Hydroxyethyl starch in balanced electrolyte solution (Hextend)--pharmacokinetic and pharmacodynamic profiles in healthy volunteers

Hextend is a new plasma volume expander containing 6% hydroxyethyl starch (HES) in a physiologically balanced medium of electrolytes, glucose, and lactate (weight average, molecular weight 670 kDa, molar substitution 0.75). This open-label study was designed to investigate the pharmacokinetic and pharmacodynamic profiles of Hextend in 21 healthy volunteers. We infused Hextend 10 ml/kg IV over 20 min and determined serum concentrations of HES at selected intervals over a 7-day period. Serum concentration-time curves indicated mixed pharmacokinetic behavior reflecting a two-compartment model in most subjects. The median serum half-life over 7 days was 38.2 h. The balanced formulation of the suspension medium did not seem to affect distribution, metabolism, or excretion of Hextend when compared with similar HES. Pharmacodynamic analysis demonstrated decreases in some plasma components compatible with the infusion of that volume of fluid and the duration of plasma volume expansion. Other plasma components remained unchanged, reflecting the benefit of a balanced electrolyte solution. Hemodilution was observed for 24--48 h after short-term infusion of Hextend. Some hemostatic indices showed moderate changes, and serum amylase demonstrated a temporary increase. Our study suggested that Hextend has pharmacokinetic and pharmacodynamic profiles that are similar to those of other HES. IMPLICATIONS: Hextend is a new plasma volume expander containing 6% hydroxyethyl starch in a physiologically balanced medium. This open-label volunteer study demonstrated that it has pharmacokinetic and pharmacodynamic profiles similar to those of established HES.     

Comparing quality of care for sexually transmitted diseases in specialized and general clinics

OBJECTIVE: The objective of this study was to compare quality of care for patients with sexually transmitted diseases (STDs) in specialized vs. general clinics. METHODS: The authors conducted a retrospective chart review evaluating compliance with a set of STD-related process of care quality indicators for adult patients seen in six Los Angeles County clinics (two STD specialized clinics and four general medical clinics). RESULTS: Thirty-two quality indicators were selected using a modified Delphi process. From March 1, 1996, to June 31, 1996, there were 205 STD-related visits to the two specialized STD clinics and 373 STD-related visits to the four general medical clinics. For patients with "classic" STDs (those for which sexual contact is the primary means of transmission), STD clinics achieved greater compliance than general medical clinics on 14 quality indicators, while general medical clinics achieved greater compliance on 4 indicators. CONCLUSION: STD clinics provide better overall STD care than general medical clinics. Possible explanations include differences in clinician experience with STD patients and greater use of standardized protocol sheets.     

The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics

BACKGROUND: Large-scale, prospective cohort studies have played a critical role in discovering factors that contribute to variability in cancer risk in human populations. Epidemiologists and volunteers at the American Cancer Society (ACS) were among the first to establish such cohorts, beginning in the early 1950s and continuing through the present, and these ACS cohorts have made landmark contributions in many areas of epidemiologic research. METHODS AND RESULTS: The Cancer Prevention Study II Nutrition Cohort was established in 1992 and was designed to investigate the relation between diet and other lifestyle factors and exposures and the risk of cancer, mortality, and survival. The cohort includes over 84,000 men and 97,000 women who completed a mailed questionnaire in 1992. New questionnaires are sent to surviving cohort members every other year to update exposure information and to ascertain new occurrences of cancer; a 90% response rate was achieved for follow-up questionnaires in 1997 and 1999. Reported cancers are verified through medical records, registry linkage, or death certificates. The cohort is followed actively for all cases of incident cancer and for all causes of death. Through a collaborative effort among ACS national and division staff, volunteers, and the American College of Surgeons, blood samples were collected from a subgroup of 40,000 cohort members and are in storage at a central repository for future investigation of dietary, hormonal, genetic, and other factors and cancer risk. Collection of DNA samples from buccal cells in an additional 50,000 cohort members is underway currently and will be completed in 2002. CONCLUSIONS: This new cohort of both men and women promises to be particularly valuable for the study of cancer occurrence, mortality, and survival as they relate to obesity and weight change, physical activity at various points in life, vitamin supplement use, exogenous hormone use, other medications (such as aspirin and nonsteroidal anti-inflammatory drugs) and cancer screening modalities.     

Reactive balance adjustments to unexpected perturbations during human walking

The purpose of this investigation was to determine the effect of unexpected forward perturbations (FP) during gait on lower extremity joint mechanics and muscle Electromyographic (EMG) patterns in healthy adults. The muscles surrounding the hip were found to be most important in maintaining control of the trunk and preventing collapse in response to the FP. Distinct lower extremity joint moment and power patterns were observed in response to the FP but an overall positive moment of support (M_s) was maintained. Therefore, reactive balance control was a synchronized effort of the lower extremity joints to prevent collapse during the FP.     

Four-dimensional fetal echocardiography with spatiotemporal image correlation (STIC): a systematic study of standard cardiac views assessed by different observers.

OBJECTIVE: To test the agreement between observers and reproducibility of a technique to display standard cardiac views of the left and right ventricular outflow tracts from four-dimensional volume datasets acquired with Spatiotemporal Image Correlation (STIC). METHODS: A technique was developed to obtain dynamic multiplanar images of the left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) from volume datasets acquired with STIC. Volume datasets were acquired from fetuses with normal cardiac anatomy. Twenty volume datasets of satisfactory quality were pre-selected by one investigator. The data was randomly assigned for a blinded review by two independent observers with previous experience in fetal echocardiography. Only one volume dataset was used for each fetus. After a training session, the observers obtained standardized cardiac views of the LVOT and RVOT, which were scored on a scale of 1 to 5, based on diagnostic value and image quality (1=unacceptable, 2=marginal, 3=acceptable, 4=good, and 5=excellent). Median scores and interquartile range, as well as inter- and intraobserver agreement were calculated for each view. RESULTS: The mean menstrual age at the time of volume acquisition was 25.5+/-4.5 weeks. Median scores (interquartile range) for LVOT images, obtained by the first and second observers, were 3.5 (2.25-5.00) and 4 (3.00-5.00), respectively. The median scores (interquartile range) for RVOT images obtained by the first and second observers were 3 (3.00-5.00) and 3 (2.00-4.00), respectively. The interobserver intraclass correlation coefficient for the LVOT was 0.693 (95% CI 0.380-0.822), and 0.696 (95% CI 0.382-0.866) for the RVOT. For the intraobserver agreement analysis, observer 1 gave higher scores to the LVOT the second time the volumes were analyzed [LVOT: 3.50 (2.25-5.00) vs. 5.00 (4.00-5.00, p=0.008)]. CONCLUSION: STIC can be reproducibly used to evaluate fetal cardiac outflow tracts by independent examiners. Slightly better image quality rating scores during the intraobserver variability trial suggests the presence of a learning curve for the manipulation and analysis of volume data obtained by STIC.     

Time-dependent influence of sensorimotor set on automatic responses in perturbed stance

 These experiments tested the hypothesis that the ability to change sensorimotor set quickly for au-tomatic responses depends on the time interval between successive surface perturbations. Sensorimotor set refers to the influence of prior experience or context on the state of the sensorimotor system. Sensorimotor set for postural responses was influenced by first giving subjects a block of identical backward translations of the support surface, causing forward sway and automatic gastrocnemius responses. The ability to change set quickly was inferred by measuring the suppression of the stretched antagonist gastrocnemius responses to toes-up rotations causing backward sway, following the translations. Responses were examined under short (10–14 s) and long (19–24 s) inter-trial intervals in young healthy subjects. The results showed that subjects in the long-interval group changed set immediately by suppressing gastrocnemius to 51% of translation responses within the first rotation and continued to suppress them over succeeding rotations. In contrast, subjects in the short-interval group did not change set immediately, but required two or more rotations to suppress gastrocnemius responses. By the last rotation, the short-interval group suppressed gastrocnemius responses to 33%, similar to the long-interval group of 29%. Associated surface plantarflexor torque resulting from these responses showed similar results. When rotation and translation perturbations alternated, however, the short-interval group was not able to suppress gastrocnemius responses to rotations as much as the long-interval group, although they did suppress more than in the first rotation trial after a series of translations. Set for automatic responses appears to linger, from one trial to the next. Specifically, sensorimotor set is more difficult to change when surface perturbations are given in close succession, making it appear as if set has become progressively stronger. A strong set does not mean that responses become larger over consecutive trials. Rather, it is inferred by the extent of difficulty in changing a response when it is appropriate to do so. These results suggest that the ability to change sensorimotor set quickly is sensitive to whether the change is required after a long or a short series of a prior different response, which in turn depends on the time interval between successive trials. Different rate of gastrocnemius suppression to toes-up rotation of the support surface have been reported in previous studies. This may be partially explained by different inter-trial time intervals demonstrated in this study. Received: 7 October 1997 / Accepted: 31 August 1998