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Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, ≥6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P < 0.05) and 8.06 (P < 0.001), respectively, when compared with the first SUA quartile (≤4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (≥5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P < 0.05) when compared with the first SUA quartile (≤4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men., (Copyright © 2015 the American Physiological Society.)

We herein report a fatal case of Legionella pneumophila pneumonia in a tocilizumab-treated rheumatoid arthritis patient who was in a state of shock on admission but remained afebrile even during severe pneumonia. Legionella antigen was detected in the urine and neutrophil CD64 expression was highly elevated. Despite undergoing intensive treatment, the patient developed sepsis and died 12 days after admission. An autopsy indicated that while the Legionella infection had almost been controlled, a subarachnoid hemorrhage was the ultimate cause of death.

Background: Mechanical discoordination (MD) is known as a myocardial deformation of opposite strain during ejection, reflecting dyssynchronous electrical activation. We used speckle tracking echocardiography to examine the relationship between MD, left ventricular (LV) function and geometry, as well as electrical dyssynchrony in various nonischemic hearts., Methods and Results: We examined 131 subjects (left bundle branch block [LBBB] 27; dilated cardiomyopathy [DCM] without LBBB 33; LV hypertrophy 28; and normal heart 43) using circumferential strain rate analysis. Integration of positive (stretch) and negative (shortening) components during the ejection time was obtained in the mid-ventricular level for 6 myocardial segments, and MD was quantified as the stretch to shortening ratio (SSR). The SSR in the septal region (anteroseptal and septal segments) was markedly elevated in the LBBB and DCM groups compared with the other groups. With univariate analysis, SSR over the septal region was found to be correlated with QRS duration, LV end-diastolic dimension, and LV ejection fraction. Multivariate analysis revealed that QRS duration and LV ejection fraction were significant independent determinants of SSR for the septal region., Conclusions: In nonischemic hearts, electrical dyssynchrony and LV dysfunction may contribute synergistically to MD in the septal region. The finding that non-LBBB DCM patients exhibited a certain amount of SSR may provide new insight into therapeutic strategies for cardiac resynchronization therapy., (© 2014, Wiley Periodicals, Inc.)

Objective: To evaluate the utility of neutrophil CD64 as a marker for monitoring the activity of nontuberculous mycobacteria (NTM) infection in patients with rheumatoid arthritis (RA)., Methods: We compared neutrophil CD64 expression in nine RA patients with NTM infection in the active and inactive phase of NTM disease chronologically. "Active phase" was here defined as present in patients admitted to hospital to receive intensive treatment for NTM, as well as outpatients with an infectious episode showing positive acid- and alcohol-fast bacillus (AFB) staining of sputa (Grade 2-3) who needed to start treatment for NTM with a multiple antibiotics regimen. The cut-off value for CD64 positivity was 2000 molecules/cell., Results: Neutrophils from patients with active-phase NTM infection expressed high levels of CD64 with a mean ± SEM of 7335 ± 784 molecules/cell. However, during the inactive phase of disease, this was significantly lower (1481 ± 103 molecules/cell, p < 0.001). The sensitivity and specificity of neutrophil CD64 to detect active-phase NTM infection was 96.3% and 84.6%, respectively. Expression of neutrophil CD64 was not affected by disease activity of the RA itself., Conclusions: Neutrophil CD64 is useful for monitoring disease activity in NTM infection of patients with RA.

The presence of septal flash (SF), an early inward/outward motion of the ventricular septum, has been reported to predict a fair response to cardiac resynchronization therapy (CRT) in patients with heart failure. Using speckle tracking echocardiography, we investigated whether the extent of pre-CRT SF was associated with left ventricular (LV) functional recovery after CRT device implantation. Fifteen patients with left bundle branch block with a mean LV ejection fraction of 23 ± 9% were enrolled in this study. The extent of presystolic ventricular flash (PSVF), which was defined if there was a peak in the radial strain curve in the preejection period, was semiquantified by counting the number of PSVF-positive segments. Patients underwent radial strain analysis before and between 3 and 6 months after CRT. After CRT device implantation, LV end-diastolic and end-systolic volumes were decreased, LV ejection fraction was increased, and LV filling time corrected by RR interval was increased. The number of PSVF-positive segments at baseline showed a graded association with improvement in both LV ejection fraction and LV filling time. In conclusion, the finding that a larger number of PSVF-positive segments before CRT predicted fair LV functional recovery after CRT suggests that PSVF may represent a substrate that is amenable to functional response to CRT., (© 2013, Wiley Periodicals, Inc.)

Cryptogenic organizing pneumonia (COP) following radiotherapy is occasionally diagnosed as radiation pneumonitis or bacterial pneumonia. The current study presents two cases of COP following radiotherapy: A 48-year-old premenopausal female with breast cancer and an 84-year-old male with non-small cell lung cancer. In the cases of breast cancer and lung cancer, patients were first diagnosed with bacterial pneumonia and radiation pneumonitis, respectively. In the two cases, computed tomography disclosed the migration of ground glass shadows, which were finally resolved without any fibrotic changes. The two cases were finally diagnosed as COP associated with radiotherapy. When an infiltrating shadow is present outside of the irradiated field, COP must be included in the differential diagnosis.

Background: Attenuation correction using segmentation with scatter and photopeak window data (SSPAC) may enable evaluation of the attenuation map in a patient-specific manner without the need for additional radiation exposure and more acquisition time. We examined the feasibility of SSPAC and compared the sensitivity, specificity, and accuracy of this new correction method with that of conventional non-corrected myocardial perfusion single-photon emission computed tomography (SPECT) among patients with suspected or diagnosed coronary artery disease., Methods and Results: One hundred sixty-one patients who underwent both (99m)Tc-tetrofosmin stress/rest SPECT examination and invasive coronary angiography were enrolled in the study. Data from the SSPAC-corrected and non-corrected methods were analyzed quantitatively using summed stress scores. Attenuation maps were obtained successfully for 150 (93%) of the patients. The SSPAC-corrected and non-corrected methods accurately predicted coronary artery disease defined as >50% luminal stenosis verified by coronary artery angiography and/or prior myocardial infarction, for 91% and 77% patients, respectively (P < .05). For diagnosis of coronary artery disease, SSPAC improved sensitivity in the left anterior descending artery territory and specificity in the right coronary artery territory., Conclusions: Attenuation correction with SSPAC may be a feasible method of correction for myocardial perfusion SPECT and in some cases may provide better accuracy for diagnosing coronary artery disease.

A 57-year-old woman with rheumatoid arthritis (RA) and limited systemic sclerosis (lSSc) was suspected to have lymphadenopathy and primary biliary cirrhosis (PBC). Lymph node biopsy showed reactive follicular lymphadenopathy with intrafollicular plasmacyte infiltration that was interleukin-6 positive by immunohistostaining. Because of gradually worsening arthritis, tocilizumab was administered and arthritis improved markedly. Interestingly, lymphadenopathy and PBC improved simultaneously. This suggested that interleukin-6 might play an important role in reactive lymphadenopathy and PBC associated with RA/lSSc.

Background: There are few reports on radiotherapy methods for treating extramammary Paget's disease (EMPD). The aim of this study was to explore the outcome of radiotherapy for EMPD., Patients and Methods: Between June 1995 and October 2010, 14 patients with EMPD (7 male and 7 female; median age 77 years) underwent radiotherapy at the Tokyo Medical University Hospital. The median total irradiation dose was 50 Gy, delivered in 20-33 fractions. Case reports of patients with EMPD were obtained from the PubMed database for the period of 1991-2012. 66 patients (median age 73 years) were identified. Radiotherapy outcomes were analyzed., Results: All patients achieved complete response within the irradiated volume during a median observation period of 71.4 months. The 5-year locoregional progression-free survival and overall survival were 91.7% (95% confidence interval (CI) 53.9-98.8%) and 84.3% (95% CI 50.3-95.8%), respectively. From the PubMed database, the 5-year local progression-free survival and locoregional progression-free survival were 84.5% (95% CI 65.3-93.6%) and 77.5% (95% CI 57.3-89.0%), respectively. 12 (18%) patients had a recurrence in the inguinal lymph nodes., Conclusion: Radiotherapy yielded good local control and survival, which suggests that it was effective for patients with EMPD and in particular medically inoperable EMPD., (© 2014 S. Karger GmbH, Freiburg.)

Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis.

This study aimed to retrospectively evaluate the efficacy of radiotherapy for primary intraocular non-Hodgkin lymphoma (PIOL). Between May 1998 and October 2010, 22 immunocompetent patients (four men, 18 women; median age 70 years, range 53-79 years) were diagnosed with PIOL. Magnetic resonance imaging showed no intracranial involvement in any patient. Patients received radiotherapy at a median total dose of 30 Gy (range 30-40 Gy). Three-year overall survival, progression-free survival and local control rates were 89% (95% confidence interval [CI]: 75, 103), 49% (95% CI: 24, 73) and 95% (95% CI: 86, 105) over a median of 36 months of observation, respectively. Twelve patients (55%) had intracranial relapse at a median of 28 months after initiation of radiotherapy. Visual acuity improved or was stable in 81% of treated eyes. The only grade ≥ 3 toxicity was cataract formation (five patients). Radiotherapy without chemotherapy for PIOL achieved high local control rates with acceptable toxicities.

Aim: Patients with T3 or more squamous cell esophageal cancer underwent low-dose preoperative radiotherapy with chemotherapy, to reduce local recurrence, followed by surgery. The aim was to ascertain tumor response and assess prognostic factors., Patients and Methods: Between May 2002 and June 2011, 37 consecutive patients with esophageal cancer underwent chemoradiotherapy followed by surgery. The numbers of patients in clinical stages IIA/IIIA/IIIB/IIIC were 2/24/7/4, respectively. All were given a dose of 30 Gy in 15 fractions, with concurrent chemotherapy using cisplatin and fluorouracil. Curative surgery was performed a median of 1.2 months after completion of chemoradiotherapy., Results: Based on the findings from surgery, 26 patients (70%) achieved a stage reduction and six patients (16%) had a complete pathological response. The numbers of patients undergoing resections microscopically complete, with microscopically positive margins, and macroscopically positive margins were 33, 3, and 1, respectively. During a median follow-up period of 22.5 months, the two-year progression-free survival and overall survival were 62.1% [95% confidence interval (CI)=45.8 to 78.4%] and 71.9% [95% CI=55.1 to 88.7%], respectively. Statistically significant prognostic factors for overall survival were age [hazard ratio=6.6; 95% CI=1.1 to 38; p=0.04] and pathological T factor [hazard ratio=10.2; 95% CI=1.4 to 77; p=0.02]. No patients died as a result of surgery., Conclusion: Seventy percent of patients with esophageal cancer who received radiotherapy dose of 30 Gy in 15 fractions combined with chemotherapy achieved a stage reduction with low toxicity.

Background and Purpose: To investigate the significance of the number of brain metastases in the treatment with stereotactic radiotherapy (SRT) with or without whole brain radiotherapy (WBRT)., Material and Methods: Between February 2003 and October 2010, 218 consecutive patients with brain metastases who underwent SRT alone or WBRT plus SRT were investigated. The prognostic factors affecting overall survival and brain progression-free survival were analyzed by multivariate and univariate analysis. By logistic regression analysis, factors associated with the number recurrences of brain metastasis after SRT were also investigated., Results: The median overall and brain progression-free survivals were 7.2 months and 4.3 months, respectively. Significant prognostic factors for overall survival in multivariate analyses were performance status (hazard ratio [HR] = 1.71, 95% confidence interval [CI] 1.13-2.57, p = 0.01) and the number of brain metastases (HR = 1.75, 95% CI 1.08-2.83, p = 0.02). Cut-off line of the number of brain metastases was between 3 and 4, and 3 or fewer brain metastases were significantly better than 4 or more in prognosis by univariate and multivariate analysis (p < 0.01, p = 0.02)., Conclusions: The patients with 3 or fewer brain metastases were associated with brain progression free survival and 3 or fewer brain relapse. Repeated SRT without WBRT may be effective for patients with 3 or fewer brain metastases.

A 46-year-old man, who had had sinusitis, developed bilateral omalgia, petechiae on his lower extremities and a congested right eye. A blood test detected elevated serum C-reactive protein level. Computed tomography incidentally found an acute lesion of thalamic hemorrhage without neurological symptoms and no specific therapy was given at the time. Thereafter, he developed vertigo, vomiting and pneumonia for which antibiotics were ineffective. He was referred and admitted to our hospital. Further, aural and renal lesions, and presence of serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) confirmed his diagnosis of granulomatosis with polyangiitis (Wegener's) (GPA). With corticosteroid and cyclophosphamide therapy, his symptoms disappeared in two months along with faded PR3-ANCA. Afterward he showed neither new cerebral lesion nor symptom. This is a rare case of GPA manifested with asymptomatic intracerebral hemorrhage. It should be noted that GPA could cause various manifestations in central nervous system such as a fatal or an asymptomatic hemorrhagic lesion, which might respond to immunosuppressive therapy.

We herein report the case of a 53-year-old man with severe coronary ischemia who underwent successful coronary artery bypass surgery. Of note, he had hypercholesterolemia and presented with multiple large tendinous xanthomas and thickened Achilles tendons that had been present for more than two decades. Together with a family history of dyslipidemia, the patient was diagnosed as having familial hypercholesterolemia. Irrespective of an extensive search for possible mutations in the genes presumably involved in the patient's pathophysiology, including low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), autosomal recessive hypercholesterolemia (ARH) and apolipoprotein B (APOB), we were not able to identify the gene mutations responsible for the phenotype observed in the present case.

Purpose: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for craniopharyngioma., Methods and Materials: Between 1999 and 2005, 16 patients with craniopharyngioma were referred to Tokyo Medical University Hospital. They received FSRT alone after histologic confirmation by needle biopsy and underwent cyst drainage via endoscopy. The median prescription dose fraction was 30 Gy in six fractions. All patients except 1 were followed up until December 2009 or death., Results: The median follow-up period was 52 months (range, 4-117 months). Of the 17 patients, 3 experienced recurrence 4 to 71 months after FSRT. The 3-year local control rate was 82.4%. One patient died of thyroid cancer, and the 3-year survival rate was 94.1%. Eight patients had improved visual fields at a median of 2.5 months after FSRT, but hormonal functions did not improve in any patient., Conclusions: FSRT after cyst drainage seems to be safe and effective for patients with craniopharyngiomas, and it may be a safe alternative to surgery., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A 59-year old woman had been suffering from myalgia, eruption and dyspnea on effort for a month. She was referred to our hospital because her symptoms were not improved by antibiotic therapy at a clinic. At first presentation she showed cutaneous manifestations including heliotrope eyelids and mechanic's hands, slightly elevated serum creatine kinase (CK), elevated serum C-reactive protein level, and interstitial pneumonia (IP), which led to a diagnosis as dermatomyositis. After admission to our hospital, her hypoxia due to IP progressed despite disappeared myalgia and normalized serum CK level. Intravenous steroid pulse therapy followed by oral cyclosporine and intravenous cyclophosphamide pulse therapy was not effective for the IP for more than a month. Gastroscopy revealed superficial depressed (0-IIc) type early gastric cancer. However, it was out of indication for endoscopic mucosal resection because of the histopathologic type (signet ring cell carcinoma) and possible submucosal invasion. In addition to those immunosuppressive therapies, proximal gastrectomy with total intravenous anesthesia was performed. One month after the operation, improvement of IP as well as cutaneous manifestations was confirmed by respiratory function test, pulmonary computed tomography, and discontinuance of oxygen inhalation. We conclude that this was a case of clinically amyopathic dermatomyositis with rapidly progressive IP and gastric cancer, which was ameliorated by a combination of medication (steroid, cyclosporine, and cyclophosphamide) and surgery (gastrectomy for early gastric cancer).

A 77-year-old woman with rheumatoid arthritis was admitted as an emergency because of pain in the right leg with purpura. She was diagnosed with severe cellulitis and sepsis and started on intravenous antibiotics; however, the lesion rapidly extended to the proximal thigh and she died only 38 h after the onset of the first symptom. Autopsy and tissue culture revealed necrotizing fasciitis caused by Streptococcus dysgalactiae subspecies equisimilis. Physicians should consider that necrotizing fasciitis may be present when soft-tissue disorder is suspected in patients receiving corticosteroid therapy, which is associated with tissue fragility and immunosuppression.

Aspirin-induced asthma (AIA) is a severe and difficult-to-treat allergic disease in which acute asthma attacks are induced by nonsteroidal anti-inflammatory drugs. Patients with AIA rarely experience asthma attacks when taking celecoxib, a specific inhibitor of cyclooxygenase (COX) 2. A 33-year-old woman had a severe asthma attack with hypoxia and lost consciousness after oral provocation testing with 15 mg of aspirin and also with 50 mg of celecoxib. After 2 months of treatment with 10 mg/day of oral prednisolone, 1600 μg/day of inhaled fluticasone propionate, montelukast as a leukotriene receptor antagonist (LTRA), and long-term beta-agonist, we again challenged her with a provocation test with up to 200 mg of celecoxib; this time there were neither allergic symptoms nor decrease in forced expiratory volume in 1 second. Patients with severe or poorly controlled asthma may experience asthma attacks even if using selective COX-2 inhibitors. However, treatment with steroids and an LTRAs may inhibit asthma attacks induced by celecoxib.

Objectives: Our purpose was to determine the feasibility and safety of transcatheter coil occlusion of a perimembranous VSD., Background: Transcatheter coil occlusion of a perimembranous ventricular septal defect (VSD) may be a useful treatment; however, there are few reports on its technical aspects and outcome., Methods: We attempted coil closure of a perimembranous VSD in 41 patients. We approached the VSD via the right ventricle (RV) in 16, via the left ventricle (LV) in 16, simultaneously deployed two coils from the RV (RV/RV) in three, and simultaneously deployed two, three, or four coils from the RV and LV (RV/LV) in six. Coils (0.038'' flipper, 0.052'' Gianturco, or 0.035'' platinum coil) were placed into the defect through the delivery catheter until any flow through the VSD disappeared or became trivial on angiography., Results: We achieved 100% complete closure in all patients in whom coils were deployed, although some patients required a second session. A flipper coil used alone was insufficient to completely occlude VSDs larger than 2.5 mm., Conclusions: Transcatheter coil occlusion of a VSD can be performed reliably and safely by selecting appropriate embolic coils. Small defects (<2.5 mm) can be closed with a flipper coil, but defects >or=2.5 mm require a 0.052'' coil., ((c) 2008 Wiley-Liss, Inc.)

Excessive nitric oxide (NO) production has been implicated in the pathophysiology of cardiomyocyte (CMC) apoptosis and necrosis induced by ischemia/reperfusion, inflammation and NO-donating chemicals. Although caspases are known to be involved in apoptosis, the present study examined whether caspases also play a role in NO-induced CMC necrosis. Neonatal rat CMCs were labeled with Annexin-V and propidium iodide, and apoptosis and necrosis were analyzed by confocal images and fluorescence activated cell sorter analysis. CMC apoptosis and necrosis were also evaluated by determining DNA fragmentation in the cell and the supernatant fractions. Treatment of CMCs with the NO donor, diethylenetriamine NO (DETA/NO) or S-nitroso-N-acetyl-penicillamine (SNAP) at concentrations of 10 and 100 microM for 24h induced predominantly apoptosis over necrosis, but a higher concentration (1mM) of DETA/NO or SNAP provoked both apoptosis and necrosis. The lower doses of DETA/NO-induced apoptosis was associated with a gradual increase in caspase-3 activity over 24h without appreciable activation of poly ADP-ribose polymerase (PARP), while the higher dose of DETA/NO induced a marked increase in caspase-3 activity and CMC apoptosis until 2h after the treatment, and increased necrotic CMCs thereafter associated with robust activation of PARP. The caspase inhibitor Z-DEVD-FMK but not the poly ADP-ribose polymerase (PARP) inhibitor 3-aminobenzamide (3-AB) abolished caspase-3 activation and CMC apoptosis induced by 100 microM DETA/NO. However, both Z-DEVD-FMK and 3-AB abolished PARP activation and CMC necrosis induced by 1mM DETA/NO. The amount of nicotinamide adenine dinucleotide (NAD) and adenine nucleotides in CMCs was not significantly affected by treatment with 10 and 100 microM DETA/NO, but was significantly reduced by treatment with 1mM DETA/NO without a decline of adenylate energy charge. The depletion of NAD and adenine nucleotides was abrogated by Z-DEVD-FMK and 3-AB. These results suggest that caspase activation play a crucial role in CMC apoptosis induced by lower concentrations of NO as well as in CMC necrosis induced by a higher concentration of and a longer exposure to NO. NO-induced CMC necrosis is likely mediated by PARP activation which occurs as a consequence of caspase activation.

A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.

An infant with double-outlet right ventricle (DORV) with intact ventricular septum (VS) is described. Hypoplastic left ventricle and mitral valve atresia were also associated. To the authors' knowledge, this appears to be the first case in which this rare form has been demonstrated with magnetic resonance imaging (MRI). The patient required balloon atrial septostomy (BAS) three times until 4 months of age because of progressive cyanosis. In such a form of DORV, surgical atrial septectomy should be performed instead of repeating BAS because the tendency to functional closure of the restrictive secundum arterial septal defect caused by incompetent foramen ovale seems to be prominent.

Twenty-three children with hypertrophic cardiomyopathy (HCM) (aged 2 months to 15 years) were followed up for more than four years using thallium myocardial imaging (TMI) and echocardiography. With echocardiography, the left ventricular end-diastolic dimension (LVDd) and fractional shortening (FS) were measured. Perfusion defect (PD) was assessed using TMI. Cardiac catheterization and right ventricular endomyocardial biopsy were performed in 18 patients within one week before or after their TMI. During the follow-up period, two patients showed a marked increase in LVDd and a marked decrease in FS at ages 13 and 16 years, respectively. These two patients were judged to have progressed to the dilated phase. In these two patients, extensive PD was detected in the left ventricular wall on TMI, 15 and 31 months prior to the appearance of the echocardiographic changes, respectively. Right ventricular endomyocardial biopsy at the time of extensive PD revealed marked interstitial fibrosis along with hypertrophy and disarray of myocardial cells. In conclusion, progression to the dilated phase is not a rare event in children with HCM and TMI appears to be a useful tool for early detection of the progression.

Laboratory and clinical studies of sulbactam/ampicillin (SBT/ABPC) in children have been carried out, and the following results were obtained. 1. Antibacterial effect MICs of SBT/ABPC were only one-tube less than or similar to those of ABPC against susceptible organisms. Against ABPC-resistant organisms at the inoculum size of 10(8) cells/ml however, SBT/ABPC was superior to ABPC when evaluated in terms of their MIC values. When MICs of SBT/ABPC were compared to those of ABPC against organisms with high beta-lactamase producing activities, it was found that many of ABPC-resistant organisms were much susceptible to SBT/ABPC. 2. Absorption and urinary excretion In 2 cases to which 50 mg/kg and 20 mg/kg SBT/ABPC were respectively given over 30 minutes by drip infusion, peak serum levels were obtained at the end of the drip infusion with peak levels of SBT of 45.5 micrograms/ml, 12.5 micrograms/ml, respectively and those of ABPC of 83.0 micrograms/ml, 22.9 micrograms/ml, respectively. The half-lives of SBT and ABPC were 0.94 hour and 0.98 hour, respectively. The mean urinary excretion rates in the first 6 hours after the end of administration were 84.4% for SBT and 63.1% for ABPC. 3. Clinical results Clinical efficacies were evaluated in 24 cases including 9 cases of pneumonia, 2 cases of upper respiratory infection, 7 cases of urinary tract infection and 1 case each of bronchopneumonia, pyothorax, tonsillitis, streptococcal infection, ++ phlegmon and staphylococcal scalded skin syndrome. Clinical efficacies were excellent or good in 19 cases with an overall efficacy rate of 86.4%. Adverse effect was found in 1 case with nausea and vomiting, and abnormal laboratory test values observed were 2 cases each of eosinophilia, slight elevation of GOT and GPT and elevation of LDH, but they were not serious.

Flomoxef (FMOX, 6315-S), a new parenteral oxacephem antibiotic was investigated for its clinical efficacy and pharmacokinetics. The results obtained are summarized below. 1. Twenty-eight patients were treated with 39-152 mg/kg per day of FMOX by intravenous administration. Diagnosis of patients were pneumonia in 15 patients, acute upper respiratory tract infection in 5, acute enterocolitis in 3, urinary tract infection in 2 and cholangitis, suppurative lymphadenitis and suspicious sepsis in 1 patient each. Clinical effect was excellent in 7 cases, good in 8, fair in 5, poor in 2 and 6 cases were excluded because therapy periods were too short and other antibiotics were used together. Efficacy rate was 68% and the rate of bacterial disappearance was 83%. 2. Rash was found in 5 cases and thrombocytosis was found in 1 out of 28 cases. However, no severe adverse reaction was encountered. 3. The peak serum level of FMOX was 51.0 micrograms/ml after 20 mg/kg of drip infusion for 30 minutes and the half-life was 17.2 minutes in alpha-phase and 58.2 minutes in beta-phase.