Red Cross Medical Center Research Articles

Factors associated with acute otitis media in children due to penicillin intermediately resistant Streptococcus pneumoniae

Objectives This study was conducted to analyze the association between recent antimicrobial use and acute otitis media (AOM) due to Streptococcus pneumoniae intermediately resistant to penicillin (PISP). The influence of drug resistance on the clinical course of AOM was also assessed. Methods A retrospective cohort study was conducted in infants at Japanese Red Cross Medical Center, Tokyo. Children included in the study were under 24 months of age and diagnosed with AOM due to infection with S. pneumoniae between April 2002 and March 2007. Crude risk ratios (cRR) of PISP infection in cases with recent antibiotic use and other factors were obtained. The Mantel–Haenszel estimate was applied for the adjustment of cRR. Results Of 35 children, 13 had AOM due to penicillin-susceptible S. pneumoniae (PSSP) and 22 had AOM due to PISP. The adjusted risk ratio (aRR) of penicillin antibiotic use within 1 month was 1.99 (95% confidence interval (CI): 1.36–2.92), and the aRR of penicillin antibiotic use within 1 week was 1.93 (95% CI: 1.33–2.67). Recent use of penicillin antibiotics was an associated factor for AOM due to PISP. The clinical course was not clearly different between cases infected with PSSP and those with PISP. Conclusion Recent use of penicillin antibiotics might be a selective pressure for PISP.

Evaluation of the risk factors for febrile neutropenia associated with hematological malignancy

Febrile neutropenia (FN) can frequently become a very serious problem. In 2002, Klastersky and colleagues established the Multinational Association for Supportive Care in Cancer (MASCC) score, which consisted of risk factors for conditions that included solid tumors. However, hematopoietic tumors, in comparison to solid tumors, are plagued by such problems as the quantity and quality of abnormalities associated with leukocytes and neutrophils and the requirement for higher dosages of both radio- and chemotherapy. FN is a complication associated with hematological malignancies that can lead to a fatal outcome, but it is avoidable if the appropriate preventive treatment is performed at an early stage. The subjects of the present study consisted of 354 patients with hematopoietic malignancies who were treated at the Japanese Red Cross Medical Center Hospital, Tokyo, between August 2000 and September 2004. They were retrospectively evaluated for the risk factors of FN by applying Wilcoxon's rank sum test. A scoring index was defined and the patients were classified into high- and low-risk groups before evaluation. The following nine risk factors, which may significantly influence the relationship between the time required for defervescence and the duration of neutropenia - age; hematological diseases; the leukocyte count during the febrile period; the reduction in leukocyte count per day before the onset of FN; the prophylactic administration of antimycotic agents; sterilization of the intestinal tract; and urine albumin content, creatine level, and C-reactive protein (CRP) level - were expressed in points and their sum was termed risk points. The range of risk points was classified as 0-3 and 4-9. The time required for defervescence was 5.1 days when the risk points were in the range of 0-3 and 8.1 days when the points were in the range of 4-9. These figures were distributed normally and there was a significant difference between the two groups (P = 0.0016). FN associated with hematological malignancies is somewhat different from that related to other malignancies; it is therefore associated with unique risk factors. Most of the risk factors used in the present study can be evaluated objectively. At the onset of FN, they were expressed in points for evaluation. Further prospective studies are needed to determine whether these risk factors are suitable for use in actual cases.

Transplantation-Related Thrombotic Microangiopathy Triggered by Preemptive Therapy for Hepatitis C Virus Infection

Various strategies exist to reduce graft loss after organ transplantation, including the use of immunosuppressants, steroids, and postoperative antivirotic agents. Combined treatment with an immunosuppressant and a corticosteroid after liver transplantation is the standard protocol to improve graft survival. However, immunosuppressants can have numerous side effects including neurological complications, and steroids can have positive effects on hepatitis C virus (HCV) reinfection (1). Transplantation-related thrombotic microangiopathy (TA-TMA) is a serious complication of organ transplantation that is associated with a variety of transplantation-related factors, including the use of immunosuppressive agents, conditioning regimens, ABO incompatibility, and opportunistic infections (2–4). Immunosuppressants such as cyclosporine A and tacrolimus (FK506) are often linked with the occurrence of TA-TMA (2, 3). Transplantation-related thrombotic microangiopathy typically presents with sudden onset thrombosis and acute organ dysfunction without clinical manifestations. We report on a rapidly progressing case of TA-TMA in a 43-year-old woman with HCV-related cirrhosis, which was strongly associated with the use of an immunosuppressant and anti-HCV preemptive therapy. The patient underwent living- donor liver transplantation because of HCV-related cirrhosis. The patient had a history of three subacute graft rejections, and underwent steroid recycle therapy (1) followed by liver biopsy. She experienced a temporary rise in FK506 level (to >18.0 ng/mL) during the steroid recycle therapy, so the dose was adjusted. She was readmitted 40 days after surgery for additional preemptive therapy for HCV. The treatment regimen comprised 80 ng pegylated interferon (INF)-α2b weekly and 800 mg ribavirin daily. Sudden onset of TA-TMA developed after the start of the therapy. Her blood chemistry measurements abruptly shifted into the abnormal range: her platelet count dropped from 36.5 to 7.8×104 mm3, her serum lactate dehydrogenase level increased from 258 to 688 IU/mL, and her peripheral blood contained more than 1.5% schistocytes. Each parameter reflected the treatment state of TA-TMA. Magnetic-resonance imaging of the brain revealed a hyperintense signal of the left temporal lobe on T2-weighted images, indicating cerebral infarction with hemorrhage, which persisted for 3 weeks. Angiography showed narrowing and irregularity of the middle cerebral artery bilaterally, and a “string of beads” pattern was observed in the posterior cerebral artery bilaterally. A biopsy specimen from the temporal artery failed to show systemic arteritis, and there was no evidence of infection. These findings suggested an FK506-mediated toxic effect of the preemptive therapeutic agent on the cerebral vessels (Fig. 1).FIGURE 1.: The MRI T2-weighted sequence shows hyperintense regions (arrowheads) in the left lateral area at the initial presentation of headache (A). The areas increased bilaterally within 3 weeks (B). The “string of beads” pattern changes resulting from narrowing and irregularity of the cerebral artery were observed bilaterally in angiography (C).A combination of INF-α2b and ribavirin preemptive antiviral therapy is becoming the standard protocol for HCV-related liver transplantation, and might provide long-term benefits in graft survival and delaying the time to HCV recurrence (5, 6). However, INF itself has a number of side effects. It enhances cellular immunity and can lead to the production of autoantibodies, even antiendothelial antibodies. There is a close correlation between the FK506 level and clinical complications related to endothelial cell injury. Thus, the preemptive therapy may have a trigger role in the occurrence of TA-TMA in present case. The ribavirin and steroid therapy was immediately discontinued, and FK506 was replaced with cyclosporine A. Intravenous heparinization (10,000 units/day), prostaglandin E1 (prostandin, 500 μg/day), and the free-radical scavenger (edaravone, 60 mg/day) were continuously administered. Although the disease followed a radical and a repetitive clinical course, the patient recovered as a result of the aggressive early intervention; she made a full recovery with the presence of mild logaphasia and left hemiplasia within 4 weeks. This case highlights the fact that HCV preemptive therapy after steroid-recycle therapy with an immunosuppressant should be performed with caution. Hepatitis C virus-related living-donor liver transplantation is a strong indicator of TA-TMA, and 9 of 26 patients in recent reports had HCV infection (2, 4). We recommend that patients who are receiving preemptive therapy for HCV after high-immunosuppressant trough levels should be closely monitored for the development of TA-TMA, to ensure early diagnosis. Earlier detection and intervention will provide opportunities to improve patient outcomes. Shintaro Yamazaki Tadatoshi Takayama Kazuto Inoue Tokio Higaki Department of Digestive Surgery Nihon University School of Medicine Tokyo, Japan Masatoshi Makuuchi Japanese Red Cross Medical Center Tokyo, Japan

Swimming in cloudy waters: Efforts to prevent HCV-related HCC

Swimming in cloudy waters: Efforts to prevent HCV-related HCC

Ruptured abdominal aortic aneurysm with Marfan's syndrome variant, a case from the family with high incidence of aortic aneurysm

M. Futami, D. Sawaki, G. Sekita, N. Kobayakawa, K. Fukushima, H. Takeuchi, K. Uehara, H. Kaneko, K. Yagyu, T. Takemura, T. Aoyagi* Department of Cardiovascular Medicine, Japanese Red Cross Medical Center, 4-1-22 Hiro-o, Shibuya, Tokyo, 150-8935, Japan Department of Cardiovascular Surgery, Japanese Red Cross Medical Center, 4-1-22 Hiro-o, Shibuya, Tokyo, 150-8935, Japan Department of Pathology, Japanese Red Cross Medical Center. 4-1-22 Hiro-o, Shibuya, Tokyo, 150-8935, Japan

Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis.

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.

Four newly identified ornithine transcarbamylase (OTC) mutations (D126G, R129H, I172M and W332X) in Japanese male patients with early-onset OTC deficiency.

Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto 860 (T. M., R. H., K. K., S . K., F. E., 1. M. ); Clinical Laboratory of Kumamoto City Medical Association, Kurnamoro 860 (E. K. ) ; Department of Pediatrics, Sapporo Medical College, Sapporo 060 (K. 0.); Department of Pediatrics, Toyohashi Municipal Hospital, Toyohhi 440 (Y. S.) ; Department of Obstetrics and Gynecology, Japanese Red Cross Nagoya First Hospitd, Nagoya 467 (K. I. ); Department of Pediatrics, lapan Red Cross Medical Center, Tokyo 1.50 ( H . Y . ) ; Department of Pediatrics, Medical School, Nagoya City University, Nagoya 467 (I. K.); Diagnostic Science Department Shionogi and Co., Ltd., Osaka 566 (S.K.); Human Genome Center, The institute of

Kawasaki Disease With Particular Emphasis on Arterial Lesions

Kawasaki disease (KD, or acute febrile mucocutaneous lymph node syndrome (MCLS)) was first described as a clinical entity in 1967 by Dr. Tomisaku Kawasaki of the Japan Red Cross Medical Center. Originally, it was thought to have a favorable prognosis, but as epidemiological surveys, augmented by pathological studies, have shown, it has come to be recognized as an often fatal disorder. In this report, the clinical symptoms, historical background, present status of research and epidemiological problems of KD are first described, and then we present a pathological and morphological outline of KD, focusing on pathological changes in the blood vessels, and the relationships of these changes to 1) the morphogenesis of arteritis, 2) the mechanism of coronary artery aneurysm formation and its sequelae, and 3) juvenile arteriosclerosis.

Division of Cardiovascular Surgery, Japanese Red Cross Medical Center

Division of Cardiovascular Surgery, Japanese Red Cross Medical Center

Hearing screening for neonates by Crib-O-Gram

The Crib-O-Gram neonatal hearing screening audiometer, invented by Prof. F. Blair Simmons, M. D., was used from February 1980 to March 1983 to screen 1, 510 newborns in the department of neonate and premature medicine, Japanese Red Cross Medical Center. Prior to implementing the Crib-O-Gram screening tests, babies were classified into high risk and low risk infants, based on our established risk factors. At the age of 6 to 10 months, all the cases of Crib-O-Gram screened infants were followed up by a questionnaire. For all cases which showed abmoralities in the questionnaire, screenings using ABR and BOA were then conducted at 10 to 12 months. These tests showed 6 infants with hearing impairments. All happened to be high risk infants, and all but one were referred after undergoing tests on the Crib-O-Gram. It follows that among the 203 infants screened by the Crib-O-Gram and referred to more testing, 5 had hearing impairments - an incidence of 1:50. We thus conclued that Crib-O-Gram screenings should be implemented for infants who weight at least 2200g and who are at least 38 weeks of gestational age. We also found that the Crib-O-Gram can detect neurological problems.

The inscrutable Kawasaki disease

Although medical investigators continue to study mucocutaneous lymph node (Kawasaki) disease from virtually every viewpoint, the cause and pathogenesis of this acute, sometimes fatal, febrile illness remain elusive. The disorder, now considered a syndrome, usually affects children younger than 5 years, although some cases now are being reported among adults (see page 1604, this issue). The death rate variously is reported to be between 0.5% and 2.8% or higher, and cardiovascular complications are not infrequent. Since Tomisaku Kawasaki, MD, Tokyo Red Cross Medical Center, reported the first cases in 1967, more than 20,000 cases have been reported in Japan. The disorder began to be recognized in the United States in 1974, and more than 650 cases have been recorded in this country since then. In fact, a cluster of 57 cases (mean age of the patients, 2.9 years), the largest so far in the United States, just occurred in Massachusetts.

Acute febrile mucocutaneous lymph node syndrome.

More than a decade ago, Tomisaku Kawasaki, a Japanese pediatrician, described an acute exanthematous disease characterized by persistent fever, mucous membrane hyperemia, cervical lymph node enlargement, and periungal desquamation in 50 infants and children who had been seen during the preceding six-year period at the Japan Red Cross Medical Center in Tokyo. 1 Individually the clinical and laboratory features seemed not unlike those of other mucocutaneous syndromes and exanthematous illnesses of childhood, but Kawasaki decided that the constellation of findings was distinctive and constituted a hitherto undescribed clinical entity. The disease was designated mucocutaneous lymph node syndrome (MCLS). 1 After this description, numerous cases were reported throughout Japan, and in 1970 the Research Committee of MCLS, supported by the Ministry of Health and Welfare of the Japanese government, was organized. The primary purpose of this group was to conduct and to coordinate investigations involving the etiology and the clinical, pathological,

The Present Status of Sex Councelling at Red Cross Medical Center(Sexual disorders and paychosomatic medicine)

The Present Status of Sex Councelling at Red Cross Medical Center(Sexual disorders and paychosomatic medicine)