Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

Noonan's and DiGeorge syndromes with monosomy 22q11

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.     

Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used

Interleukin-10 (IL-10), a cytokine involved in many aspects of the immune response shows interindividual variations in their expression. However, genetic variations of the 5'-flanking region of the IL-10 gene (PIL-10) are poorly characterised with respect to different stimuli. New extended haplo- and genotypes are identified present at differing frequencies in three geographically separated populations. Their influence on IL-10 expression have been assessed in vitro after stimulation of leukocytes with lipopolysaccharide (LPS), dibutyryl-cAMP or following immortalisation with Epstein-Barr virus (lymphoblastoid cell line (LCL)). Interindividual differences of IL-10 production were found to be related to single-nucleotide polymorphisms (SNP) haplotype -6752/-6208 in LCLs (P<0.02), and for haplotypes comprising SNPs -6752/-6208/-3538 after LPS stimulation (P<0.03). Carriers of the IL10.G microsatellite with 22, 24 or 26 dinucleotide repeats linked with the -1087G SNP, exhibited the highest levels of IL-10 expression. Contrasting IL-10 secretion patterns were found for IL10.R microsatellite alleles characterised by 15 dinucleotide repeats: after LPS stimulation this allele was associated with high IL-10 production (P<0.007), but with low IL-10 levels in LCLs (P< 0.038). Thus, the effects of mosaics of genetic elements in the PIL-10 on the capacity of leukocytes to produce IL-10 depend on the agent inducing IL-10 expression.     

No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline

The polymorphic enzyme cytochrome P450 CYP2D6 is involved in the metabolism of many antidepressants, including nortriptyline and fluoxetine. Some 7%-10% Caucasians have inactivating mutations in both alleles of the CYP2D6 gene, and are referred to as poor metabolizers (PMs). Several case reports and clinical studies suggest that CYP2D6 PMs are at a greater risk of developing adverse drug reactions (ADRs) on antidepressant medication than extensive metabolizers (EMs). However, few clinical trials have investigated whether CYP2D6 PM genotype is predictive of ADRs during antidepressant treatment. This paper explores the link between CYP2D6 genotype and antidepressant-associated ADRs in outpatients being treated for major depression with either nortriptyline or fluoxetine. Patients were randomized to fluoxetine (n=65) or nortriptyline (n=60) for the 6 week trial. CYP2D6 genotypes predicted that of these patients 115 were EM and the remaining 10 were PMs. ADRs attributed to antidepressant usage were recorded over the 6-week trial. Although the type of ADR was, as expected, different between drugs, the frequency of ADRs experienced did not differ significantly between the two antidepressants or between CYP2D6 PMs and EMs. In addition, the frequency at which PMs discontinued antidepressant medication was not noticeably different from EMs, although with only 10 PMs the study is under powered to detect moderate or small differences. These findings suggest that inability to efficiently metabolize antidepressants that are CYP2D6 substrates does not necessarily lead to increased occurrence of antidepressant-associated ADRs. Thus, for clinicians prescribing antidepressant monotherapy, CYP2D6 polymorphisms are probably not of relevance to antidepressant side effects and therapy.     

Age may affect response to antidepressants with serotonergic and noradrenergic actions

BACKGROUND: Multiple lines of evidence suggest continuity from adolescent to adult depression, but treatment response is different in the two groups. There is some consensus that noradrenergic drugs are ineffective in adolescent depression. The aim of this study was to see whether this poor response extended to young adults. METHODS: Patients from two randomised studies on prediction of antidepressant response were used. The subjects were divided into a youth sample (ages 18-24) and an older sample (ages 25 and over). The 6-week percentage response, based on HDRS scores, and the number of patients in remission (i.e., HDRS < or =7) at 6 weeks were compared in subjects who received a serotonergic (clomipramine (mean dose 145 mg) and fluoxetine (mean dose 27 mg)) or a noradrenergic (desipramine (mean dose 200 mg) and nortriptyline (mean dose 100 mg)) antidepressant. RESULTS: There were no significant differences between the two studies, except for a small variation in baseline Hamilton scores. Young adults had a poorer response to noradrenergic antidepressants than they did to serotonergic antidepressants, whereas there was no differential response in the older age group. Young adults had a lower rate of remission on a noradrenergic antidepressant (38% noradrenergic versus 72% serotonergic) but there was no significant difference in remission rates in older adults (65% noradrenergic versus 57% serotonergic) or the sample as a whole (54% noradrenergic versus 62% serotonergic). LIMITATIONS: The age cut-off at 24 is somewhat arbitrary. One study was double-blind while the other was open. There was no placebo control. DISCUSSION: While the response rate to noradrenergic antidepressants in young adults is lower, it is not clear whether this is comparable to adolescents. The reasons for a reduced response may be related to maturation of the noradrenergic system in the brain. Our results suggest that age may be one factor to consider when choosing antidepressants for patients.     

Comparison between noradrenergic and serotonergic medications using the social adjustment scale: is drive enhancement necessary for recovery of social functioning?

The Social Adjustment Scale (SAS) was used to assess social functioning sequentially over 13 weeks in a group of 188 depressed outpatients randomized to either the noradrenergic antidepressant, nortriptyline, or the selective serotonin reuptake inhibitor, fluoxetine. Over the period of 13 weeks, there were no differences in total SAS scores between the nortriptyline and the fluoxetine group. In comparing the SAS subscale scores, which may measure different areas of motivation and behaviour (drive), there were differences between the two groups in only two subscales. At 13 weeks, the group randomized to fluoxetine were more impaired in marital role (p = 0.026) whereas, at 6 weeks, the group randomized to nortriptyline were more impaired in friction scores (p = 0.012). These results do not support the concept of specific augmentation of drive-related behaviour by noradrenergic medication. This challenges the earlier findings relating to drive enhancement and social adjustment using such medication.     

Childhood neglect and abuse as predictors of antidepressant response in adult depression

Background: Childhood neglect and abuse are recognized as risk factors for depression, but are not often studied as predictors of treatment response in depression. Methods: Clinically depressed outpatients (n=195) were asked about childhood experiences before beginning a randomized antidepressant trial with either fluoxetine or nortriptyline. Three treatment outcomes were measured: Adequate trial, six‐week response and two months sustained recovery. Results: Patients reporting low paternal care (paternal neglect), as measured by the Parental Bonding Instrument (PBI), were less likely to complete an adequate six‐week trial of medication. Patients who reported high maternal protection (maternal overprotection) on the PBI had poorer treatment response in the short‐term at six weeks, and longer term, for two months of sustained recovery. However, abuse, whether sexual, physical, or psychological in nature, did not predict treatment response. Conclusions: The experience of having a neglectful father or an overprotective mother was more predictive of response to treatment for depression than abuse, suggesting that the quality of ongoing intra‐familial relationships has a greater impact on treatment outcomes for depression than experiences of discrete abuse in childhood. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.