Improving brain cell survival after brain injury

Scientists at Melbourne's Howard Florey Institute have found a protein in the brain that can save neurons from dying after experiencing traumatic brain injury from incidents such as stroke, car accidents and falls.

The team, led by Professor Seong-Seng Tan, has discovered that this naturally occurring protein, called BP5, is produced more than usual in brain cells after they have experienced traumatic injury.
Prof Tan said that because this protein is "over-expressed", it can prevent the neuron's cells from dying, thus reducing brain damage.
"BP5's pattern of expression indicates that it allows neurons to survive in a stressed environment," Professor Tan said.
"We have tested this hypothesis in mice by expressing BP5 in stressed neurons and this proof-of-principle experiment showed that BP5 can prevent neurons from undergoing cell death.
"BP5 works by using the cell's waste disposal system to flush away toxic and damaged proteins produced after injury, which appears to tip the balance towards nerve cell survival, instead of death," he said.
Professor Tan is the first to show that this mechanism can be fruitfully manipulated to prevent brain cells from dying. For this reason, his work has been published by the Journal of Neuroscience, the peak body journal of the American Society for Neuroscience.
"Now our challenge is to understand how BP5 performs it neuron-saving function and develop drugs that can do the same thing," Professor Tan said.
"Ultimately, we want to deliver the drug to patients suffering brain injury from stroke or trauma so save as many neurons as possible.
"Such a drug would limit damage to the brain after the injury, as well as the subsequent few days when injured nerves release 'suicide factors' that cause surrounding, healthy neurons to die en masse.

Novel therapy combinations gain ground in treating hepatitis

LOS ANGELES (May 21, 2006) - According to recent estimates, hepatitis has become a worldwide health problem, affecting millions of people in the U.S. and abroad.

Researchers are experimenting with combinations of anti-inflammatory medicines like interferons to improve hepatitis symptoms. In research presented today at Digestive Disease Week� 2006 (DDW), new combinations of therapies are making significant progress to improve symptoms of the disease. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Hepatitis is caused by a virus that attacks the liver, triggering painful inflammation and often leading to more serious conditions like liver failure and even death. Several different forms of hepatitis exist, including hepatitis A, B and C. Hepatitis A is generally food-borne, while hepatitis B and C are spread primarily through parenteral or sexual routes. The disease is often caused by a virus, but can also result from alcohol, toxins or drugs.
"Despite the significant number of people suffering from hepatitis, treatment options have been lagging in comparison to other major diseases," said John Vierling, M.D., FACP, president, the American Association for the Study of Liver Diseases (AASLD); professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas; and director of Baylor Liver Health and Chief of Hepatology. "We hope that continued research like these studies will lead to more significant breakthroughs and relief for these patients."
Valopicitabine (NM283), Alone or with Peg-Interferon, Compared to Peg Interferon/Ribavirin (pegIFN/RBV) Retreatment in Hepatitis C Patients with Prior Non-Response to PegIFN/RBV: Week 24 Results [Abstract 4]
More than half of currently treated hepatitis patients are infected with strains of hepatitis C that do not respond to current interferon therapies and have no other effective treatment options. Combination treatment using a new antiviral therapy is showing promise in suppressing the virus, according to a phase II US multi-center study. The therapy, valopicitabine, has shown anti-HCV activity alone and in combination with pegIFN (pegylated interferon) in early trials, without viral breakthrough for study periods up to six months.
The current study compared the outcomes of five different treatments in patients who have not experienced remission with standard therapies: valopicitabine alone (800 mg/d), one of three combination arms with the drug at 400 mg/d, 800 mg/d or dose-ramping 400 to 800 mg/d plus pegIFN, or pegIFN with ribavirin as a control group.
For the 162 patients who have completed the trial period at 24 weeks, results show that the two higher-dose combination arms had much better response rates than the control group, experiencing on average a 2.5 to 3.0 log decrease in hepatitis RNA reductions by week 24, a significantly better response than the comparator. No viral breakthrough has been seen to date. However, vomiting and dehydration requiring hospitalization occurred in three patients taking the highest dose (800 mg), forcing the research team to halt the use of that dose and continue using only the lower doses of 200 to 400 mg of the drug.
"For patients whose disease has not responded to current therapies, this new combination treatment may produce excellent results, at the maximally acceptable dosage," according to Paul Pockros, M.D., of Scripps Clinic in California, and lead study author. "Continued treatment will determine if these encouraging early responses will result in a sustained response, hopefully improving patient quality of life and long-term survival."

Five new facts could change our understanding of starvation

In a "Viewpoint" published in The Lancet, Rainer Gross, PhD, UNICEF's chief of nutrition, and Patrick Webb, PhD, dean for academic affairs at the Friedman School of Nutrition Science and Policy at Tufts University, discuss five facts about world hunger, children and wasting, a condition that represents severe malnutrition.
Wasting is defined by a low weight-to-height ratio; it is visible in the form of skeletally thin children usually found in the middle of a famine. The authors note that a public health disaster is generally declared if more than 15% of the children in a country suffer from wasting. Gross and Webb analyzed countries with the highest child mortality rates and child wasting rates. Based on their assessment of the data, the authors present five surprising facts about severe children malnutrition and argue that such conditions must be resolved in non-emergency settings to prevent future public health crises.
First, contrary to popular belief, Africa does not have the most children suffering from wasting. "Although in the past 10 years, every subregion of Africa saw a rise in both the number of wasted children under the age of five and in the overall rate of wasting, about 78% of the world's 5.5 million wasted children live in India, Pakistan, and Bangladesh; nearly two thirds of those in India alone," says Webb.
Secondly, the absence of conflict, such as political instability, does not prevent or resolve wasting in children. When the authors compared countries without recent conflict to countries that have recently emerged from periods of conflict or remain continually unstable, they found that, "�stability, economic growth, and even political transparency are not in themselves sufficient factors to overcome the persistence of wasting in marginalized vulnerable groups." Wasting is a complex condition that is not simply caused by conflict or famine alone. Gross and Webb conclude that "effective, targeted actions are needed as part of the development agenda."
Third, HIV does not appear yet to contribute substantially and directly to severe wasting in children, although the authors state that "as the pandemic progresses, high HIV/AIDS rates will contribute to worsening nutrition, both from the direct effects of the disease and from an indirect impact on household food security and childcare. Without dual action against wasting and HIV/AIDS, the deadly synergy of these two factors is likely to grow in coming years."

Remicade Phase 3 data show long-term psoriasis response

Findings from the EXPRESS II trial, a placebo-controlled, dose-ranging study of REMICADE 3 mg/kg and 5 mg/kg, showed that every eight week maintenance therapy resulted in greater long-term skin clearance compared with "as-needed" therapy regimens within each dose. At week 10, after infusions at weeks 0, 2 and 6, 70 percent of patients treated with REMICADE 3 mg/kg and 75 percent of patients receiving 5 mg/kg achieved at least 75 percent improvement in psoriasis as measured by Psoriasis Area Severity Index (PASI 75), compared with two percent of patients receiving placebo (P < 0.001). At week 50, patients receiving REMICADE 5 mg/kg every eight-week maintenance therapy achieved the highest level of sustained PASI improvement with the majority of the patients achieving PASI 75 versus the REMICADE 3 mg/kg eight-week maintenance therapy and the REMICADE 3 mg/kg and 5 mg/kg "as-needed" therapy regimens. Results from EXPRESS II and the previous Phase 3 EXPRESS study were presented today at the 64th annual American Academy of Dermatology meeting.
"We now have data showing that the majority of patients receiving scheduled REMICADE maintenance therapy achieved long-term clinical response in psoriasis, a lifelong, chronic inflammatory disease" said Alan Menter, MD, chairman, Division of Dermatology, Baylor University Medical Center, and lead study investigator. "These findings support previous clinical results and show that patients treated with REMICADE achieved rapid and marked improvement in the moderate to severe category of psoriasis, which impacts the lives of nearly two million Americans."
Consistency of response of REMICADE 5 mg/kg maintenance therapy: Data from EXPRESS and EXPRESS II
In order to evaluate the consistency of response across both Phase 3 studies, data was analyzed from the REMICADE 5 mg/kg every eight week maintenance arm of each trial, the only regimen common to both EXPRESS and EXPRESS II. At week 10, after infusions at weeks 0, 2, and 6, the proportions of patients achieving PASI 75 were 80 percent versus three percent of placebo patients for EXPRESS and 75 percent versus two percent of placebo patients for EXPRESS II, (both P < 0.001 versus placebo). At week 10, the proportions of patients achieving PASI 90, or nearly complete skin clearance, were 57 percent versus one percent of placebo patients for EXPRESS and 45 percent versus 0.5 percent of placebo patients for EXPRESS II, (both P < 0.001 versus placebo). PASI 75 responses achieved at week 10 were maintained through week 26 in both EXPRESS and EXPRESS II (81 percent and 78 percent of patients achieved at least PASI 75 improvement from baseline, respectively), and the majority of patients achieved PASI 75 at week 50 in the REMICADE 5 mg/kg every eight-week maintenance groups.
"These data show great potential for REMICADE in the treatment of a disease that often carries great physical and emotional challenges," said Robert Matheson, MD, Oregon Medical Research Center, and study investigator. "The potential of achieving nearly complete skin clearance is exciting and holds great promise for patients with this difficult to treat disease."
Investigators reported that at week 10 patients in both EXPRESS and EXPRESS II receiving REMICADE experienced improvements in the Dermatology Life Quality Index (DLQI) and Physician's Global Assessment (PGA), measures of quality of life and psoriasis severity, respectively. In both studies, following 5 mg/kg induction therapy, REMICADE-treated patients experienced a median improvement of nine points in DLQI, a change that is considered to be a clinically meaningful decrease in psoriasis-related burden for the patient, compared to no improvement for placebo patients (REMICADE vs. placebo, -9.0 versus 0.0, P < 0.001 for both studies). The proportions of patients with a PGA of cleared, excellent/minimal were 83 percent vs. 4 percent (EXPRESS) and 76 percent vs. 1 percent (EXPRESS II) for the REMICADE and placebo groups respectively (both P < 0.001 vs. placebo). The PGA scale indicates a physician's assessment of the severity of psoriasis and scores of cleared, excellent/minimal are consistent with complete or almost complete clearing of the disease.
In November 2005, Centocor, Inc. announced that the United States Food and Drug Administration (FDA) accepted its filing of a supplemental Biologics License Application (sBLA) for the use of REMICADE in the treatment of moderate to severe plaque psoriasis. The acceptance of the sBLA file for psoriasis follows the September 2005 European Commission approval of REMICADE for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or have a contraindication to, or are intolerant of other systemic therapy including cyclosporine, methotrexate or psoralen plus ultraviolet light A (PUVA). REMICADE is approved in the U.S. and the European Union (EU) for the treatment of active psoriatic arthritis.

Alcohol abuse increases the risk of suffering from pneumonia

Although mortality did not differ significantly, an increase of the severeness of the disease was shown, and consequently, an increase of the morbidity and the complications was revealed. This study was conducted by the Pneumonia Multidiscipline Group of Hospital Clínic de Barcelona, led by Dr. Antoni Torres, from the Institut Clínic del Tórax, and leader of the IDIBAPS Group Management and Prevention of the Pulmonary Disease.

The increase of the risk of suffering from pneumonia in alcoholic patients exists due to the fact that the activity of their immune system decreases. This decrease not only is observed in alcoholic, but also in ex alcoholic patients. The daily quantity of alcohol consumption in order to include patients in the group of alcohol abuse was of 80 g in man and 60 g in women, the equivalent of 2 or 3 beers and 3 or 4 cups of wine.

Results are especially relevant since alcohol is the more abused drug in Spain, and causes a total of 12,000 deaths every year. In addition, pneumonia is a very frequent disease, with 10 patients every 1,000 inhabitants in Catalonia. This number is much higher if we take into account in the population over 65. This is the reason why the consequences of this study, and the possible vaccination of alcoholic of ex-alcoholic individuals against Pneumococcus, would affect a very high number of people. Alcohol consumption could turn into a new risk factor or a worsening factor to take into account in cases of community acquired pneumonia.

Causes and diagnosis of chest pain in young females

Chest pain is one of the common complaints heard in medical OPDs as well as at the GP�s clinic. Chest pain causes a lot of anxiety in the patient as it is many a time related to �heart attack� or angina and people are quite aware of the serious consequences of the symptom. Anyone having a chest pain would first think of the heart and would like to know if he/she is having a �heart attack�.

However not all times is a chest pain necessarily originating from or caused by diseases of the heart. There are plenty of other structures in the thoracic cavity and a systematic approach is needed to arrive at the correct diagnosis or in other words to find out the �real culprit� causing the chest pain.
Of special importance is the issue of chest pain in women, as this group is less liable to get heart disease till menopause. Estrogen is said to confer a protective effect and prevents the development of atherosclerosis. Myocardial infarction or Coronary artery disease (CAD) is very rare in menstruating women. As menopause approaches and estrogen levels go down, the probability of development of CAD catches up with those in men.
Even then, there are lots of young to middle aged, menstruating women complaining of chest pain and quite distressed about it. Before I highlight the special features of this particular issue lets first review the differential diagnosis of chest pain.

Differential Diagnosis of Chest Pain

1. Angina Pectoris/Myocardial Infarction
2. Other Cardiovascular Causes

a. Possibly Ischemic Pain

1) Aortic Stenosis
2) Hypertrophic Cardiomyopathy
3) Severe Systemic Hypertension
4) Severe Right Ventricular Hypertension
5) Aortic Regurgitation
6) Severe Anemia/hypoxia

b. Non Ischemic in Origin

1) Aortic Dissection
2) Pericarditis
3) Mitral Valve Prolapse

3. Gastrointestinal

a. Esophageal Spasm
b. Esophageal Reflux
c. Esophageal Rupture
d. Peptic Ulcer Disease

4. Psychogenic

a. Anxiety
b. Depression
c. Cardiac Psychosis
d. Self Gain

5. Neuromusculoskeletal

a. Thoracic Outlet syndrome
b. Lesions of Cervical/Thoracic Spine
c. Costochondritis[Tietze�s Syndrome]
d. Herpes Zoster
e. Chest wall pain

6. Pulmonary

a. Pulmonary Embolus/Infarction
b. Pneumothorax
c. Pneumonia with pleural involvement

7. Pleurisy
As most patients are anxious of their chest pain being that of Heart origin, we shall first have a look at the features of Cardiac Pain.