Characterization of ovine utero-placental interface tensile failure.

Data on the strength of the utero-placental interface (UPI) would help improve understanding of the mechanisms of placental abruption (premature separation of the placenta from the uterus) during motor-vehicle crashes involving pregnant occupants. An ovine model was selected for study because like the human, its placenta has a villous attachment structure. Uteri with intact placentas were obtained from three sheep as by-products of another research study. The samples were harvested between 102 and 119 days of the 145-day gestational period. Rectangular specimens with areas measuring 15 mm × 5 mm were cut through the thickness of the placenta and uterus. Each subject provided eight samples, of which four were tested at a nominal strain rate of 0.10 strains/sec and the remainder was tested at a nominal strain rate of 1.0 strains/sec. Sutures were used to secure the uterine side of the specimens to the test fixture, while mechanical clamps were used to attach the placenta side. A FARO arm scanner recorded the initial geometry of the tissue, and a random dot pattern applied to the placenta and uterus tissue allowed visualization of displacement. For the structure of the UPI, mean tensile failure strain and standard deviations are 0.37 (0.11) and 0.37 (0.18) for the 0.10 and 1.0 strain rates, respectively (p-value = 0.970) while the associated failure stresses are 6.5 (1.37) and 15.0 (5.08) kPa, (p-value = 0.064). The results from sheep UPI testing provide the first estimate of the human UPI structural failure tolerance.

Factors influencing the patterns of injuries and outcomes in car versus car crashes compared to sport utility, van, or pick-up truck versus car crashes: Crash Injury Research Engineering Network Study.

BACKGROUND: Data using crash dummies suggest that motor vehicle crashes (MVCs) involving passenger sedans (S) vs sport utility, vans, or light trucks (SUVTs) produce more severe injuries than those involving two sedans (SvS). However, no detailed data regarding pattern of injuries or force mechanisms involved have been presented in real patients. METHODS: The relationship of injury patterns and severities with MVC reconstruction data were obtained in 412 MVC patients, drivers or front seat passengers. Crashes were examined with regard to impact direction, frontal (F) or lateral (L) crashes, vehicle mass ratio, ISS, DELTA V, seat belt use, and airbag deployment (AB). RESULTS: In 309 F-MVC, AB reduced overall ISS (24.3 to 17.9) with a reduction in the mean severity of traumatic brain injury (TBI) GCS < or = 12, from 48% to only 28%. This AB protection from TBI was preserved as DELTA V increased to > 30 mph even though non-AB protected body areas (thorax, lung, liver, and lower extremity injuries) all increased. When vehicles of incompatible size and mass (SUVT) had F-MVC with sedans the incidence of severe TBI rose as did face lacerations despite AB or belt use. In L-MVC between SUVT and sedans compared with SvS MVC, there was a cephalad shift in body injuries with increased thorax, but decreased lower extremity injuries. The incidence of TBI increased. Analysis of injury contact sites (hits) showed more hits and a wider distribution of contract sites in SUVT vs sedan MVC. These appeared due to the greater mass excess and larger mass ratio, hood height, and width in the F-SUVT vs S crashes. All of these factors plus the increased bumper height above the body frame side-door sill were injury causal factors in the L-SUVT vs S MVCs. CONCLUSION: Both F and L crashes between sedans and SUVT with a high mass ratio shift the pattern of injury cephalad with increased thorax and intrathoracic organ injuries, and more severe TBI. These data suggest that improved head and thorax side-impact buffering and design features which transmit MVC forces from the higher front end of the larger mass SUVT to the frame of the sedan may better protect sedan occupants from side-impacts.

Abdominal impact response to rigid-bar, seatbelt, and airbag loading.

This study was conducted to resolve discrepancies and fill in gaps in the biomechanical impact response of the human abdomen to frontal impact loading. Three types of abdominal loading were studied: rigid-bar impacts, seatbelt loading, and close-proximity (out-of-position) airbag deployments. Eleven rigid-bar free-back tests were performed into the mid and upper abdomens of unembalmed instrumented human cadavers using nominal impact speeds of 6 and 9 m/s. Seven fixed-back rigid-bar tests were also conducted at 3, 6, and 9 m/s using one cadaver to examine the effects of body mass, spinal flexion, and repeated testing. Load-penetration corridors were developed and compared to those previously established by other researchers. Six seatbelt tests were conducted using three cadavers and a peak-loading rate of 3 m/s. The seatbelt loading tests were designed to maximize belt/abdomen interaction and were not necessarily representative of real-world crashes. The results were compared to data previously obtained by other researchers using swine and were used to establish a new abdominal load-penetration corridor for belt loading. Passenger frontal airbags were deployed into the closely positioned abdomen of three unembalmed cadavers. The penetration-time histories were used to guide the development of a repeatable high-speed surrogate airbag-loading device that uses a low-mass cylinder to simulate the initial breakout phase of close-proximity passenger airbag loading of the abdomen. This device was used to conduct simulated out-of-position airbag tests into three cadaver abdomens. The abdomen response data from these standardized tests were used to develop a load-penetration corridor for abdomen response to out-of-position airbag deployments.

Development of a Reusable, Rate-Sensitive Abdomen for the Hybrid III Family of Dummies.

The objective of this work was to develop a reusable, rate-sensitive dummy abdomen with abdominal injury assessment capability. The primary goal for the abdomen developed was to have good biofidelity in a variety of loading situations that might be encountered in an automotive collision. This paper presents a review of previous designs for crash dummy abdomens, a description of the development of the new abdomen, results of testing with the new abdomen and instrumentation, and suggestions for future work. The biomechanical response targets for the new abdomen were determined from tests of the mid abdomen done in a companion biomechanical study. The response of the abdominal insert is an aggregate response of the dummy's entire abdominal area and does not address differences in upper versus lower abdominal response, solid versus hollow organs, or organ position or mobility. While the abdomen developed has demonstrated good biofidelity in rigid bar, seat belt and airbag loading situations, some work remains to be done before it can be used in crash testing.

Development and Testing of a Prototype Pregnant Abdomen for the Small-Female Hybrid III ATD.

A new prototype pregnant abdomen for the Hybrid III small-female ATD is being developed and has been evaluated in a series of component and whole-dummy tests. The new abdomen uses a fluid-filled silicone-rubber bladder to represent the human uterus at 30-weeks gestation, and incorporates anthropometry based on measurements of pregnant women in an automotive driving posture. The response of the new pregnant abdomen to rigid-bar, belt, and close-proximity airbag loading closely matches the human cadaver response, which is thought to be representative to the response of the pregnant abdomen. In the current prototype, known as MAMA-2B (Maternal Anthropomorphic Measurement Apparatus, version 2B), the risk of adverse fetal outcome is determined by measuring the peak anterior pressure within the fluid-filled bladder. Peak internal bladder pressures measured in a series of sled-test simulations of frontal crashes of different severities and occupant-restraint conditions have been correlated to the likelihood of adverse fetal outcome based on risk curves developed from in-depth investigations of real-world crashes involving pregnant occupants. Compared to the original pregnant abdomen, the new prototype has improved geometry and improved impact response to a range of potential in-vehicle loading conditions, However, additional instrumentation development and more rigorous testing are needed before the MAMA-2B can be confidently used to assess restraint system performance with regard to reducing the likelihood of adverse fetal outcome in motor-vehicle crashes.

Prediction of airbag-induced forearm fractures and airbag aggressivity.

This study continued the biomechanical investigations of forearm fractures caused by direct loading of steering-wheel airbags during the early stages of deployment. Twenty-four static deployments of driver airbags were conducted into the forearms of unembalmed whole cadavers using a range of airbags, including airbags that are depowered as allowed by the new federal requirements for frontal impact testing. In general, the depowered airbags showed a reduction in incidence and severity of forearm fractures compared to the pre-depowered airbags tested. Data from these twenty-four tests were combined with results from previous studies to develop a refined empirical model for fracture occurrence based on Average Distal Forearm Speed (ADFS), and a revised value for fifty-percent probability of forearm-bone fracture of 10.5 m/s. Bone mineral content, which is directly related to forearm tolerance, was found to be linearly related to arm mass. The ADFS criterion was found to be effective in predicting forearm fracture, regardless of the airbag system, subject size, and age. Additional testing was conducted to examine the principles underlying the ADFS criterion. Specifically, static airbag-deployments were conducted into cylinders of different mass to study the relationships between forearm mass and forearm-to-airbag module distance relative to ADFS. ADFS was found to be linearly but inversely related to cylinder mass, and to the distance between the forearm and airbag module. The suitability of using existing surrogate arms to assess airbag aggressivity relative to forearm fractures using ADFS was explored as well.

A comprehensive program to improve safety for pregnant women and fetuses in motor vehicle crashes: a preliminary report.

OBJECTIVE: A program was developed to study the mechanisms of abruptio placentae and pregnancy loss caused by motor vehicle crashes. The results were intended to be used to develop strategies to improve protection of the fetus in this setting. STUDY DESIGN: Four integrated projects were conducted: (1) seated anthropometric measurements and belt fit determination during pregnancy, (2) development of new models of traumatic abruptio placentae, (3) investigations of crashes involving pregnant women, and (4) the development of the second-generation pregnant crash dummy from these data and others. RESULTS: Twenty-two different pregnant subjects in five different height groups underwent serial measurements of abdominal surface contours, seat belt fit, and distances between the subjects and various landmarks in the automobile interior with a laboratory-designed "automobile seat" (seating buck). The abdomen was significantly closer to the steering wheel in the shorter stature group than among the taller women. Beginning at approximately 20 weeks' gestation the fundus of the uterus was above the lower rim of the steering wheel. Lap belts fit properly over the anterior superior iliac spine throughout gestation, but the lap belt overlapped the uterus in the midsagittal plane. Two separate mechanisms for traumatic abruptio placentae were tested: shear failure and tensile failure. In the shear failure model large circumferential strains in the uterine wall induce a shear strain across the uteroplacental interface, and the model predicts placental separation at a mean circumferential strain of -58% +/- 8%. By means of finite-element modeling, it was demonstrated that tensile failure might also be a mechanism that causes abruptio placentae during rapid deceleration of the uterus. Crash investigations were performed in 43 cases involving pregnant women beyond 20 weeks' gestation. There were a total of 8 fetal losses and 8 major complications (fetal survival with abruptio placentae, direct fetal injury, or preterm delivery before 34 weeks' as a result of the accident). The best predictors of fetal loss or adverse outcome were impact severity and proper seat belt use. With these newly acquired data a second-generation crash dummy, known as the Maternal Anthropomorphic Measurement Apparatus version 2b (MAMA-2b), is being developed. It incorporates strain gauges in the fundal region of the fluid-filled uterus plus pressure transducers in both the anterior and posterior uterus. Criteria are being developed to associate the likelihood of abruptio placentae with measurements from these instruments that correspond to the two major hypothesized mechanisms of abruptio placentae. CONCLUSION: An improved understanding of the elements of automobile crashes that cause fetal loss and other major pregnancy complications has been gained through this series of investigations.

Effects of vehicle interior geometry and anthropometric variables on automobile driving posture.

The effects of vehicle package, seat, and anthropometric variables on posture were studied in a laboratory vehicle mockup. Participants (68 men and women) selected their preferred driving postures in 18 combinations of seat height, fore-aft steering wheel position, and seat cushion angle. Two seats differing in stiffness and seat back contour were used in testing. Driving postures were recorded using a sonic digitizer to measure the 3D locations of body landmarks. All test variables had significant independent effects on driving posture. Drivers were found to adapt to changes in the vehicle geometry primarily by changes in limb posture, whereas torso posture remained relatively constant. Stature accounts for most of the anthropometrically related variability in driving posture, and gender differences appear to be explained by body size variation. Large intersubject differences in torso posture, which are fairly stable across different seat and package conditions, are not closely related to standard anthropometric measures. The findings can be used to predict the effects of changes in vehicle and seat design on driving postures for populations with a wide range of anthropometric characteristics.

Investigations of crashes involving pregnant occupants.

Case reports of 16 crashes involving pregnant occupants are presented that illustrate the main conclusions of a crash-investigation program that includes 42 crashes investigated to date. Some unusual cases that are exceptions to the overall trends are also described. The study indicates a strong association between adverse fetal outcome and both crash severity and maternal injury. Proper restraint use, with and without airbag deployment, generally leads to acceptable fetal outcomes in lower severity crashes, while it does not affect fetal outcome in high-severity crashes. Compared to properly restrained pregnant occupants, improperly restrained occupants have a higher risk of adverse fetal outcome in lower severity crashes, which comprise the majority of all motor-vehicle collisions.

Chronic immune activation in the eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a multisystem illness of uncertain pathogenesis that occurred in an epidemic related to the ingestion of contaminated L-tryptophan. To investigate the role of immune dysfunction in EMS we prospectively measured a serologic index of T-cell activation, the soluble interleukin-2 receptor (sIL-2R), in 7 patients followed into the late stages of the illness. As a group, EMS patients had significantly elevated sIL-2R levels throughout the study. Five patients suffered chronic symptoms of myalgia, arthralgia, muscle cramps, fatigue, or subjective memory impairment and all had persistently elevated sIL-2R levels. Two patients had near-resolution of EMS and normal sIL-2R levels. We conclude that chronic symptoms are common in EMS and are associated with persistent T-cell activation as measured by serum sIL-2R levels. These findings suggest that immunosuppressive treatment may be beneficial in EMS.

Calcium and ionophore A23187 stimulates deposition of extracellular matrix and acetylcholinesterase release in cultured myotubes.

Calcium (Ca2+) and calcium-transporting ionophores stimulate protein secretion in many cellular systems. We demonstrate here than increases in intracellular calcium concentration induce a time- and concentration-dependent deposition of extracellular matrix and an increase in acetylcholinesterase secretion. Scanning and transmission electron-microscopy revealed that treatment with the calcium ionophore A23187, or high extracellular Ca2+ levels (5 mM to 15 mM) produce significant deposits of extracellular matrix around the myotubes, as well as a marked increase in the acetylcholinesterase reaction-product. Blocking muscle contraction was not necessary for the induction of AChE secretory activity. Sucrose density-gradients of media conditioned by muscle cells revealed 3 separate acetylcholinesterase molecular forms. However, incubation with A23187 increased only the 4.5 S and the 7.2 S molecular forms, whereas the 12.0 S form showed no significant differences from controls. Polyacrylamide gel electrophoresis, and autoradiography using [3H]diisopropyl fluorophosphate revealed a broad band at 65,000 daltons. This band was broader than for controls when medium was obtained from A23187-treated cells. Our results show that increasing intracellular Ca2+ concentration induces marked deposition of extracellular matrix and increased acetylcholinesterase secretion, with an apparent selectivity for the monomeric and dimeric acetylcholinesterase molecular forms.

Phorbol esters inhibit the synthesis of acetylcholine receptors in cultured muscle cells.

The acetylcholine receptor (AChR) synthesis, insertion and degradation rates are regulated by numerous intracellular and extracellular agents. Recent studies have shown that Ca2+ and Ca2+ ionophores have a profound regulatory effect on the appearance of AChR clusters and AChR synthesis. These regulatory effects may be mediated through the activation of calcium and phospholipid-dependent protein kinases by agents such as phorbol esters. In this study, we have utilized 4-beta-phorbol-12-myristate-13-acetate (PMA) in order to determine whether the activation of protein kinase C exerts a regulatory effect on the expression of AChRs in cultured chick myotubes. Our results show that 4-beta-phorbol-12-myristate-13-acetate decreased intracellular AChRs and suppressed AChR synthesis without affecting the turnover rate. Control and PMA treated cells labeled with [35S] methionine and immunoprecipitated with a monoclonal antibody to the alpha subunit of AChRs (mAb35) revealed a significant decrease in radioactivity precipitated after exposure to PMA. Polyacrylamide gel electrophoresis revealed no major changes in protein patterns, or in newly synthesized proteins as determined by [35S] methionine incorporation and autoradiography. Other enzymes important in muscle metabolism were not affected by PMA treatment. Our results indicate that activation of protein kinase C results in the suppression of AChRs synthesis and dispersal of AChR clusters.

Evaluation of the bioavailability of sarpicillin, the methoxymethyl ester of hetacillin, in humans.

The relative bioavailability of sarpicillin (the methoxymethyl ester of hetacillin) from three different oral dosage forms was compared in humans employing a three-way crossover study design. Each unit dose contained 250 mg of sarpicillin in terms of anhydrous ampicillin activity. The comparative bioavailability of a tablet containing added buffer, a liquid-filled capsule, and a standard powder-filled capsule was determined. The bioavailability parameters were Cmax, tmax, and AUC of intact plasma sarpicillin levels and saliva ampicillin levels. Significant correlation was found between plasma sarpicillin levels and saliva ampicillin levels following the administration of sarpicillin. All three formulations yielded statistically similar Cmax and AUC values with respect to plasma sarpicillin and saliva ampicillin levels. However, a more rapid absorption of intact sarpicillin was observed with the buffered tablet formulation, as reflected by significantly smaller tmax for both plasma sarpicillin and saliva ampicillin levels. The faster absorption from the tablet formulation gave more precise absorption among subjects.

Prediction of head/neck dynamic response of selected military subjects to -Gx acceleration.

Eighteen young male subjects with NAMRL sled test experience to 15 G in --Gx acceleration were measured for physical characteristics of the head and neck and general body anthropometry. Measurements taken include head/neck range of motion, neck muscle stretch reflex time, neck muscle isometric strength capabilities, and seated and standard anthropometry. Data from these tests were tabulated and five subjects whose physical characteristics were most similar were selected for use in simulations. Experimental data from NAMRL sled tests were obtained for the five subjects in 6- and 15-G test runs. Measurements data from the five subjects were used to establish a data set for the MVMA-2D Crash Victim Simulator and acceleration profiles for 6- and 15-G sled runs were used as input to the model. Simulation results for head angular acceleration, head angular velocity, head angular position, head resultant acceleration, and T1 resultant acceleration were compared with the averaged experimental curves for the five subjects. In general, excellent agreement between simulation and experimental results was obtained although some consistent differences were noted. Effects of varying levels of muscle activation were investigated. Variations in muscle tension level were found to have significant effects on simulation results at both 6 and 15, G, especially on head angular position. The effects were noticeably greater at lower acceleration's, however. The model was also used to investigate some of the biomechanical mechanisms behind observed response characteristics.