Cases of the 2009 H1N1 influenza A virus has been confirmed in a Crawford County adult and a Miami County child. These are the first cases identified in both counties.

Local health departments are following the guidance provided by the Kansas Department of Health and Environment (KDHE) when dealing with a confirmed case. This includes a thorough case investigation and management of the patient and close contacts.

As of today, KDHE has identified the following cases of the 2009 H1N1 influenza A virus in Kansas. In all cases, the local health departments are following the guidance provided by KDHE when dealing with a confirmed case.

Confirmed Cases – 132 total

- Butler County – One case involving an adult
- Cowley County – Two cases total involving one adult and one child
- Crawford County – One case involving an adult
- Dickinson County – Two cases involving adults
- Douglas County – Four cases involving adults
- Ford County – One case involving a child
- Geary County – 25 cases total involving nine adults and 16 children
- Gove County – One case involving an adult
- Jefferson County – One case involving an adult
- Johnson County – 14 cases total involving five adults and nine children
- Kiowa County – One case involving an adult
- Labette County – Two cases involving adults
- Leavenworth County – Two cases involving children
- Miami County – One case involving a child
- Morton County – Three cases involving two adults and one child
- Neosho County – Two cases involving children
- Ottawa County – One case involving a child
- Pottawatomie County – Two cases involving children
- Reno County – One case involving an adult
- Republic County – One case involving a child
- Riley County – 25 cases total involving 17 adults and eight children
- Saline County – Eight cases total involving one adult and seven children
- Sedgwick County – 14 cases total involving nine adults and five children
- Shawnee County – Two cases involving adults
- Wyandotte County – 15 cases total involving two adults and 13 children

The symptoms of the 2009 H1N1 influenza A virus are similar to the symptoms of seasonal flu and include:

- Fever greater than 100 degrees
- Body aches
- Coughing
- Sore throat
- Respiratory congestion
- In some cases, diarrhea and vomiting

Individuals who experience the above symptoms should contact their health care provider, who will determine whether testing or treatment is needed. There is no vaccine available right now to protect against the 2009 H1N1 influenza A virus, but there are effective treatments available once the infection is diagnosed.

As with any influenza virus, individuals are encouraged to take the following steps to reduce spread:

- Wash your hands thoroughly with soap and warm water or use an alcohol-based hand sanitizer to get rid of most germs and avoid touching your eyes, nose and mouth.
- Stay home when you are sick to avoid spreading illness to co-workers and friends.
- Cough or sneeze into your elbow or a tissue and properly dispose of used tissues.
- Stay healthy by eating a balanced diet, drinking plenty of water and getting adequate rest and exercise.

It is important to know that the 2009 H1N1 influenza A virus is not transmitted by food. You cannot get this virus from eating pork or pork products. Eating properly handled and cooked pork and pork products is safe.

KDHE has established a phone number for concerned Kansans to call with questions about the 2009 H1N1 influenza A virus. The toll-free number is 1-877-427-7317. Operators will be available to answer questions from 8 a.m. – 5 p.m. Monday through Friday. Persons calling will be directed to press “1″ on their touch-tone phone to be directed to an operator who can answer questions.

Source
Kansas Department of Health and Environment

Although more than two fifths of lung cancers are diagnosed in patients over 70, data from clinical trials on the safest and most effective treatments for this age group are scarce. Now Italian oncologists are conducting a number of trials targeting elderly patients with non-small cell lung cancer (NSCLC), and offer a review of the latest findings – and their recommendations – in the current issue of Therapeutic Advances in Medical Oncology, published by SAGE.

According to Paolo Maione, Antonio Rossi, Cesare Gridelli and colleagues from S.G. Moscati Hospital in Avellino, Italy, elderly patients have more co-morbidity and don’t tend to tolerate toxic medical treatments as well as younger patients. This means that clinical findings from studies on younger populations don’t necessarily apply to the majority of elderly patients with NSCLC.

More than half of all cases of advanced NSCLC are diagnosed in patients over 65, and recent Surveillance, Epidemiology and End Results (SEER) Program data from the United States show that patients aged 70 years or older account for 47 percent of all lung cancers. Most prospective clinical data on chemotherapy and molecularly targeted therapy for elderly NSCLC patients come from studies in advanced disease. Unfortunately, by the time most patients from any age group receive a lung cancer diagnosis, the majority already have metastatic disease and a systemic, palliative treatment is their primary therapeutic option.

Cisplatin-based chemotherapy is currently recommended as the standard approach for patients with advanced NSCLC. However, to date, no prospective phase III study has explored the reproducibility of this benefit in elderly patients, the authors say. “The evaluation of cisplatin-based chemotherapy in elderly patients, in our opinion should be a priority,” says one of the study authors, Cesare Gridelli.

A number of phase II and III clinical trials show that single-agent chemotherapy with third-generation agents (vinorelbine, gemcitabine or taxanes) is the routine standard of care in elderly advanced NSCLC patients. The authors performed their own phase I/II trials looking at attenuated doses of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced NSCLC. Their results were published in 2007, and in particular show that gemcitabine combined with cisplatin deserves comparison with single agent therapy for this patient group. The researchers are now launching a phase III randomized trial of cisplatin plus gemcitabine versus gemcitabin.

In addition to these chemotherapy treatments, targeted therapies are also available. Oncologists have tested epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, erlotinib and gefitinib, in phase II prospective trials on older patients. They showed that these drugs were a good first line treatment option. The United States Food and Drug Administration (FDA) has recently approved gefitinib for first-line treatment of patients whose tumors are positive for EGFR gene mutations. This means that screening lung cancer patients for EGFR gene mutations will have an important role in decisions about treatment, and will benefit elderly patients, too.

However, another targeted treatment option for the general patient population, using the monoclonal antibody bevacizumab combined with chemotherapy, may be less suitable for the elderly due to their higher likelihood of co-morbid cardiovascular illnesses.

“The lack of data on octogenarians suggest that clinicians should exercise caution when applying the existing data on chemotherapy and targeted therapies for patients aged 70-79 years to those aged over 80 years,” the authors stress. “Further specifically designed clinical trials are needed to optimize medical treatment of NSCLC in elderly patients.”

Since 2000, oncologists have noticed that incidence of and death from lung cancer among women aged 50 and below has actually decreased. However, for women aged 70 and older these have increased. For men, mortality has been decreasing for all age groups except among men aged 70-74, where it has leveled off.

Lung cancer is the most common cancer in the world and the leading cause of cancer-related deaths in western countries. NSCLC constitutes between 80% and 85% of all lung cancers. Elderly cancer patients often present with medical and physiological challenges that make the selection of their optimal treatment daunting for oncologists. Despite this (or perhaps because of it), the elderly are sorely underrepresented in clinical trials, even though most phase II and III trials now have no upper age limit.

“Elderly-specific trials provide quality care in the elderly, particularly among the oldest of the old,” says Gridelli. “This patient population is at risk of both empirical under treatment resulting in poor survival or excessive toxicity from standard therapy.”

The authors are continuing to conduct and publish their prospective trials of a number of lung cancer treatments on elderly patients, to ensure that the data is available for oncologists to make the best choices for their oldest patients in years to come.

Treating advanced non small cell lung cancer in the elderly by Paolo Maione, Antonio Rossi, Paola Claudia Sacco, Maria Anna Bareschino, Clorinda Schettino, Marianna Luciana Ferrara, Marzia Falanga, Rita Ambrosio and Cesare Gridelli will be published in Therapeutic Advances in Medical Oncology published by SAGE on the 29th April 2010. DOI: 10.1177/1758834010366707 and will be available free of charge for a limited time at tam.sagepub

Source:
Jayne Fairley
SAGE Publications UK

A study published this week in the Proceedings of the National Academy of Sciences of the United States of America shows that Aflunov®, the Novartis investigational pre-pandemic avian influenza vaccine formulated with Novartis’ proprietary MF59® adjuvant, can elicit a broadly cross-reactive immune response covering all known H5N1 antigenic variants, even when that booster dose is administered six years after the initial priming dose.

The data show that the Novartis investigational adjuvanted vaccine elicited a long-lasting immune response that could be rapidly boosted following a single dose of the vaccine. This may provide public health officials additional flexibility to help protect citizens well in advance of an avian influenza pandemic. The study also showed that the adjuvanted vaccine created an immune memory not only against the H5N1 strain contained in the vaccine but also provided cross-protection against several other H5N1 strains.

“These data reinforce the potentially broad applicability of the MF59 adjuvant and the role it can play in pandemic preparedness efforts around the world,” said Andrin Oswald, CEO of Novartis Vaccines and Diagnostics. “Cross-reactivity is an important element for a pre-pandemic vaccine given that variations are a common feature of emerging influenza strains. We will use these new insights, as well as our strong leadership position in cell based flu manufacturing, as part of our efforts to develop a vaccine against the current swine flu outbreak.”

“The findings published about the H5N1 vaccine suggest a way forward for the present swine flu outbreak, ” added Rino Rappuoli, Head of Research at Novartis Vaccines. “We are working closely with the World Health Organization, U.S. Centers for Disease Control and Prevention (CDC), PAHO and other government agencies worldwide on developing a strong and effective response to the outbreak.”

These data are part of several new studies presented this week at the Third International Conference on Influenza Vaccines for the World (IVW) in Cannes, France. Selected Aflunov data were previously presented in September 2008 at ESWI in Portugal, and announced at that time. Aflunov has not been tested on swine flu and has not been approved for sale in the U.S., Europe or other markets. A Phase II study has also demonstrated that Aflunov provided a protective immune response in children as young as 6 months to 17 years of age1. It is the first and only -pre-pandemic avian vaccine with a good safety profile and which is effective in building an immune response as early as 6 months of age3.

“To have a pre-pandemic vaccine that can produce a protective immune response in children as young as 6 months of age, as well as seniors is essential,” said Timo Vesikari, M.D., Professor of virology and pediatrics and Director of the Vaccine Research Center at the University of Tampere, Finland. “Children are not only at the biggest risk of complications from influenza, but they have been identified as the prime population for spreading the virus to all ages. We need to ensure that they are protected against a potential pandemic, which can strike at any time.”

In a third study presented at IVW, Aflunov demonstrated that it could potentially be used to prime the general public against a potential influenza pandemic through a flexible dosing regimen, which would allow public health officials to immunize their citizens by administering the vaccine well in advance of a potential outbreak. The trial showed that a single priming dose of the vaccine was sufficient to develop immune memory in more than 90 percent of healthy adults, which could then be boosted one year later with either the same or a different strain of the avian influenza virus2.

MF59 is the only flu adjuvant in a pre-pandemic program with an established safety profile, supported by more than 10 years of clinical safety data and more than 40 million doses of commercial use in Europe. The adjuvant has been studied in clinical trials involving more than 26,000 people, including children, and has been licensed for use in people 65 years of age and over in the seasonal influenza vaccine, Fluad®, since 1997 in the European Union4. Fluad is not licensed for sale in the U.S.

Study details

The first study was a Phase II trial that involved 472 subjects aged 6 months to 17 years. The subjects were divided into three cohorts: toddlers 6-36 months of age, children 3-9 years of age and adolescents 9-17 years of age. Each age group was randomized in a 3-to-1 ratio to receive either the adjuvanted pre-pandemic vaccine (Aflunov) or Fluad, a seasonal influenza vaccine. Participants in the adjuvanted pre-pandemic vaccine arm received two 0.5 mL doses. Those in the Fluad arm received two 0.25 mL doses if they were younger than 3 years of age and one 0.5 mL dose if they were 3 years of age or older. Antibody responses were measured using standard hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization antibody response (MN) methods.

After the first dose of adjuvanted pre-pandemic vaccine, HI results demonstrated that two Committee for Medicinal Products for Human Use (CHMP) criteria were reached by the adolescent group and one was reached by the toddler and children groups. SRH results showed that all three cohorts fulfilled CHMP for geometric mean ratio and seroconversion. Following the second vaccination with the adjuvanted pre-pandemic vaccine, all three CHMP immunogenicity criteria were met in all three age groups as measured by HI and SRH. Further, 94 percent of toddlers, 92 percent of children and 72 percent of adolescents achieved at least a fourfold increase in MN titer over baseline and 99 percent of all three groups achieved an MN titer of ≥ 40 – common measures of seroprotection1.

The second study was a Phase II open-label trial that involved participants from 18 to 40 years of age. A subset of 99 subjects received one dose of adjuvanted pre-pandemic vaccine (H5N1 clade 1 [Vietnam]) either three weeks before or after one dose of Agrippal (2007 season). A heterologous (H5N1 clade 2 [Turkey]) adjuvanted pre-pandemic vaccine booster dose, mixed with Agrippal, was administered one year later.

Antibody responses were measured one, two and three weeks later to assess cross-reactivity by HI, MN and SRH and measure seroconversion and seroprotection. After priming, the vaccine gave similar seroconversion (>40 percent) and seroprotection (>40 percent) rates against homologous virus as seen in previous studies three weeks post-vaccination. All three EMEA licensure criteria were met using both HI and SRH assays2.

Heterologous boosting produced memory immune responses, evident within one week, in more than 90 percent of the subjects. Seroconversion and seroprotection rates were equivalent to those seen after homologous priming2.

Novartis Vaccines commitment to pandemic preparedness

Novartis Vaccines is supportive of the WHO’s leadership role in global pandemic planning as discussed in the organization’s “THE WORLD HEALTH REPORT 2007: Global Public Health Security in the 21st Century.” The WHO is a key global hub for pandemic preparedness, ensuring cohesion and coordination among all players involved, including the industry, governments of both developed or developing countries and their populations.

Novartis Vaccines is working closely with government and regulatory officials worldwide to support pandemic preparedness efforts, including providing vaccines for stockpiling. The company has also been involved in discussions to educate government agencies about the benefits of proactive use of pre-pandemic vaccination in pandemic preparedness planning. The Company also recognizes the importance of pandemic influenza preparedness planning within the business community in an effort to protect the global economy. With this commitment, Novartis Vaccines is working with business leaders to support their continuity planning for pandemic preparedness.

Novartis is the only vaccines manufacturer that has an established, licensed FCC (Flu cell culture) facility which is operating in Marburg, Germany. A second facility, a collaboration with HHS, Department of Health and Humans Services, U.S, is under construction in Holly Springs, North Carolina.

References

1. Anke Hilbert, Elena Fragapane Nicola Groth, Sandrine Tilman, Timo Vesikari. A Phase II, randomized, controlled, observer-blind, single-center study to evaluate the immunogenicity, safety and tolerability of two doses of MF59®-adjuvanted H5N1 influenza vaccine, AFLUNOV®, in subjects aged 6 months to 17 years. Accessed March 24, 2009.

2. Angelika Banzhoff, Elena Fragapane, Volker Brauer, Emanuele Montomoli, Chiara Gentile, Anke Hilbert, Sandrine Tilman, Pio Lopez; Novartis AG. M459-Adjuvanted H5N1 Prepandemic Influenza Vaccine Demonstrates Flexible Prime Boosting. Accessed March 23, 2009.

3. Timo Vesikari. Aphase II randomized, controlled, observer-blind, single center study to evaluate the immunogenicity, safety and tolerability of two doses of MF59-adjuvanted HF5N1 influenza vaccine, AFLUNOV, in subjects aged 6 months to 17 years. University of Tampere Medical School, Finland. Accessed March 23, 2009

4. Ott Garyet al. The Adjuvant MF59: A 10-Year Perspective, Methods in Molecular Medicine., Vol 42: Vaccine Adjuvants: Preparation Methods and Research Protocols

Source
Novartis

UroToday- In this article published in the October issue of the Journal of Urology, Steven and Poulsen report the 5-year cancer specific and overall survival on 336 consecutive patients with invasive bladder cancer who underwent a radical cystectomy and extended lymph node dissection that included the common iliac and peri-aortic lymph nodes up to the inferior mesenteric artery. None of the patients received neo adjuvant or adjuvant chemotherapy.

The percentage of patients with lymph node metastases was 19% (64) while 34% of these 64 patients (18% of the total patient population) had nodal involvement above the common iliac vessels. As expected, lymph node involvement of any kind had a significant impact on cancer-specific and overall survival. Patients with lymph node metastases had a 5-year cancer-specific survival of 39% compared to 76% in node negative patients. Interestingly, there was no difference in 5-year survival between patients with nodal involvement below the bifurcation of the common iliac vessels (42%), those with metastases above the bifurcation (37%), or those with any nodal involvement (41%).

The authors suggest that extended lymph node dissection is important for diagnostic and therapeutic reasons. Nodal involvement above the true pelvis (bifurcation of the common iliac vessels) is staged as metastatic (M1) disease rather than node positive disease (N+) in the current TNM staging system. The results showing surgery alone having a 5-year survival rate of 37% without chemotherapy is significantly better than historical controls of patients with M1 disease, though most of those had lung metastases. By this comparison, node dissection is therapeutic. A larger question is if retroperitoneal nodal disease should be considered metastatic (M+) or node positive (N+). In addition, only a randomized study can answer the therapeutic effect of an extended node dissection. However, this article adds to the body of literature that a more extensive node dissection in patients with muscle invasive bladder cancer is beneficial.

Steven K, Poulsen AL

J of Urol. 178(4): 1218- 1224, October 2007
doi:10.1016/j.juro.2007.05.160

Reported by UroToday Contributing Editor David P. Wood, M.D

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
www.urotoday

—————————-
Copyright © 2007 – UroToday
Reproduced for blog with permission of UroToday.
—————————-
 

A new study by UT Southwestern Medical Center researchers sheds light on the challenges involved in identifying which high-risk population would benefit most from bladder-cancer screening.

Large-scale screening of people at high risk for developing invasive bladder cancer could result in earlier diagnosis and improved survival rates. Bladder cancer is the fourth most common cancer in men and the fifth most common cancer overall. In the early stages of the disease, it’s common to have no signs or symptoms. Smoking has been proven to increase the risk of the disease.

“At this time bladder cancer screening is not the standard of care,” said Dr. Yair Lotan, associate professor of urology and senior author of the study appearing online and in a future edition of The Journal of Urology. “Although progress has been made in diagnosis, those efforts have translated into minimal survival benefit. In order to get the most benefit from the added cost of screening, we need to identify the appropriate population to screen.”

In the study researchers used a point-of-care urine-based test called NMP22 BladderChek to screen 1,502 subjects without symptoms who are at high risk for bladder cancer based on age, smoking history and occupational exposure.

Patients for the study were recruited from well-patient clinics at UT Southwestern and the Dallas Veterans Affairs Health Care System from March 2006 to November 2007. Those selected were over 50 years old, had smoked for 10 years or more, or had worked for 15 years or more in a high-risk occupation, such as in the dye, petroleum or chemical industries. Participants with other conditions that might lead to false-positive tests were excluded from the study.

Of the 1,502 participants, 85 tested positive for proteins that indicate the possible presence of a bladder tumor; 69 of those agreed to undergo cystoscopy. Only two, however, were found to have noninvasive bladder cancer. The majority of these participants had undergone urinalysis within three years of screening. At the one-year follow-up, two more were found to have cancer, and these patients were over 60 and had more than 42 pack-years of smoking.

“We did expect to find more cases,” Dr. Lotan said. “The significance is that even with high-risk patients, only a few had cancer. What that means is we need to find a higher-risk group either by increasing screening to over the age of 60 instead of 50 or looking at individuals with a longer smoking history.”

Dr. Lotan said that abstaining from or quitting smoking is the most effective way to prevent bladder cancer and that people should see a urologist immediately if they see blood in their urine or are found to have microscopic blood in their urine.

Other UT Southwestern researchers involved in the study were Dr. Arthur Sagalowsky, professor of urology; Dr. Brett Moran, associate professor of internal medicine; Dr. Geoffrey Nuss, urology resident; Dr. Aditya Bagrodia, family practice resident; Keren Elias, research study coordinator; and Dr. Robert Svatek, a fellow in urologic oncology at UT M.D. Andersen Cancer Center.

Source:
Erin Prather Stafford

UT Southwestern Medical Center

Research published by Army scientists indicates that a minor reduction in levels of one particular gene, known as CD45, can provide protection against two divergent microbes: the virus that causes Ebola hemorrhagic fever and the bacterium that causes anthrax. Taken together, the results suggest a common host restriction factor and a promising approach to drug development for treating two completely different infections.

Writing in the August 20 online issue of Cell Host and Microbe, scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) reported that mice expressing reduced levels of CD45 (between 11 and 77 percent) were protected against Ebola virus. In addition to an overall survival rate of 90 to 100 percent, these mice had reduced levels of virus load in the major organs, and had completely cleared the virus 10 days after challenge.

In contrast, mice that had naturally occurring levels of CD45 – or none at all – failed to clear the virus and succumbed to infection within 7 to 8 days following challenge.

The protein encoded by CD45 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, cell division, and the development of malignancies that can lead to tumor formation.

Scientists created various “knockdown” mice, which expressed reduced levels of CD45, to determine how those changes may alter the body’s immune response to microbial pathogens such as Ebola virus. According to the authors, the “knockdown” mice retained greater control of gene expression and immune cell proliferation following Ebola virus infection. These factors contributed to enhanced viral clearance, increased protection against the virus, and a reduction in cell death.

The team’s results suggest that host susceptibility to Ebola virus is dependent on the delicate balance of the body’s natural immune system, which can be determined by the levels of a single regulator gene.

Ebola virus, which causes hemorrhagic fever with human case fatality rates up to 80 percent, is a global health concern and a potential biological threat. Currently there are no available vaccines or therapies. Scientists at USAMRIID study the Ebola virus to support development of medical products to prevent and treat infection.

The recently published work builds upon a related study that appeared in the Journal of Biological Chemistry in May of this year. That research showed that CD45 also plays a role in protection from Bacillus anthracis, the causative agent of anthrax. Specifically, the USAMRIID team demonstrated that in mice expressing 62 percent of the CD45 gene, about 70 percent were protected following exposure to anthrax.

Bacillus anthracis causes three types of disease – cutaneous, gastrointestinal, and inhalational – depending upon the route of exposure. A licensed vaccine is available, and is protective if administered before exposure. Inhalational anthrax is difficult to diagnose early, and despite antibiotic therapy, has a high fatality rate. In addition, because anthrax spores can remain in the body for extended periods, antibiotic treatment is typically recommended for 60 days or more following exposure.

“This report demonstrates the critical connection between basic research and the potential development of medical products,” said COL John P. Skvorak, commander of USAMRIID. “Understanding pathogenesis of disease and host response is critical to the Department of Defense’s investment in broad spectrum countermeasures.”

The next step for investigators is to look at the mechanism of action to better understand how reduced expression of this gene regulates the pathogenesis of both diseases. That information could one day lead to the identification and discovery of additional promising compounds for treating Ebola and anthrax infections.

Both studies were supported by grants from the Defense Threat Reduction Agency, the National Institutes of Health, the National Cancer Institute, and the National Institute of Allergy and Infectious Diseases.

USAMRIID, located at Fort Detrick, Maryland, is the lead medical research laboratory for the U.S. Biological Defense Research Program, and plays a key role in national defense and in infectious disease research. The Institute conducts basic and applied research on biological threats resulting in medical solutions (such as vaccines, drugs and diagnostics) to protect the warfighter. While USAMRIID’s primary mission is focused on the military, its research often has applications that benefit society as a whole. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command.

References:

Rekha G. Panchal, Steven B. Bradfute, Brian D. Peyser, Kelly L. Warfield, Gordon Ruthel, Douglas Lane, Tara A. Kenny, Arthur O. Anderson, William C. Raschke and Sina Bavari. “Reduced Levels of Protein Tyrosine Phosphatase CD45 Protect Mice from the Lethal Effects of Ebola Virus Infection,” Cell Host and Microbe (August 2009).

Rekha G. Panchal, Ricky L. Ulrich, Steven B. Bradfute, Douglas Lane, Gordon Ruthel, Tara A. Kenny, Patrick L. Iversen, Arthur O. Anderson, Rick Gussio, William C. Raschke, and Sina Bavari. “Reduced Expression of CD45 Protein-tyrosine Phosphatase Provides Protection against Anthrax Pathogenesis,” Journal of Biological Chemistry (May 2009).

Source:
Caree Vander Linden

US Army Medical Research Institute of Infectious Diseases

In the world of Down syndrome, ‘Mr. C’ is a rarity. A real person whose progress has been tracked for the past 16 years, at seventy, ‘Mr. C’ has well surpassed the average life expectancy of a person with Down syndrome, currently in the late fifties, but in the teens when ‘Mr. C’ was born. Further, ‘Mr. C’ does not exhibit clinical symptoms of Alzheimer’s disease, which is almost a given for people with typical Down syndrome over 65 yeas of age. ‘Mr. C’, while remaining nameless, puts an optimistic face on the future of aging for people with Down Syndrome, as scientists ask the critical question: What is it about ‘Mr. C”s individual characteristics and experiences that have made him not only live longer, but also age successfully despite having Down syndrome? The case of ‘Mr. C’, including descriptions of comprehensive cognitive, behavioral, and genetic analyses and implications for research is published in the June 2008 issue of the journal, Intellectual and Developmental Disabilities. To read “Successful Aging in a 70-Year-Old Man With Down Syndrome: A Case Study” by Sharon J. Krinsky-McHale et al., click here.

“‘Mr. C’ paints an optimistic picture for people with Down syndrome who are aging, and says that an ordinary person with Down syndrome ought to be able to make it to seventy, once you find ‘Mr. C”s secret,” explains Dr. Sharon J. Krinsky-McHale, lead author of the study and Research Scientist at the New York State Institute for Basic Research in Developmental Disabilities.

People with Down syndrome are born with an extra copy of Chromosome 21, and these third copies of genes on Chromosome 21 lead to an overproduction of certain proteins that cause the phenotype of Down syndrome, including familiar facial features, congenital heart diseases, cognitive impairments, and other conditions. Previous studies of people with Down syndrome over 75 years of age have found that they usually do not have typical Down syndrome, which ‘Mr. C’ does. That is, these previous cases did not have three complete copies of Chromosome 21 throughout all the cells in their bodies, but had an atypical Down syndrome genotype, explaining why they may have been less severely affected and why they had a higher life expectancy. However, ‘Mr. C’ is aging successfully despite having complete Trisomy 21, making this the first case of its kind reported in scientific literature.

“The understanding in the field [until] very recently was that if you had Down syndrome and were lucky enough to make it to 70 years of age, then you would have to have Alzheimer’s disease,” explains Wayne Silverman, the study’s co-author and Director of Intellectual Disabilities Research at the Kennedy Krieger Institute in Baltimore. “But now, we have ‘Mr. C’, who clearly contradicts this longstanding assumption and offers a new benchmark and tremendous hope for all people with Down Syndrome to live longer and healthier lives.”

The processes regulating aging and dementia are complex and it is unlikely that any single mechanism can fully explain the array of changes that occur with aging. While future research could take several directions, including studies of risk factors like cholesterol or the bio availability of estrogen, Silverman explains that the area of gene expression offers promise at this time. While an extra copy of Chromosome 21 in a person causes an overabundance of some proteins, one possible explanation for ‘Mr. C”s successful aging and increased life expectancy is that, for one reason or another, he does not actually have an overexpression of all the genetic material that comes along with his extra copy of Chromosome 21.

###

An article published Online First and in a future edition of The Lancet describes the procedures involved in a near-total face transplant. The patient is US citizen Connie Culp. In 2004, she was shot in the face with a shotgun by her husband. The article details her ground-breaking surgery and recovery to date. It is the work of Professor Maria Siemionow, of the Cleveland Clinic, Cleveland, Ohio, USA, and collaborators.

Connie, 46 years old and mother of two, was left with most of the middle part of her face missing after the shooting. She lost her nose, mouth, nerve, skin and other structural damage. She was fortunate to survive the attack, but her face was completely disfigured. She could not drink from a cup and her speech was slurred. She lost her sense of smell as well. From 2004 to 2008, she underwent 23 major reconstructive operations. But unfortunately they failed to restore her disfigured structures and left her feeling humiliated in public. Doctors determined that the final option to allow her to recover facial function and a normal appearance was a full face transplant. Connie was informed of the risk of serious complications. These involved the need for lifelong immunosuppression. She signed the consent form.

A brain-dead woman matching ConnieВґs age, race, and skin complexion was the donor. In December 2008 the operation was carried-out by an eight-surgeon team, including Professor Siemionow. The surgery lasted twenty-two hours. The donor face covered 80 percent of the area of where Connie’s face had been, and contained various structures including the nose, upper lip, lower eyelids, and the upper jaw including incisor teeth, palate, and various glands. After the bone components of the graft were secure, connections of the arteries and veins were made. Around 2 hours and 40 minutes after the connections were completed, the donor tissue began to pink up. This confirmed the graft’s viability. The facial nerves were then connected.

Immediately following the operation, an assortment of immunosuppressant drugs was given to Connie. She remains on immunosuppressant medication to prevent rejection of her new face. Up to now, she remains negative for cytomegalovirus and other infections. She began physiotherapy and speech therapy 48 hours after the surgery and continued to do so once a day for the first six weeks, then three times per week during follow up. Connie was regularly evaluated on her ability to speak, smell, swallow, make facial expressions, and other muscle control functions in her new face. She also received psychological support once a day during the first six weeks, then three times per week.

There was one occurrence of rejection of the graft lining on day 47, but this was reversed with a 1g dose of methylprednisolone. Facial sensation returned, after 6 months. Motor muscle recovery is slow but progressing. It is assessed by repose (expressionless features), pucker, smile, and pronunciation of vowels. Connie’s upper lip and lower eyelid movements remain imperfect but it is too soon to expect complete recovery in this area. On the other hand, major functions which she had lacked for four years are now restored. Now, she can smell, eat solid foods, drink from a cup, and her speech is intelligible. Before the transplant she felt pain which she rated as 8 out of 10 in severity. It was due to scarring and contracted tissues in the affected area. She now rates the pain as 1 out of 10.The authors write: “Aesthetic outcome will be improved by excision of the redundant skin, which is planned about 1 year after transplantation…Psychologically, she is doing well. She has no symptoms of depression or post-traumatic stress disorder.”

She rated her own appearance as 5 out of 10 three weeks post-transplantation. Then 5 months after the procedure this had improved to 8 out of 10. The authors explain: “Since surgery, she has recovered self-confidence, and looks forward to rebuilding her social life and to helping others who have been similarly disabled by trauma.”

The authors point out that there are ethical challenges remaining for patient selection for future operations, as well as medical support, appreciation of the moral, professional, and financial responsibilities of the patient. All of these factors will be determined by the geographic, cultural, and economic conditions of each particular patient. The authors add: “Nevertheless, in complex physically and functionally disabling cases, the patient’s ethical right to make decisions should be respected, after being informed of the risks and benefits of the procedure and the need for life-long immunosuppression.”

They say in closing: “We show the feasibility of reconstruction of severely disfigured patients in a single surgical procedure using complete facial allotransplantation. Therefore, this should be taken in consideration as an early option for severely disfigured patients.”

Professor Siemionow explains: “The outcome of this particular case supports facial allotransplantation as a means of early intervention for patients with severe facial deformities. It is with great pride that we share the outcome of this surgery; our patient is doing remarkably well and is very pleased with the result.”

In an associated note, Dr Chenggang Yi and Dr Shuzhong Guo,from the Institute of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China, comment: “In our view, all of the problems in human facial transplantation, immunological status, selection of the recipient and donor, surgical technique, and psychological considerations are all important…Technically, Siemionow and colleagues’ surgery was very complex, and the patient gained good functional recovery. So far, total facial transplantation has not been reported. We think the most difficult part of the face transplantation is the aesthetic and functional recovery of the upper eyelids.”

“Some key points in facial transplantation remain intractable. Therefore the objective is to identify potential problems, and develop management strategies to resolve them. The day may not be far when facial transplantation becomes the standard of care for disfigured patients.”

“Near-total human face transplantation for a severely disfigured patient in the USA”
Maria Siemionow, Frank Papay, Daniel Alam, Steven Bernard, Risal Djohan, Chad Gordon, Mark Hendrickson, Robert Lohman, Bijan Eghtesad, Kathy Coffman, Eric Kodish, Carmen Paradis, Robin Avery, John Fung
DOI: 10.1016/S0140-6736(09)61155-7
thelancet

Stephanie Brunner (B.A.)

Summer, in all its blazing, sunny glory, is back! There’s plenty of time to get out on the fairway with your golf clubs or onto a court with your racquet. However, this also means there’s time for a sports injury to put an end to your summer fun. Golfer’s elbow, climber’s finger and runner’s knee are just a few of the problems that can plague the boys (and girls) of summer.

Dr. William Levine, chief of sports medicine at NewYork-Presbyterian Hospital/Columbia University Medical Center, recommends the following rules of the game to avoid athletic injuries:

- Your best bet is to prevent injuries before they happen. First of all, start slow. Don’t expect to be in the same playing condition that you ended up in last fall, even if you have been maintaining your fitness level. New activities require muscles and joints to respond in a different way. This may result in minor soreness while your body adjusts. If you push yourself too hard too soon, that minor soreness could turn into something more serious.

- Don’t forget to warm up. Although you may feel warm in good weather, you still have to give your muscles a chance to go through the motions and get blood pumping to all the necessary areas. Gentle stretching before finishing your activity will help those hard-working muscles retain and improve flexibility.

- For tennis elbow, runner’s knee, and similar injuries, try R.I.C.E. — Rest, Ice, Compression and Elevation. Rest means that the injured area is not put through any undue strain. When icing a body part, apply the ice in a covering so that it is not in direct contact with the skin. A cotton handkerchief covering the ice is helpful. Ice the affected area several times a day, for about 20 minutes at a time. Compression is applying pressure to the injured area to stop bleeding (if any is occurring) or to reduce swelling. Elevation helps in these respects as well. Compression and elevation are to be used in the case of acute injuries, such as a twisted ankle.

- Take frequent breaks. Even tennis pros rest between sets. Taking a rest doesn’t mean that you have to completely stop all activity, although it may be advisable sometimes. Just rest the body parts that are working hard and are susceptible to injury.

- The single most important thing you can do is pay attention to your body. Don’t ignore the little aches and pains in the joints and muscles. They are early signals that could help you prevent more serious injuries.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

Urinary tract infections are common in women, costing an estimated $2.5 billion per year to treat in 2000 in the United States alone. These infections frequently recur, affecting 2 to 3 percent of all women. A depletion of vaginal lactobacilli, a type of bacteria, is associated with urinary tract infection risk, which suggests that replenishing these bacteria may be beneficial. Researchers conducted a double-blind placebo-controlled trial to investigate this theory. Their results are published in Clinical Infectious Diseases and now available online.

In the study, young women with a history of recurrent urinary tract infections received antibiotics for acute urinary tract infections. They were then randomized to receive either a Lactobacillus crispatus intravaginal suppository probiotic, called LACTIN-V, or a placebo for five days, then once a week for 10 weeks.

The results suggest that the probiotic may reduce the rate of recurrent urinary tract infections in women prone to these infections. Of the 100 women who participated in the study, 50 received LACTIN-V, and 50 received the placebo. Seven of the women who received LACTIN-V had at least one urinary tract infection, compared to 13 in the placebo group.

According to study author Ann Stapleton, MD, of the University of Washington in Seattle, “Larger efficacy trials of this novel preventive method for recurrent urinary tract infections are warranted to determine if use of vaginal Lactobacillus could replace long-term antimicrobial preventive treatments.”

Source
Clinical Infectious Diseases