Interscorers' agreement of the human figure drawings with a referred group of children.

Agreement of two scorers using the Koppitz scoring system for emotional indicators on the Human Figure Drawings with 30 subjects randomly chosen from 132 students referred for special education services was .85. Implications for clinicians using the Human Figure Drawings in a battery of tests are discussed.

Pharmacokinetic features, immunogenicity, and toxicity of B43(anti-CD19)-pokeweed antiviral protein immunotoxin in cynomolgus monkeys.

We studied the pharmacokinetic features, immunogenicity, and toxicity of B43-pokeweed antiviral protein (PAP) immunotoxin in 13 cynomolgus monkeys. The disposition of B43-PAP in two monkeys, when administered as a single i.v. bolus dose, was characterized by a slow clearance (1-2 ml/h/kg) with a very discrete peripheral distribution. B43-PAP was retained and distributed largely in the blood as the sole compartment with no significant equilibration with the extravascular compartment. The circulating B43-PAP immunotoxin detected in monkey plasma samples by ELISA and protein immunoblotting was both immunoreactive with, and active against, human leukemic cells in vitro. In systemic immunogenicity and toxicity studies, which involved 11 cynomolgus monkeys, each monkey received a total of seven i.v. doses of B43-PAP at a specific dose level of the dose escalation schedule. B43-PAP-treated monkeys mounted a dose-dependent humoral immune response against both the mouse IgG and PAP moieties of the immunotoxin. When administered i.v. either on an every-day or every-other-day schedule, B43-PAP was very well tolerated, with no significant clinical or laboratory signs of toxicity at total dose levels ranging from 0.007 to 0.7 mg/kg. A transient episode of a mild capillary leak with a grade 2 hypoalbuminemia and 2+ proteinuria was observed at total dose levels equal to or higher than 0.35 mg/kg. At total dose levels of 3.5 and 7.0 mg/kg, B43-PAP caused dose-limiting renal toxicity due to severe renal tubular necrosis. The present study completes the preclinical evaluation of B43-PAP and provides the basis for its clinical evaluation in children with therapy-refractory B-lineage acute lymphoblastic leukemia.

Relation of scores on WISC-III and WRAT-3 for a sample of referred children and youth.

This investigation compared the Wechsler Intelligence Scale for Children-III with the Wide Range Achievement Test-3 for a sample of 60 children and youth who were referred for special education services. Pearson product-moment correlations for the criterion measures for the WRAT-3 showed a significant positive association with the WISC-III scores. Implications for concurrent validity between the tests are discussed.

Differences in levels of parental stress among mothers of learning disabled, emotionally impaired, and regular school children.

This study examined the stress among mothers of children in regular and special education. The sample of 45 mothers had children enrolled in public schools from Kindergarten to Grade 8. To three groups, Group 1 of mothers with children in regular education, Group 2 of mothers with children classified as learning disabled, and Group 3 of mothers with children classified as emotionally impaired, the Parenting Stress Index was given to examine whether differences in stress among groups were significant. An analysis of variance and Tukey's HSD indicated significant differences in the Child Domain and on certain child subscales (Acceptability, Mood, Distractibility, Reinforcement), with Group 3 scoring significantly higher than Group 1. Groups 2 and 3 scored significantly higher on the Total Child Domain than Group 1. Group 3 also scored higher than Group 1 on the Parent Domain and on the sum of both domains.

The pharmacokinetics and absorption of recombinant human relaxin in nonpregnant rabbits and rhesus monkeys after intravenous and intravaginal administration.

Recombinant human relaxin (rhRlx) is being developed as a potential cervical ripening agent to be applied intravaginally or intracervically prior to parturition. The pharmacokinetics and absorption of rhRlx were determined in nonpregnant female rabbits and rhesus monkeys after intravenous bolus (iv) and intravaginal administration of 0.1 mg/kg; additionally, rabbits were dosed with 0.5 mg/kg intravaginally. In rabbits (n = 6), mean (+/- SD) peak concentrations following iv bolus administration were 1554 +/- 296 ng/mL. The weight-normalized clearance (CL/W) was 5.9 +/- 0.4 mL/min/kg, initial volume of distribution (V1/W) was 57 +/- 9 mL/kg, and volume of distribution at steady state (Vss/W), assuming central compartment elimination, was 240 +/- 20 mL/kg. Vss/W could be as large as 2000 +/- 400 mL/kg without this assumption. The estimated amounts of rhRlx absorbed in rabbits following intravaginal administration of 0.1 and 0.5 mg/kg (n = 5/dose) were 3.1 +/- 1.4 and 0.7 +/- 0.3%, respectively; peak concentrations were 600 +/- 297 and 1066 +/- 584 pg/mL, respectively. In rhesus monkeys (n = 5) after iv administration, peak concentrations were 971 +/- 277 ng/mL; CL/W was 4.1 +/- 0.6 mL/min/kg, V1/W was 78 +/- 25 mL/kg, and Vss/W, assuming central compartment elimination, was 690 +/- 220 mL/kg. The upper limit for Vss/W was 1600 +/- 200 mL/kg when no assumptions were made regarding site (compartment) of elimination. After intravaginal administration (n = 6), two monkeys had undetectable rhRlx concentrations throughout the 48-hr sampling interval; one monkey had only one sample containing measurable rhRlx (51 pg/mL) at 24 hr; and three monkeys absorbed < 2% of the 0.1 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Differentiation of Alzheimer and cerebrovascular patients with the Minnesota Percepto-Diagnostic Test--Revised.

60 adult patients with focal cerebrovascular accidents (30 with left cerebral hemisphere lesions, 30 with right cerebral lesions) and 30 adults with Alzheimer disease were compared to 30 normal adults on the Minnesota Percepto-Diagnostic Test--Revised (MPD--R). The regular scoring variables plus the two-step method of diagnosis for brain damage with the MPD--R were used. One-way analyses of variance with age and mental status as covariates yielded a significant difference between control subjects and brain-damaged patients on most of the MPD--R variables. The controls scored the best, followed by the Alzheimer and cerebrovascular groups. Planned comparisons for cerebrovascular vs Alzheimer subjects were significant across all MPD--R scores except distortion of dots; the Alzheimer subjects scored better than the cerebrovascular subjects. The two cerebrovascular groups were not differentiated by the MPD--R scoring variables. The MPD--R correctly identified 96% of each of the two brain-damaged groups and 70% of the control group. Findings are described in terms of the utility of the MPD--R in differential diagnosis with elderly populations.

Differential diagnosis of disturbed adolescents with the Minnesota Percepto-Diagnostic Test-Revised.

Two groups of psychiatric adolescent patients (19 schizophrenics, 22 nonschizophrenics) on an acute inpatient ward of a general hospital were compared for their performance on the Minnesota Percepto-Diagnostic Test--Revised. The effects of admission on test performance were also investigated. Results supported the efficacy of the test in differentiating between the two groups. The schizophrenic adolescents scored significantly less well (higher rotation scores) than the nonschizophrenics. It was shown that the groups' test performance significantly improved from admission to nine days later.

Visual-motor ability of children with articulation disorders.

The present study was done to assess differences between children with diagnosed functional articulation disorders and a control group on the variable of visual-motor ability. A group of 34 elementary children with articulation problems were matched with a control group of 34 for sex, age, and grade. Both groups were administered the Goldman-Fristoe Test of Articulation and the Minnesota Percepto-Diagnostic Test--Revised. Analysis indicated that children with articulation problems performed significantly lower on visual-motor skills.

Role of endogenous opiates in the modulation of gonadotropin secretion in infant monkeys (Macaca mulatta): effects of naltrexone.

A potential inhibitory role of endogenous opioids in the gonadotropin decline from infancy to the prepubertal period in primates was assessed by examining the effect of the specific opioid antagonist naltrexone on gonadotropin levels in infant rhesus monkeys. Paradoxically, both chronic administration of naltrexone to neonatally castrate males as well as acute administration of graded doses to intact infant females resulted in gonadotropin suppression compared to appropriate vehicle-treated controls. Thus, naltrexone behaves as a gonadotropin secretory antagonist in infant monkeys and cannot be used to unmask a putative inhibitory mechanism involving endogenous opiates.

Gonadotropin responsiveness to estrogens and low-level progesterone in the ovariectomized rhesus monkey.

When estrogen is administered to gonadectomized rhesus monkeys in sufficient quantity, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are initially suppressed and gonadotropin secretion is subsequently augmented. This study was designed to examine the ability of various orally administered estrogens to elicit biphasic pituitary responses in adult castrate rhesus monkeys and to investigate the role of low-level progesterone in altering these responses. In an incomplete block design, 13 treatments were constructed: (E2): 0.5, 5.0, 50 micrograms/kg; (DES): 0.05, 0.5, 5.0 micrograms/kg; zearalenone (Z): 10, 100, 1000 micrograms/kg; or oil vehicle, each combined with progesterone. The remaining treatments (5.0, 0.5, and 100 micrograms/kg of E2, DES, and Z, respectively) did not include progesterone. During six intervals, E2, DES, or Z was administered orally on Days 1, 2, and 3 and blood was sampled on Days 0, 3, and 8 of each period. A main effect of estrogen treatment was observed for LH and FSH secretion on Day 3 but not Day 8. There was no main effect of progesterone alone on release of either LH or FSH on days 3 or 8, nor were significant carry-over effects of progesterone, E2, DES, or Z on LH or FSH concentration apparent by Day 8 of any treatment. However, progesterone synergized with E2 to suppress Day 3 LH levels. Conversely, DES and Z interacted with progesterone to facilitate LH secretion at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term testosterone exposure on ovarian function and morphology in the rhesus monkey.

This study was aimed at developing a model in the rhesus monkey for the human gynecologic disorder termed the polycystic ovary syndrome (PCOS). The effects of chronic constant androgen exposure upon quantitative ovarian morphology and ovulatory function were examined. Twenty-five normally cycling females, aged 4-12 yr and weighing 3.3-8.2 kg, were enrolled in the study in random fashion. Seventeen animals were implanted subcutaneously (s.c.) with 10 or 25 mg testosterone-filled silastic tubing so as to maintain steady serum levels of testosterone averaging 80 ng/dl (low-dose group, n = 8) and 115 ng/dl (high-dose group, n = 9) for 13-16 months. Eight animals served as controls (sham implants); in these, mean serum testosterone levels averaged 24 ng/dl. No effect of androgen treatment was observed on ovulatory function as gauged by periodic luteal phase progesterone determinations and the presence of a fresh corpus luteum at laparoscopy. Menstrual cycle frequency (number of cycles over number of months of observation) was, however, slightly but significantly (P less than 0.05) reduced in the high-dose (88.9%) vs. the control (96.7%) and low-dose (95.0%) groups. Quantitative morphology, performed by light microscopy on a single ovary obtained from 16 of the 25 animals and read in a blinded fashion, revealed no differences in ovarian weight, capsular width and numbers, size, or proportion of healthy and atretic follicles among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine.

Two forms of human GH (hGH) have been produced by recombinant DNA technology. One form has an amino acid sequence identical to that of the natural pituitary hormone (rhGH) and the other form has an additional N-terminal methionine (Met-hGH). The biological potencies of these 2 polypeptides have been compared in hypophysectomized rats in a multidose study measuring body weights and several long bone growth parameters. The pharmacokinetic profiles after iv and sc injection were determined in cynomolgus monkeys in a 4-period cross-over study. All of the measured parameters in all the studies indicated that there was no difference in the two forms of hGH. Measurements taken after 27 daily injections of rhGH or Met-hGH (30-500 micrograms/kg.day) indicated that femur length and width of the proliferative zone in the tibial epiphysis showed dose-related effects for both forms of hGH but no difference between them. The relative potency, based on body weight gain, was calculated using a parallel line bioassay. Weight gain after 8 daily injections in the 5-dose long bone growth study indicated a rhGH potency of 0.80 (95% confidence interval, 0.5-1.23) relative to Met-hGH. It was concluded that the presence of an N-terminal methionine on hGH has no effect on potency in this model. The pharmacokinetic parameters after iv administration were estimated by fitting serum concentration-time data to a 2-compartment model. Parameters after sc injection were computed by compartment-independent methods. Met-hGH and rhGH had very similar pharmacokinetic profiles after both routes of administration. Comparison of the pharmacokinetic parameters indicated that the clearance after iv administration (rhGH, 15 ml/min; Met-hGH, 13 ml/min) and the sc bioavailability (rhGH, 0.72 +/- 0.21; Met-hGH, 0.59 +/- 0.21) were not significantly different for the 2 forms of hGH. It was concluded that rhGH and Met-hGH have equivalent bioavailability and pharmacokinetics in cynomolgus monkeys.

Pharmacokinetics of recombinant human interferon-gamma in the rhesus monkey after intravenous, intramuscular, and subcutaneous administration.

The pharmacokinetics of recombinant human interferon-gamma (rIFN-gamma) were studied in rhesus monkeys. Intravenous administration of 0.1 mg/kg yielded half-lives of 12.3-13.4 min and 130 min. Clearance after intravenous administration was 18.7 ml/min/kg, and the steady-state volume of distribution (Vdss) was 510 ml/kg. The peak serum concentrations after intramuscular and subcutaneous administration of 0.25 mg/kg rIFN-gamma were 50.7 and 52.3 ng/ml, respectively. The time to reach the peak serum concentration was 480 min for both routes. The mean bioavailabilities after intramuscular and subcutaneous administration were 109 and 90%, respectively. Intravenous administration of 0.25 mg/kg rIFN-gamma resulted in no significant change in the clearance, half-life, or Vdss, suggesting that the kinetics of rIFN-gamma are linear over the range of doses tested. Nearly all of the animals developed antibodies to rIFN-gamma after three doses. The presence of nonneutralizing antibodies to rIFN-gamma had no discernible effect on the calculated pharmacokinetic parameters.

The relationship between the Millon Clinical Multiaxial Inventory and the MMPI in a private outpatient mental health clinic population.

The concurrent validity of the MCMI as compared to the MMPI was assessed by administering both tests to 106 newly admitted outpatients and calculating the intercorrelations between these two tests. Of the 20 MCMI scales, 12 were found to correlate with the MMPI in a manner that suggested that they do measure some degree of personality dysfunction, emotional disturbance, or specific psychological symptomatology. Eight of the MCMI scales failed to show correlations that would indicate that they effectively measure any of the pathological personality characteristics or clinically significant symptom patterns known to be measured by the MMPI.

Influence of restraint and ketamine anesthesia on adrenal steroids, progesterone, and gonadotropins in rhesus monkeys.

Changes in gonadotropins, progesterone, cortisol, DHA, and DHAS were monitored in 10 female rhesus monkeys (Days 20-23 of the menstrual cycle) subjected to cage restraint with or without ketamine anesthesia for successive venipunctures. All animals were bled without sedation for 2 hr at 30-min intervals. Then 4 of the animals were anesthetized with ketamine-HCl and bleedings in all animals were continued for an additional 2.5 hr. FSH and progesterone were not appreciably affected by either restraint technique. LH declined steadily for the duration of the bleedings (P less than 0.05). Serum levels of cortisol and the adrenal androgens increased twofold (P less than 0.05). Anesthesia with ketamine had no effect on any of the six variables when compared with saline controls. Cortisol and dehydroepiandrosterone (DHA) levels tended to plateau (P less than 0.01) after 2 hr in both treated and control groups. In contrast, dehydroepiandrosterone sulfate (DHAS) levels increased continuously throughout the entire study period. These data indicate that ketamine anesthesia does not alter endocrine responses to venipuncture when administered following cage restraint of conscious animals. These findings further confirm the difficulties in obtaining estimates of basal levels of hormones which are responsive to stress and suggest that the first sample may provide the best estimate.