"Solid Red Line": An Observational Study on Death from Refractory Intracranial Hypertension.

The index of cerebrovascular pressure reactivity (PRx) correlates independently with outcome after traumatic brain injury (TBI). However, as an index plotted in the time domain, PRx is rather noisy. To "organise" PRx and make its interpretation easier, the colour coding of values, with green when PRx <0 and red when PRx> 0.3, has been introduced as a horizontal colour bar on the ICM+ screen. In rare cases of death from refractory intracranial hypertension, an increase in intracranial pressure (ICP) is commonly preceded by values of PRx >0.3, showing a "solid red line".Twenty patients after TBI and one after traumatic subarachnoid haemorrhage (SAH) from six centres in Europe and Australia have been studied. All of them died in a scenario of refractory intracranial hypertension. In the majority of cases the initial ICP was below 20 mmHg and finally increased to values well above 60 mmHg, resulting in cerebral perfusion pressure less than 20 mmHg. In three cases initial ICP was elevated at the start of monitoring. A solid red line was observed in all cases preceding an increase in ICP above 25 mmHg by minutes to hours and in two cases by 2 and 3 days, respectively. If a solid red line is observed over a prolonged period, it should be considered as an indicator of deep cerebrovascular deterioration.

Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group.

Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefore, a working group was initiated (Amsterdam, 2008) to discuss and propose standards for FC in MDS. In 2009 and 2010, representatives from 23, mainly European, institutes participated in the second and third European LeukemiaNet (ELN) MDS workshops. In the present report, minimal requirements to analyze dysplasia are refined. The proposed core markers should enable a categorization of FC results in cytopenic patients as 'normal', 'suggestive of', or 'diagnostic of' MDS. An FC report should include a description of validated FC abnormalities such as aberrant marker expression on myeloid progenitors and, furthermore, dysgranulopoiesis and/or dysmonocytopoiesis, if at least two abnormalities are evidenced. The working group is dedicated to initiate further studies to establish robust diagnostic and prognostic FC panels in MDS. An ultimate goal is to refine and improve diagnosis and prognostic scoring systems. Finally, the working group stresses that FC should be part of an integrated diagnosis rather than a separate technique.

Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea.

BACKGROUND AND AIMS: The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT(3)) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea. METHODS: Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus. RESULTS: While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT(3) receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe(6),Leu(17))-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (p<0.01). EDIM infected mice treated with granisetron had a significantly shorter duration of diarrhoea (5.6 (0.4) days) compared with untreated mice (8.0 (0.4) days; p<0.01). Experiments with neurokinin 1 receptor antagonists suggest that this receptor may possibly be involved in the secretory response to rotavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice. CONCLUSIONS: Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.

Role of the enteric nervous system in the fluid and electrolyte secretion of rotavirus diarrhea.

The mechanism underlying the intestinal fluid loss in rotavirus diarrhea, which often afflicts children in developing countries, is not known. One hypothesis is that the rotavirus evokes intestinal fluid and electrolyte secretion by activation of the nervous system in the intestinal wall, the enteric nervous system (ENS). Four different drugs that inhibit ENS functions were used to obtain experimental evidence for this hypothesis in mice in vitro and in vivo. The involvement of the ENS in rotavirus diarrhea indicates potential sites of action for drugs in the treatment of the disease.