Differential effect of steady versus oscillating flow on bone cells

Loading induced fluid flow has recently been proposed as an important biophysical signal in bone mechanotransduction. Fluid flow resulting from activities which load the skeleton such as standing, locomotion, or postural muscle activity are predicted to be dynamic in nature and include a relatively small static component. However, in vitro fluid flow experiments with bone cells to date have been conducted using steady or pulsing flow profiles only. In this study we exposed osteoblast-like hFOB 1.19 cells (immortalized human fetal osteoblasts) to precisely controlled dynamic fluid flow profiles of saline supplemented with 2% fetal bovine serum while monitoring intracellular calcium concentration with the fluorescent dye fura-2. Applied flows included steady flow resulting in a wall shear stress of 2 N m(-2), oscillating flow (+/-2 Nm(-2)), and pulsing flow (0 to 2 N m(-2)). The dynamic flows were applied with sinusoidal profiles of 0.5, 1.0, and 2.0 Hz. We found that oscillating flow was a much less potent stimulator of bone cells than either steady or pulsing flow. Furthermore, a decrease in responsiveness with increasing frequency was observed for the dynamic flows. In both cases a reduction in responsiveness coincides with a reduction in the net fluid transport of the flow profile. Thus. these findings support the hypothesis that the response of bone cells to fluid flow is dependent on chemotransport effects.     

Three-dimensional quantitative structure-activity relationship study of nonsteroidal estrogen receptor ligands using the comparative molecular field analysis/cross-validated r2-guided region selection approach

A newly developed comparative molecular field analysis (CoMFA) technique, the cross-validated r2-guided region selection (CoMFA/q2-GRS) method, has been used to build a quantitative structure-activity relationship (3D-QSAR) for nonsteroidal estrogen receptor (ER) ligands. Ligands included in this study belong to a series of diethylstilbestrol (DES) and indenestrol analogues whose affinities for the mouse ER (mER) have been determined in our laboratory. The final model utilized 30 compounds and yielded a q2GRS (cross-validated r2, guided region selection) of 0.796, as compared to a q2 of 0.720 for conventional CoMFA, with a standard error of prediction of 0.594 at 3 principal components. This model was used to visualize steric and electrostatic features of the ligands that correspond with ER binding affinity. Results obtained from the CoMFA steric and electrostatic plots of this model have also been compared to information from the ER binding affinities of substituted estradiol analogues. This is in an effort to determine structural features of compounds in the CoMFA analysis that may correspond to those of the estradiol analogues and to further clarify the mode of binding of nonsteroidal ER ligands.     

Clinimetrics of postural instability in Parkinson's disease

Judgement of the ability to recover balance after a sudden shoulder pull is used as a clinical measure of postural instability in Parkinson's disease. To further evaluate its merits, we compared this 'retropulsion test' with dynamic posturography in 23 Parkinson patients. Dynamic posturography involved 20 serial 'toe-up' support surface rotations, which induced backward body sway. We found a moderate correlation (Spearman's p = 0.54; P < 0.05) between the retropulsion test and body sway after platform rotations during the 'off' phase, but no correlation during the 'on' phase (Spearman's p = 0.43; P = 0.11). These results cast doubt on the use of the retropulsion test as a measure of postural instability in Parkinson's disease.     

Are boxer shorts really better? A critical analysis of the role of underwear type in male subfertility

PURPOSE: Elevation of testicular temperature may result in arrest of spermatogenesis, abnormal semen parameters and sterility. It has been proposed that brief style underwear may produce scrotal hyperthermia and lead to clinical subfertility. Although this idea is regarded as dogma by many in the lay community and the changing of underwear type is a therapy frequently recommended by medical practitioners, there is a paucity of data measuring scrotal temperature as a function of underwear type. MATERIALS AND METHODS: Scrotal, core and skin temperatures were measured in 97 consecutive men presenting for evaluation of primary clinical subfertility. These cases were categorized by underwear type to boxer or brief group. Semen analyses were obtained in all patients. Individuals from each group were compared to ascertain differences in temperature when wearing and not wearing underwear. Baseline semen parameters also were compared. In 14 subjects (crossover group) underwear type was changed to the alternative type and scrotal temperature measurements were repeated. Literature regarding underwear type, testicular temperature and/or fertility was reviewed and critically analyzed. RESULTS: Mean scrotal temperature plus or minus standard deviation was 33.8 +/- 0.8 C and 33.6 +/- 1.1 C in the boxer and brief group, respectively. There were no significant temperature differences between the groups. Differential temperatures comparing core to scrotal temperature and semen parameters also were not significantly different. These observations remained constant in the crossover group. CONCLUSIONS: The hyperthermic effect of brief style underwear has been exaggerated. In our study there was no difference in scrotal temperature depending on underwear type. It is unlikely that underwear type has a significant effect on male fertility. Routinely advising infertility patients to wear boxer shorts cannot be supported by available scientific evidence.     

Laparoscopic visual field. Voice vs foot pedal interfaces for control of the AESOP robot

BACKGROUND: In order for robotic devices to be introduced successfully into surgical practice, the development of transparent surgeon/machine interfaces is critical. METHODS: This study evaluated the standard foot pedal for the AESOP robot compared to a voice control interface. Speed, accuracy, learning curves, durability of learning at 2 weeks, and operator-interface failures were analyzed in an ex vivo model. RESULTS: Foot control was faster and had less operator-interface failures. Voice control was more accurate as measured by "pass points." The foot control learning curve reached a plateau at the third trial, while the voice control did not fully plateau. Durability of learning favored the foot control but was not significantly different. CONCLUSIONS: Currently, the voice control is more accurate and has the advantage of not requiring the surgeon to look away from the operative field. However, it is slower and may require more attention as an interface. As voice recognition software continues to advance, speed and transparency are anticipated to improve.     

A randomised placebo controlled trial of oral misoprostol in the third stage of labour

OBJECTIVE: To compare oral misoprostol 400 microg with placebo in the routine management of the third stage of labour. DESIGN: A double-blind placebo controlled trial. Setting The labour ward of an academic hospital in Johannesburg, South Africa with 7000 deliveries per annum. PARTICIPANTS: Low-risk women expected to deliver vaginally. METHODS: Women in labour were randomly allocated to receive either misoprostol 400 microg orally or placebo after the birth. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan. Side effects were recorded. MAIN OUTCOME MEASURES: Measured blood loss > or = 1000 ml within the first hour after birth. Use of additional oxytocics. RESULTS: The groups were well matched. Measured blood loss > or = 1000 ml occurred in 15/250 (6%) after misoprostol and 23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35-1.22). The difference may have been reduced by the greater use of conventional oxytocics in the placebo group, which was statistically significant for intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence interval 0.14-0.77). Shivering was more common in the misoprostol group (19% vs 5%, relative risk 3.69; 95% confidence interval 2.05-6.64). CONCLUSIONS: Shivering has been shown in this study to be a specific side effect of misoprostol administered orally in the puerperium. No serious side effects were noted. Misoprostol shows promise as a method of preventing postpartum haemorrhage. Because of the potential benefits for childbearing women, particularly those in developing countries, further research to determine its effects with greater certainty should be expedited.     

Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction

Pediococcus sp. is a nonpathogenic heat-resistant spoilage organism that has been used as a test organism in milk pasteurization studies. These characteristics make this bacterium an attractive test organism to study the mode of bacterial thermal inactivation in a food pilot plant. We report here the effect of growth medium on the thermal D value of this organism in skim milk, whole liquid egg, 10% glucose solution, pineapple juice, apple juice, tomato juice, and water at 60 degrees C. Thermal inactivation was done in a submerged coil; D values were calculated from the linear portion of the survival curves by linear regression analysis. The range of D values of stationary-phase cells grown at 28 degrees C in tryptone glucose yeast extract (TGY) or tryptic soy broth (TSB) was 0.14 to 12.05 min in all heating menstrua tested. The TSB-grown cells exhibited the highest thermal resistance with skim milk and 10% glucose solution as the heating menstrua. Survival curves of the TGY-grown cells indicated the presence of a cell population heterogeneous in thermal resistance. The TSB-grown cells exhibited a cell population uniform in thermal resistance and with a lag time for thermal inactivation. When compared to TGY-grown cells, Pediococcus sp. grown in TSB showed a significant (P < 0.05) increase in D values by up to eightfold in all heating menstrua. Results from this study suggested that thermal inactivation of Pediococcus sp. was dependent on the growth medium and on the heating menstruum with respect to both pH and composition.     

Phylogenetic and physiological diversity of sulphate-reducing bacteria isolated from a salt marsh sediment

Xenopus blastula cells activate different mesodermal genes as a concentration-dependent response to activin, which behaves like a morphogen. To understand how cells recognize morphogen concentration, we have bound naturally labeled activin to cells and related this to choice of gene activation. We find that the increasing occupancy of a single receptor type can cause cells to switch gene expression. Cells sense ligand concentration by the absolute number of occupied receptors per cell (100 and 300 molecules of bound activin induce Xbra and Xgsc, respectively, i.e., 2% and 6% of the total receptors) and not by a ratio of occupied to unoccupied receptors. The long duration of occupancy explains a previously described ratchet effect. Our results suggest a new concept of morphogen gradient formation and interpretation that is particularly well suited to the needs of early development.     

S-phase fractions of breast carcinomas. Relationships to morphology, estrogen and progesterone receptors, and early recurrence

Analysis of the S-phase fractions (SPF) measured by in vitro thymidine labeling, morphological appearances, and estrogen receptor (ER) assays of primary invasive breast carcinomas demonstrated several interrelationships. Lobular, mucinous, tubular, and adenocystic carcinomas consistently had low SPF and were usually positive for ER. The same was true for the carcinomas of no special histologic type [the not otherwise specified (NOS) group of E. R. Fisher including "infiltrating ductal" and undifferentiated carcinomas] with minimal anaplasia. Medullary, atypical medullary, and morphologically unclassifiable carcinomas with marked nuclear anaplasia nearly always had high SPF and were usually negative for ER. High SPF was associated with advanced stages of carcinoma initially or with early recurrence following mastectomy.