An indentation-based framework for probing the glycosaminoglycan-mediated interactions of collagen fibrils.

Microscale deformation processes, such as reorientation, buckling, and sliding of collagen fibrils, determine the mechanical behavior and function of collagenous tissue. While changes in the structure and composition of tendon have been extensively studied, the deformation mechanisms that modulate the interaction of extracellular matrix (ECM) constituents are not well understood, partly due to the lack of appropriate techniques to probe the behavior. In particular, the role of glycosaminoglycans (GAGs) in modulating collagen fibril interactions has remained controversial. Some studies suggest that GAGs act as crosslinkers between the collagen fibrils, while others have not found such evidence and postulate that GAGs have other functions. Here, we introduce a new framework, relying on orientation-dependent indentation behavior of tissue and computational modeling, to evaluate the shear-mediated function of GAGs in modulating the collagen fibril interactions at a length scale more relevant to fibrils compared to bulk tests. Specifically, we use chondroitinase ABC to enzymatically deplete the GAGs in tendon; measure the orientation-dependent indentation response in transverse and longitudinal orientations; and infer the microscale deformation mechanisms and function of GAGs from a microstructural computational model and a modified shear-lag model. We validate the modeling approach experimentally and show that GAGs facilitate collagen fibril sliding with minimal crosslinking function. We suggest that the molecular reconfiguration of GAGs is a potential mechanism for their microscale, strain-dependent viscoelastic behavior. This study reveals the mechanisms that control the orientation-dependent indentation response by affecting the shear deformation and provides new insights into the mechanical function of GAGs and collagen crosslinkers in collagenous tissue.

Orientation-dependent indentation reveals the crosslink-mediated deformation mechanisms of collagen fibrils.

The spatial arrangement and interactions of the extracellular matrix (ECM) components control the mechanical behavior of tissue at multiple length scales. Changes in microscale deformation mechanisms affect tissue function and are often hallmarks of remodeling and disease. Despite their importance, the deformation mechanisms that modulate the mechanical behavior of collagenous tissue, particularly in indentation and compression modes of deformation, remain poorly understood. Here, we develop an integrated computational and experimental approach to investigate the deformation mechanisms of collagenous tissue at the microscale. While the complex deformation arising from indentation with a spherical probe is often considered a pitfall rather than an opportunity, we leverage this orientation-dependent deformation to examine the shear-regulated interactions of collagen fibrils and the role of crosslinks in modulating these interactions. We specifically examine tendon and cervix, two tissues rich in collagen with quite different microstructures and mechanical functions. We find that interacting, crosslinked collagen fibrils resist microscale longitudinal compressive forces, while widely used constitutive models fail to capture this behavior. The reorientation of collagen fibrils tunes the compressive stiffness of complex tissues like cervix. This study offers new insights into the mechanical behavior of collagen fibrils during indentation, and more generally, under longitudinal compressive forces, and illustrates the mechanisms that contribute to the experimentally observed orientation-dependent mechanical behavior. STATEMENT OF SIGNIFICANCE: Remodeling and disease can affect the deformation and interaction of tissue constituents, and thus mechanical function of tissue. Yet, the microscale deformation mechanisms are not well characterized in many tissues. Here, we develop a combined experimental-computational approach to infer the microscale deformation mechanisms of collagenous tissues with very different functions: tendon and cervix. Results show that collagen fibrils resist microscale forces along their length, though widely-used constitutive models do not account for this mechanism. This deformation process partially modulates the compressive stiffness of complex tissues such as cervix. Computational modeling shows that crosslink-mediated shear deformations are central to this unexpected behavior. This study offers new insights into the deformation mechanisms of collagenous tissue and the function of collagen crosslinkers.

Heterogeneous microstructural changes of the cervix influence cervical funneling.

The cervix acts as a dynamic barrier between the uterus and vagina, retaining the fetus during pregnancy and allowing birth at term. Critical to this function, the physical properties of the cervix change, or remodel, but abnormal remodeling can lead to preterm birth (PTB). Although cervical remodeling has been studied, the complex 3D cervical microstructure has not been well-characterized. In this complex, dynamic, and heterogeneous tissue microenvironment, the microstructural changes are likely also heterogeneous. Using quantitative, 3D, second-harmonic generation microscopy, we demonstrate that rat cervical remodeling during pregnancy is not uniform across the cervix; the collagen fibers orient progressively more perpendicular to the cervical canals in the inner cervical zone, but do not reorient in other regions. Furthermore, regions that are microstructurally distinct early in pregnancy become more similar as pregnancy progresses. We use a finite element simulation to show that heterogeneous regional changes influence cervical funneling, an important marker of increased risk for PTB; the internal cervical os shows ∼6.5x larger radial displacement when fibers in the inner cervical zone are parallel to the cervical canals compared to when fibers are perpendicular to the canals. Our results provide new insights into the microstructural and tissue-level cervical changes that have been correlated with PTB and motivate further clinical studies exploring the origins of cervical funneling. STATEMENT OF SIGNIFICANCE: Cervical funneling, or dilation of the internal cervical os, is highly associated with increased risk of preterm birth. This study explores the 3D microstructural changes of the rat cervix during pregnancy and illustrates how these changes influence cervical funneling, assuming similar evolution in rats and humans. Quantitative imaging showed that microstructural remodeling during pregnancy is nonuniform across cervical regions and that initially distinct regions become more similar. We report, for the first time, that remodeling of the inner cervical zone can influence the dilation of the internal cervical os and allow the cervix to stay closed despite increased intrauterine pressure. Our results suggest a possible relationship between the microstructural changes of this zone and cervical funneling, motivating further clinical investigations.

An optomechanogram for assessment of the structural and mechanical properties of tissues.

The structural and mechanical properties of tissue and the interplay between them play a critical role in tissue function. We introduce the optomechanogram, a combined quantitative and qualitative visualization of spatially co-registered measurements of the microstructural and micromechanical properties of any tissue. Our approach relies on the co-registration of two independent platforms, second-harmonic generation (SHG) microscopy for quantitative assessment of 3D collagen-fiber microstructural organization, and nanoindentation (NI) for local micromechanical properties. We experimentally validate our method by applying to uterine cervix tissue, which exhibits structural and mechanical complexity. We find statistically significant agreement between the micromechanical and microstructural data, and confirm that the distinct tissue regions are distinguishable using either the SHG or NI measurements. Our method could potentially be used for research in pregnancy maintenance, mechanobiological studies of tissues and their constitutive modeling and more generally for the optomechanical metrology of materials.

Consumption of a high-fat meal was associated with an increase in monocyte adhesion molecules, scavenger receptors, and Propensity to Form Foam Cells.

BACKGROUND: Macrophage-derived foam cells are the predominant component of arterial plaques in the early stages of atherosclerosis. One factor that poses a major risk for plaque development is high levels of plasma low-density lipoprotein (LDL) as a result of a high-fat meal. In order to better understand how an individuals' diet affects arterial plaque deposition via the process of foam cell formation, we measured the acute circulating monocyte activity response after consuming a high-fat meal (85% of daily fat allowance). MATERIALS AND METHODS: Venous blood samples from 17 participants were acquired on a FlowSight. Samples were analyzed to identify nonclassical (CD14+/16+) and classical (CD14+/16-) monocytes. We measured monocyte concentration, adhesion molecule expression, CD36 expression, and oxidized LDL (oxLDL) endocytosis for preprandial 1, 3, and 5 h postprandial. RESULTS: Consuming a high-fat meal caused increases in oxLDL uptake, adhesion molecule expression, and CD36 expression in both classical and nonclassical monocytes, with the nonclassical monocytes responding with larger increases than the classical monocytes. CONCLUSION: These results suggest that consumption of a high-fat meal increased the potential of monocytes to become foam cells, and implicates nonclassical monocytes as having greater potential than classical monocytes to become foam cells. © 2016 International Clinical Cytometry Society.

Consumption of a high-fat breakfast on consecutive days alters preclinical biomarkers for atherosclerosis.

BACKGROUND/OBJECTIVES: Recent research has speculated that the risk of developing atherosclerosis is due to the accumulation of the effects of daily diet choices. The purpose of this study was to examine which of our previously identified preclinical disease risk biomarkers were further elevated when consuming a high-fat (644±50 kcal; 100% recommended dietary allowance for fat), high-calorie (1118±100 kcal; 70% daily caloric needs) breakfast on consecutive days. Young, normal weight females (N=7) participated in this study. SUBJECTS/METHODS: Blood samples were taken premeal and hourly for 5-h postprandial. Serum biomarkers (C-peptide, eotaxin, gastric inhibitory polypeptide, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), insulin, leptin, monocyte chemoattractant protein 1, pancreatic polypeptide (PPY) and tumor necrosis factor-α), monocyte concentration, and adhesion molecule expression (CD11a, CD18 and CD54) were measured. Area under the curve was calculated for each outcome variable as a function of day and data were analyzed for significance. RESULTS: We found significant (P<0.05) increases on Day 2 for: GM-CSF (+47%; P=0.041), G-CSF (+31%; P=0.012), PPY (+51%; P=0.049), total monocyte (+110%; P=0.043), pro-inflammatory (PI) monocyte (+60%; P=0.012), PI monocyte CD18 (+960%; P=0.003), PI monocyte CD11a (+230%; P=0.006), and PI monocyte CD54 (+208%; P=0.015). CONCLUSIONS: To our knowledge, the present study is the first to report changes in selected biomarkers and monocytes following eating a high-fat, high-calorie breakfast on consecutive days in humans. More research is needed to determine how transient the observed changes are and what the long-term implications for disease risk are.

Considerations to maximize fat mass gain in a mouse model of diet-induced weight gain.

Mouse experimental models of diet-induced weight gain are commonly used as analogs to human obesity; however, a wide variety of feeding methods have been used and the most effective way to maximize weight gain is not known. Maximizing weight gain may allow for a reduction in the number of animals required for a given experiment. The purpose of this study was how to cause the greatest amount of weight gain in CD-1 mice by modifying the composition and source of their diet. To accomplish this goal, we completed two experiments: (1) Effect of dietary macronutrient fat intake (60% (HF60), 45% (HF45), 30% (HF30), or 13.5% (CON) fat diet for 18 weeks); and (2) Effect of 1:1 mixed HF60 and CON diets. Outcome measures included food intake, body mass, and body composition, which were measured bi-weekly and statistically analyzed using a repeated measures analysis of variance (RM-ANOVA). In Experiment 1, the greatest increase in body and fat mass was observed in HF60 (36%) and HF45 (29%) compared with HF30 and CON (P < 0.05). In Experiment 2, HF + stock diet (SK) gained 25% more body mass and 70% more fat mass than HF (P < 0.05). Collectively, these findings suggest that using a high-fat based diet (>45% calories from fat), mixed with a stock diet, results in substantially more weight gain over a similar period, of time, which would allow an investigator to use ~40% fewer animals in their experimental model.

Application of Fourier transform-second-harmonic generation imaging to the rat cervix.

We present the application of Fourier transform-second-harmonic generation (FT-SHG) imaging to evaluate the arrangement of collagen fibers in five nonpregnant rat cervices. Tissue slices from the mid-cervix and near the external orifice of the cervix were analyzed in both two-dimensions (2D) and three-dimensions (3D). We validate that the cervical microstructure can be quantitatively assessed in three dimensions using FT-SHG imaging and observe collagen fibers oriented both in and out-of-plane in the outermost and the innermost layers, which cannot be observed using 2D FT-SHG analysis alone. This approach has the potential to be a clinically applicable method for measuring progressive changes in collagen organization during cervical remodeling in humans.

Baker's yeast ß-glucan supplementation increases monocytes and cytokines post-exercise: implications for infection risk?

Strenuous aerobic exercise is known to weaken the immune system, and while many nutritional supplements have been proposed to boost post-exercise immunity, few are known to be effective. The purpose of the present study was to evaluate whether 10 d of supplementation with a defined source of baker's yeast ß-glucan (BG, Wellmune WGP®) could minimise post-exercise immunosuppression. Recreationally active men and women (n 60) completed two 10 d trial conditions using a cross-over design with a 7 d washout period: placebo (rice flour) and baker's yeast BG (250 mg/d of ß-1,3/1,6-glucans derived from Saccharomyces cerevisiae) before a bout of cycling (49 ± 6 min) in a hot (38 ± 2°C), humid (45 ± 2 % relative humidity) environment. Blood was collected at baseline (before supplement), pre- (PRE), post- (POST) and 2 h (2H) post-exercise. Total and subset monocyte concentration was measured by four-colour flow cytometry. Plasma cytokine levels and lipopolysaccharide (LPS)-stimulated cytokine production were measured using separate multiplex assays. Total (CD14⁺) and pro-inflammatory monocyte concentrations (CD14⁺/CD16⁺) were significantly greater at POST and 2H (P<0·05) with BG supplementation. BG supplementation boosted LPS-stimulated production of IL-2, IL-4, IL-5 and interferon-γ (IFN-γ) at PRE and POST (P<0·05). Plasma IL-4, IL-5 and IFN-γ concentrations were greater at 2H following BG supplementation. It appears that 10 d of supplementation with BG increased the potential of blood leucocytes for the production of IL-2, IL-4, IL-5 and IFN-γ. The key findings of the present study demonstrate that BG may have potential to alter immunity following a strenuous exercise session.

Mouse blood monocytes: standardizing their identification and analysis using CD115.

Monocytes have been used to assess immune dysfunction and disease. While mouse models are a useful longitudinal analog, few researchers have assessed changes in mouse monocytes. The purpose of this study was to provide recommendations for the sample processing and flow cytometric analysis of mouse blood monocytes. Blood was drawn in a non-lethal manner from CD-1 male mice to be used in three experiments. Experiment 1 compared commonly used mouse monocyte markers. Experiment 2 compared the stability of CD115 expression after immediate (0h) and delayed (2 and 4h) processing following blood collection under various experimental conditions (laser strength, anticoagulant, and storage temp.). Experiment 3 compared the consistency of CD115(+) monocyte and subset concentrations using decreasing (40, 20, 10 and 5µL) volumes of blood. In experiment 1, >95% of CD115(+) events co-expressed CD11b; >85% co-expressed CD14. 70% of CD14(+) and 50% of CD11b(+) events co-expressed CD115. In experiment 2, CD115 expression decreased by 33% between 0 and 4h when stored at room temperature. Blood treated with EDTA and refrigerated maintained CD115 stability. In experiment 3, calculated concentrations for total monocyte events varied by <10% when 40, 20 and 10µL of blood were stained. While CD115 staining provides the most distinct monocyte population, it is important to treat blood with EDTA and refrigerate if sample processing will be delayed over 2h. Collectively, the findings of the present study outline important considerations that must be addressed when examining mouse monocytes in small, non-lethal blood samples.

Ultrasonic attenuation estimation of the pregnant cervix: a preliminary report.

OBJECTIVE: Estimates of ultrasonic attenuation (the loss of energy as an ultrasonic wave propagates through tissue) have been used to evaluate the structure and function of tissues in health and disease. The purpose of this research was to develop a method to estimate ultrasonic cervical attenuation during human pregnancy using a clinical ultrasound system. METHODS: Forty women underwent a cervical scan once during pregnancy with the Zonare z.one clinical ultrasound system using a 4-9-MHz endovaginal transducer. This ultrasound system provides access to radiofrequency (RF) image data for processing and analysis. In addition, a scan of a tissue-mimicking phantom with a known attenuation coefficient was acquired and used as a reference. The same settings and transducer used in the clinical scan were used in the reference scan. Digital data of the beam-formed image were saved in Digital Imaging and Communications in Medicine (DICOM) format on a flash drive and converted to RF data on a personal computer using a Matlab program supplied by Zonare. Attenuation estimates were obtained using an algorithm that was independently validated using tissue-mimicking ultrasonic phantoms. RESULTS: RF data were acquired and analyzed to estimate attenuation of the human pregnant cervix. Regression analysis revealed that attenuation was: a predictor of the interval from ultrasound examination to delivery (beta = 0.43, P = 0.01); not a predictor of gestational age at time of examination (beta = - 0.23, P = 0.15); and not a predictor of cervical length (beta = 0.077, P = 0.65). CONCLUSIONS: Ultrasonic attenuation estimates have the potential to be an early and objective non-invasive method to detect interval between examination and delivery. We hypothesize that a larger sample size and a longitudinal study design will be needed to detect gestational age-associated changes in cervical attenuation.

Resistive exercise blunts LPS-stimulated TNF-alpha and Il-1 beta.

To examine the influence of acute resistive exercise and "hormone status" on cytokine profile, 35 postmenopausal women (72 +/- 6.2 yr) underwent a moderate-high-intensity resistive exercise bout or rested. There were 4 groups: no hormone replacement (NHR, n = 9), hormone replacement (HRT, n = 12), selective estrogen receptor modulator (SER, n = 7), or resting control (no hormone replacement, CON, n = 7). NHR, HRT, and SER exercised (3 sets, 10 exercises @ 80 % 1RM). Blood was collected pre-exercise (PR), postexercise (PO), and two hours (2H) postexercise (same times for CON). Blood was diluted 1 : 10 in culture medium and incubated (37 degrees C, 5 % CO2, 24 h) with lipopolysaccharide (LPS, 25 microg . ml (-1)). Serum and supernatant from LPS-stimulated blood were analyzed for IL-6, IL-1 beta, and TNF-alpha using ELISA. Resistive exercise increased PO serum IL-6, and PO LPS-stimulated IL-6 and IL-1 beta in the exercise groups (HRT, NHR, SER collapsed; EX, n = 28). LPS-stimulated IL-1 beta remained elevated at 2H in EX and was significantly higher than PR in CON at 2H. Expressed per monocyte, EX had significantly lower IL-1 beta and TNF-alpha LPS-stimulated production at PO and 2H compared to CON, indicating an exercise-induced blunting of an apparent diurnal response on cytokine production. In postmenopausal women, acute resistive exercise increased circulating IL-6, but reversed an apparent diurnal increase in LPS-stimulated IL-1 beta and TNF-alpha production with no influence of hormone replacement or raloxifene.

Measurement of body composition changes with weight loss in postmenopausal women: comparison of methods.

BACKGROUND: The accurate measurement of body composition changes is important when evaluating the efficacy of medical nutrition therapy and weight management programs, yet is not well documented in older women. OBJECTIVE: We compared methods of estimating energy-restriction-induced body composition changes in postmenopausal women. DESIGN: 27 women (59 +/- 8 y; BMI 29.0 +/- 2.9 kg/m2; mean +/- SD) completed a 9-wk energy restriction period (5233 kJ/d, (1250 kcal/d)). Changes in % body fat (delta%BF), fat mass (deltaFM), and fatfree mass (deltaFFM) were measured by hydrostatic weighing (HW), air-displacement plethysmography (ADP), dual-energy x-ray absorptiometry (DXA), and deuterium oxide dilution (D2O). The Baumgartner et al. (Am J Clin Nutr 53:1345-1353, 1991) four-compartment (4C) model with body volume from HW was the criterion method. The 4C model with body volume from ADP was also compared. Regression equations were developed based on 4CHW (dependent variable) utilizing results of change (POST-PRE) for each method. RESULTS: The women lost 6.8 +/- 3.2 kg; 9% of baseline weight. Based on 4CHW, the body composition changes were -2.4 +/- 4.5 delta%BF, -4.7 +/- 3.3 kg deltaFM, and -2.6 +/- 4.4 kg deltaFFM. No differences were detected by ANOVA for delta%BF, deltaFM, and deltaFFM among 4CHW, HW, ADP, DXA, D2O, and 4CADP. Bland-Altman limits of agreement showed differences between methods that ranged from 14.5 to -14.1 delta%BF, 7.8 to -8.1 kg deltaFM, and 7.5 to -8.4 kg deltaFFM for individuals. A bias was shown with 4CADP overestimating delta%BF (1.4 %) and FM (0.6 kg) and underestimating deltaFFM (-1.2 kg) compared to 4CHW. The regression model was acceptable for %BF (4CADP, 2CHW, and 2CD2O); FM and FFM (4CADP, 3CDXA, 2CHW, and 2CD2O), but not for other estimates of %BF, FM, FFM. CONCLUSIONS: These body composition assessment methods may be used interchangeably to quantify changes in % body fat, fat mass, and fat-free mass with weight loss in groups of postmenopausal women. 4CADP overestimates delta%BF and underestimates deltaFFM. When utilizing one of these comparison methods (4CADP, 3CDXA, 2CHW, 2CD2O) to quantify changes in fat mass and fat-free mass for an individual postmenopausal woman, regression equations may be used to relate the data to 4CHW.

The effect of pre-exercise cooling on high intensity running performance in the heat.

The purpose of this study was to determine the effect of pre-exercise cooling on high intensity, moderate duration running performance and thermoregulatory responses in a hot environment (38 degrees C, 40 %RH). On separate days, 11 male subjects completed two treadmill runs to exhaustion at 100% of maximal aerobic power with (CL) and without (CT) pre-exercise cooling. Cooling consisted of 20 min of standing rest in a 22 degrees C environment with fan cooling (4.0 m x sec -1) and water spraying (50 ml x min -1) applied to both anterior and posterior body surfaces. Core temperature (T(c)) was determined with an esophageal T(es) probe, and skin temperatures (T(sk)) were measured using surface thermistors positioned at four sites. Finger prick blood samples were taken before and after exercise for the determination of blood lactate. Heart rates and ratings of thermal sensations and comfort were also recorded. Time to exhaustion was significantly shorter in the CL condition (368.9 +/- 56.2) compared to the CT condition (398.8 +/- 55.5 sec). Peak T(es) (37.51 +/- 0.57 vs. 38.56 +/- 0.30 degrees C for CL and CT, respectively), T(sk) (34.18 +/- 1.22 vs. 36.15 +/- 0.70 degrees C for CL and CT, respectively), rates of heat gain (0.20 +/- 0.05 vs. 0.28 +/- 0.05 degrees C x min -1 for CL and CT, respectively), and net heat storage (238.4 +/- 109.6 vs. 531.9 +/- 78.3 kJ for CL and CT, respectively) were all lower in the CL compared to CT throughout the treadmill runs. There were no differences in lactate accumulation between the two conditions. Based on these data, it can be concluded that pre-exercise cooling influences thermoregulatory responses during high intensity, moderate duration exercise; however, performance is impaired compared to a control trial in which no cooling procedures were employed.

Interleukin-6 expression after repeated bouts of eccentric exercise.

Plasma interleukin-6 (IL-6) is known to increase in response to eccentric exercise due to an acute-phase immune response. However, the severity of muscle injury is reduced with repeated bouts of eccentric exercise, possibly as a result of decreases in plasma IL-6. This study determined the response of IL-6 mRNA and IL-6, troponin-I (sTnI), muscle strength, and soreness as a result of repeated bouts of eccentric exercise. Eight males underwent two eccentric exercise bouts (3 wk apart) involving 7 sets of 10 repetitions at 150 % of the isotonic 1-RM of the dominant knee extensors. Blood samples were taken before, after and 2, 4, 6, 24, 48 and 96 h post-exercise. Strength and soreness ratings were assessed before and at 24, 48 and 96 h-post. Data were analyzed with 2 x 4 and 2 x 8 ANOVAs and the non-parametric Friedman test (p < 0.05). Both IL-6 mRNA and IL-6 underwent peak increases (p < 0.05) at 4 h-post and 6 h-post, respectively, but were not different between bouts. However, there were significant changes (p < 0.05) in sTnI, strength, and soreness that were greater after the first bout than the second, characteristic of the repeated bout effect. These results indicate that changes in sTnI, strength and soreness were less with the second eccentric exercise bout whereas the changes in both IL-6 mRNA and protein were not effected between bouts.

A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice.

To document the use of herbal preparations for cervical ripening, induction, and augmentation of labor by certified nurse-midwives (CNMs) and nurse-midwifery education programs, a national survey of 500 members of the American College of Nurse-Midwives was conducted. Forty eight nurse-midwifery education programs were also surveyed to determine whether they were formally or informally educating students in the use of herbal preparations for cervical ripening, induction, or augmentation of labor. The results of this study, a review of the literature, professional issues, and recommendations for clinical practice are presented in this article. Of 500 questionnaires mailed to ACNM members, 90 were returned from CNMs who used herbal preparations to stimulate labor and 82 were returned from CNMs who did not use herbal preparations to stimulate labor. Three questionnaires were excluded due to incomplete data or blank questionnaires. No significant differences were noted in relations to geographical region, midwifery education, or highest level of education between the CNM respondents who did and those who did not use alternative methods to stimulate labor. Of the CNMs who used herbal preparations to stimulate labor, 64% used blue cohosh, 45% used black cohosh, 63% used red raspberry leaf, 93% used castor oil, and 60% used evening primrose oil. CNMs who used herbal preparations to stimulate labor were younger (43 versus 45 years, P < .01) and more likely to deliver at home or in an in-hospital or out-of-hospital birthing center (P < .0006), than CNMs who never used herbal preparations to stimulate labor. The most cited reason for using herbal preparations to stimulate labor was that they are "natural," whereas the most common reason for not using herbal preparations was the lack of research or experience with the safety of these substances. Sixty-nine percent of CNMs who used herbal preparations to stimulate labor learned about using them from other CNMs, 4% from formal research publications, and none from their formal education programs. Although 78% of the CNMs who used herbal preparations to stimulate labor directly prescribed them and 70% indirectly suggested them to clients, only 22% had included them within their written practice protocols. Seventy-five percent of the CNMs who used herbal preparations to stimulate labor used them first or instead of pitocin. Twenty-one percent reported complications including precipitous labor, tetanic uterine contractions, nausea, and vomiting. Sixty-four percent of the nurse-midwifery education programs included instruction in the use of herbal preparations to stimulate labor in their formal curricula, and 92% included informal discussions on the use of herbal preparations. Evening primrose oil was the most common herbal preparation discussed in nurse-midwifery education programs. Castor oil was the most commonly used herbal preparation used by nurse-midwives in clinical practice.

Maternal syphilis: the next pregnancy.

We sought to determine: (1) the perinatal outcomes in the subsequent pregnancy; (2) the natural history of serologic titers over the course of the two pregnancies; and (3) the incidence and risk factors for delivering an infant with congenital syphilis in the subsequent pregnancy. Over a five-year period, we reviewed the charts of 46 women with maternal syphilis during pregnancy who had a subsequent pregnancy and delivered in our institution. The initial and subsequent pregnancy outcomes were contrasted. To characterize the subsequent pregnancy risk of congenital syphilis, those women with recurrent congenital syphilis were contrasted to women who delivered infants without congenital syphilis. Rapid plasma reagin (RPR) titers in the initial and subsequent pregnancy were analyzed by neonatal outcome. Forty percent of the women who delivered an infant with congenital syphilis in their first pregnancy delivered yet another infant with congenital syphilis in the subsequent pregnancy. Continued cocaine use was the single most important risk factor for delivering another infant with congenital syphilis (p < 0.0001). Forty-two percent of the women who delivered an infant without congenital syphilis in the initial pregnancy delivered an infant with congenital syphilis in the subsequent pregnancy. Birthweight, the number of neonatal hospital days, and the incidence of respiratory distress syndrome (RDS), neonatal pneumonia, abruption, and positive meconium drug screens were not significantly different between the initial and subsequent pregnancies. As with the initial pregnancy, women continued to experience poor pregnancy outcomes in the subsequent pregnancy.

Maternal syphilis in Michigan: the challenge to prevent congenital syphilis.

Syphilis has re-emerged as a significant public health problem for pregnant women and their babies in Michigan, US, and in many areas of the world. In the US over 50,000 cases of primary and secondary syphilis were reported to the Centers for Disease Control (CDC) in 1990. Due to the current epidemic of maternal syphilis in pregnancy in our city, we studied 253 cases of maternal syphilis over a one-year period. Our objective was to determine maternal risk factors during pregnancy predicting congenital infection. Women with high venereal disease research laboratory (VDRL) titres during pregnancy and unknown duration of disease had the highest incidence of delivering an infant with congenital syphilis. Even with treatment according to the current CDC guidelines there was a 27% incidence of congenital syphilis if disease duration was < 1 year and a 49% incidence of congenital syphilis for unknown duration of disease. Maternal syphilis during pregnancy was associated with significant neonatal morbidity and a preterm delivery incidence of 28%. The clinical evaluation, management, and current treatment guidelines are reviewed in this paper.

The biophysical profile as a tool for prediction of preterm delivery.

Our objective was to determine if any of the following parameters is a predictor of preterm delivery: gestational age, cervical dilatation, or biophysical profile score.Sixty-two women with certain dates, intact membranes, and preterm contractions more frequent than 300 min underwent a 30-min ultrasonographic assessment of fetal breathing movements, fetal tone, fetal movement and amniotic fluid volume, each of which was scored as 0, 1, or 2 before any tocolytics were given. The total score (0-8) was calculated and cervical dilatation was recorded. All women were subsequently placed on tocolytics. Data were analyzed using survival analysis with stepwise regression of the covariates to determine the predictive values of the total score, its individual parameters, gestational age, and cervical dilatation to the outcome variable of hours to delivery. Gestational age, cervical dilatation and time interval to delivery were categorized and entered into a logistic regression model with the total score and its components to determine predictive odds.Total score (p < 0.0001) and cervical dilatation (p < 0.0001) were the most significant variables associated with time interval to delivery, followed by gestational age (p = 0.035). When the individual biophysical parameters were entered into the model, fetal tone (p < 0.0001), cervical dilatation (p < 0.0001) and gestational age (p < 0.014) were the only variables related to time interval to delivery. Predictive odds of delivery in less than 48 h in relation to fetal tone and cervical dilatation were calculated. Total score, fetal tone, and cervical dilatation were strongly associated with time interval to delivery. Our study did not support fetal breathing movements as a predictor of preterm delivery.

Prenatal diagnosis.

The standards for the practice of nurse-midwifery declare competence in prenatal diagnosis as one of the core competencies for basic nurse-midwifery practice. Encompassing the most frequently encountered situations that involve prenatal diagnostic counselling, this article aims at providing insight to the practicing nurse-midwife into the risks and benefits of invasive prenatal diagnostic procedures and prenatal diagnostic testing, thereby enabling the midwife to counsel the woman and help her to choose an invasive procedure according to her individual needs.