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PubMed1996

Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S. typhimurium delta cya delta crp: persistence, stability and immune response in swine.

The spike protein from transmissible gastroenteritis virus (TGEV) was expressed in attenuated S. typhimurium delta cya delta crp delta asd chi 3987. Three partially overlapping fragments of TGEV S gene, encoding the amino-terminal, intermediate, and carboxy-terminal end of the protein, as well as the full length gene were inserted into the asd+ plasmid pYA292 to generate recombinant plasmids pYATS-1, pYATS-2, pYATS-3, and pYATS-4, respectively, which were transformed into S. typhimurium chi 3987. Recombinant S. typhimurium chi 3987 (pYATS-1) and chi 3987 (pYATS-4) expressing constitutively a 53 kDa amino-terminal fragment of the S protein and the full length protein (144 kDa), respectively, showed high stability. After 50 generations in vitro 60% and 20% of the bacteria transformed with pYATS-1 and pYATS-4, respectively, expressed the S-protein antigen. Since S. typhimurium chi 3987 (pYATS-1) showed a better level of expression and stability in vitro, this recombinant strain was selected as a potential bivalent vector to induce both immunity to Salmonella and TGEV in swine. In order to study colonization of swine tissues by S. typhimurium delta cya delta crp, a gene conferring resistance to rifampicin was cloned into the chromosome of S. typhimurium chi 3987, generating chi 4509 strain. Both S. typhimurium chi 4509 (pYA292) and chi 4509 (pYATS-1) colonized the ileum of orally inoculated swine with clearance of bacteria between days 10-20 post-infection. The expression of the amino-terminal fragment of the S protein diminished the ability of S. typhimurium chi 4509 (pYATS-1) to colonize deep tissues. The recombinant strain S. typhimurium chi 3987 (pYATS-1) induced TGEV specific antibodies in both serum and saliva of orally inoculated swine.

Animals↗
PubMed1992

Early degenerative joint disease simulating impingement syndrome: arthroscopic findings.

Eighteen patients who underwent shoulder arthroscopy for impingement syndrome were shown at operation to have coexisting glenohumeral degenerative joint disease (DJD) which was not apparent during preoperative clinical and radiographic evaluation. Because traditional ("open") techniques of anterior acromioplasty do not allow inspection of the glenohumeral joint, it is almost certain that this pathology would have been missed at operation if open acromioplasty had been performed. We conclude that arthroscopic subacromial decompression (ASD), by allowing easy inspection of the glenohumeral joint, offers a distinct advantage over traditional acromioplasty. Furthermore, arthroscopic evaluation of some of these patients' glenohumeral joints provided us with evidence supporting the existence of subluxation arthropathy. We have also developed a new clinical test, the "compression-rotation" test, which has been helpful in distinguishing patients with both impingement syndrome and early DJD syndrome from those with isolated impingement syndrome. Although patients in this study appeared to be doing well at short-term follow-up status post-ASD and glenohumeral debridement, no long-term results are yet available.

Adult↗
PubMed1995

Arthroscopic subacromial decompression: two- to seven-year follow-up.

Arthroscopic subacromial decompression (ASD) was performed in 88 patients (90 shoulders) with stage II or early III impingement syndrome of the shoulder unresponsive to nonoperative treatment. The purpose of this retrospective study was to evaluate the follow-up an average of 41 months (range 24 to 82 months) after surgery. We wished to compare results in (1) patients with and without rotator cuff tears, (2) in athletes and nonathletes, and (3) in throwers and nonthrowers. Patients were evaluated by (1) Neer's Criteria for Satisfactory Result, (2) the UCLA Shoulder RAting Scale, (3) the Shoulder and Elbow Surgeons Rating Scale, (4) a detailed questionnaire, and (5) patient satisfaction. In the follow-up group (n = 90), 80% met Neer's criteria for satisfactory result; 94% had satisfactory results by the UCLA Shoulder Scale; 95% had a satisfactory result by the Shoulder and Elbow Society Scale; and 93% of shoulder patients expressed satisfaction at follow-up. There were no statistically significant differences in function between the group without rotator cuff tear (n = 47) and the group with rotator cuff tear (n = 43). Satisfactory results were obtained in 68% of throwing athletes and in 90% of nonthrowing athletes (P < .05) by the Neer Rating, whereas only 50% of competitive baseball and softball pitchers had satisfactory results. Out impression is that ASD is an acceptable alternative to open anterior acromioplasty with comparable results for the treatment of the impingement lesion. There were no differences in result in patients who had a partial rotator cuff tear and those who had no tear.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromion↗
PubMedDate not supplied

Protein antigens of Mycobacterium leprae.

Protein antigens of Mycobacterium leprae have been identified by screening the lambda gt11, pYA626 and pHC79::M. leprae genomic libraries with pooled sera from leprosy patients and with antiserum to M. leprae cell wall protein (CWP) aggregate. Immunological screening of the lambda gt11 library with pooled sera from 21 lepromatous (LL) leprosy patients resulted in the identification of 19 antigens that are apparently different from previously identified M. leprae antigens. Five additional antigens were identified by screening the lambda gt11 library with pooled sera from 30 borderline tuberculoid or tuberculoid patients. Four other antigens were identified by screening the lambda gt11 library with anti-CWP. Two groups of recombinant cosmids were identified by screening the pHC79 library with LL patients' sera: one group specified proteins that reacted with monoclonal antibodies (mAb) against the 65-kDa protein and against the 18-kDa protein; the other group specified a 15-kDa protein that did not react with any of the mAb that were tested. One pYA626 clone also specified a 15-kDa protein that reacted with LL patients' sera, but did not react with any mAb. Genes specifying several of these antigens have been subcloned into the Asd+ plasmid vector pYA292 and have been introduced into a delta cya delta crp delta asd Salmonella typhimurium strain to evaluate the ability of individual M. leprae proteins to elicit immune responses against M. leprae infection.

Animals↗
PubMed1993

Orthotopic heart transplantation for congenital heart disease. Technical considerations.

Heart transplantation for congenital heart disease poses unique problems because of structural anomalies and previous corrective and palliative surgery. In the period between May 1985 and February 1992 a total of 231 orthotopic heart transplants were performed at our hospital -22 of these procedures were carried out in patients with congenital heart disease. The patient's ages ranged from 1 month to 51 years (median 10 years). There were 13 patients in the paediatric group (under 16 years) and 9 patients in the adult group (16 years or older). The diagnoses included univentricular connections (8 patients), complex morphology (4 patients), congenitally corrected transposition of the great arteries (TGA) (3 patients), hypoplastic left heart syndrome (2 patients), Fallot's tetralogy, tricuspid atresia, TGA, pulmonary atresia with intact ventricular septum and atrial septal defect (ASD) and ventricular septal defect (VSD). These patients had protected pulmonary circulation due to previous surgery or as a result of intrinsic pulmonary stenosis. Seventeen patients (77%) had undergone 29 prior operations (21 palliative and 8 corrective) including Blalock-Taussig shunts, pulmonary artery (PA) banding, ASD and VSD repair, Fontan procedure and Mustard operation. There were 2 early deaths in the paediatric group and 4 early deaths in the adult group, but no late deaths. The cause of death was multi-organ failure following uncontrollable haemorrhage in 3 patients, sepsis in 1 patient and donor organ failure in the 2 paediatric patients. Specific surgical manoeuvres were required to create the normal anatomical configuration. These included the rerouting of venous circulation, pulmonary artery reconstruction and atrial septation. Adequate donor tissue was taken to permit satisfactory reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Real-time 3-dimensional echocardiography in assessing atrial and ventricular septal defects: an echocardiographic-surgical correlative study.

OBJECTIVE: The aim of this study is to explore the feasibility and the value of real-time 3-dimensional echocardiography (RT3DE) in quantitative evaluation of the size of atrial septal defect (ASD) and ventricular septal defect (VSD) and to correlate with the surgical findings. METHODS: Thirty eight patients with ASD and/or VSD were examined with RT3DE. Three-dimensional image data-base was post-processed using 3D work-station. The results were compared with the results measured by 2-dimensional echocardiography and surgical findings. RESULTS: RT3DE produced novel views of congenital septal defects and improved quantification of the size of the defect. The sizes obtained from 3DE have better correlation with surgical findings than diameter measured by 2-dimensional echocardiography (r = 0.69 vs r = 0.92). CONCLUSIONS: RT3DE offers additional special information in congenital heart disease without extending examining time, permits quantitative recording of septal defect dynamics, and enhances the understanding of complex cardiac anatomy and elucidation of the disease mechanism. It is a potentially valuable clinical tool for diagnosing and managing patients with congenital heart disease.

Adolescent↗
PubMed2005

Effect on right ventricular volume of percutaneous Amplatzer closure of atrial septal defect in adults.

In adult patients with atrial septal defects (ASDs), right ventricular (RV) cavity size may return to normal after operative closure. This study demonstrated improved RV volumes and right atrial areas in 20 adult patients after successful transcatheter closure of large ASDs. RV volumes decreased by 22%, 30%, and 41% at 1 day, 1 month, and 6 months, respectively, after the procedure. Right atrial areas decreased by 5%, 23%, and 26%, respectively, over the same time.

Adult↗
PubMed2005

Effect of transcatheter atrial septal defect closure in children on left ventricular diastolic function.

The acute impact of transcatheter atrial septal defect (ASD) closure on left ventricular (LV) diastolic function was assessed in 15 consecutive children, and pre- and postclosure data were compared with those in a matched group of controls. The data indicate that transcatheter ASD closure leads to an immediate improvement in LV diastolic function as assessed by septal myocardial Doppler tissue imaging and LV inflow velocity propagation. The improvement in LV diastolic properties correlates with the degree of right ventricular volume overload.

Adolescent↗
PubMed2005

Global and regional left ventricular function in patients undergoing transcatheter closure of secundum atrial septal defect.

This study sought to evaluate global and regional left ventricular (LV) function before and early after device closure of atrial septal defects (ASDs) in patients with normal pulmonary pressure. Global LV diastolic function was unaffected by ASD closure. An improvement in global LV systolic function at rest resulted in an increase in stroke volume at rest. Nevertheless, total cardiac output did not change after the procedure, because of a decrease in heart rate at rest counterbalancing the increase in stroke volume. Thus, lateral and inferior LV regional systolic function were preserved after device implantation. Moreover, no changes in regional LV diastolic function were highlighted during the study.

Adolescent↗
PubMed2005

Maternal health in pregnancy and intellectual disability in the offspring: a population-based study.

PURPOSE: The aim of the study is to investigate the relationship between common maternal conditions and intellectual disability (ID) of unknown cause in the offspring. METHODS: Information about the maternal health of children with and without ID was obtained by using record linkage. For mothers with specific medical conditions, proportions of children with mild to moderate ID, severe ID, and autism spectrum disorder (ASD) with ID were compared with those who did not have ID. RESULTS: There was an increased risk for mild to moderate ID in children of mothers with asthma (odds ratio [OR], 1.52; confidence interval [CI], 1.26-1.83]), diabetes (OR, 1.69; CI, 1.26-2.27), a renal or urinary condition (OR, 2.09; CI, 1.39-3.14), and epilepsy (OR, 3.53; CI, 2.56-4.84). ASD risk was increased for children of women with diabetes (OR, 2.89; CI, 1.28-6.51) and epilepsy (OR, 4.57; CI, 1.69-12.31). For anemia (n = 1101), there was an increased risk for severe ID (OR, 5.26; CI, 2.16-12.80). CONCLUSIONS: The increased risk for ID in offspring of mothers with such conditions as asthma and diabetes is particularly important for disadvantaged or ethnic populations, for whom these conditions are more prevalent and may be less well managed.

Adolescent↗
PubMed2005

Recovery after arthroscopic subacromial decompression: prognostic value of the subacromial injection test.

PURPOSE: To evaluate the use of a steroid/local anesthetic subacromial injection as a prognostic tool for patient recovery following arthroscopic subacromial decompression (ASD). TYPE OF STUDY: Prospective cohort study. METHODS: A local anesthetic/steroid subacromial injection was administered to all patients with a clinical diagnosis of subacromial impingement syndrome. In the event of a negative result to the injection test, the diagnosis was confirmed by computed tomographic arthrography or magnetic resonance imaging. All patients underwent standard ASD. The outcome was assessed using the Constant score, performed preoperatively, at 3 weeks, 3 months, and at discharge. The eventual functional outcome was correlated with the results of the injection test and the operative findings. RESULTS: There were 101 patients (53 male, 48 female), with a mean age of 52 years (range, 21 to 77 years) in the study. Patients were followed-up for a mean of 14 months (range, 3 to 24 months). All patients had an impingement lesion noted at arthroscopy. The mean preoperative Constant score for the entire group was 48 points (range, 20-67) with a postoperative mean of 81 (range, 46-98). Sixteen patients had a negative preoperative injection test. The mean improvement in this group was 21 points (47 rising to 68) compared with 35 points (48 to 83) in the positive group (P < .05, Mann-Whitney U test). The groups were otherwise similar for age, gender, and operative findings. CONCLUSIONS: The steroid/local anesthetic injection test is a useful tool both diagnostically and prognostically in patients with subacromial impingement syndrome. In patients with a confirmed diagnosis but a negative test there is still a significant improvement in the postoperative Constant score, but this is of a lesser degree than in those with a positive result to local anesthetic injection. LEVEL OF EVIDENCE: Level III, Diagnostic Study of Nonconsecutive Patients.

Adult↗
PubMed2006

Right-sided Maze procedure for atrial tachyarrhythmias in congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) that causes right atrial dilatation is commonly associated with atrial flutter and/or fibrillation (AFl/F). To reduce late recurrence of AFl/F in patients undergoing repair of CHD, we utilized a concomitant right-sided maze procedure. METHODS: From 1993 to 2003, 99 patients with CHD and associated AFl/F underwent a concomitant right-sided maze procedure at the time of CHD repair. Ages ranged from 9 to 72 years (median, 43 years). Atrial flutter and/or fibrillation was paroxysmal in 81 and chronic in 18; duration ranged from less than 1 month to 39.5 years (median, 2.9 years). Primary cardiac diagnoses were Ebstein anomaly (n = 47), other congenital tricuspid regurgitation (n = 19), univentricular heart (n = 11), isolated atrial septal defect (ASD, n = 8), tetralogy of Fallot (n = 8), and other (n = 6). RESULTS: Other concomitant procedures included tricuspid valve repair or replacement (n = 70), ASD closure (n = 39), and pulmonary valve procedures (n = 18). There were 6 early deaths. At hospital dismissal, 83 patients were free of AFl/F and 63 were in sinus rhythm. Follow-up in 87 of the 93 early survivors extended up to 8 years (mean, 2.7 years). There were 4 late deaths, all from noncardiac causes. Of the 83 known late survivors, 77 (93%) were free of AFl/F. Eighty-two of the 83 survivors were in New York Heart Association class I or II. CONCLUSIONS: In patients with AFl/F associated with CHD, a concomitant right-sided maze procedure at the time of intracardiac repair is effective in reducing late recurrent AFl/F. Most patients enjoy an excellent quality of life.

Adolescent↗
PubMed2006

Abnormal social behaviors in young and adult rats neonatally infected with Borna disease virus.

Autism spectrum disorders (ASD) have been the focus of a great deal of research and clinical speculation. This intense interest relates to both the perplexing pathogenesis and devastating consequences of these disorders. One of the obstacles to understanding the pathogenesis of autism and to developing efficient treatment has been the paucity of animal models that could be used for hypotheses-driven mechanistic studies of abnormal brain and behavior development and for the pre-clinical testing novel pharmacological treatments. In this report, we briefly review our animal model of ASD based on neonatal Borna disease virus (BDV) infection and present new data about abnormal social interaction in adult BDV-infected rats. We found that neonatal BDV infection profoundly affected social behaviors in adult rats. Compared to the control rats, both 90- and 180-day-old infected rats spent less time in active social interaction and more time in following their partners. In the intruder-resident test, the BDV-infected resident rats exhibited less aggression towards the intruders and showed more the following-the-intruder behavior. The following-the-partner behavior may be an example of "stereotypic" activity due to BDV-induced abnormal social communication between rats. The previously published results and present findings indicate that neonatal BDV infection significantly altered the normal pattern of social interaction in rats. Co-localization of activated microglia and dying Purkinje cells in BDV-infected rats suggests that the BDV model could be used to study a pathogenic link of Purkinje cell dropout and neuroinflammation to abnormal social behaviors.

Age Factors↗
PubMed2006

Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders.

Clinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy and some inheritable metabolic disorders. Propionic acid (PPA) is a short chain fatty acid and an important intermediate of cellular metabolism. PPA is also a by-product of a subpopulation of human gut enterobacteria and is a common food preservative. We examined the behavioural, electrophysiological, neuropathological, and biochemical effects of treatment with PPA and related compounds in adult rats. Intraventricular infusions of PPA produced reversible repetitive dystonic behaviours, hyperactivity, turning behaviour, retropulsion, caudate spiking, and the progressive development of limbic kindled seizures, suggesting that this compound has central effects. Biochemical analyses of brain homogenates from PPA treated rats showed an increase in oxidative stress markers (e.g., lipid peroxidation and protein carbonylation) and glutathione S-transferase activity coupled with a decrease in glutathione and glutathione peroxidase activity. Neurohistological examinations of hippocampus and adjacent white matter (external capsule) of PPA treated rats revealed increased reactive astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 immunoreactivity) suggestive of a neuroinflammatory process. This was coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3' immunoreactivity), and an increase in phosphorylated CREB immunoreactivity. We propose that some types of autism may be partial forms of genetically inherited or acquired disorders involving altered PPA metabolism. Thus, intraventricular administration of PPA in rats may provide a means to model some aspects of human ASD in rats.

Animals↗
PubMed2005

Functional disconnectivity of the medial temporal lobe in Asperger's syndrome.

BACKGROUND: Autistic spectrum disorders (ASD) are neurodevelopmental conditions that may be caused by abnormal connectivity between brain regions constituting neurocognitive networks for specific aspects of social cognition. METHODS: We used three-way multidimensional scaling of regionally parcellated functional magnetic resonance imaging (fMRI) data to explore the hypothesis of abnormal functional connectivity in people with ASD. Thirteen high-functioning individuals with Asperger's syndrome and 13 healthy volunteers were scanned during incidental processing of fearful facial expressions. RESULTS: Using permutation tests for inference, we found evidence for significant abnormality of functional integration of amygdala and parahippocampal gyrus (p < .05, false discovery rate [FDR] corrected) in people with Asperger's syndrome. There were less salient abnormalities in functional connectivity of anterior cingulate, inferior occipital, and inferior frontal cortex, but there was no significant difference between groups in whole brain functional connectivity. CONCLUSIONS: We conclude there is evidence that functional connectivity of medial temporal lobe structures specifically is abnormal in people with Asperger's syndrome during fearful face processing.

Adult↗
PubMed2026

CACNA1C Genetic Variants Differentially Affect Neuronal Networks Through Divergent Pathways.

BACKGROUND: CACNA1C encodes the pore-forming subunit of the L-type calcium channel Cav1.2. Common variants in CACNA1C are associated with psychiatric disorders, whereas rare single nucleotide variants cause CACNA1C-related disorder, a multisystem disorder with symptoms that include autism spectrum disorder (ASD), intellectual disability, and seizures. However, the cellular mechanisms linking CACNA1C dysfunction to neurodevelopmental phenotypes remain poorly understood. METHODS: We generated isogenic CACNA1C loss-of-function induced pluripotent stem cell lines and reprogrammed a line from an individual carrying a novel predicted gain-of-function variant (p.Ala1521Pro) in CACNA1C. Neuronal activity was assessed using multielectrode arrays, pharmacological manipulation, and gene expression analysis. Early developmental phenotypes were examined using quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry, and RNA sequencing. RESULTS: Neurons carrying CACNA1C variants displayed opposing alterations in network dynamics, depending on variant type. Pharmacological and molecular assays indicated that these network differences were associated with dysregulated GABAergic (gamma-aminobutyric acidergic) signaling. Early developmental analysis revealed that loss of CACNA1C altered rosette morphology, CREB (cAMP response element binding protein) phosphorylation, and transcriptional programs related to axonogenesis and synaptic signaling, indicating effects on neuronal differentiation. The patient line exhibited opposing effects on rosette morphology and CREB signaling, reflecting variant-specific effects. CONCLUSIONS: These findings demonstrate that Cav1.2 regulates excitatory-inhibitory balance, network organization, and aspects of neurodevelopment. Divergent effects of CACNA1C variants highlight how altered Cav1.2 signaling contributes to variable neurodevelopmental phenotypes, including ASD and epilepsy, and establish a framework for defining CACNA1C variant effects in human neurons.

CACNA1C↗
PubMed2006

The organisation and content of trauma memories in survivors of road traffic accidents.

We investigated the trauma narratives of 131 road traffic accident survivors prospectively, at 1 week, 6 weeks, and 3 months post-trauma. At 1 and 6 weeks, narratives of survivors with acute stress disorder (ASD) or post-traumatic stress disorder (PTSD) were less coherent and included more dissociation content. By 3 months, their narratives also contained more repetition, more non-consecutive chunks, and more sensory words. Traumatic brain injury was associated with a separate characteristic, confusion, at all three time points. Three aspects of narrative organisation at 1 week--repetition, non-consecutive chunks, and coherence--predicted PTSD severity at 3 months after controlling for initial symptoms. The results suggest both a strong concurrent and predictive relationship between narrative disorganisation and ASD/PTSD but that as people recover from ASD, their narratives do not necessarily become less disorganised.

Accidents, Traffic↗
PubMed2006

The effectiveness of a pain and anxiety protocol to treat the acute pediatric burn patient.

This retrospective review of 286 acute pediatric burn survivors treated in 2001 evaluated the effectiveness of a pharmacotherapeutic protocol for pain, anxiety, and itching. Background pain, procedural pain, exercise pain, anxiety, incidence of acute stress disorder (ASD), and itch were measured with standardized instruments. When this review was compared to similar reviews done in 1993-1994 and 1998, a steady trend toward using more potent pain medications in this patient population is evident. While the use of acetaminophen alone decreased from 50.6% of patients in 1993-1994 and 26.3% in 1998 to 7.3% in 2001, the use of opiates increased from 44.8% in 1993-1994 and 66.9% in 1998 to 81.3% of patients in 2001. Likewise, the use of benzodiazepines for anxiety has increased from 59.8% in 1998 to 77.5% of patients in 2001. During that same period the incidence of ASD decreased from 12.1% in 1993-1994 to 8.7% of patients in 2001. For effective pain and anxiety management, the average administered dose of lorazepam and morphine also increased, providing impetus to revise the pharmacotherapeutic pain protocol. Having a standard pain protocol furnishes a framework for periodic review and facilitates updating of pain and anxiety treatment practices.

Acute Disease↗