Anxiety and depression in end-stage COPD.

Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), estimates of their prevalence vary considerably. This probably reflects the variety of scales and methods used to measure such symptoms. Regardless of whether anxiety and depression are considered separately or as a single construct, their impact on COPD patients is important. A heightened experience of dyspnoea is likely to be a contributing factor to anxiety. Feelings of depression may be precipitated by the loss and grief associated with the disability of COPD. Smoking has been associated with nicotine addiction, and the factors that contribute to smoking may also predispose to anxiety and depressive disorders. Randomised controlled trials indicate that exercise training and carefully selected pharmacological therapy are often effective in ameliorating anxiety and depression. Most medical illnesses are influenced by the psychological responses and coping mechanisms that patients use. However, anxiety and depression are associated with dyspnoea, fatigue and altered sleep, all of which also occur in COPD. An understanding of the psychological history and coping mechanisms of patients and the role of anxiety and depressive reactions to illness may enable clinicians to reduce these symptoms and improve quality of life among patients with chronic obstructive pulmonary disease.

Comparison of family therapy and family group psychoeducation in adolescents with anorexia nervosa.

OBJECTIVE: To compare the effects of 4 months of 2 family-oriented treatments, family therapy and family psychoeducation, on female adolescents with newly diagnosed restrictive eating disorders. METHOD: Twenty-five female adolescents requiring hospitalization were randomized into either family therapy or family group psychoeducation. Outcome measures included medical (body weight) and psychosocial (specific and nonspecific eating disorder psychopathology) variables at baseline and after 4 months of treatments every 2 weeks. RESULTS: A significant time effect was found in both treatment groups for the restoration of body weight (percentage of ideal body weight, P < 0.00001). The group averages ranged from 75% to 77% ideal body weight before treatment to 91% to 96% after it. A time effect was also seen on the Family Assessment Measure (P < 0.018), in that the patients of both groups acknowledged more family psychopathology at the end of treatment. No significant group differences were found on any of the self-report measures of specific and nonspecific eating disorder pathology. CONCLUSIONS: Weight restoration was achieved following the 4-month period of treatment in both the family therapy and family psychoeducation groups, but no significant change was reported in psychological functioning by either adolescents or parents. Family group psychoeducation, the less expensive form of treatment, is an equally effective method of providing family-oriented treatment to newly diagnosed, medically compromised anorexia nervosa patients and their families.

[The Zavanelli maneuver--back to the womb].

The Zavanelli maneuver is the manual replacement of a partially-born fetus due to severe shoulder dystocia. It is described in obstetrical textbooks as being among the last to be tried in a series of maneuvers to rescue the fetus with severe shoulder dystocia, as it is considered a very difficult and heroic maneuver. Few obstetricians have seen it and fewer have done it themselves. It is even more rare when a single obstetrician has done the Zavanelli maneuver repeatedly. Therefore, both experienced obstetricians and certainly young residents are fearful when they have to use this maneuver and can lose control in cases of shoulder dystocia. We have found descriptions of 93 cases of use of the Zavanelli maneuver in vertex presentations. We also describe a recent case in our experience. We conclude that this maneuver is safe and not too difficult to perform even without previous experience. Fetal and maternal complications are few, but there is of course a bias against reporting bad results. We recommend that every obstetrician become familiar with this maneuver so as to feel sure that it is safe for him to use in severe cases of shoulder dystocia.

A comparison of male and female adolescents referred to an eating disorder program.

OBJECTIVE: To compare gender-related psychopathology and psychiatric diagnoses in male and female adolescents referred to an adolescent eating disorder program. METHOD: All adolescents presenting at the Eating Disorder Program at our hospital completed the semistructured Diagnostic Interview for Children and Adolescents-Revised (DICA-R) and self-report scales, including the Children's Depression Inventory (CDI), the Brief Symptom Inventory (BSI), the Eating Disorder Inventory (EDI-2), and the Family Assessment Measure (FAM-III), during their initial assessment. The 157 subjects (21 male, 136 female) were classified into Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) eating disorder (ED) subtypes and then recombined into male and female restricters (R) and ED-related groups: showing eating-related concerns but not having a DSM-IV diagnosis. We compared the male and female restricter groups and ED-related group on 5 specific psychological dimensions to examine comorbid psychiatric diagnosis, ED-specific and nonspecific psychopathology, EDI clinical and provisional subscales, and family functioning using multivariate analyses of covariance (MANCOVAs). RESULTS: Males endorsed statistically significant lower drive for thinness and body dissatisfaction than did females. However, there are no representative norms for adolescent males on these variables. The ED-related group also endorsed statistically significant lower drive for thinness and body dissatisfaction (specific ED psychopathology) than did the ED-restricter groups. The males in both groups endorsed fewer EDI items than did their female counterparts, but the differences were not statistically significant. Comorbid psychiatric diagnoses of depression and anxiety in male and female restricters were common but did not distinguish the groups. CONCLUSIONS: Our results suggest that male and female adolescents with EDs are clinically similar to each other and therefore resemble adults for lack of gender-specific effects on self-reported psychopathology, family functioning, and comorbid psychiatric disorders.

Innovative continuing medical education program for paediatricians: A model for the delivery of mental health services.

Paediatricians have described themselves as feeling insufficiently trained to manage young people (and their families) with significant psychosocial distress and mental illness - who can comprise a large proportion of their practices. A continuing medical education program for a group of four paediatricians who treat the paediatric mental health needs of a large Ontario catchment area with few mental health resources is described. At a monthly educational and consultation clinic, the paediatricians discuss and personally interview their own patients and referrals while a child psychiatrist and a psychiatric social worker, using a two-way mirror, assist them to develop psychosocial interviewing skills and techniques, and diagnostic formulations.

Binge/purge symptoms and comorbidity in adolescents with eating disorders.

OBJECTIVE: To identify the diagnostic subtypes of eating disorders (EDs), the psychiatric comorbid diagnoses, and associated specific and nonspecific psychopathology in a series of 120 adolescents undergoing standardized assessment for an ED. METHOD: Consecutive patients referred to our large pediatric hospital for ED assessment completed a semistructured diagnostic interview for children and adolescents. The following self-report scales were administered to assess specific and nonspecific psychopathology: the Children's Depression Inventory (CDI), the Brief Symptom Inventory (BSI), the Eating Disorder Inventory 2 (EDI-2), and the Family Assessment Measure (FAM-III) of family functioning. RESULTS: Female subjects with a mean age of 14.5 years and a mean body mass index (BMI) of 18.1 comprised 93% of the sample. The restrictive subtypes of anorexia nervosa (AN) (43%) and eating disorder not otherwise specified (EDNOS) (16%) were the most common diagnoses. Patients with restricting symptoms (R) could be grouped together because they were more similar to each other with respect to self-report symptoms of psychopathology than they were to patients with binge/purge (B/P) symptoms and vice versa. Patients with R endorsed significantly fewer subjective symptoms, both ED-specific and nonspecific, and rated their families functioning better than did B/P patients. Comorbid, current major depressive disorders and dysthymic disorders occurred in 66% of subjects, but depressive, dysthymic, and oppositional disorders occurred in 96% of those with B/P symptoms. Severity of the CDI was the best single discriminator between R and B/P subjects. CONCLUSIONS: Adolescents with EDs in the early stage of their illness are similar to adults with EDs in the following ways: they meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for subtypes of EDs (excluding amenorrhea) and commonly have comorbid psychiatric disorders, especially depressive disorders. Patients with B/P symptoms can be distinguished from restricting subjects because they endorse significantly more ED-specific and nonspecific psychopathology and have a higher frequency of comorbid Axis I diagnoses (especially depressive disorders) than restricting patients. Oppositional defiant disorder (ODD) occurs more commonly in adolescents with EDs associated with B/P symptoms.

Managing exposure to chickenpox during pregnancy. New program.

QUESTION: Every year several of my pregnant patients ask me what to do about being exposed to a child who later comes down with chickenpox. What is your recommendation? ANSWER: Whether or not a mother had chickenpox in childhood often does not accurately determine her immunity. A rapid test, such as the latex agglutination test, is useful. If test results are negative, or if testing is not feasible, varicella zoster immunoglobulin should be administered within 96 hours of exposure.

Defects in neurofibromatosis 2 protein function can arise at multiple levels.

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has revealed some general genotype-phenotype correlations. Severe disease has been associated with mutations that produce a premature termination while more mild disease has been associated with missense mutations. Here, we provide experimental proof for these genotype-phenotype correlations by demonstrating that nonsense mutations fail to produce stable merlin protein while missense mutations result in the generation of merlin proteins defective in negative growth regulation. This inability to suppress cell growth may result from defects in the function of merlin at several levels, including failure to form an intramolecular complex. Based on these findings, we propose a model for merlin growth suppression that provides a framework for analyzing NF2 patient mutations and merlin function.

Interdomain binding mediates tumor growth suppression by the NF2 gene product.

The neurofibromatosis 2 (NF2) tumor suppressor gene encodes an intracellular membrane-associated protein, called merlin (or schwannomin), that belongs to the band 4.1 family of cytoskeleton-associated proteins. Inactivating NF2 mutations occur in several sporadic tumor types and have been linked to the NF2 disease, whose hallmark is the development of bilateral Schwann cell tumors (schwannomas) of the eighth cranial nerve. Two major alternatively spliced NF2 variants are expressed in normal tissues: 'NF2-17' lacking exon 16 and 'NF2-16' that contains exon 16 and encodes a merlin protein truncated at the C-terminus. We report that overexpression of NF2-17 in rat schwannoma cells inhibits their growth in vitro and in vivo, while NF2-16 fails to influence schwannoma growth. Tumor growth inhibition by merlin depends on an interdomain association occurring either in cis or in trans between the N- and C-termini. This association does not occur in the truncated NF2-16 protein nor in a mutant NF2-17 protein lacking C-terminal sequences. These data indicate that merlin has a unique mechanism of tumor suppression, inhibiting cell proliferation via self-association.

Expression of a developmentally-regulated neuron-specific isoform of the neurofibromatosis 1 (NF1) gene.

Neurofibromatosis 1 (NF1) is a common autosomal dominant disorder in which affected individuals develop benign and malignant tumors as well as non-tumor-related abnormalities, such as seizures and learning disabilities. Here, we report an NF1 isoform arising from the alternative splicing of exon 9a with predominant central nervous system (CNS) expression. Exon 9a expression is enriched in neurons of the forebrain, specifically septum, striatum, cortex, hippocampus and olfactory bulb with significantly less expression in brainstem, cerebellum and spinal cord. This pattern of NF1 exon 9a expression correlates with the postnatal maturation of these neurons and suggests a role for NF1 in neuronal differentiation.

Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues.

Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected individuals manifest mental retardation, seizures, and a variety of benign and malignant tumors. The TSC2 tumor suppressor gene was recently identified by positional cloning and its protein product, tuberin, shown to represent one member of the rap GTPase activating protein (rapGAP) family. In order to determine the contribution of tuberin to the development of mental retardation and seizures in patients with TS, we examined the expression of tuberin in adult and developing nervous system tissues. Since tuberin is the second rapGAP found in the nervous system, the expression of tuberin was compared to the expression of rapGAP, rap1, and rap2. In this study, we demonstrate that tuberin is expressed at greatest levels in the spinal cord and cerebellum as opposed to rapGAP, which is not enriched in these tissues. Tuberin expression in the adult CNS is restricted to the olfactory bulb, several CNS neuronal populations, brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral spinal cord. In contrast, rapGAP is expressed in many different cell types in the adult CNS, but not in cerebellar Purkinje cells or motor neurons in the ventral spinal cord. However, there is significant expression of rapGAP in astrocytes. The restricted distribution of tuberin expression relative to rap1 and rapGAP suggests that tuberin may be the primary rap1 regulator in a subpopulation of CNS neurons.

Increased expression of the neurofibromatosis 1 (NF1) gene product, neurofibromin, in astrocytes in response to cerebral ischemia.

Tumor suppressor genes encode proteins involved in growth regulation in differentiating and proliferating cells. Previous work from our laboratory has demonstrated that the neurofibromatosis 1 (NF1) tumor suppressor gene is dramatically upregulated in astrocytes stimulated with dibutyryl cyclic AMP and proinflammatory cytokines. To explore the possibility that the NF1 gene product, neurofibromin, plays a role in the reactive gliosis seen in response to cerebral ischemia, expression of NF1 was examined in both focal and global models of rat cerebral ischemia. In this report, we demonstrate the increased expression of both neurofibromin and glial fibrillary acidic protein (GFAP) in astrocytes surrounding areas of focal ischemia. Similar increases in neurofibromin and GFAP immunoreactivity were also observed in reactive astrocytes in the hippocampal region in a global model of ischemia. These results suggest a novel role for the NF1 tumor suppressor gene in growth regulatory pathways involved in cellular remodeling and in response to injury.