Platypnea - orthodeoxia syndrome with atrial septal defect.

A 75-year old man was referred to hospital for symptomatic hypoxemia. He did not complain of dyspnea while supine, but while sitting or standing, he experienced dyspnea with severe hypoxemia. He did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography revealed an atrial septal aneurysm with a small atrial septal defect (ASD) and a mild left-to-right shunt through the ASD when the patient was supine. However, when he became upright, a severe right-to-left shunt occurred and the arterial oxygen saturation decreased from 96% to 80% with dyspnea. Cardiac catheterization revealed normal pulmonary artery pressure. He was therefore diagnosed as having platypnea - orthodeoxia syndrome. Magnetic resonance imaging of the chest showed a deformity of the atrium associated with elongation of the ascending aorta. The ASD was closed surgically and the dyspnea and hypoxemia that occurred while he was upright completely resolved.     

Tentative diagnostic criteria and disease severity classification for Castleman disease: A report of the research group on Castleman disease in Japan

Objectives: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population.

Methods: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry.

Results: We proposed the preliminary diagnostic criteria and disease severity classification for CD based on our discussion. In addition, we made a proposal for the disease activity score. We identified clinical and pathological features of patients with iMCD diagnosed by these diagnostic criteria. In the disease severity classification, 37, 33 and 30% patients were categorized into mild, moderate and severe diseases, respectively.

Conclusion: This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.     

Multiple logistic regression analysis of risk factors for the development of steroid-dependent asthma in the elderly: a comparison with younger asthmatics

BACKGROUND: The percentage of the aged among all patients with bronchial asthma is increasing. OBJECTIVE: To investigate the risk factors for the development of steroid-dependent asthma in the elderly. METHODS: A multiple logistic regression analysis involving various clinical factors between steroid-dependent and -independent asthma was carried out for 59 asthmatics aged over 60 years, including 16 patients with steroid-dependent asthma. The calculated risk for each factor was compared with that obtained from 122 younger asthmatics aged 20-59 years. RESULTS: Among the factors examined (sex, age, period from onset of asthma, type of asthma and family history of asthma, plus history of smoking, atopic dermatitis, allergic rhinitis, chronic sinusitis and nasal polyps), the significant risk factors for the development of steroid dependency in the elderly asthmatics were only family history of bronchial asthma (relative risk 3.6) and smoking history (relative risk 6.9). CONCLUSIONS: Some risk factors for steroid-dependent asthma in younger individuals were not significant in the elderly. Since the smoking history was most closely associated with the development of steroid dependency in the elderly, even though most of them had quit smoking, it is important for patients with asthma to avoid smoking.     

Association of hyperadiponectinemia with severity of ventricular dysfunction in congestive heart failure.

BACKGROUND: Adiponectin, which is a collagen-like plasma protein produced by adipose tissue, has anti-atherogenic and anti-inflammatory effects. Plasma adiponectin levels in patients with congestive heart failure (CHF) were determined, as well as relationships between the plasma levels of adiponectin and other hormones. METHODS AND RESULTS: The study group comprised 90 patients with CHF and 20 control subjects, who were divided into 4 subgroups according to New York Heart Association (NYHA) functional class. Plasma levels of adiponectin, tumor necrosis factor (TNF)-alpha and brain natriuretic peptide (BNP) and cardiac hemodynamics were determined. Plasma adiponectin levels were significantly increased according to the severity of NYHA class in the patients with CHF; control: 6.2+/-1.0; NYHA I: 8.5+/-1.9, NYHA II: 12.0+/-2.2, NYHA III: 13.0+/-2.7, NYHA IV: 14.9+/-2.7 microg/ml (p=0.0008). Similarly, plasma BNP levels were significantly increased in accordance with the NYHA class. Plasma adiponectin levels correlated positively with BNP (r=0.40, p=0.0002) and TNF-alpha (r=0.49, p=0.0001), and correlated negatively with cardiac index (r=-0.27, p=0.05). In 24 of 46 patients in the NYHA III and IV subgroups, according to the prompt improvement in cardiac function, levels of both plasma adiponectin and BNP were significantly reduced (p<0.0001). CONCLUSION: Plasma adiponectin levels increased according to the severity of CHF and, moreover, they correlated with the plasma levels of BNP and TNF-alpha. These results indicate that augmented release of adiponectin is involved in the pathogenesis of CHF and further study is needed to elucidate its exact role.     

Vaccination with clumping factor A and fibronectin binding protein A to prevent Staphylococcus aureus infection of an aortic patch in mice

Staphylococcus aureus is a leading cause of ventricular assist device-related infections. This study evaluated the protective effect against S. aureus infection of active and passive immunization that targeted 3 proteins involved in bacterial attachment to a murine intra-aortic polyurethane patch. Active immunization of mice with a combination of the A domains of clumping factor A (ClfA), fibronectin-binding protein A (FnBPA) and fibronectin-binding protein B or passive immunization with monoclonal antibodies against ClfA and FnBPA resulted in a higher level of protection than that obtained by vaccination with either protein or antibody alone. The combination of antibodies or protein antigens appears to provide enhanced protection against prosthetic-device infection.     

Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization

AIMS: We recently demonstrated that aldosterone induces a non-genomic vasoconstrictor effect on rat coronary arterioles and that this effect was blocked by angiotensin II type 1 receptor (AT1) blockers. Intracellular transglutaminase enhances AT1 signalling by cross-linking AT1 homodimers. The purpose of this study was to confirm the AT1-dependency of the vasoconstrictor effect of aldosterone using AT1a knockout (AT1aKO) mice and to investigate the role of intracellular transglutaminase and AT1 dimerization in this effect. METHODS AND RESULTS: The mesenteric arterioles (60-160 microm) were isolated from C57BL/6J (wild-type, WT) and AT1aKO mice, and the internal diameter was measured by video microscopy. Aldosterone (10(-13) to 10(-6) M), but not hydrocortisone, produced a dose-dependent vasoconstriction in WT mice; the maximal diameter change was -8.6 +/- 0.3% from the baseline (P < 0.001). This vasoconstrictor effect was unaffected by the mineralocorticoid receptor antagonist spironolactone or eplerenone, the AT2 antagonist PD123319, the glucocorticoid receptor antagonist RU486, or endothelium denudation. Aldosterone's vasoconstrictor effect was negligible in AT1aKO mice. The AT1 blockers valsartan or candesartan suppressed aldosterone-induced vasoconstriction in WT mice. The transglutaminase inhibitors cystamine and monodansyl cadaverine also suppressed the vasoconstrictor effect of aldosterone, without affecting the vasoconstrictor effect of angiotensin II in WT mice. AT1 dimer protein levels were increased in WT mesenteric arterioles treated with 10(-7) M aldosterone, and the transglutaminase inhibitor and AT1 blocker blocked this aldosterone-induced formation of AT1 dimer. Treatment with 10(-7) M aldosterone for 10 min increased the transglutaminase activity by 2.5 +/- 0.2-fold in cultured vascular smooth muscle cells and by 1.2 +/- 0.1-fold in the mesenteric arterioles. These increases were abolished by transglutaminase inhibitors. CONCLUSION: Aldosterone produces a non-genomic, endothelium-independent vasoconstrictor effect by enhancing intracellular transglutaminase activity and presumably inducing AT1 dimer formation in mesenteric arterioles.     

Immediate and 3-month follow-up outcome after cutting balloon angioplasty for bifurcation lesions

Balloon angioplasty of a bifurcation lesion is associated with lower rates of success and higher rates of complications than such treatment of lesions of most other morphologies. To date, the best device or procedure for bifurcation lesions has not been determined. The aim of this study was to compare the immediate and 3-month follow-up outcome of cutting balloon angioplasty (CBA) versus conventional balloon angioplasty (PTCA) for the treatment of bifurcation lesions. We treated 87 consecutive bifurcation lesions with CBA (n = 50) or PTCA (n = 37). Paired angiograms were analyzed by quantitative angiography, and angiographic follow-up was achieved for 93% of the lesions. The procedural success was 92% in the CBA group and 76% in the PTCA group (P < 0.05). Major in-hospital complications occurred in two lesions in the CBA group and six in the PTCA group (P = 0.05). The incidence of bail-out stenting in the CBA group was lower than in the conventional PTCA (8% vs 24%, P < 0.05). At the 3-month follow-up, the restenosis rate was 40% in the CBA group versus 67% in the PTCA group (P < 0.05). Clinical events during follow-up did not differ between the two groups. In conclusion, in comparison with PTCA, procedural success was greater and the restenosis rate lower with CBA. The results of this study support the use of the cutting balloon as optimal treatment for bifurcation lesions. (J Interven Cardiol 2004;17:1–7)     

Successful treatment of chronic granulomatous disease with fludarabine-based reduced-intensity conditioning and unrelated bone marrow transplantation

Allogeneic hematopoietic stem-cell transplantation (HSCT) for chronic granulomatous disease (CGD) with a reduced-intensity conditioning regimen can be expected to lead to less therapy-related mortality and late-onset impairment, whereas it has also been reported to increase the risk of unsustained mixed donor chimerism and late rejection after transplantation. Herein, we report a 4-year-old boy with CGD who was successfully treated with unrelated bone marrow transplantation with a reduced-intensity conditioning regimen (RIC). Fludarabine-based RIC, 4 Gy of total body irradiation, 120 mg/kg of cyclophosphamide, and 125 mg/m² of fludarabine, was adopted for transplantation, followed with 8.9 × 10⁸/kg mononucleated donor cells infused without T-cell depletion. Although hematopoietic engraftment was rapidly obtained by day +17, he developed unstable donor chimerism. After tacrolimus withdrawal, the patient showed grade III acute graft-versus-host disease (GVHD), and subsequently reached full donor chimerism by day +61. Twelve months post-transplant, the patient has remained well with stable and durable engraftment, 100% donor chimerism, and normal superoxide production, without the requirement of donor lymphocyte infusions (DLI).