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A medical student today will go through their entire career without ever seeing a case of polio. The polio virus was feared throughout the early 20th century, leaving millions paralyzed or dead. During Summer and Autumn, polio epidemics spread human to human with this highly contagious disease. In the 1940’s and 50’s, negative pressure ventilators called the “iron lung” were used to support patients with paralyzed respiratory muscles. In 1952 the worst polio epidemic struck the United States, with 58,000 cases and 3,145 deaths. Over 21 thousand victims were left paralyzed.

By 1964, the oral polio vaccine, developed by Albert Sabin, had become the recommended vaccine. It was easy to administer and large populations could be vaccinated.

The effort to eradicate polio was launched in 1988 and involved the World Health Organization, Rotary International, the CDC and UNICEF. Through everyone pulling together, more than 210 polio endemic countries were targeted for childhood vaccination. Today only 4 countries - Afghanistan, India, Nigeria and Pakistan have polio. Fewer than 2000 children were paralyzed by the disease in 2006.

If the Global Polio Eradication Initiative is able to stick to its strategic plan, polio will be completely eradicated from the human population. This shows that political will and governments and industry working together can achieve wonderful things for mankind. This initiative had corporate support, pharmaceutical support, non governmental organizations (NGOs), the Gates Foundation and many small countries involved with donating funds to stop polio. Ireland, Bangladesh, Russia, Norway Canada, Germany, the U.K. ,India and the United States were all heavy contributors.

This success story shows that political will, oversight and responsibility are the ingredients for saving our planet. Let the End of Polio show us that we can work together successfully for a common good.

ScienceDaily (Oct. 30, 2007) — Scientists in the United Kingdom have “decoded” the inscrutable language of traditional Chinese medicine (TCM), revealing its strong chemical foundation in a way that may help scientists mine age-old Chinese medicines to develop tomorrow’s new drugs.
David J. Barlow, Thomas M. Ehrman, and Peter J. Hylands point out that traditional Chinese medicine (TCM) - regarded by many Western experts as an archaic system doomed to extinction 50 years ago - has undergone a “remarkable renaissance” in recent years.
However, the arcane language used to describe categories of medication in TCM has hindered effective understanding of one of the most developed and mature systems of alternative medicine in existence.
To overcome that barrier, the researchers analyzed patterns among 8411 compounds from 240 Chinese herbs in relation to the categories found in traditional Chinese medicine. Organizing their findings in a kind of herbal “map,” their results reveal that many categories in Chinese medicine are amenable to translation to Western terminology. TCM’s “fire poison” group, for example, is comparable to today’s family of anti-inflammatory medicines.
Now, future researchers will better understand the chemical basis of remedies that have been in use for thousands of years, the study indicated.
“This is likely to be of benefit both in the search for new drugs and, equally significantly, in understanding how Chinese medicine works,” say the authors.
The study is “Phytochemical Informatics of Traditional Chinese Medicine and Therapeutic Relevance” is scheduled for the Nov./Dec. issue of ACS’ Journal of Chemical Information and Modeling.
Adapted from materials provided by American Chemical Society.

Fausto Intilla
www.oloscience.com

Psoriasis patients should undergo a comprehensive work-up for associated diseases, a Canadian investigator said here at a journalists workshop held in support of World Psoriasis Day.

Wayne Gulliver, MD, Chairman of the Division of Dermatology at the Memorial University of Newfoundland in St. John’s, made the recommendation on the basis of research demonstrating a strong association between psoriasis and multiple co-morbidities. The data also show an increased mortality risk in psoriasis patients.

His team has been conducting a study to examine the link between psoriasis and co-morbidities using information gathered from four databases covering the Newfoundland and Labrador founder population, which include a total of 713,000 individuals.

Thusfar, analyses have revealed that the incidence of diabetes is 10% in individuals with mild to moderate psoriasis and 12% in those with severe psoriasis compared with only 4% in the general population. Also, 44% of deaths in psoriasis patients are apparently due to cardiovascular causes versus 36% of deaths in the general population.

Results also document an increased prevalence of death due to genitourinary disease and an increased prevalence of genitourinary disease in psoriasis patients.

Patients with psoriasis have an average life expectancy that is 10 years shorter than the Canadian average. Psoriasis patients whose psoriasis develops when they are less than 25 years of age have a life expectancy that is decreased by 25 to 30 years.

Dr. Gulliver maintained that shared pathogenetic mechanisms may explain the link between psoriasis and several chronic illnesses. “In short, cytokines in the skin are also driving the risk for cardiovascular disease, hypertension, and diabetes,” he explained.

“The message to clinicians treating psoriasis patients is clear,” he said. “You need to check their blood pressure, blood sugar, and lipids, and you also need to do an electrocardiogram. Essentially, what you need to do is screen patients for these common, complex diseases that are occurring at a much higher rate in psoriasis patients than in the general population.”

“At present, no treatment can alter the course of psoriasis, and existing therapies are aimed at controlling symptoms, Torello Lotti, MD, professor of dermatology at the University of Florence, observed. Treatment may involve topical therapies for mild disease while phototherapy and/or systemic therapy are prescribed for more severe disease. Traditional systemic treatments are frequently limited by adverse side effects, poor convenience, or low efficacy, he said.

While new biological therapies offer patients a safer, well-tolerated, and long-term treatment, all biologicals are not the same, he added. “In fact, each biological agent has a distinct safety and efficacy profile,” he added.

Efalizumab (Raptiva), which specifically targets and modulates T-cells involved in the immunopathogenesis of psoriasis, is the only biological treatment that has shown longlasting disease reduction over three years in patients with chronic moderate-to- severe symptoms, he said.

Dr. Lotti reviewed the results of a phase III trial in which the medication achieved clinically meaningful sustained responses in up to 94 percent of responding patients who continued treatment. In addition, Psoriasis Area Severity Index (PASI) 75 was obtained in 73 percent of responders after three years of treatment. “Importantly,” he noted, “the study is the longest to date to examine continuous therapy with a biological.”

He added that safety data in over 3,500 patients who have participated in clinical trials have documented a good safety record with this drug. “Proven three-year favorable safety profile enables patients with chronic moderate-to- severe plaque psoriasis to be treated long-term and continuously with efalizumab,” he said.

http://www.raptiva.com

HIV, the virus that causes AIDS, probably came into the US from Haiti around the year 1969, a decade earlier than most scientists believed, says new research from the US.

The study is due to be published this week in the Early Online issue of the Proceedings of the National Academy of Sciences and is the work of Michael Worobey, an assistant professor of ecology and evolutionary biology at The University of Arizona in Tucson, and colleagues. The title of the study is “The emergence of HIV/AIDS in the Americas and beyond”.

“Our results show that the strain of virus that spawned the US AIDS epidemic probably arrived in or around 1969. That is earlier than a lot of people had imagined,” said Worobey in a prepared statement.

“Haiti was the stepping stone the virus took when it left central Africa and started its sweep around the world. Once the virus got to the US, then it just moved explosively around the world,” added Worobey.

The researchers found that most HIV/AIDS strains in the US came from a single common ancestor that predates the well storied “Patient Zero” theory. The Patient Zero theory came from a misrepresentation for Patient O (Oh), for “Out of California”, where early research on AIDS by the US Centers for Disease Control and Prevention (CDC) suggested HIV in the US spread in the late 1970s, early 1980s from one man in California.

According to the work of Worobey and colleagues, the strain that came to the US in 1969 was HIV-1 group M subtype B and is the first discovered human immunodeficiency virus. This strain is the most dominant of the AIDS strains that exist in most countries outside of sub-Saharan Africa, nearly all of which descended from the one that came out of Haiti, said the researchers.

Worobey and colleagues analysed the genes in stored blood samples of five AIDS patients to pinpoint the date HIV arrived in the US. All the patients had recently emigrated from Haiti. Using these samples and those of 117 AIDS patients from around the world who were also infected with subtype B, they constructed a family tree of HIV genes.

First they analysed the gene sequences and then using Bayesian statistics they sifted through all possible HIV family trees to find the ones that most closely matched the sequences they found.

The likelihood that the virus went from Africa directly to the US was practically zero, a probability of 0.003.

The most likely route was Africa to Haiti then the US, which yielded a probability of 99.8 per cent.

The gene sequence analysis also showed that most viruses in the US can be traced to one ancestor, the one that entered the US from Haiti in and around 1969.

Worobey and colleagues found that Haiti had a greater genetic diversity of the subtype B virus than the US, Australia, Europe and other countries. They estimated the virus travelled from Africa to Haiti in 1966.

Establishing the genetic diversity of the virus within the subtype B could help develop vaccines against HIV fur use in Haiti said the researchers. This research explained why there was such a large variation of the virus in Haiti, it had “simply been there longer”, they said.

Worobey said the next thing he and his colleagues plan to do is trace the ancestry of HIV back even further, using older archived blood samples.

African American women are diagnosed with breast cancer at a younger age and have larger tumors and more lymph node involvement than Caucasian women, a Yale School of Medicine researcher reported recently.

Speaking at the American Society for Therapeutic Radiology and Oncology meeting in Los Angeles, Meena Moran, M.D., assistant professor of therapeutic radiology and Yale Cancer Center member, said her results were based on 2,164 Caucasian women and 207 African American women followed over a 30-year period-the largest most comprehensive study of its kind to date. All underwent lumpectomies in which the tumor, not the entire breast, was removed.

“The incidence of breast cancer is actually lower in African American women compared to Caucasian women, yet their mortality rates are higher,” Moran said. “We were surprised. Previous reports did not show higher relapse rates in African American women after surgery to conserve breast tissue. This might be because we had so many African American patients and a longer follow-up period.”

She said there are several possible biological risk factors that need to be explored more fully. African American women have a lower level of estrogen/progesterone receptors, which means existing anti-estrogen therapies are not effective on these tumors. African American women have a higher rate of “triple negative tumors,” which have been associated with a worse outcome in early stage breast cancer. They also have a higher rate of mutation in the p53 gene, which normally acts to suppress tumors.

“In terms of outcomes after treatment,” Moran said, “African American patients were found to have a significantly higher rate of relapse in the breast and lymph nodes after breast conservation treatment compared to Caucasians. We did not, however, find any differences in the rate of cancer spreading to other locations such as the lung, bone, or liver, or in the overall survival in the two groups of patients.”

Moran said she hoped that the study would increase awareness of the aggressive nature of breast cancer in African American women. She said this does not mean that African American women should not have lumpectomies. She emphasized that greater attention should be paid to ensure the tumor is completely removed and that follow up radiation therapy is adequate and includes the entire breast and lymph nodes.

“We hope that patients and physicians will help reduce the gap in the disparities between the two populations by improving early detection/screening, better access to care and compliance with chemotherapy and radiation,” Moran said. “These patients can modify their lifestyles to decrease risk factors, such as obesity. There also is a need for African American patients to take part in large breast cancer studies to better understand the ethnicity based differences in breast cancer.”

http://www.yale.edu

A phase II trial on axitinib, a new experimental drug for treating patients with cytokine-refractory, metastatic kidney cancer who have a poor response to more traditional drugs has shown promising results according to a new study published in the The Lancet Oncology.

Professor Olivier Rixe of the University of Paris, France, and colleagues assessed the activity and safety of axitinib in a group of patients with metastatic renal-cell cancer who had failed to respond to cytokine-based treatments.

The researchers enrolled 52 patients between October 2003 and April 2004. Each patient had at least one measurable lesion that could be targeted and was given an oral dose of axitinib starting at 5 mg twice a day.

Rixe and colleagues assessed the percentage of patients who responded either completely or partially using the Response Evaluation Criteria In Solid Tumors (RECIST) method, as well as how long they took to respond, the time to progression, overall survival, safety and other measures.

In an intention to treat analysis, the study produced the following results:

* Of the 52 patients, 2 responded completely and 21 partially.

* This equated to an objective response rate of 44.2 per cent.

* The median response rate was 23.0 months (range 4.2 to 29.8 months).

* But 12 of 23 initial responders progressed with response durations of 4.2 to 26.5 months.

* Also, 22 patients showed stable disease for more than 8 weeks, with 13 of them for 24 weeks or more.

* 4 patients had early disease progression, 3 had missing response data.

* Median time to progression was 15.7 months (range 0.03 to 31.5 months).

* Median overall survival was 29·9 months (range 2·4 to 35·8 months).

* Adverse events linked to treatment included diarrhoea, hypertension, fatigue, nausea, and hoarseness.

* High blood pressure was found in 30 patients.

* Of these, all but 8 responded to blood pressure treatment. 7 of the 8 had a history of high blood pressure at enrollment.

The researchers concluded that:

“Axitinib shows clinical activity in patients with cytokine-refractory metastatic renal-cell cancer. Although 28 patients had grade 3 or grade 4 treatment-related adverse events, these adverse events were generally manageable and controlled by dose modification or supportive care, or both. Further studies are needed to confirm these findings.”

Condom awareness has increased significantly among sexually active men and women in India, according to a report released on Wednesday, the IANS/India eNews reports. The report assessed a three-year HIV/AIDS awareness campaign that was formed jointly by UNAIDS and India’s National AIDS Control Organization.

The campaign targeted six districts — Aizwal, Bellary, Guntur, Kanpur, Kishanganj and Udaipur — with high HIV prevalence. According to the report, 95% of men in India believe condoms can prevent the spread of HIV, and 70% percent of women know where to obtain condoms.

The report found that the incidence of sexually transmitted infections across the six districts dropped from 55% to 17%. It also showed that 5% of young women in Guntur, 6% in Kanpur and 8% in Kishanganj were willing to accept husbands with extramarital relationships. According to the report, the belief that condoms protect against HIV/AIDS has increased from 65% to 95% among men in all six districts. Awareness of single-partner sex as a preventive measure against STIs also increased from an average of 40% of residents to 76% across the districts, the study found. In addition, the study showed that the percentage of young women who knew where to obtain male condoms has increased significantly. About 84% of women in Guntur responded that they know where to find condoms in the recent survey, compared with 30% in 2004. Similarly, awareness among women in Aizwal increased from 42% to 91% during the same time period.

Reaction
Minister of State for Labour and Employment Oscar Fernandes, who released the report’s findings, said, “The results attained in three years have clearly demonstrated the effectiveness of a grassroots, district-level intervention that empowers women to protect themselves and a possible route-map to rid the nation of this devastating pandemic.” NACO Director-General Sujatha Rao said, “Given the vulnerability and risk of young women and the difficulty of mass reach of awareness programs,” the campaign has been “successful in building effective models of district-level interventions which address women’s empowerment through an expanded response.” She said the recommendations of the joint campaign will be included in the upcoming National Aids Control Program (IANS/India eNews, 10/24).

New data from the combined RESIST studies (RESIST-1 and RESIST-2) show that Aptivus (tipranavir), used with Norvir (ritonavir), provides a superior and durable treatment response for up to three years in treatment-experienced HIV patients versus a comparator group of protease inhibitors.(1) The research was presented at the 11th European AIDS Conference (EACS) in Madrid, Spain.

At 156 weeks, Aptivus combined with ritonavir (Aptivus/r), continues to outperform a group of ritonavir-boosted comparator protease inhibitors that includes low dose ritonavir boosted lopinavir, amprenavir, saquinavir and indinavir. When compared to these protease inhibitors, through three years of therapy, treatment response rates were almost three times higher in the Aptivus/r arm compared to the comparator arm (20.9% vs. 7.5%).

Moreover, patients taking Aptivus/r combined with first-time use of enfuvirtide achieved four-fold greater treatment response rates than patients with comparator protease inhibitors (37.9% vs. 8.2%). In this group, the proportion of patients who achieved a viral load of less than 50 copies/mL at week 156 was more than twice as high with Aptivus/r as with comparator protease inhibitors (21.8% vs. 9.3%).

The new data show that for patients who achieve successful HIV suppression with tipranavir, the results are usually maintained over the long term. In a patient population for which treatment options are limited, this is an important achievement, said lead author Charles Hicks, associate professor of medicine at Duke University, USA.

The adverse event profile for Aptivus/r was comparable with what has been reported in previous analysis. The patient exposure years (PEY)-adjusted adverse event profile was similar between Aptivus and the comparator protease inhibitors group.

Giulio Maria Pasinetti and colleagues at Mount Sinai School of Medicine, New York, have identified one antihypertensive medication with the ability to reduce AD-like disease in mice.

Alzheimer disease (AD), a neurodegenerative disease that is the most common form of dementia, is characterized by the formation in the brain of plaques containing misfolded beta-amyloid protein. Recent evidence indicates that some drugs used to treat high blood pressure (antihypertensive medications) might reduce the risk of developing AD. In a new study, in which they screened 55 antihypertensive medications in vitro for potential AD-modifying activity, Giulio Maria Pasinetti and colleagues at Mount Sinai School of Medicine, New York, have identified one antihypertensive medication with the ability to reduce AD-like disease in mice.

Only 7 of the 55 antihypertensive medications screened were able to reduce AD-like accumulation of beta-amyloid protein in cultured neurons isolated from mice engineered to be susceptible to an AD-like disease (Tg2576 mice). Of these 7, only 1 (valsartan) was able to markedly reduce the oligomerization of beta-amyloid protein, a feature of memory deterioration. As treatment of Tg2576 mice with valsartan, both before and after the onset of AD-like disease, reduced the severity of disease, the authors suggested that treatment with certain antihypertensive agents might be of benefit to individuals with, or at high risk of developing, AD.

TITLE: Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease

AUTHOR CONTACT:
Giulio Maria Pasinetti
Mount Sinai School of Medicine, New York, New York, USA.