[Infective endocarditis of the mitral valve complicated with preoperative rupture of the mycotic iliocolic artery aneurysm].

A 55-year-old man was diagnosed with infective endocarditis( IE) of the mitral valve caused by Streptococcus sanguinis. His IE was controlled immediately after the initiation of intravenous antibiotic therapy lasting for 4 weeks. A few days before surgery, he complained of abdominal discomfort and computed tomography (CT) scan revealed rupture of the mycotic iliocolic artery aneurysm. Emergency transcatheter arterial embolization( TAE) was successfully conducted. After additional 4 weeks' intravenous antibiotic therapy, the mitral valve was replaced. Mycotic visceral artery aneurysms are rare in IE. Early diagnostic approaches and interventions such as TAE are crucial.

[Distal aortic repair after aortic arch replacement].

BACKGROUND: It is crucial to expose the proximal aorta in distal aortic repair, i.e., replacement of the descending thoracic aorta (DTA) or the thoracoabdominal aorta (TAA), after aortic arch replacement. With the elephant trunk (ET), it is usually easy to expose and clamp it. On the other hand, without the ET, it may be difficult or impossible to expose the proximal aorta and deep hypothermic circulatory arrest (DHCA) will be required. METHODS: Between April 1989 and March 2007, 17 patients underwent distal aortic repair after aortic arch replacement. Five patients underwent replacement of DTA and 12 of TAA. Five patients without the ET needed DHCA and open proximal anastomosis [OP (+) group], while in 12 patients, the ET or proximal aorta was successfully clamped [OP (-) group]. RESULTS: The mean extracorporeal circulation time in OP (+) group was significantly longer than that in OP (-) group (415 +/- 131 min v.s. 267 +/- 109 min, p < 0.05). There was no hospital death, cerebral infarction, fatal arrhythmia or low output syndrome in either group, and paraplegia in 2 patients and renal failure requiring hemodialysis in one were found only in OP (+) group. CONCLUSION: The ET procedure enables to avoid DHCA and may contribute to improving operative results in distal aortic repair after aortic arch replacement.

Increase of child car seat temperature in cars parked in the outpatient parking lot.

BACKGROUND: A guideline for the safe use of child car seats (CS) was published by the Japan Pediatric Society in 2008. There have been few studies of the increase of temperature of a CS in parked cars. The aim of this study was to determine the change in the temperature of the CS in cars parked in full sun. METHODS: The temperature of CS was measured during summer (July and August) in 2006, 2007, and 2008. The CS used in this study (n= 50) were for children (≤ 6 years old) who were taken by car to Sugimura Children's Medical Clinic. Temperatures were only measured on sunny days. Measurements were performed from 09.00 to 17.00 hours. Thermochron (Thermochron i-Button: G type, Maxim Integrated Products, CA, USA) was used to measure the temperatures. The maximum temperatures of CS were compared in time at the clinic, taking into consideration seat colors, and car colors. RESULTS: Of the 50 cars, three cars were excluded due to being in the shade while the temperature was measured. A total of 47 cars were used for this study. The temperature of the CS ranged from 38.0 to 65.5°C (47.8 ± 5.8°C). Eighteen CS (38.3%) reached a temperature of 50°C or above. The maximum temperature of the 13.00-15.00-hours group was significantly higher than that of the 09.00-11.00-hours group (P= 0.035). The CS temperatures in the black car group were significantly higher than those of the white car group (P= 0.013). CONCLUSION: CS may become very hot while a car is parked in sun, especially if the car and the CS are black, so the CS should be cooled before a young child is placed in it. Guardians of small children should be aware of this risk.

Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations.

The objective of the present work is to develop an extended-release dosage form of cevimeline. Two types of extended-release tablets (simple matrix tablets and press-coated tablets) were prepared and their potential as extended-release dosage forms were assessed. Simple matrix tablets have a large amount of hydroxypropylcellulose as a rate-controlling polymer and the matrix is homogeneous throughout the tablet. The press-coated tablets consisted of a matrix core tablet, which was completely surrounded by an outer shell containing a large amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the release of cevimeline effectively. In contrast, the press-coated tablets showed a slower dissolution rate compared with simple matrix tablets and the release curve was nearly linear. The dissolution of cevimeline from the press-coated tablets was not markedly affected by the pH of the dissolution medium or by a paddle rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was constantly released from the press-coated tablets in the gastrointestinal tract and the steady-state plasma drug levels were maintained in beagle dogs. These results suggested that the designed PC tablets have a potential for extended-release dosage forms.

Mumps virus reinfection is not a rare event confirmed by reverse transcription loop-mediated isothermal amplification.

Clinically apparent mumps reinfection is considered extremely rare, but several cases have been suspected of reinfection in an out-patient clinic. In this study, virological examination, virus isolation, the reverse transcription loop-mediated isothermal amplification (RT-LAMP), and IgG and IgM EIA antibodies, were examined in order to identify mumps reinfection. Patients were divided into three categories; the reinfection group comprised 29 patients with a history of natural infection, the vaccine-failure group consisted of 37 patients with an immunization history, and two patients had histories of both immunization and mumps infection. Another 25 patients were enrolled as a primary infection group. Mumps virus was isolated in 5 (17%) and the genome was detected in 12 (41%) of 29 in the reinfection group. Reinfection was confirmed in 21/28, demonstrating high avidity of IgG EIA. Mumps virus was isolated in 15 (41%) and there was a higher positivity of genome amplification in 25 (68%) of 37 patients in the vaccine-failure group. Among these, 23 were confirmed as secondary vaccine failure by high avidity IgG EIA serology. In the primary infection group, the isolation rate and genome detection rate was higher in 16 (64%) and in 18 (72%) of 25 patients, respectively. There was no significant difference in virus load among the three groups but high mumps virus load was suspected in the IgM EIA-positive group based on the shorter amplification time on RT-LAMP. Mumps virus reinfection was confirmed by RT-LAMP and an IgG avidity test and was not a rare event.

A comparative study of the incidence of aseptic meningitis in symptomatic natural mumps patients and monovalent mumps vaccine recipients in Japan.

To compare the incidence of aseptic meningitis associated with symptomatic natural mumps infection and in mumps vaccine recipients, we conducted a prospective comparative study. Consecutive samples of 1051 children with mumps were enrolled by 10 pediatricians and 21,465 vaccine recipients by 143 pediatric primary care practitioners, from January 1, 2000 to January 1, 2003. Parents used a daily diary to record symptoms during the period of illness (15 days) or 30-day period following immunization. Mumps infection was confirmed by virus isolation and/or detection of mumps virus genome in salivary and CSF samples. The incidence of aseptic meningitis was 13/1051 (1.24%) in patients with symptomatic natural mumps infection and was estimated to be 0.7-1.1% of overall infection in considering asymptomatic infection, and 10/21,465 (0.05%) in vaccine recipients. Although aseptic meningitis is a clear side effect of the mumps vaccine, the incidence is considerably lower than among those with symptomatic natural infection. Our results provide an informative data for consideration to resume mumps vaccine as a part of routine immunization schedule for Japanese children.

Efficacy of inactivated trivalent influenza vaccine in alleviating the febrile illness of culture-confirmed influenza in children in the 2000-2001 influenza season.

During the 2000/2001 influenza season in Japan, children ranging in age from 6 months to 13 years with fever exceeding 37.5 degrees C were recruited. Vaccine efficacy was evaluated by comparing the rates of pre-seasonal vaccination between groups stratified by fever severity. Seven hundred and sixty one patients (33.1%), culture positive for influenza were enrolled for analysis. The numbers of patients for A/H1N1 and A/H3N2 were insufficient for statistical analysis. For influenza B the odds ratio for vaccinated children to have a maximum fever exceeding 39.5 degrees C was 0.52 (95% CI, 0.30-0.92) Our findings suggest modest impact of influenza vaccination on limiting severity of disease symptoms.

Mitral valve replacement after percutaneous transluminal mitral commissurotomy.

OBJECTIVES: We reviewed our experience of mitral valve replacement (MVR) after percutaneous transluminal mitral commissurotomy (PTMC) for mitral stenosis (MS). METHODS: From December 1987 to December 2001, PTMC was conducted in 75 patients with symptomatic rheumatic MS. At mean follow-up of 8.4+/-3.5 years, 11 patients (14.7%) underwent MVR for mitral restenosis (9 cases) and mitral regurgitation (MR) (2 cases). The mean interval between PTMC and MVR was 5.2+/-3.2 years. RESULTS: There were 2 hospital deaths (due to low output syndrome and mediastinitis) and 2 complications (prosthetic valve endocarditis and left ventricular rupture). The mitral valve area (MVA) at pre-PTMC, post-PTMC and pre-MVR was 1.02+/-0.48 cm2, 1.55+/-0.59 cm2, 1.04+/-0.23 cm2, respectively. The MVA significantly increased after PTMC (p<0.01), but decreased significantly to the pre-PTMC value at pre-MVR (p<0.05). The left atrial dimension (LAD) significantly increased from 50.4+/-10.8 mm at pre-PTMC to 61.1+/-13.1 mm at pre-MVR (p<0.05). The number of significant tricuspid regurgitation (TR) cases increased from 2 at pre-PTMC to 5 at pre-MVR. The New York Heart Association class got better after PTMC (3 cases in class III at pre-PTMC to 0 at post-PTMC), but at pre-MVR, deteriorated to the same level at pre-PTMC (4 cases in class III). CONCLUSIONS: Our results of MVR after PTMC were reasonable to be considered despite their high risk at MVR resulting in 2 hospital deaths. For the reliable relief of MS and control of TR, not PTMC but MVR combined with tricuspid annuloplasty may be preferable in such two cases suffering from congestive heart failure with significant TR at first intervention. Close follow-ups like periodic ultrasonic cardiography studies should be conducted to gain more information on the mitral restenosis, TR deterioration and dilatation of the cardiac chambers.

Molecular epidemiology of mumps virus in Japan and proposal of two new genotypes.

We isolated 872 strains of mumps virus from naso-pharyngeal secretions in seven different districts of Japan from January 2000 to July 2001. Among them, 57 strains were geno-typed by nucleotide sequencing in part of the hemagglutinin-neuraminidase (HN) and small hydrophobic (SH) protein regions. Four different genotypes (B, G, K, and L) of mumps virus were co-circulating in Japan and the distribution of genotypes varied in geographically different districts. Two new clusters designated as genotypes K and L had more than 7% nucleotide variation in the SH gene. Among the 57 strains, 11 were classified as B, 35 as G, three as K, and eight as L, which was mainly isolated in Tokyo. We also examined 104 stains isolated in a clinic in Mie prefecture from 1993 to 2003. Genotype B was the indigenous strain and genotype K was introduced in 1994. Genotypes B and K co-circulated in the 1990s and were replaced by genotype G in 2000. There was no significant change in neutralizing test antibody titers against genotypes B, G, K, and L using seven post-vaccination sera with Hoshino strain (genotype B) and these four genotypes had a different antigenicity from genotype A. We should continue to watch on mumps virus molecular epidemiology.

Left ventricular rupture following mitral valve replacement due to oversize prosthesis.

Left ventricular rupture following mitral valve replacement is one of the most serious complications. We report our experience in successful treatment of type III left ventricular rupture following mitral valve replacement probably due to an oversize prosthesis. A 67-year-old woman, with the history of percutaneous transluminal mitral commissurotomy 11 years previously, underwent mitral valve replacement for mitral restenosis with a 27 mm CarboMedics mechanical bileaflet valve (Sulzer CarboMedics Inc., Austin, TX, U.S.A.). There were some difficulties in placing the entire prosthesis into the annulus at the posterior because of the oversize prosthesis. After the complete placement of the prosthesis, bulge of the left ventricular muscle was evident around the left lateral region. Following the cessation of cardiopulmonary bypass, type III left ventricular rupture, half a circular rip between the papillary muscles and posterior mitral annulus, occurred. The rip was suture-closed and a 23 mm CarboMedics valve was placed. Postoperative ultrasonic cardiography showed no prosthetic stenosis, periprosthetic leak, left ventricular pseudoaneurysm, nor left ventricular asynergy. Under cardioplegic arrest, we should not select the oversize prosthesis to prevent left ventricular rupture.

Acute type A aortic dissection complicated with acute inferior myocardial infarction following aortic valve replacement.

Acute aortic dissection complicated with acute myocardial infarction (AMI) is the most fatal situation. We experienced the successful treatment for acute type A aortic dissection complicated with inferior AMI following aortic valve replacement (AVR). A 60-year-old man had had AVR for aortic regurgitation. Sixteen months after the AVR, he had a sudden onset of severe chest pain with complete atrioventricular block. Immediately, temporary pacing and cardiac catheterization were conducted, showing the occlusion of the right coronary artery due to acute type A aortic dissection. On his way to our hospital, direct current shock was conducted 3 times for ventricular fibrillation. We replaced the ascending aorta combined with coronary artery bypass grafting and the postoperative course was uneventful. The key to treat acute aortic dissection complicated with AMI is early accurate diagnosis, prompt temporary pacing for bradycardia, defibrillation for lethal arrhythmia and insertion of a perfusion catheter if possible. These preoperative hemodynamic stabilization gives us the chance to save these patients.

Left pulmonary artery occlusion due to compression by aortic aneurysm.

A 72-year-old man with shock was transferred to our emergency room. The computed tomograms revealed a ruptured giant thoracic aortic aneurysm obstructing the left pulmonary artery. Emergency total aortic arch replacement was performed, and the postoperative course was uneventful. The postoperative angiography confirmed the total occlusion in the left pulmonary artery which was due to compression by the aortic aneurysm.

Surgery for coronary artery disease with penetrating atherosclerotic ulcer of the ascending aorta.

Penetrating atherosclerotic ulcer (PAU) is most often found in the descending aorta but rarely in the ascending aorta. In such a rare case, a 63-year-old man with ischemic change at precordial leads in electrocardiography was found in coronary angiography to have the left main trunk stenosis and in aortography (aortic phase of left ventriculography) to have PAU in the ascending aorta. We conducted 3-vessel coronary artery bypass grafting and replaced the ascending aorta. Preoperative evaluation of the ascending aorta is thus important in cardiac surgery as in this case.

Cyclodextrin conjugate-based controlled release system: repeated- and prolonged-releases of ketoprofen after oral administration in rats.

6(A)-O-[2-(3-Benzoylphenyl)propinoyl]-alpha-cyclodextrin (KP-alpha-CyD conjugate), in which an anti-inflammatory drug, ketoprofen (KP), is covalently bound to one of the primary hydroxyl groups of alpha-cyclodextrin, was prepared, and its release behavior in vitro and in vivo was investigated. Further, the CyD conjugate-based repeated- and prolonged-release systems were designed by combining the conjugate (used as a delayed-release fraction) with the KP-2-hydroxypropyl-beta-CyD (HP-beta-CyD) complex (used as a fast-release fraction) or with KP-ethylcellulose (EC) solid dispersion (used as a slow-release fraction), respectively. The conjugate released KP only in rat cecum and colonic contents, whereas it was stable in other biological fluids of rats. The conjugate showed a typical delayed-release pattern after oral administration to rats, i.e., plasma levels of KP increased after a lag time of about 3 h and reached a maximum concentration at about 7 h. On the other hand, the non-covalent inclusion complex of KP with HP-beta-CyD gave a rapid increase in plasma drug levels, and the KP-EC solid dispersion retarded slightly the increase of plasma levels. The co-administration of the conjugate and the HP-beta-CyD complex gave a typical repeated release profile, i.e., double peaks were observed at about 1-2 and 8-12 h in plasma KP levels. On the other hand, the co-administration of the conjugate and the EC solid dispersion gave a typical sustained-release pattern of KP, i.e., a constant plasma KP level was maintained for at least 24 h. These repeated or long circulating release patterns in plasma KP levels after oral administration were clearly reflected in the anti-inflammatory effect using rats with carageenan-induced acute edema in paw. The results suggest that various release-controlled preparations can be designed by employing CyD conjugates in combination with other carriers with different releasing properties.

Colon-specific delivery of prednisolone-appended alpha-cyclodextrin conjugate: alleviation of systemic side effect after oral administration.

Prednisolone (PD), a typical glucocorticoid, has been widely used for the treatment of inflammatory bowel disease (IBD). However, when PD is administered orally, a large amount of the drug is absorbed from the upper gastrointestinal (GI) tract and causes systemic side effects. In this study, the anti-inflammatory effect and systemic side effect of the PD succinate/alpha-cyclodextrin (PDsuc/alpha-CyD) ester conjugate after oral administration were studied using IBD model rats. The anti-inflammatory effect of the PDsuc/alpha-CyD conjugate was comparable to those of PD alone. On the other hand, the systemic side effect of the PDsuc/alpha-CyD conjugate was much lower than that of PD alone when administered orally. The lower side effect of the conjugate was attributable to passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specifically in the large intestine. The oral administration of PD alone gave higher plasma concentrations of PD, giving the significant systemic side effect. The results suggested that the PDsuc/alpha-CyD conjugate is useful as a delayed-release type prodrug of PD for colon-specific delivery, owing to alleviation of the systemic side effect, while maintaining the therapeutic effect.