ULTRASTRUCTURE OF PAPAIN AND PEPSIN DIGESTION FRAGMENTS OF HUMAN IgM GLOBULINS

The ultrastructure of papain and pepsin-digested products of human IgM globulins has been analyzed. Papain digestion was performed both in the presence and absence of cysteine. The Fcµ fragment was found to represent the central ring structure in the intact IgM molecule, plus a minor part of the appendages extending from the ring. The Fcµ ring structure was occasionally seen to be composed of dimers of short rods, probably identical with the endpieces of two µ-chains. Such dimeric structures, released from the intact Fcµ rings, had a tendency to aggregate sidewise, producing complexes of varying size. The dimensions of the Fcµ fragments were: outer diameter approximately 85 A, inner diameter about 40 A. The length of the protrusions varied from 20–30 A. The Fabµ preparations contained long strands of sidewise aggregated, short rod-shaped fragments. No aggregates were seen in the F(ab')₂µ preparations. The two Fab'µ units in the dimeric F(ab')₂µ fragments were usually parallel to each other. The dimensions of the Fabµ and F(ab')₂µ fragments were 50–80 A x 30 A and 75–80 A x 55 A, respectively. These findings provide morphological evidence that the C-terminal ends of the µ-chains (the Fcµ fragment) make up the central ring structure in the IgM molecule. They further indicate that the F(ab')₂µ fragments constitute about ¾ of the appendages extending from this ring structure.     

Increased resting heart rate with pollutants in a population based study

BACKGROUND: Air pollution is associated with cardiovascular mortality. Changes in the autonomic nervous system may contribute to cardiac arrhythmias and cardiovascular mortality. This study investigated the relations between air pollutant concentrations of sulphur dioxide (SO(2)), ozone (O(3)), nitric dioxide (NO(2)), and resting heart rate (RHR) in a population based study. METHODS: A sample of 863 middle aged men and women, living in Toulouse (MONICA centre) area, was randomly recruited. A cross sectional survey on cardiovascular risk factors was carried. RHR was measured twice in a sitting position after a five minute rest. Multivariate analyses with quintiles of RHR were performed using polytomous logistic regression. Models were adjusted for temperature, season, relative humidity, sex, physical activity, blood pressure, C reactive protein, and cardiovascular drugs. RESULTS: For NO(2), the OR (odds ratio) (95% CI) associated with an increase of 5 microg/m(3) in the current day of medical examination was 1.14 (1.03 to 1.25) in quintile Q5 of RHR compared with Q1, p for trend = 0.003. For SO(2), OR was 1.16 (0.94 to 1.44) in Q5 compared with Q1, p for trend = 0.05, and for O(3), OR was 0.96 (0.91 to 1.01) in Q5 compared with Q1, p for trend = 0.11. No significant association was seen when the daily mean concentration of NO(2), SO(2), and O(3) was considered during the previous day as well as when day lag 2 or 3 was considered. The cumulative concentration (three consecutive days) of O(3) is negatively associated with RHR (p for trend = 0.02). CONCLUSION: Changes in pulse rate could reflect cardiac rhythm changes and may be part of the pathophysiological link between pollution and cardiovascular mortality.     

Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study

PURPOSE: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE. METHODS: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T(1)-weighted three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects. RESULTS: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC-Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec-Hip coupling. CONCLUSIONS: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.     

Host response after reconstruction of abdominal wall defects with porcine dermal collagen in a rat model

OBJECTIVE: The purpose of this study was to compare the inflammatory response after implantation of Pelvicol with Prolene in a rat model. STUDY DESIGN: Full-thickness abdominal wall defects were created in 64 Wistar rats, and reconstructed with either Pelvicol or Prolene. Animals were sacrificed on days 7, 14, 30, and 90 to evaluate the presence of herniation, infection, adhesions, and changes in thickness and tensile strength of the implants. Histopathology and immunohistochemistry were performed to evaluate the collagen deposition and the inflammatory response. Statistics were done with unpaired t test and Mann-Whitney rank test. RESULTS: Pelvicol implantation induced infiltration of granulocytes, macrophages, and NK cells, which showed up-regulated expression of surface activation markers ICAM-1 and CD11b. This inflammatory response was significantly milder, and declined faster than in Prolene-implanted rats, and was also associated with fewer adhesions. Moreover, Pelvicol induced a slower, but more orderly collagen deposition, paralleling the surface of the implant. Pelvicol implants showed a slower increase in thickness and tensile strength early on, but this difference disappeared by day 90. CONCLUSION: Pelvicol induces a milder inflammatory response, less adhesion formation, more orderly collagen deposition than Prolene, and reaches a comparable tensile strength only after 90 days.     

Clinical review: Corticotherapy in sepsis

The use of glucocorticoids (corticotherapy) in severe sepsis is one of the main controversial issues in critical care medicine. These agents were commonly used to treat sepsis until the end of the 1980s, when several randomized trials casted serious doubt on any benefit from high-dose glucocorticoids. Later, important progress in our understanding of the role played by the hypothalamic–pituitary–adrenal axis in the response to sepsis, and of the mechanisms of action of glucocorticoids led us to reconsider their use in septic shock. The present review summarizes the basics of the physiological response of the hypothalamic–pituitary–adrenal axis to stress, including regulation of glucocorticoid synthesis, the cellular mechanisms of action of glucocorticoids, and how they influence metabolism, cardiovascular homeostasis and the immune system. The concepts of adrenal insufficiency and peripheral glucocorticoid resistance are developed, and the main experimental and clinical data that support the use of low-dose glucocorticoids in septic shock are discussed. Finally, we propose a decision tree for diagnosis of adrenal insufficiency and institution of cortisol replacement therapy.     

Effect of ski binding parameters on knee biomechanics: a three-dimensional computational study

INTRODUCTION: Downhill skiing is a relatively safe sport, but many potentially avoidable injuries do occur. Whereas tibia and ankle injuries have been declining, severe knee sprains usually involving the anterior cruciate ligament (ACL) have increased from the 1970s to the 1990s. The goal of the present study was to evaluate the effect of the position of the binding pivot point and binding release characteristics on ACL strain during a phantom-foot fall. METHODS: We computed ACL strain using a biomechanical computer knee model to simulate the phantom-foot ACL-injury mechanism. This mechanism, which is one of the most common mechanisms of ACL injury in downhill skiing, occurs when the weight of the skier is on the inner edge of the ski during a backward fall, resulting in a sharp uncontrolled inward turn of the ski. RESULTS: The model predicts, that under simulated phantom-foot conditions, a binding with fast-release characteristics with a pivot positioned in front of the center of the boot produces less strain on the ACL. Current bindings have their pivot point approximately at the center of the heel radius. A pivot positioned at the back of the binding is more effective for sensing loads that occur at the tip of the ski. However, it is less effective for sensing loads that occur at the tail of the ski and, therefore, offers less protection during a phantom-foot fall. CONCLUSION: A binding with two pivot points, one positioned in front and the other at the back, could sense twist loads applied to the ski both at the front and at the back, and might, therefore, be a solution to reduce the occurrence of ACL injuries.     

Discrimination of osteoporotic patients with quantitative ultrasound using imaging or non-imaging device

OBJECTIVES: Quantitative ultrasound (QUS) has emerged as a new tool in the assessment of fracture risk. The aim of this study was to compare the clinical utility of QUS parameters measured using imaging and non-imaging devices in the discrimination of osteoporotic patients. METHODS: QUS (Broadband Ultrasound Attenuation, BUA dB/MHz, and Speed of Sound, SOS m/s) were measured and then statistical analyses were performed. RESULTS: The 106 women included were 65 +/- 8 years aged. Using DXA, T score was < or = -2.5 at either lumbar spine or hip in 59% of patients, and 25% had osteoporotic fractures. QUS results were different among devices, and these differences were highly dependent on the measured value. There was a similar effect of age and duration of menopause for all parameters. To obtain 90% of sensitivity for the diagnosis of osteoporosis, the thresholds were 50.80 and 71.70 dB/MHz for BUA and 1544.80 and 1551.50 m/s for SOS, using imaging and non-imaging devices, respectively. Belonging to the highest tertile of QUS had a negative predictive value for osteoporosis ranging from 59% to 65%. In the lowest tertile of QUS, the proportion of osteoporotic women was between 73% and 80%. All QUS parameters, except BUA measured with the non-imaging device, were able to discriminate post-menopausal women with fractures after adjustment for age and hip BMD. CONCLUSIONS: Our data suggest that an imaging system improves the utility of BUA measurement, but not SOS, for post-menopausal osteoporosis assessment.