Hormone replacement therapy

Hormone Replacement Therapy (HRT) is replacement of depleted endogenous estrogen for postmenopausal women. Usually progestin is used in combination to avoid endometrial proliferation. As for bone metabolism, estrogens exert bone protective effect through inhibition of bone absorption. HRT has been shown to improve bone mineral density and to lower the risk of osteoporotic bone fracture. However, the results of recent large scale clinical studies in the U.S. indicate that HRT not only raise the risk of breast cancer, but also increase the incidence of atherosclerotic cardiovascular diseases. According to these studies, the benefit of HRT does not outweigh its risk except the treatment of postmenopausal vasomotor symptoms. To resolve this problem, low dose HRT and SERM (selective estrogen receptor modulator) regimens are under investigation.     

Catheter ablation of atrial fibrillation in patients with severely impaired left ventricular systolic function

Little is known about the outcome of catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) and a severely reduced left ventricular ejection fraction (LVEF). We aimed to clarify the effectiveness of catheter ablation of AF in patients with a severely low LVEF. This retrospective study included 18 consecutive patients with HF and an LVEF of ≤35 % who underwent catheter ablation of AF. We investigated the clinical parameters, echocardiographic parameters and the incidence of hospitalizations for HF. During a median follow-up of 21 months (IQR, 13–40) after the final procedure (9 with repeat procedures), 11 patients (61 %) maintained sinus rhythm (SR) (6 with amiodarone). The LVEF and NYHA class significantly improved at 6 months after the CA in 12 patients (67 %) who were in SR or had recurrent paroxysmal AF (from 25.8 ± 6.3 to 37.0 ± 11.7 %, P = 0.02, and from 2.3 ± 0.5 to 1.5 ± 0.7, P < 0.01, respectively) but not in patients who experienced recurrent persistent AF. The patients with SR or recurrent paroxysmal AF had significantly fewer hospitalizations for HF than those with recurrent persistent AF after the AF ablation (log-rank test; P < 0.01). Catheter ablation of AF improved the clinical status in patients with an LVEF of ≤35 %. A repeat ablation procedure and amiodarone were often necessary to obtain a favorable outcome.     

Syncope due to paroxysmal atrioventricular block in a patient with systemic sclerosis: a case report

A 79-year-old woman with systemic sclerosis was admitted to our hospital because of syncope. On admission, electrocardiogram showed progression of intraventricular conduction defect. Chest radiograph showed marked cardiomegaly. Echocardiogram revealed deterioration of left ventricular systolic function. We suspected progressive myocardial disease with Stokes-Adams attack. When we were preparing a temporary pacemaker, paroxysmal atrioventricular block with asystole for 15 seconds and convulsion occurred. Electrophysiological study showed His-ventricular block and sinus node dysfunction. A permanent pacemaker was implanted. In systemic sclerosis, progression of ventricular conduction defect may warrant prompt electrophysiological study and prophylactic pacemaker implantation.     

Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia

Interleukin 18 (IL-18) was discovered as an interferon-gamma (IFN-gamma)-inducing factor and plays important roles in natural killer (NK) cell activation. IL-18 also induces proinflammatory cytokines; chemokines; helper T-cell 2 (T(H)2) cytokines (eg, IL-4, IL-13); and immunoglobulin E (Ig-E) and IgG1 production. The combination of IL-18 plus IL-2 or IL-12 up-regulates IFN-gamma gene expression and NK cytotoxicity and has synergistic antitumor activity in vivo and in vitro. Here it is reported that daily administration of IL-18 with IL-2, but not of IL-18 or IL-2 alone, induces lethal lung injury in normal mice, but not in IL-18 receptor alpha (IL-1 receptor-related protein)-deficient (IL-18 receptor alpha(-/-)) mice. Marked interstitial infiltration of lymphocytes, composed mainly of NK cells, was found in the lungs of IL-18/IL-2-treated mice. Increased cytokine and chemokine levels were observed in the sera and lungs of IL-18/IL-2-treated mice. Administration of IL-18/IL-2 was also lethal to mice treated with a metalloproteinase inhibitor, which inhibited tumor necrosis factor-alpha and Fas-ligand release. While IFN-gamma(-/-) mice were partially resistant to the treatment, IL-4(-/-), IL-13(-/-), IL-4/IL-13(-/-), and Stat6(-/-) mice were sensitive to IL-18/IL-2, indicating that these genes were not involved in the host response. The lethal effect by IL-18/IL-2 was completely eliminated in severe combined immunodeficient mice pretreated with antiasialo-GM1 antibody and normal mice pretreated with anti-NK1.1 but not with anti-CD4 or anti-CD8, monoclonal antibody. These results suggest that specific cytokines, chemokines, and NK cells are involved in the pathogenesis of interstitial pneumonia. These results suggest that the clinical use of this interleukin may result in unexpected physiological consequences.     

A three-year review of acute respiratory tract infections caused by Streptococcus milleri group

The objective of our study is to understand the clinical features of patients with acute respiratory tract infection associated with Streptococcus milleri group (SMG). Fifteen patients with SMG respiratory tract infection visited our hospital from July, 1997 through May, 2000. There were seven cases of pneumonia, two pulmonary abscess, three thoracic empyema and three acute bronchitis. The mean age of the patients was 57.8 years (range 16-87), twelve were males, and seven were smokers. The moderately to severe underlying diseases existed in thirteen patients (86.7%) and included the following: respiratory diseases (20.0%), history of the esophageal or gastric surgery (26.7%), central nerve system diseases (13.3%), alcohol intake (60.0%), hepatitis and pancreatitis (33.3%), diabetes mellitus (13.3%) and malignancy (6.7%). The species of SMG detected were as follows: S. constellatus, 8, S. anginosus, 6 and S. intermedius, 1. Anaerobic organism and other microorganisms were detected in five patients. A patient with SMG nosocominal pneumonia who previously had thoracic surgery for esophageal cancer died. Antibiotics therapy with carbapenem or combination therapy, drainage and no surgery, were successful in 14 of the 15 cases (93.3%). The number of intermediately or complete resistant strains against penicillin G, ampicillin and cefmetazole were 5 (33.3%), 8 (53.3%) and 12 (80.0%), respectively in this series. Recently, it is seemed that acute respiratory tract infections caused by SMG are increasing in the patients with moderately to severe underlying diseases, and several clinical strains of SMG are acquiring a tolerance to antibiotics.     

Difference in coronary blood flow dynamics between patients with hypertension and those with hypertrophic cardiomyopathy.

We studied twelve patients with hypertensive left ventricular hypertrophy (LVH), 10 patients with hypertrophic cardiomyopathy (HCM) and 10 control subjects to examine the differences in coronary blood flow (CBF) dynamics between patients with hypertensive LVH and those with HCM. All subjects had normal coronary arteriograms. Measurements of CBF using Doppler Flo-Wire were performed at rest, and after infusions of acetylcholine and papaverine. The baseline CBF was significantly increased in both hypertensive LVH patients and HCM patients compared to that noted in control subjects (64.1+/-36.9, 80.0+/-38.1, 32.3+/-8.0 ml/min, respectively, p<0.01). Coronary flow reserve and endothelium-dependent vasodilatation were significantly lower in hypertensive LVH patients and HCM patients than in control subjects, but there was no significant difference between the hypertensive LVH and HCM patients themselves. In contrast, the diastolic/systolic velocity ratio at baseline was significantly lower in hypertensive LVH patients than in HCM patients (1.53+/-0.40, 6.31+/-7.50, p<0.05). Although CBF and coronary flow reserve correlated positively and negatively, respectively, with left ventricular mass index (r=0.51, -0.59, respectively), the diastolic/systolic velocity ratio at baseline did not show a significant correlation to left ventricular mass index. In conclusion, the diastolic/systolic velocity ratio differed between hypertensive LVH and HCM patients, independent of left ventricular mass. These results suggest that the difference of phasic pattern of CBF may be essential for coronary circulation in patients with hypertensive LVH and in those with HCM.     

Non-invasive assessment of coronary arterial tone using trans-thoracic Doppler echocardiography.

BACKGROUND: As coronary flow velocity (CFV) is inversely related to the luminal size that exists for the myocardial bed, the elevated arterial tone can be assessed as the higher flow velocity in the epicardial artery. We examined the usefulness of transthoracic Doppler echocardiography (TTDE) for the assessment of coronary arterial tone. METHODS AND RESULTS: A total of 32 patients underwent TTDE and angiography. The luminal diameter (LD) in the left anterior descending artery (LAD) was measured by using quantitative coronary angiography before and after nitroglycerin (NTG) administration. The ratio of post NTG LD to the control (LD(NTG/Pre)) was assessed as a standard parameter of coronary arterial tone. We also measured CFV and CFV reserve (CFVR) at the LAD by TTDE. We evaluated the change of CFV (CFV(NTG/Pre)) and CFVR (CFVR(NTG/Pre)) following NTG administration. The LD increased from 1.98+/-0.46 to 2.51+/-0.34 mm (p<0.001), while the CFV decreased from 23.9+/-10.0 to 16.3+/-5.6 cm/s (p<0.03), and the CFVR increased from 2.39+/-0.65 to 3.56+/-1.12 (p<0.001). There were significant correlations between CFV(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.532), and between the CFVR(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.715). CONCLUSION: TTDE can assess the coronary arterial tone by measuring the responses of CFV and CFVR to NTG administration.     

Helicobacter pylori Infection and Gastric Cancer (A Nested Case-Control Study in a Rural Area of Japan)

We conducted a seroepidemiological nested case-control study to determine the association of gastriccancer with Helicobacter pylori infection and atrophicgastritis. A cohort of 2858 participants in an annual multiphasic health check-up werefollowed for eight years. Data for 45 gastric cancercases and 225 sex-, age-, and address-matched controlsubjects were analyzed. Helicobacter pylori infectionwas determined by IgG antibodies, and atrophicgastritis was diagnosed by both serum pepsinogen I level(70 ng/ml) and the pepsinogen I/II ratio (3.0).Univariate analysis showed that Helicobacter pylori and atrophic gastritis were significantlyassociated with gastric cancer. In a multivariateanalysis, atrophic gastritis was associated withsignificantly increased risk of cancer (odds ratio,3.38; 95% confidence interval, 1.54-7.42); however,Helicobacter pylori was not associated with cancer (oddsratio, 1.84; 95% confidence interval, 0.59-5.72). Theseresults suggest that Helicobacter pylori infection alone is not directly associated with gastriccarcinogenesis but has an indirect relation to gastriccancer through the development of atrophicgastritis.