Treatment for Churg-Strauss syndrome: induction of remission and efficacy of intravenous immunoglobulin therapy.

Churg-Strauss syndrome (CSS) is characterized by the presence of asthma, eosinophilia, and small-vessel vasculitis with granuloma. It is a distinct entity, as determined from all classifications of systemic vasculitis. The poor prognostic factors in CSS are renal insufficiency, cardiomyopathy, severe gastrointestinal (GI) tract, and central nervous systems (CNS) involvement. The initial management of CSS should include a high dose of a corticosteroid: prednisone at 1 mg/kg/day or its equivalent for methylprednisolone with tapering over 6 months. In patients with severe or rapidly progressing CSS, the administration of methylprednisolone pulse at 1 g/body/day for 3 days is recommended. When corticosteroid therapy does not induce remission, or when patients have poor prognostic factors, immunosuppressive cytotoxic therapy is indicated. However, some patients with severe CSS often show resistance to conventional treatment. We think that IVIG therapy is a hopeful candidate for second-line treatment for CSS patients, particularly in the case of neuropathy and/or cardiomyopathy, which are resistant to conventional therapy. However, there is not much evidence supporting the effectiveness of IVIG in CSS, and the mechanisms underlying the action of IVIG remain unclear. Now we are performing clinical trials of IVIG therapy for CSS patients who are resistant to conventional treatment, through a nationwide double-blinded placebo-controlled study in Japan.     

Rapidly growing mural thrombus in an abdominal aortic aneurysm

Summary While mural thrombus accompanied by an abdominal aortic aneurysm (AAA) is not rare, the growth rate of such a thrombus has not yet been adequately documented. We present here a very rare case of a 62-year-old female patient with an AAA in whom the mural thrombus in the aneurysm grew very rapidly over a short period. We could follow the growth of the mural thrombus in the AAA by two-dimensional (2-D) abdominal echography. Patients with an AAA must be closely monitored by this technique which is able to detect the presence of the thrombus and allow evaluation of its growth.     

Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide.

Endothelin is a potent vasoconstrictor/pressor peptide, which we recently characterized from the conditioned culture medium of porcine aortic endothelial cells. We report here the cloning and partial sequencing of the rat endothelin gene. The nucleotide sequence predicted a 21-residue peptide similar to, but distinct from, porcine endothelin; 15 residues of rat endothelin were identical and 3 residues were substitutions by chemically similar amino acid residues to those in the porcine peptide. Synthetic rat endothelin was then prepared according to its deduced amino acid sequence. This synthetic peptide had (i) potent vasoconstrictor activity in the rat aortic strip and in perfused rat heart and (ii) a characteristically long-lasting in vivo pressor activity by intraaortic bolus injection in the conscious rat.     

A lipoprotein lipase activator,NO-1886 prevents impaired endothelium-dependent relaxation of aorta caused by exercise in aged rats

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether the lipoprotein lipase activator NO-1886 had an effect on the prevention of atherosclerosis in aged rats which undergo exercise. Exercise for 3 months did not affect plasma lipids but decreased the accumulation of visceral fat in 2-year-old rats (aged rat). Exercise also resulted in an elevation of plasma lipid peroxide (LPO) levels and impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in aged rats. On the other hand, NO-1886 decreased plasma triglycerides and increased HDL cholesterol and suppressed the elevation of plasma LPO levels caused by exercise. Furthermore, NO-1886 prevented impaired endothelium-dependent relaxation caused by exercise. In summary, the results of our study indicate that exercise may cause impaired endothelium-dependent relaxation by elevation of LPO in aged rats, and that NO-1886 prevents this impaired endothelium-dependent relaxation of aorta by reducing plasma triglycerides, elevating HDL cholesterol, and suppressing the elevation of plasma LPO caused by exercise.     

Characteristics of Inoperable Patients with Severe Aortic Valve Stenosis —In the Era of Transcatheter Aortic Valve Replacement

Purpose: Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option for severe aortic valvular stenosis (AS). To determine the indication for TAVR, it is mandatory to clarify the characteristics of the patients who were judged as inoperable for conventional aortic valve replacement (cAVR).Methods: Of 185 patients newly diagnosed as severe AS from March 2010 to April 2011, we studied the characteristics of 61 (33%) patients (mean age, 86 ± 8 years) who were judged as inoperable.Results: Younger patients (<85 years old, n = 22) had more major comorbidities and lower left ventricular ejection fraction than older patients (≥85 years old, n = 39). Mean estimated mortality for cAVR by Japan score was 7.0% ± 7.4%. Japan score did not correlate to age and was calculated relatively low in the older age group (6.2% ± 7.0%) than the younger age group (8.3% ± 8.1%).Conclusion: One thirds of severe AS patients were judged as inoperable. In advanced age patients, age itself and other factors, which are not included in the conventional scoring systems, might have contributed to the decision making not to perform cAVR by cardiologists. Further study is necessary to define risk factors except for age.     

Radiofrequency ablation of pulmonary tumors and normal lung tissue in swine and rabbits

OBJECTIVE: The purpose of the present study was to examine the following during radiofrequency ablation (RFA): (1) the risk of hemorrhage from intrapulmonary large vessels; (2) the risk of incomplete ablation of pulmonary tumors; and (3) the late effect on lung tissue. MATERIALS AND METHODS: A 17-gauge, cool-tip-type radiofrequency electrode was used. The damage to the vessels and bronchi was examined by the injection of a colored silicone rubber, a liquid compound that hardens after injection. To examine the risk of hemorrhage from intrapulmonary large vessels, RFA was conducted at eight sites near the central pulmonary vessels in two swine. To examine the risk of an incomplete ablation for pulmonary tumors, 10 pulmonary nodules were made from a gelatin mixture in another two swine and were treated by RFA. To examine the late effect on lung tissue, RFA was conducted on the peripheral lung in 10 rabbits, and then the ablated regions were examined on days 1, 7, 14, 21, and 28 after RFA. RESULTS: The use of colored silicone rubber enabled us to examine the intrapulmonary vessels and bronchi for opening and leakage. RFA did not damage the large intrapulmonary vessels, even when they were located within the ablated regions. Lung tissue surrounding the gelatin nodules was hardly ablated over its entire circumference. Six of 10 gelatin nodules (60%) showed nonablated areas on the peripheral edges of the nodules. From 21 days after RFA, the ablated rabbit lung formed noninfectious cavities by communicating with the surrounding bronchi. CONCLUSION: It was improbable for hemorrhage to occur even when RFA was conducted near the large intrapulmonary large vessels. Because an incomplete ablation that left tumor cells at the site of ablation could occur during surgery due to the difficulty of ablating the entire tumor circumference, CT scan-guided RFA would be preferable to a surgical approach for making a safe margin. Cavity formation can occur beginning 21 days after RFA, which should be carefully followed up in a clinical setting to identify infection, especially in immunocompromised patients.     

Changes in coronary resistance related to the stages of the female life cycle.

BACKGROUNDS: Estrogen is known to dilate the coronary vascular system mainly through nitric oxide (NO) release. However, it has not been determined whether or not this effect occurs equally throughout all stages of the female life cycle. We examined the changes in coronary flow properties in adolescent, adult and ovariectomized (OVX) female rats using the endothelial NO synthetase blocker, L-N (omega) nitroarginine (L-NNA). METHODS AND RESULTS: Female rats were divided into 3 groups: adolescent (13 weeks, n=6), adult (19 weeks, n=8) and OVX (20 weeks, n=7, 12 weeks after oophorectomy). Coronary effluent was measured using the Langendorff non-working heart model before and 15 min after the use of L-NNA. In OVX rats, coronary effluent was significantly decreased in comparison with adolescent and adult rats (adolescent vs OVX: p<0.001; adult vs OVX: p<0.05). After treatment with L-NNA, coronary effluent was significantly higher in the adolescent group compared with the adult and OVX groups (adolescent vs adult: p<0.01; adolescent vs OVX: p<0.0005). CONCLUSIONS: Oophorectomy brought about an increase in coronary vascular resistance. L-NNA exacerbated coronary vascular resistance in relation to maturation. It is suggested that the effect of estrogen on vascular dilatation in adolescents is largely dependent on a non-NO pathway, whereas adults are largely dependent on an NO pathway.     

Practical Approach to Evaluate Asymptomatic Coronary Artery Disease in End‐Stage Renal Disease Patients at the Initiation of Dialysis

The high prevalence of significant asymptomatic coronary artery disease (CAD) has been reported in patients with end‐stage renal disease (ESRD) at the initiation of dialysis. However, the approach to evaluate asymptomatic CAD for these patients has not been established. The aim of this study is to assess the applicability of our practical approach at the initiation of dialysis. We prospectively enrolled 182 consecutive ESRD patients who initiated dialysis. After echocardiography as primary screening, pharmacologic stress thallium‐201 scintigraphy and/or coronary angiography (CAG) were performed to diagnose CAD. The patients were classified into two groups: those with coronary artery stenosis by CAG (CAD+ group), those without coronary artery stenosis by CAG or with negative scintigraphy examination (CAD? group). Of the eligible 93 patients without the history of CAD, 22 patients were allocated to the CAD+ group (18 of 26 patients with abnormal echocardiography and 4 of 13 patients with positive scintigraphy examination) and 71 patients to the CAD? group. Patients were followed up for an average of 520 ± 304 days. The event‐free survival rate of major adverse cardiac events was significantly lower in the CAD+ group than in the CAD? group (P < 0.001). There was no cardiovascular event including major adverse cardiac events, unstable angina, coronary revascularization or stroke in the CAD? group during the first year of dialysis. Patients without CAD diagnosed by our approach had favorable clinical outcomes. Our approach may be useful for screening of occult CAD in ESRD patients at the initiation of dialysis.