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PubMed1998

Atrial septal defect in cyanotic CL/Fr mice.

OBJECTIVE: It is widely known that some newborn CL/Fr mice with cleft lip and palate (CLP) also have cyanotic symptoms, which have been thought to depend on an atrial septal defect (ASD). In a previous study, we found that cyanotic mice tended to have more severe types of CLP. We hypothesize that the mechanical airway obstruction due to a poorly developed palatal shelf and unmoved tongue in CLP(+) mice might be related to the occurrence of cyanosis. The purpose of this study was to examine the relationships between ASD and cyanosis in CLP(+) newborns. METHOD: The newborn hearts from CLP(-), noncyanotic CLP(+), cyanotic CLP(+), CL/Fr mice and ICR mice were examined histologically, and the incidence and size of ASD was determined on neonatal day (ND) 0. In CLP(-) newborns, similar procedures were performed from ND 1 to ND 4. Furthermore, in CLP(+) newborns, development of the palatal shelf was examined. RESULTS: While all the ICR mice had a well-developed atrial septum, and the incidence of ASD was 0%, about 80% of CL/Fr mice had ASD, irrespective of the presence or absence of CLP and cyanosis. On ND 0, the septum primum was significantly shorter in cyanotic CLP(+) mice than in CLP(-) mice. It also tended to be shorter in CLP(+) mice than in CLP(-) mice. Between the cyanotics and noncyanotics, there were no significant differences in the incidences of ASD and the rate of septal development. In CLP(-) mice, the septum primum developed well later and no ASD was observed on ND 4. Cyanotic newborns had significantly less developed palatal shelves than did noncyanotics. CONCLUSIONS: Cyanosis may not be related to ASD and the rate of septal development, but may be related to the occurrence of CLP in this strain. Furthermore, we confirmed that some relationship exists between the development of the palatal shelf and cyanosis. The present study supports our hypothesis concerning the cause of cyanosis in CL/Fr mice.

Airway Obstruction↗
PubMed2005

4-acetoxyscirpendiol of Paecilomyces tenuipes inhibits Na(+)/D-glucose cotransporter expressed in Xenopus laevis oocytes.

Cordyceps, an entomopathogenic fungus, contains many health-promoting ingredients. Recent reports indicate that the consumption of cordyceps helps reduce blood-sugar content in diabetics. However, the mechanism underlying this reduction in circulatory sugar content is not fully understood. Methanolic extracts were prepared from the fruiting bodies of Paecilomyces tenuipes, and 4-beta acetoxyscirpendiol (4-ASD) was eventually isolated and purified. Na(+)/Glucose transporter-1 (SGLT-1) was expressed in Xenopus oocytes, and the effect of 4-ASD on SGLT-1 was analyzed utilizing a voltage clamp and by performing 2-deoxy-D-glucose (2-DOG) uptake studies. 4-ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose-dependent manner. In the presence of the derivatives of 4-ASD (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited in an 4-ASD-like manner. Of these derivatives, 15-acetoxyscirepenol inhibited SGLT-1 as well as 4-ASD, whereas diacetoxyscirpenol was slightly less effective. Taken together, these results strongly indicate that 4-ASD in P. tenuipes may lower blood sugar levels in the circulatory system. We conclude that 4-ASD and its derivatives are effective SGLT-1 inhibitors.

Animals↗
PubMed2000

Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer.

Lung carcinogenesis is assumed to be a multistep process, but detailed understanding of the sequential morphological and molecular changes preceding invasive lung cancer remains elusive. To better understand early lung carcinogenesis, we initiated a program of fluorescence bronchoscopy in smokers at high risk for lung cancer. In the bronchial biopsies from these subjects, we observed a unique lesion consisting of capillary blood vessels closely juxtaposed to and projecting into metaplastic or dysplastic squamous bronchial epithelium, angiogenic squamous dysplasia (ASD). Serial sections of the capillary projections confirmed that they represent intramucosal capillary loops. Microvessel density in ASD was elevated in comparison to normal mucosa (P = 0.0003) but not in comparison to other forms of hyperplasia or dysplasia. ASD thus represents a qualitatively distinct form of angiogenesis in which there is architectural rearrangement of the capillary microvasculature. Genetic analysis of surface epithelium in a random subset of lesions revealed loss of heterozygosity at chromosome 3p in 53% of ASD lesions. No confirmed p53 mutations were identified. Compared with normal epithelium, proliferative activity was markedly elevated in ASD lesions. ASD occurred in 54 of 158 (34%) high-risk smokers without carcinoma and in 6 of 10 patients with squamous carcinoma who underwent fluorescence bronchoscopy. One early-stage invasive carcinoma was noteworthy for the occurrence of ASD juxtaposed to invasive tumor. Seventy-seven (59%) of the ASD lesions were detected by abnormal fluorescence alone. Twenty bronchial sites (11 patients) were rebiopsied 1 year after the initial diagnosis. At nine (45%) of these sites, the lesion was found to persist. The lesion was not present in biopsies from 16 normal nonsmoker control subjects. The presence of this lesion in high-risk smokers suggests that aberrant patterns of microvascularization may occur at an early stage of bronchial carcinogenesis.

Aged↗
PubMed1992

Partial biventricular repair of pulmonary atresia with intact ventricular septum. Use of an adjustable atrial septal defect.

BACKGROUND: Repair of pulmonary atresia with intact ventricular septum (PA-IVS) is one of the more challenging problems in congenital heart surgery. The hypertrophied but hypoplastic right ventricle is suddenly presented with an increased volume load as the right-to-left shunt is abolished by closure of the atrial septal defect (ASD) as part of definitive repair. We have proposed that a restrictive, adjustable ASD that allows a controlled right-to-left shunt may prevent excessive venous hypertension and allow adequate left-sided filling after biventricular repair of PA-IVS. METHODS AND RESULTS: From 1982 through 1991, 39 patients presented for definitive repair of PA-IVS. Nineteen of these patients were thought to be suitable candidates for biventricular repair, and the other 20 underwent a modified Fontan procedure. An adjustable ASD was used in 12 of the 19 patients undergoing biventricular repair. Mean age was 24 months (age range, 5-66 months). Two patients had their ASD snared closed in the operating room after coming off bypass. In the other 10 patients, closure of the ASD could not be tolerated at the time of surgery as evidenced by elevation of right atrial pressures by > 15 mm Hg and decreased blood pressure when closure was attempted. Seven patients had their open ASDs closed by the snare device, and one patient had his ASD narrowed in the early postoperative period. One patient underwent delayed closure 16 months after surgery. There was one hospital death. CONCLUSIONS: The snare-controlled adjustable ASD allows partial biventricular repair of PA-IVS, reducing the risk of low cardiac output and severe venous hypertension in the postoperative period.

Aortic Valve↗
PubMed2004

Apoptosis induction by 4beta-acetoxyscirpendiol from Paecilomyces tenuipes in human leukaemia cell lines.

The carpophores of Paecilomyces tenuipes are known in the Orient for their strong antitumor activity. In continuation of our study on acetoxyscirpendiol (ASD, 4beta-acetoxyscirpene-3alpha,15-diol) as a cytotoxic component from this fungus, we report particularly on the mode of action of ASD in inducing apoptosis in human MOLT-4, THP-1 and Jurkat T cell leukaemia in vitro. The antiproliferative effects of ASD seem attributable to its induction of apoptosis in the cells, as it blocked the cell cycle, induced hypodiploidity and bound annexin V and also cleaved poly-(ADP-ribose) polymerase (PARP) in these cell lines. The 50% inhibitory concentrations (IC50) of ASD on MOLT-4, THP-1 and Jurkat T cells were found to be 60, 85 and 60 ng/ml, respectively. ASD arrested the cell cycle at the G1/S transition and showed hypodiploidity due to the accumulation of sub-G0 population. Annexin V binding was increased in the presence of ASD in the MOLT-4 cell line in a time-dependent manner. ASD and three of its derivatives also induced cleavage of PARP in both MOLT-4 and Jurkat T cell lines. From these data, it is suggested that ASD exerts its cytotoxic activity by inducing apoptosis in leukaemia cell lines in vitro.

Annexin A5↗
PubMed2004

Changes in the cardiovascular system during pregnancy in women with secondary atrial septal defect.

BACKGROUND: The secundum atrial septal defect (ASD II) is, after bicuspid aortic valve, the second most frequent congenital heart disease. In the majority of females with ASD II the course of pregnancy is uncomplicated, however, pregnancy-related cardiovascular changes may affect hemodynamic parameters of the defect. AIM: To assess cardiovascular changes in pregnant females with ASD II. METHODS: The study group consisted of 54 pregnant females with ASD II and 30 control healthy pregnant women. NYHA class, standard ECG, 24-hour ambulatory ECG monitoring and echocardiography were analysed in the second and third trimester of pregnancy as well as during puerperium. RESULTS AND CONCLUSIONS: (1) Due to the relatively small sample of population studied and limitations of the usage of NYHA classification in pregnant women, the relationship between ASD II and the development of heart failure during pregnancy could not be definitely proved. (2) An increase in the right ventricular and right atrial enlargement was significantly greater in pregnant women with ASD II compared with healthy pregnant females. Also indirect parameters of the right ventricular strain (paradoxical systolic movement of the interventricular septum or tricuspid regurgitation) were more frequent in patients with ASD II rather than in controls. These alterations were accompanied by a significant decrease in the mean value of the Qp/Qs index which may suggest pregnancy-related favourable changes in the hemodynamic consequences of the defect - a decrease in the left-to-right shunt. (3) Paroxysmal supraventricular tachycardia was the most frequent cardiac arrhythmia in pregnant women with ASD II.

Adolescent↗
PubMed2004

Transcatheter device occlusion of atrial septal defects and patent foramen ovale under intracardiac echocardiographic guidance.

BACKGROUND: Transcatheter device occlusion of atrial septal defects is becoming an effective alternative to surgery. In order to avoid the discomfort of transesophageal echocardiography and the need for general anesthesia we started using intracardiac ultrasound (ICUS) to guide device implantation in adult patients. OBJECTIVE: To assess the efficacy and safety of transcatheter closure of atrial septal defect (ASD) and patent foramen ovale (PFO) assisted by ICUS. METHODS: Between April 2001 and November 2002, 27 patients with ASD and four patients with PFO were selected for transcatheter device occlusion. Patient selection was based on previous transesophageal echocardiogram and clinical data. All patients were treated without anesthesia or sedation. The percutaneous occlusion technique was assisted by ICUS and fluoroscopy. Morphological aspects of the defect and measurement of its largest diameter were used to select device diameter. RESULTS: Thirty-one patients were treated (27 with ASD, four with PFO); 21 (68%) were female, mean age was 40.1+/-13.5 years, and mean ASD diameter was 20.1+/-6.4 mm. We implanted ASD Amplatzer occluding devices in all ASD patients, the size being selected by adding 4 to 6 mm to the maximum ASD diameter. The patients with PFO had an Amplatzer PFO occluder. Mean total procedure time was 50.1+/-18.9 minutes and mean fluoroscopy time was 11.7+/-5.9 minutes. All devices were successfully deployed. We had neither complications nor mortality. Follow-up evaluation was performed by transthoracic echocardiography at 24 hours, one, six and 12 months after occlusion. During a mean follow-up period of 8.5+/-7.1 months, all patients were free of symptoms and on transthoracic echocardiographic evaluation at 24 hours all but three patients had complete occlusion (three ASD patients had insignificant residual shunt), with 100% occlusion rate at six months. CONCLUSIONS: Transcatheter occlusion of atrial septal defects can be effectively and safely performed using ICUS to guide device implantation in selected adult patients.

Adult↗
PubMedDate not supplied

Surgical treatment of the atrial septal defect in adults: effective reduction in cardiac size and excellent overall clinical outcome.

OBJECTIVE: Atrial septal defect (ASD), one of the commonest congenital heart lesions, is asymptomatic in most cases and therefore remains undiagnosed until adulthood in a significant number of patients. Despite the employment of transcatheter modalities in its treatment, surgery remains a reliable alternative. This study summarizes our experience in surgical correction of ASD in adult patients. METHODS: Over a 9-year period (September 1997-August 2006), 171 patients, 73 males and 98 females, aged 18-72 (median 35) years, underwent surgical repair of ASDs'. Of these, 141 patients (82%) had ASD of the secundum type and 30 (18%) sinus venosus ASD with partial anomalous pulmonary venous connection (PAPVC). Fifteen patients with different principal diagnoses and concomitant ASD's were excluded, as were those with ostium primum ASDs'. Eighty six patients (50%) were asymptomatic and 11 (6.4%) had established arrhythmias. Two patients had recurrent lesions, 5 had a previously failed attempted transcatheter closure of which 3 were admitted as emergencies. All underwent complete surgical repair. RESULTS: Two patients (aged 53 and 69 years) with chronic atrial fibrillation suffered embolic strokes (1.16%), with one of the two subsequently dying from cerebral haemorrhage (0.6%). Other postoperative complications (including atrial arrhythmias) were treated successfully. Median ICU and hospital stay were 1 and 6 days respectively. Significant reduction in heart size was noted postoperatively as defined by the reduction in the cardiothoracic ratio (p=0.003). At mean follow up of 55+/-28 months, there was one late death from heart failure in a patient with advanced preoperative disease. All other patients remain in excellent clinical condition. CONCLUSION: Surgical correction of ASD is associated with low morbidity and mortality. Arrhythmias and their complications could be prevented by early surgical treatment.

Adolescent↗
PubMed1984

[Left ventricular function in patients with right ventricular overload evaluated by exercise echocardiography: comparison of pulmonary hypertension and atrial septal defects].

To evaluate left ventricular function in patients (pts) with right ventricular overload, exercise echocardiographic studies using a bicycle ergometer were performed for seven pts with pulmonary hypertension (PH), two with cor pulmonale (CP) and 16 with atrial septal defects (ASD), and the results were compared with those of 10 (control I) and 27 (control II) normal persons. These subjects were categorized in two study groups; study I consisting of PH, CP and control group I with an exercise workload of 25 watts for 3 min; and study II consisting of ASD and control group II with an exercise workload of 50 watts for 3 min. The results were as follows: M-mode echocardiography revealed that: During exercise, the stroke volume (SV) was increased with a significant decrease of left ventricular end-systolic dimension (LVDs), but without a change in left ventricular end-diastolic dimension (LVDd) in control groups I and II, with a marked increase of LVDd and a slight decrease of LVDs in the ASD group. By contrast, the SV in the PH group tended to decrease during exercise with a slight decrease of LVDd, but without a significant change in LVDs. Right ventricular dimension (RVD) was significantly increased during exercise in the PH group, but was decreased in the ASD group. In control groups I and II, RVD did not change during exercise. In ASD, and control groups I and II, the peak velocity of circumferential fiber shortening (Vcf) was increased during exercise, and the peak negative Vcf was significantly decreased. However, these parameters exhibited impaired responses during exercise in the PH group. Abnormal interventricular septal (IVS) motion at rest tended to become normal during exercise in 12 of 16 pts with ASD. In all pts with PH, however, IVS motion did not change substantially during exercise. There were similar parameter responses between the PH and CP groups. Two-dimensional echocardiography showed that: The left ventricular short-axis view demonstrated a diastolic left ventricular configuration which changed from oblique to relatively circular orientation during exercise in the ASD group. In four of five pts with PH, the diastolic configuration of the left ventricle was oblique because of a loss of the normal curvature of the IVS at rest and during exercise. The diastolic left ventricular configuration improved during exercise in only one pt with PH, with slightly elevated pulmonary arterial systolic pressure as in the ASD group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Serum ferritin and isoferritins are tools for diagnosis of active adult Still's disease.

OBJECTIVE: Still's disease is an acute systemic inflammatory disorder. There are no pathognomonic symptoms or specific laboratory abnormalities. Serum ferritin concentration in rheumatoid arthritis together with some plasma glycoproteins such as alpha 2-glycoprotein and C-reactive protein are part of the response to inflammation. Ferritin in plasma is glycosylated and the sialoglycosylated forms increase its microheterogeneity. Our purpose was to confirm in a large series that high values of ferritin can be found in adult Still's disease (ASD) and to see if a specific isoferritin can be isolated in this disease compared with the other systemic diseases. METHOD: Thirty-one sera were investigated from 11 men and 9 women with ASD and compared with 27 sera from 27 patients with systemic diseases. We studied the course of one case of ASD for 15 months. Serum ferritin was determined by immunoenzymology (Abbott Ferrizin). The isoferritins were investigated by isoelectric focussing and the percentage of glycosylation by affinity for concanavalin A (Con-A). RESULTS: In patients with active ASD, the ferritin levels were higher than in patients with inactive ASD or other systemic diseases: p < 0.001. The glycoforms of ferritin were basic and the proportion of ferritin bound to Con-A was lower than other ASD: p < 0.001. CONCLUSIONS: Serum ferritin levels have a diagnostic value for acute ASD. The study of sialylation and abnormalities in the glycosylation of ferritin helps to discriminate ASD from arthritis or other systemic diseases. In conclusion, the glycoform of isoferritins and the percentage of glycosylation offers an additional tool for the diagnosis of Still's disease.

Adolescent↗
PubMed1978

Hereditary atrial septal defect. Update of a large kindred.

A large pedigree wherein members are predisposed to atrial septal defect (ASD) and associated cardiovascular anomalies has been studied. There were ten direct line relatives with ASD verified by cardiac catheterization and/or surgery and in one case by reliable medical history. The pedigree shows vertical transmission of ASD through four generations. Estimates of the genetic segregation ratio were near 50%, indicating that predisposition to ASD among family members was due to a deleterious autosomal dominant gene. Family members have also manifested other congenital heart anomalies, consistent with pleiotropic effects of the putative gene. Electrocardiograms in six ASD patients revealed an absence of prolonged P-R interval. In the light of prior studies showing prolonged P-R interval in familial ASD, we suggest the existence of at least two distinct hereditary varieties of ASD, one with and one without a prolonged P-R interval.

Adolescent↗
PubMed2005

Validation of the phenomenon of autistic regression using home videotapes.

CONTEXT: To date, there has been no objective validation of the phenomenon of autistic regression early in life. OBJECTIVE: To validate parental report of autistic regression using behavioral data coded from home videotapes of children with autism spectrum disorder (ASD) vs typical development taken at 12 and 24 months of age. DESIGN: Home videotapes of 56 children's first and second birthday parties were collected from parents of young children with ASD with and without a reported history of regression and typically developing children. Child behaviors were coded by raters blind to child diagnosis and regression history. A parent interview that elicited information about parents' recall of early symptoms from birth was also administered. SETTING: Participants were recruited from a multidisciplinary study of autism conducted at a major university. PARTICIPANTS: Fifteen children with ASD with a history of regression, 21 children with ASD with early-onset autism, and 20 typically developing children and their parents participated. MAIN OUTCOME MEASURES: Observations of children's communicative, social, affective, repetitive behaviors, and toy play coded from videotapes of the toddlers' first and second birthday parties. RESULTS: Analyses revealed that infants with ASD with regression show similar use of joint attention and more frequent use of words and babble compared with typical infants at 12 months of age. In contrast, infants with ASD with early onset of symptoms and no regression displayed fewer joint attention and communicative behaviors at 12 months of age. By 24 months of age, both groups of toddlers with ASD displayed fewer instances of word use, vocalizations, declarative pointing, social gaze, and orienting to name as compared with typically developing 24-month-olds. Parent interview data suggested that some children with regression displayed difficulties in regulatory behavior before the regression occurred. CONCLUSION: This study validates the existence of early autistic regression.

Age of Onset↗
PubMed1996

Photoreactive analog of peptide FN-C/H-V from the carboxy-terminal heparin-binding domains of fibronectin supports endothelial cell adhesion and spreading on biomaterial surfaces.

The extracellular matrix protein fibronectin (FN) plays an important role in cell adhesion, spreading, and motility. Several cell-adhesion promoting domains exist within fibronectin, and peptide sequences from these domains have been shown to play an important role in cell interactions with fibronectin. Recently, a peptide sequence (FN-C/H-V) from the 33/66 kD carboxy-terminal heparin-binding domains of fibronectin was shown to promote the adhesion and spreading of vascular endothelial cells in vitro. Endothelial cell spreading on this peptide was followed by cytoskeletal reorganization, focal contact formation, and, ultimately, cell migration. In the current study, a photoreactive analog of FN-C/H-V (ASD-V) was generated using a heterobifunctional photoreactive crosslinking agent, sulfosuccinimidyl 2-(pazidosalicylamido) ethyl-1,3'-dithio-propionate. ASD-V was then covalently coupled to polystyrene (PS) and polyethylene terephthalate film (PET) in order to assess the utility of ASD-V for preparing biomaterial surfaces with endothelial cell-adhesion promoting properties. The effects of pre-adsorption time and initial coating concentration on the efficiency of ASD-V coupling to PS and to PET were examined. Contact angle measurements and atomic force microscopy were used to characterize ASD-V-modified surfaces. Finally, the adhesion and spreading of vascular endothelial cells on ASD-V-modified surfaces was assessed. Our results suggest that photoreactive peptides are an effective and convenient means of modifying biomaterial surfaces to impart adhesion-promoting properties and that ASD-V, when coupled to PS and PET, promotes endothelial cell adhesion and spreading and may therefore be useful as a biomaterial surface modification in applications where re-endothelialization is desired (e.g., autologous endothelial seeding of vascular grafts, or transplantation of genetically engineered endothelial cells via polymer-coated stents.

Animals↗
PubMed1996

Acute stress disorder, subsequent posttraumatic stress disorder and depression after a series of typhoons.

From August to November 1992, five typhoons struck the U.S. Pacific island territory of Guam. Three hundred and twenty subjects exposed to all five typhoons participated in a population survey measuring their acute stress symptoms and subsequent diagnoses of posttraumatic stress disorder (PTSD) and depression. A 23-item scale approximating the new DSM-IV diagnosis of acute stress disorder (ASD) was used to classify subjects into three groups based on their symptoms one week after the first typhoon: (1) probable ASD, (2) an early traumatic stress response (ETSR) of fear, intrusion, avoidance, and arousal, without dissociation, and (3) no acute diagnosis. A multi-dimensional measure of PTSD and the Zung Self-Rating Depression Scale were used to assess PTSD and depression 8 months after the first storm. The point prevalence of ASD at one week was 7.2%. An additional 15% of subjects had ETSR. Subjects with probable ASD at one week had significantly increased rates of PTSD and somewhat higher rates of depression at 8 months than those without ASD. In contrast, subjects with ETSR at one week did not have a poorer outcome than those with no acute diagnosis. These findings suggest that ASD is prognostically important, but also indicate that all acute stress symptoms do not have the same discriminative value. In this study, the acute dissociative symptoms of emotional numbing and derealization differentiated highly symptomatic subjects at risk for subsequent psychopathology (ASD) from others who were highly symptomatic at one week, but then had a more benign, posttraumatic course (ETSR).

Adult↗
PubMed2000

Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders.

BACKGROUND: Family studies have demonstrated that the autism spectrum disorders (ASDs) have a major genetic etiologic component, but expression and penetrance of the phenotype are variable. Mice with null mutations of Hoxa1 or Hoxb1, two genes critical to hindbrain development, have phenotypic features frequently observed in autism, but no naturally occurring variants of either gene have been identified in mammals. METHODS: By sequencing regions of genomic DNA of patients with autism spectrum disorders, we detected a substitution variant at HOXA1 and an insertion variant at HOXB1, both in coding regions of the genes. Fifty-seven individuals ascertained for a diagnosis of an ASD, along with 166 of their relatives, were typed for these variants. Two non-ASD populations were typed, and the frequency of the newly identified alleles was determined in all groups. The genotypes of the ASD families were tested for conformation to Hardy-Weinberg proportions and Mendelian expectations for gene transmission. RESULTS: The frequency of the variants was 10-25% in persons of European or African origin. In the ASD families, there was a significant deviation from the HOXA1 genotype ratios expected from Hardy-Weinberg proportions (P = 0.005). Among affected offspring, a significant deviation from Mendelian expectation in gene transmission (P = 0.011) was observed. No statistically significant effects were detected when the same analyses were applied to the HOXB1 locus, but there was evidence of an interaction between HOXA1, HOXB1, and gender in susceptibility to ASDs. CONCLUSIONS: The results support a role for HOXA1 in susceptibility to autism, and add to the existing body of evidence implicating early brain stem injury in the etiology of ASDs.

Abnormalities, Multiple↗
PubMed2001

Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still's disease.

OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine that is involved in immunologically mediated tissue damage, but its bioactivity is regulated in vivo by its soluble decoy receptor, IL-18 binding protein (IL-18BP). This study was undertaken to determine levels of IL-18 and IL-18 binding inhibition in the blood of patients with adult-onset Still's disease (ASD). METHODS: Serum concentrations of IL-18 in ASD patients were compared by enzyme-linked immunosorbent assay (ELISA) with those in patients with other systemic rheumatic diseases and healthy controls. The biologically active mature protein of IL-18 was detected by Western blot analysis with anti-IL-18 antibody and its induction of interferon-gamma (IFNgamma) secretion from IL-18-responding human myelomonocytic KG-1 cells. The inhibitory activity on IL-18 binding to its receptor was determined by 125I-IL-18 binding inhibition assay using the Chinese hamster ovary cell line transfected with a murine IL-18 receptor (CHO-K1/mIL-18R). RESULTS: Concentrations of serum IL-18 were extremely elevated in patients with active ASD compared with those in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, Sjogren's syndrome, or healthy individuals. Levels of IL-18 were found to correlate with serum ferritin values and disease severity in ASD. Western blot analysis revealed that serum samples from patients with active ASD contained an 18-kd polypeptide of IL-18, corresponding in size to the mature form. Accordingly, the samples were able to induce IFNgamma secretion from KG-1 cells, which was largely abolished by neutralizing anti-IL-18 antibody. However, the level of IL-18 bioactivity was more than 10-fold weaker than the concentration of IL-18 protein measured by ELISA. Serum samples from patients with active ASD showed an inhibitory effect on the binding of 125I-IL-18 to CHO-K1/mIL-18R cells, and this activity was associated with elevation of IL-18. CONCLUSION: These data indicate that systemic overproduction of IL-18 may be closely related to the pathogenesis of ASD, despite the restriction on its inflammatory activity by IL-18 binding inhibitors such as IL-18BP. The disease activity appears to be determined on the basis of the relative levels of IL-18 and its specific inhibitors.

Adult↗
PubMed2006

Comparison of outcome and complications using different types of devices for percutaneous closure of a secundum atrial septal defect in adults: a single-center experience.

The objective of this study was to find differences in outcome and complications using three different types of devices for percutaneous atrial septal defect (ASD) closure in adults. Percutaneous closure of a secundum-type ASD is increasingly performed in adult patients. All adult patients who underwent a percutaneous closure of a secundum-type ASD in our center between November 1996 and November 2004 were included. Failure was defined as dislocation or embolization of the device, which required surgical intervention. Periprocedural and mid-term complications were registered. Sixty-five patients, mean age 45.7+/-18.1 years (18 men, 47 women), underwent a percutaneous closure of an ASD with an ASDOS in 3, an Amplatzer in 36, and a Cardioseal/Starflex closure device in 26 patients. During an overall median follow-up of 1.2 years (range, 0.1-6.7 years), the failure occurred in four patients, all Cardioseal/Starflex (P=0.04). Within the Cardioseal/Starflex subgroup, the ASD and device diameters were significantly higher in those patients in whom the primary endpoint occurred compared to the others, 18.8+/-3.8 vs. 13.0+/-3.8 mm for ASD diameter (P=0.01) and 40 (range, 40-43) vs. 33 mm (range, 20-40) for device diameter (P=0.008). Overall complications were transient arrhythmias in 15.4%, pericardial effusion in 1.5%, and transient ischemic attack in 1.5%. Complete closure 6 months after the procedure occurred in 79.6%, without difference between the devices. Percutaneous ASD closure seems to be a relatively safe and effective procedure. However, using the larger Cardioseal/Starflex devices for closure seems to be related to a higher rate of device dislocation and embolization.

Adult↗
PubMed2004

Closure of defects of the atrial septum in adults using the Amplatzer device: 100 consecutive patients in a single center.

BACKGROUND: Transcatheter device closure of atrial septal defects (ASD) is an alternative to surgery, but experience is limited in adults, especially in those with large (> 26 mm) defects. HYPOTHESIS: We investigated the safety, efficacy, and learning curve for closure of ASD and patent foramen ovale (PFO) using the Amplatzer device. METHODS: In all, 101 procedures were carried out in 100 consecutive adult patients in a single cardiac center between July 1998 and August 2002. RESULTS: Preprocedure diagnosis was ASD and PFO in 50 patients each. A device was deployed in 94 of 101 attempts (93%) in 94 of 100 patients (94%). Atrial septal defect device sizes were 10-38 mm, median 24 mm, and 40% were > 26 mm. Major complications occurred in 2 of 100 patients (2%). One ASD device displaced requiring surgery within 24 h and one patient with PFO experienced pericardial tamponade; there were no deaths. Local vascular complications occurred in 4 of 100 (4%) and late complications in 4 of 100 (4%) patients. Patent foramen ovale closure was quicker (p<0.001), required less radiation (p=0.04), and was associated with fewer local vascular complications than ASD closure (p=0.04). Deployment of ASD devices > 26 mm was not associated with increased complications, length of procedure, or radiation compared with devices < or = 26 mm (all p>0.05). Complications in the first 35 patients were more frequent than in subsequent patients: 7 of 35 (20%) versus 3 of 65 (4.6%) (p=0.04); procedure and fluoroscopy times (both p<0.001) and radiation doses (p=0.001) were also higher. CONCLUSION: The Amplatzer device is an effective method for transcatheter closure of interatrial defects in adults, including large ASDs up to 38 mm. Major complications are uncommon. A learning curve of approximately 35 cases was suggested by the decline of complications, procedure times, and radiation exposure.

Adult↗