Cancer risk in individuals with autism spectrum disorder.

BACKGROUND: Whether individuals with autism spectrum disorders (ASDs) have a higher-than-expected risk of cancer remains unknown. PATIENTS AND METHODS: We carried out a population-based cohort study including 2.3 million individuals live-born to mothers from Nordic countries during 1987-2013 in Sweden with follow-up through 2016 (up to age 30 years). Individuals with ASD were ascertained through the Swedish National Patient Register. We estimated the relative risk of cancer in relation to ASD by odds ratios (ORs) and associated 95% confidence intervals (CIs) derived from logistic regression, after detailed adjustment for potential confounders. We also carried out a sibling comparison to address familial confounding and a genetic correlation analysis using the genome-wide association study summary statistics to address confounding due to potential polygenetic pleiotropy between ASD and cancer. RESULTS: We observed an overall increased risk of any cancer among individuals with ASD (OR 1.3, 95% CI 1.2-1.5), compared with individuals without ASD. The association for any cancer was primarily noted for narrowly defined autistic disorder (OR 1.7, 95% CI 1.3-2.1) and ASD with comorbid birth defects (OR 2.1, 95% CI 1.5-2.9) or both birth defects and intellectual disability (ID; OR 4.8, 95% CI 3.4-6.6). An association was also suggested for ASD with comorbid ID (OR 1.4; 95% CI 0.9-2.1), but was not statistically significant. ASD alone (i.e. without comorbid ID or birth defects) was not associated with an increased risk of any cancer (OR 1.0, 95% CI 0.8-1.2). Sibling comparison and genetic correlation analysis showed little evidence for familial confounding or confounding due to polygenetic pleiotropy between ASD and cancer. CONCLUSIONS: ASD per se is not associated with an increased risk for cancer in early life. The increased cancer risk among individuals with ASD is likely mainly attributable to co-occurring ID and/or birth defects in ASD.

Polygenic risk for psychiatric disorders correlates with executive function in typical development.

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed.

Plasma kallikrein activates the epithelial sodium channel in vitro but is not essential for volume retention in nephrotic mice.

AIM: Recent work has demonstrated that activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases causes sodium retention in nephrotic syndrome. The aim of this study was to elucidate a potential role of plasma kallikrein (PKLK) as a candidate serine protease in this context. METHODS: We analysed PKLK in the urine of patients with chronic kidney disease (CKD, n = 171) and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in PKLK-deficient mice (klkb1-/- ) with experimental nephrotic syndrome induced by doxorubicin injection. RESULTS: In patients with CKD, we found that PKLK is excreted in the urine up to a concentration of 2 µg mL-1 which was correlated with albuminuria (r = .71) and overhydration as assessed by bioimpedance spectroscopy (r = .44). PKLK increased ENaC-mediated whole-cell currents, which was associated with the appearance of a 67 kDa γ-ENaC cleavage product at the cell surface consistent with proteolytic activation. Mutating a putative prostasin cleavage site in γ-ENaC prevented channel stimulation by PKLK. In a mouse model for nephrotic syndrome, active PKLK was present in nephrotic urine of klkb1+/+ but not of klkb1-/- mice. However, klkb1-/- mice were not protected from ENaC activation and sodium retention compared to nephrotic klkb1+/+ mice. CONCLUSION: Plasma kallikrein is detected in the urine of proteinuric patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site. However, PKLK is not essential for volume retention in nephrotic mice.

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.

Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.

The utilization of antidepressants in community-dwelling and institutionalized elderly--results form a representative survey in Germany.

Given its widespread occurrence and consequences, old-age depression has to be regarded as a major public health problem. Drug treatment has been proven effective in the majority of elderly individuals suffering from depression. This study presents pharmacoepidemiological data regarding the use of prescribed antidepressants and those purchased over the counter in the elderly. Furthermore, it links the data to simultaneously assessed depressive symptomatology. A representative survey on the utilization of prescription and over-the-counter antidepressant drugs and depressive symptomatology in community-dwelling (n = 1193) and institutionalized elderly individuals (n = 470) aged 75 and over was conducted in an urban region of Germany. Antidepressant use was found to be remarkably low (synthetic antidepressants: 2.2% of community dwelling individuals, 3.6% of institutionalized individuals; phytopharmaca containing hypericum perforatum: 4.2% of community dwelling individuals, 2.8% of institutionalized individuals). Two-thirds of the individuals treated with synthetic antidepressants received tri- and tetracyclic drugs, which were given at lower dosages than recommended for depression treatment. Selective serotonin reuptake inhibitors (SSRIs) were introduced in community-dwelling individuals only; none of the individuals cared for in residential and nursing homes received SSRIs. Only a minority of individuals with depressive symptoms were treated with antidepressants. The data suggests underutilization of antidepressants in the elderly, in which institutionalized elderly seem especially disadvantaged. The results call for increased efforts to discuss mental health issues in the public and to share scientific knowledge about symptoms, course and treatment options for depression. Furthermore, geronto-psychiatric competence of medical professionals, especially GPs, has to be systematically developed.

[Dementia patients in general practice--results of a survey]. / Demenzkranke in der Hausarztpraxis--Ergebnisse einer Befragung.

In line with the current demographic trends, the number of elderly suffering from dementia is increasing. GPs have a key position in dealing with these patients at the primary care level. Different aspects of care for patients suffering from dementia provided in general practice in Germany were assessed by means of a questionnaire (n = 563). The results highlight the role of GPs in the delivery of medical and psychosocial care. However, diagnosing dementia seems challenging and co-operation could be improved. Three fourths of the GPs diagnose vascular dementia more often than Alzheimer's disease, which is contrary to what is known from epidemiological findings. One third refers patients to a specialist on a regular basis for establishing the diagnosis. Only 4% of the German GPs entertain co-operative relationships with the "Alzheimer society" and the "Brain league". Consequences for improving these for patients with dementia and their families are discussed.

[Subjective memory loss--a sign of cognitive impairment in the elderly? An overview of the status of research]. / Subjektive Gedächtnisstörungen--ein Zeichen für kognitive Beeinträchtigung im Alter? Ein Uberblick zum Stand der Forschung.

According to the growing clinical interest in early indicators of dementia, numerous studies have examined the association between subjective memory complaints and cognitive performance in old age. Their results are contradictory. In this paper, studies carried out over the last 10 years are compared with regard to the study design and the assessment instruments used. The results are discussed with particular reference to the diagnostic validity of subjective memory complaints. The majority of case-control studies and cross-sectional studies of non-representative samples could not demonstrate an association between subjective memory complaints and cognitive performance. Most field studies of larger representative population samples, however, have come to the opposite conclusion. A consistent assessment of these statistically significant associations against the background of diagnostic validity showed that memory complaints cannot be taken as a clear clinical indicator for cognitive impairment. Subjective memory complaints may reflect depressive disorders and a multitude of other processes, of which an objective impairment of cognitive performance is just one aspect. As a consequence, an inclusion of subjective memory complaints as a diagnostic criterion for the diagnosis of "mild cognitive disorder" according to ICD-10 is not justified.

Recruitment procedures and their impact on the prevalence of dementia. Results from the Leipzig Longitudinal Study of the Aged (LEILA75+).

Recruitment procedures may exert a considerable influence on the outcome of health surveys in the elderly. Their impact on the prevalence of dementia will be measured in an epidemiological field study in a sample of 1,692 randomly selected individuals (75+). Face-to-face interviews were conducted using SIDAM (structured interview for the diagnosis of dementia of Alzheimer type, multi-infarct dementia and dementias of other etiology according to ICD-10 and DSM-III-R). Furthermore, proxy interviews were performed with relatives of fragile and functionally dependent individuals. Considering face- to-face interviews of community-dwelling individuals, a prevalence of moderate and severe dementia of 5.3% was found. When including information on respondents by proxy and institutionalized individuals, the prevalence rate increased to 6.3 and 10.5%, respectively. It will be argued that covering the whole population in question and ensuring high response rates are central issues to minimize selection bias.

The role of referrals in diagnosing dementia at the primary care level.

BACKGROUND: Demographic changes indicating a general aging of the population suggest that the key role of general practitioners (GPs) in the diagnosis and management of dementia becomes more salient. The encouragement of GPs to collaborate with specialists is one chance to support GPs in performing a variety of functions associated with the diagnosis and management of dementia. METHOD: We used a questionnaire to investigate the role of referrals in diagnosing dementia at the primary care level and variables potentially influencing the referral behavior of German GPs (n = 563). RESULTS: Only 31% of the GPs stated that the diagnosis of dementia was made predominantly in the context of referral to a specialist. The chance that referrals were made was increased for those GPs who entertained extensive cooperative relationships with self-help groups, psychologists, or the "Alzheimer Society"/"Brain League" (odds ratio [OR] 1.74) and for those GPs who perceived a great preparedness on the part of the relatives of the patient to comply with a referral (OR 2.29) as well as who noticed a great readiness among specialists to accept patients for the diagnosis of dementia (OR 2.55). GPs whose therapeutic orientation was shaped by further training and scientific literature were more likely to refer (OR 3.54). DISCUSSION: Enhancing the liaison between GPs and specialist physicians by improving the psychogeriatric competence of GPs as well as the connection to nonmedical services is discussed.

Do memory complaints indicate the presence of cognitive impairment? Results of a field study.

BACKGROUND: In the context of suspected cognitive disorders, the validity of memory complaints is subject to considerable debate. This investigation documents the prevalence of memory complaints and assesses the validity of memory complaints for detecting cognitive impairment. METHODS: The sample comprises 349 randomly selected non-institutionalized individuals, aged 75 and over living in the city of Leipzig. Twenty individuals who suffer from moderate and severe dementia according to DSM-III-R were excluded. Memory complaints were measured by means of a single item question. The Mini-Mental State Examination (MMSE) and a wider range of cognitive tests which constitute the short neuropsychological battery of the SIDAM (Structured Interview for the Diagnosis of dementia of Alzheimer type, Multi-infarct dementia and dementias of other etiology according to ICD-10 and DSM-III-R) were used to test cognitive performance. RESULTS: One in three individuals aged 75 and over complained about memory deficits. The MMSE is not significantly related to memory complaints, whereas poorer performance on 2 out of 8 tests regarding specific areas of cognitive function (immediate recall, short-term memory) were found to be significantly associated with memory complaints. Despite these statistically significant associations, it is shown that memory complaints do not have diagnostic validity in detecting cognitive impairment on the individual level. CONCLUSION: Memory self-assessment should not be used as a substitute measure of cognitive performance. Initiation of further diagnostic and therapeutic steps should be based on cognitive performance testing. Relaying solely on memory complaints would miss individuals in need and allocate resources to worried but cognitively healthy persons.

[Gerontopsychiatric competence is in demand. The current psychopharmacologic treatment practice in homes for the aged and nursing homes]. / Gerontopsychiatrische Kompetenz ist gefragt. Die aktuelle psychopharmakologische Behandlungspraxis in Alten- und Altenpflegeheimen.

OBJECTIVE: A growing proportion of residents of residential and nursing homes is mentally ill and subject to intensive pharmacotherapy. This study presents data on the use of psychotropic drugs use in residential and nursing homes for the elderly in the new Länder. METHOD: The psychotropic drug use of 560 residents of 4 old-people's homes in Leipzig (Germany) was reviewed and analysed descriptively. RESULTS: Half of the population of residential and nursing homes receives psychotropic drug treatment, a substantial part with 2 or more drugs a day. Middle- and long-acting benzodiazepines were prescribed strikingly often and used for long-term treatment. Antidepressants, taken regularly by 3.6% of the nursing homes residents and 2.6% of the residential home residents, are considered to be under-used. The introduction of new substances (e.g. atypical neuroleptics, SSRI's) which might be more appropriate in vulnerable and multimorbide elderly persons was found to be delayed. CONCLUSIONS: The treatment of mental disorders in residential and nursing homes lags far behind the "state of the art" and demonstrates the need for gerontopsychiatric input into institutional care for the elderly.

The relationship between dental disease and cerebral vascular accident in elderly United States veterans.

We report here information obtained from a cross-sectional study of 401 veterans, who were at least 60 years of age, which showed that several dental/oral conditions can be significantly associated with the diagnosis of a cerebral vascular accident (CVA), when included in a multivariate logistic regression model with and without many of the known risk factors for a CVA. The dental findings relative to the prevalence of dental caries and periodontal disease were not distinctly different between the subjects with and without a CVA in the bivariate analysis. A higher stimulated salivary flow was negatively associated with a CVA in the multivariate models. The plaque index and oral hygiene habits relating to brushing, flossing, and frequency of having teeth cleaned by a dentist/hygienist were significantly associated with a CVA in the bivariate analysis. Among these oral hygiene parameters, *needing help in brushing one's teeth" and the reported annual visit to the dentist/hygienist for teeth cleaning remained significant in the multivariate models involving the dependent-living subjects. The need for help in brushing one's teeth could reflect the fact that many subjects had reduced manual dexterity as a result of the CVA and required this extra care. However, the finding that those dependent-living individuals who reported that they did not have their teeth cleaned at least once a year were 4.76 times more likely to have had a CVA, suggests that a pattern of oral neglect might be associated with developing a CVA. The implications of this in terms of an intervention strategy for CVA warrants further consideration. However, caution is recommended because the data were obtained from a convenience sampling of older veterans and may not be generalizable to other populations.

Assessing the relationship between dental disease and coronary heart disease in elderly U.S. veterans.

Several recent studies have shown a link between dental disease and coronary heart disease. The authors studied 320 U.S. veterans in a convenience sample to assess the relationship between oral health and systemic diseases among older people. They present cross-sectional data confirming that a statistically significant association exists between a diagnosis of coronary heart disease and certain oral health parameters, such as the number of missing teeth, plaque benzoyl-DL-arginine-naphthylamide test scores, salivary levels of Streptococcus sanguis and complaints of xerostomia. The oral parameters in these subjects were independent of and more strongly associated with coronary heart disease than were recognized risk factors, such as serum cholesterol levels, body mass index, diabetes and smoking status. However, because of the convenience sample studied, these findings cannot be generalized to other populations.

Predictors of aspiration pneumonia: how important is dysphagia?

Aspiration pneumonia is a major cause of morbidity and mortality among the elderly who are hospitalized or in nursing homes. Multiple risk factors for pneumonia have been identified, but no study has effectively compared the relative risk of factors in several different categories, including dysphagia. In this prospective outcomes study, 189 elderly subjects were recruited from the outpatient clinics, inpatient acute care wards, and the nursing home care center at the VA Medical Center in Ann Arbor, Michigan. They were given a variety of assessments to determine oropharyngeal and esophageal swallowing and feeding status, functional status, medical status, and oral/dental status. The subjects were followed for up to 4 years for an outcome of verified aspiration pneumonia. Bivariate analyses identified several factors as significantly associated with pneumonia. Logistic regression analyses then identified the significant predictors of aspiration pneumonia. The best predictors, in one or more groups of subjects, were dependent for feeding, dependent for oral care, number of decayed teeth, tube feeding, more than one medical diagnosis, number of medications, and smoking. The role that each of the significant predictors might play was described in relation to the pathogenesis of aspiration pneumonia. Dysphagia was concluded to be an important risk for aspiration pneumonia, but generally not sufficient to cause pneumonia unless other risk factors are present as well. A dependency upon others for feeding emerged as the dominant risk factor, with an odds ratio of 19.98 in a logistic regression model that excluded tube-fed patients.

Half-life determination of serum free prostate-specific antigen following radical retropubic prostatectomy.

OBJECTIVES: Prostate-specific antigen (PSA) continues to be the the most clinically useful tumor marker for prostate cancer. Recently, several molecular forms of PSA have been detected and characterized. These specific forms, including free PSA and PSA complexed to alpha 1-antichymotrypsin, can be measured and their proportions determined. In doing so, the sensitivity of PSA as a tumor marker can be maintained while the specificity is improved. In order to maximize the clinical utility of free PSA, the half-life and elimination kinetics of free PSA from the serum were determined. METHODS: Twenty-five patients, ages 43-74 years (mean 60 years) with biopsy proven, organ-confined adenocarcinoma of the prostate who underwent anatomic radical retropubic prostatectomy, were identified. For each patient, venous blood samples were obtained preoperatively, and at 60-minute intervals beginning 1 hour after the prostate was removed. The specimens were handled and stored in a consistent fashion. Using the AxSYM immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL), the serum free PSA values were determined and plotted as a function of time for each patient. From the 25 individual elimination curves that were generated, the half-life of serum free PSA was determined. RESULTS: The mean half-life of serum free PSA was 110 minutes +/- 18.6 minutes (SD). Analysis of the individual and cumulative elimination curves indicates that the elimination of free PSA from the serum following radical prostatectomy follows a biphasic pattern. CONCLUSIONS: Unlike PSA, which has a half life of 2-3 days, the half-life of serum free PSA is 110 minutes (1.83 hours). This short half-life may have significant implications for the use of percentage of free PSA as a clinically useful tool in distinguishing patients with early, curable prostate cancer from men with benign prostatic hyperplasia (BPH) only.

Elevated parathyroid hormone-related peptide associated with lactation and bone density loss.

OBJECTIVE: To investigate the hypothesis that parathyroid hormone-related peptide (PRHrP) may be involved with bone loss and recovery as a means of providing adequate calcium and phosphate to infants. DESIGN: An 18-month prospective cohort study. SETTING: General community setting with recruitment occurring at birthing education classes. PARTICIPANTS: Volunteer sample of 115 postpartum healthy women aged 20 to 40 years, and 0 or 1 parity prior to parturition with no intent to breast-feed or intent to breast-feed at least 6 months. MAIN OUTCOME MEASURES: Parathyroid hormone-related peptide, prolactin, estradiol, 1,25-dihydroxyvitamin D, 24-hydroxyvitamin D, femoral bone mineral density, and bone turnover markers were measured in 115 postpartum women at 2 weeks, 2 months, 4 months, 6 months, 12 months, and 18 months postpartum. Lumbar bone mineral density was measured at 2 weeks, 6 months, 12 months, and 18 months postpartum. RESULTS: Elevated PTHrP values were significantly associated (P<.001) with breast-feeding status, elevated prolactin levels, and lower serum estradiol levels, conditions occurring during lactation. Furthermore, elevated PTHrP levels were negatively and significantly associated (P<.01) over time with bone mineral density change at both the spine and the femoral neck, even after accounting for prolactin levels, breast-feeding status, return of menstruation, estradiol levels, PTH levels, 1,25-dihydroxyvitamin D levels, dietary calcium intake, physical activity, and body size. CONCLUSION: These data clearly support the hypothesis that PTHrP is an alternative mechanism associated with bone loss and recovery during and subsequent to lactation.

Follow-up of coil occlusion of patent ductus arteriosus.

OBJECTIVE: We sought to determine the prevalence and fate of residual ductal shunting following coil occlusion of patent ductus arteriosus. BACKGROUND: Although transcatheter coil occlusion of patent ductus arteriosus has gained popularity, few follow-up data have been reported. METHODS: A review of 75 patients who underwent coil occlusion was performed. Residual shunting was investigated by Doppler echocardiography in follow-up. Angiograms were reviewed to obtain minimal ductal diameter and ductal angiographic type. RESULTS: Residual shunts were found in 31 patients (41%) on the day of the procedure, and of these, spontaneous closure was noted in 17 (55%) at 2 weeks to 20 months of follow-up. Of the 75 patients studied, 5 (7%) required a second coil procedure, and 10 (13%) remained with persistent residual shunts at most recent follow-up. Actuarial analysis estimated a 6 +/- 5% prevalence of residual shunts 20 months after a single coil procedure and 3 +/- 3% after all coil procedures. Minimal ductal diameter was associated with immediate complete ductal occlusion by a single coil. These patients had significantly smaller (p = 0.003) minimal ductal diameters (1.2 +/- 0.7 mm) than those who required two coils during their initial procedure to achieve immediate occlusion (1.9 +/- 0.7 mm), those who required a second coil procedure (2.0 +/- 0.9 mm), those who had spontaneous closure of residual shunts (1.9 +/- 0.7 mm) and those with persistent residual shunts (2.0 +/- 0.9 mm). No association was identified between ductal angiographic type and outcome of coil occlusion. No late adverse clinical events of coil occlusion or evidence of recanalization was found. CONCLUSIONS: Small residual shunts are common after coil embolization of patent ductus arteriosus, but most close spontaneously. Actuarial analysis estimates complete closure in 94% at 20 months, and reintervention was required in only 7% of patients.

Relationship of amiodarone to postoperative complications of transthoracic implantation of automatic implantable cardioverter defibrillators.

The purpose of this study is to report the results and complications associated with transthoracic placement of an implantable defibrillator and their relationship to amiodarone, and to identify clinical predictors of complications. There were 159 men and 41 women. The mean patients age was 61 +/- 11 years, and the mean ejection fraction was 0.33 +/- 0.14. Fifty one percent of patients developed complications including death in 14 patients (7%). Variables which differed in patients who died and those that did not were age, ejection fraction and New York heart failure classifications. Postoperative mortality was unrelated to amiodarone therapy. Twenty patients (10%) developed pneumonia and 15 patients (7.5%) developed respiratory failure. Clinical variables associated with the development of respiratory failure were age, amiodarone therapy and a prior history of pulmonary disease. Patients receiving amiodarone had a higher incidence of an elevated defibrillation threshold (> or = 25 joules) as compared with those not being treated with amiodarone. Clinical factors associated with an elevated defibrillation threshold were a history of a myocardial infarction, prior bypass surgery, and amiodarone. The results of this study demonstrate that placement of an implantable defibrillator using a transthoracic approach is associated with a high incidence of complications. Amiodarone therapy is associated with an increased incidence of pneumonia, respiratory failure, and elevated defibrillation thresholds.