Reading disability, attention-deficit hyperactivity disorder, and the immune system.
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Biomedical subjects
Publications and source records attributed to A R Torres.
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OBJECTIVE: The complement system is a group of blood proteins that play an important role in defending against viral and bacterial infections. The objective of this investigation was to study the plasma levels of the C4B protein in attention-deficit hyperactivity disorder (ADHD) in an attempt to associate infections with the development of some cases of this disorder. METHOD: C4B plasma protein levels were studied using an enzyme-linked immunosorbent assay in a group of 23 subjects meeting DSM-III-R criteria for ADHD and a similar number of age- and sex-matched controls. Also studied were parents of the ADHD subjects. RESULTS: C4B plasma levels (157.0 micrograms/mL) in the ADHD subjects were significantly (p < .01) lower than those (239.3 micrograms/mL) in the normal age-matched subjects. Mothers of the ADHD subjects also had significantly lower C4B values compared with mothers of normal children. On the other hand, C4B values in the fathers were not significantly altered. CONCLUSIONS: Decreased C4B levels in ADHD, if replicated, may represent an important marker for ADHD (or a subgroup of ADHD). It also seems plausible that C4B levels are an important etiological factor for ADHD.
Autism likely results from several different etiologies or a combination of pathological mechanisms. Recent studies suggest that this disorder may be associated with immune abnormalities, pathogen-autoimmune processes and perhaps the major histocompatibility complex (MHC). In a preliminary study we found that 22 autistic subjects had an increased frequency of the extended or ancestral MHC haplotype B44-SC30-DR4. The current study attempted to confirm this observation by studying 23 additional randomly chosen autistic subjects, most of their parents and 64 unrelated normal subjects. In agreement with earlier findings B44-SC30-DR4 was associated with autism. In combining the data from the original and current studies, B44-SC30-DR4 or a substantial fragment of this extended haplotype was represented in 40% of the autistic subjects and/or their mothers as compared to about 2% of the unrelated subjects. It is concluded that one or more genes of the MHC is (are) involved in the development of some cases of autism.
OBJECTIVE: To determine complement C4 protein concentrations in the plasmas of autistic subjects and their family members. DESIGN: Cross-sectional study. SETTING: Center for Persons with Disabilities and the Department of Biology, Utah State University, Logan. PARTICIPANTS: Forty-two autistic subjects (34 males [81%] and eight females [19%]), 50 of their biologic parents, 21 siblings, and 105 normal subjects (56 females [53%] and 49 males [47%]; all white) living in northern Utah. INTERVENTIONS: None. METHODS: The enzyme-linked immunosorbent assay was used to determine C4 protein concentrations in autistic subjects. MAIN RESULTS: Plasma concentration (median, 14.7 g/L of the C4B protein) in autistic patients was significantly (P = .01) decreased compared with that of normal subjects (median, 22.4 g/L). The C4B concentrations in parents and siblings of autistic children were decreased, but not significantly. The C4A protein concentrations in the plasma of autistic subjects and their family members were normal. CONCLUSION: Decreased protein concentrations of C4B may be associated with autism.
BACKGROUND: Late postoperative arrhythmias and right ventricular dysfunction may occur after classic repair of tetralogy of Fallot. METHODS AND RESULTS: During a mean follow-up of 8.9 years (range, 5 to 14 years), 24-hour ambulatory electrocardiographic studies were done in 107 patients after repair of tetralogy of Fallot. Radionuclide angiography was performed in 97, and 78 patients also underwent postoperative heart catheterization. The patients were divided into two groups: group A consisted of 71 patients aged 2 months to 61 years (mean, 6.8 years) in whom the right ventricular approach was used; group B included 36 patients aged 8 months to 39 years (mean, 7.9 years) whose repair was through the right atrium. A transannular patch was employed in 42 (59.2%) patients in group A and in 23 (63.9%) patients in group B. Eighteen patients were adults (> 18 years old) at the time of surgery: 13 (18.3%) in group A and 5 (13.8%) in group B. During a mean follow-up of 9.7 years, 57 (80.3%) group A patients were in New York Heart Association (NYHA) functional class I. Atrial flutter was present in 3 (4.2%) patients, and 28 (39.4%) had significant ventricular arrhythmias (> or = Lown grade 2). Postoperative heart catheterization showed good hemodynamic results in 36 of 54 group A patients studied (12 of whom had ventricular arrhythmias); moderate-to-severe pulmonary regurgitation was present in 14 (25.9%) patients; only 2 (3.7%) patients had right ventricular hypertension. On electrophysiological study, 8 of 28 (28.6%) patients in group A had inducible sustained ventricular tachycardia. Despite antiarrhythmic therapy, 2 of these patients died suddenly, presumably from ventricular arrhythmias. Two other late deaths in group A were caused by heart failure. During a mean follow-up of 7.2 years, 33 of 36 (91.7%) patients in group B were in NYHA functional class I. Atrial flutter was not found in any patient in this group. Only 1 (2.8%) patient, who had moderate-to-severe pulmonary regurgitation, had significant ventricular arrhythmias (> or = Lown grade 2). Postoperative catheterization showed good hemodynamic results in 20 of 24 patients; 3 (12.5%) had moderate-to-severe pulmonary regurgitation, and 1 (4.2%) patient had right ventricular hypertension. Sustained ventricular tachycardia could not be induced in any of the 5 adult patients who underwent electrophysiological studies. One late death (caused by endocarditis) occurred in group B. CONCLUSIONS: The right atrial approach significantly reduced the risk of life-threatening ventricular arrhythmias after repair of tetralogy of Fallot (P < .001) without increasing the incidence of supraventricular arrhythmias. Right ventricular dysfunction and severe pulmonary regurgitation were also more prevalent (P < .01) when the right ventricular approach was used.
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In cases of interrupted aortic arch type A, the end-to-end aortic anastomosis can be enlarged with a left subclavian flap. In type B interruption, the divided left carotid artery is anastomosed to the distal aorta, and the anastomosis can be augmented with a reversed left subclavian flap. These techniques provide a tension-free, much wider, and noncircumferential anastomosis with potential for growth. Using a combined lateral and anterior approach, the duration of circulatory arrest for the intracardiac repair is minimized.
Recent, mostly "in vitro", studies indicate that certain stress protocols may affect differentially immune mechanisms. In agreement with these studies, our "in vivo" results show that 4 consecutive days of intermittent footshock, in rats, depressed the primary antibody response, to a thymic dependent antigen, but enhanced the graft-versus-host response and the capacity to reject an inocula of Walker carcinoma cells. Thus it is concluded that footshock stress is capable of oppositely affecting "in vivo" produced humoral and cellular immune responses.
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Fourteen patients with scimitar syndrome, aged from 4 days to 20 years, underwent surgical treatment between September 1980 and August 1988. Patients were separated into two groups. Group A comprised four neonates with heart failure and severe pulmonary hypertension; part of the right lung was supplied by large aberrant systemic subphrenic arteries (ASSAs) in each. Group B included ten patients (nine children and one adult) with mild to moderate symptoms, normal pulmonary artery pressures; only two had ASSAs. In group A, one neonate with multiple ventricular septal defects underwent pulmonary artery banding but later required a lobectomy because of a lung abscess. The other three neonates underwent ligation of ASSAs; two improved rapidly, and one died of sepsis. In group B, all patients survived intracardiac repair and remain asymptomatic during a follow-up of 24 to 108 (mean 54.9) months. In summary, prognosis after intracardiac repair is excellent in patients without pulmonary hypertension. Neonates with heart failure usually improve after ligation of ASSAs, and pulmonary resection is only indicated in patients with intractable pulmonary sequestrations.
Primary cardiac tumors of the ventricles are very uncommon. During an 8-year period only, nine such patients were encountered: the tumor was primarily in the right ventricle in six, in the left ventricle in two and biventricular in one. There were seven children and two adults in this series. Histologically, the neoplasm was benign in all patients. The tumor was obstructive in six patients, five of whom underwent surgery (complete resection in three, partial excision in one and a Fontan-Kreutzer procedure in one); one neonate died before an operation could be performed. In addition, one patient with an epicardial tumor underwent complete resection. There were no early or late deaths among the six patients treated surgically. The tumor was small and non-obstructive in two patients, who were not operated on: one died suddenly, and the other was followed without intervention. In summary, complete or partial excision of ventricular neoplasms can usually be accomplished with good long-term results. If resection is not possible, effective palliation may be achieved with a Fontan-type operation, excluding the right ventricle from the circulation.
Between September 1980 and August 1988, 21 patients, of mean age 7.3 (range 1-19) years, with ventricular septal defect and aortic valve prolapse, underwent surgery. Aortic insufficiency was mild in three patients, moderate in 13 and severe in five. Surgical repair was performed using a combined transaortic and transpulmonary approach. The prolapsed leaflets were evaluated through the ventricular septal defect before and after valvuloplasty. Using the Trusler technique, the prolapsed cusps were plicated at the level of the commissures; only one patient required aortic valve replacement. After functional assessment of the valve repair, through the ventricular septal defect, during infusion of cardioplegia in the aortic root, the defects were closed through the pulmonary artery, or through a right atriotomy. Mean follow-up was 51.5 (range 3-108) months. One patient developed bacterial endocarditis and died 3 months after surgery. The other 20 patients remained symptom-free. There are no residual ventricular septal defects, and mild residual aortic insufficiency is present in six patients. The mean(s.d.) cardiothoracic ratio decreased from 0.61(0.07) before to 0.49(0.05) after surgery. In summary, preservation and repair of the prolapsed aortic valve is possible even in the presence of severe aortic insufficiency. The combined approach through both great arteries enables good visualization with minimal traction, and accurate assessment of the aortic valvuloplasty through the ventricular septal defect. In addition, problems associated with a right ventriculotomy are avoided.
The proliferation and activation of murine and human T-lymphocytes in a high-protein lymphocyte culture fluid (LCF) is compared to that of cells cultured in 10% fetal bovine serum (FBS). Tumor-infiltrating lymphocytes (TIL) proliferate exponentially in the LCF for up to 46 days and generate cell numbers that are nearly 100,000-fold greater than cells cultured in FBS. This rapid growth of T cells in LCF could have an important impact in adoptive immunotherapy and gene therapy since cell growth is a limiting factor in these technologies.
The anion-exchange separation of complex protein mixtures by displacement chromatography using spacer displacers driven by high-affinity final displacers is demonstrated. Guinea pig serum was separated on a medium-resolution adsorbent using a single heterogeneous mixture of carboxymethyldextran displacers to space the protein components. Mouse liver cytosol was separated on a low-resolution adsorbent using six carboxymethyldextran spacer displacers of increasing column affinity. The demonstration of the purification of alkaline phosphatase from E. coli periplasm by displacement chromatography on a high-performance liquid chromatography column is reviewed. The benefits of spacer displacers for separating minor components from complex biological protein mixtures is discussed. A simplified method for preparing carboxymethyldextran displacers is presented.
Intraoperative placement of catheters to monitor pulmonary artery pressure and cardiac output by oximetry can easily be accomplished under direct vision. The insertion through a saphenous vein cutdown assures a much safer removal, eliminating the risk of bleeding, tamponade, and catheter entrapment.
An agamma calf serum (ACS) was compared to fetal bovine serum (FBS) and calf serum supplemented growth media for both murine and human fusion partners and derived hybridoma cells. The variables analyzed were cloning efficiencies, growth characteristics, and MAb production levels. Cultures were established in each serum source, and supernatants were kept for analysis. For cloning efficiencies, the results indicate that although there is no clear advantage in the performance of FBS-supplemented medium, ACS-supplemented RPMI 1640 medium can be used to clone hybridomas and the fusion partners. When analyzed for MAb production in the various sera, the hybridoma cell lines used in this study appeared to produce up to twice as much immunoglobulin when grown in ACS as when grown in supplemented medium. IgG- and IgM-secreting hybridoma cultures should be checked independently for antibody production. Six out of eight murine and human hybridoma cell lines produced higher levels of MAbs when grown in ACS.
A right submammarian incision with anterior thoracotomy was performed in 89 female patients to repair simple and complex forms of atrial septal defects. Patients' ages ranged from 8 to 38 years (mean 21.5 years). Seventy-seven had secundum-type atrial septal defects, one had the primum type, and 11 had an associated partial anomalous pulmonary venous connection. The patients were divided into two groups: 57 patients in group A, in whom, after a breast flap was elevated, a transpectoral approach was used to enter the chest; 32 patients in group B, in whom the pectoral muscle was not divided and a subpectoral approach was used. Aortic cannulation was accomplished without difficulty in all 89 patients. There were no early or late deaths in either group. Follow-up ranged from 24 to 108 months (mean 63.7 months) and included 86 patients, who were free of symptoms. In group A, however, among 54 patients examined, the volume of the right breast and pectoral muscle was smaller than the left in four patients (7.4%), and 21 (38.8%) had persistent right periareolar numbness. In 32 patients evaluated in group B, no difference was noted in the size of the breasts, and persistent numbness was present in four patients (12.5%). In summary, atrial septal defects or anomalous pulmonary venous connections can be safely repaired through a right submammarian thoracotomy in female patients. The subpectoral approach offers better results because breast asymmetry and paresthesias are significantly less prevalent (p less than 0.01).
Between September 1980 and August 1988, 47 patients younger than 12 months (27 neonates and 20 infants) underwent repair of aortic coarctation. Three surgical techniques were used: patch aortoplasty (group A: 5 neonates and 3 infants, mean age 4.5 months), subclavian flap (group B: 11 neonates and 8 infants, mean age 3.1 months), and the combined resection-flap procedure (group C: 11 neonates and 9 infants, mean age 2.7 months). There were 8 early deaths (3 in group A, 3 in group B, and 2 in group C) and 2 late deaths (both in group B), all of which occurred in patients with complex coexisting anomalies. Follow-up included 37 patients (5 in group A, 14 in group B, and 18 in group C) and ranged from 28 to 108 months (mean 68.0, 60.8, and 51.7 months, respectively). Residual arm-leg pressure gradients greater than 10 mm Hg were detected in 4 of 5 patients in group A, 11 of 14 patients in group B, and 1 of 18 patients in group C (p less than 0.005). There were no reoperations in any infant operated on after 1 month of age in any group (0% risk). However, 4 patients who underwent repair during their neonatal period, with recurrent gradients greater than 20 mm Hg, have required reoperation: in group A, 1 of 5 patients (20% risk) (1 of 2 neonates or 50% risk); in group B, 3 of 14 patients (21% risk) (3 of 9 neonates or 33% risk); and none in group C (0% risk in infants and neonates) (p less than 0.001). In summary, residual gradients and risk of recoarctation are significantly higher when a patch or a subclavian flap had been used for repair. The combined resection-flap procedure (an end-to-end anastomosis enlarged with a subclavian flap) is more effective in avoiding gradients and preventing recoarctation, especially in neonates.