Biomedical subjects

Masato Takahashi

Publications and source records attributed to Masato Takahashi.

At least 19 recordsLinked to original sources

PubMed2026

Pembrolizumab plus chemotherapy followed by pembrolizumab in participants in Asia with early triple-negative breast cancer: An updated subgroup analysis of the KEYNOTE-522 randomized clinical trial.

BACKGROUND: In KEYNOTE-522 (NCT03036488), addition of perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR), event-free survival (EFS), and overall survival (OS) in early-stage triple-negative breast cancer (TNBC). pCR and EFS results in participants enrolled in Asia were consistent with those in the overall population. We report OS, updated EFS, and safety outcomes in participants enrolled in Asia. METHODS: Participants with newly diagnosed, high-risk, early-stage TNBC (T1c [N1‒N2] or T2‒T4 [N0‒N2] per AJCC 7th edition) were randomized 2:1 to 8 cycles of neoadjuvant pembrolizumab 200 mg Q3W or placebo plus chemotherapy. After definitive surgery, participants received adjuvant pembrolizumab 200 mg Q3W or placebo for ≤9 cycles. Primary endpoints were pCR (ypT0/Tis ypN0) and EFS. OS was a secondary endpoint. RESULTS: Of 1174 randomized participants, 216 were enrolled in Asia. At data cutoff (March 22, 2024), EFS events occurred in 18/136 participants (13.2%) in the pembrolizumab + chemotherapy group versus 22/80 (27.5%) in the placebo + chemotherapy group (HR, 0.43 [95% CI, 0.23‒0.81]); 60-month EFS rates (95% CIs) were 87.4% (80.6%‒92.0%) and 72.1% (60.7%‒80.6%), respectively. In the respective groups, 12/136 (8.8%) and 16/80 participants (20.0%) died (HR, 0.41 [95% CI, 0.19‒0.86]); 60-month OS rates (95% CIs) were 91.9% (85.8%‒95.4%) and 81.1% (70.5%‒88.1%). Treatment-related AEs led to treatment discontinuation in 19/136 participants (14.0%) with pembrolizumab + chemotherapy and 7/79 (8.9%) with placebo + chemotherapy. CONCLUSIONS: OS and updated EFS outcomes in KEYNOTE-522 participants enrolled in Asia were consistent with those in the overall population and support use of perioperative pembrolizumab + neoadjuvant chemotherapy as a standard-of-care treatment in this setting.

Adjuvant↗

PubMed2006

AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma.

OBJECTIVE: To determine whether detection of hepatocellular carcinoma (HCC) cells by real-time quantitative RT-PCR targeting of alpha-fetoprotein mRNA (AFP mRNA) before or after curative hepatectomy predicts HCC recurrence and patient survival. SUMMARY BACKGROUND DATA: The presence of cancer cells in peripheral blood and/or bone marrow in patients with malignant disease has been reported to correlate with outcome. METHODS: Between July 2000 and June 2005, 136 consecutive HCC patients underwent primary curative hepatectomy. Bone marrow aspirated preoperatively, and peripheral blood samples collected before and after operation were subjected to real-time quantitative RT-PCR analysis using AFP mRNA as a target molecule. Median follow-up was 23 months (range, 6-54 months). Patient survival (PS), disease-free survival (DFS), and clinicopathologic features were compared between patients with positive and negative AFP mRNA. RESULTS: Twenty-four patients died (22 from HCC). HCC recurred in 66 patients (hepatic in 37 [56.1%]; hepatic and remote in 17 [25.8%], and remote alone in 12 [18.2%]). Bone marrow was positive for AFP mRNA in 38 patients (27.9%) and negative in 98 (72.1%). One- and 3-year PS was 96.6% and 91.4%, respectively, with negative AFP mRNA versus 86.2% and 55.5%, respectively, with positive AFP mRNA (P < 0.0001). One- and 3-year DFS were 73.2% and 44.8%, respectively, with negative AFP mRNA versus 54.5% and 25.8%, respectively, with positive AFP mRNA (P = 0.0399). Portal vascular invasion, tumor size, multiple tumors, and tumor differentiation correlated with inferior PS and DFS on univariate analysis. On multivariate analysis, positive AFP mRNA was the most important risk factor for PS (P = 0.001) and DFS (P = 0.0165). In addition, positive AFP mRNA in peripheral blood after operation tended to predict reduced DFS. CONCLUSION: AFP mRNA in the bone marrow and systemic circulation during the perioperative period predicts patient survival and recurrence after curative hepatic resection for HCC.

Biomarkers, Tumor↗

PubMed2006

[Efficacy and toxicity of combination treatment with epirubicin (EPI) plus docetaxel (DOC) in advanced breast cancer].

Thirty women (mean age 50.4 years, range 31-63) with primary advanced breast cancer were given EPI 40-60 mg/m(2) and DOC 50-60 mg/m(2) intravenously every three weeks. The efficacy was evaluated after 4 cycle treatments. There were 5 complete responses (CR) and 14 partial responses (PR), giving an overall response rate of 63.3%. There were 2 pathological CR (8%) which showed complete disappearance of cancer cells. The high dose group showed a better response than the low-dose group. The most common grade 3/4 adverse events were neutropenia (26.7%) and general fatigue (6.7%). The simultaneous combination treatment of EPI and DOC is effective for primary chemotherapy and can be performed safely even for outpatients.

Adult↗

PubMed2005

Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.

BACKGROUND: Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. METHODS AND RESULTS: This work represents the third iteration of an infective endocarditis "treatment" document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. CONCLUSIONS: The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management.

Ambulatory Care↗

PubMed2005

Pathologic characteristics and surgical indications of superacute type A intramural hematoma.

BACKGROUND: The treatment policy for acute intramural hematoma involving the ascending aorta remains controversial. METHODS: This study compared the pathologic characteristics of intramural hematoma with those of acute aortic dissection with a false lumen. The study group comprised 69 patients with intramural hematoma and 156 with acute aortic dissection who underwent emergency operation between 1995 and 2003. RESULTS: Patients were significantly older in the intramural hematoma group than in the dissection group (67.7 +/- 7.2 years compared with 59.8 +/- 11.6 years; p < 0.0001). Pericardial hemorrhage was present in a higher proportion of patients in the intramural hematoma group than in the dissection group (66.7% compared with 50.6%; p = 0.0257). Three patients (4.3%) died in the intramural hematoma group, whereas 26 patients (16.7%) died in the dissection group (p = 0.011). Histopathologic examination showed no difference in the severity of medial changes, but the site of dissection differed. The thickness of the residual media of the adventitia side was 0.21 +/- 0.12 mm in the intramural hematoma group compared with 0.32 +/- 0.22 mm in the acute aortic dissection group. Dissection was significantly nearer the adventitia in the intramural hematoma group (p = 0.0016). CONCLUSIONS: Dissection is nearer the adventitia in intramural hematoma than in dissection, leading to a greater probability of rupture. These results suggest that operation as soon as possible after the onset of intramural hematoma will contribute to improved survival.

Acute Disease↗

PubMed2005

Effect of dielectric properties of solvents on the quality factor for a beyond 900 MHz cryogenic probe model.

A previous report by Kelly et al. [J. Am. Chem. Soc. 124 (2002) 12013] indicated that the ionic conductivity of aqueous solution produces a significant contribution to the sensitivity loss in high-resolution NMR equipped with a cryogenically cooled probe. The loss in a sample solution contains two contributions: one from the ionic conductivity and the other from the dielectric loss; the latter is especially important at high frequencies such as above 900 MHz. Here, we investigated the effect of the dielectric conductivity on the quality factor of a 930 MHz cryogenic probe model; in particular, it deals with the ionic aqueous solutions and organic solvents commonly used for NMR in biological research and the chemistry of natural compounds. The sample quality factor, Qs, at first increases with the real part of the relative dielectric permittivity epsilon' and then saturates. In the case of polar organic solvents, the transverse electric field on the sample decreases with epsilon', resulting in an increase of Qs. In the case of non-polar organic solvents, the dielectric conductivity is so small that the gradient of the increase is steep, resulting in much larger Qs though the epsilon' is small. The effect of the transverse electric field is negligible if the epsilon' becomes large, thus the loss for ionic aqueous solution is mainly governed by a loop current induced in the sample solution. As the induced electromotive force is independent of the epsilon', the Qs is saturated at high values of epsilon'. Based on the Qs obtained with the cryogenic probe model, the sensitivity for the cryogenic probe is expected to be as follows: the loss in sensitivity by loading water is more than 66%, i.e., the effect of the dielectric conductivity of water is remarkable at high frequencies; polar organic solvent suffers much larger losses, which is due to the enhancement of the effective sample resistance by the effect of epsilon'; a non-polar organic solvent is nearly free of the sensitivity loss as the dielectric conductivity is negligible; the reverse micelle behaves similarly.

Computer Simulation↗

PubMed2005

Side-to-side linking of myocardial cells in hypertrophic cardiomyopathy: whole heart microscopic observation with tangential sections.

By cross-section or longitudinal section, it is difficult to investigate longitudinal features of myocardial cells in the whole heart. Here, introducing the use of tangential sections to obtain longitudinal aspect of myocardial cells in any part of myocardium, the authors evaluated myocardium in the left ventricle in 10 normal hearts and four hearts with hypertrophic cardiomyopathy (HCM). Tangential sections were obtained by peeling the superficial layer of myocardium. After peeling the whole surface, secondary deep layer was peeled. These procedures were repeated more than five times through the wall. Intercalated discs (ICD) were observed immunohistochemically with anti-N-cadherin and antidesmoplakin. In normal hearts, myocardial cells were cut longitudinally and ran parallel in tangential sections. They linked end-to-end with simple and regular ICD with average lengths of 120-130 microm and average sarcomere numbers of 56-65. In HCM hearts, many myocardial cells were cut almost longitudinally running approximately parallel in tangential sections. Myocardial cells frequently showed side-to-side linking characterized by skewed ICD, indistinct ICD counterparts, and longitudinally arranged ICD. Two young HCM hearts had circle-shaped ICD and vacuole-like structures highlighted by immunostaining for N-cadherin, which were actually extracellular structures comparable with irregular side-to-side linking. It is considered that side-to-side linking of myocardial cells is a characteristic microscopic feature in HCM rather than myocardial disarray.

Adolescent↗

PubMed2005

Clinical study on eruption of permanent canines after secondary alveolar bone grafting.

OBJECTIVE: Eruption of cleft-associated permanent canines was studied in 190 patients with unilateral cleft lip/palate and whose permanent canines had not erupted at the time of alveolar bone grafting. In 162 of these patients, width of bone defect was compared between patients who underwent surgical exposure of canines and those whose canines erupted naturally. RESULTS: Cleft-associated canines naturally erupted after bone grafting in 150 patients (78.9%) and required surgical exposure in 36 patients (18.9%). Cleft-associated canines had not yet erupted in two patients. Two patients were lost to follow-up. Nasal-side bone defects were significantly wider in patients who underwent surgical exposure of cleft-associated permanent canines than in those whose cleft-associated permanent canines erupted naturally. CONCLUSIONS: The present results suggest that nasal-side cleft width is related to the need for surgical exposure of permanent canines in children with cleft lip/palate.

Adolescent↗

PubMed2005

Normalization of high-flow or removal of flow cannot stop high-flow induced endothelial proliferation.

Endothelial cells (ECs) are activated in response to high-flow. Our previous studies using arteriovenous fistula (AVF) model have demonstrated that high-flow in blood vessels induces an early and rapid proliferation of ECs before arterial dilatation. Here, we investigated the proliferation of ECs, which had once been stimulated by high-flow loading, in a situation without the influence of high-flow. First, we induced high-flow in the rabbit common carotid artery by using AVF. Then, we removed the influence of high-flow by normalization of high-flow with the closure of AVF or by removal of flow itself with tissue isolation and organ culture or with cell culture of ECs, at the timing considered that ECs began to proliferate. Kinetics of ECs was investigated by a laser scanning confocal microscopy, phase-contrast microscopy and light microscopy using bromodeoxyuridine labeling method. We found that ECs, which had once been stimulated by high-flow, transiently proliferated even after normalization of high-flow or removal of flow. We assume that proliferation of ECs is promised when these cells start to proliferate after high-flow loading.

Animals↗

PubMed2005

The impact of bilateral breast cancer on the prognosis of breast cancer: a comparative study with unilateral breast cancer.

BACKGROUND: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We assessed the impact of synchronous and metachronous bilateral breast cancer on the prognosis compared with unilateral breast cancer. METHODS: Between January 1, 1960 and December 31, 2001, 1,214 women were treated for primary operable breast cancers. Thirteen (1.1%) had synchronous bilateral breast cancer; 33 (2.7%) had a metachronous contralateral breast cancer. We compared age at operation, menopausal status, clinical stage, tumor size and histology, lymph node status, hormone receptor status, and use of adjuvant chemotherapy or hormone therapy, and we analyzed the impact of these factors on recurrence and survival in the 46 patients with bilateral breast cancer and the 1,168 patients with unilateral breast cancer. RESULTS: The 5-and 10-year disease-free survival rates, respectively, were 65% and 65% in metachronous cases, 85.7% and 64.3% in synchronous cases, and 77.9% and 72.1% in unilateral cases. There was no significant difference in overall survival among the three groups. On multivariate analysis, metachronous bilaterality, tumor size, lymph node status and adjuvant hormone therapy were each independent risk factors for recurrence, whereas bilaterality of breast cancer did not influence overall survival. CONCLUSIONS: Our data suggest that metachronous bilateral breast cancer is associated with shorter disease-free survival than synchronous bilateral or unilateral breast cancer, although overall survival does not differ among the 3 groups. Patients with metachronous bilateral breast cancer should be followed particularly closely in order to detect recurrence early and maximize quality of life.

Adult↗

PubMed2005

Involvement of NF-kappaB and mitochondrial pathways in docetaxel-induced apoptosis of human oral squamous cell carcinoma.

Apoptosis induced by docetaxel that interferes with microtubule polymerization dynamics and is used clinically to treat advanced cancers, has not been fully defined in squamous cell carcinoma. In this study, apoptotic events involved in docetaxel treatment were investigated. When the human oral squamous cell carcinoma cell line HSC-3 was exposed to docetaxel for 72 h, a dose-dependent effect was observed in apoptosis using the TUNEL method. We observed activation of caspase cascade including activities like caspase-3, -8, and -9. And the pan-caspase inhibitor z-VAD-fmk prevented apoptosis induced by docetaxel (0.1 microM), showing participation of caspases in this process. Since an antagonistic CD95-antibody (ZB4) exerted no effect on docetaxel-induced apoptosis, CD95/CD95L interaction was not involved in this pathway. The caspase-8-like activity was inhibited not only by IETD-fmk (caspase-8) but also by DEVD-fmk (caspase-3). The results indicate that the caspase-8-like activation occurred downstream of DEVDase. Docetaxel promoted the formation of reactive oxygen species (ROS) in mitochondria, and preincubation of cells with anti-oxidants such as N-acetyl cysteine and pyrrolidine dithiocarbamate, protected against apoptosis mediated by docetaxel. Furthermore, treatment with docetaxel elicited reduction of mitochondrial membrane potential, and release of cytochrome c to cytosol, after 48 h of treatment. We observed binding activity to NF-kappaB consensus site and interference with the mitochondrial function via NF-kappaB after docetaxel treatment. Preventing pro-apoptotic property of NF-kappaB inhibited docetaxel-induced apoptosis. Thus, these results suggest that, following the activation of NF-kappaB by docetaxel, apoptosis is elicited through a mitochondria-dependent pathway.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds.

Selenium (Se) is a very effective anti-cancer agent. We studied the effects of inorganic Se compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Se for 72 h, in the form of SeO2 and Na2SeO3, but not Na2SeO4, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 microM SeO2 resulted in the caspase-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (DeltaPsim), but did not induce the generation of reactive oxygen species. Treatment with SeO2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Se. Treatment with N-acetyl-L-cysteine, or exogenous GSH, prevented the SeO2-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of DeltaPsim caused by SeO2, while buthionine sulfoximine augmented the SeO2- or Na2SeO3-induced apoptosis. These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspase-9-mediated apoptosis without a concurrent increase in ROS.

Apoptosis↗

PubMed2004

Synthesis and structure-activity relationships of potent 3- or 4-substituted-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors.

Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. A series of 2-cyanopyrrolidines are among the most potent of DPP-IV inhibitors. We focused our attention on substitutions at the 3- or 4-position of 2-cyanopyrrolidines and synthesized and evaluated various derivatives. Among them, the 4-fluoro derivative was found to exhibit better DPP-IV inhibitory activity and higher plasma drug concentrations after oral administration to rats than the 4-unsubstituted derivative. We report here on the synthesis and biological data of the aforementioned derivatives.

Adenosine Deaminase Inhibitors↗

PubMed2004

Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association.

BACKGROUND: Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately 15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. METHODS AND RESULTS: A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for > or =5 days and < or =4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-alpha antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. CONCLUSIONS: Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.

Algorithms↗

PubMed2004

Magnetic resonance imaging for preoperative evaluation of breast cancer: a comparative study with mammography and ultrasonography.

BACKGROUND: The widespread use of mammographic screening has led to increased detection of small tumors that are often difficult to diagnose with conventional imaging modalities such as mammography and ultrasonography. Intraductal spread of breast cancer, a principle risk factor for local recurrence, is also difficult to diagnose with mammography and ultrasonography. We investigated the clinical usefulness of magnetic resonance imaging of the breast in the therapy of breast cancer and we compared it with mammography and ultrasonography. STUDY DESIGN: A total of 183 patients with primary breast cancer underwent surgery at our institute between September 1, 1999, and November 30, 2002. They were examined preoperatively with magnetic resonance imaging, mammography, and ultrasonography. Magnetic resonance imaging evaluation included contrast-enhanced dynamic studies using IV injection of gadolinium-diethylenetriamine pentaacetic acid. RESULTS: Detection rates of breast cancers by magnetic resonance imaging, mammography, and ultrasonography were 93.7%, 84.6%, and 97.3%, respectively (magnetic resonance imaging versus mammography, p < 0.05). Patterns of time-intensity curves in dynamic magnetic resonance imaging differed with histologic types. Sensitivity, specificity, and accuracy of detection of intraductal spread were 66.7%, 64.2%, and 65.6% with MRI; 22.2%, 85.7%, and 50% with mammography; and 20.6%, 85.2%, and 50% with ultrasonography, respectively (sensitivity, specificity, and accuracy; p < 0.05, respectively). CONCLUSIONS: Magnetic resonance imaging can diagnose breast cancer as accurately as ultrasonography and more accurately than mammography. Patterns of time-intensity curves correlated with tumor histology. In addition, magnetic resonance imaging can detect intraductal spread more accurately than the other two methods. Magnetic resonance imaging appears to be indispensable in breast-conserving surgery to minimize local recurrence.

Adult↗

PubMed2004

Endocrinological and pathological effects of anabolic-androgenic steroid in male rats.

Many athletes use drugs, especially anabolic androgenic steroids (AAS), but there are few reports on the endocrinological and pathological changes in AAS abusers. In this study we reported the results of endocrinological examinations in rats administered AAS and also physical changes. We separated 37 male Wistar rats (7 weeks old) into 3 groups: Group A was medicated with nandrolone decanoate, metenolone acetate, and dromostanolone; Group B with nandrolone decanoate and saline; and Group C was given only saline. They were given subcutaneous injections of the medications or the control vehicle once a week for 6 weeks. Medications were stopped for 4 weeks, and then resumed for another 6 weeks. After that, rats were sacrificed. Serum testosterone level in Group A was significantly higher than that in Group C. Serum dihydrotestosterone in Group A was significantly higher than that in both Groups B and C. Serum estradiol-17beta levels in Groups A and B were significantly higher than that in Group C. In pathological evaluation, heart, testis, and adrenal gland were severely damaged. These findings indicate that there is a high degree of risk related to the use of AAS.

Adrenal Glands↗

PubMed2004

Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association.

BACKGROUND: Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately 15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. METHODS AND RESULTS: A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for > or =5 days and < or =4 classic criteria should undergo echocardiography [correction], receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-alpha antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. CONCLUSIONS: Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.

Algorithms↗

PubMed2004

Decreased expression of the candidate tumor suppressor gene ING1 is associated with poor prognosis in advanced neuroblastomas.

ING1 has been identified as a novel candidate tumor suppressor gene using a genetic suppressor element (GSE) strategy. Ectopic expression of ING1 in mammalian cultured cells causes cell cycle arrest and apoptosis through a p53-dependent and/or p53-independent pathway. However, there has been no report on the prognostic significance of the ING1 expression level in human cancers, though the expression of the wild-type ING1 gene is significantly decreased in breast, lymphoid and gastric cancers as compared with their corresponding normal tissues. In order to explore the possible involvement of ING1 in tumorigenesis of neuroblastoma, we examined the expression levels of ING1 mRNA in 32 primary neuroblastomas by using a quantitative real-time PCR. ING1 mRNA was expressed independently of the disease stages. however, low levels of ING1 mRNA were significantly associated with a poor prognosis (log-rank test, p=0.017). Multivariate analysis showed that the expression level of ING1 was closely related to survival (p=0.020), even after controlling with age (p=0.008) or stage (p=0.025), while it was only marginally significant after controlling with TrkA expression (p=0.063). Mutation analysis revealed that there was no mutation or deletion of the ING1 gene except 1 silent mutation at codon 188 in primary neuroblastomas examined. Taken together, our results suggest for the first time that a decreased level of ING1 expression is a novel indicator of poor prognosis in advanced stages of neuroblastoma, and that ING1 may play a crucial role in genesis and progression of neuroblastoma.

Blotting, Northern↗