National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease

A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation.     

AGRICOH: a consortium of agricultural cohorts

AGRICOH is a recently formed consortium of agricultural cohort studies involving 22 cohorts from nine countries in five continents: South Africa (1), Canada (3), Costa Rica (2), USA (6), Republic of Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). The aim of AGRICOH, initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC), is to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e.g., use of infrequently applied chemicals) or relatively rare outcomes (e.g., certain types of cancer, neurologic and auto-immune diseases). To facilitate future projects the need for data harmonization of selected variables is required and is underway. Altogether, AGRICOH provides excellent opportunities for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides.     

Neuronal growth cone collapse triggers lateral extensions along trailing axons

Axonal outgrowth is generally thought to be controlled by direct interaction of the lead growth cone with guidance cues, and, in trailing axons, by fasciculation with pioneer fibers. Responses of axons and growth cones were examined as cultured retinal ganglion cell (RGC) axons encountered repellent cues. Either contact with cells expressing ephrins or mechanical probing increased the probability of lead growth cone retraction. Lateral extension of filopodia and lamellipodia hundreds of microns behind the lead growth cone was correlated with its collapse. Transmission electron microscopy showed that some of the lateral extensions originate from the pioneer axon, whereas others represent growth cones of defasciculating trailing axons.     

Results after Norwood procedure and subsequent cavopulmonary anastomoses for typical hypoplastic left heart syndrome and similar complex cardiovascular malformations.

OBJECTIVE: From October 1989 to June 1998, 60 patients have undergone the Norwood procedure (stage I) at our institution. The results of the staged surgical reconstruction and risk factors were analysed. Typical hypoplastic left heart syndrome (HLHS) and complex lesions with aortic hypoplasia were compared with each other. PATIENTS: Typical HLHS: N = 48, median age 15 days (5-190 days), median weight 3.6 kg (2.6-5.3 kg). Complex lesions (dominant left ventricle): N = 12, median age 59 days (10-884 days), median weight 3.4 kg (2.4-12 kg). RESULTS: Typical HLHS: The stage-I hospital survival was 73% (35/48). It improved from 60% (95% confidence interval: 49-71%) during 1989-1994 to 91% (95% CI: 81-100%) during 1997-1998. Seven patients were lost late. The right ventricular end diastolic diameter (P = 0.015), shortening fraction (P = 0.027), and the presence of an obstructed pulmonary venous return (P = 0.0032) were significant risk factors. 23 children underwent stage-II operation with four (17%) deaths. All survivors experienced an improvement of their statomotoric development. Stage-III operation was performed in 13 patients with no hospital death. Follow up after stage-III procedure was 7 months to 7 years. 4 year actuarial survival, including hospital mortality and deaths at subsequent stages, improved from 28% (95% CI: 18-38%) during 1989-1994 to 58% (95% CI: 48-68%) during 1994-1997. No patient had signs of myocardial insufficiency. Complex lesions: Stage-I hospital survival was 83% (10/12) with no late death. Stage-II was performed in 8 and stage-III in 6 patients with no death respectively. CONCLUSION: In typical HLHS the results have improved over time. Both size and function of the right ventricle determined significantly stage-I survival. An early operation prevents the natural progression of pulmonary blood flow and may weaken all three risk factors. Patients with complex lesions seemed to have better chances of surviving the early postoperative period. The multistage reconstructions have become a realistic option for patients with HLHS and similar lesions, regardless of the morphologic subtype or diminutiveness of the aorta, and lead to an acceptable quality of life.     

Blood Product Supply for a Helicopter Emergency Medical Service

BackgroundLong patient transport times to trauma centers are a well-known problem in sparsely populated regions with a low hospital density. Transfusion of red blood cell concentrates (RBC) and plasma improves outcome of trauma patients with severe bleeding. Helicopter emergency services (HEMS) are frequently employed to provide early advanced medical care and to reduce time to hospital admission. Supplying HEMS with blood products allows prehospital transfusion and may help to prevent exsanguination or prolonged hemorrhagic shock. We have investigated the maintenance of blood product quality under air transport conditions and the logistical steps to introduce a HEMS blood depot into routine practice.MethodsA risk analysis was performed and a validation plan developed. A special, commercially available transport container for blood products was identified. Maintenance of temperature conditions between 2 and 6°C in the box were monitored at ambient temperatures up to 35°C over 48 h. Quality of blood products before and after helicopter air transport were evaluated including (1) for RBCs: hemoglobin, hematocrit, hemolysis rate; (2) for thawed plasma: aPTT, INR, single clotting factor activities. The logistics for blood supply of the regional HEMS were developed by the transfusion service of the Greifswald University Hospital in collaboration with the in-hospital transport team, the HEMS team, and the HEMS operator.ResultsThe transport container maintained a temperature below 6°C up to 36 h at 35°C ambient temperature. Vibration during helicopter operation did not impair quality of RBC and thawed plasma. To provide blood products for HEMS at least two transport containers and an additional set of cooling tiles is needed as the cooling tiles need a special temperature priming over 20 h. The two boxes were used at alternate days. To reduce wastage, RBCs and thawed plasmas were exchanged every fourth day and reintegrated into the blood bank inventory for further in-hospital use.ConclusionsSupplying HEMS with RBCs and plasma is feasible. Helicopter transport has no negative impact on blood product quality. The logistic challenges require close collaboration between the HEMS team and the blood transfusion service.     

An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta

Summary The aim of the present study was to assess the different processes contributing to the contraction induced by noradrenaline (NA, 1 gmol/l) in the rat isolated aorta. Pretreatment with maximally effective concentrations of nifedipine or cromakalim reduced the NA-induced contraction to 80 ± 3.5% or 63 ± 2.0%, respectively, without alteration of the shape of the response. After pretreatment with Mn²⁺, NA caused a transient phasic contraction followed by a sustained tonic component, comparable to the response obtained in Ca²⁺-free medium. Ryanodine — in the presence of extracellular Ca²⁺ — caused a slight increase of resting tension, but did not modify the NA-induced contraction. In Ca²⁺-free medium the contraction elicited by NA consisted of a transient phasic and a sustained tonic component. The amplitude of the phasic contraction decreased exponentially with the time of exposure to Ca²⁺-free medium. The phasic component was identified as elicited by Ca²⁺ released from the sarcoplasmic reticulum (SR) by means of ryanodine. If Ca²⁺ depleted tissues (80 min in Ca²⁺-free solution) were exposed to Ca²⁺ in the presence of Mn²⁺ or cromakalim, the NA-induced phasic response was inhibited, suggesting that Mn²⁺ and cromakalim blocked the refilling of the store. It can be concluded that activation of ₁-adrenoceptors in the rat aorta by NA elicits Ca²⁺-entry processes which have a different sensitivity to nifedipine, cromakalim and Mn²⁺. The Ca²⁺ released from SR contributes about 20% to the overall contractile response. Our data suggest that the depleted SR can be refilled from the extracellular space via a direct cromakalim- and Mn²⁺-sensitive pathway. Send offprint requests to: B. Wilffert at the above address     

Innovation in care for individuals with cognitive impairment: Can reimbursement policy spread best practices?

There is now an unprecedented opportunity to improve the care of the over 5 million people who are living with Alzheimer's disease and related dementias and many more with cognitive impairment due to brain injury, systemic diseases, and other causes. The introduction of a new Medicare care planning benefit—long sought openly by advocacy organizations and clinicians and badly needed by patients and families—could greatly improve health care quality, but only if widely and fully implemented. We describe the components of this new benefit and its promise of better clinical care, as well as its potential to create a new platform for clinical and health outcomes research. We highlight external factors—and some that are internal to the benefit structure itself—that challenge the full realization of its value, and we call for broad public and professional engagement to ensure that it will not fail.