Sunday, January 19, 2014

Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome


Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome

  • Madlen Loebel equal contributor mail,
  • Kristin Strohschein equal contributor,
  • Carolin Giannini,
  • Uwe Koelsch,
  • Sandra Bauer,
  • Cornelia Doebis,
  • Sybill Thomas,
  • Nadine Unterwalder,
  • Volker von Baehr,
  • Petra Reinke,
  • Michael Knops,
  • Leif G. Hanitsch,
  • Christian Meisel,
  • Hans-Dieter Volk,
  • Carmen Scheibenbogen
  •  [ view less ]
  • Published: January 15, 2014
  • DOI: 10.1371/journal.pone.0085387


Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported. In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients. Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients. Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4+ and CD8+ T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses. When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication. Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response in CFS patients and suggest an impaired ability to control early steps of EBV reactivation. In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS.

Tuesday, January 14, 2014

Dr Gary Hartstein provides in-depth insight into Michael Schumacher's head injury

Gary Hartstein was Formula 1's official medical delegate from 2005-12. He has been following news of Michael Schumacher's head injury closely, he provides in-depth insight into the clinical situation at present.

Let's take a look at what's happened to Michael Schumacher, from his fall until roughly now. It goes without saying that this is based on what we've been told at the press conferences, viewed and interpreted through my eyes.

I will not speculate, but will rather read between the caring physicians' lines and put this into the context of the treatment of severely head-injured patients.

It's useful to think of the impact against the rock as having done two things: it essentially immediately created a series of severe lesions, and it set into motion processes that, left to themselves, would aggravate the damage already done.

What about the initial lesions? There were probably at least four types of injury produced by the fall.

The first is formation of haematomas. Torn and damaged blood vessels let blood escape in sufficient quantity to coalesce. They are dangerous both because they are markers of severe impact as well as because they cause the intracranial pressure (ICP) to rise.

Gary Hartstein
Gary Hartstein © XPB
We've been told that Michael had a right-sided extradural haematoma (between the skull and the dura, a membrane surrounding the brain) that was evacuated surgically, and a series of intracerebral (within the brain tissue itself) haematomas. One of these, on the left, was evacuated during the week after the fall, but there are several others, located on the left, on the right and in the centre.

The second type of injury is contusions. These are bruises, just like when you bang your arm or leg. Tiny quantities of blood seep from the vessels, but not enough to collect. This gives that black-and-blue look. There's also swelling of course, which adds to the ICP increase caused by the haematomas.

Third is the possibility of damage to the long 'cables' in the brain. Injury to these axons is harder to see with modern imagery, but is often associated with poor neurological outcome.

Last, I have heard insistent stories of damage to one of the four arteries feeding the brain. Even if true, the significance of this is hard to assess, as most people have extensive connections between the four arteries, allowing flow through one to compensate for blockages in another.

What about the vicious circles I alluded to above? The most important revolves around the ICP. Increased ICP compresses the tiny blood vessels nourishing the brain.

The problem is, when the brain isn't receiving enough blood, what do you think it does? Right - it swells. This aggravates the already high ICP, and the already low blood flow.

Taking care of severely head-injured patients involves rigorous adherence to a few principles. Basically, the brain needs to consistently receive adequate amounts of oxygen and nutrients.

For this to happen, the air passages are maintained open and secure by a tube placed in the windpipe. Oxygenation and ventilation are provided by sophisticated ventilators, and adjusted to values as close to normal as possible. In order to ensure proper brain blood flow, it is urgent to control elevated ICP.

Ferrari fans pay tribute to Schumacher outside the hospital
Ferrari fans pay tribute to Schumacher outside the hospital
The first step in controlling high ICP was done on the Sunday and Monday after Schumacher's accident. The surgically accessible haematomas were evacuated.

In addition, the bone flaps opened by the surgeon weren't closed, allowing the brain to physically swell a bit before the pressure rises.

It turns out that cooling the patient just a few degrees can help make sure that energy delivery is adequate. This is because cooling slows the brain's metabolism. That means that any given level of oxygen and nutrient delivery is more likely to be sufficient for the brain's needs. Hypothermia is also very effective against elevated ICP.

It's also important to understand what is meant by, and the role of, the 'medically-induced coma'.

I mentioned controlling the airway with a tube in the trachea, controlling breathing with a ventilator and reducing body temperature. Now, realistically you just can't do this to a patient, even a severely head-injured patient (especially not a head-injured patient!) without anaesthetising them. So all these patients are put to sleep.

This also helps ensure that the patient doesn't shiver during the period of hypothermia (usually 48-72 hours). If despite all the above the ICP stays elevated, the anaesthesia is deepened significantly. This aims at temporarily abolishing electric activity in the brain, in order that all available energy be used for vital cellular maintenance, not 'superfluous' activity.

The future? A long, long road. Months at least. Short term, the anaesthetic needs to be lightened when the ICP is normal and stable. That's the next big step.

Friday, January 3, 2014

Happy Birthday Champ ! We're all praying for you ! get well soon Mr. Schumacher !

Michael Schumacher's family say they have been "overwhelmed" by fans' support for the seven-time Formula 1 world champion as he continues to be treated in hospital following his skiing accident.

On the German's 45th birthday on Friday, more than 200 Ferrari fans joined a silent tribute outside the University Hospital in Grenoble where Schumacher remains in a critical condition.

With those attending the event wearing Ferrari red team kit, and unfolding a large Prancing Horse banner, the Schumacher family said it was in no doubt how deep the feeling of support was.

"We are overwhelmed!" said a short statement on Schumacher's official website. "The incredible sympathies shown today by the Ferrari fans outside the hospital has utterly overwhelmed us and moved us all to tears.

"We are deeply grateful for it and also for all the heart warming and heartfelt wishes for Michael to get well soon, which have reached us from all over the world."
Schumacher suffered serious head injuries in the crash last weekend, and although his condition is now stable, he remains in an induced coma following two brain operations.


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