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Biomedical subjects

J S Knisely

Publications and source records attributed to J S Knisely.

At least 19 recordsLinked to original sources

Psychopathology in substance abusing women reporting childhood sexual abuse.

This study compared MMPI-2 profiles and evaluated the ability of the MMPI-2 and its two new post-traumatic stress scales (PK and PS) to discriminate women in outpatient substance abuse treatment reporting positive (n = 24) and negative (n = 69) child sexual abuse histories. T-tests revealed significantly higher mean scores for the sexual abuse group for the following scales: F, 1, 2, 3, 4, 6, 7, and 8. A discriminant analysis yielded a linear function of L, F, 3, 5, 8, and PK that correctly categorized 75% with positive histories and 77% with negative histories. The optimal cutoff PK score was 17, which correctly classified 75% and 46% of those reporting positive and negative abuse histories, respectively. These findings support early identification of abuse survivors among substance abusing women and suggests that the MMPI-2 may be useful in patient-treatment matching.

Adolescent↗

The evaluation of a consultation service for delivery of substance abuse services in a hospital setting.

OBJECTIVE: This study evaluated the institutional impact of a substance abuse consultation service in a hospital setting. METHOD: Treatment and matched comparison groups were compared on five outcome variables: length of stay, total cost, reimbursement, readmission, and appropriateness of care. The treatment group consisted of patients with discharge diagnoses falling into targeted Diagnostic Resource Groups (DRGs) and who received a substance abuse consultation. The comparison group consisted of patients with the same targeted DRGs, a coexisting substance abuse diagnosis, and who did not receive a substance abuse consultation. RESULTS: No statistically significant differences were found for the five outcome variables. Findings closely approached statistical significance for rate of readmission with treatment patients being less likely to be readmitted during the 12 months following the consultation. CONCLUSIONS: Although cost savings were not found during the hospitalization when the substance abuse consultation was provided, the data suggests that the consultation may reduce the need for readmission during the year following discharge.

Adolescent↗

Changes in immunologic cell surface markers during cocaine withdrawal in pregnant women.

To evaluate the effects of acute cocaine withdrawal on the immune system of pregnant women, we analyzed changes in a panel of cell surface markers and plasma proteins that have immunological importance. The cell surface markers included complement receptors [CR1 (CD35), CR2 (CD21), CR3 (CD11b, CD18)], immunoglobulin Fc receptors [FcgammaRII (CD32), FcgammaRIII (CD16)], proteins important for lymphocyte function [CD3, CD4, CD8, CD19, CD25, CD45RA], and the framework antigen HLA-ABC. We also measured levels of the plasma proteins C3, C4, IgG, IgM, and IgA, along with the cytokine interleukin-2, soluble lymphocyte markers sCD25, sCD4, sCD8, IL-2, and soluble immune complexes. While no significant changes were seen in the levels of plasma proteins, changes paralleling the course of acute withdrawal were seen in complement receptors and immunoglobulin Fc receptors on leukocyte subpopulations. By contrast, proteins important for lymphocyte function were relatively unperturbed. There was an increase in receptor expression at the onset of withdrawal that peaked 3-5 days after last cocaine use, followed by a decrease in expression to initial (pre-withdrawal) levels. These changes in cell surface receptors may reflect altered immune function in the women who were withdrawing from cocaine.

Adult↗

Decreased carbon dioxide sensitivity in infants of substance-abusing mothers.

OBJECTIVE: To determine whether there is a demonstrable abnormality in control of breathing in infants of substance-abusing mothers during the first few days of life. METHODS: We enrolled 12 drug-free control infants and 12 infants of substance abusing mothers (ISAMs). These infants experienced otherwise uncomplicated term pregnancies and deliveries. The infants were assigned to a group based on the results of maternal histories and maternal and infant urine toxicology screens. Studies were performed during quiet sleep during the first few days of life. We measured heart rate, oxygen saturations via a pulse oximeter, end-tidal carbon dioxide (ET-CO2) level, respiratory rate, tidal volume, and airflow. The chemoreceptor response was assessed by measuring minute ventilation and the ET-CO2 level after 5 minutes of breathing either room air or 4% carbon dioxide. RESULTS: The gestational ages by obstetrical dating and examination of the infants were not different, although birth weights and birth lengths were lower in the group of ISAMs. Other demographic data were not different, and there were no differences in the infants' median ages at the time of study or in maternal use of tobacco and alcohol. The two groups had comparable baseline (room air) ET-CO2 levels, respiratory rates, tidal volumes, and minute ventilation. When compared with the group of ISAMs, the drug-free group had markedly increased tidal volume and minute ventilation on exposure to 4% carbon dioxide. These increases accounted for the difference in sensitivity to carbon dioxide, calculated as the change in minute ventilation per unit change in ET-CO2 (milliliters per kg/min per mm Hg). The sensitivity to carbon dioxide of control infants was 48.66 +/- 7.14 (mean +/- SE), whereas that of ISAMs was 16.28 +/- 3.14. CONCLUSIONS: These data suggest that ISAMs are relatively insensitive to challenge by carbon dioxide during the first few days of life. We speculate that this reflects an impairment of the chemoreceptor response.

Breath Tests↗

Drug-using and nonusing women: potential for child abuse, child-rearing attitudes, social support, and affection for expected baby.

Eighty pregnant women (25 substance using, 55 nonusing) from an American prenatal clinic serving lower-income to working-class women responded to questionnaire measures of child-rearing attitudes. The drug users' primary substance of misuse was cocaine (68%), alcohol (16%), amphetamines (12%), or sedatives (4%); polydrug use was documented for 80% of the women. The two (user and nonuser) groups were not different on demographic (age, race, marital status, education, SES, source of income) or obstetrical factors (number of pregnancies, number of children). Drug-using women scored significantly higher on a measure of child abuse potential; more than half scored in the range of clinical criterion for extreme risk. As their babies were not yet born, no actual physical abuse was documented, only a higher potential for abuse. The subgroup who were both drug users and had lower social support scored higher on child abuse potential than all other subgroups. The drug users also had lower self-esteem scores than the nonusers. The two groups did not differ on measures of overall social support, authoritarian/democratic child-rearing beliefs, or affection for the expected baby.

Adult↗

Social support and anxiety in pregnant drug abusers and nonusers: unexpected findings of few differences.

Drug-abusing (n = 25) and nonusing (n = 55) pregnant women from a publicly supported prenatal clinic were tested for level of social support and of pregnancy anxiety during the last half of pregnancy. Differences found between the groups were fewer than expected. Drug abusers did not differ from nonusers in overall level of social support or in Appraisal, Belonging, or Tangible subscales. Abusers were found to report lower levels of self esteem; lower self esteem was predicted by drug abuse, having more children and lower socioeconomic status. Drug abusers did not differ from nonusers in their overall feelings of pregnancy anxiety, but they did indicate higher fears for themselves and for the baby, and there was a tendency for higher depression and withdrawal.

Adolescent↗

Perinatal substance abusers. Psychological and social characteristics.

Forty perinatal substance abusers were administered multiple psychosocial, addiction, and psychological measures before beginning treatment. Results indicate that these patients are limited intellectually, educationally, financially, and emotionally. Psychiatric comorbidity was high, with 45% having non-substance abuse axis I diagnoses and 75% having confirmed (by two or more tests) axis II pathology. The most frequently identified axis I disorders were depression and anxiety. The most frequently detected personality disorders were antisocial, borderline, paranoid, and dependent. The average IQ was 87 (low average range) and nearly one third of the sample were found to be somewhat impaired intellectually. These data suggest that treatment programs must take psychological characteristics into account if they are going to succeed in helping these women achieve and maintain abstinence.

Anxiety Disorders↗

Effects of ethanol and toluene on fixed-ratio performance in short sleep and long sleep mice.

This study examined the effects of ethanol (EtOH) and toluene on fixed-ratio (FR) responding in mice selectively bred for sensitivity to the effects of EtOH on sleep time. Although the more sensitive long sleep (LS) mice showed greater EtOH-induced impairment in a motor performance task than did the less sensitive short sleep (SS) mice, changes in FR performance in the two lines did not differ in response to EtOH, regardless of route (oral or intraperitoneal) or time (40 vs. 60 min pre-session) of administration. These results emphasize the importance of considering task variables in determination of the behavior of different genotypes. In contrast to results with EtOH, the volatile inhalant toluene produced different effects on FR responding in the selected lines, with SS mice being more sensitive than LS mice.

Administration, Inhalation↗

Electroencephalographic sleep and mood during cocaine withdrawal.

We report on nine patients between the ages of 21 and 39 years who were admitted to an inpatient substance abuse treatment unit for cocaine treatment. The patients' sleep was studied in the laboratory for 4 nights during the first week, and 2 nights during the second and third weeks of their hospitalization. Daily mood ratings, cocaine craving scores and sleep logs were also recorded on each patient. During the first week of withdrawal, these patients had a markedly shortened REM latency, an increased REM sleep percentage, a very high REM density and a long total sleep period time. During the third week, REM latencies were very short and total percentage of REM sleep was increased. By week three of withdrawal the sleep continuity pattern was similar to that found in chronic insomnia, with a long sleep latency, an abnormally increased total time awake after sleep onset and a poor sleep efficiency. The subjects' ratings of cocaine craving, total POMS scores and depression fell precipitously after the first week of withdrawal and were at sub-clinical levels by week three of withdrawal.

Adult↗

Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use.

OBJECTIVES: To compare the efficacy of structured questionnaire screening and prenatal urine toxicology for the detection of substance use by pregnant women, and to describe substance use patterns in a group of women presenting to a university-based obstetric clinic. METHODS: All patients presenting to our obstetric clinic for their first prenatal visit were evaluated for evidence of current use of alcohol or any illicit substances. Nursing personnel administered an extensive questionnaire, which included detailed questions about past and current substance use patterns. Urine samples were examined by a commercial laboratory for alcohol and a number of illicit substances. Current users were defined as those who admitted use within the past 30 days or who had positive urine toxicology. RESULTS: Fifty-eight of 302 patients (19.2%) were identified as current users of alcohol or illicit substances. Only 17 of 41 women (41.5%) with toxicologic evidence of recent use admitted to current use. Only 17 of 34 (50.0%) admitting to current use had toxicology positive for any substance. Patients with a history of multiple past substance use were significantly more likely to have positive urine toxicology than those without such a history (26.1 versus 7.4%; P < .005). Among current users, multiple substance use (34.5%) and cigarette smoking (52%) were common. CONCLUSION: A screening combination of structured questionnaire and universal urine toxicology identifies more current users than either technique alone, and neither is clearly superior to the other. A history of multiple substance use may be an important indicator of current use.

Adolescent↗

Adaptation of body temperature and nociception to cold stress in preweanling rats.

In order to investigate the response of rat pups to stress, 10-day-old rats (N = 10) were exposed to cold water (14 degrees C) for 5 min or to a control treatment (N = 10) for 5 consecutive days. On the sixth day when the rats were 15 days of age, all rat pups were immersed in cold water for 5 min. Body temperature and nociceptive threshold were recorded as functional indexes of the stress response to cold water. Results revealed that the rat pups that had been previously exposed to the cold stressor demonstrated a smaller decline in body temperature and a smaller increase in nociceptive threshold following cold-water immersion than rat pups which had no prior experience with the stressor. Thus, as measured by thermoregulatory and nociceptive function, 15-day-old rat pups are capable of adapting to repeated stressful experiences.

Acclimatization↗

Assessment of the abuse potential of acetorphan, an enkephalinase inhibitor.

The discriminative stimulus properties, reinforcing effects and physical dependence potential of acetorphan, a parenterally-active enkephalinase (E.C. 3.4.21.11) inhibitor, were assessed in the present studies. Rats trained to discriminate 2 mg/kg morphine from saline did not generalize to acetorphan at any dose tested (5-50 mg/kg). Acetorphan also had minimal reinforcing effects in rhesus monkeys. When acetorphan was substituted for cocaine, one dose (300 micrograms/kg per inj.) maintained responding somewhat above the range of vehicle values in only two of the four monkeys tested. In physical dependence studies, acetorphan also failed to produce opioid-like effects. In morphine-dependent monkeys and rats, acetorphan failed to suppress withdrawal. Additionally, there were no overt withdrawal signs observed following the termination of chronic acetorphan infusion in the rat. Together, these results indicate that acetorphan appears to have minimal abuse potential.

Animals↗

Developmental aspects of nociception.

Research has documented the existence of multiple, endogenous systems that modulate nociception. Based on the effects of opioid antagonists and endocrine lesions, endogenous analgesia systems have been organized into four classes: neural-opioid, neural-nonopioid; hormonal-opioid; hormonal-nonopioid. Developmental research on the ontogeny of endogenous analgesic function has revealed differential rates of maturation. Front-paw shock, a stimulus that activates a neural-opioid analgesic response, has been shown to be functionally mature by 28 days of age in the rat. Similarly, hind-paw shock, a stimulus that elicits a neural-nonopioid analgesic response, reaches maturity after two months of age. However, the hormonal-opioid analgesic system activated by cold-water immersion reaches adult levels by 10 days of age. Food deprivation produces a hormonal-opioid analgesic response in adult rats, and food deprivation/isolation of rat pups has been found to elicit an analgesic response in 6-day-old rats. From these data it seems that the rate of development of the different endogenous analgesic systems is related to the activation of neural or hormonal components. Whether the differential rates of development and the neural-hormonal distinction are related to the ecological validity of the activating stimulus remains to be determined.

Aging↗

Discriminative stimulus properties of toluene in the mouse.

Little is known about the nature of the acute intoxication produced by exposure to high concentrations of toluene such as that which occurs with spills and in solvent abusers. The intoxication may be similar to that produced by classic central nervous system depressants such as the barbiturates. To investigate this hypothesis, drug discrimination procedures were used to compare the acute effects produced by toluene and pentobarbital (PB). Mice were trained to discriminate toluene (100 mg/kg, ip) from vehicle in a two-lever task in which responding was under the control of a fixed-ratio 20 (FR20) schedule of food presentation. Generalization tests were conducted after 20-min inhalation exposures to toluene (150-3600 ppm) and 20 min after injections with either PB (5-30 mg/kg) or morphine (3-20 mg/kg). Most mice generalized to inhaled toluene and to PB in a concentration- or dose-related fashion, but not to morphine. These results show that the effects of injected toluene can be established as a discriminative stimulus in mice, and that these stimulus effects are independent of route of administration. Shared discriminative stimulus properties with PB suggest that toluene produces an acute intoxication like that of other classic CNS depressants.

Administration, Inhalation↗

Developmental differences in the analgesia produced by the central cholinergic system.

In order to study the ontogenesis of cholinergically mediated analgesia in the central nervous system (CNS), 10-day-, 28-day-, and 3-month-old rats were injected with .025, .05, and .10 mg/kg of oxotremorine, a muscarinic receptor agonist. To restrict the effect of oxotremorine to the CNS, methylscopolamine, a peripheral muscarinic antagonist, was injected simultaneously (.19 mg/kg, a dose equimolar to .10 mg/kg of oxotremorine). Following drug injections the tail-flick procedure was used to assess analgesia. Results revealed that oxotremorine was completely ineffective in producing analgesia in the 10-day- and 28-day-old age groups. By 3 months of age oxotremorine produced a dose-dependent analgesia. Since most neurochemical markers of cholinergic receptor function are at mature or near mature levels by 28 days of age, neurochemical indexes of receptor function overestimate the analgesic function of the central cholinergic system.

Age Factors↗

Ontogeny of an endogenous, nonopioid and hormonally mediated analgesic system.

Rats of different ages (10-day, 28-day, and 3-month-old) were exposed to cold-water stress in order to activate an endogenous analgesic system. The effects of naltrexone (7 mg/kg) and dexamethasone (.4 mg/kg) were also studied to examine the role of the opioid and hormonal systems in cold-water-induced analgesia. Following cold-water exposure, nociception was measured with the tail-flick procedure for 2 hr. Results revealed that cold water produced a significant level of analgesia in the 10-day, 28-day, and 3-month-old age groups with no differences between age groups. In addition, in each age group naltrexone did not block the analgesia while dexamethasone attenuated the analgesia produced by cold water. The effects of naltrexone and dexamethasone confirm that cold-water immersion activates a nonopioid, hormonally mediated analgesic system in each age group. Thus, this experiment found that the endogenous, nonopioid, and hormonally mediated analgesic system activated by cold water is functional early in the development of the rat. The early development of this hormonally mediated analgesic system is in contrast to the slower development of endogenous analgesia systems that are mediated by the central nervous system.

Aging↗

Pentobarbital-like discriminative stimulus properties of halothane, 1,1,1-trichloroethane, isoamyl nitrite, flurothyl and oxazepam in mice.

Volatile inhalants represent a diverse group of chemicals which pose a public health problem because of their abuse potential and neurobehavioral toxicity. Although relatively little is known about their pharmacology, they share certain pharmacological properties with classic central nervous system depressants. Drug discrimination procedures were used to compare the effects produced by pentobarbital (PB), oxazepam and several inhalants. Mice were trained to discriminate PB from saline injections in a two-lever operant task. Stimulus generalization was examined after 20-min inhalation exposures to halothane (500-8000 ppm), 1,1,1-trichloroethane (500-12000 ppm), isoamyl nitrite (150-1050 ppm), flurothyl (562-1300 ppm) and injections of oxazepam (0.1-20 mg/kg). Halothane, 1,1,1-trichloroethane and oxazepam produced discriminative stimulus effects similar to those produced by PB. Isoamyl nitrite and flurothyl, while decreasing rates of responding, were not consistently generalized from PB. Differences are apparent in the PB-like discriminative effects of inhalants. Toluene, as shown in a previous study, as well as halothane and 1,1,1-trichloroethane have PB-like discriminative effects which are also shared by oxazepam and may be another common effect of central nervous system depressants. Other chemicals, like isoamyl nitrite and flurothyl, are representative of qualitatively different classes of behaviorally active inhalants.

Administration, Inhalation↗