Biomechanical comparison of stimulated and nonstimulated skeletal muscle pulled to failure

We compared the biomechanical properties of passive and stimulated muscle rapidly lengthened to failure in an experimental animal model. The mechanical parameters compared were force to tear, change in length to tear, site of failure, and energy absorbed by the muscle-tendon unit before failure. Paired comparisons were made between 1) muscles stimulated at 64 Hz (tetanic stimulation) and passive (no stimulation) muscles, 2) muscles stimulated at 16 Hz (wave-summated stimulation) and passive muscles, and 3) muscles stimulated at 64 Hz and at 16 Hz. Both tetanically stimulated and wave-summation contracted muscles required a greater force to tear (at 64 Hz, 12.86 N more, P less than 0.0004; and at 16 Hz, 17.79 N more, P less than 0.003) than their nonstimulated controls, while there was no statistical difference in failure force between muscles stimulated at 16 Hz and 64 Hz. The energy absorbed was statistically greater for the stimulated muscles than for the passive muscles in Groups 1 and 2 (at 64 Hz, 100% more, P less than 0.0003; and 16 Hz, 88% more, P less than 0.0002). In Group 3, the tetanically contracted muscle-tendon units absorbed 18% more energy than the wave-summated stimulated muscles (P less than 0.01). All muscles tore at the distal musculotendinous junction, and there was no difference in the length increase at tear between muscles in each group. These findings may lead to enhanced understanding of the mechanism and physiology of muscle strain injuries.     

Interaction of a plasminogen activator proteinase, LV-PA with human alpha2-macroglobulin.

Lachesis venom plasminogen activator (LV-PA) is a 33-kDa serine proteinase isolated from bushmaster (Lachesis muta muta) snake venom, which activates the fibrinolytic system in vitro. This study has examined the effect of the plasma proteinase inhibitor alpha2-macroglobulin (alpha2-M) towards LV-PA and compares it with the effect on tissue type plasminogen activator (t-PA). The proteolytic activity of LV-PA alone or previously incubated with human plasminogen (Plg) on the large molecular mass protein substrates, dimethylcasein (DMC) and fibrinogen (Fg) was completely inhibited by human alpha2-M. However, the synthetic peptides Tos-Gly-Pro-Lys-pNA and H-D-Pro-Phe-Arg-pNA (S-2302) were hydrolyzed with almost no reduction in rate. At pH 7.4 and 37 degrees C the proteinase (0.15 microM over 15 min) interacted with alpha2-M, and each mole of alpha2-M bound 2 mol of enzyme. Sodium dodecyl sulfate gel electrophoresis of reduced samples showed that the interaction of alpha2-M with either LV-PA or t-PA preincubated with Plg resulted in the formation of approximately 90 kDa fragments and high molecular mass complexes (Mr 180 kDa), generated by the incubation mixture (LV-PA or t-PA) and Plg. The data suggest that LV-PA is a direct-type PA and its fibrinolytic effect can be reduced by alpha2-M in vivo.     

Spontaneous splenic rupture following infectious mononucleosis

Four cases of spontaneous splenic rupture after infectious mononucleosis (IM) have been treated at this institution since 1978. The condition is rare, occurring in 0.1-0.5 per cent of patients with proven infectious mononucleosis. Splenectomy is considered the treatment of choice for these patients. However, because recent trends in the management of traumatic splenic rupture are moving towards nonoperative treatment with selected patients, a similar approach has been considered for the patient with spontaneous splenic rupture following IM. The major reason for avoiding splenectomy is the increased incidence of sepsis in splenectomized patients. Yet, splenic rupture is accompanied by hemorrhage and the risks associated with blood transfusion for ongoing hemorrhage are of similar magnitude as those of sepsis following splenectomy. In addition, the grossly abnormal spleens seen at operation tend to include large, contained hematomas that may also be prone to rupture. Therefore, operative management still appears to be the preferred treatment for spontaneous splenic rupture following IM. Splenectomy is curative, safe, and obviates the need for transfusion, extended hospitalization, and activity restriction.     

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: A replication study and CT/MRI comparison

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT-and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (>0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.     

Determination of elimination of pefloxacin and of its derivatives in continuous hemodiafiltration

Continuous venovenous hemofiltration with dialysis (CVVHD) is being increasingly used to treat acute renal failure. However, because of the-lack of data on the clearance of therapeutic agents during this treatment, there is a risk of using inappropriate dosages. This in vitro study was undertaken to determine the clearance of pefloxacin (P) and its two main metabolites (active N-desmethyl P and inactive N-oxide P) during CVVHD. Acitrate-dextrose (ACD) anticoagulated fresh human blood containing P and its two metabolites in the usual therapeutic levels was circulated at a rate of 100 ml min.-1 through a closed-circuit continuous venovenous hemofiltration with dialysis unit (BSM 22-Hospal hemofilter). Temperature and ionic composition of the blood were controlled. Dialysate (L2D, Hospal) was circulated on the other side of the continuous venovenous hemofiltration with dialysis membrane at three different flow rates (Qdi) (0, 500 and 1,000 ml.h-1. The dialysate/ultrafiltrate outflow was adjusted using a withdrawal pump to obtain nul ultrafiltration. Arterial blood, venous blood and ultrafiltrate were sampled simultaneously at different time points for High Performance Liquid Chromatography (HPLC) assays and determination of the clearances (Cl) and sieving coefficients (s) of each compound. Pefloxacin had a sieving coefficient of 0.42 and a clearance of 6.8 ml min-1 when Qdi was nul. With the blood flow used, clearances were found to be correlated with the dialysate flow rate; when this rate was 500 ml h-1, a pefloxacin clearance similar to that seen in healthy subjects was obtained (15.2 ml min-1). The two bacteriologically active forms of the drug (pefloxacin and N-desmethyl P) had similar elimination parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

A simple mechanical model using a piston to produce localized cerebral contusions in pigs

Summary A simple mechanical model using a piston to produce localized cerebral contusions in pigs, is presented.The precision and reproducibility of the method are described by the biomechanical and pathological results.There are only pathological changes with haemorrhage and laceration close to the place of entry of the piston. The changes in the physiological parameters also indicate that the damage is focal.In this model, when kept intact, the dura mater offers considerable protection as no pathological changes in the brain are observed even when the energy at the time of the contusion is increased to twice the values which, when the dura is open, cause considerable damage.     

Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure.

The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the Wernicke-Korsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro- and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcohol-exposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71% of the variance associated with percentage of small fibers. Significant abnormalities in the alcohol/pyrithiamine group and lack of abnormality in the alcohol-exposed/thiamine-replete group indicate that thiamine deficiency caused white matter damage. The graded abnormalities across the dually to singly treated animals support a compounding effect of alcohol exposure and thiamine depletion, and indicate the potential for interaction between alcohol and thiamine deficiency in human alcohol-related brain damage.     

Comparison of the antithrombotic effects of heparin, enoxaparin and prostacycline in continuous hemofiltration

Continuous anticoagulation is required during haemofiltration to prevent the deposition of fibrin and the formation of thrombus which would lead to early clotting of the haemofilter. This study aimed to compare the efficiencies of 3 different anticoagulation protocol: 150 IU.kg-1.day-1 heparin (group HEP), 1.2 mg.kg-1.day-1 enoxaparin (group ENX), and a combination of 0.8 mg.kg-1.day-1 enoxaparin with 5 ng.kg-1.min-1 prostaglandin I2 (group ENX and PGI2). A flat ANS69S (Hospal) haemofilter was used for continuous venovenous haemofiltration. Antithrombotic efficiency was assessed with a haemofilter permeability index (HPI) including the transmembraneous pressure gradient and the rate of production of ultrafiltrate. The time required for HPI to decrease to 1/3 of its initial value (HPI1/3) was used to compare the 3 protocols. Treatment tolerance was judged by monitoring the usual haemodynamic and haemostatic parameters. No adverse effects (bleeding, thrombosis, hypotension) were observed. HPI1/3 was 15.1 +/- 2.4 h, 18.3 +/- 3.1 h and 28.2 +/- 4.2 h in groups HEP, ENX and ENX and PGI2 respectively. High dose enoxaparin reached antithrombotic efficiency without increasing the risk of haemorrhage. The use of low doses of prostaglandin I2 greatly increased HPI1/3, without any deleterious haemodynamic effects. However, the high cost of prostaglandin I2 needs to be put in the balance with the increase in duration of haemofilter life. Therefore, further investigations are required to evaluate the possible synergy between heparin and prostaglandin I2, as well as the biological parameters which need to be monitored.     

Differential effect of catechol-O-methyltransferase Val158Met genotype on emotional recognition abilities in healthy men and women.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates executive functions and working memory and recent neuroimaging studies implicate an association with emotional processing. We examined the relationship between the COMT Val158Met polymorphism and facial emotion recognition and differentiation in 100 healthy individuals. Compared to Met homozygosity, Val homozygosity was associated with better and faster recognition of negative facial expressions such as anger and sad. Our study provides evidence for a possible influence of the COMT polymorphism on emotion recognition abilities in healthy subjects. Additional research is needed to further define the neurocognitive phenotypes associated with COMT polymorphisms.