Duration of complete atrioventricular block after congenital heart disease surgery

Children with complete heart block following surgery for congenital heart diseases were prospectively followed to assess the timing for recovery of atrioventricular conduction, and to determine if there were clinical variables that reliably predict permanent heart block. Recovery of atrioventricular conduction occurred by postoperative day 9 in 97% of patients with transient heart block.     

Relationship of cell survival, drug dose, and drug uptake after 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine treatment

The mechanisms that govern the activity and the factors that control the anticancer activity of synthetic ether lipids have not been fully elucidated. In this study, three factors were studied in relationship to cell survival after treatment with 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3): (1) exposure dose, (2) drug uptake, and (3) cell density and cell-cycle distribution. In BG-1 human ovarian carcinoma cells, cell survival was an exponential function of exposure dose and was dependent on drug concentration. Drug uptake was dependent on the concentration of ET-18-OCH3, whereas the reduction in cell survival was directly related to the uptake of drug only in the first decade of cell kill. When the quantity of cells per flask was tripled from 4 to 12 x 10(6) cells, ET-18-OCH3 failed to induce a G2 block. Furthermore, the cell kill induced by a 72-h exposure to 2 microM ET-18-OCH3 was decreased by a factor of 2 when the cell density increased. Therefore, exposure dose and cell density are important parameters in determining the cell kill induced by ET-18-OCH3.     

Selective serotonin reuptake inhibitors dissociate fenfluramine's anorectic and neurotoxic effects: importance of dose, species and drug

Fenfluramine, a clinically prescribed appetite suppressant, has been found to damage brain serotonin (5-HT) neurons in every animal species tested to date. Recent findings indicate that fluoxetine, a selective 5-HT reuptake inhibitor (SSRI), can prevent fenfluramine-induced 5-HT neurotoxicity without blocking fenfluramine-induced appetite suppression. The purpose of our studies was several-fold: 1) To determine whether the ability for fluoxetine to dissociate fenfluramine-induced anorexia and neurotoxicity is dose-related; 2) to ascertain whether other SSRIs also prevent fenfluramine-induced neurotoxicity without altering its anorectic effect; 3) to determine whether similar fluoxetine/fenfluramine interactions are seen in another animal species (i.e., mice) and 4) to determine whether decreases in food intake seen after the fluoxetine/fenfluramine combination can be attributed to nonspecific behavioral suppression. Results from our studies indicate that fluoxetine's effects are, indeed, dose-related, because higher doses of fluoxetine are required to protect against the 5-HT neurotoxic effects of higher doses of fenfluramine. Further, our results indicate that fluoxetine's effects generalize to all other SSRIs tested (citalopram, paroxetine and sertraline), as well as to other species (mice). Finally, our results demonstrate that anorexia in animals receiving the fenfluramine/fluoxetine combination is not secondary to nonspecific behavioral suppression, because water intake is increased although food intake is decreased in the same animals. Together, these data suggest that the anorectic and 5-HT neurotoxic effects of fenfluramine may involve different mechanisms, and that by combining fenfluramine with SSRIs, it may be possible to exploit fenfluramine's clinically useful properties (e.g., anorexia) without risking brain 5-HT neural injury.     

Time of peak drug concentration after a single dose and a dose at steady state

The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter.     

Buprenorphine dose self-selection: Effects of an alternative reinforcer, behavioral economic analysis of demand, and examination of subjective drug effects.

Buprenorphine (BUP)-maintained patients were first exposed to various BUP doses and then chose between BUP doses and money. In the choice phase, they had 10 units exchangeable for units of BUP (constant at 3 mg/unit) or money (varied from $0.30 to $20/unit). They chose BUP exclusively (30 mg) when the money alternative was low. As available money increased, they selected lower daily BUP doses (down to 3 mg). An economic analysis indicated demand for BUP was inelastic; changes in drug intake were proportionally lower than changes in price. Subjective reports of agonist and withdrawal effects increased >200% when high and low BUP doses, respectively, were given during the exposure phase. In the choice phase, subjective drug effects were constant regardless of the BUP dose selected. Thus, BUP dose selection varies with the magnitude of alternative reinforcers, and subjective drug effects depend on whether doses are self- or experimenter-selected. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heroin craving and drug use in opioid-maintained volunteers: Effects of methadone dose variations.

Recent data indicate that opioid agonist and antagonist challenges decrease and increase (respectively) heroin craving in physically dependent individuals. This study investigated effects of methadone dose variations on craving and new drug use in 18 outpatients who were given money contingencies. In Phase 1, volunteers were told in different test sessions that methadone dose would increase, decrease, or stay the same; drug-abstinence contingencies were suspended for 24 hr. Craving significantly increased and new heroin use marginally increased (relative to maintenance dose) only when a dose reduction was paired with a dose decrease instruction. In Phase 2 (detoxification), craving and heroin use significantly increased as methadone dose decreased. Thus, loss of μ-receptor agonist effect increased craving and risk of relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Platelet adhesion onto segmented polyurethane surfaces modified by PEO- and sulfonated PEO-containing block copolymer additives

Polyethylene oxide (PEO) surfaces were prepared by the addition of PEO- and sulfonated PEO-containing amphiphilic block copolymers as surface-modifying additives in a segmented polyurethane (PU). PEO-PPO-PEO triblock copolymers (Pluronics) with different PEO chain lengths (from 2 to 80) were used as additives. The prepared film surfaces were characterized by the measurement of dynamic water contact angles and electron spectroscopy for chemical analysis. It was observed that the PU films containing 10 wt% of PEO additives were surface-saturated with the additives regardless of their PEO chain length, but the PEO chains were more projected from the film surfaces containing the additives with longer PEO chains. The water absorption of the films increased largely with the increasing PEO chain length of the additives. The addition of PEO additives produced film surfaces that were in a gel-like state. The films demonstrated some extraction of the PEO additives. However, the additives with higher molecular weights were entrapped more stably into the PU matrix. The mechanical properties (tensile strength and elongation) of the films were changed by the addition of PEO additives, but the differences were not significant compared to the control PU. The platelet adhesion on the film surfaces decreased with increasing PEO chain length of the additives. The film surface containing additives with long PEO chains (chain length of 80) was particularly effective in preventing platelet adhesion. The effect of negatively charged sulfonate groups on the prevention of platelet adhesion appeared only on the film surfaces containing additives with short PEO chains. For longer PEO chains, the chain mobility effect was more dominant than the negative charge effect on the prevention of platelet adhesion.     

Patterns of smoking and methadone dose in drug treatment patients.

Cigarette smoking prevalence is very high, and cessation rates are very low, among people in methadone treatment. This may in part be due to interactions between methadone administration and cigarette smoking. The present study explores relationships between methadone dose timing and smoking rates. Twenty methadone patients, over a period of 19 days, used electronic cigarette packs to record their smoking patterns and called a voice mailbox daily to report their methadone dose and timing. The average proportion of daily cigarettes smoked was calculated for 2-hr blocks preceding and following methadone dose administration. For all participants, peak smoking rates occurred after methadone administration. Participants smoked a greater proportion of cigarettes in their first 2-hr block after methadone dosing (M = 0.368, SD = 0.135) than during their first 2-hr block of smoking of the day (M = 0.245, SD = 0.010; S = 85.5, p     

Comparison of dose standard units for drug utilisation studies

Primary malignant melanoma of the esophagus is rare. We identified one patient over a period of 15 years. This patient was a 80 years-old caucasian man. No association was found with tobacco or ethanol use, nor was there a personal or family history of malignant melanoma. Symptoms were related to obstruction. This tumor was polypoid in its upper part and ulcero-infiltrant in its lower part. Histologically the melanoma had epithelioid spindle cells. The neoplasm was immunoreactive for S-100 protein and non reactive with anti-cytokeratins. This patient was treated by Garlock type, esophagectomy with excision of 13 cm of esophagus and 2 cm of stomach. The survival was of only 3 days, because he developed acute respiratory and cardiac disease syndrome and died.     

Ultrasonic absorbed dose, dose rate, and produced lesion volume

Histological preparations of ultrasonically produced lesions in cat brain, at 3 and 4 MHz, have been studied microscopically. The relationship of the delivered acoustic intensity at the lesion site, the energy absorbed per unit volume of the lesion, and the lesion volume is exhibited. It is suggested that universal responses to ultrasonic exposure may exist for different tissues.     

Duration, satisfaction, and perceived effectiveness of cross-cultural counseling.

The relationship between cultural dissimilarity and the duration, satisfaction, and perceived effectiveness of counseling was studied in the context of 70 actual treatment dyads that varied as to the race of the counselor and the client (White or non-White). White counselors provided fewer sessions than non-White counselors, and non-White clients expressed lower levels of overall satisfaction with counseling, regardless of counselor race. No differences in counseling effectiveness were observed as measured by counselor and client ratings of perceived relief, understanding, and coping. Relative to other treatment dyads, however, White clients seeing White counselors attributed their change more to counseling than to other, outside factors. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response prevention and extinction of escape behavior: Duration, frequency, similarity, and retraining variables in rats.

Describes 3 experiments in which a total of 158 female hooded rats received escape training, response prevention, and then regular extinction. Following training, Ss in Exp I received 1 response-prevention trial lasting 0, 120, 240, or 400 sec, or multiple trials (6, 12, or 20) lasting 20 sec each. Extinction was faster as prevention duration or frequency increased. At each duration, extinction was faster following multiple- than following single-prevention trials. In Exp II Ss received "prevention" in the original escape situation or in similar or dissimilar situations. Extinction was faster as prevention and training situations increased in similarity. To evaluate the persistence of prevention effects, in Exp III Ss received shock retraining between prevention and regular extinction. Retraining attenuated but did not eradicate the effects of prevention. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depression in university students: Duration, relation to calendar time, prevalence, and demographic correlates.

The duration, relation to calendar time, prevalence, and demographic correlates of depression in university students were studied by administering the Beck Depression Inventory to 4 independent samples (N?=?222) either once or twice at 3 points in time separated by 3-wk intervals. The 3-wk test–retest reliability was .78. There was no significant effect of the 3 points in time sampled. 17% of the Ss scored depressed; of these, 67% still scored depressed 3 wks later. Depression was significantly negatively correlated with year level but was not significantly associated with sex, marital status, their interaction, or age. There was no difference between the rates of depression in lowerclassmen in 1974 and 1977. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of ring block, dorsal penile nerve block, and topical anesthesia for neonatal circumcision: a randomized controlled trial

CONTEXT: Beliefs about the safety and effectiveness of current anesthetics have resulted in many newborns being circumcised without the benefit of anesthesia. OBJECTIVE: To compare ring block, dorsal penile nerve block, a topical eutectic mixture of local anesthetics (EMLA), and topical placebo when used for neonatal circumcision. The placebo represented current practice, with no anesthetic for neonatal circumcision. DESIGN: A randomized controlled trial. SETTING: Antenatal units in 2 tertiary care hospitals in Edmonton, Alberta. PARTICIPANTS: A consecutive sample of 52 healthy, full-term, male newborns, aged 1 to 3 days. INTERVENTIONS: Physiological and behavioral monitoring occurred in a series of trials: baseline, drug application, preparation, circumcision, and postcircumcision. Surgical procedures defined the following 4 stages of the circumcision: cleansing, separation, clamp on, and clamp off. Methemoglobin level was assessed 6 hours after surgery. MAIN OUTCOME MEASURES: Heart rate, cry, and methemoglobin level. RESULTS: Newborns in the untreated placebo group exhibited homogeneous responses that consisted of sustained elevation of heart rate and high-pitched cry throughout the circumcision and following. Two newborns in the placebo group became ill following circumcision (choking and apnea). The 3 treatment groups all had significantly less crying and lower heart rates during and following circumcision compared with the untreated group. The ring block was equally effective through all stages of the circumcision, whereas the dorsal penile nerve block and EMLA were not effective during foreskin separation and incision. Methemoglobin levels were highest in the EMLA group, although no newborn required treatment. CONCLUSIONS: The most effective anesthetic is the ring block; EMLA is the least effective. It is our recommendation that an anesthetic should be administered to newborns prior to undergoing circumcision.     

Skills training for drug abusers: Generalization, maintenance, and effects on drug use.

This study reports on the follow-up data for the treatment of drug abuse by J. D. Hawkins et al (see record 1987-08465-001). In the original study, 130 clients in the reentry phase of residential drug treatment programs were randomly assigned to a control group (n?=?60) or to a 10-week supplemental behavioral skills training course (n?=?70). Eighty-two percent of the sample was male, and 75% was White. Subjects' ages ranged from 15 to 55 years, though the majority (71%) were in their twenties. A role-play test assessing skill levels was administered as a pretest, following the 10-week skill training course, and again at 6 and 12 months as follow-ups. Although skills decayed slightly over time, the skill levels of experimental subjects were higher than the control group 12 months after training. Generalization of skills to role-play situations for which no training had been received was also found. However, with the exceptions of marijuana and amphetamine use, skill training did not affect drug use after treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory and N-methyl-D-aspartate receptor antagonists APV and MK-801: Memory impairments depend on familiarity with the environment, drug dose, and training duration.

Rats given N-methyl-D-aspartate (NMDA) antagonists were tested in the radial maze in spatial working memory (WM) and reference memory (RM) tasks. 16 female rats given (+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d] cycloheptene-5,10 imine (MK-801; 0.0625 mg/kg intraperitoneal/ly (ip)) before daily testing in an 8-arm WM task were impaired even after 70 days. Control rats learned quickly, were assigned to a group given MK-801 or saline, and were trained to avoid 4 of the 8 arms. MK-801 impaired this reversal learning but did not affect WM performance. 15 male rats were trained on an 8-arm WM task for 19 days and then given intracranial aminophosphonovaleric acid (APV; 33 mM), which impaired both WM and motor behavior. 24 male rats were trained for 65 days to enter 4 of 8 arms and then given intracranial APV (20 or 30 mM). WM and RM were normal in the familiar environment but were both impaired in an unfamiliar environment. Results suggest that the mnemonic effects of NMDA antagonists depend on environmental familiarity, dose, and training duration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adolescent drug use and adult drug problems in women: Direct, interactive, and mediational effects.

The authors studied effects of variables assessed in adolescence on problems from drug use in adulthood in a community sample of women. One focus of this 13-year longitudinal study was moderators, which were hypothesized to exacerbate, or attenuate, the effects of early drug consumption on later drug problems. Potential moderators were sensation seeking, social conformity, academic orientation, parental support, depression, and drug problems in parents. Direct and mediating effects of these variables, as well as of drug consumption, were also evaluated. Results showed that most of the significant effects involved sensation seeking and social conformity. In addition, adolescent drug use significantly predicted adult polydrug problems. The effects of sensation seeking are consistent with the view that this variable reflects a sensitivity to drug use, which makes it more likely that drug use gets translated into drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Duration of human singleton pregnancies in Ibadan, Nigeria

Analysis of gestation length in an obstetric population of indigenous African women revealed a mean pregnancy duration of 274.8 days, which is similar to values recorded in women of African descent elsewhere, but about 1 week less than what generally has been reported in women of European ancestry and Japanese women. Factors associated with lower pregnancy duration among these women include increasing maternal age and gravidity, and the birth of a male infant. It is concluded that mean pregnancy duration in Nigerian women is shorter than the 280 days normally used in obstetric calculations. The consistent finding of a shorter length of gestation in these and other black women suggests earlier maturity of the fetoplacental unit. Earlier institution of antepartum fetal monitoring in women of African descent, particularly women > 30 years old and those with high parity, may reduce the risks of fetal morbidity and mortality attributable to postmaturity in their offspring.