Influence of Overweight on Cardiac Function Examined by Echocardiography

The effects of overweight on right and left ventricular function in the absence of associated cardiovascular disease are not well known. In the present study, we assessed the influence of overweight on systolic and diastolic function of 314 normal subjects, ranging from 30 to 59 years, by a Doppler echocardiography. The ratio of A wave to E wave of left and right ventricular inflow (LV E/A, RV E/A) and left ventricular ejection fraction (LVEF) were measured. LV E/A, RV E/A and LVEF correlated inversely with body mass index (BMI) (p<0.01, p<0.01, p<0.05 respectively). LV E/A, RV E/A and LVEF were also significantly lower in the overweight group (BMI≧25) than those in the normal weight group (BMI<25). These results suggest that overweight may worsen the left and right ventricular diastolic function in addition to the left ventricular systolic function

Neutrophil-mediated Phagocytosis and Killing against Cryptococcus neoformans and Inhibition of These Activities by Its Capsular Polysaccharides

Cryptococcus neoformans is an opportunistic fungal pathogen, which frequently causes fatal meningoencephalitis in patients with acquired immunodeficiency syndrome (AIDS). This fungal microorganism is an intracellular parasite, and the host defense is usually mediated by cellular immunity. By contrast, the role of polymorphonuclear leukocytes (PMN) is reported to play a limited role. At the end stage of AIDS, the host defense by cellular immunity is no longer expected, but the potential of PMN is not completely excluded. On this background, we examined the activity of human peripheral blood PMN to phagocyte and kill this fungal pathogen. PMN showed the potent phagocytosis and killing against acapsular strain of C. neoformans only when it was opsonized by serum. This activity was strongly enhanced by the addition of either interferon(IFN)-γ or granulocyte macrophage colony-stimulating factor (GM-CSF), but completely abrogated by the capsular polysaccharides of this fungal microorganism, including much of glucuronoxylomannan. The present study re-evaluated the capacity of PMN in the host defense to C. neoformans and provided an implication in the immune-based treatment of this infectious diseases

Clinical response of levofloxacin 500 mg qd to respiratory tract infection

日本人呼吸器感染症患者152例を対象にlevofloxacin（LVFX）500 mgを1日1回7日間投与し，有効性および安全性を非盲検非対照試験にて検討した。また，各患者の血漿中薬物濃度を測定し，ベイズ推定により患者ごとの薬物動態パラメータを算出し，有害事象および副作用発現との相関を検討した。　臨床効果の有効率は95.1％（136/143例），微生物学的効果（陰性化）の陰性化率は100％（45/45例）であった。主な原因菌はStreptococcus pneumoniae，Haemophilus influenzae，Moraxella （Branhamella） catarrhalis，Staphylococcus aureusおよびKlebsiella pneumoniaeであり，これらを含めて微生物学的効果（消失）判定が可能であった原因菌50株はすべて消失した。　副作用発現率は39.5％（60/152例）であり，重篤な副作用として1例に肝障害がみられたがLVFXの投与を中止し，入院加療により回復した。重度の副作用はなく，いずれの副作用もLVFXの副作用として従来報告されている事象であった。本試験の血漿中薬物濃度の範囲では，LVFXの曝露量の増加に伴い有害事象または副作用の発現率に上昇傾向は認められなかった。　以上のとおり，LVFXの500 mg 1日1回投与は呼吸器感染症に対して100 mg 1日3回投与と同等以上の十分な効果が期待され，その安全性に重大な問題はないと考えられた。We evaluated the efficacy and safety of LVFX 500 mg qd administered for 7 days to 152 Japanese patients with respiratory tract infection in an open uncontrolled clinical study. We also studied the possible correlation of the incidence of adverse event and adverse drug reactions(ADRs) with individual pharmacokinetic (PK) parameters estimated by the Bayesian method. Clinical efficacy was 95.1% (136/143 patients), and bacteriological efficacy 100% (45/45 patients). All causative organisms (50 strains), including those commonly separated, i.e., Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, Staphylococcus aureus, and Klebsiella pneumoniae, were eradicated with treatment in patients eligible for bacteriological efficacy assessment. ADRs were reported in 60 patients at an incidence of 39.5%. A liver disorder was reported as a serious adverse drug reaction in a patient administered LVFX. The patient discontinued taking LVFX and recovered through hospitalization and medical treatment. No ADRs were severe and all had already been reported as LVFX ADRs. Neither the incidence of adverse events nor ADRs was exposure-dependent in the LVFX plasma concentration range observed in this study. In conclusion, LVFX 500 mg qd appears to have efficacy comparable or superior to that of the current standard dosage and presents no significant safety problem

Multicenter open-label phase II/III study of intravenous levofloxacin in subjects with respiratory tract infection

キノロン系薬であるlevofloxacin（LVFX）注射剤の呼吸器感染症（市中肺炎または慢性呼吸器病変の二次感染）に対する有効性および安全性を検討する目的で，非盲検非対照臨床試験を実施した。用法・用量および投与期間は，LVFX 500 mgを1日1回，7～14日間点滴静注とした。　臨床効果：投与終了・中止時の呼吸器感染症全体の有効率は95.6％（173/181例）であり，診断名別には市中肺炎で95.9％（140/146例），慢性呼吸器病変の二次感染で94.3％（33/35例）であった。また，呼吸器感染症の主要な原因菌であるStreptococcus pneumoniaeが分離された患者での有効率は100％（35/35例）であった。　細菌学的効果：投与終了・中止時の陰性化率は97.6％（80/82例），菌消失率は97.8％（91/93株）であった。　安全性：全体の副作用発現率は44.2％（91/206例）であり，80歳以上の高齢者での副作用発現率は25.0％（4/16例）であった。5％以上に発現した副作用は，注射部位紅斑13.6％（28/206例），ALT増加9.7％（20/206例），AST増加8.7％（18/206例）であった。特に，注射部位反応（注射部位紅斑，注射部位そう痒感，注射部位疼痛，注射部位腫脹，および注射部位硬結）は高頻度に認められ，その発現率は16.5％（34/206例）であった。なお，注射部位反応は，すべて軽度であり，いずれも処置を必要とせず発現日当日に消失し，投与を中止した症例はなかった。　以上の成績から，LVFX注射剤500 mg 1日1回7～14日間点滴静注は，呼吸器感染症に対して十分な治療効果が期待でき，安全性に大きな問題はないと考えられた。This open-label study evaluated the efficacy and safety of an injectable preparation of levofloxacin(LVFX), a quinolone antibacterial, in the treatment of respiratory tract infection(RTI). Subjects with communityacquired pneumonia or secondary infection of chronic respiratory disease were enrolled and treated with LVFX administered at 500 mg once daily by intravenous infusion for 7―14 days. Clinical efficacy: Of 181 evaluable subjects with RTI, 173 (95.6％) showed a clinical response at the end of treatment. Clinical response rate by diagnosis was 95.9％ (140 146) for community-acquired pneumonia and 94.3％ (33 35) for secondary infection of chronic respiratory disease. A clinical response was achieved in 35 35 subjects (100％) with isolates of Streptococcus pneumoniae the predominant RTI causative organism. Bacteriological efficacy: Bacteriological response rate per subject was 97.6％ (80 82) and overall pathogen eradication rate was 97.8％ (91 93), at the end of treatment. Safety: The adverse drug reaction incidence was 44.2％ (91 206) in the overall population and 25.0％ (4 16) in the elderly ( 80 years of age). Adverse drug reactions reported in at least 5％ of those treated and evaluable for safety included injection site erythema (13.6％ [28 206]), ALT increased (9.7％ [20 206]), and AST increased (8.7％ [18 206]). Injection site reactions―erythema, pruritus, pain, swelling, and induration―were especially frequent, occurring in 34 of 206 subjects (16.5％). All injection site reactions were mild and resolved within the day of onset without treatment. None required treatment discontinuation. In conclusion, LVFX administered by intravenous infusion at 500 mg once daily for 7―14 days is effective and safe in RTI treatment

Clinical phase III comparative study of intravenous levofloxacin and ceftriaxone in community-acquired pneumonia treatment

成人の非定型病原体を除く細菌性市中肺炎に対するlevofloxacin（LVFX）注射剤の有効性，安全性を検討する目的で，ceftriaxone（CTRX）注射剤を対照薬として，多施設共同，無作為化（中央登録方式）, オープンラベル，非劣性検証試験を実施した。用法・用量および投与期間は，LVFX群は1回500 mg 1日1回，CTRX群は1回1 g 1日2回点滴静注，投与期間は7～14日間とした。　臨床効果：投与終了・中止時の有効率は，LVFX群で88.5％（92/104例），CTRX群で88.8％（79/89例），群間差は－0.3％（95％信頼区間：－9.3～8.7）であり，LVFXのCTRXに対する非劣性が検証された。　細菌学的効果：投与終了・中止時の陰性化率はLVFX群で96.7％（59/61例），CTRX群で97.8％（44/45例），群間差は－1.1％（95％信頼区間：－7.3～5.1）であった。　安全性：副作用発現率は，LVFX群で53.7％（73/136例），CTRX群で56.9％（70/123例）であり，群間差は－3.2％（95％信頼区間：－15.4～8.9）であった。　以上のことから，LVFX注射剤は，非定型病原体を除く細菌性市中肺炎に対して1回500 mg 1日1回投与でCTRX 1回1 g 1日2回投与と同様に十分な治療効果ならびに安全性の高い薬剤であることが確認された。To evaluate the efficacy and safety of intravenous levofloxacin(LVFX) in adults with community-acquired bacterial but not atypical organismic pneumonia, we conducted a multicenter randomized open-label noninferiority study using ceftriaxone(CTRX) as a comparator. Subjects were randomized through central registration to be administered LVFX 500 mg once daily or CTRX 1 g twice daily as an intravenous infusion for 7 to 14 days. Clinical efficacy: At the end of treatment, clinical response was 88.5％ (92 104) in LVFX-treated and 88.8％ (79 89) in CTRX-treated. The intergroup difference was －0.3％ (95％ confidence interval, －9.3 to 8.7) and non-inferiority of LVFX versus CTRX was established. Microbiologic efficacy: Eradication at the end of treatment was achieved in 96.7％ (59 61) treated with LVFX and 97.8％ (44 45) treated with CTRX. The intergroup difference was －1.1％ (95％ confidence interval, －7.3 to 5.1). Safety: Adverse drug reactions were reported in 53.7％ (73 136) treated with LVFX and 56.9％ (70 123) treated with CTRX. The intergroup difference was －3.2％ (95％ confidence interval, －15.4 to 8.9). Our results showed that intravenous LVFX 500 mg once daily is as effective and safe as CTRX 1 g twice daily in treating community-acquired bacterial pneumonia