Sienna:
RISTORI G (pubmed.org RISTORI +Bcg) and Dr Denise L Faustman, see pubmed.org faustman DL, faustmanlab.org, clinicaltrials.gov faustman provide you with a firm economic path. Bcg may be used to treat autoimmune diseases. It is safe, cheap and effective. You may leapfrog the us which kills Americans by having made faustman test Bcg at less than avaccination dose. I have shot Bcg and it works for plaque psoriasis. The published work of RISTORI and faustman may be applied in sienna for the benefit of all. I would much like to sightsee and enjoy food without my type one diabetes getting I the way. The us is a backward ignorant nation with respect to the manyusesof Bcg.
Bcg also lessens the chance of contracting multidrug resistant tb which is unknown in the u.s.
Sincerely your,
Better science and art in sienna than in the us.
You might think that bcgwould be available to all in the us who seek same?
Shingles seldom kills. Tb kills and the treatment for it may be intolerable.
With a little tinkering multi drug resistant tb will be ready for prime time as a weaponized aerosol
Bcg also works well for improving the lives of those with autoimmune diseases
Airlines may raise revenue by offering Bcg vaccinations
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Dr. Jeffrey Cirillo, right, professor at the Texas A&M Health Science Center, and research associate Suat Cirillo remove a diagnostic tuberculosis test from its kit. Dr. Cirillo and his team are working on faster, cheaper diagnosis alternatives for the disease. PHOTO: TEXAS A&M HEALTH SCIENCE
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As U.S. health officials treat an Indian woman who entered the country with drug-resistant tuberculosis, scientists at Texas A&M Health Science Center are trying to develop faster and more accurate ways to diagnose the infectious disease.
The timely detection of TB remains one of the greatest difficulties in dealing with the condition. The main symptoms, like long-lasting cough and fever, are common to other illnesses. The bacteria are also slow-growing. That’s why patients with TB often aren’t diagnosed until they’ve had the infection for many months, risking infecting others. The increase in drug-resistant versions of the bug adds to the urgency in detecting TB more quickly.
Researchers, such as Jeff Cirillo and colleagues at the Texas A&M facility in Bryan, Texas, are working on faster, cheaper diagnosis alternatives. They have developed a test that signals when enzymes produced only by TB bacteria are present, whittling the process to just 10 minutes from several days. They now are studying how it could be used to determine drug-resistance as well.
“The challenge is absolutely the diagnosis,” says Andrew Steenhoff, a pediatrics professor at the Children’s Hospital of Philadelphia and TB specialist.
Tuberculosis can affect any organ in the body, but the most common—and most important, from a public-health perspective—is the lungs. TB isn’t as contagious as many other infectious diseases, like measles, but it is a particular concern for children and people with weakened immune systems. The bacteria are transmitted through the air, and infection occurs after spending significant time in a confined space. Transmission in public places, including airplanes, is unlikely but possible, Dr. Steenhoff says.
One-third of the world’s population has tuberculosis, though many carry it without displaying any symptoms. Between 1.5 and 2 million people a year die from it, the World Health Organization says.
Latently infected people cannot pass the disease on to others unless the tuberculosis, which can lie dormant in people for years, flares into acute disease, sometimes during a period of weakened immunity.
In recent years, strains of bacteria that are resistant to both the first and second line of conventional medications have emerged, raising a public-health alarm world-wide.
This month, a woman from India who had arrived at Chicago’s O’Hare Airport in April was found to have extensively drug-resistant TB after feeling ill and seeking treatment in May in McHenry County, Ill, according to a spokeswoman for the county health department. The woman, whose name hasn’t been released for reasons of patient confidentiality, was admitted to the hospital at the National Institutes of Health in Bethesda, Md. She is likely to remain there for weeks while doctors try to figure out which drugs work on her strain of TB, according to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a member of the infectious disease team treating her.
Meanwhile, the Centers for Disease Control and Prevention and state and local authorities are trying to trace all those she had contact with since her arrival in the U.S. to make sure they haven’t contracted the disease, says Philip LoBue,director of the tuberculosis-elimination division at the CDC.
Test results from the diagnostic TB test developed by Dr. Cirillo. The picture shows samples of patient sputum. The brighter the colored areas, the more bacteria are contained within the sputum, indicative of positive samples. The samples without colors are negative samples. PHOTO:TEXAS A&M HEALTH SCIENCE
The most accurate way of diagnosing TB today is to take a sample of mucus from the patient and grow the organism in culture tubes or plates. This method is usually positive in two to three weeks, but it can take up to eight weeks to say the result is definitely negative.
Another diagnostic technique, looking directly at the sputum after it’s been stained through a microscope, may miss half of all cases, according to Dr. LoBue. This technique is highly dependent on how many bugs are in the sample; bacteria could be missed if there aren’t many. X-ray also may be used for diagnosis, though facilities aren’t widely available around the world, experts say.
In the U.S., doctors perform chest X-rays on people with respiratory symptoms or a positive TB skin or blood test. But it isn’t possible to definitely determine whether an abnormality on a chest X-ray is due to TB and other respiratory infections or other lung diseases, Dr. LoBue says. The main advancement in TB diagnosis in recent years is in molecular testing, which identifies the bacteria through its DNA.
A device, called GeneXpert in the U.S. and endorsed by the World Health Organization, churns out a result within two hours. But experts say a need for alternative diagnostic methods remains.
The team at Texas A&M has been developing another approach using a compound that binds specifically to enzymes produced by TB bacteria. If TB bacteria are present, the combination, placed in a tube or cup, will light up and can be detected after 10 minutes using a battery-operated, portable light reader.
The main challenge in the research was configuring a compound that would bind to the TB enzyme but not to other enzymes, Dr. Cirillo says. The team spent about six years analyzing the structure of the TB enzyme.
One technique they used was crystallography, where they created a solid form of the enzyme, took an X-ray of it and scrutinized the position of every atom. The development of the light reader took an additional two years. They first published some of this work in 2010 in the Proceedings of the National Academy of Sciences.
A doctor checks an X-ray film for tuberculosis at a public clinic of a poor district in Lima, Peru on April 14. PHOTO: CRIS BOURONCLE/AGENCE FRANCE-PRESS/GETTY IMAGES
The reader device, which is expected to cost $500, is being tested in World Health Organization-sponsored field trials in Africa. Earlier work was funded by the Wellcome Trust in the U.K., and the Bill and Melinda Gates Foundation. Each sample test is expected to cost $2 or less. The scientists hope the technique will be cost-effective and can be used widely across the globe.
Dr. Cirillo’s team is studying how the same technology could be used to determine which drugs the TB might be resistant to based on a simple rationale: If the bacteria die in the presence of a drug, they stop making the enzyme and the light ceases. They published early work demonstrating the concept in 2014 in the German journal Angewandte Chemie.
If subsequent research supports the accuracy of the drug-resistance test, clinicians could have results in two hours. Doctors today need six weeks to grow the bacteria and determine which drugs the patient requires.
“We’re always looking for better, simpler, cheaper and more rapid diagnostics,” says Dr. Fauci of the National Institute of Allergy and Infectious Diseases, who wasn’t involved in the work.
Write to Shirley S. Wang at shirley.wang@wsj.com
Corrections & Amplifications
People with tuberculosis are not contagious when only latently infected with the disease. An earlier version of this story misstated that they are infectious. (June 16, 2015)
(Reuters Health) - Diabetes researchers are hoping that an almost century-old vaccine for preventing tuberculosis may also reverse type 1 diabetes.
The FDA has approved a mid-stage trial to test the vaccine, called bacillus Calmette-Guerin (BCG), in 150 adults with advanced cases of the disease.
The approval was announced Sunday at the 75th Scientific Sessions of the American Diabetes Association by Dr. Denise Faustman, director of the Massachusetts General Hospital Immunobiology Laboratory in Boston and principal investigator of the study.
According to the American Diabetes Association, 5 percent of people with diabetes - or roughly three million individuals - have type 1, in which the immune system attacks and destroys insulin-producing beta cells in the pancreas.
Faustman told Reuters Health that the BCG vaccine temporarily raises levels of a substance called tumor necrosis factor, or TNF – and the higher TNF levels can eliminate the damaging T cells in the blood of individuals with type 1 diabetes.
In a small preliminary trial, Faustman’s team found that two BCG injections given four weeks apart temporarily eliminated diabetes-causing T cells. Patients also showed evidence of small, temporary return of insulin secretion.
This summer, she and her colleagues will begin enrolling patients ages 18 to 60 in a larger five-year trial. Participants will have low but detectable levels of insulin secretion from the pancreas. They'll receive two injections, four weeks apart, of either BCG or placebo, and then annual injections for the next four years.
If this trial is successful, the next step would be an even larger study in a greater number of patients.
"In the phase I (preliminary) trial we demonstrated a statistically significant response to BCG, but our goal in (this trial) is to create a lasting therapeutic response," Faustman said in a statement. "We will be working again with people who have had type 1 diabetes for many years. This is not a prevention trial; instead, we are trying to create a regimen that will treat even advanced disease.”
The BCG vaccine was first used in humans in 1921 as a vaccine against tuberculosis. More recently, its most common use in the U.S. has been in the treatment of bladder cancer.
“It’s a drug with an impeccable safety record,” Faustman said, noting that it has more than 90 years of clinical use and safety data.
Some diabetes specialists are skeptical about its potential to reverse diabetes, however. Robert Sobel, an assistant professor of endocrinology at Northwestern University’s Feinberg School of Medicine, says everyone working in diabetes is rooting for big discoveries, but he believes prevention will likely come before cure.
“I think it’s a stretch to say this would have a huge impact on the millions plus type I diabetes patients in this country,” Sobel said. “We would love to do something to preserve or repopulate their beta cell mass. Historically, we have watched it dwindle and have not been able to do something (in time).”
“Even people who have challenges with the science, they are certainly hoping that this works,” said Dr. Sethu Reddy, chief of the Adult Diabetes Section at Joslin Diabetes Center in Boston.
Reddy, who is working with Faustman on the BCG trial, added, “Those working in type 1 diabetes have been looking for a good treatment for many years. A lot of treatments have been successful in the short-term but have been challenged in the long-term setting.”
More than $19 million has been secured for the $25 million total needed for the study. Much of that has been granted by the Iacocca Foundation, which funds type 1 diabetes research.
From The Web
(Reuters Health) - Diabetes researchers are hoping that an almost century-old vaccine for preventing tuberculosis may also reverse type 1 diabetes.
The FDA has approved a mid-stage trial to test the vaccine, called bacillus Calmette-Guerin (BCG), in 150 adults with advanced cases of the disease.
The approval was announced Sunday at the 75th Scientific Sessions of the American Diabetes Association by Dr. Denise Faustman, director of the Massachusetts General Hospital Immunobiology Laboratory in Boston and principal investigator of the study.
According to the American Diabetes Association, 5 percent of people with diabetes - or roughly three million individuals - have type 1, in which the immune system attacks and destroys insulin-producing beta cells in the pancreas.
Faustman told Reuters Health that the BCG vaccine temporarily raises levels of a substance called tumor necrosis factor, or TNF – and the higher TNF levels can eliminate the damaging T cells in the blood of individuals with type 1 diabetes.
In a small preliminary trial, Faustman’s team found that two BCG injections given four weeks apart temporarily eliminated diabetes-causing T cells. Patients also showed evidence of small, temporary return of insulin secretion.
This summer, she and her colleagues will begin enrolling patients ages 18 to 60 in a larger five-year trial. Participants will have low but detectable levels of insulin secretion from the pancreas. They'll receive two injections, four weeks apart, of either BCG or placebo, and then annual injections for the next four years.
If this trial is successful, the next step would be an even larger study in a greater number of patients.
"In the phase I (preliminary) trial we demonstrated a statistically significant response to BCG, but our goal in (this trial) is to create a lasting therapeutic response," Faustman said in a statement. "We will be working again with people who have had type 1 diabetes for many years. This is not a prevention trial; instead, we are trying to create a regimen that will treat even advanced disease.”
The BCG vaccine was first used in humans in 1921 as a vaccine against tuberculosis. More recently, its most common use in the U.S. has been in the treatment of bladder cancer.
“It’s a drug with an impeccable safety record,” Faustman said, noting that it has more than 90 years of clinical use and safety data.
Some diabetes specialists are skeptical about its potential to reverse diabetes, however. Robert Sobel, an assistant professor of endocrinology at Northwestern University’s Feinberg School of Medicine, says everyone working in diabetes is rooting for big discoveries, but he believes prevention will likely come before cure.
“I think it’s a stretch to say this would have a huge impact on the millions plus type I diabetes patients in this country,” Sobel said. “We would love to do something to preserve or repopulate their beta cell mass. Historically, we have watched it dwindle and have not been able to do something (in time).”
“Even people who have challenges with the science, they are certainly hoping that this works,” said Dr. Sethu Reddy, chief of the Adult Diabetes Section at Joslin Diabetes Center in Boston.
Reddy, who is working with Faustman on the BCG trial, added, “Those working in type 1 diabetes have been looking for a good treatment for many years. A lot of treatments have been successful in the short-term but have been challenged in the long-term setting.”
More than $19 million has been secured for the $25 million total needed for the study. Much of that has been granted by the Iacocca Foundation, which funds type 1 diabetes research.
From The Web
SIENA, Italy — Operators of kindergartens and ambulance services had to find new sources of funds. A biotech company filed for bankruptcy. The local professional soccer team slipped into the minor leagues after it could no longer afford the salaries of its top players.
And twice a year, when it is time for the Palio, Siena’s famed bareback horse race, neighborhood clans must pay for their own costumes.
Siena, a city in central Tuscany, is scrambling to fill the financial hole caused by the near collapse of Banca Monte dei Paschi di Siena, the world’s oldest bank.
The foundation that owned the bank bankrolled a broad range of social services and cultural events, showering 150 million euros a year, about $170 million, on Siena and the surrounding region. The bank was the city’s largest private sector employer.
Now, Siena is trying to attract outside investments and show that, contrary to Italy’s reputation for being unfriendly to businesses, it can foster entrepreneurship and create jobs. It is the same challenge facing all of Italy, which has barely grown since the 1990s and has weighed on the broader European economy.
“Everyone is aware that a new growth engine is needed,” said Angelo Riccaboni, head of the University of Siena. “In Siena, people have to change their mentality. Now you need to be a risk-taker.”
Since its founding in 1472, Monte dei Paschi and its wealth have been at the center of life in Siena. The bank survived plagues, panics and wars. Its headquarters are still located inside a medieval fortress.
But modern financial hubris felled the centuries-old bank. In 2008, Monte dei Paschi acquired a rival to become Italy’s third-largest bank. The €9 billion price tag was considered too high, even at the time, and bank management compounded the blunder by engaging in a series of derivatives transactions that later produced huge losses.
Last week, Monte dei Paschi completed a sale of shares valued at €3 billion and replenished its capital. But the bank is gasping under a pile of bad loans and has effectively put itself up for sale, which could mean moving its headquarters away from Siena. Fabrizio Viola, the bank’s chief executive, said that Monte dei Paschi will continue to support Siena as a bank, though not as a benefactor. “We are ready to support the economy with good credit at the right price,” he said.
Siena is slowly adjusting to life with a greatly diminished Monte dei Paschi.
Some of the changes have been small. The Misericordia di Siena, which provides ambulance service and other health care services, is making up the lost funds by renting out real estate and collecting more money from members and other private sources.
“Had we survived only with the foundation’s money, we’d have gone belly up,” said Mario Marzucchi, president of the Misericordia, which has been operating for more than seven centuries.
Other activities financed by the foundation were less essential, like a club for the spouses of doctors, and the colorful costumes that members of the city’s Contrada, ancient neighborhood associations, wore in processions that preceded the Palio races.
“There was too much money. Everything was easy,” Marcello Clarich, the president of the Monte dei Paschi Foundation, said in his office overlooking the Piazza del Campo. “Now we are going back to normality.”
A broader economic overhaul will take longer.
As Siena looks to reinvent itself, the city, in part, is looking to that past. With a large and well-preserved medieval center, Siena is crowded with tourists in the summer but is often underbooked the rest of the year.
Work has long been underway to improve the highway that connects Siena with Florence, and local officials have staged off-season running and cycling events to attract sports tourists. Such events helped increase tourism by an estimated 10 percent last year.
But tourism will not replace the high-paying jobs Monte dei Paschi once provided.
To fill that gap, local and regional officials are trying to turn Siena and the surrounding province of Tuscany into “Pharma Valley,” an international center for drug research and development. (The region has a long history of vaccine research.) The British drugmaker GlaxoSmithKline has a large research and production operation in Siena.
The effort suffered a blow when one of the most visible start-ups, Siena Biotech, filed for bankruptcy in April. Despite spending 14 years and €160 million seeking treatments for Alzheimer’s and Huntington’s diseases, the company never produced any marketable therapies.
The failure of Siena Biotech, which depended entirely on the Monte dei Paschi Foundation, is seen as a cautionary tale about the insular old ways of doing things.
“The concept was wrong,” said Mr. Clarich, a law professor who has been chairman of the foundation since last year. “The foundation had a lot of money and said, ‘We can do it alone.’”
Earlier this year, Siena Biotech workers occupied the headquarters for more than two months, sleeping on air mattresses and demanding more funding. “We are all very attached to research. We all grew up here,” said Michele Midollini, a 35-year-old former manager at Siena Biotech who was taking part in the occupation, which ended May 1.
Now officials are trying a new strategy.
In a plain concrete building just down the street from Siena Biotech, Toscana Life Sciences is serving as an incubator for 16 start-ups developing new technologies and related services. It is trying to mold the small pharmaceutical companies scattered around the region into a cluster that can feed off each other and take better advantage of the proximity of GlaxoSmithKline as well as Eli Lilly, which has a drugmaking plant outside Florence.
The organization, a public-private partnership, is providing space as well as some funding. For example, the organization is supporting research into the therapeutic qualities of ingredients found in local products like olive oil and red wine, among other activities. It is also working with local universities.
But the effort — along with the rest of the economic overhaul — also requires a government rethink.
Investors won’t come to Tuscany “just because it’s more beautiful and has better wine,” said Andrea Paolini, director general of Toscana Life Sciences. Entrepreneurs here, as with much of Italy, face a mountain of red tape and a slow-moving justice system that make it difficult to resolve business disputes.
So officials are trying to reduce the bureaucracy. For example, the regional government has consolidated the number of committees it needs to approve a clinical trial to one, from 16.
“This is critical for companies,” said Luigi Marroni, the regional minister of health. “If it takes six months to get an approval in Tuscany and two months in New Jersey, they’ll go to New Jersey.”
The local government, too, is adopting a new attitude.
In January, the University of Pittsburgh Medical Center, a nonprofit health care provider, decided to open a center to diagnose liver and digestive ailments in Chianciano Terme, a town near Siena known for its healing waters. Officials in Siena helped accelerate the approval process, and the center opened in June.
“Our impression is that the local government is really pushing hard,” said Bruno Gridelli, the executive vice president of U.P.M.C. International. “They understand that if they want to improve the economy, particularly after the problems of Monte dei Paschi, they need to attract investment.”
The city of Siena is also trying to become more efficient.
The city government cut its municipal debt by more than 25 percent to €74 million, sold city real estate and stopped using an outside contractor to collect taxes, in order to save costs. Officials are also working on centralizing procedures like building permits, a process that can take years.
“The only way to save the city is to renew it,” said Bruno Valentini, the mayor of Siena.
Still, Siena is at the start of the process.
Throughout Italy, attempts to streamline government still face huge resistance from civil servants who fear for their jobs. And remaking Siena is not any easier without the riches once bestowed by the bank.
“We started out with a cruise liner and ended up with a wooden raft,” Mr. Paolini said. “I can’t say I’m pleased.”
