Pharmacokinetics and pharmacodynamics of orally administered clonidine: a model-based approach.

BACKGROUND/AIMS: The oral clonidine test is a diagnostic procedure performed in children with suspected growth hormone (GH) deficiency. It is associated with untoward effects, including bradycardia, hypotension and sedation. Serum clonidine levels have not previously been assessed during this test. METHODS: In 40 children referred for an oral clonidine test, blood samples were drawn for clonidine and GH. Vital statistics and sedation scores were recorded until 210 min post-dose. We explored the relationship between clonidine concentrations and effects such as GH peak and blood pressure. RESULTS: Of 40 participants, 5 children were GH deficient. Peak clonidine concentrations of 0.846 ± 0.288 ng/ml were reached after 1 h. Serum levels declined slowly, with concentrations of 0.701 ± 0.189 ng/ml 210 min post-dose. A large interindividual variation of serum levels was observed. During the procedure, systolic blood pressure dropped by 12.8%, diastolic blood pressure by 19.7% and heart rate by 8.4%. Moderate sedation levels were observed. Concentration-effect modeling showed that the amount of GH available for secretion as determined by previous bursts was an important factor influencing GH response. CONCLUSION: Clonidine concentrations during the test were higher than necessary according to model-based predictions. A lower clonidine dose may be sufficient and may produce fewer side effects.

Hyperechogenicity of the thalamus and basal ganglia in very preterm infants: radiological findings and short-term neurological outcome.

Cerebral ultrasound of preterm infants may show diffuse, bilateral, hyperechogenic "haze" over the thalami and basal ganglia (hyperechogenicity BGT). We explored whether this could be a pathological phenomenon. All cerebral ultrasound examinations performed in 2001 on infants < 35 weeks of age were reviewed. This resulted in a hyperechogenicity and non-hyperechogenicity group. The character of the hyperechogenicity BGT and the presence of concomitant brain lesions were noted. Detailed clinical and follow-up data from a selected group of infants < 32 weeks were reviewed and compared between the 2 groups. The incidence of hyperechogenicity BGT was 11 % (39/359) in infants < 35 weeks and 26 % (37/143) in infants < 32 weeks. Birth weight and gestational age were significantly lower and clinical course was more complicated in the hyperechogenicity group. Concomitant brain lesions were always present. In 12/39 infants with hyperechogenicity BGT, MRI (always performed for other reasons) was available, showing signal intensity changes in thalamic region in 5 infants. The neurological outcome at term was less favorable in the hyperechogenicity group, but similar at 1 year. Thus hyperechogenicity BGT mainly occurred in very small, sick infants and was always associated with cerebral pathology. MRI did not consistently show abnormalities in the thalamic region. It was not associated with a poorer outcome at 1 year.

Termination in group psychotherapy from the perspectives of contemporary object relations theory and self psychology.

Throughout the development of object relations theory and self psychology, the importance of attachments, availability, absences, limitations, and endings have been factors that have informed theory and practice. This article examines the multiple meanings and impacts of terminations in group psychotherapy at the intrapsychic, interpersonal, and group-as-a-whole levels, from the perspective of contemporary object relations theory and self psychology. Emphasis is placed on the initiation of a mourning process, with the dynamics of guilt, shame, and aggression toward objects who are separate or inaccessible, and the experience of a shortcoming or absence, associated with a loss of self-object oneness, soothing, and idealization from the narcissistic sector of the personality. Therapeutic opportunities afforded by terminations and the importance of resolving countertransference reactions are highlighted.

The Axis II group: treating severely characterologically disturbed patients.

Treating the chronically mentally ill involves not only working with patients suffering from schizophrenia and other prolonged or recurrent psychotic illnesses, it also means providing treatment for patients with severe personality disorders. Many of these patients are also active substance abusers. This article examines the therapeutic and management issues raised for outpatient clinicians who work with these patients. Consideration is devoted to the special problems in treating the dual diagnosis patient, issues of patient and therapist safety, limit setting, splitting dynamics, and countertransference reactions. A set of recommendations is offered for conducting outpatient group therapy, specifying what is needed from both the clinicians and the facility in which this type of treatment is provided.

The relationship between psychological distress and knowledge of disease among hemophilia patients and their families: a pilot study.

As part of a large scale, comprehensive study of the psychosocial functioning of hemophilic patients and their families, 12 pilot families were assessed using objective measures of psychiatric symptomatology and general knowledge of hemophilia. Although the small number of subjects in this pilot study precludes any detailed statistical analyses, some preliminary findings are presented concerning the level of psychological distress reported by patients and their family members and the subjects' level of general knowledge about hemophilia. Of most interest was the presence of significant negative correlations between knowledge of hemophilia and extent of self-reported psychological distress for mothers and patients under 15 yr of age. Maintenance of this relationship with a larger sample would have important implications for patient and family education.

Response-contingent learning in children at risk.

Ninety-nine male offspring at ages 7 and 10, from schizophrenic, affective psychotic, nonpsychotic patient, and normal control parents performed a nonsense syllable discrimination task administered under each of three reinforcement conditions: neutral information feedback, and two response-contingent conditions, praise and censure. Index (patient) parent diagnosis was determined using DSM-III criteria. Although the four groups did not differ significantly in mean number of errors in learning the task under the neutral condition, when reinforcement was provided by the subject's mother during both praise and censure conditions, schizophrenics' and nonpsychotic patients' offspring made significantly more errors than offspring of affective psychotics and normal controls. Either form of social reinforcement administered by the mother, or merely the mother's voice itself, had a disruptive effect on the learning efficiency of the offspring of schizophrenic and nonpsychotic patients. Chronicity and comprehensibility of these parent's disturbances are considered as possible explanations of their children's performance.

Habituation and conditioning of skin conductance responses in children at risk.

This investigation extends the findings reported by Salzman and Klein (1978) concerning the skin conductance response (SCR) of the offspring of parents who had been hospitalized for a psychiatric illness. Skin conductance during rest and during experiments testing habituation and conditioning of the SCR was recorded in 7-year-old (n = 42) and 10-year-old (n = 57) children. Among the 7-year-olds, 11 had a parent with a diagnosis of schizophrenia, 12 had a parent with a diagnosis of affective psychosis and 19 had a nonpsychotic parent. Among the 10-year-olds, the corresponding distribution was 13 (schizophrenic), 20 (affective), and 24 (nonpsychotic). The results indicate (1) no marked tendency toward either rapid or absent habituation in the offspring of schizophrenics; (2) evidence of significantly greater conditioning among the 10-year-old offspring of schizophrenics; (3) only very weak evidence of greater responsiveness to intense stimuli among the offspring of schizophrenics; (4) no evidence of differences in SCR recovery time among the three groups of children; and (5) differences between diagnostic groups among the 10-year-old children in the pattern of tonic skin conductance levels across experiments. Differences in results between the two age groups were unexpected, but may represent either heterogeneity of diagnosis in the parents or developmental trends in electrodermal activity in the children. In sum, the results of this study produce only partial confirmation of the findings reported in the earlier investigation.

The late positive component of the evoked response in acute schizophrenics during a test of sustained attention.

To investigate the relationship between behavioral and cortical measures of impaired attention in schizophrenia, 17 hospitalized acute schizophrenics and 16 hospitalized nonpsychotic patients were studied. Event-related potentials (ERP) were obtained while subjects performed the Continuous Performance Test (CPT) under three conditions: First base line, Auditory-Visual Distraction, and Second base line. Schizophrenics made more errors of omission and commission and had longer reaction times. Analysis of the Late Positive Component (LPC) of the ERP revealed that both groups had an attenuated LPC during distraction and a larger LPC to the critical compared to the noncritical stimulus throughout all conditions. Schizophrenics had a smaller LPC and a smaller amplitude difference between the critical and noncritical stimulus than the nonpsychotics throughout all conditions.