Anomalous origin of the left coronary artery from the pulmonary trunk. Clinical features and midterm results after surgical treatment

OBJECTIVE: To report the authors' experience with the anomalous origin of the left coronary artery (AOLCA) from the pulmonary trunk, emphasizing preoperative data, surgical aspects and midterm results of the follow-up. METHODS: Retrospective analysis of 11 patients operated upon at the Royal Brompton Hospital from October, 84 to April, 97. RESULTS: Nine infants had heart failure (HF) and two other children presented with dyspnea and chest pain. All had ECG changes. The echocardiogram identified the anomalous origin of the coronary artery in 7 (64%) patients and hemodynamic studies were performed in 7 patients. All infants were operated upon between the 2nd and 10th month of life. Six patients were treated with aortic reimplantation of the left coronary artery, whereas five were operated upon according to the Takeuchi technique. All patients are alive, with clear improvement of the ECG changes and ventricular function, as evaluated by echocardiography. Two patients operated upon according to the Takeuchi technique required additional surgery due to severe supravalvular pulmonary stenosis. CONCLUSION: AOLCA is a rare disease. Most patients show early signs of severe HF associated with ECG findings. Surgical therapy must be instituted early in the disease, preferentially through aortic implantation of the anomalous coronary artery, with a high possibility of success. Shortly after surgery, clinical and ECG improvement, as well as normalization of left ventricular function, should be expected.

Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats

Abstract Background: Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective: To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods: Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05). Results: Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05). Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion: The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction.

Pulmonary artery pressure and cardiac function in children and adolescents after rapid ascent to 3,450 m.

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.

Cystatin C as a marker of early changes of renal function in Fabry nephropathy.

BACKGROUND: A sensitive, feasible and reproducible marker for renal function is necessary to evaluate the clinical efficacy of enzyme replacement therapy (ERT) in Fabry nephropathy. Serum creatinine has some limitations and cystatin C has been proposed, in other nephropathies, as a useful marker of renal function. The use of cystatin C as a marker of glomerular filtration rate (GFR) was investigated in Fabry patients receiving ERT. METHODS: Renal function was evaluated with serum creatinine, serum cystatin C and estimated GFR (through Modification of Diet in Renal Disease [MDRD], Cockcroft-Gault [C&G] and Hoek formulae) in 21 Fabry patients receiving ERT with agalsidase alfa for 3 years and in 13 Fabry patients receiving agalsidase alfa for 4 years. RESULTS: During years of ERT while serum creatinine remained stable, cystatin C values showed a significant, increasing trend right from the first year of ERT. CONCLUSIONS: In Fabry disease, cystatin C is a sensitive and reliable marker of renal function, and it should be taken into account when evaluating GFR trends during ERT.

Pretransplant pulmonary hypertension and long-term allograft right ventricular function.

Background: Graft right ventricular (RV) function is compromised directly posttransplant, especially in heart transplantation (HTx) recipients with pretransplant pulmonary hypertension (PH). Graft RV size and systolic function, and the effect of the recipient's pulmonary haemodynamics on the graft extracellular matrix are not well characterised in the patients long-term after HTx. Aim: Comparison of RV size and systolic function in HTx recipients' long-term posttransplant stratified by the presence of pretransplant PH. Methods: HTx survivors >/=2 years posttransplant were divided into group I without pretransplant PH (pulmonary vascular resistance, PVR <2.5Wood units, n=37) and group II with PH (PVR >/=2.5Wood units, n=16). RV size and systolic function were measured using cardiac magnetic resonance imaging (CMR). The collagen content was assessed in septal endomyocardial biopsies obtained at HTx and at study inclusion. Results: Mean posttransplant follow-up was 5.2+/-2.9 years (group I) and 4.9+/-2.2 years (group II) (p=0.70). PVR was 1.5+/-0.6 vs 4.1+/-1.7Wood units pretransplant (p<0.001), and 1.2+/-0.5 vs 1.3+/-0.5Wood units at study inclusion (p=0.43). Allograft RV size and systolic function were similar in both groups (p always >/=0.07). Collagen content at transplantation and at follow-up were not different (p always >/=0.60). Conclusion: Posttransplant normalisation of pretransplant PH is associated with normal graft RV function long-term after HTx.

Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1)

Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO), an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control), as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells), alpha3 (93.3 ± 7.0%), alpha5 (50.4 ± 12.0%) and alpha6 (34.1 ± 4.9%) integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0%) and fibronectin (40.0 ± 2.0%) substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5%) while simultaneously reducing alpha5 (24.2 ± 19%) and alpha6 (14.3 ± 10.8%) expression as well as c-myc mRNA (7-fold), the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells), was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

Age-related changes of the multidrug resistance P-glycoprotein function in normal human peripheral blood T lymphocytes

The multidrug resistance P-glycoprotein is a transmembrane efflux pump expressed by lymphocytes and is involved in their cytolytic activity. In the present study, we investigated the age-related changes of P-glycoprotein function in normal peripheral blood lymphocytes. Blood samples from 90 normal volunteers (age range, 0 to 86 years) were analyzed. P-glycoprotein function was assessed by the flow cytometric rhodamine 123 assay. P-glycoprotein function was highest in cord blood and progressively declined with age in peripheral blood T CD4+ and CD8+ cells. In contrast, P-glycoprotein function did not vary with age in CD19+ B or CD16+CD56+ natural killer cells. These data suggest that the decline in P-glycoprotein function in T CD4+ and CD8+ lymphocytes as a function of age may contribute to the decrease in T cell cytolytic activity with aging.

131I-induced changes in rat thyroid gland function

Therapeutic doses of 131I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of 131I (64-277 µCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before 131I administration (4-month-old animals) and three times following 131I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 ± 8.16 to 55.0 ± 6.1 nM in the control group and from 69.4 ± 6.9 to 25.4 ± 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after 131I administration to rats, which was not 131I dose dependent.

Noninvasive assessment of endothelial function and ST segment changes during exercise testing in coronary artery disease

Endothelial function (EF) plays an important role in the onset and clinical course of atherosclerosis, although its relationship with the presence and extent of coronary artery disease (CAD) has not been well defined. We evaluated EF and the ST segment response to an exercise test in patients with a broad spectrum of CAD defined by coronary angiography. Sixty-two patients submitted to diagnostic catheterization for the evaluation of chest pain or ischemia in a provocative test were divided into three groups according to the presence and severity of atherosclerotic lesions (AL): group 1: normal coronaries (N = 19); group 2: CAD with AL <70% (N = 17); group 3: CAD with AL ≥70% (N = 26). EF was evaluated by the percentage of flow-mediated dilatation (%FMD) in the brachial artery during reactive hyperemia induced by occlusion of the forearm with a pneumatic cuff for 5 min. Fifty-four patients were subjected to an exercise test. Gender and age were not significantly correlated with %FMD. EF was markedly reduced in both groups with CAD (76.5 and 73.1% vs 31.6% in group 1) and a higher frequency of ischemic alterations in the ST segment (70.8%) was observed in the group with obstructive CAD with AL ≥70% during the exercise test. Endothelial dysfunction was observed in patients with CAD, irrespective of the severity of injury. A significantly higher frequency of ischemic alterations in the ST segment was observed in the group with obstructive CAD. EF and exercise ECG differed among the three groups and may provide complementary information for the assessment of CAD.

Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (9.2 ± 0.9; 13.8 ± 1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (2.8 ± 1.1; 4.4 ± 1.1) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.

Investigating Changes in Parent Knowledge about Obsessive Compulsive Behaviour Following Group Function-Based Cognitive Behavioural Therapy for Children with High Functioning Autism

This study investigated improvements in parent knowledge of effective intervention strategies following participation in a group function-based CBT treatment (GFbCBT) package for children with comorbid OCD and ASD. Nineteen parents of children ages 7-12 years with High Functioning Autism (HFA) participated in the 9-week treatment program. Key components of treatment included psychoeducation and mapping, cognitive-behavioural skills training, function-based interventions and exposure and response prevention (ERP). Treatment sessions also included direct parent education, which followed a behavioural skills training model (Miltenberger, 2008). Parent knowledge (N = 19) was measured pre and post treatment using a vignette about a child demonstrating obsessive-compulsive behaviour. Results of a one-tailed pairwise t-test indicated statistically significant changes (p=.036) in overall parent knowledge following participation in treatment. Statistically significant changes were also found in parents’ ability to generate ERP and function-based intervention strategies. These results provide preliminary evidence that parents benefit from active involvement in the GFbCBT treatment package.

Brain Glutamate Dehydrogenase Changes In Streptozotocin Diabetic Rats As A Function Of Age

Kinetic parameters of brain glutamate dehydrogenase (GDH) were compared in the brain stem, cerebellum and cerebral cortex of three weeks and one year old streptozotocin (STZ) induced four day diabetic rats with respective controls. A single intrafemoral dose of STZ (60mg/Kg body weight) was administered to induce diabetes in both age groups. After four days the blood glucose levels showed a significant increase in the diabetic animals of both age groups compared with the respective controls. The increase in blood glucose was significant in one year old compared to the three weeks old diabetic rats. The Vmm of the enzyme was decreased in all the brain regions studied, of the three weeks old diabetic rats without any significant change in the Km. In the adult the Vmax of GDH was increased in cerebellum and brain stem but was unchanged in the cerebral cortex. The K. was unchanged in cerebellum and cerebral cortex but was increased in the brain stem. These results suggest there may be an important regulatory role of the glutamate pathway in brain neural network disturbances and neuronal degeneration in diabetes as a function of age.

Changes in liking for a no added salt soup as a function of exposure

Multiple exposures have been shown to increase preference for novel foods or flavours. This "mere exposure" effect is also well known anecdotally for changes in preference for tastants within foods, for example reducing sugar in tea or coffee. However, to date, this phenomenon has received little scientific attention. The present study addressed this issue in relation to changes in preference for salt within soup. Following an initial assessment of liking, familiarity and saltiness of six soups varying in salt content (0 - 337 mg NaCl/ml), thirty-seven participants, previously assessed for their preferred salt level in soup, were allocated to either an exposure group that received 20 ml soup samples with no added salt, to a group that received a 280 ml bowl of this soup, or to a control group that received 20 ml soup samples containing salt at 280mg/100g (within normal, commercial range). Soups were presented on eight occasions, at approximately daily intervals. The two groups receiving the no added salt soup showed increases in liking starting at the third exposure, and also evident in a repeat assessment following the exposures. Increases in familiarity of the no added salt soup were also evident during exposure. Rated saltiness of all soups increased as a function of exposure, so a change in saltiness perception could not account for changes in liking for just the no added salt soups. These data suggest that simple exposure to the taste of the no added salt soup was sufficient to increase liking to a level equivalent to the initially more preferred salt level.

Effect of Fish Oil Supplementation for Two Generations on Changes of Lymphocyte Function Induced by Walker 256 Cancer Cachexia in Rats

Fish oil supplementation has been shown to improve the cachectic state of tumor-bearing animals and humans. Our previous study showed that fish oil supplementation (1 g per kg body weight per day) for 2 generations had anticancer and anticachetic effects in Walker 256 tumor-bearing rats as demonstrated by reduced tumor growth and body weight loss and increased food intake and survival. In this study, the effect of fish oil supplementation for 2 generations on membrane integrity, proliferation capacity, and CD4/CD8 ratio of lymphocytes isolated from mesenteric lymph nodes, spleen, and thymus of Walker 256 tumor-bearing animals was investigated. We also determined fish oil effect on plasma concentration and ex vivo production of cytokines [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6, and IL-10]. Lymphocytes from thymus of tumor-bearing rats presented lower viability, but this change was abolished by fish oil supplementation. Tumor growth increased proliferation of lymphocytes from all lymphoid organs, and fish oil supplementation abolished this effect. Ex vivo production of TNF-alpha and IL-6 was reduced in supplemented animals, but IL-4 and IL-10 secretion was stimulated in both nontumor and tumor-bearing rats. IL-10 and IFN-gamma plasma levels was also decreased in supplemented animals. These results suggest that the anticachetic effects of fish oil supplementation for a long period of time (2 generations) in Walker 256 tumor-bearing rats may be associated to a decrease in lymphocyte function as demonstrated by reduced viability, proliferation capacity, and cytokine production.