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Biomedical subjects

S Hutchins

Publications and source records attributed to S Hutchins.

10 recordsLinked to original sources
PubMed2001

Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2).

Prostaglandin (PG) E(2) is a potent inducer of cortical and trabecular bone formation in humans and animals. Although the bone anabolic action of PGE(2) is well documented, the cellular and molecular mechanisms that mediate this effect remain unclear. This study was undertaken to examine the effect of pharmacological inactivation of the prostanoid receptor EP(4), one of the PGE(2) receptors, on PGE(2)-induced bone formation in vivo. We first determined the ability of EP(4)A, an EP(4)-selective ligand, to act as an antagonist. PGE(2) increases intracellular cAMP and suppresses apoptosis in the RP-1 periosteal cell line. Both effects were reversed by EP(4)A, suggesting that EP(4)A acts as an EP(4) antagonist in the cells at concentrations consistent with its in vitro binding to EP(4). We then examined the effect of EP(4) on bone formation induced by PGE(2) in young rats. Five- to 6-week-old rats were treated with PGE(2) (6 mg/kg/day) in the presence or absence of EP(4)A (10 mg/kg/day) for 12 days. We found that treatment with EP(4)A suppresses the increase in trabecular bone volume induced by PGE(2). This effect is accompanied by a suppression of bone formation indices: serum osteocalcin, extent of labeled surface, and extent of trabecular number, suggesting that the reduction in bone volume is due most likely to decreased bone formation. The pharmacological evidence presented here provides strong support for the hypothesis that the bone anabolic effect of PGE(2) in rats is mediated by the EP(4) receptor.

Animals↗
PubMed2001

Effect of foot orthoses on rearfoot complex kinematics during walking gait.

The aim of this study was to quantify the effect of anti-pronatory and anti-supinatory foot orthoses on the angular displacement, velocity and accelerations of the rearfoot complex during gait. The transverse plane motion of the leg relative to the foot was used to indicate rearfoot complex pronation and supination. Three dimensional gait analysis on 12 subjects was used to derive the changes in the rearfoot kinematics due to the orthoses. The anti-pronatory orthoses decreased the range of pronation during the contact phase (p=0.0002) and the total range of rearfoot complex motion (p=0.000002), whereas anti-supinatory orthoses increased the range of pronation during the contact phase (p=0.00006) and the total range of rearfoot motion (p=0.049). Anti-pronatory orthoses also decreased the initial peak in pronation velocity during the contact phase of gait (p=0.006). Neither orthosis had a statistically significant effect on rearfoot complex acceleration.

Adult↗
PubMed2000

Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators.

BACKGROUND: We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. METHODS AND RESULTS: One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21+/-1%) who had a pulmonary capillary wedge pressure >/=15 mm Hg and a cardiac index </=2.5 L x min(-1) x m(-2) were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 microg x kg(-1) x min(-1) to a maximum rate of 0.4 microg x kg(-1) x min(-1) and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28% and 39%, respectively. Heart rate increased modestly (8%) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, right atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. CONCLUSIONS: Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure.

Cardiotonic Agents↗
PubMed2000

Shank rotation: A measure of rearfoot motion during normal walking.

Motion of the shank in the transverse plane is coupled with pronation and supination of the rearfoot, and so its motion relative to the foot can be used as an indicator of the pattern of motion in the rearfoot. Compared to the more commonly used assessment of motion in the frontal plane between the heel and the shank, motion of the shank in the transverse plane relative to the foot provides a more complete measure of the pattern of motion of the rearfoot because it reflects the motion in all three joints of the rearfoot (the ankle, subtalar joint and mid-tarsal joint) not solely the ankle and subtalar components. This work aimed to provide normative data for this alternative measure of rearfoot function. Data on angular displacement, angular velocity and angular acceleration were derived from motion-analysis conducted on 25 subjects. The results suggest a difference between the pattern of angular displacement indicated when motion of the shank relative to the foot is examined and the pattern of angular displacement indicated when motion in the frontal plane between the shank and heel is examined. Specifically, the former suggests that resupination of the rearfoot after rearfoot pronation during the initial period of gait, starts at the beginning of mid-stance, while the latter suggests resupination beginning in late mid-stance. Where comparisons were possible, data on the velocity and acceleration appeared reasonable and provide further parameters with which to investigate the role of motion in the rearfoot in the development of pathologic conditions and the effects of intervention on motion in the rearfoot.

Ankle Joint↗
PubMed1996

Measles outbreaks in the United States, 1987 through 1990.

BACKGROUND: During 1989 and 1990 reported measles cases in the United States increased 6- to 9-fold over the annual mean of 3000 between 1985 and 1988. To evaluate recent epidemiology we summarized measles outbreaks. METHODS: Confirmed measles cases reported to the National Notifiable Disease Surveillance System during 1987 through 1990 were analyzed. An outbreak was defined as > or = 5 epidemiologically linked cases. RESULTS: There were 815 outbreaks, accounting for 94% of the 52,846 cases reported. Similar to 1985 and 1986, 3 patterns of measles transmission during outbreaks were identified: (1) predominantly among unvaccinated pre-school age children < 5 years of age (38% of outbreaks); (2) predominantly among vaccinated school age children 5 to 17 years of age (40%); and (3) predominantly among unvaccinated and vaccinated post-school age persons > or = 18 years of age (22%). Most outbreaks were small (median, 12 cases), but very large outbreaks occurred (maximum size, 10,670). Although school age outbreaks (58%) predominated during 1987 and 1988, preschool age (40%) and post-school age (23%) outbreaks were more important during 1989 and 1990. CONCLUSIONS: Recent epidemiology suggests that to achieve elimination of measles, ACIP recommendations must be fully implemented, including (1) routine administration of the first dose of measles vaccine from 12 to 15 months of age and (2) use of a routine two-dose schedule to prevent school age and post-school age outbreaks.

Adolescent↗
PubMed1980

Active immunotherapy for the treatment of acute myelogenous leukaemia: report of two controlled trials.

Over 6 1/2 years, 182 patients with acute myelogenous leukaemia were treated with one of two combinations of chemotherapy containing cytosine arabinoside and an anthracycline (daunorubicin or doxorubicin). Eighty-one patients achieved remission and 79 of them were entered into one of two trials of active immunotherapy. The first trial compared maintenance chemotherapy and i.v. BCG immunotherapy with chemotherapy alone. The results have shown that the group given i.v. BCG survived for a significantly longer time (P = 0.035) than the group treated only with chemotherapy. The i.v. BCG treated group also had a significantly longer survival (P = 0.042) after their first relapse and a higher incidence of subsequent remissions. However, there was no difference in the length of first remissions for the two groups. The second trial compared two different types of active immunotherapy. The results show no significant difference in remission duration or survival after first relapse for 34 patients randomly allocated to treatment with i.v. BCG or irradiated leukaemic blast cells. Sixteen patients relapsed and subsequently 10 patients entered a second remission after reinduction chemotherapy. These patients were distributed evenly between the two immunotherapy groups and this high rate of second remissions is similar to that for the immunotherapy group in the first Cardiff Trial. In the two trials, 21 (62%) of 34 patients receiving immunotherapy entered a second remission after reinduction chemotherapy and six patients achieved third remissions.

Adolescent↗