Incentives improve outcome in outpatient behavioral treatment of cocaine dependence.

OBJECTIVE: To assess whether incentives improved treatment outcome in ambulatory cocaine-dependent patients. METHOD: Forty cocaine-dependent adults were randomly assigned to behavioral treatment with or without an added incentive program. The behavioral treatment was based on the Community Reinforcement Approach and was provided to both groups. Subjects in the group with incentives received vouchers exchangeable for retail items contingent on submitting cocaine-free urine specimens during weeks 1 through 12 of treatment, while the group without incentives received no vouchers during that period. The two groups were treated the same during weeks 13 through 24. RESULTS: Seventy-five percent of patients in the group with vouchers completed 24 weeks of treatment vs 40% in the group without vouchers (P = .03). Average durations of continuous cocaine abstinence documented via urinalysis during weeks 1 through 24 of treatment were 11.7 +/- 2.0 weeks in the group with vouchers vs 6.0 +/- 1.5 weeks in the group without vouchers (P = .03). At 24 weeks after treatment entry, the voucher group evidenced significantly greater improvement than the no-voucher group on the Drug scale of the Addiction Severity Index (ASI), and only the voucher group showed significant improvement on the ASI Psychiatric scale. CONCLUSIONS: Incentives delivered contingent on submitting cocaine-free urine specimens significantly improve treatment outcome in ambulatory cocaine-dependent patients.

Twenty four-hour rhythm of gonadotropin release induces cyclic progesterone secretion by the ovary of prepubertal and adult golden hamsters.

Cyclic release of gonadotropin (GTH) begins on day 16 or 17 of age, about 2 weeks before ovulatory estrous cycles are initiated in female golden hamsters (Mesocricetus auratus). The daily cycles of LH and FSH are characterized by surges that peak at about 1700 h. The timing of this daily surge is similar to that observed in adult photoperiod-induced anovulatory or lactating females and to that of ovulatory females on the afternoon of proestrus. The purpose of this investigation was to determine if initiation of cyclic GTH release during the prepubertal period results in significant changes in ovarian function. A second objective was to examine the similarity between cyclic secretion of GTH in the prepubertal animal and that in the short day anovulatory adult. Groups of prepubertal females were killed throughout a 24-h period on days 13-14, 19-20, and 27-28, i.e. both before and after the expected onset of cyclic GTH release. LH did not vary significantly on days 13-14, but thereafter showed a significant rhythm, with a maximum at 1700 h. Levels of progesterone (P) were low and nonvarying on days 13-14, but a significant rhythm was measured in samples collected on days 27-28. When samples were collected from photoperiod-induced anovulatory adults, the rhythm of circulating LH and P was similar to that in the late prepubertal female. Ovariectomy of 22-day-old females resulted in low and tonic levels of P when the animals were killed 3 days later at 1400, 1700, and 2000 h, showing that the cyclical rhythm of P measured in these samples results from ovarian, not adrenal, secretion. The response of the daily cycle of LH to phenobarbital (PB) blockade in prepubertal females was identical to that in the adult: the LH surge did not occur on the afternoon of PB injection, but reappeared 24 h later at the expected time. The late afternoon surge of P was also blocked by PB administration. These results show 1) that the initiation of cyclic GTH secretion by the prepubertal female hamster influences ovarian maturation as reflected by changes in the levels and patterns of secretion of P; 2) that the rhythms of LH, FSH, and P secretion in the prepubertal female are similar to those in the photoperiod-induced anovulatory adult; and 3) that the response of the prepubertal female to barbiturate blockade is identical to that of the adult.(ABSTRACT TRUNCATED AT 400 WORDS)

Temporal relationship between the onset of daily gonadotrophin surges and of puberty in female golden hamsters.

Daily rhythms of LH and FSH release commence on day 16 or 17 of age in the prepubertal female golden hamster, 2-3 weeks before regular 4-day oestrous cycles begin. We tested the hypothesis that the daily surges of gonadotrophin regulate, at least in part, rate of sexual maturation and, hence, age at puberty. We predict that an advance or a delay in the initiation of the daily rhythm should result in a corresponding advance or delay in the day of puberty. In the first test, the onset of daily gonadotrophin surges was advanced by gonadotrophin-releasing hormone (GnRH) injections; in the second test, the onset was delayed by daily injection of phenobarbital sodium (PB). The day of the first of at least three consecutive post-ovulatory vaginal discharges was used as an index of the age at puberty. Gonadotrophin-releasing hormone (50 ng/0.1 ml saline per animal) was injected at 16.30 h on days 8-17 of age. These injections initiated a daily mid-afternoon surge of LH about 8 days before the onset of the daily rhythm of gonadotrophins in saline-injected controls and the day of first vaginal discharge was advanced by 4 days compared with saline-injected controls (32.0 +/- 1.8 days vs 36.3 +/- 1.0 days; P less than 0.001). Phenobarbital sodium (100 mg/kg body wt), injected at 13.30 h from 16 to 25 days of age, blocked daily surges of gonadotrophin observed in controls by day 18.(ABSTRACT TRUNCATED AT 250 WORDS)

Tension pneumocephalus after posterior fossa craniotomy: report of four additional cases and review of postoperative pneumocephalus.

Four cases of tension pneumocephalus after either posterior fossa craniotomy or translabyrinthine resection of acoustic neuroma with or without nitrous oxide anesthesia are described. Three of the operations were performed with the patient in the sitting position, and one was done with the patient in the lateral position. Of the three cases operated in the sitting position, no nitrous oxide was used at any time during anesthesia in one. Two patients failed to regain consciousness after the termination of anesthesia, and the other two developed the sudden onset of neurological symptoms 1 to 1.5 hours after the operation. In all cases computed tomography disclosed a large subdural collection of air. Re-exploration of the surgical wound or twist drill aspiration of the subdural air resulted in prompt recovery of neurological status in three patients, whereas the other patient's neurological status improved gradually without any specific treatment. The role played by nitrous oxide, the mechanisms by which air enters the intracranial space, the contributory factors, and the predisposing surgical conditions of tension pneumocephalus are reviewed and discussed. Dependent drainage of the cerebrospinal fluid, especially in a patient with coexisting hydrocephalus, seems to be the most important factor for the development of this complication.

Static and dynamic stresses during valve closure of a bileaflet mechanical heart valve prosthesis.

The effect of contact geometry and component compliance on the magnitude, distribution, and state of various types of stresses on a bileaflet mechanical heart valve prosthesis during valve closure was analyzed using an Edwards-Duromedics mitral valve as example. Static and dynamic stresses developing on both the leaflet and pivot ball during valve closure were modeled using finite element analysis (FEA). Uniform contact between the leaflet and housing as well as between the pivot ball and pivot slot can significantly reduce both static and dynamic stresses around the contact area. The level of the dynamic flexural stresses can be an order of magnitude higher than that of the static stresses. When both the radial and axial compliance of the housing are taken into consideration, peak dynamic stress was more than 40% less than that generated through the impact between a moving leaflet and a non-compliant rigid housing.

Monitoring the resuscitation of preterm infants in the delivery room using pulse oximetry.

The first few minutes after birth are a critical time of adaptation of the newborn infant to extrauterine life. The adequacy of that adaptation has been evaluated by means of the summed Apgar score. In preterm infants, Apgar score may correlate less with adequacy of cardiopulmonary function because of developmental immaturity. Measurement of arterial oxygen saturation by means of pulse oximetry offers a physiologic, real time method of monitoring the progress of cardiopulmonary adaptation by which the clinician can evaluate the need for and success of resuscitative efforts. Four preterm infants are reported in whom pulse oximetry was useful in assessing the changes in oxygen saturation during resuscitation.

Rationale and indications for microfiltration of blood in emergency medicine.

Documentation in the literature shows that massive transfusions for severe, nonthoracic trauma contribute to development of progressive pulmonary failure in some patients. Further review shows embolic phenomena in cardiopulmonary bypass procedures contribute to a number of postoperative complitions. These complications are related to the numbers and physical characteristics of aggregates in banked whole blood and to the morphology of the pulmonary circulation. Many of these complications can be prevented or markedly attenuated by microfiltration of banked blood. It is concluded that all transfusions of banked whole blood and blood products should be administered through microfiltration units.

Neonatal androgen abolishes clock-timed gonadotrophin release in prepubertal and adult female hamsters.

Testosterone propionate (100 micrograms) or oil was injected within 24 h of birth. At 25 days of age blood samples were obtained at 14:00, 17:00 and 20:00 h. There was a significant increase in serum LH, FSH and progesterone concentrations between 14:00 and 17:00 h in the controls, followed by a decrease at 20:00 h. These rhythms were absent in testosterone propionate-injected animals. Ovariectomy of adults was followed by similar increases of LH and FSH in androgenized and oil-injected females (gonadectomy response) but the large surge of gonadotrophins observed in controls 1 day after implantation of an oestradiol-containing capsule (positive feedback) was not detectable in androgenized females. These results show that the initial effects of neonatal androgenization on cyclic gonadotrophin release in the female are present before puberty and are separable from effects on steroid modulation of gonadotrophin secretion.

The peripubertal golden hamster and the transition between daily and estrous cycle hormone rhythms.

Transitional patterns of LH, FSH, and progesterone (P4) in the circulation were studied in peripubertal female golden hamsters. A daily rhythm, with afternoon surges of these hormones, is typical of the immature female, whereas 4-day rhythms characterize the estrous cycle of the adult. Blood samples were collected repeatedly from maturing individuals at either 1400 or 1700 h. Each animal was examined daily for the appearance of regular vaginal estrous cycles as indicated by a mucous exudate on the morning of ovulation. Between Days -10 and -5 relative to first vaginal estrus (FVE), afternoon surges of LH, FSH, and P4 were often observed. From Days -5 to -1 relative to FVE, afternoon surges of LH and FSH were less frequent, but P4 retained the daily rhythmicity until Day -2. A 4-day pattern of LH secretion, but not of FSH or P4, was established prior to FVE. To determine whether or not ovulations were occurring prior to the appearance of external vaginal estrous cycles, reproductive tracts were collected from 26-34 days of age and examined for evidence of ovulation. Of 124 females, concordance between the record of daily vaginal examinations and the examinations of the ovaries and oviducts was found in 103 cases (83%). The development of ovarian follicles was correlated with FVE in peripubertal hamsters by unilateral ovariectomy. Antral follicles were found only in the last 3 days prior to vaginal estrus.

Daily rhythms of pituitary-ovarian function in the immature hamster are independent of adrenal and pineal influence.

In female hamsters, the daily rhythm of LH appeared on the 15th or 16th day after birth with a peak occurring at about 16:00 h (14L:10D, lights on 06:00 h). Progesterone concentrations increased and became rhythmic a few days later. In serum samples collected at 14, 16, 18, 20, 25, 30, 40 and 60-62 days of age between 13:00 and 23:00 h, significant rhythms of serum cortisol and corticosterone concentrations were not detected before 25 days of age; furthermore, the phase of the rhythms did not stabilize to the adult pattern until about 40 days of age. As in the adult, significant rhythms were present in both sexes and the levels of cortisol were greater than those of corticosterone. Injection of pig ACTH (50 i.u./kg body wt, i.p.) significantly increased serum cortisol by 10 days of age, but corticosterone did not respond until 25 days of age. Thus, for cortisol at least, the appearance of 24-h rhythms in the serum is probably not dependent on the ability of the adrenal to respond to ACTH. Ovariectomy had no effect on the late afternoon surge of serum cortisol; similarly, adrenalectomy of immature females did not abolish the surge of LH. Ovariectomy did not alter the daily rhythm of pineal melatonin content and pinealectomy had no effect on the daily afternoon surge of LH. These results demonstrate functional independence of circadian rhythms in the pituitary-gonadal axis and the pituitary-adrenal axis of the immature hamster and also independence of daily rhythms of pineal melatonin and pituitary release of LH.

Accuracy of pulse oximetry during arterial oxyhemoglobin desaturation in dogs.

An animal model was developed to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation. The fractional inspired oxygen concentration was varied from 0.03-1.0 in five anesthetized dogs. One hundred and twelve simultaneous pulse oximeter oxygen saturation measurements (SpO2) and IL 282 CO-Oximeter arterial oxygen saturation (SaO2) measurements were made. Variance of SpO2 was increased for SaO2 less than 22%. Linear regression analysis of the data for SaO2 greater than 22% produced the equation y = 0.93x + 9.8 (r2 = 0.97). The mean difference between SpO2 and SaO2 was +5.5% +/- 4.2% (SD) over the range of 22-100%. Spectral analyses of oxygenated (O2Hb) and reduced (RHb) canine and human hemoglobins were performed. The absorption spectra of canine O2Hb and RHb were nearly identical to those of human O2Hb and RHb. Therefore, 1) SpO2 measurements in dogs at SaO2 greater than 22% are relatively accurate, and 2) hemoglobin absorption characteristics support the contention that such canine pulse oximeter studies can be extrapolated to humans.

Dissociation of the reproductive and prolactin photoperiodic responses in male golden hamsters.

The response of prolactin (PRL) and that of the pituitary-testicular axis to inhibitory photoperiods were compared in immature and young adult hamsters. In the first experiment, 14-day-old hamsters were transferred from 14L:10D to 12L:12D or 8L:16D. At 21, 28, 35, and 49 days of age, body weights, testes weights, and plasma LH were similar in all groups. In contrast, the levels of PRL were lower in animals on 8L:16D or 12L:12D than in those on 14L:10D and 49 days of age. In a second experiment, 80-day-old hamsters were transferred from 14L:10D to either 12L:12D or 8L:16D. At 5-wk intervals, they were weighed and bled by cardiocentesis and the length of the testes was measured. Photoperiods of 12L:12D and 8L:16D induced testicular regression, which was complete by 15 wk. Thereafter, augmented levels of FSH preceded spontaneous recrudescence of the testes in animals on both photoperiods. Serum PRL levels were significantly depressed within 5 wk after transfer to either 8L:16D or 12L:12D. After 15 wk as the testes were increasing in size in both groups, circulating PRL levels increased in animals exposed to 8L:16D, whereas in animals exposed to 12L:12D, PRL remained at or below the sensitivity of the assay. In a final experiment, on the day before parturition, pregnant hamsters were transferred to either 6L:18D, 6L:30D, 6L:42D, or 6L:54D or were held on 14L:10D. There were no differences in testicular weights, plasma LH, or plasma thyroxine (T4) of the pups from these dams at 21, 36, or 48 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Daily rhythms of serum luteinizing hormone in the immature hamster are estradiol-dependent.

In the female Syrian hamster (Mesocricetus auratus), daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) begin several weeks before regular vaginal estrous cycles are initiated. These rhythms, which appear rather abruptly at about 16 days of age, are dependent on the presence of the ovaries. The experiments described here were intended to determine the nature of the ovarian information required for the initiation and maintenance of the daily LH surge. This surge characterizes the daily cycle of LH and occurs each afternoon at about 1700 h in the intact animal between 2 and 5 weeks of age. Females were ovariectomized at 14 or 15 days of age and implanted with constant-release Silastic capsules of estradiol (E) or progesterone (P). Blood samples were collected at 21 days of age at 1400 or 1700 b, and the serum was assayed for LH, P, and E. While ovariectomy abolished the afternoon surge of serum LH that was observed in sham-operated controls, implantation of E effectively replaced the ovaries. Implantation of P was without effect on LH levels; when P plus E was implanted, the effect was similar to that of E alone. These results suggest that ovaries of the 2-week-old hamster secrete estrogen necessary for the initiation of cyclical LH release.

Naloxone administration to female hamsters advances puberty by enhancing luteinizing hormone release.

In the female hamster, a daily rhythm of gonadotropin release begins almost 3 weeks prior to the initiation of 4-day estrous cycles. A temporal relationship exists between the onset of this cyclic release of gonadotropin and age at puberty. We hypothesized that since opiate agonists depress circulating gonadotropins and antagonists increase them in both adult and immature rodents, endogenous opiates may influence the mechanism controlling cyclical gonadotropin release in the prepubertal female hamster and thus affect rate of sexual maturation and hence the age at puberty. This proposal was tested by chronic administration of naloxone (NAL), an opiate receptor antagonist. We predicted that NAL might induce the early initiation of daily surges of luteinizing hormone (LH) if endogenous opiates inhibit sexual maturation. Naloxone was injected daily (50 mg/kg body wt) at about 1300 hr from Days 1 through 17 of age. The NAL injections increased serum LH and significantly advanced the age at which first estrus vaginal discharge was observed (32 vs 38 days for saline-injected controls in Experiment I and 31 vs 37 days in Experiment II). However, the NAL injections did not correspondingly advance the age of initiation of endogenously generated daily cycles of circulating LH. We conclude that blockade of opiate receptors accelerates sexual maturation by directly inducing the release of LH and not by advancing the age of initiation of endogenous gonadotropin surges.

Daily rhythms of follicle-stimulating hormone in adult anestrous and prepubertal female Turkish hamsters (Mesocricetus brandti).

We tested the hypothesis that daily FSH surges are correlated with the anestrous condition in adult Turkish hamsters. Blood samples were collected from anestrous hamsters on short (12L:12D) and long photoperiods (16L:8D) by cardiac puncture. Both photoperiod-induced anestrous (PIA) and spontaneously anestrous adult Turkish hamsters had a daily rhythm of FSH secretion with maximum hormone concentrations occurring late in the afternoon. We also hypothesized that daily FSH and progesterone surges are correlated with the reproductive response to short photoperiod in prepubertal female Turkish hamsters. Prepubertal hamsters reared on 16L:8D were sampled at 13, 15, 17, 19, and 21 days of age. Only at 19 days was a rhythm of FSH present. Prepubertal female hamsters reared on 12L:12D were sampled at 30, 35, 55, 75, 95, and 115 days of age or until estrous cycles were established. Those hamsters that delayed puberty in response to this short photoperiod had a daily rhythm of FSH and progesterone secretion. Conversely, no daily rhythms were observed in female hamsters that failed to respond to the inhibitory photoperiod with a delay in puberty. These results indicate that the daily rhythm of FSH secretion in the female Turkish hamster is correlated with reproductively inhibited physiological states.

Dissociation of spontaneous testicular recrudescence and photorefractoriness in the Syrian hamster.

In male Syrian hamsters, short days induce regression of the reproductive system, but eventually spontaneous recrudescence occurs ensuing from refractoriness to the inhibitory photoperiod. Although the photoperiod of 12 L:12 D (12 h light:12 h dark) may act like a short day by inducing the testicular cycle outlined above, it may fail to evoke the increase of circulating concentrations of prolactin that accompanies testicular recrudescence. This photoperiod may fail to induce photorefractoriness, as indicated by the prolonged low concentrations of prolactin in the blood. Herein, hamsters were exposed to either 8 L:16 D or 12 L:12 D from weaning and by 28 weeks exposure to either photoperiod, the hamsters had large testes following recrudescence from a photoperiod induced-regression). Transfer to 8 L:16 D from 12 L:12 D at 28 weeks resulted in a second testicular regression and recrudescence. In a second experiment, the testes of hamsters moved to 8 L:16 D from 12 L:12 D after 29 weeks exposure to the latter photoperiod similarly regressed and then regrew. Serum concentrations of prolactin decreased in these males after transfer to the shorter daylength but also decreased in hamsters kept under 12 L:12 D both groups were usually below those of hamsters moved to 14 L:10 D. These results show that exposure for 28 or 29 weeks to 12 L:12 D was insufficient to induce photorefractoriness, despite the recrudescence of the testes following involution.

Daily rhythms of luteinizing hormone and follicle-stimulating hormone persist in female hamsters sterilized by neonatal administration of monosodium glutamate.

Monosodium glutamate (MSG) was used to evaluate the importance of the arcuate nucleus of the hypothalamus in the expression of daily gonadotropin rhythms in female golden hamsters. These daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which also occur in prepubertal females, are characterized by afternoon surges. Neonatal administration of MSG induces degeneration of perikarya in the arcuate nucleus and renders females permanently anovulatory. MSG was injected at 8 days of age; at 21 days, the animals were weaned and sorted by sex into groups of 5-7. Blood samples were obtained at 1300 and 1700 h at 25, 30, 35, 40, 50, 62, and 192 days of age from MSG-sterilized animals. Saline-injected controls were bled at 25 days and after estrous cycles had been initiated (29-37 days of age). In both control and MSG-injected groups, there was an afternoon surge of LH and FSH at 25 days of age. These daily surges persisted in MSG-injected animals. The ovaries of these animals were characterized by an abundant interstitium and arrested follicular development. Progesterone levels of MSG-anovulatory animals also reflected the rhythmicity of LH and FSH, with a significant increase occurring between 1300 and 1700 h. Thus, MSG did not affect the daily circadian-based rhythmicity in gonadotropin secretion even though adult-age animals were infertile. These results suggest that perikarya of the arcuate nucleus affected by MSG are not required for generation of daily LH and FSH rhythms.

Absorption characteristics of human fetal hemoglobin at wavelengths used in pulse oximetry.

The absorption characteristics of fetal and adult human hemoglobin samples were determined for the range of 600 to 1,050 nm. Over this range, fetal hemoglobin absorption is nearly identical to that of adult hemoglobin. Since currently available two-wavelength pulse oximeters base their calculations of arterial oxyhemoglobin saturation on absorption at the wavelengths of 660 and 920 nm, we conclude that the accuracy of two-wavelength pulse oximetry previously demonstrated in adults can be extrapolated to infants with high concentrations of fetal hemoglobin.

Effects of ovariectomy on clock-timed daily gonadotropin rhythms in prepubertal golden hamsters.

Daily rhythms of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are measurable in the serum of prepubertal female golden hamsters by 17 days after birth. These rhythms, which are characterized by peak levels at 1700 h, persist until they are replaced by a 4-day rhythm as ovulatory cycles begin, approximately 3 wk later. We have tested the proposition that the ovaries are required for the onset and maintenance of clock-timed gonadotropin release by removing the ovaries and measuring the levels of LH and FSH in prepubertal hamsters. Ovariectomy was performed both before and after the onset of the rhythm and the effect of removal was determined by subsequent collection of blood samples during the mid- to late-prepubertal period. Ovariectomy on 7, 10 or 13 days after birth results in tonic levels of LH and FSH in blood samples collected at 1400, 1700 and 2000 h on Days 17 through 29. Sham-operated or intact controls had significantly elevated levels of these hormones at 1700 h. Ovariectomy on Day 21 and killing on Day 25 at the same times of day abolished the rhythm of serum LH measured in sham-ovariectomized controls. Ovariectomy on Day 21 and killing on Days 26, 28 or 30 at hourly intervals resulted in variable but nonrhythmic patterns of circulating LH. Thus, ovariectomy before the initiation of clock-timed gonadotropin release prevented its initiation; ovariectomy after its initiation abolished the rhythm. These results show that the ovary provides an essential "message" to the brain-pituitary axis for the initiation and maintenance of clock-timed gonadotropin release in prepubertal females.

Age, photoperiodic responses, and pineal function in meadow voles, Microtus pennsylvanicus.

We tested whether juvenile males of Microtus pennsylvanicus were more sensitive than adults to the suppressive effects of short photoperiods. Voles were transferred to short photoperiods (10L:14D) at 20 or 80 d of age, and 60 d later (i.e. at 80 or 140 d) the animals were killed at intervals throughout the day and night. Pineal glands were collected for measurement of melatonin, and the testes were weighed. There were no differences in paired testicular weights of 80 and 140 d old animals held on long days (median testicular weights: 1,953 and 1,843 mg). In contrast, median testicular weights of voles held on short days were 504 and 1,112 mg, respectively, at 80 and 140 d of age; the testicular weights of both groups were significantly different from their age-matched controls (P less than .001, two-sample t-tests on log transformed data). The responses of the two age groups were compared by normalizing the individual values by the mean and variance of the respective long-day controls. This comparison suggests that the responsiveness to photoperiod decreases as the animals age (t-test, P = .01). Duration and amplitude of the nocturnal rise in pineal melatonin content were similar in differently aged animals. In two experiments, voles were injected daily with melatonin from 20 to 80 or 80 to 140 d of age. Melatonin-injected animals had smaller testes than did saline-injected controls (ANOVA: P = .01), and injections were more effective in the afternoon than in the morning (P = .01). Comparison of the effectiveness of short day and melatonin injections in juvenile and adult voles suggests that while short days inhibited testicular development of young animals more than it induced regression of adults, this decrease in responsiveness may involve factors other than alterations in the nocturnal pattern of melatonin production.