Medical decision making in the choice of a thrombolytic agent for acute myocardial infarction. Quebec Acute Coronary Care Working Group.

Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.     

Vascular smooth muscle mechanics in isolated perfused segments of carotid arteries

BACKGROUND: We hypothesized that smooth muscle contraction and relaxation responses in a muscle bath (isometric tension) would be different than responses of intact vessels (isotonic tension). METHODS: Bovine carotid artery contractile responses to the catecholamine, norepinephrine, and smooth muscle relaxant, 3-isobutyl-1-methylxanthine, were examined in strips of vessels in a muscle bath and in intact whole vessels in an isolated perfused whole-vessel perfusion apparatus. RESULTS: The maximal tension in the muscle bath depended on the length of the strip. The responses of whole vessels to increasing pressure was curvilinear. The maximal decrease in vessel diameter in intact vessels in response to the catecholamine and norepinephrine occurred at low intraluminal pressures. The dose-response curve to norepinephrine was shifted to the left in intact vessels compared with strips of vessels in the muscle bath, which suggests that whole vessels were more sensitive to norepinephrine. The maximal increase in diameter to increasing intraluminal pressure occurred in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, which suggests that there was significant intrinsic tone in the vascular smooth muscle. CONCLUSIONS: These results suggest that there are differences in the contractile properties of the vascular smooth muscle that are related to the ex vivo system used to examine smooth muscle responses. Responses obtained in isolated perfused whole vessels may more closely approximate in vivo responses.     

Treatment of Status Epilepticus: An International Survey of Experts

Background

As part of the development of the Neurocritical Care Society (NCS) Status Epilepticus (SE) Guidelines, the NCS SE Writing Committee conducted an international survey of SE experts.

Methods

The survey consisted of three patient vignettes (case 1, an adult; case 2, an adolescent; case 3, a child) and questions regarding treatment. The questions for each case focused on initial and sequential therapy as well as when to use continuous intravenous (cIV) therapy and for what duration. Responses were obtained from 60/120 (50%) of those surveyed.

Results

This survey reveals that there is expert consensus for using intravenous lorazepam for the emergent (first-line) therapy of SE in children and adults. For urgent (second-line) therapy, the most common agents chosen were phenytoin/fosphenytoin, valproate sodium, and levetiracetam; these choices varied by the patient age in the case scenarios. Physicians who care for adult patients chose cIV therapy for RSE, especially midazolam and propofol, rather than a standard AED sooner than those who care for children; and in children, there is a reluctance to choose propofol. Pentobarbital was chosen later in the therapy for all ages.

Conclusion

There is close agreement between the recently published NCS guideline for SE and this survey of experts in the treatment of SE.     

Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin‐2

Deficiency of the major constituent of central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type‐2 patients and in Plp1^null‐mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role in myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate that the abundance of the structurally related tetraspanin‐2 (TSPAN2) is highly increased in CNS myelin of Plp1^null‐mice. Unexpectedly, Tspan2^null‐mutant mice generated by homologous recombination in embryonic stem cells displayed low‐grade activation of astrocytes and microglia in white matter tracts while they were fully myelinated and showed no signs of axonal degeneration. To determine overlapping functions of TSPAN2 and PLP, Tspan2^null*Plp1^null double‐mutant mice were generated. Strikingly, the activation of astrocytes and microglia was strongly enhanced in Tspan2^null*Plp1^null double‐mutants compared with either single‐mutant, but the levels of dysmyelination and axonal degeneration were not increased. In this model, glial activation is thus unlikely to be caused by axonal pathology, and vice versa does not potentiate axonal degeneration. Our results support the concept that multiple myelin proteins have distinct roles in the long‐term preservation of a healthy CNS, rather than in myelination per se. GLIA 2013;61:1832–1847