Pharmacologic management of isolated low high-density lipoprotein syndrome

High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibiting a variety of properties like prostacyclin production stimulation, decrease in platelet aggregation, endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologic studies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. Low HDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death, peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associated with longevity and protection against atherosclerotic disease development. Given the evolving epidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL will continue to rise. In the United States, low HDL is present in 35% of men, 15% of women, and approximately 63% of patients with coronary artery disease. Data extracted from the Framingham study highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovascular disease. There is no doubt regarding clinical importance about isolated low HDL, but relatively few clinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestyle measures should be the first-line strategy to manage low HDL levels. On the other hand, pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce risk preferentially in patients with low HDL with metabolic syndrome, whereas statins reduce risk across all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, represented a hope to raise this lipoprotein; however, all clinical trials on this drug had ceased after ILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates of myocardial infarction, angina, and heart failure. In the near future, drugs as beta-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this condition.     

Analysis of low velocity frontal impacts

OBJECTIVES: The objectives of the study were to determine the phasic recruitment of cervical muscles with increasing magnitudes of low velocity frontal impacts, and to determine quantitative effects of awareness of impending impact in comparison to being impacted unawares. BACKGROUND: Biomechanics of low velocity frontal impact is poorly understood and requires more work. METHODS: Ten healthy young adults were subjected to frontal impacts causing accelerations of 5.3, 8.6, 11.0 and 14.0 m/s(2) (0.54, 0.88, 1.12 and 1.43 gs) while the subjects were unaware of the impending impact and after being told that they were going to be impacted. Electromyograph from sternocleidomastoids, splenius capitis and upper trapezius was recorded bilaterally. Triaxial accelerometers recorded the acceleration of the sled, torso and head of the subjects. RESULTS: The normalized electromyograph magnitude progressively rose with the level of acceleration whereas the time to onset generally decreased. At 14 m/s(2) sled acceleration the trapezius muscle generated 79% of their maximal voluntary contraction whereas the sternocleidomastoids generated 32% of their maximum voluntary contraction. The normalized peak electromyograph, the time to onset, the time of the peak electromyograph were significantly affected by the level of acceleration (P<0.01), the expectation of impact (P<0.01) and muscle group studied (P<0.01). The subject gender did not have a significant effect. The kinematic variables and the electromyograph regressed significantly on acceleration (P<0.01). CONCLUSIONS: The muscle responses were greater with higher levels of acceleration, particularly the trapezius in frontal impacts. Since the muscular components play a significant and central role in head/neck complex motion abatement at higher levels of acceleration, it may be a primary site of injury at low velocity whiplash phenomenon. RELEVANCE: An understanding of the pattern of biomechanical loading may assist in a more specific treatment of the patient injured in a low velocity frontal impact.     

Increased serum malondialdehyde and decreased nitric oxide within 24 hours of thrombotic stroke onset

BACKGROUND AND PURPOSE: Ischemia/reperfusion generates free oxygen radicals, which react with the unsaturated lipids of biomembranes resulting in the generation products such as malondialdehyde. Malondialdehyde could be a sensor for tissue damage and reperfusion. Nitric oxide, released due to the early arrival of leukocytes in the brain parenchyma, could be a sensor for nonflow phenomenon. Thereby, the purpose of this research was to evaluate the behavior of malondialdehyde and nitric oxide within the 24 hours after the stroke onset. METHODS: Fifteen patients up to an age of 49 years, admitted to the emergency of University Hospital and Chiquinquirá Hospital in Maracaibo, Venezuela, were examined by a neurologist and underwent 12-lead electrocardiograms and computed tomography for the diagnosis of thrombotic stroke. Serum malondialdehyde and nitric oxide were measured as thiobarbituric acid adducts and total nitrites. Data were collected within the 24 hours after the stroke onset. RESULTS: Malondialdehyde for patients with stroke had a significant increase (P<0.001) when compared with healthy controls (47.9 +/- 7.1 vs. 1.7 +/- 0.2 micromol/L). Conversely, serum nitric oxide for patients with stroke had a significant decrease (P<0.001) when compared with the control group (14.5 +/- 1.4 vs. 41.3 +/- 3.7 micromol/L). The lowest values of malondialdehyde and the highest values of nitric oxide were observed in two patients, who died. CONCLUSIONS: Serum levels of malondialdehyde increase, and serum levels of nitric oxide diminish within 24 hours after the onset of thrombotic stroke onset. This suggests that serum malondialdehyde level could be used as potentially reliable and sensitive marker for reperfusion, whereas nitric oxide levels could acts as potential biochemical sensor for nonreflow phenomenon.     

Cervical strength of young adults in sagittal, coronal, and intermediate planes

OBJECTIVES: To measure the cervical isometric force generation capacity of men and women reliably while seated in upright neutral posture. DESIGN: The cervical muscle isometric strength was determined in flexion, extension, lateral flexion, anterolateral flexion and posterolateral extensions in an upright seated neutral posture. For this measurement a device was designed, fabricated and its reliability established. BACKGROUND: To-date only a few studies on cervical strength data have been published. Of these, validity of some data is suspected due to the use of unstandardized methodology. No studies were identified which reported cervical strengths in lateral and oblique planes. METHODS: A testing device consisting of sturdy, stable and strong telescopic adjustable square metal tube was firmly bolted in the floor. Another rotating metal tube was pivoted and adjustably counterweighted and attached to an immovable object with a load cell in its path. Using a horizontal bar upholstered at the terminal end attached to the rotating tube 40 young subjects were tested. They exerted their maximal voluntary isometric contraction in flexion, extension, lateral flexion, anterolateral flexion, and posterolateral extension bilaterally. RESULTS: Cervical muscle strength was maximum in extension and minimal in anterolateral flexion (which was very close to flexion strength). With progressive change in direction towards posterior region the strength progressively increased. There was a significant difference between male and female strengths (P < 0.01). The flexion/extension ratio of males was 1:1.37 and for females 1:1.79. There was a significant difference in strength values in different directions (P < 0.01). CONCLUSIONS: The cervical strength is direction dependent. The extension generates maximum force and flexion close to minimum. A progressive change from anterior to posterior direction generates increasing force. RELEVANCE: There is insufficient information regarding cervical strength, which may at least indirectly and in part, indicate the force bearing capacity of cervical musculature. The present study furnishes some data to this end.     

Development of a Computer-Based Clinical Decision Support Tool for Selecting Appropriate Rehabilitation Interventions for Injured Workers

Purpose To develop a classification algorithm and accompanying computer-based clinical decision support tool to help categorize injured workers toward optimal rehabilitation interventions based on unique worker characteristics. Methods Population-based historical cohort design. Data were extracted from a Canadian provincial workers’ compensation database on all claimants undergoing work assessment between December 2009 and January 2011. Data were available on: (1) numerous personal, clinical, occupational, and social variables; (2) type of rehabilitation undertaken; and (3) outcomes following rehabilitation (receiving time loss benefits or undergoing repeat programs). Machine learning, concerned with the design of algorithms to discriminate between classes based on empirical data, was the foundation of our approach to build a classification system with multiple independent and dependent variables. Results The population included 8,611 unique claimants. Subjects were predominantly employed (85 %) males (64 %) with diagnoses of sprain/strain (44 %). Baseline clinician classification accuracy was high (ROC = 0.86) for selecting programs that lead to successful return-to-work. Classification performance for machine learning techniques outperformed the clinician baseline classification (ROC = 0.94). The final classifiers were multifactorial and included the variables: injury duration, occupation, job attachment status, work status, modified work availability, pain intensity rating, self-rated occupational disability, and 9 items from the SF-36 Health Survey. Conclusions The use of machine learning classification techniques appears to have resulted in classification performance better than clinician decision-making. The final algorithm has been integrated into a computer-based clinical decision support tool that requires additional validation in a clinical sample.     

Electromyography of superficial cervical muscles with exertion in the sagittal, coronal and oblique planes

The purpose of the current study was twofold: (1) to determine the isometric force and electromyographic (EMG) relationship of the sternocleidomastoid, splenii and trapezii muscles bilaterally in graded and maximal exertions in the sagittal, coronal and oblique planes. and (2) to develop regression equations to predict force based on the EMG scores. A newly designed and validated cervical isometric strength testing device was used to measure the cervical muscle isometric strength and force/EMG relationship in cervical flexion, extension, bilateral lateral flexion, bilateral anterolateral flexion, and bilateral posterolateral extension, all beginning with an upright seated neutral posture. A group of 40 healthy subjects were asked to exert their cervical motions in the directions of interest, while the force output and EMG from the sternocleidomastoids, splenii, and trapezii were sampled bilaterally at 1 kHz. ANOVA, correlation, and regression analyses were carried out. The force and EMG scores were significantly different between the directions of effort (P<0.01). All regressions were significant (P<0.01). All subjects registered the highest forces in pure extension and the lowest in pure flexion, showing a gradual decrease from the posterior to anterior direction. There was a modest correlation between EMG of the investigated muscles and force (r=0.15-0.76, P<0.01). EMG output was, for example, approximately 66% higher in flexion than in extension (while force output was roughly 30% less in flexion than extension) - thus relatively more muscle activity was required in flexion than extension to generate a given force. The intermediate positions (i.e. anterolateral flexion) revealed force/EMG ratio scores that were intermediate in relation to the force/EMG ratios for pure flexion and pure extension. The cervical muscle strength and cervical muscle EMG are therefore dependent on the direction of effort.     

The effect of glucocorticoids on the maturation of premature lung membranes. Preventing the respiratory distress syndrome by glucocorticoids

The effect of glucocorticoid on the maturation of premature lung membranes was studied in 121 premature infants by administering variable dosages of Decadron to the 114 mothers prior to delivery. The results were compared with findings in a group of 390 infants born in the same hospital during this study. Administration of all three test doses, 8, 16, and 24 mg., significantly decreased the incidence of RDS in all gestational age and birth weight categories. For infants less than 32 weeks, the incidence was decreased from 75 to 46.2%; those 32 to 36 weeks, from 58 to 20.2%; and in those older than 36 weeks, from 24.4 to 0 per cent. The incidence in infants less than 1,000 grams was reduced from 100 to 71.5%; 1,000 to 1,500 grams, from 67.4 to 21.6%; 1,500 to 2,000 grams, from 52.3 to 22.6%; and in heavier than 2,000 grams, from 38.1 to 13.4%. The results also showed that glucocorticoid does not significantly reduce RDS if administered less than 24 hours prior to delivery. The incidence is reduced more than 50% if administered more than 24 hours prior to delivery.