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PubMed2002

The influence of a restrictive atrial septal defect on pulmonary vascular morphology in patients with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) with a restrictive atrial septal defect (ASD) is a form of congenital heart disease with considerable morbidity and mortality. This morphologic analysis assesses the pulmonary vasculature in this patient population. Pulmonary arteries, the persistence of high-resistance fetal arterioles, pulmonary veins, and lymphatics from multiple lung sections from each of five patients with HLHS and a restrictive ASD were compared to those of five patients with HLHS and nonrestrictive ASD. Lung sections from each patient were qualitatively graded in severity of pathology from 0 to 3 for each of the structures described previously, with the pathologist blinded to the status of the ASD. Patients with a restrictive ASD exhibited more significant pulmonary venous thickening and lymphatic dilatation (p = 0.02), with a tendency toward persistence of high-resistance fetal vessels (p = 0.2), compared to patients with a nonrestrictive ASD. These findings imply that patients with HLHS and a restrictive ASD possess pulmonary vascular abnormalities that place them at higher risk for the current surgical interventions available compared to patients with a nonrestrictive ASD.

Female↗
PubMed2025

Systematic Review of Symptoms of Catatonia in Autism Spectrum Disorder.

Catatonia is a complex neuropsychiatric syndrome characterized by disturbances in mood, motor function, behavior and speech. It is increasingly recognized in individuals with autism spectrum disorder (ASD), although its identification remains challenging due to the overlapping clinical features of the two conditions. Shared characteristics, such as echophenomena, mannerisms, social indifference and repetitive behaviors can obscure accurate diagnosis. Although reports suggest a significant prevalence of catatonia among individuals with ASD, the condition remains poorly understood and frequently under recognized, leading to substantial diagnostic and treatment challenges. A systematic review was conducted to characterize the symptoms of catatonia in individuals with ASD. The literature search included peer-reviewed journal articles published in English from 1980 onward, focusing on studies examining co-occurring catatonia and ASD. A qualitative framework analysis was implemented to evaluate 45 peer-reviewed studies, with findings interpreted in relation to, and extending beyond, the diagnostic criteria for catatonia outlined in the International Classification of Diseases, 11th revision (ICD-11). The objective was to identify symptom patterns extending beyond current diagnostic frameworks and to support improved clinical recognition and diagnostic precision in ASD populations. The review identified six primary symptom clusters associated with catatonia in individuals with ASD: (1) psychomotor activity, (2) speech disturbances, (3) changes in behavior/skills/functions, (4) mental health symptoms, (5) physiological symptoms, and (6) symptoms related to arousal and awareness. Notably, several symptoms observed within these clusters are not currently included in the ICD-11 diagnostic criteria for catatonia. These additional symptoms include tics, motor compliance, incoherent speech, self-injury, impaired cognition, and appetite changes, suggesting a broader clinical presentation of catatonia in ASD populations than is presently captured in existing diagnostic frameworks. The findings of this review highlight the significance of enhancing clinicians' awareness and understanding of how catatonia manifests in individuals with ASD. Most notably, six symptom clusters, psychomotor changes, speech disturbances, behavioral and functional regression, affective and psychiatric symptoms, physiological symptoms, and arousal/awareness disturbances, were observed. Several symptoms identified in this review are not included in the current diagnostic criteria, and their recognition may facilitate in earlier identification and timely intervention, potentially preventing the severe consequences of untreated catatonia in this population.

Humans↗
PubMed1991

Relationship of echocardiographic, shunt flow, and angiographic size to the stretched diameter of the atrial septal defect.

Stretched diameter of the atrial septal defect (ASD), measured by balloon sizing, is generally used as a guide to the selection of the size of the device utilized for transcatheter closure of the ASD. Balloon sizing is a cumbersome procedure and sometimes requires the use of very large size balloon catheters. Several methods of assessment of ASD size, namely, echographic, pulmonary-to-systemic flow ratio (Qp:Qs), and angiographic measures, were undertaken in a group of 16 patients, aged 7 months to 45 years (median, 4.5 years), who were being evaluated for transcatheter closure of ASD; the results were compared with the stretched diameter. Although the echographic size of the ASD (9.9 +/- 4.1 mm, mean +/- SD) is similar (p greater than 0.1) to the angiographic size (7.9 +/- 2.5 mm), it is much smaller (p less than 0.01) than the stretched diameter (16.1 +/- 5.3 mm). When the relationship between various measures of ASD was examined, although the Qp:Qs ratio and angiographic size have a significant (p less than 0.05) correlation with the stretched diameter (r = 0.55 and 0.54, respectively), the echo diameter has the best correlation coefficient, r = 0.82, p less than 0.001. The stretched diameter can be estimated by the equation: 1.05 x echo + 5.49 mm. It is concluded that the echographic diameter is a useful adjunct in the estimation of the stretch ASD diameter, which in turn can be used in the selection of the size of the device for transcatheter occlusion of the ASD.

Cardiac Catheterization↗
PubMed1991

Partial Fontan: advantages of an adjustable interatrial communication.

Systemic venous hypertension after the Fontan procedure is a major cause of mortality and morbidity, accounting for 11 of 16 deaths in our series of 228 Fontan procedures. A partial Fontan with a residual atrial septal defect (ASD) would allow controlled right-to-left shunting to reduce venous pressure and improve cardiac output while maintaining a reduced but acceptable arterial oxygen saturation. This allows complete or graded closure of the ASD after the discontinuation of cardiopulmonary bypass in the operating room or at any time in the postoperative period by exposing the snare under local anesthesia. From 1987 to 1990, 36 patients undergoing the modified Fontan procedure had placement of an adjustable interatrial communication. Indications for placement of an adjustable ASD included increased pulmonary artery pressures, increased pulmonary vascular resistance, reactive airway disease, previously increased or unknown pulmonary vascular resistance, small pulmonary arteries, and borderline ventricular function. Fourteen patients had the adjustable ASD closed at the time of operation, 8 patients underwent narrowing, and 12 underwent closure of the ASD in the postoperative period. Eight patients were discharged with the ASD partially open, and 2 patients underwent delayed closure. The partial Fontan with an adjustable ASD may increase the safety of the Fontan procedure for high-risk groups such as those with increased pulmonary vascular resistance, pulmonary hypertension, and impaired left ventricular function and for infants, who tolerate venous hypertension poorly. The ability to adjust the ASD in stages depending on the hemodynamic response increases flexibility and safety.

Animals↗
PubMedDate not supplied

Acute stress disorder and posttraumatic stress disorder symptoms among patients severely injured in motor vehicle accidents in Japan.

OBJECTIVE: The prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in seriously injured survivors of motor vehicle accidents (MVAs) in Japan was investigated. Furthermore, predictive factors in the early stage for development of PTSD were evaluated. METHOD: Subjects were consecutive samples (N=100) of patients hospitalized with severe MVA injuries surveyed at two time points: within 1 month after the MVA and then 6 months later. In the first survey, we conducted the Acute Stress Disorder Interview and compiled results of a self-rating questionnaire; in the second survey, we conducted a structured clinical interview via telephone. RESULTS: The prevalence of ASD and PTSD were 9.0% and 8.5%, respectively. The shift from ASD to PTSD was more pronounced when we included partial diagnoses of ASD and PTSD. Three predictive factors for PTSD were identified through multiple logistic analysis: ASD-positive, presence of persistent physical disability and physical injury severity. CONCLUSIONS: Even among severely injured MVA survivors, most acute stress symptoms subside over time. However, having ASD or partial ASD in the early stage, and the presence of physical disability as an aftereffect are strong predictive factors for PTSD. These findings validate the importance of evidence-based intervention for ASD to forestall PTSD.

Accidents, Traffic↗
PubMed2005

Improvements in cardiac form and function after transcatheter closure of secundum atrial septal defects.

OBJECTIVES: We set out to study the effect of transcatheter closure of atrial septal defect (ASD) on right ventricular (RV) and left ventricular (LV) function assessed by myocardial performance index (MPI), as well as left atrial (LA) volumes. BACKGROUND: The hemodynamic response to the closure of ASD is well-documented in surgically treated patients. However, few studies have documented echocardiographic evaluation of ventricular function in patients undergoing transcatheter closure of ASDs. METHODS: Pre- and post-ASD device closure echocardiograms of 25 consecutive patients were retrospectively reviewed. Measurements of RV and LV MPI and LA volumes were made. RESULTS: Twenty-five patients with an average age of 45.5 +/- 16.3 years underwent transcatheter closure of ASD. There was statistically significant improvement in RV MPI (0.35 to 0.28, p = 0.004), LV MPI (0.37 to 0.31, p = 0.04), and LA volume index (25.7 to 21.8 ml/m(2), p < 0.001) after closure of ASD. CONCLUSIONS: Device closure of ASDs leads to improvement of both RV and LV function as well as reduction in LA volume. These hemodynamic improvements provide insights into the symptomatic benefits gained in closure of ASDs using the transcatheter approach.

Adult↗
PubMed2005

Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders.

OBJECTIVE: To evaluate an association between cytokine production with common dietary proteins as a marker of non-allergic food hypersensitivity (NFH) and gastrointestinal (GI) symptoms in young children with autism spectrum disorders (ASD). STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (-) ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19). Diarrhea and constipation were the major GI symptoms. We measured production of type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory cytokines by PBMCs stimulated with whole cow's milk protein (CMP), its major components (casein, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and soy. RESULTS: PBMCs obtained from GI (+) ASD children produced more tumor necrosis factor-alpha (TNF-alpha)/interleukin-12 (IL-12) than those obtained from control subjects with CMP, beta-lactoglobulin, and alpha-lactoalbumin, irrespective of objective GI symptoms. They also produced more TNF-alpha with gliadin, which was more frequently observed in the group with loose stools. PBMCs obtained from GI (-) ASD children produced more TNF-alpha/IL-12 with CMP than those from control subjects, but not with beta-lactoglobulin, alpha-lactoalbumin, or gliadin. Cytokine production with casein and soy were unremarkable. CONCLUSION: A high prevalence of elevated TNF-alpha/IL-12 production by GI (+) ASD PBMCs with CMP and its major components indicates a role of NFH in GI symptoms observed in children with ASD.

Autistic Disorder↗
PubMed2006

Examination of cancer in mouse models using high-frequency quantitative ultrasound.

Two mouse models of mammary cancer (a carcinoma and sarcoma) were examined using quantitative ultrasound (QUS). Scatterer property estimates, i.e., the average scatterer diameter (ASD) and average acoustic concentration (AAC), were estimated from regions-of-interest (ROIs) inside the tumors. Initially, the spherical Gaussian model was used over an analysis bandwidth of 10 to 25 MHz to obtain ASD and AAC estimates. ASD estimates were 31.7 +/- 9.36 microm and 31.0 +/- 7.20 microm for the carcinomas and sarcomas, respectively. AAC estimates were 6.77 +/- 8.75 dB[mm(-3)] and 9.87 +/- 9.24 dB[mm(-3)], respectively. The initial ASD and AAC estimates did not yield statistically significant differences between the two kinds of tumors (p = 0.83, 0.86 for the ASD and AAC estimates, respectively). However, optical photomicrographs revealed distinct morphologic differences between the tumors. F-tests on the average power spectra from the tumors revealed statistically significant differences between the spectra over the range of 16 to 25 MHz. ASD and AAC estimates using the spherical Gaussian model were then obtained over the new analysis bandwidth of 16 to 25 MHz. The new ASD estimates were 42.1 +/- 4.01 microm and 32.1 +/- 3.81 microm for the carcinomas and sarcomas, respectively. The new AAC estimates were 16.4 +/- 17.1 dB[mm(-3)] and 36.4 +/- 11.9 dB[mm(-3)], respectively. Statistically significant differences were observed for both the ASD and AAC estimates when using the new analysis bandwidth. Structural differences between the tumors were revealed by both QUS and optical photomicrographs.

Animals↗
PubMed1982

Influence of age on atrioventricular conduction intervals in children with and without atrial septal defect.

His bundle electrograms were recorded in 42 patients with secundum atrial septal defects (ASD) and in 50 controls, aged 1 month to 16 years, in normal sinus rhythm and with normal PR intervals. Intervals PA (P less than 0.01) and PR (P less than 0.02) were found to be significantly prolonged in ASD patients. Analyzing the results according to age, a significant increase for intervals AH (P less than 0.05), HV (P less than 0.001) and PR (P less than 0.001) was noted in the oldest ASD children as compared to the younger ASD children, whereas in controls only the PR interval was found to be significantly prolonged (P less than 0.05) in the oldest subgroup. Under the age of three years, atrioventricular conduction intervals were not significantly different whether or not an ASD was present. However, in older children with ASD as compared to controls, a significant increase was noted for interval PA (P less than 0.03) in children four to eight years old and for intervals HV (P less than 0.01) and PR (P less than 0.001) in children 9 to 16 years old. ASD patients showed a more significant correlation with age for interval PR with a significantly steeper slope of the regression line. Results show the impact of ASD on AV conduction to be age-related, with involvement not only of the PA interval but also of the HV interval.

Adolescent↗
PubMed2006

Shared susceptibility region on chromosome 15 between autism and catatonia.

We have compiled significant linkage results from 20 genome scans for the autism syndrome disorder (ASD) and 2 for catatonia in schizophrenia (SZ). Localization of the markers has been updated across the studies using the same cytological (Genetic Location Database), physical (National Center for Biological Information), and genetic (Marshfield) maps. Eight autosomal chromosomes (1, 2, 3, 7, 9, 13, 15, and 17) showed significant linkages with ASD, and one with catatonia (15). Chromosome 15 was further characterized for SZ genome scans (N = 4) since catatonia was observed in SZ patients, for candidate genes for ASD and catatonia, and for the numerous chromosomal rearrangement and abnormalities associated to ASD. From these results, we observed that four potential susceptibility regions for ASD could be observed on chromosome 15 at 15q11-q13, 15q14-q21, 15q22-q23, and 15q26, respectively. All the four regions were shared between ASD and SZ, with 15q15-q21 being also shared with catatonia. Strong candidate genes, such as gamma-aminobutyric acid receptor B3, A5, and G3, have shown associations with ASD at 15q11-q13 susceptibility region where the majority of the chromosomal rearrangements are also found. On the other hand, negative association results were observed at 15q14-q21 susceptibility region for catatonia with the genes encoding the zinc transporter SLC30A4, the cholinergic receptor nicotinic alpha polypeptide 7, and the delta-like 4 Drosophila. Further, fine mapping and candidate gene analyses are needed to highlight potential common genes between ASD and catatonia for this chromosome.

Autistic Disorder↗
PubMed2006

Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP).

BACKGROUND: Recent reports have suggested that the prevalence of autism and related spectrum disorders (ASDs) is substantially higher than previously recognised. We sought to quantify prevalence of ASDs in children in South Thames, UK. METHODS: Within a total population cohort of 56 946 children aged 9-10 years, we screened all those with a current clinical diagnosis of ASD (n=255) or those judged to be at risk for being an undetected case (n=1515). A stratified subsample (n=255) received a comprehensive diagnostic assessment, including standardised clinical observation, and parent interview assessments of autistic symptoms, language, and intelligence quotient (IQ). Clinical consensus diagnoses of childhood autism and other ASDs were derived. We used a sample weighting procedure to estimate prevalence. FINDINGS: The prevalence of childhood autism was 38.9 per 10,000 (95% CI 29.9-47.8) and that of other ASDs was 77.2 per 10,000 (52.1-102.3), making the total prevalence of all ASDs 116.1 per 10,000 (90.4-141.8). A narrower definition of childhood autism, which combined clinical consensus with instrument criteria for past and current presentation, provided a prevalence of 24.8 per 10,000 (17.6-32.0). The rate of previous local identification was lowest for children of less educated parents. INTERPRETATION: Prevalence of autism and related ASDs is substantially greater than previously recognised. Whether the increase is due to better ascertainment, broadening diagnostic criteria, or increased incidence is unclear. Services in health, education, and social care will need to recognise the needs of children with some form of ASD, who constitute 1% of the child population.

Autistic Disorder↗
PubMed1992

Transcatheter atrial septal defect occlusion devices: normal radiographic appearances and complications.

Three transcatheter atrial septal defect (ASD) occlusion devices have been used in clinical trials during the past decade: the Rashkind ASD occluder, the Lock Clamshell occluder, and the buttoned double-disk device. The normal radiographic appearance of these three devices and radiographic findings in complications are presented. Of 12 transcatheter ASD occlusions performed, the buttoned double-disk device was used in eight patients, the Rashkind ASD occluder in three, and the Lock Clamshell occluder in one. Complications included both improper placement and partial dislodgment of the Rashkind ASD occluder device (n = 2), fracture of a metal arm of the Lock Clamshell device (n = 1), and detachment of the buttoned double-disk device with embolization into the right pulmonary artery (n = 1). Knowledge of the normal radiographic appearance of ASD occlusion devices and the findings in various complications will be necessary for radiologists as transcatheter ASD closure becomes more commonplace. Chest radiography is the primary method of detecting short- and long-term complications in patients following transcatheter ASD closure.

Adolescent↗
PubMed2003

Autism spectrum disorders in children with active epilepsy and learning disability: comorbidity, pre- and perinatal background, and seizure characteristics.

The aim of this study was to examine the comorbidity pattern, seizure characteristics, and aetiology in a representative group of children with a combination of autism spectrum disorder (ASD), active epilepsy, and learning disability. Ninety children (47 males, 43 females; mean age 11 years 2 months, range 8 to 16 years at the time of psychiatric examination) with active epilepsy and learning disability, identified in a population-based study in Göteborg, Sweden, were subdivided into those with and those without ASD and compared with respect to aetiology, additional neuroimpairments, and seizure characteristics. In addition, the cohorts were examined for trends of prevalence over a period of time. Results indicated that established aetiology was much more often present in the prenatal period than in the peri- or postnatal periods in the ASD group. Cerebral palsy and visual impairment were under-represented in the ASD group. Partial seizures tended to be more common and generalized seizures less common in the ASD group compared with the non-ASD group. Seizure onset was later in the ASD group. Many of the significant differences were accounted for by a large group of psychiatrically unclassifiable participants in the non-ASD group. There was no trend towards an increase of affected children over the 12-year period. There was no increase in the prevalence of active epilepsy and learning disability nor in the rate of autism with active epilepsy and learning disability in children born between 1981 and 1986 compared with those born from 1976 to 1980, indicating no statistical association with the general measles-mumps-rubella vaccination introduced in the early 1980s.

Adolescent↗
PubMed2006

Autism spectrum disorder and psychopathy: shared cognitive underpinnings or double hit?

BACKGROUND: We measured psychopathic traits in boys with autism spectrum disorder (ASD) selected for difficult and aggressive behaviour. We asked (i) whether psychopathic tendencies can be measured in ASD independent of the severity of autistic behaviour; (ii) whether individuals with ASD with callous-unemotional (CU) traits differ in their cognitive profile from those without such traits; and (iii) how the cognitive data from this study compare with previous data of youngsters with psychopathic tendencies. METHOD: Twenty-eight ASD boys were rated on psychopathic tendencies, autistic traits and a range of cognitive measures assessing mentalizing ability, executive functions, emotion recognition and ability to make moral-conventional distinction. RESULTS: Our results indicate that psychopathic tendencies are not related to severity of ASD. In addition, such tendencies do not seem to be related to core autistic cognitive deficits, specifically in 'mind-reading' or executive function. Boys with co-occurring ASD and CU tendencies share some behaviours and aspects of cognitive profile with boys who have psychopathic tendencies alone. CONCLUSIONS: Callous/psychopathic acts in a small number of individuals with ASD probably reflect a 'double hit' involving an additional impairment of empathic response to distress cues, which is not part and parcel of ASD itself.

Antisocial Personality Disorder↗
PubMed2005

The relationship between acute stress disorder and posttraumatic stress disorder following cancer.

In this study, the authors investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) following cancer diagnosis. Patients who were recently diagnosed with 1st onset head and neck or lung malignancy (N=82) were assessed for ASD within the initial month following their diagnosis and reassessed (n=63) for PTSD 6 months following their cancer diagnosis. At the initial assessment, 28% of patients had ASD, and 32% displayed subsyndromal ASD. At follow-up, PTSD was diagnosed in 53% of patients who had been diagnosed with ASD and in 11% of those who had not met criteria for ASD; 36% of patients with PTSD did not initially display ASD. In this study, the authors question the use of the ASD diagnosis to identify recently diagnosed patients at risk of PTSD.

Aged↗
PubMed2024

Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients' neurons.

Autism spectrum disorders (ASDs) are highly heritable and result in abnormal repetitive behaviors and impairment in communication and cognitive skills. Previous studies have focused on the genetic correlation between ASDs and other neuropsychiatric disorders, but an in-depth understanding of the correlation to other disorders is required. We conducted an extensive meta-analysis of common variants identified in ASDs by genome-wide association studies (GWAS) and compared it to the consensus genes and single nucleotide polymorphisms (SNPs) of Schizophrenia (SCZ). We found approximately 75% of the GWAS genes that are associated with ASD are also associated with SCZ. We further investigated the cellular phenotypes of neurons derived from induced pluripotent stem cell (iPSC) models in ASD and SCZ. Our findings revealed that ASD and SCZ neurons initially follow divergent developmental trajectories compared to control neurons. However, despite these early diametrical&#xa0;differences, both ASD and SCZ neurons ultimately display similar deficits in synaptic activity as they mature. This significant genetic overlap between ASD and SCZ, coupled with the convergence towards similar synaptic deficits, highlights the intricate interplay of genetic and developmental factors in shaping the shared underlying mechanisms of these complex neurodevelopmental and neuropsychiatric disorders.

Humans↗
PubMed2026

Prenatal cell-free DNA methylome detects association with autism and maternal obesity.

Early identification of autism spectrum disorder (ASD) remains a critical challenge, particularly in utero when non-genetic factors such as maternal obesity (MO) are implicated. Here, we report results of whole-genome bisulfite sequencing of cell-free DNA (cfDNA) from third-trimester maternal plasma in a high-likelihood ASD pregnancy cohort associated with child (3&#x2009;y) ASD diagnosis and/or MO. Differentially methylated regions (DMRs) between ASD and control cfDNA are strongly enriched for synaptic functions and genes previously implicated in ASD. These cfDNA ASD DMRs recapitulate those observed in ASD placenta and postmortem cortex and significantly overlap with MO DMRs. Our findings establish cfDNA methylation derived from maternal blood as a minimally invasive window into fetal brain ASD etiology, providing a framework for future mechanistic and early intervention studies. Future studies could investigate additional prenatal environmental exposures interacting with genetics during neurodevelopment.

Journal Article↗
PubMed1999

Induction of albuminuria in mice: synergistic effect of two monoclonal antibodies directed to different domains of aminopeptidase A.

BACKGROUND: Aminopeptidase A is an enzyme that is present on podocytes and is involved in the degradation of angiotensin II. In previous studies in mice, we administered single monoclonal antibodies directed against aminopeptidase A. We observed that only monoclonal antibodies that inhibited aminopeptidase A enzyme activity caused albuminuria. METHODS: In this study, the effects of the combined injections of two monoclonal anti-aminopeptidase A antibodies (mAbs) were studied, using a combination of anti-aminopeptidase A mAbs that were directed against two different domains involved in the aminopeptidase A enzyme activity (ASD-3 or ASD-37) and an anti-aminopeptidase A mAb not related to the enzyme active site (ASD-41). RESULTS: An injection of the combinations ASD-3/37 (total 4 mg, 1:1 ratio) and ASD-37/41 (total 4 mg, 1:1 ratio) in doses that do not cause albuminuria when given alone (4 mg) induced massive albuminuria at day 1 after injection. The combination ASD-3/41 had no effect. This albuminuria was not dependent on systemic immune mediators of inflammation and could not merely be related to a blockade of aminopeptidase A enzyme activity. However, a correlation was observed between the induction of albuminuria and the aggregation of the mAbs injected and aminopeptidase A on the podocytes. An injection of the combinations ASD-3/37 or ASD-37/41 did not cause an increase in systemic blood pressure. The treatment with a combination of enalapril and losartan lowered blood pressure (53 +/- 10 vs. 90 +/- 3 mm Hg in untreated mice) and reduced the acute albuminuria by 55% (11,145 +/- 864 vs. 24,517 +/- 2448 micrograms albumin/18 hr in untreated mice). However, similar effects were observed using triple therapy. Therefore, the reduction of albuminuria by the combined treatment of enalapril/losartan seems to be the consequence of the reduction in the systemic blood pressure. These findings argue against a specific role for angiotensin II in this model. CONCLUSIONS: The combined injection of two mAbs directed against different domains of aminopeptidase A induces a massive albuminuria in mice, which is not merely dependent on angiotensin II. We hypothesize that the direct binding of mAbs to at least two pathogenic domains on aminopeptidase A triggers the podocyte to release mediators that are involved in the observed albuminuria.

Albuminuria↗