Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Sustained ventricular tachycardia responsive to verapamil in patients with hypertrophic cardiomyopathy. Clinical and electrophysiological assessment of drug efficacy

Recently, we examined 2 cases of hypertrophic cardiomyopathy (HCM) presenting with sustained ventricular tachycardia (VT). One case was a 62 year old male with midventricular hypertrophy and monomorphic sustained VT. After admission, the efficacies of procainamide, disopyramide, aprindin, flecainide, mexiletine and verapamil were evaluated by means of continuous electrocardiographic monitoring. Verapamil prevented the recurrence of sustained VT and markedly reduced the frequency and number of runs of nonsustained VT. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular apex. Intravenous verapamil at a dose of 10 mg prevented the induction of VT. The patient was discharged on verapamil and remains asymptomatic after 3 months of follow up. The other case was a 34 year old female who was a survivor of cardiac arrest. Monomorphic VT was observed on emergency admission and was converted to sinus rhythm by direct current cardioversion after resuscitation. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular outflow tract. Verapamil at a dose of 10 mg prevented the induction of VT. These 2 cases of HCM are rare in that they presented with sustained VT. It is also of interest that verapamil, which has been used conventionally in HCM, prevented VT.     

Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.     

Dorsal inlay graft urethroplasty for primary hypospadiac repair

OBJECTIVE: Tubularized incised plate urethroplasty has become a popular technique for repairing distal and proximal hypospadias in many institutions. Dorsal inlay graft urethroplasty has been used in our institution since 2003 to reduce the risk of meatal stenosis. In the present study, we evaluated the results of the dorsal inlay graft procedure. METHODS: A total of 28 patients with no deep groove and no severe curvature underwent one-stage urethroplasty using an inner preputial-based dorsal inlay graft. The medical records of all patients were retrospectively reviewed with regard to complication rate and cosmetic appearance. RESULTS: Mean patient age at surgery was 21 months (range, 14 months to 4.6 years). Preoperatively the urethral meatus was coronal in two cases, distal shaft in 17, proximal shaft in six and penoscrotal in three. Nine patients required testosterone therapy before surgery. Mean operative time was 200 min (range, 154-249 min). Mean length of inlay graft was 20.9 mm (range, 12-30 mm). In all patients, a straight penis was achieved without dorsal plication of the corposa cavernosa, and the neomeatus with a slit-like appearance was positioned at the glans tip. At a mean of 22 months of follow up, a urethrocutaneous fistula developed in only one patient (3.6%), requiring repair surgery 6 months after urethroplasty. No patient had meatal stenosis, neourethral stricture or urethral diverticulum along the inlay graft. CONCLUSION: Dorsal inlay graft urethroplasty is an effective method for hypospadiac repair and leads to good cosmetic outcome with low risk of complications.