Outcome of using vaginal misoprostol for treatment of retained products of conception after first trimester miscarriage: a retrospective cohort study.

PURPOSE: Standard treatment for retained products of conception (RPOC) is dilation and curettage (D&C), however, this brings a risk of intrauterine synechiae and subsequent fertility issues. A treatment strategy to avoid D&C is medical management with misoprostol. The justification for misoprostol in this setting is extrapolated from miscarriage and termination literature, however, no studies have looked specifically in the setting of RPOC. The purpose of this study is to determine the efficacy of misoprostol as definitive management of RPOC. MATERIALS AND METHODS: A retrospective cohort study was conducted from January 2016 to March 2017 at an Early Pregnancy Assessment Clinic. Patients diagnosed with RPOC with clinical symptoms and ultrasound findings of endometrial mass and/or doppler flow treated expectantly, medically with vaginal misoprostol or with a suction D&C underwent a chart review. Primary outcome was resolution of RPOC without surgical intervention. RESULTS AND CONCLUSIONS: Of 1743 unique pregnancies, 189 women were diagnosed with RPOC. 34% (65/178) chose misoprostol for management of RPOC. Baseline demographics between the three treatment modalities (expectant, medical, surgical) were comparable. 65% (42/65) of patients who took misoprostol avoided D&C. Misoprostol is most effective (76%) in the setting of RPOC if the primary treatment for miscarriage was expectant management, with less success with primary medical management (44%) and primary surgical management (40%).

Light treatment for NASA shiftworkers.

Intense artificial light can phase-shift circadian rhythms and improve performance, sleep, and well-being during shiftwork simulations. In real shiftworkers, however, exposure to sunlight and other time cues may decrease the efficacy of light treatment, and occupational and family responsibilities may make it impractical. With these considerations in mind, we designed and tested light-treatment protocols for NASA personnel who worked on shifted schedules during two Space Shuttle missions. During the prelaunch week, treatment subjects self-administered light of approximately 10,000 lux at times of day that phase-delay circadian rhythms. Treatment continued during the missions and for several days afterward. No treatment was administered to subjects in the control group. Treatment subjects reported better sleep, performance, and physical and emotional well-being than control subjects and rated the treatment as highly effective for promoting adjustment to their work schedules. Light treatment is both feasible and beneficial for NASA personnel who must work on shifted schedules during Space Shuttle missions.

Dark goggles and bright light improve circadian rhythm adaptation to night-shift work.

We compared the contributions of bright light during the night shift and dark goggles during daylight for phase shifting the circadian rhythm of temperature to realign with a 12-hour shift of sleep. After 10 baseline days there were 8 night-work/day-sleep days. Temperature was continuously recorded from 50 subjects. There were four groups in a 2 x 2 design: light (bright, dim), goggles (yes, no). Subjects were exposed to bright light (about 5,000 lux) for 6 hours on the first 2 night shifts. Dim light was < 500 lux. Both bright light and goggles were significant factors for producing circadian rhythm phase shifts. The combination of bright light plus goggles was the most effective, whereas the combination of dim light and no goggles was the least effective. The temperature rhythm either phase advanced or phase delayed when it aligned with daytime sleep. However, when subjects did not have goggles only phase advances occurred. Goggles were necessary for producing phase delays. The most likely explanation is that daylight during the travel-home window after a night shift inhibits phase-delay shifts, and goggles can prevent this inhibition. Larger temperature-rhythm phase shifts were associated with better subjective daytime sleep, less subjective fatigue and better mood.

3-(2-Carboxyindol-3-yl)propionic acid-based antagonists of the N-methyl-D-aspartic acid receptor associated glycine binding site.

A series of substituted 3-(2-carboxyindol-3-yl)propionic acids was synthesized and tested as antagonists for the strychnine-insensitive glycine binding site of the NMDA receptor. Chlorine, and other small electron-withdrawing substituents in the 4- and 6-positions of the indole ring, greatly enhanced binding and selectivity for the glycine site over the glutamate site of the NMDA receptor; one of the most potent compounds is 3-(4,6-dichloro-2-carboxyindol-3-yl)propionic acid (IC50 = 170 nM; greater than 2100-fold selective for glycine). The importance of a heteroatom NH and the enhancing effect of the propionic acid side chain were demonstrated and are consistent with previous results which suggest the presence of a pocket on the receptor which can accept an acidic side chain. Substitution of a sulfur at C3 led to the most potent compound 3-[(carboxymethyl)thio]-2-carboxy-4,6-dichloroindole (IC50 = 100 nM).

Effects of green or white light for treatment of seasonal depression.

Twelve subjects with winter depression were treated with equal quanta of green or white light in a randomized crossover study. Each treatment condition consisted of 2 hours of exposure each morning for 1 week, with at least 1 interventing week without treatment. Ratings made without knowledge of treatment condition were done before and after each condition. Both treatments significantly reduced depression ratings. White light was significantly more effective than green light in reducing endogenous symptoms, but not the "atypical" symptoms that are common features of winter depression. Furthermore, sequence of treatment conditions influenced antidepressant responses. Broad-band white light may be optimal for maximizing therapeutic response.

Circadian rhythmicity and behavioral depression: II. Effects of lighting schedules.

Two studies explore the relationship between rhythmicity and behavioral depression. Behavioral depression was induced using inescapable footshock, and assessed by measuring subsequent responses to escapable shock, in rats housed under different light-dark conditions. Experiment 1 compared escape performance in free-running and entrained animals following inescapable shock. Free-running and entrained animals did not exhibit differential vulnerability to the effects of inescapable shock. In addition, there were no systematic effects on phase following shock. However, several free-running animals showed increased circadian period following shock, and lengthening of period was significantly correlated with escape performance. Individual differences in baseline period or phase were not predictive of escape performance. In Experiment 2, "aftereffects" of entrainment to long or short light-dark cycles were utilized to create groups of animals with long or short free-running periods. After the administration of inescapable shock, escape performance was tested. There were no significant differences among experimental groups in escape performance. These results suggest that plasticity of circadian period, but not baseline period per se, may be associated with the ability to adapt to environmental challenges.

Circadian rhythmicity and behavioral depression: I. Effects of stress.

Rats were exposed to repeated sessions of inescapable footshock, and behavioral depression was subsequently assessed by measuring escape performance during exposure to escapable shock in a different testing environment. Free-running circadian activity rhythms were assessed using running wheels for approximately three weeks before and after administration of inescapable shock. Several animals showed lengthening of free-running period and decreases in activity level following shock. Similar effects were also seen in rats that were removed from their running wheels, placed within the shock apparatus, and not given shock, but not in nonhandled control animals. Furthermore, period lengthening in shocked and handled rats was positively correlated with escape performance, suggesting that circadian rhythm alterations occurred in those animals that were best able to cope with shock or handling-related stressors. In contrast, individual differences in circadian period and activity level during baseline conditions were not predictive of either escape performance or circadian rhythm alterations. These results suggest that successful behavioral adaptation to stress may be associated with alterations of circadian rhythmicity.

Thyroparathyroidectomy produces a progressive escape deficit in rats.

Abnormal thyroid status and affective disorders have been associated in the human clinical literature. It has recently been shown that pretreatment with thyroid hormone can prevent escape deficits produced by inescapable shock in an animal analogue of depression. In this report we provide evidence that hypothyroid status can produce an escape deficit in rats. While sham-operated rats improved their performance on a simple escape task over three days of testing, thyroparathyroidectomized rats showed a pronounced decrease in their responses. Markov transition analysis was used to obtain conditional probabilities of escaping given a prior escape or failure to escape for the two groups. This analysis shows that the structure of the data set may be similar for the two groups. These results suggest that if intact rats learn to escape, then hypothyroid rats may learn not to escape.

2- versus 4-hour evening phototherapy of seasonal affective disorder.

Seasonal affective disorder (SAD) has been successfully treated with bright light, and morning exposure has been deemed more effective than exposure at other times. Evening treatment may offer a practical advantage, but the optimal duration of exposure has not been established. Six SAD patients were treated at home for 1 week with 2500 lux of light given either from 6 p.m. to 8 p.m. or from 6 p.m. to 10 p.m. using a counterbalanced crossover design with a minimal withdrawal period of 1 week between conditions. Both treatments were effective in reversing SAD symptoms, but neither treatment was superior. These results suggest that evening phototherapy for as little as 2 hours may be a useful and reasonable alternative for the treatment of SAD.

Light-induced plasma melatonin suppression in seasonal affective disorder.

1. Subjects with seasonal affective disorder were exposed to 0, 500 and 1000 lux of white light for one hour beginning at 0300 hours. 2. Plasma samples were taken periodically and analysed for melatonin. 3. Plasma melatonin levels were suppressed by exposure to both 500 and 1000 lux light levels, suggesting that SAD patients show no neuroendocrine insensitivity to light but may show supersensitive responses to light.

Treatment of winter depression with a portable, head-mounted phototherapy device.

1. A portable, head-mounted device was developed for administration of light therapy. A randomized crossover protocol was used to test the therapeutic efficacy of this device, compared to a standard light box, for treatment of winter depression. 2. Depressive symptoms were significantly reduced by both the head-mounted device and the light box. 3. Therapeutic efficacy of the two devices was not significantly different. 4. The head-mounted device was rated by patients as significantly more convenient than the conventional light box; this may be important in improving patient compliance.

Interactions between nocturnal feeding and wheel running patterns in the rat.

The purpose of this experiment was to investigate the relationship between daily patterns of wheel running activity and feeding behavior. Wheel running and bar pressing for food were continuously recorded from rats which had concurrent access to both wheels and food. In a second condition, wheel running and (non-reinforced) bar pressing were recorded during food deprivation. In a third condition, bar pressing for food was recorded while wheel running was prevented. During ad lib access to wheels and food, both behaviors occurred primarily during the dark phase of the light-dark cycle. However, the nocturnal distribution of these responses differed: the early dark hours were primarily devoted to running, while feeding occurred in small, frequent meals. Maximal food intake occurred during the late dark hours, when meals were larger and less frequent, and there was little running. During three days of complete food deprivation, both wheel running and meal initiation attempts (as indicated by nonreinforced bar pressing) maintained their normal daily patterns. However, during wheel deprivation, changes occurred in the temporal distribution of meals which equalized early and late dark food intake. These results show that the availability of an alternative activity, like wheel running, can be an important determinant of daily feeding patterns. However, the daily pattern of wheel running is not influenced by food availability. Different behaviors may show differential plasticity in the coordination of an overall daily behavioral program.

(2-Piperidine)- and (2-pyrrolidine)ethanones and -ethanols as inhibitors of blood platelet aggregation.

(E)-4-[4-(Methylthio)phenyl]-1-(2-piperidinyl)-3-buten-2-one hydrochloride (44, RMI 14 133A) was found to inhibit ADP-induced aggregation of blood platelets. It was selected from a large series of (2-piperidinyl)- and (2-pyrrolidinyl)ethanones synthesized by a modified Schopf reaction from enolate magnesium salts of beta-keto acids and 2,3,4,5-tetrahydropyridine trimer or 3,4-dihydro-2H-pyrrole trimer, respectively. Evaluation of the compounds was carried out in vitro on human blood platelets. Structure-activity relationships are discussed. 44 also inhibited platelet aggregation ex vivo in guinea pigs. Subacute toxicity evaluation in dogs and guinea pigs showed it to have an unfavorable therapeutic ratio. 1-[4'-Chloro(1,1'-biphenyl)-4-yl-a1-2-(2-piperdinyl)ethanone hydrochloride (18, RMI 12436A) was found to lower serum cholesterol levles in rats with concurrent accumulation of (3beta)-cholesta-5,7-dien-3-ol, suggesting inhibition of 7-dehydrocholesterol delta7-reductase.