Profiles of Neurological Outcome Prediction Among Intensivists

Background  

Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability.     

The Intubation Difficulty Scale (IDS): Proposal and Evaluation of a New Score Characterizing the Complexity of Endotracheal Intubation

Background: A quantitative scale of intubation difficulty would be useful for objectively comparing the complexity of endotracheal intubations. The authors have developed a quantitative score that can be used to evaluate intubating conditions and techniques with the aim of determining the relative values predictive factors of intubation difficulty and of the techniques used to decrease such difficulties.

Methods: An Intubation Difficulty Scale (IDS) was developed, based on parameters known to be associated with difficult intubation. It was then evaluated prospectively in a group of 311 consecutive prehospital intubations and 315 intubations in an operating room. In the operating room, the IDS was compared with two other parameters: the time to completion of intubation and the visual analog scale (VAS). Time was measured by an independent observer. Operators in both groups completed a checklist regarding the conditions of intubation.

Results: There is a good correlation between the IDS scale and the VAS assessment of difficulty and time to completion of intubation. VAS and time to completion have a significant but lesser correlation to each other. Comparison of IDS with operator-assessed subjective categorical impression of difficulty by Kruskall-Wallis was statistically significant.     

Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine,captopril, CGP 37 849, and strychnine in mice

Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the NMDA blocker CGP 37 849, and the glycine antagonist strychnine in a passive-avoidance test in mice. The memory-disturbing effects of phenobarbitone, diazepam, CGP 37 849 and scopolamine were not influenced by the hormonal pretreatment. These findings could indicate the involvement of a steroid-sensitive mechanism in drug-induced improvement of memory. In the light of clinical observations showing elevated cortisol levels in Alzheimer patients, the results might also explain why only a limited number of these patients respond to therapy with memory enhancers.     

Psychiatric disorders in adopted children: a profile from the Ontario Child Health Study.

Studies of clinical populations suggest that adopted children are overrepresented among children using mental health facilities, whereas studies using non clinical populations of adopted children have reached mixed conclusions about whether or not there is an increased psychological risk associated with adoption. Data from the Ontario Child Health Study, a community survey of children aged four to 16 years, which included a subpopulation of adopted children, were used to: 1. profile the characteristics of adoptive families; 2. examine the strength of adoptive status as a marker for psychiatric and educational morbidity; and 3. determine the extent to which adoptive status has an independent relationship with psychiatric and educational morbidities. The findings were: 1. adoptive mothers were significantly older than non adoptive mothers, but otherwise adoptive families did not differ significantly from non adoptive families, 2. adoption in boys, but not in girls, was a significant marker for psychiatric disorder and poor school performance; adoption in adolescent girls was a significant marker for substance use; and 3. multivariate analyses demonstrated no independent effect of adoption on psychiatric disorder or poor school performance; for adolescents, adoptive status did have an independent relationship with substance use for girls. The implications of these findings will be discussed.     

Ontario Child Health Study follow-up: evaluation of sample loss

This article presents an analysis of sample loss in a 4-year follow-up of children aged 4 to 12 who participated in the Ontario Child Health Study in 1983. Of the 1,617 children participating in the original Ontario Child Health Study, 1,172 (72.5%) were located and enlisted at follow-up in 1987. Based on wave-one assessments, nonparticipants at follow-up tended to have higher levels of psychopathology and family risk variables. Respondents were matched with nonparticipants and differentially weighted to compensate for selective loss. In comparing estimates based on actual (observed) and weighted responses in the follow-up sample, it was found that the effects of sample loss depended on the analytical focus. Evaluations of outcome of disorder and risk for disorder were not affected by sample loss. Evaluation of variables that predict persistence of disorder (prognosis) was affected by a bias toward the null.     

Effects of phenytoin, carbamazepine, and clonazepam on cortex- and amygdala-evoked potentials in partially kindled rats

The kindling technique has been reported to produce a long-lasting enhancement in both the early and late phases of evoked potentials triggered from the kindled focus. It also alters paired-pulse facilitation and depression in the pathways which support these phenomena. The present experiment was designed to determine whether the drugs which antagonize secondary generalization in the kindling model also antagonize kindling-enhanced excitation in the pathways leading out of the focus. Multiple doses of phenytoin, carbamazepine, and clonazepam were therefore tested against single- and double-pulse evoked potentials triggered from the focus in rats that had been subjected to parital kindling from either the amygdala or the cortex. Responses were recorded in monosynaptic sites and in the mesencephalic reticular formation--a polysynaptic site thought to play an important role in secondary generalization. No drug-related effects were found on early evoked potential components, either in the single-pulse or the double-pulse paradigm. Kindling-enhanced late components ("late waves"), however, were clearly and selectively antagonized by clonazepam.     

Eucaryotic Expression of the Nucleocapsid Protein Gene of Porcine Circovirus Type 2 and Use of the Protein in an Indirect Immunofluorescence Assay for Serological Diagnosis of Postweaning Multisystemic Wasting Syndrome in Pigs

The purpose of this study was to develop a sensitive, rapid, and inexpensive immunofluorescence assay (IFA) using a recombinant porcine circovirus type 2 (PCV2) nucleocapsid protein for the serological detection of PCV2-specific antibodies in pig sera. The viral nucleocapsid protein encoded by the PCV2 ORF2 gene has recently been identified as the most immunoreactive viral protein that carries type-specific antigenic determinants. The ORF2 sequence of the IAF-2897 strain of PCV2 has been cloned into a pCEP5 eucaryotic expression vector under the control of the cytomegalovirus promoter, downstream of a polyhistidine sequence tag. The recombinant plasmid was used in transfection experiments with human epithelial kidney 293 cells that were further tested, and positive expression of the viral nucleocapsid protein was confirmed by IFA and Western blotting. Strong, specific fluorescence was observed in the nuclei of transfected cells. Test specificity to PCV2 was verified with several related infectious agents. Sensitivity was compared to that of standard IFA using PCV2-infected cells by evaluating the reactivities of 44 field serum samples from pigs on farms with a porcine population suffering from postweaning multisystemic wasting syndrome. The recombinant nucleocapsid-based test was able to detect 15 more positive-testing pigs than the PCV2-based IFA. Therefore, the relative sensitivity of the latter test was estimated at only 57.1% compared to that of the recombinant nucleocapsid-based test. The recombinant fusion protein has been purified by affinity chromatography and is being used to develop further sensitive serological tests.     

Hearing impairment as an early sign of alpha‐mannosidosis in children with a mild phenotype: Report of seven new cases

Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDE^R) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.