Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder.

Although some areas of adult ADHD knowledge remain unclear, there isa strong sense of how to proceed with diagnosis using current DSM-IV criteria as a guide. Thorough clinical interview, aided by the use of rating scales for current symptoms and collateral information about childhood from parents or siblings, forms the backbone of the assessment. The poor psychosocial outcomes of patients with ADHD. often a consequence of unrecognized,untreated disorder manifestation, also can serve as a diagnostic indicator. Diagnostic and symptom assessment scales also can be a significant helpin diagnosing and establishing the symptoms of ADHD in adults. It is important to remember that according to DSM-IV, the cardinal criteria for making the diagnosis are the presence of sufficient current symptoms and impairment in two realms (home, school/work, and social interactions). Accordingly, adult ADHD remains a clinical diagnosis, and the clinician-administered interview remains the cornerstone of diagnostic evaluation.     

In vivo and in vitro rat model for cyclosporine-induced proximal tubular toxicity

Cyclosporine is used widely to prevent transplant rejection. Unfortunately, this drug causes both renal glomerular and tubular damage. To develop a stable reproducible noncatabolic animal model of cyclosporine nephrotoxicity, rats were fed a special liquid diet and daily administered 7.5 mg/kg of cyclosporine intramuscularly. Twenty-one days after this regimen was started, the body weight of cyclosporine-treated rats had increased 15%, a value only 38% less than the increase in pair-fed controls. After 21 days, glomerular filtration rate fell 34% in cyclosporine-treated rats (p less than 0.001) compared with the pair-fed controls. Simultaneously, citrate and N-acetylglucosaminidase excretion increased significantly. When isolated proximal tubules obtained after 21 days from the cyclosporine and pair-fed rats were incubated by using 1.0 mmol/L glutamine and 1.0 mmol/L citrate substrates, ammonia production was reduced 40% and glucose production reduced 20% (p less than 0.001) in the cyclosporine-treated rats. Discontinuing cyclosporine for 7 days partially reversed all these changes. The glomerular filtration rate in cyclosporine-treated rats now was only 15% below that in controls (p less than 0.05), N-acetylglucosaminidase excretion was the same in both groups, and urinary citrate excretion in the cyclosporine-treated rats fell from 122% to 62% above that in controls. In vitro differences in tubular ammonia and glucose production also narrowed. In summary, these experiments describe a stable reproducible noncatabolic and at least partially reversible rat model for studying cyclosporine nephrotoxicity.     

Codistribution of a sensory gating deficit and schizophrenia in multi-affected families.

Because the clinical diagnosis of schizophrenia has not generally been an adequate phenotypic marker to detect the genes that convey risk for schizophrenia, efforts have been directed toward the identification of more elementary neuronal dysfunctions in schizophrenic patients and their families. Psychophysiological studies of sensory gating and selective attention suggest that defects in these brain functions are present in schizophrenic patients and some of their relatives. This study examines one of these defects in sensory gating, failure to suppress the P50 evoked response to repeated auditory stimuli. Six pedigrees, chosen because of the presence of large sibships containing several cases of schizophrenia, were studied. A mathematical model was developed to assess the familial association of the P50 defect with schizophrenia. The model preserves the quantitative nature of the data and is suitable for use in a sample with small numbers of pedigrees comprising many individuals. It is thus suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers. The results suggest that the P50 defect is familially associated with schizophrenia.     

Early Intervention for Trauma: Current Status and Future Directions

Although psychological debriefing (PD) represents the most common form of early intervention for recently traumatized people, there is little evidence supporting its continued use with individuals who experience severe trauma. This review identifies the core issues in early intervention that need to be addressed in resolving the debate over PD. It critiques the available evidence for PD and the early provision of cognitive-behavioral therapy (CBT). Based on available evidence, we propose that psychological first aid is an appropriate initial intervention, but that it does not serve a therapeutic or preventive function. When feasible, initial screening is required so that preventive interventions can be used for those individuals who may have difficulty recovering on their own. Evidence-based CBT approaches are indicated for people who are at risk of developing posttraumatic psychopathology. Guidelines for managing acutely traumatized people are suggested and standards are proposed to direct future research that may advance our understanding of the role of early intervention in facilitating adaptation to trauma.     

Gating of the Auditory Evoked Potential in Children and Adults

Auditory evoked potentials were recorded from 163 subjects, aged IS months to 55 years. A conditioning-testing paradigm was used to assess sensory gating. In this paradigm, click stimuli are presented in pairs to the subjects with a 0.5-second intrapair interval. In normal adults, the first stimulus activates or “conditions” sensory gating mechanisms. The strength of these mechanisms is “tested” by the second stimulus, which produces a response whose amplitude is significantly suppressed. This aspect of sensory gating was not reliably observed in our subjects until age 18 years. Younger subjects varied widely in their ability to demonstrate sensory gating. Mean levels of suppression increased during late childhood and adolescence, with no relationship to other changes in evoked potential amplitude and latency. Sensory gating would appear to be a late developing aspect of human sensory physiology.     

Time trends of haemologbin levels and anaemia prevalence in infancy in a total community

In order to determine the trends in haemoglobin (Hb) levels and the prevalence of anaemia in infancy in an entire community, 3,147 infants aged 9-11 months attending the Mother and Child Health Clinics of the teaching and research Health Center in Kiryat Hayovel, Jerusalem, were examined. From 1971 to 1979 infants diagnosed as anaemic were given treatment. From 1980 to 1988 supplement was given to all infants from the age of 3 to 12 months. There was a mean increase of 0.6 g/dlHb between the two periods, with a larger increase in the Hb levels in 1980-88 as compared to 1971-79 (P = .0001). The prevalence of anaemia less than 11 g/dlHb decreased from 36% in 1971 to 27% in 1979 and to 19% in 1988. The prevalence of anaemia less than 10 g/dlHb decreased from 13.7% in 1971 to 8.7% in 1979 and to 3.6% in 1988. The time trend is probably due to changes in the socio-demographic characteristics of the population, an overall change in infant feeding practices in relation to iron source and the supplementation programme.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Childhood through the eyes of child psychiatrists and paediatricians.

Attitudes to childhood in general and towards one's own childhood in particular are compared in a survey of 152 Australian and New Zealand child psychiatric and paediatric trainees. Results confirm the findings of Enzer et al that paediatricians view childhood more positively than do child psychiatrists. Although there is a significant difference between the two groups on measures of their perceptions of the parenting they received with child psychiatrists rating their own parents as less caring than do paediatricians, there is no relationship between attitudes to childhood and perceptions of the parenting they received. Implications of these findings are examined, both in terms of motivation for choosing one or other specialty and for the working relationship between the two professions.