A novel mutation Lys273Glu in the cardiac troponin T gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy.

Familial hypertrophic cardiomyopathy (HC) can be caused by mutations in 9 different genes encoding sarcomere proteins expressed in cardiac muscle. To date, only 13 different mutations in the cardiac troponin T (cTnT) gene have been reported to cause HC. Clinical characteristics and prognosis associated with mutations of this gene have not been well characterized owing to the small size and composition of affected families. The aim of this study was to determine the characteristic phenotype of patients with HC caused by a novel cTnT gene mutation, Lys273Glu. Two hundred Japanese probands with HC were screened for mutations in the cTnT gene. The Lys273Glu missense mutation was present in 9 persons from 2 unrelated pedigrees. They exhibited different cardiac morphologies: 1 had a dilated cardiomyopathy-like feature, 7 had left ventricular hypertrophy with normal left ventricular systolic function, and the 6 of them had asymmetric septal hypertrophy. A 1-year-old boy was not evaluated with echocardiography. The mean maximum wall thickness was 18.0 +/- 5.5 mm (range 8 to 24). There were 7 histories of sudden death in 1 of the 2 families. The Lys273Glu substitution in the cTnT gene shows a high degree of penetrance (100% in persons aged >20 years), a high incidence of sudden death, and a partial transition from hypertrophic to dilated cardiomyopathy. Because the location of a mutation appears to influence the development of a phenotype, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members.     

The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias

OBJECTIVE: An overdiagnosis bias occurs with the diagnosis of a disease that does not produce signs or symptoms before the patient dies from other causes. We sought to determine whether overdiagnosis bias is a factor when screening for squamous cell carcinoma of the lung. DESIGN: Retrospective study of the Miyagi Population-Based Lung Cancer Screening Registry for high-risk patients who were seen between January 1, 1982 (when sputum cytology tests were added for men with long smoking histories), and December 31, 1996. SETTING: Miyagi Prefecture, Japan. PATIENTS: A total of 251 patients (all men) who had sputum cytology test results that were positive for squamous cell carcinoma but had normal radiograph findings, 44 of whom declined cancer treatment (mean age, 70 years) and 207 of whom were treated with resection within 12 weeks of diagnosis (mean age, 65.5 year). END POINTS: Five-year and 10-year survival rates from primary lung cancer in both groups as of August 15, 2001. RESULTS: Among the 44 untreated patients, 15 (34%) remained asymptomatic. The survival rate due to primary lung cancer death in the untreated group was 53.2% at 5 years and 33.5% at 10 years. The survival rate among treated patients was 96.7% at 5 years and 94.9% at 10 years. Of the 125 treated patients who died, 14 (11.2%) died from primary lung cancer. CONCLUSION: Given that the two thirds of the untreated patients with squamous cell carcinoma of the bronchus died from lung cancer within 10 years, overdiagnosis bias does not appear to be a factor in screening for this disease. Thus, we recommend that patients with radiographically occult squamous cell carcinoma of the bronchus undergo tumor treatment after localization.     

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.     

CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese

Cholesteryl ester transfer protein (CETP) is one of the factors that regulate plasma levels of HDL-cholesterol. To identify the factors that may regulate CETP activity, and to determine to what extent CETP is correlated with physiologic concentrations of lipoprotein, we performed an epidemiologic study in 586 healthy volunteers (317 males and 269 females, mean age 52.2 ± 10.9 years). CETP activity in these subjects was 192.96 ± 48.73 (mean ± S.D.) nmol/ml/h and distributed to a wide range (60–450 nmol/ml/h). Using multiple regression analysis, we found significant positive correlations between CETP activity and LDL-cholesterol (P < 0.03), apolipoprotein (apo) E (P < 0.005) and LCAT activity (P < 0.001). CETP activities showed significant negative correlation with apo A-I (P < 0.03). However, CETP activity showed no significant correlation either with HDL cholesterol or with apo B. One-way layout analysis of variance showed that alcohol drinking and cigarette smoking significantly reduced CETP activity, but there was no significant association between CETP activity and body mass index. Although CETP activities were significantly higher in females than in males (P < 0.001), multiple regression analysis showed no correlation between CETP activity and age in either the males or the females. Our results suggest that CETP activity regulates the concentration of apo A-I and LDL-cholesterol, and that such activity may be influenced by gender, alcohol consumption and cigarette smoking.     

Myelodysplastic syndrome (MDS)-associated inhibitory activity on haemopoietic progenitor cells

We studied MDS-associated inhibitory activity, which inhibited colony formation in vitro of granulocyte-macrophage progenitors (CFU-GM). Macrophages obtained from MDS bone marrow mononuclear cells (BM-MNC) when pretreated with granulocyte-macrophage colony stimulating factor (GM-CSF) suppressed the growth of normal CFU-GM. These macrophages were designated as 'MDS-derived inhibitory macrophages'. Media conditioned by MDS-derived inhibitory macrophages (MDS-CM) also suppressed the growth of normal CFU-GM. In the MDS-CM, high levels of prostaglandin E2 (PGE2) and ferritin were found. However, MDS-CM did not contain detectable levels of tumour necrosis factor (TNF) or gamma-interferon (gamma-IFN). Antiserum against human placental ferritin and/or against PGE2 blocked the haemopoietic inhibitory activity to some extent. These results suggest that inhibitory macrophages may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors including PGE2 and ferritin.     

Relation between white blood cell counts and myocardial reperfusion in patients with recanalized anterior acute myocardial infarction.

BACKGROUND: The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. METHODS AND RESULTS: The relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6 h of symptom onset. Patients were classified according to the WBC count on admission: Group L (n=75), WBC count <12,000 cells/mm(3) and group H (n=60), WBC count >or=12,000 cells/mm(3). Peak creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a myocardial blush grade of 0/1, was more frequent in group H than in group L. Among the patients in group H, those with early (3 h) recanalization; however, peak CK and the incidence of impaired myocardial reperfusion were similar in these subgroups of patients. Multivariate analysis showed that WBC count >or=12,000 cells/mm(3) on admission was an independent predictor of impaired myocardial reperfusion in patients with early recanalization (odds ratio 7.9, p=0.04), but not in those with late recanalization. CONCLUSIONS: A higher WBC count may be associated with progression of myocardial damage after recanalization in patients with early recanalization of an anterior AMI.     

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat

Abstract: In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/macrophage population contributes to liver damage.     

C2 Deficiency Vasculitis: Complication of Enterocolitis, Cutaneous Ulcers, and Neuropsychiatric Disorder

A rare case of systemic vasculitis with second component of complement (C2) deficiency was documented in a patient who developed colonic ulcerations, jejunal edema and dilatation, cutaneous ulcers, peripheral neuropathy, and psychosis. Colonoscopy revealed typical features of ischemic colitis and radiological examination showed ischemic changes in the jejunum and ileum. Histopathological examination of the cutaneous biopsy revealed typical necrotizing vasculitis. It is very likely that multiorgan involvement, including ischemic changes of the intestine, developed secondary to vasculitis associated with C2 deficiency.     

Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection.     

Evaluation of a Free-Coupon Program for Cervical Cancer Screening Among the Young: A Nationally Funded Program Conducted by a Local Government in Japan

Background

Finding ways to improve the cervical cancer screening rates among young women has been seen as a critical national health problem in many countries, including Japan. The aim of the present study was to evaluate the effects of a free-coupon program for cervical cancer screening conducted by a local government under financial support from the Japanese national government.

Methods

The personal cervical cancer screening information was analyzed for all female residents of Toyonaka City, including any past screening history and clinical results since the year 2009, when a free-coupon program for screening was started. These results were compared to results from 2008, prior to implementation of the free-coupon screening program.

Results

The screening rates of women eligible for the free-coupon peaked dramatically compared to women of similar age who paid for their screening; however, the rates for the ineligible-age population also increased significantly in parallel to those in the free-coupon program, possibly by indirect peer and publicity effects. In women aged 20 to 25 years, the consecutive screening rate after a free-coupon screening was significantly lower than for those women who received a regular residential screening. After a free-coupon screening, the rate for participating in consecutive screenings depended significantly on the institution where the participant received her first screening test.

Conclusions

These results suggest that, for a generation of young women 20–25 years of age, a free-coupon program for cervical cancer screening was effective in increasing the first-time participation rate for screening; however, the increase in first-time participation did not lead to the expected increase in consecutive screenings.Key words: cervical cancer screening, free-coupon, screening rate, consecutive screening