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Biomedical subjects

G Zhang

Publications and source records attributed to G Zhang.

At least 19 recordsLinked to original sources
PubMed2006

Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid-associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid-deposition.

OBJECTIVES: This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model. METHODS: Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically. RESULTS: The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group. CONCLUSION: PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.

Adrenal Cortex Hormones↗
PubMed2006

Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats.

Our laboratory has previously characterized age-dependent changes in nociception upon acute morphine withdrawal. This study characterizes changes in mechanical and thermal nociception following acute, intermittent, or continuous morphine administration in infant (postnatal days 5-8) and young (postnatal days 19-21) rats. Morphine was given as a single acute administration (AM), intermittently twice a day for 3 days (IM), or continuously for 72 h via pump (CM). AM did not produce long-term changes in mechanical or thermal nociception in either infant or young rats. CM produced changes in mechanical nociception that included the development of tolerance, opioid-induced mechanical allodynia and withdrawal-associated mechanical allodynia in young rats, but only tolerance and a prolonged withdrawal-associated mechanical allodynia in infant rats. IM produced withdrawal-associated mechanical allodynia in both infant and young rats. Measuring paw withdrawal responses to thermal stimuli, infant and young rats showed tolerance without opioid-induced thermal hyperalgesia or withdrawal-associated thermal hyperalgesia following CM. In contrast to CM, withdrawal-associated thermal hyperalgesia was seen in both ages following IM. In conclusion, CM versus IM differentially modified mechanical and thermal nociception, suggesting that opioid-dependent thermal hyperalgesia and mechanical allodynia can be dissociated from each other in infant and young rats. Furthermore, tolerance, opioid-induced hypersensitivity, and withdrawal-associated hypersensitivity are age-specific and may be mediated by distinct mechanisms.

Aging↗
PubMed2006

Spacer inhalation technique and deposition of extrafine aerosol in asthmatic children.

The aim of the present study was to measure airway, oropharyngeal and gastrointestinal deposition of (99m)Tc-labelled hydrofluoroalkane-beclomethasone dipropionate after inhalation via a pressurised metered-dose inhaler and spacer (Aerochamber Plus) in asthmatic children. A group of 24 children (aged 5-17 yrs) with mild asthma inhaled the labelled drug. A total of 12 children took five tidal breaths after each actuation (tidal group). The other 12 children used a slow maximal inhalation followed by a 5 - 10-s breath-hold (breath-hold group). Simultaneous anterior and posterior planar gamma-scintigraphic scans (120-s acquisition) were recorded. For the tidal group, mean+/-sd lung deposition (% ex-actuator, attenuation corrected) was 35.4+/-18.3, 47.5+/-13.0 and 54.9+/-11.2 in patients aged 5-7 (n = 4), 8-10 (n = 4) and 11-17 yrs (n = 4), respectively. Oropharyngeal and gastrointestinal deposition was 24.0+/-10.5, 10.3+/-4.4 and 10.1+/-6.2. With the breath-hold technique, lung deposition was 58.1+/-6.7, 56.6+/-5.2 and 58.4+/-9.2. Oropharyngeal and gastrointestinal deposition was 12.9+/-3.2, 20.1+/-9.5 and 20.8+/-8.8. Inhalation of the extrafine formulation with the breath-hold technique showed significantly improved lung deposition compared with tidal breathing across all ages. Oropharyngeal and gastrointestinal deposition was markedly decreased, regardless of which inhalation technique was applied, compared with a previous paediatric study using the same formulation delivered via a breath-actuated metered-dose inhaler.

Administration, Inhalation↗
PubMed2006

Transcatheter closure of patent ductus arteriosus with severe pulmonary arterial hypertension in adults.

BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) with severe pulmonary arterial hypertension in adults carries higher risk than in children. OBJECTIVES: To investigate the application of self-expandable occluders for transcatheter closure of PDA associated with severe pulmonary arterial hypertension in adults, and the assessment of immediate and short-term results. METHODS: 29 adult patients (6 men, 23 women) underwent attempted transcatheter closure of PDA at a mean (standard deviation (SD)) age of 31.1 (11.4) years (range 18-58 years) and a mean (SD) weight of 54.1 (7.1) kg (range 42-71 kg). On the basis of haemodynamic and clinical data obtained before and after trial occlusion, the final duct occlusion was determined and carried out. Radiographs of the chest, electrocardiograms and echocardiograms were used for follow-up evaluation of the treatment within 1 day, 1 month and 3-6 months after successful closure. RESULTS: 20 of the 29 patients had successful occlusion (group 1), and 9 patients failed (named group 2). In group 1, in which occlusion was successful, mean (SD) pulmonary arterial pressures decreased markedly after trial occlusion: 78 (19.3) mm Hg (range 50-125 mm Hg) before occlusion and 41 (13.8) mm Hg (range 23-77 mm Hg) after occlusion. Systemic arterial oxygen saturation was found to be >90% in 19 patients and <90% in the remaining patient before inhalation of oxygen, and >95% during inhalation of oxygen or after occlusion in all 20 patients. In group 2, the occlusion was not successful, because in two patients the device was not available; another two patients showed worsening of symptoms. The other five patients showed increased pulmonary arterial pressures after trial closure; their mean (SD) pulmonary arterial pressures increased by 10.3 (6) mm Hg (4-16 mm Hg) after trial occlusion, and systemic arterial oxygen saturation was 85.5% (2.6%) (range 82.6-88%) before inhalation of oxygen and 94.7% (1.7%) (range 90.7-99.1%) during inhalation of oxygen. In group 1, the dimensions of the left atrium, left ventricle and pulmonary artery increased considerably in 3-6-months of follow-up compared with those of preocclusion. CONCLUSIONS: Transcatheter closure is an effective treatment for adults with PDA associated with reversible severe pulmonary arterial hypertension. Further research is needed for the evaluation of long-term results.

Adolescent↗
PubMed2006

Quantification and thickness correction of EFTEM phosphorus maps.

We describe a method for correcting plural inelastic scattering effects in elemental maps that are acquired in the energy filtering transmission electron microscope (EFTEM) using just two energy windows, one above and one below a core edge in the electron energy loss spectrum (EELS). The technique is demonstrated for mapping low concentrations of phosphorus in biological samples. First, the single-scattering EELS distributions are obtained from specimens of pure carbon and plastic embedding material. Then, spectra are calculated for different specimen thicknesses t, expressed in units of the inelastic mean free path lambda. In this way, standard curves are generated for the ratio k0 of post-edge to pre-edge intensities at the phosphorus L2,3 excitation energy, as a function of relative specimen thickness t/lambda. Thickness effects in a two-window phosphorus map are corrected by successive acquisition of zero-loss and unfiltered images, from which it is possible to determine a t/lambda image and hence a background k0-ratio image. Knowledge of the thickness-dependent k0-ratio at each pixel thus enables a more accurate determination of the phosphorus distribution in the specimen. Systematic and statistical errors are calculated as a function of specimen thickness, and elemental maps are quantified in terms of the number of phosphorus atoms per pixel. Further analysis of the k0-curve shows that the EFTEM can be used to obtain reliable two-window phosphorus maps from specimens that are considerably thicker than previously possible.

Animals↗
PubMed2006

Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene.

In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested Hp alpha1/Hp alpha2 (Hp 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia is accompanied by both an altered expression of Hp protein and a different genotype distribution of Hp gene, demonstrating that Hp is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs.

Acute-Phase Proteins↗
PubMed2006

Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment.

Recent evidence indicates that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that breast carcinoma and tumorigenic breast cell lines have higher 5alpha-reductase and lower 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha-HSO activities and mRNA expression levels than normal tissue and non-tumorigenic cell lines. The 5alpha-reduced progesterone metabolites such as 5alpha-dihydroprogesterone (5alphaP) promote both mitogenic and metastatic activity in breast cell lines in culture, whereas the 4-pregnene metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaHP) have the opposite (anti-cancer-like) effects. The 5alpha-reductase inhibitor dutasteride has been shown to inhibit 5alpha-reduction of testosterone to 5alpha-dihydrotestosterone in prostate tissue, resulting in decreased prostate volume. The aim of this study was to determine if dutasteride is an effective inhibitor of progesterone 5alpha-reduction in human breast cell lines and if such inhibition reduces mammary cell proliferation and detachment. The effect of dutasteride on progesterone metabolizing enzyme activities and mRNA expression were examined in tumorigenic MCF-7 and non-tumorigenic MCF-10A human breast cell lines. Dutasteride (10(-6)M) inhibited progesterone conversion to 5alpha-pregnanes by >95% and increased 4-pregnene production. The results indicated that effects of dutasteride on the progesterone metabolizing enzymes are due to direct inhibition of 5alpha-reductase activity and to altered levels of expression of 5alpha-reductase and HSO mRNAs. Treatment of cells with progesterone without medium change for 72 h resulted in significant conversion to 5alpha-pregnanes and increases in cell proliferation and detachment. The increases in proliferation and detachment were blocked by dutasteride and were reinstated by concomitant treatment with 5alphaP, providing proof-of-principle that the effects were due not to progesterone but to the 5alpha-reduced metabolites. This study provides the first evidence that dutasteride is a potent progesterone 5alpha-reductase inhibitor and that such inhibition may be beneficial in breast cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2006

Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression.

Squamous cell carcinoma (SCC) is an invasive malignancy of epidermal keratinocytes. Surgical excision is currently the main treatment; however, this can cause scarring and disfigurement. There is accordingly, an acute need for alternative strategies to treat SCC. The transcription factor c-Jun is expressed in human SCC and another common form of invasive skin cancer, basal cell carcinoma together with the mitogenic marker-proliferating cell nuclear antigen. Here, we have employed DNAzymes (catalytic DNA molecules) targeting c-Jun (Dz13) to inhibit c-Jun expression in SCC cells. Dz13 inhibits SCC proliferation and suppresses solid SCC tumor growth and tumor angiogenesis in severe combined immunodeficient mice. We further demonstrate that Dz13 inhibits c-Jun, together with matrix metalloproteinase (MMP)-2 and MMP-9 expression in the tumors, consistent with DNAzyme inhibition of MMP-2 and MMP-9 gelatinolytic activity by zymography. Dz13 also suppressed the expression of vascular endothelial growth factor and fibroblast growth factor-2 in the tumors. These findings demonstrate that c-Jun regulates SCC growth and suggest that DNAzymes targeting this transcription factor may potentially be useful as inhibitors of cutaneous carcinoma.

Animals↗
PubMed2006

Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone.

AIMS: The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). METHODS: Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically. RESULTS: Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P<0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P<0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P<0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period. CONCLUSION: Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.

Animals↗
PubMed2006

Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting.

BACKGROUND: There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms. OBJECTIVES: The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts. SELECTION CRITERIA: Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both. DATA COLLECTION AND ANALYSIS: Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes. MAIN RESULTS: Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. AUTHORS' CONCLUSIONS: This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Acupuncture Points↗
PubMed2006

Assessment of the relationship between cerebral and splanchnic oxygen saturations measured by near-infrared spectroscopy and direct measurements of systemic haemodynamic variables and oxygen transport after the Norwood procedure.

OBJECTIVES: To evaluate the clinical utility of near-infrared spectroscopic (NIRS) monitoring of cerebral (ScO2) and splanchnic (SsO2) oxygen saturations for estimation of systemic oxygen transport after the Norwood procedure. METHODS: ScO2 and SsO2 were measured with NIRS cerebral and thoracolumbar probes (in humans). Respiratory mass spectrometry was used to measure systemic oxygen consumption (O2). Arterial (SaO2), superior vena caval (SvO2) and pulmonary venous oxygen saturations were measured at 2 to 4 h intervals to derive pulmonary (Qp) and systemic blood flow (Qs), systemic oxygen delivery (DO2) and oxygen extraction ratio (ERO2). Mixed linear regression was used to test correlations. A study of 7 pigs after cardiopulmonary bypass (study 1) was followed by a study of 11 children after the Norwood procedure (study 2). RESULTS: Study 1. ScO2 moderately correlated with SvO2, mean arterial pressure, Qs, DO2 and ERO2 (slope 0.30, 0.64. 2.30, 0.017 and -32.5, p < 0.0001) but not with SaO2, arterial oxygen pressure (PaO2), haemoglobin and O2. Study 2. ScO2 correlated well with SvO2, SaO2, PaO2 and mean arterial pressure (slope 0.43, 0.61, 0.99 and 0.52, p < 0.0001) but not with haemoglobin (slope 0.24, p > 0.05). ScO2 correlated weakly with O2 (slope -0.07, p = 0.05) and moderately with Qs, DO2 and ERO2 (slope 3.2, 0.03, -33.2, p < 0.0001). SsO2 showed similar but weaker correlations. CONCLUSIONS: ScO2 and SsO2 may reflect the influence of haemodynamic variables and oxygen transport after the Norwood procedure. However, the interpretation of NIRS data, in terms of both absolute values and trends, is difficult to rely on clinically.

Animals↗
PubMed2006

Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.

The mechanisms involved in the pathogenesis of ovarian cancer are poorly understood, but evidence suggests that aberrant activation of Wnt/beta-catenin signalling pathway plays a significant role in this malignancy. However, the molecular defects that contribute to the activation of this pathway have not been elucidated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a candidate for the regulation of cytoplasmic beta-catenin. In this study, we developed in situ hybridisation probes to evaluate the presence of FRAT1 and used an anti-beta-catenin antibody to evaluate by immunohistochemistry the expression levels and subcellular localisation of beta-catenin in ovarian cancer tissue microarrays. Expression of FRAT1 was found in some human normal tissues and 47% of ovarian adenocarcinomas. A total of 46% of ovarian serous adenocarcinomas were positive for FRAT1 expression. Accumulation of beta-catenin in the nucleus and/or cytoplasm was observed in 55% ovarian adenocarcinomas and in 59% of serous adenocarcinomas. A significant association was observed in ovarian serous adenocarcinomas between FRAT1 and beta-catenin expression (P<0.01). These findings support that Wnt/beta-catenin signalling may be aberrantly activated through FRAT1 overexpression in ovarian serous adenocarcinomas. The mechanism behind the overexpression of FRAT1 in ovarian serous adenocarcinomas and its significance is yet to be investigated.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption.

AIM: Factorial design was used to test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its preventive effects on estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. MATERIALS AND METHODS: Forty-five 12-month-old female Wistar rats were used and randomly assigned into sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS (FE + CS group). Daily oral administration of FE (10 mg/kg/day) and/or CS (56 mg/kg/day) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators related to intestinal calcium absorption, regulator for calcium homeostasis, and markers of bone turnover. The left proximal femur was dissected for evaluation of the primary end-point (failure force), the second end-points (pQCT-quantified densitometry, geometry, and micro-CT-quantified 3-D trabecula micro-architecture), and pQCT-defined cross-sectional envelope. RESULTS: FE was found to be able to prevent OVX-induced reduction in failure force as well as the above second end-points, without resulting in an increased uterus weight. CS had no preventive effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis did not provide link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, the discrepancies between the enhanced intestinal calcium absorption and the un-enhanced end-point measures as well as anabolic effect were also revealed by the interaction analysis. CONCLUSION: The present study suggested that FE inhibited bone resorption, stimulated bone formation, and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model, which was however independent of an enhancement in intestinal calcium absorption.

Animals↗
PubMed2006

Association of haplotypes of beta2-adrenoceptor polymorphisms with lung function and airway responsiveness in a pediatric cohort.

We evaluated the influence of haplotypes of beta(2)-adrenergic receptor (ADRB2) polymorphisms on lung function and airway responsiveness (AR) in a pediatric cohort recruited before birth and followed up to 11 years of age. The subjects (180) were the participants in a prospective study of lung function and AR. They have been assessed five times (at 1 month, 6 months, 12 months, 6 and 11 years of age) for lung function and AR. The two ADRB2 single nucleotide polymorphisms (SNPs): Arg16Gly and Gln27Glu were genotyped by PCR-RLFP and their haplotypes inferred using the program PHASE. An association between the haplotype arg16gln27 and the prevalence of positive AR was found at age 6 years (P = 0.009). The gly16gln27 haplotype was associated with higher FEV1 (P = 0.015) at age 6 and both higher FEV1 and FVC (P = 0.018 and P = 0.001, respectively) at age 11. In contrast, arg16gln27 was associated with both lower FEV1 and FVC (P = 0.028 and P = 0.011, respectively) at age 11. Children with the gly16gln27 haplotype were less likely to have asthma-ever or doctor-diagnosed asthma at age 11 (OR: 0.38; P = 0.019 and OR: 0.31; P = 0.041, respectively). In conclusion, haplotypes of beta(2)-adrenoceptor polymorphisms are associated with lung function, AR, and asthma susceptibility in childhood.

Airway Resistance↗
PubMed2006

Long-term results of surgical treatment of tetralogy of Fallot in adults.

BACKGROUND: The long-term results of patients with tetralogy of Fallot surgically treated in adulthood were evaluated to define the real benefit of surgical correction. METHODS: Between August 1990 and February 2004, 57 patients older than 18 years of age with tetralogy of Fallot received total correction. Forty-two patients (73.7 %) required transannular patch. RESULTS: Hospital and late mortality were 7.0 % (n = 4) and 5.7 % (n = 3), respectively. One patient was reoperated on to close residual ventricular septal defect. Four patients were lost. Of the remaining 49 patients, the mean follow-up was 65 +/- 38 months (range 11 - 173 months). Actuarial survival was 97.4 +/- 2.5 %, 91 +/- 7 % and 72.8 +/- 17.1 % at 5, 10 and 14 years, respectively. At the latest follow-up, 35 (76.1 %) of the surviving patients presently have NYHA functional class I ( P < 0.01). CONCLUSION: The overall survival of surgically treated adult patients with tetralogy of Fallot is acceptable. The greatest benefit of total correction at this age is the functional improvement.

Adolescent↗
PubMed2006

Autoantibody against beta1-adrenergic receptor and left ventricular remodeling changes in response to metoprolol treatment.

Autoantibodies specific for the beta(1)-adrenoceptor (beta(1)-AR) have been implicated in the pathology of congestive heart failure (CHF). We hypothesized that the presence of autoantibodies against beta(1)-AR (anti-beta(1)-AR) is associated with left ventricular (LV) remodelling in response to metoprolol. Synthetic beta(1)-AR peptides served as the target antigen in an ELISA (enzyme-linked immunosorbent assay) were used to screen the sera of 106 CHF patients. Patients were separated into positive (+) anti-beta(1)-AR or negative (-) anti-beta(1)-AR groups according to their anti-beta(1)-AR reactivity. Echocardiography (ECG) was performed at baseline and after one year of metoprolol therapy in combination with standard treatment regime for CHF, that is, digoxin, diuretics and an ACEI (angiotensin-converting enzyme inhibitor). The dose of metoprolol was doubled on a biweekly basis up to 50 mg x 2 daily (b.i.d./day) or attainment of maximum tolerated dose. Ninety-six patients completed final data analysis. Fifty-four patients with (+) anti-beta(1)-AR had greater improvements than 42 patients with (-) anti-beta(1)-AR in LVEDD (left ventricular end-diastolic dimension) (P < 0.01, from 69 +/- 0.8 to 58.0 +/- 0.5 mm vs. 69.0 +/- 0.8-63.6 +/- 0.9 mm) and LVESD (left ventricular end-systolic dimension) (P < 0.01, from 57.1 +/- 1.4 to 43.9 +/- 0.8 mm vs. 56.2 +/- 0.9-48.6 +/- 1.0 mm), and LVEF (left ventricular ejection fraction) (P < 0.01, from 35.4 +/- 1.3 to 49.8 +/- 0.6% vs. 34.4 +/- 1.0-44.3 +/- 1.1%) by metoprolol therapy in combination with standard treatment regime for one year. Of the CHF patients with (+) anti-beta(1)-AR, 65.4% responded to target metoprolol dose as compared to 21.4% of CHF patients without anti-beta(1)-AR (P < 0.01). Response to target metoprolol dose occurred more rapidly in (+) anti-beta(1)-AR than (-) anti-beta(1)-AR of CHF patients (67.5 +/- 2.4 vs. 100.8 +/- 3.0 days, P < 0.01). These results demonstrated that CHF patients with (+) anti-beta(1)-AR had greater improvements in LV remodelling and heart function by metoprolol as compared to (-) anti-beta(1)-AR patients. Moreover, patients with (+) anti-beta(1)-AR have better tolerance to metoprolol therapy than patients without anti-beta(1)-AR.

Adrenergic beta-Antagonists↗