[Substitution with thyroid hormones in the elderly : Goals and risks]. / Substitution mit Schilddrüsenhormonen im höheren Lebensalter : Ziele und Gefahren.

Substitution with thyroid hormones is indicated in elderly patients with overt hypothyroidism, especially, when they present with typical symptoms of hypothyroidism. In light of the current study situation, the use of levothyroxine to treat clinical hypothyroidism in elderly patients is still controversial. In a recent double-blind, randomized, placebo-controlled study, levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. The impact of levothyroxine therapy in patients with subclinical hypothyroidism on cardiovascular risk is not completely clear. Levothyroxine treatment is safe and free of side effects, when the thyroid-stimulating hormone (TSH) levels remain within the normal range. Prescription of levothyroxine in patients with only slightly elevated TSH levels often leads to overtreatment, which is associated with an increased risk of fractures, neurological and psychological symptoms, and atrial fibrillation. The recommendations of the European Thyroid Association is to treat elderly patients only when the TSH value is greater than 10 mU/l and the patient is symptomatic or the patient has a high cardiovascular risk. The therapeutic TSH range in elderly patients in the case of levothyroxine treatment should be 1.0-5.0 mU/l. Follow-up of the TSH level is mandatory in order to not oversee a developing overt hypothyroidism and to avoid overtreatment in case of levothyroxine treatment.

Cross talk between stimulated NF-kappaB and the tumor suppressor p53.

Nuclear factor-kappaB (NF-kappaB) and p53 critically determine cancer development and progression. Defining the cross talk between these transcription factors can expand our knowledge on molecular mechanisms of tumorigenesis. Here, we show that induction of replicational stress activates NF-kappaB p65 and triggers its interaction with p53 in the nucleus. Experiments with knockout cells show that p65 and p53 are both required for enhanced NF-kappaB activity during S-phase checkpoint activation involving ataxia-telangiectasia mutated and checkpoint kinase-1. Accordingly, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) also triggers formation of a transcriptionally active complex containing nuclear p65 and p53 on kappaB response elements. Gene expression analyses revealed that, independent of NF-kappaB activation in the cytosol, TNF-induced NF-kappaB-directed gene expression relies on p53. Hence, p53 is unexpectedly necessary for NF-kappaB-mediated gene expression induced by atypical and classical stimuli. Remarkably, data from gain- and loss-of function approaches argue that anti-apoptotic NF-kappaB p65 activity is constitutively evoked by a p53 hot-spot mutant frequently found in tumors. Our observations suggest explanations for the outstanding question why p53 mutations rather than p53 deletions arise in tumors of various origins.

Social competence and emotional/behavioural problems in children of psychiatric inpatients.

The social competence and emotional/behavioural problems among 80 5-16-year-old children of 46 inpatients with various psychiatric disorders were assessed by the parents using a Swedish version of the Child Behavior Checklist (CBCL). The ratings of these children were compared to a normative sample of school children, but also whether type of psychiatric disorder among the parents was related to psychosocial functioning in their children. Fifty percent of the parents had a psychotic disorder; other common diagnoses were depressive, neurosis or personality disorders. Overall, children of psychiatric inpatients were perceived by the parents to be less socially competent and to have more emotional/ behavioural problems than school children in the same age groups. However, 25% of the children of psychiatric parents were rated as having more severe problems (corresponding to the 90th percentile of the normative sample). About 15% of the children had total problem levels comparable to child psychiatric samples, but only 5% did actually receive ongoing help from the child psychiatric service. Parents with a depressive disorder or a crisis reaction also regarded their children to be more anxious/depressed, and to have more social problems than those of parents with other psychiatric disorders. Four CBCL items were found to be strong predictors of being a child of a psychiatric parent or parent in the normative sample. We suggest that the CBCL might be a valuable clinical tool in the screening and identification of those children of psychiatrically ill parents, who show more extreme problem scores and therefore might need help because of psychological problems.