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The goal of our research is to augment gait rehabilitation for persons with gait asymmetry through a real-time feedback system that can be used independently by patients in the community. Our wireless, wearable, real-time gait asymmetry detection system called the lower extremity ambulatory feedback system (LEAFS) is a low-cost, in-shoe gait detection device that provides real-time auditory feedback based on the stance time symmetry ratio between the right and left limbs. This study evaluated the performance of the LEAFS in three study subjects with gait asymmetry secondary to unilateral transtibial amputation. Study subjects used the LEAFS for six 30-min training sessions under the supervision of a physical therapist. Two subjects demonstrated improved gait symmetry, with one subject reducing trunk sway by 85.5%, and the other subject reducing trunk sway by 16.0% and increasing symmetry ratio toward unity by 26.5%, as measured by a clinical motion analysis lab. The third subject did not demonstrate any objective improvements in gait symmetry or trunk sway. While testing with a larger number of subjects is necessary, this initial study using LEAFS with persons with transtibial amputations suggests that it can assist in improving gait symmetry in this population.

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This study investigated the mechanisms of the stimulatory effect of hyaluronic acid on motility in human sperm in vitro. A method, involving the measurement of forward progression through an agarose gel. was used to measure sperm motility quantitatively. Changes in intracellular Ca2+ concentrations in sperm were detected using the fluorescent dye Fluo-3. The effects of hyaluronic acid (6.5, 65, 650 ng/mL) and nifedipine (32 nM) on sperm motility were investigated. The effects of hyaluronic acid, nifedipine (32 nM), A23187 (32 microM), and a monoclonal antibody to human CD44 (1 microg/mL) on changes in intracellular CA2+ concentrations were investigated. Hyaluronic acid significantly (p < .008) stimulated sperm motility and this was partially inhibited by nifedipine. A23187 significantly (p < .005) increased intracellular CA2+ concentrations. Hyaluronic acid significantly (p < .04) increased intracellular Ca2+ concentrations and this was inhibited by nifedipine and a monoclonal antibody to human CD44. Hyaluronic acid stimulated human sperm motility by increasing intracellular Ca2+ concentration, partially via an influx of extracellular Ca2+.

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Normal human bone marrow stroma cells include stem cells for both haemopoietic and osteochondrogenic lineages and express both bone morphogenetic protein (BMP) type I and type II receptors. As a member of the TGF-beta super-family, BMP-6 binds to both BMP type I and type II receptors and is involved in the developmental processes of renal and hepatic systems as well as of human foetal intestine. Also, BMP-6 induces osteoblastic differentiation of pluripotent mesenchymal cells and is an autocrine stimulator of chondrocyte differentiation. The present study was carried out to investigate the effect of BMP-6 on human cobblestone-area-forming cells (CAFC), that represent the functional primitive repopulating haemopoietic stem cell in long-term bone marrow culture. Also, the effect of BMP-6 on marrow stroma production of interleukin-6, -11 and their common receptor gp130 that is expressed in haemopoietic stem cells and is indispensable for their proliferation and tri-lineage differentiation was examined. Moreover, the effect of BMP-6 on marrow stroma release of soluble adhesion molecule VCAM-1 mediating the primitive haemopoietic stem cell adhesion to marrow stroma was examined. The number of CAFC was significantly reduced after BMP-6 treatment from 88+/-10 per 10(5)cells in control cultures in a dose dependent manner to only 48+/-3 per 10(5)cells in 50 ng/ml BMP-6-treated cultures, P< 0.01. Quantitative ELISA measurement revealed 50 ng/ml BMP-6 was able to significantly reduce IL-6 and IL-11 production from marrow stroma, P< 0.01. Also, BMP-6 significantly increased soluble gp130 release by 7.4-fold in 50 ng/ml BMP-6-treated marrow stroma cultures. The profound rapid increase in this natural antagonist of human IL-6 cytokine family may reduce the gp130 signaling. Also, the soluble VCAM-1 released increased by two-fold in 50 ng/ml BMP-6-treated marrow stroma cultures. The marked increase in the soluble form may exert an antagonist effect on the function of VCAM-1 (ligand for VLA4). Recently, blocking the VLA4/VCAM-1 adhesion pathway was shown to mobilise haemopoietic CD34 positive cells in normal individuals. Also, we previously observed a significantly lower expression of VLA4 (CD49d) on G-CSF-mobilised blood CD34 positive cells than on bone marrow CD34 positive cells before mobilisation in the same normal donors. Since BMP are currently being used in clinical trials for bone repair and fracture healing, the present results suggest a possible role for BMP-6 in mobilising CD34 positive cells for transplantation. Further in vitro tests are required to evaluate this potential mobilising role of BMP-6 in human long-term bone marrow culture.

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The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.

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The development of intimal hyperplasia (IH) near the anastomosis of a vascular graft to artery is directly related to changes in the wall shear rate distribution. Mismatch in compliance and diameter at the end-to-end anastomosis of a compliant artery and rigid graft cause shear rate disturbances that may induce intimal hyperplasia and ultimately graft failure. The principal strategy being developed to prevent IH is based on the design and fabrication of compliant synthetic or innovative tissue-engineered grafts with viscoelastic properties that mirror those of the human artery. The goal of this review is to discuss how mechanical properties including compliance mismatch, diameter mismatch, Young's modulus and impedance phase angle affect graft failure due to intimal hyperplasia.

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Interleukin-8 (IL-8) is produced by human decidual cells in culture, and may play a role in the initiation of parturition. beta-endorphin is released in significant amounts into the maternal and fetal circulation during labour. The effect of beta-endorphin on IL-8 production by human chorio-decidual cells in culture was investigated. Mixed cells were obtained from the decidual surfaces of 35 term placentas. The cells were plated out at 10x10(6) cells per well in Roswell Park Memorial Institute 1640 culture medium. After 48 h the cells were washed and incubated with either plain culture medium (control), 1 micromol/l progesterone, 1-100 nmol/l beta-endorphin or 1 nmol/l N-acetyl beta-endorphin. After 48 h, IL-8 concentrations were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Experiments were repeated in the presence of naloxone (1 micromol/l) and using calcium-deficient culture medium. Progesterone (P < 0.0002) and beta-endorphin (P < 0. 0005) significantly inhibited the production of IL-8. The inhibitory effect of beta-endorphin was blocked by naloxone and by using calcium-deficient medium. N-acetyl beta-endorphin had no significant effect on IL-8 production. These findings suggest that beta-endorphin has an inhibitory effect on IL-8 production by decidual cells, and that the effect is mediated via opioid receptors and is calcium-dependent.

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Polyurethanes have unique mechanical and biologic properties that make them ideal for many implantable devices. However, certain polyurethanes are affected by some in vivo degradation mechanisms. For example, poly(ester)urethanes are subject to hydrolytic degradation and are no longer used in long-term implanted devices. Poly(ether)urethanes while hydrolytically stable, are subject to oxidative degradation in several forms, including environmental stress cracking and metal ion oxidation. We have developed a second-generation poly(carbonate)urethane with superior biostability. This material has been fabricated by our patented method into small diameter microporous vascular grafts. We evidenced the biodurability of our vascular graft by in vitro qualification tests which compared the poly(carbonate)urethane with a traditional poly(ether)urethane. This poly(carbonate)urethane graft has also proven to be biodurable in in vivo experimental implants up to twenty months duration with no evidence of hydrolysis or environmental stress cracking (ESC).

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Premature labour is a major medical problem. At present, premature labour cannot be predicted. Premature labour cannot be prevented effectively at present. Currently used drugs are not effective overall in reducing infant mortality. There is a need for further research and the development of effective agents for the prevention of premature labour.

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Degradative cracking, more commonly known as "environmental stress cracking" (ESC) has been observed in many implanted polyetherurethane elastomers. This phenomenon has been attributed to biochemical and cellular interactions at the surface of the implanted material causing polymer chain cleavage. This may result in surface fissuring followed by the deep cracking associated with considerable biodegradation of the polymer, resulting in loss of mechanical strength and the formation of aneurysms in an in vivo situation. These cracking effects are believed to be due to mechanical stress combined with the oxidising actions of macrophages and giant cells, as surface cracking has been observed to occur directly under adherent macrophages on a polyetherurethane implant. These cells form part of the body's immune response which uses enzymes and reactive oxygen species (O2, O2-, and HO. and H2O2) to degrade foreign material. We describe a modification of an in vitro test method developed by Zaho et al. [1] using glass wool and a Hydrogen Peroxide/Cobalt (II) Chloride (H2O2/CoCl2) mixture to replicate the oxidising effects of macrophages in vivo. The modifications were made to establish a routine testing system for resistance to biodegradation which could be used to screen a range of polymers designed for use in microporous vascular grafts. The grafts are pre-stressed by a method devised by Stokes et al. [2] where each graft is stretched to a predetermined elongation over a mandrel and the strain is fixed by tying PTFE tape around each end of the mandrel.

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PURPOSE: To produce biodurable small diameter microporous vascular grafts with self-sealing properties for vascular access, for peripheral vascular and potentially for coronary artery bypass. The prosthesis should retain compliance and pulsatile flow in situ using a unique modus operandi permitting wall compression which accommodates changes in volume. METHOD: We have utilized efficient low temperature coagulation technology to develop a unique range of small diameter microporous vascular grafts using ChronoFlex, a biodurable polycarbonate urethane. RESULTS: Grafts have been subjected to a range of in vitro and in vivo testing, demonstrating excellent physical and mechanical characteristics, self-sealing, maintenance of compliance and pulsatile flow in situ and patency up to twenty-two weeks.

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The effect of epidural opioids on gastric emptying was studied in 36 women in labour. Women who had received one dose of epidural bupivacaine were randomised to receive 10 ml of bupivacaine 0.25% alone (n = 8) with fentanyl 50 microg (n = 8) or with diamorphine 2.5 mg (n = 8), or 10 ml of bupivacaine 0.125% alone (n = 4) or with fentanyl 100 microg (n = 4) or with diamorphine 5 mg (n = 4) when they first requested a top-up. Mean+/-SD fentanyl concentrations measured at delivery were, in maternal venous plasma (MV) 0.72+/-0.19 ng/ml and in umbilical venous plasma (UV) 0.75+/-0.3 ng/ml. The mean dose-delivery interval was 280 min (range 107-608 min) and there was a negative correlation between UV/MV and dose-delivery interval. Gastric emptying was assessed by measuring paracetamol absorption following an oral dose of 1.5 g given 30 minutes after the study top-up. Time to peak plasma paracetamol concentration was significantly delayed in the groups given fentanyl 50 and 100 microg and diamorphine 5 mg, compared to the groups given bupivacaine alone, and peak concentration was significantly reduced in the group given diamorphine 5 mg. It is concluded that epidural fentanyl 50 and 100 mg and epidural diamorphine 5 mg delay gastric emptying. The addition of 2.5 mg diamorphine has no significant effect.

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Twenty pregnant New Zealand white rabbits (mean body weight 4.6 kg) within 3 days of term were anaesthetized and given an intravenous infusion of bupivacaine 1.25 mg/ml with pethidine 1.25 mg/ml at a rate of 12 ml/h for 20 min, 6 ml/h for 60 min and 3 ml/h thereafter. In 10 of the does the solution also contained adrenaline 1.25 microg/ml. Up to 8 fetuses were removed at 15 min intervals from the start of the infusion and umbilical vein pH was measured, together with bupivacaine and pethidine concentrations, in fetal plasma, fetal brain and maternal plasma sampled synchronously. Mean umbilical vein pH fell with time with no significant difference between the groups. Maternal plasma concentrations of both drugs did not alter significantly during the experiment. Maternal clearance of bupivacaine was 85.6 ml/min and of pethidine was 249 ml/min. Despite the three-fold higher maternal plasma concentrations of bupivacaine, concentrations of pethidine in fetal plasma and brain were consistently higher than those of bupivacaine. Fetal plasma pethidine concentrations rose 0.276 microg x ml(-1)h(-1) and bupivacaine concentrations rose 0.184 microg x ml(-1)h(-1). The mean (+/-SD) maximum fetal: maternal plasma ratio for bupivacaine was 0.361+/-0.127 and for pethidine 1.78+/-0.81. The fetal brain:plasma ratio of pethidine was consistently higher than that of bupivacaine and did not change significantly with time, whereas that of bupivacaine fell significantly (P<0.05). Concentrations of bupivacaine and pethidine in fetal and maternal brain were consistently higher with adrenaline, although adrenaline had no significant effect on the concentrations in this or any compartment.

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Bupivacaine 12.5 mg and pethidine 12.5 mg were administered as an i.v. infusion over 80 min in 15 near-term pregnant New Zealand white rabbits. After the infusion, pups were removed via individual hysterotomies every 30 min. Bupivacaine and pethidine were measured by gas chromatography in amniotic fluid, placenta, fetal plasma, fetal brain and maternal plasma, sampled as each fetal sac was opened. Pethidine was cleared from all compartments more rapidly than bupivacaine and for both drugs elimination rates were maternal plasma > placenta > amniotic fluid > fetal brain > fetal plasma. Concentrations of both drugs in fetal plasma correlated significantly only with those in fetal brain and not with those in maternal plasma, placenta or amniotic fluid, while there were positive correlations between the last three compartments. Nested analysis of covariance showed that only maternal plasma and placental concentrations of the two drugs decreased significantly with time. Maternal plasma half-lives for pethidine and bupivacaine were 1.0 and 2.0 h, and placental half-lives 1.9 and 2.5 h, respectively. The apparent fetal plasma half-life of pethidine was 9.9 h while there was apparently no net elimination of bupivacaine from fetal plasma.

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The purpose of this study was to explore the effect that fetal acidosis and poor maternal placental blood flow may have on the rate of passage across the placenta of drugs commonly used in labor: bupivacaine and meperidine. The rabbit placenta perfused in situ on the fetal side was used, and antipyrine (phenazone) was included as an index of placental exchange and of maternal placental flow. Bupivacaine and meperidine (both 1.25 mg/mL) and antipyrine (4 mg/mL) were infused into a maternal external jugular vein, at 3 mL/h, after loading, in seven anesthetized does. A single placenta in each doe was perfused via the umbilical arteries with Krebs' bicarbonate buffer at pH 7.5 (phase 1), 7.0 (phase 2), and 7.5 (phases 3-5). During phase 4 maternal blood was withdrawn so as to reduce maternal arterial pressure by 35%, and in phase 5 it was reinfused. Concentrations of drugs were measured during each of the five phases in maternal arterial plasma (Cma) and in the effluent perfusate collected from the umbilical vein (Cuv). From these data, placental clearance rates (Cuv x umbilical flow/Cma) were calculated for each drug at each phase. Clearance of bupivacaine and meperidine increased (P less than 0.03) during phase 2, whereas that of antipyrine did not. Clearance of meperidine and antipyrine, but not of bupivacaine, decreased during phase 4. If these results can be extrapolated to the clinical situation, they suggest that the adverse effects of drugs may well be exacerbated in the presence of fetal compromise.

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Adrenaline may decrease uterine blood flow and influence transplacental distribution of bupivacaine. Sixteen pregnant rabbits received an i.v. infusion of 0.125% bupivacaine either plain (n = 8) or with adrenaline 1.25 microgram ml-1. At 15-min intervals following the start of the infusion, rabbit fetuses were removed serially and bupivacaine concentrations measured in maternal arterial plasma, fetal plasma and brain, amniotic fluid and placenta. The presence of adrenaline was associated with increased bupivacaine concentration in placenta; there was no other significant effect on fetal bupivacaine concentrations or ratios. Fetal:maternal plasma ratios increased (P less than 0.05), while fetal brain:fetal plasma ratios decreased (P less than 0.05) significantly with time.

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Following general anaesthesia, each of 18 pregnant rabbits received an i.v. infusion, at a declining rate, of 0.125% bupivacaine, either plain solution followed by adrenaline (1.25 micrograms ml-1)-containing solution (n = 10) or vice versa (n = 8). All solutions contained antipyrine as an index of placental exchange. In each rabbit, a single fetal sac was opened, the umbilical vessels were cannulated and the placenta was perfused in situ with buffered Krebs solution containing Dextran. Bupivacaine and antipyrine concentrations were measured in effluent perfusate (fetal) and in maternal plasma sampled simultaneously. Mean maternal arterial pressure and mean placental perfusion pressure were not altered by adrenaline. Fetal:maternal concentration (F:M) ratios of antipyrine decreased significantly (P less than 0.05) during the second half of the experiment. In contrast, F:M ratios of bupivacaine were unchanged during the time course of the experiment and unaltered by the addition of adrenaline. It is concluded that neither adrenaline nor minor alterations in maternal placental flow affect placental transfer of bupivacaine.

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Bupivacaine was infused i.v. in nine anaesthetized pregnant rabbit does near term. Pups were removed at 10-15 min intervals and bupivacaine concentrations measured in fetal plasma, brain, placenta, amniotic fluid, maternal plasma sampled synchronously and maternal brain at the end of the experiment. Mean maximum fetal:maternal (F:M) ratio was 0.31 (SD 0.16) (range 0.18-0.64). Mean fetal brain:plasma ratios ranged from 2.04 to 5.09. There was no progressive increase in fetal brain bupivacaine concentration with time. Maternal brain:plasma ratio was 1.62 (0.81). However, maximum fetal brain concentration was only 0.27-0.86 of maternal. Concentrations increased with time in amniotic fluid, but did not exceed those in maternal plasma. Although there was some accumulation of bupivacaine in rabbit fetuses, tissue uptake could not account for low F:M ratios persisting beyond 80 min.

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