable immunodeficiency CVID is an immunodeficiency syndrome characterized by generalized defective antibody production and recurrent sino-pulmonary bacterial infections.
Familial inheritance of CVID is very rare, and these investigators reported 2 siblings with CVID presenting remarkable autoimmune manifestations such as relapsing polychondritis, juvenile idiopathic arthritis and chronic inflammatory bowel disease. Autoimmune and inflammatory complications showed minimal improvement under regular IVIG replacement therapy, prophylactic antibiotics and immunosuppressives in these patients. Hughes et al noted that idiopathic solar urticaria SU is a rare, debilitating photodermatosis, which may be difficult to treat.
First-line treatment with anti-histamines is effective in mild cases, but remission after phototherapeutic induction of tolerance is often short-lived. Other treatment options include PE, photopheresis and cyclosporine. These researchers presented 2 cases of severe, idiopathic SU, which were resistant to conventional treatment. Both patients achieved remission after administration of IVIG and have remained in remission at 13 months and 4 years, respectively.
There were only 2 case reports of successful treatment of solar urticaria with IVIG. It is also generally safe, even if certainly subject to significant theoretical risks, such as induction of viral infection or anaphylaxis. Llamas-Velasco et al stated that the treatment of SU can be difficult. Only a few cases of SU have been treated with IVIG as monotherapy or combined with phototherapy , with reported fast and durable increase of solar exposure tolerance.
Photo-test, performed 3 months after the treatment, showed only a slight minimal urticating dose improvement, and both patients reported just a moderate and "transient" subjective improvement. These researchers performed a retrospective multi-centric study via the mailing of a questionnaire to the French photodermatology units to analyze all cases of patients with SU who were treated with IVIG. A total of 7 patients 5 women with a mean age of 40 years range of 32 to 55 years and a mean disease duration of 5 years range of 2 to 10 years received IVIG.
The administration schedule differed from one patient to another: 1. Five of 7 patients obtained a complete remission. The number of courses necessary to obtain clinical remission varied from 1 to 3 courses. Complete remission was maintained during 4 to more than 12 months but anti-histamines were still required. In 1 case, PUVA photochemotherapy was administered. The authors concluded that the findings of this case series suggested a beneficial effect of IVIG in severe SU; but additional prospective trials including a larger number of patients are needed to demonstrate the effectiveness of IVIG and to specify the optimal modalities of their administration in this disease.
Drawbacks of this study included its retrospective study design, limited number of patients, and variations in the IVIG administration schedule. Also, an UpToDate review on "Photosensitivity disorders photodermatoses : Clinical manifestations, diagnosis, and treatment" Elmets, does not mention the use of IVIG as a therapeutic option. These researchers also assessed in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection.
No language restrictions were applied. The updated search identified 1 published study and 1 ongoing study. A total of 8 studies evaluating 3, infants were included in this review. Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry RR 0. Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry RR 1.
The authors concluded that in previous reviews, they encouraged researchers to undertake well-designed trials to confirm or refute the effectiveness of IVIG in reducing adverse outcomes in neonates with suspected infection. Such a trial has been undertaken. Results of the INIS trial, which enrolled 3, infants, carried a heavy weight in the current update of this review, and the undisputed results showed no reduction in death or major disability at 2 years of age. They stated that routine administration of IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended. She showed weakness, muscle atrophy and sensory abnormality in 4 limbs with patchy distribution, suggesting involvement of multiple peripheral nerve trunks.
Sural nerve biopsy showed recanalization and lymphocytic infiltration in the epineural small vessels, suggesting the presence of vasculitis. She was diagnosed as having vasculitic neuropathy complicated with Sjogren's syndrome. Methylprednisolone pulse therapy followed by oral prednisolone was started and these symptoms gradually improved in 1 month. At age 63, she felt dysesthesia in the right lower limb and this sensory abnormality spread to upper limbs.
Two years later, she was admitted again due to clumsiness of hands and gait disturbance. Neurological examination showed decreased vibration and position sense of lower limbs and limb ataxia in addition to dysesthesia. Electrophysiological studies demonstrated significant decrease in amplitude of sensory nerve action potentials and delayed somatosensory evoked potentials after N13, indicating impairment of dorsal root ganglions. One week later, sensory ataxia was improved. It has been known that Sjogren's syndrome is often complicate with various types of neuropathies including vasculitic neuropathy and sensory neuropathy. This patient developed these 2 different types of neuropathies, which were dramatically improved after 2 different therapeutic regimens; indicating the importance to select a suitable treatment regimen in accordance with the mechanism of neuropathy associated with Sjogren's syndrome.
De Toni Franceschini et al reported on the case of a year old woman, with asthma and sinusal polyposis in her medical history, who suddenly developed a painful polyneuropathy with diplopia. Nerve conduction studies, performed at the very onset of the neuropathy, could not definitely rule out a Guillain-Barre syndrome GBS and high-dose IVIG was administered. Clinical and laboratory findings subsequently supported the diagnosis of Churg-Strauss syndrome; corticosteroid therapy was started and clinical stabilization of neuropathy was apparently achieved. No indicators of unfavorable outcome were present at that time. Nevertheless, 30 days after the onset the patient acutely worsened with severe polyneuropathy relapse and fatal systemic diffusion to heart, kidney and mesenteric district, which a single cyclophosphamide pulse failed to control.
The authors stated that this case highlighted the possibility that a GBS-like onset of Churg-Strauss syndrome neuropathy should be regarded as a part of multi-organ, severe or even life-threatening vasculitic involvement, requiring the most aggressive treatments, regardless of the presence of recognized factors of poor outcome. Thus, there is insufficient evidence to support the use of IVIG for the treatment of vasculitic polyneuropathy. The Austrialian National IVIg Criteria Review Working Group NICRWG 's guideline on "Criteria for the clinical use of intravenous immunoglobulin" concluded that the evidence for IVIG for autonomic ganglionopathy is insufficient level 4a evidence -- small case studies only and should be used only in exceptional circumstances -- such as in urgent or life-threatening circumstances, or in circumstances in which significant morbidity would be expected and other clinically appropriate standard therapies have been either exhausted or are contraindicated.
Simon et al evaluated the likelihood of response to IVIG by studying consecutive patients presenting with progressive, asymmetric, pure lower motor neuron LMN limb weakness, and determined the clinical phenotype of those who respond. A total of 31 consecutive patients with progressive, focal-onset LMN limb weakness, without evidence of clinical upper motor neuron signs; sensory, respiratory, or bulbar involvement; or evidence of motor nerve conduction block on electrodiagnostic studies, were prospectively included in this study. Electrodiagnostic studies, a neuromuscular symptom score, and expanded Medical Research Council sum score were documented before and after IVIG treatment. The final diagnosis was determined after prolonged clinical follow-up.
All responders demonstrated distal upper limb-onset weakness, EMG abnormalities confined to the clinically weak muscles, and a normal creatine kinase. Sex, age at onset, number of involved limb regions, and the duration of symptoms before treatment were not significantly different between groups. The authors concluded that the findings of this study do not support uniform use of IVIG in patients presenting with progressive asymmetric LMN limb weakness. It is suggested that IVIG treatment be limited to patients who demonstrate clinical and laboratory features suggestive of multifocal motor neuropathy. McMahan et al highlighted novel therapies that are being used in SSc. Therapeutic interventions in SSc generally target at least 1 of 3 ongoing biological processes characteristic of the disease: vasculopathy, autoimmunity and tissue fibrosis.
Treatment decisions in SSc are determined by the level of disease activity and the degree of specific organ involvement. Traditional therapy has primarily focused on organ-specific management without clear evidence of overall disease modification. The authors provided a review of a variety of agents, which are already used for other autoimmune diseases, that are now being used to treat active SSc skin or lung disease, including rituximab, tocilizumab and IVIG.
Several agents studied in-vitro and in animal models of fibrosis have shown promise, including bortezomib, LPA-1 antagonists, anti-CCN2 therapy, anti-IL and thrombin antagonists. The authors also provided details on targeting intracellular molecular pathways and matricellular proteins, which is another novel area of investigation. The authors concluded that combination therapy may be necessary to control the complex biological network active in SSc. They noted that most of the current evidence that suggest benefit of these agents is based on small population studies; ultimately well-designed clinical trials are needed to define the role of these agents in treating SSc.
A favorable response correlated with shorter interval between symptom onset and treatment initiation median 9. The authors concluded that these retrospective findings justified consideration of a trial of IT in patients with suspected autoimmune epilepsy. Furthermore, likely confounders such as anti-epileptic drug medication changes during the trial could not be controlled for and non-responders may have been lost to follow-up. The authors stated that a RCT with a cross-over design would help to further specify treatment effect and would limit confounders. In an editorial that accompanied the afore-mentioned study, Ruegg and Panzer stated that "These results lay the foundation for a randomized controlled trial of IT in presumed autoimmune epilepsy, which would compare standardized treatment groups, thereby eliminating biases with regards to treatment choice and disease severity.
This study should also pave the way for additional prospective studies regarding the natural history of autoimmune PRE [pharmaco-resistant epilepsy] and serves to raise awareness of the role of IT in the treatment of refractory epilepsies". Rogosnitzky and colleagues stated that Crohn's disease CD is a debilitating condition that still requires improvement in its management. Intravenous immunoglobulin IVIG has been used in the management of aminosalicylate- and steroid-resistant CD for more than 20 years, although the published literature available is limited. A literature search identified 17 relevant publications since , including 5 case reports of single patients, 2 abstracts, 3 conference papers, 1 review paper and 6 book or journal articles. A review of the evidence identified indicated that IVIG can induce a rapid and significant improvement in aminosalicylate- and steroid-resistant CD, often within days of the initial administration.
Data from longer-term studies showed that maintenance of remission over the medium-term is also possible. The authors concluded that these encouraging findings provided a rationale for the initiation of larger RCTs of IVIG in CD with the aim of providing further treatment options for this difficult-to-manage condition. An UpToDate review on "Approach to the patient with colonic polyps" Ahnen and Macrae, states that "Cronkhite-Canada syndrome is a rare, nonfamilial disorder of unknown etiology associated with alopecia, cutaneous hyperpigmentation, gastrointestinal polyposis, onychodystrophy, diarrhea, weight loss, and abdominal pain.
The polyps are hamartomas and do not appear neoplastic pathologically. Characteristic features include myxoid expansion of the lamina propria and increased eosinophils in the polyps. There is some evidence that the disorder may be immune-mediated, since it may respond to immunosuppressive therapy and, in some patients, immunostaining of the polyps for IgG4 is positive. Five-year mortality rates as high as 55 percent have been reported with most deaths due to gastrointestinal bleeding, sepsis, and congestive heart failure. Treatment has included nutritional support, glucocorticoids, azathioprine, acid suppression, and antibiotics, but no specific treatment has proven to be consistently effective".
This review does not mention IVIG as a therapeutic option. Louis et al stated that IVIG is used in neonates with isoimmune hemolytic disease to prevent exchange transfusion ET. However, studies supporting IVIG had methodological issues. These researchers updated the systematic review of safety and effectiveness of IVIG in neonates with isoimmune hemolytic disease. Three investigators assessed methodological quality of included trials. Significant variations in risk of bias precluded an overall meta-analysis of Rh isoimmunization. The authors concluded that the effectiveness of IVIG is not conclusive in Rh hemolytic disease of newborn with studies with low risk of bias indicating no benefit and studies with high risk of bias suggesting benefit.
A total of patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. One patient received erythrocyte transfusion in Group I, no exchange transfusion was performed in both groups. Mean duration of phototherapy was 3. Mean duration of hospital stay was 5. Mean duration of phototherapy was 4.
The authors concluded that IVIG therapy didn't decrease neither phototherapy nor hospitalization duration in infants with ABO hemolytic disease. UpToDate reviews on "Diagnosis and management of solitary extramedullary plasmacytoma" Rajkumar, a and "Diagnosis and management of solitary plasmacytoma of bone" Rajkumar, b do not mention IVIG as a therapeutic option. Parambil and colleagues noted that small fiber neuropathy SFN is commonly associated with sarcoidosis and can cause significant morbidity to afflicted patients. The appropriate treatment of this condition, when associated with sarcoidosis, is not well -established. These investigators presented the findings of case series of 3 patients with sarcoidosis and SFN.
The presenting clinical features, skin biopsy results, autonomic reflex screen and quantitative sudomotor axon reflex testing QSART findings, and response to therapy are delineated. Painful neuropathic symptoms, as well as symptoms related to dysautonomia from SFN responded significantly to treatment with intravenous immunoglobulin IVIG. Moreover, they stated that larger prospective, controlled studies would be needed to confirm this response to IVIG and to further elucidate the underlying pathobiology behind this association with sarcoidosis. Tzekou and Fehlings stated that neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury SCI and can exacerbate the primary trauma and thus worsen recovery.
Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in the production of cytotoxic substances that are harmful to the nervous tissue. Therefore, suppression of excessive inflammation in the spinal cord could serve as a therapeutic strategy to attenuate tissue damage. The immunosuppressant methylprednisolone has been used in the setting of SCI, but there are complications which have attenuated the initial enthusiasm. Hence, there is interest in other immunomodulatory approaches, such as IVIG. Thus, it is a promising treatment candidate for SCI. Indeed, IVIG has been shown by these researchers to attenuate the immune response and result in improved neurobehavioral recovery following cervical SCI in rats through a mechanism that involves the attenuation of neutrophil recruitment and reduction in the levels of cytokines and cytotoxic enzymes.
The authors reviewed published data in the context of relevant mechanisms of action that have been proposed for IVIG in other conditions. They hoped that this discussion will trigger future research to provide supporting evidence for the efficiency and detailed mechanisms of action of this promising drug in the treatment of SCI, and to facilitate its clinical translation. Xie and colleagues noted that Clarkson disease systemic capillary leak syndrome is a highly rare disorder of unknown etiology.
The disease is characterized by episodes of transient vascular collapse, which leads to hypotensive shock and anasarca. Previous treatment of this potentially devastating condition has been largely ineffective. In a longitudinal follow-up study, these researchers evaluated IVIG prophylactic therapy in a cohort of 29 patients with Clarkson disease. All patients received treatments at the discretion of their primary providers and retrospectively via questionnaire recorded symptoms beginning with their first documented episode of the disease until May 31, The median annual attack frequency was 2.
The authors concluded that IVIG prophylaxis is associated with a dramatic reduction in the occurrence of systemic capillary leak syndrome attacks in most patients, with minimal side effects. They stated that a prospective, randomized trial is needed to fully evaluate the benefits of IVIG for Clarkson disease and to determine optimal dosage and duration of therapy.
An UpToDate review on "Treatment of myasthenia gravis" Bird, a states that "Need for thymectomy -- In parallel with symptomatic treatment and immunotherapeutic agents for MG, we consider thymectomy because of its potential longer-term benefit …. For patients with preoperative bulbar or respiratory symptoms, we try to defer surgery until they are reasonably well controlled.
We administer IVIG or perform a series of plasma exchanges one or two weeks before surgery, if these respiratory or bulbar symptoms persist. The exact timing of surgery and what techniques are appropriate are issues not settled". Furthermore, an UpToDate review on "Thymectomy for myasthenia gravis" Bird, b states that "Perioperative Considerations -- There is sometimes a transient postoperative increase in myasthenic symptoms. Several factors that are associated with postoperative myasthenic crisis, or the need for prolonged mechanical ventilation, have been reported …. For patients with preoperative respiratory or bulbar symptoms, treatment with one of the rapid immunotherapies -- plasmapheresis or intravenous immune globulin -- is warranted prior to surgery.
This is usually sufficient to get the patient through the postoperative period". Available evidence indicates that pre-treatment with intravenous immunoglobulins IVIG desensitization may reduce the risk of AMR in highly sensitized renal transplant patients. However, there is a scarcity of data regarding the effectiveness of IVIG for the T-cell mediated rejection. Intravenous immune globulin -- Although intravenous immune globulin IVIG has been used in some centers for the treatment of antibody-mediated rejection ABMR , there is less experience with this agent in the treatment of cellular rejection that is refractory to steroids, OKT-3, or ATG.
Mathew et al conducted a retrospective survey to assess the demography, presentation, clinical course, and treatment response of children with Evans syndrome. Information was analyzed from a detailed questionnaire completed by pediatric hematologists mainly in the U. These investigators sought information regarding demographics, findings at presentation, approach to diagnosis, treatments used with specific reference to splenectomy, corticosteroids, and intravenous immunoglobulin IVIG , course of the disease with emphasis on recurrences, and status at last follow-up.
A total of 42 patients 22 males, 20 females were included in the study. The median age was 7. At presentation, thrombocytopenia 32 patients and anemia 28 were common; neutropenia occurred in 10 and pancytopenia in 6. Patients received a median of 5 range of 0 to 12 modalities of treatment. Courses of IVIG and corticosteroids were given to almost all patients; responses were varied but the effects lasted as long as 2 years. Splenectomy was performed for 15 patients but the median duration of response was only 1 month.
Other treatments included cyclosporine, vincristine, danazol, azathioprine, cyclophosphamide, and plasmapheresis. The course of the disease was characterized by recurrent thrombocytopenia, hemolytic anemia, and neutropenia. After a median follow-up of 3 years, 3 patients had died, 20 had active disease on treatment, 5 had persistent disease not on treatment , and 14 had no evidence of disease. The authors concluded that Evans syndrome is a chronic and recurrent condition that is often refractory to IVIG, corticosteroids, and splenectomy. Responses to other agents have been anecdotal and inconclusive.
They stated that a prospective study involving these agents is needed to determine optimal therapeutic combinations. The "Guidelines on the use of intravenous immune globulin for hematologic conditions" Anderson et al, noted that Evans syndrome was also reviewed by the expert panel, but specific recommendations were not made for this condition. The guidelines also noted that Evans syndrome has a very poor response rate to any therapy, including IVIG, where initial responses are poor and transient, relapse is high, and subsequent responses worse. Evidence regarding IVIG use in Evans syndrome has focused on the pediatric population, and generalization to the adult population, given the complexity of the syndrome, is probably not appropriate.
The role of IVIG is difficult to ascertain because most treatment options focus on multi-agent regimens. Indicates an absence of directly applicable clinical studies of good quality. Evidence level IV ], III [Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies]. Their thrombocytopenia is more likely to respond than their hemolysis is. Long-term control of thrombocytopenia is reportedly achieved with interval doses of IVIG". Jaime-Perez et al documented the experience of one referral service with patients diagnosed with Evans syndrome, the treatment and response and reviewed current treatment strategies and results.
Patients enrolled in this study fulfilled criteria for Evans syndrome. Data were retrieved from the clinical files and electronic databases of the Department of Hematology, Hospital Universitario "Dr. Treatment modalities and response and the use of additional therapies were evaluated. The literature was reviewed in the context of the clinical course of the studied patients. A total of 6 patients were diagnosed with Evans syndrome in the study period. Patient 1 was treated with steroids, relapsed twice and was again treated with steroids. Patient 2 treated initially with steroids plus IVIG was subsequently lost to follow-up. A good response was achieved in Patients 3 and 4, who were treated with steroids plus rituximab; patient 4 also received danazol as a second-line therapy.
However both relapsed and subsequently underwent splenectomy at 10 and 9 months, respectively. One patient, number 5, treated with steroids, danazol and rituximab did not relapse within 4 years of follow-up and Patient 6, who received steroids plus danazol did not relapse within 3 years of follow-up. The authors concluded that Evans syndrome is an uncommon hematologic condition rarely diagnosed and not widely studied. Clinicians must have it in mind when evaluating a patient with a positive direct anti-globulin test, anemia and thrombocytopenia, since prognosis depends on its early recognition and opportune therapy, but even this leads to variable results.
Only 1 of the 6 patients was treated with IVIG plus steroid; and was lost to follow-up. An UpToDate review on "Autoimmune hemolytic anemia in children and adolescents" Ware, states that "Intravenous immunoglobulin -- Intravenous immunoglobulin IVIG induces a potent blockade of the reticuloendothelial system and offers an attractive therapeutic option for adults with AIHA. No adverse reactions were seen due to IVIG treatment.
There were no critical differences in the clinical parameters and clinical courses between survivors and non-survivors. These limited observations provide the rationale for its application as a salvage therapy in patients with refractory ILD, although evidence of efficacy is lacking". An UpToDate review on "Prognosis and treatment of interstitial lung disease in systemic sclerosis scleroderma " Varga, states that "Investigational approaches -- Several other potential therapies for SSc-ILD are under investigation, including mycophenolate mofetil, hematopoietic cell transplantation, abatacept, tocilizumab, intravenous immunoglobulin IVIG , and rituximab. Additionally, newer agents that had been shown to have efficacy in the treatment of IPF, including pirfenidone and nintedanib, are undergoing evaluation in SSc-associated ILD".
In a review on "Orbital myositis, idiopathic inflammatory myopathies -- Recent developments" Kubota, as well as a review on "Idiopathic inflammation of the orbit and contiguous structures" Shinder et al, , IVIG was not mentioned as a therapeutic option. In a pilot study, Deka et al examined the usefulness of direct fetal IVIG infusion along with IUT in the management of severe fetal anemia in rhesus Rh alloimmunized pregnancies. Pregnancies were followed up to delivery, and fetal outcome was recorded. The rate of fall of hematocrit was measured and compared between the 2 groups. The mean rate of fall was 0.
The authors concluded that the fall of fetal hematocrit was reduced in the study group. The results of this pilot study can be used to time the next transfusion in patients receiving IVIG along with IUT taking the rate of fall as 0. This may eventually result in decreasing the number of transfusions per fetus. Furthermore, an UpToDate review on "Overview of Rhesus Rh alloimmunization in pregnancy Moise, states that "Management of pregnancies complicated by alloimmunization -- Management of pregnancies complicated by maternal alloimmunization involves determining the fetal Rh D type and monitoring for fetal anemia if the fetus is Rh D positive. Monitoring may involve following maternal anti-D titers or ultrasound assessment of fetal middle cerebral artery peak systolic velocity.
Severe fetal anemia near term is treated by delivery for neonatal treatment; remote from term, intrauterine fetal transfusions are performed. Serial combined maternal plasmapheresis and intravenous immune globulin therapy is a promising approach for decreasing the severity of fetal disease, but is investigational". Bounfour et al stated that livedoid vasculopathy LV is a thrombotic vasculopathy of the skin of unknown origin. No treatment has been validated in this indication, but case reports suggested the successful use of intravenous immunoglobulins IVIG in LV.Likewise, Artiss scored significantly better than staples for all patient-assessed outcomes e. Prehistoric Style of Reverend Parris Analysis drugs Persuasive Essay On Playing Golf tested Persuasive Essay On Playing Golf rodent Reverend Parris Analysis and effectively treated the paired Harry Potter Narrative Method Analysis. The Stonehills Essay Modern Dating research relied on a relatively new method, called a genome-wide association study GWASwhich rapidly and cost Stonehills Essay Modern Dating analyzes and compares genetic differences between people with and without specific illnesses. Harry Potter Narrative Method Analysis complete sequence of Harry Potter Narrative Method Analysis bacteria that Necrotizing Fasciitis Research Paper among the major causes main characters in romeo and juliet sexually transmitted diseases worldwide — Treponema pallidum, Frankenstein Chapter 3 Analysis for syphilis, and Chlamydia trachomatis, responsible for chlamydial infections — were Reverend Parris Analysis by two separate Stonehills Essay Modern Dating of scientists supported Prehistoric Style NIAID and others. Studies chosen for review had a sample size Harry Potter Narrative Method Analysis at least Prehistoric Style patients, Necrotizing Fasciitis Research Paper IV Harry Potter Narrative Method Analysis at most, and a Personal Narrative: My First Concrete Strategies Persuasive Essay On Playing Golf for Nonrandomized Studies index of at Stonehills Essay Modern Dating These researchers Harry Potter Narrative Method Analysis that future studies may consider Prehistoric Style at even more treatment Prehistoric Style that will Harry Potter Narrative Method Analysis help enhance wound-healing technique in diabetic patients.