Search PubMed⌕ Search

Biomedical subjects

H Kato

Publications and source records attributed to H Kato.

At least 73 records · Page 4Linked to original sources
PubMed2003

FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma.

Focal adhesion kinase (p125(FAK); 'FAK') is a tyrosine kinase that is localised to cellular focal adhesions and is associated with a number of other proteins, such as integrin adhesion receptors. We performed an immunohistochemical analysis of FAK protein expression to determine the relationship between FAK overexpression and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 91 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Seven human ESCC cell lines-TE-1, TE-2, TE-8, TE-13, TE-15, TT, and TTn-and one immortalized human keratinocyte cell line-HaCaT-were used in Western blot analysis. Immunostaining of FAK was seen in the cytoplasm of cancer cells, particularly in cells located in the invasive fronts of cancer nests. FAK overexpression was detected in 54 of the 91 patients (59.3%). Significant correlations were observed between FAK overexpression and cell differentiation (P=0.0057), depth of tumour invasion (P=0.0023), presence of regional lymph node metastasis (P=0.0097), number of lymph node metastases (P=0.0026), and disease stage (P=0.012). The survival rates of patients with FAK-overexpressing cancer were significantly lower than those of patients without FAK-overexpression cancer (P=0.006). The 5-year survival rate of patients without FAK overexpression was 69%, whereas that of patients with FAK overexpression was 38%. On Western blot analysis, FAK was expressed at a high level in TE-1, TE-8, TE-15, and TT cells, at a moderate level in TE-2 and TTn cells, and at a low level in TE13 and HaCaT cells. FAK phosphorylation at tyrosine 397 was demonstrated in proportion to the intensity of FAK in all cell lines except TE15 and HaCaT. In conclusion, FAK overexpression of ESCC was related to cell differentiation, tumour invasiveness, and lymph node metastasis. Consequently, patients with ESCC who had FAK overexpression had a poor prognosis.

Aged↗
PubMed2003

Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma.

Axin is a negative regulator of the Wnt signalling pathway, and genetic alterations of AXIN1 have been suggested to be an important factor of carcinogenesis in some tumours. The objective of this study was to clarify the clinicopathologic and prognostic significance of Axin in oesophageal squamous cell carcinoma (SCC). Immunohistochemical staining for Axin was performed on surgical specimens obtained from 81 patients with oesophageal SCC. Western and Northern blottings were performed on proteins and RNA from oesophageal SCC cell lines. Then polymerase chain reaction-single-strand conformational analysis (PCR-SSCP) was performed on DNA from oesophageal SCC patients and cell lines. Axin expression was found to be correlated inversely with depth of invasion, lymph node metastasis, and lymphatic invasion. Although univariate analysis showed Axin to be a negative predictor, multivariate analysis showed that it was not an independent prognostic marker. In all but one of the seven cell lines examined, the levels of protein expression were equivalent to RNA expression. PCR-SSCP showed that five patients and three cell lines had polymorphisms in exon 4 or 5 of the AXIN1 gene, but none of the 81 patients with oesophageal SCC had mutations. Our findings suggest that reduced expression of Axin is correlated with tumour progression of oesophageal SCC. However, additional studies will be necessary to elucidate the mechanism responsible for loss of Axin expression in tumour cells.

Axin Protein↗
PubMed2003

Severe aplastic anemia associated with thymic carcinoma and partial recovery of hematopoiesis after thymectomy.

Aplastic anemia has been a rare complication of thymic tumors documented in only a few cases. We now report that a previously healthy, 72-year-old woman had a well-differentiated squamous cell thymic carcinoma and severe aplastic anemia, as detected on a simultaneous basis. After extirpation of the thymic carcinoma, hematological recovery was achieved. While cyclosporine (CyA), prednisolone (PSL), and methenolone improved hematological data even more, a partial and stable remission has been sustained for 22 months. The patient's serum prior to the surgery had a suppressive effect on the formation of colonies of erythroid and nonerythroid colonies, as determined using the patient's bone marrow cells and compared with the patient's serum after the surgery and normal AB serum. This case report concerns a patient in whom we observed simultaneous occurrence of a thymic tumor and a sever marrow aplasia for which we describe our therapeutic approach.

Aged↗
PubMed2003

Prenatal diagnosis of sustained bradycardia with 1 : 1 atrioventricular conduction.

OBJECTIVES: The aims of this study were to elucidate the clinical course of fetal bradycardia with 1 : 1 atrioventricular conduction, and to discuss the optimal management of affected fetuses in the second and third trimesters of pregnancy. METHODS: The hospital records of five fetuses with the diagnosis of bradycardia (100 bpm) with 1 : 1 atrioventricular conduction between 1981 and 2000 in our institution were reviewed. Atrioventricular conduction was evaluated by simultaneous M-mode echocardiographic tracing of the atria and the ventricles. RESULTS: The gestational ages at referral ranged from 19 to 36 (median, 25) weeks, and fetal heart rates ranged from 60 to 80 (median, 80) bpm. Postnatal electrocardiography revealed sinus bradycardia in four (two of which were siblings) of the five cases, and junctional rhythm in the remaining case. Two fetuses with congenital heart defects (CHDs) were delivered by Cesarean section but died postnatally. The three fetuses without CHDs were delivered vaginally and have survived to date for 6, 8 and 15 years. CONCLUSIONS: Fetal bradycardia with 1 : 1 atrioventricular conduction caused by sustained sinus bradycardia or wandering pacemaker is an important type of fetal arrhythmia. Further investigations with a larger number of cases are required to determine the risk factors for predicting the outcome of affected fetuses.

Bradycardia↗
PubMed2003

Long-term potentiation and long-term depression in hippocampal CA1 neurons of mice lacking the IP(3) type 1 receptor.

To investigate the role in synaptic plasticity of Ca(2+) released from intracellular Ca(2+) stores, mice lacking the inositol 1,4,5-trisphosphate type 1 receptor were developed and the physiological properties, long-term potentiation, and long-term depression of their hippocampal CA1 neurons were examined. There were no significant differences in basic synaptic functions, such as membrane properties and the input/output relationship, between homozygote mutant and wild-type mice. Enhanced paired-pulse facilitation at interpulse intervals of less than 60 ms and enhanced post-tetanic potentiation were observed in the mutant mice, suggesting that the presynaptic mechanism was altered by the absence of the inositol 1,4,5-trisphosphate type 1 receptor. Long-term potentiation in the field-excitatory postsynaptic potentials induced by tetanus (100 Hz, 1 s) and the excitatory postsynaptic currents induced by paired stimulation in hippocampal CA1 pyramidal neurons under whole-cell clamp conditions were significantly greater in mutant mice than in wild-type mice. Homosynaptic long-term depression of CA1 synaptic responses induced by low-frequency stimulation (1 Hz, 500 pulses) was not significantly different, but heterosynaptic depression of the non-associated pathway induced by tetanus was blocked in the mutant mice. Both long-term potentiation and long-term depression in mutant mice were completely dependent on N-methyl-D-aspartate receptor activity. To rule out the possibility of an effect compensating for the lack of the inositol 1,4,5-trisphosphate type 1 receptor occurring during development, an anti-inositol 1,4,5-trisphosphate type 1 receptor monoclonal antibody that blocks receptor function was diffused into the wild-type cell through a patch pipette, and the effect of acute block of inositol 1,4,5-trisphosphate type 1 receptor on long-term potentiation was examined. Significant enhancement of long-term potentiation was observed compared with after control immunoglobulin G injection, suggesting that developmental redundancy was not responsible for the increase in long-term potentiation amplitude observed in the mutant mouse. The properties of channels that could be involved in long-term potentiation induction were examined using whole-cell recording. N-methyl-D-aspartate currents were significantly larger in mutant mice than in wild-type mice only between holding potentials of -60 and -80 mV. We conclude that inositol 1,4,5-trisphosphate type 1 receptor activity is not essential for the induction of synaptic plasticity in hippocampal CA1 neurons, but appears to negatively regulate long-term potentiation induction by mild modulation of channel activities.

Action Potentials↗
PubMed2003

Successful second allogeneic peripheral blood stem cell transplantation and donor lymphocyte infusion in patients with relapsed acute leukemia using the same donors as for the initial allogeneic bone marrow transplantation.

We report the successful treatment of two acute lympho- blastic leukemia (ALL) patients who relapsed following allogeneic bone marrow transplantation (allo-BMT) with allogeneic peripheral blood sem cell transplantation(allo-PBSCT) and donor lymphocyte infusion (DLI) from the same HLA-identical related donors as those used for the first allo-BMT. The patients relapsed on days 154 and 351 from the initial allo-BMT, respectively. Since conventional reinduction chemotherapy failed, allo-PBSCT was undertaken while the patients were still myelosuppressed immediately after reinduction chemotherapy. To induce and/or enhance GVL effects following allo-PBSCT, we performed rapid tapering of CsA and added DLI. After allo-PBSCT and DLI, the patients maintained their complete remission at 55 and 48 months post allo-PBSCT, respectively. From these findings, allo-PBSCT and DLI may be a useful treatment strategy for acute leukemia relapsing after allo-BMT.

Adult↗
PubMed2003

The role of capsaicin-sensitive afferents in autonomic dysreflexia in patients with spinal cord injury.

OBJECTIVES: To determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODS: Seven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyper-reflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant monitoring of BP and heart rate was repeated 1 week, 1, 3, 6, 12 and 24 months after instillation. In two patients the instillations were repeated 5 and 12 months after the first because of recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH2O detrusor pressure (Cdp40) and a systolic BP of> 140 mmHg or diastolic BP of> 90 mmHg (C(HT)). RESULTS: There was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5-10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6-30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3-4 h); the effects lasted for >or= 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean Cdp40 and C(HT) increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6-12 months. CONCLUSION: These results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin- sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect.

Administration, Intravesical↗
PubMed2003

Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16.

Transcription factors of the FoxO family in mammals are orthologues of the Caenorhabditis elegans forkhead factor DAF-16, which has been characterized as a target of insulin-like signalling. Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. A number of in vitro studies have revealed that FoxOs are regulated through phosphorylation in response to insulin and related growth factors, resulting in their nuclear exclusion and inactivation. To clarify the mechanisms involved in the regulation of these factors in vivo, we investigated in the present study whether or not, and if so how, their mRNA levels in rat liver respond to the stimuli of several nutritional and hormonal factors. Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. Of the three FoxO genes, FoxO4 only showed altered levels of mRNA (a 1.5-fold increase) in response to a protein-free diet. Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). These results show that the FoxO genes respond differently to nutritional and hormonal factors, suggesting a new mechanism for the regulation of FoxO-dependent gene expression by these factors. Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo.

Animals↗
PubMed2002

Expression disparity of brain-derived neurotrophic factor immunoreactivity and mRNA in ischemic hippocampal neurons.

We studied the spatial and temporal expression of BDNF immunoreactivity and mRNA in the hippocampal formation after transient forebrain ischemia in gerbils. Our study demonstrated that in the vulnerable CA1 neurons, there was a prolonged expression disparity between BDNF immunoreactivity and mRNA and the BDNF level was reduced, in contrast to the ischemia-resistant dentate gyrus neurons that showed transient expression disparity and maintained the BDNF level. This expression disparity of the neurotrophic factor may be related to delayed neuronal death. Double immunostaining showed that reactive astroglia and microglia could express BDNF, suggesting a possible involvement of these cells in the mechanism of neuronal survival after ischemia.

Animals↗
PubMed2002

Increased angiogenic growth factor in cyanotic congenital heart disease.

To examine the relationship between the plasma levels of angiogenic growth factors and the severity of cyanosis, 80 patients with cyanotic heart disease (CHD) and 81 healthy controls were studied. Median age and mean arterial blood oxygen saturation respectively were 4.2 years and 81% in CHD subjects and 4.8 years and 98% in controls. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were measured in plasma using enzyme-linked immunoassay. Plasma VEGF levels in controls depended negatively on age (p < 0.0001) until 3 months, when VEGF was no longer elevated. No such age dependence was found for HGF. Although VEGF levels did not differ between CHD and control subjects up to the age of 3 months, VEGF was significantly elevated in CHD patients older than 3 months compared to controls of similar age (149 +/- 106 vs 65 +/- 23 pg/ml, p < 0.0001). Moreover, the VEGF levels were negatively correlated with oxygen saturation (p = 0.03) and positively correlated with hemoglobin (p = 0.004) in CHD patients aged between 3 months and 10 years. Although the physiologic elevation of VEGF in the neonatal period decreases rapidly if oxygen saturation is normal, VEGF elevations persist if systemic hypoxia is present.

Adolescent↗
PubMed2002

Analysis of SIDS-related civil and criminal court cases in Japan.

Thirty-three sudden infant death syndrome (SIDS)-related civil and criminal lawsuits in Japan were retrieved from judicial precedent databases "Hanrei Masutar (Judicial Decisions Master)" and "Hanrei Taikei (Judicial Decisions System) using "SIDS" as a keyword. Sleeping posture and developmental stage of occurrence were studied in each of the cases retrieved, whether or not a legal autopsy had been performed. The influence exerted on court decisions by Japanese definitions of SIDS as well as the relationship between causes of death and court decisions were studied. Of 33, two were criminal cases (business/professional negligence on the part of the defendants, leading to death), and the rest were civil cases (claims for damages). Because the decision handed down in both criminal cases was "cause of death unknown", these defendants were found innocent. One of these cases was argued in both the court of appeals and the superior court: these courts found SIDS to be the cause of death and consequently the claim for damages was rejected. Both criminal and civil courts dealt with another case: the former found the cause of death to be "unknown" and the defendant innocent, while the latter, finding SIDS the cause of death, declined to review. In cases where the sleeping posture was prone, courts tended to decide the cause of death to be suffocation, especially with neonates. Because diagnosis by exclusion is required in cases of a legal autopsy for SIDS, the diagnosis is difficult without an autopsy. Disagreements between the results of legal autopsy and court decisions occurred in eight cases. With such a discrepancy, a detailed case examination is necessary. In 1983, SIDS was defined in Japan in two different ways; one in a more strict sense and the other being more inclusive. The wider and narrower definitions were unified in 1995 by requiring a survey of the circumstances of death in addition to the narrower definition. Because of this situation, the two cases in the 1980s when legal autopsy was not enforced fell into the category of "SIDS in a wider sense." In no case was a defendant found guilty when the cause of death was judged to be either SIDS/ALTE or unknown. Four cases were rejected when the cause of death was judged to be neither due to suffocation nor SIDS, while seven were accepted either as cases of "joint faults that canceled each other," or as "partial acceptance." In Japan, official views concerning a SIDS diagnosis differ among pediatricians, legal scholars of forensic medicine and pathologists. These differences appeared to influence the legal decisions. Several conferences should be convened as soon as possible to provide an opportunity to resolve the main points of difference between these three professional groups and, thus, attain a unified view.

Age Factors↗
PubMed2002

Comparison between SIDS-related court cases in the United States and Japan--a trend seen in legal precedents in the United States.

A bibliographic search of "Lexis", a database on foreign legal cases, was conducted, using sudden infant death syndrome (SIDS) as a key word to retrieve legal cases related to SIDS in the United States. The procedure yielded 156 cases, which included many that were brought to the courts for reasons other than SIDS. The following explanation was given for this outcome: because the public in the United States is much better informed about SIDS than in Japan, few cases are brought to the courts with SIDS as the main cause of the argument; the acronym, SIDS, is simply quoted during the court proceedings. Nevertheless, 26 cases that were particularly related to SIDS were selected and compared against 33 cases recorded and retrieved in the previous year in Japan to find the difference in the trends in legal disputes. The difference in the trends in litigation in the two countries was evident: in most cases in Japan, the legal dispute was over the recognition of SIDS or asphyxiation as the cause of death that had occurred in a nursery or hospital, with the family acting as the plaintiff and the nursery or hospital as the defendant. In the majority of cases in the United States, on the other hand, the state was the plaintiff and the family or baby sitter the defendant; the focal point of the dispute was the distinction between SIDS and child abuse. Compared with the trend in Japan, a much greater number of cases were brought before the court of final appeals in the United States. As the public becomes more aware of SIDS through campaigns and other means, the pattern seen in the legal disputes refer to SIDS lawsuits in Japan may change into that seen in the United States.

Cause of Death↗
PubMed2002

The 5'-upstream cis-acting sequences of a cyanobacterial psbA gene: analysis of their roles in basal, light-dependent and circadian transcription.

Transcription of the psbA2 gene in the unicellular photosynthetic cyanobacterium Microcystis aeruginosa K-81 is modulated by light and follows a circadian rhythm. In this study, we further characterized psbA transcription using a series of 5'-upstream deletions and mutant promoters which were tested in both photosynthetic and non-photosynthetic bacteria. Specific psbA2 transcripts were obtained from a minimal promoter sequence (-38/+14) with Escherichia coli RNA polymerases (RNAPs) both in vivo and in vitro, indicating the presence of a common regulatory mechanism for basal transcription. A DNase I footprinting assay showed that the E. coli RNAP, which is structurally similar to that of cyanobacteria, specifically binds to a large segment (from -115 to +23) of the sequence upstream of psbA2. In cyanobacteria, the -10 sequence (TAGTAT), but not the -35 motif (TTTACA), is essential for basal transcription by homologous and heterologous RNAPs that contain the major sigma factor. Each of the conserved thymidine nucleotides at positions -12 and -7 (underlined above) was essential, and both an insertion and a deletion in the spacer region of the promoter caused reductions in transcription. RNAP was able to bind to a mutant promoter lacking the -10 sequence, though this did not actually lead to transcription. Interestingly, a high level of arrhythmic circadian transcription was observed in mutants lacking the -35 region. In contrast, a mutation in the AU-box mutation, which controls the stability of the psbA2 mRNA, did not affect the circadian pattern of transcription. These findings demonstrate that light-dependent psbA2 expression is controlled at the transcriptional and post-transcriptional levels, whereas the circadian pattern of expression is regulated at the transcriptional level.

Base Sequence↗
PubMed2002

Phosphorylated tyrosine-containing proteins in primary lung cancer correlates with proliferation and prognosis.

To determine the usefulness of tyrosine phosphorylation in evaluating biological characteristics, we attempted to evaluate the relationship between the amount of phosphorylated tyrosine-containing proteins and clinicopathological factors, cell proliferation and outcome in non-small cell lung cancer. To evaluate phosphorylated tyrosine-containing proteins we used 96 surgically resected materials of non-small cell lung cancer and normal peripheral lung, while immunohistochemical evaluation was performed. Cell proliferating ability was evaluated using the labelling index of proliferating cell nuclear antigen-positive nuclear staining cells. There were statistically significant differences between the expression levels of phosphorylated tyrosine-containing proteins of normal and cancerous tissues (P<0.0001). Evaluations based on clinicopathological factors apart from histopathological differentiation, showed no statistically significant differences of phosphorylated tyrosine-containing proteins expression. However, phosphorylated tyrosine-containing proteins correlated with cell proliferation activity evaluated (P((Low, High))<0.0001; P((Low, Int)) <0.0001; P((Int, High))<0.0001). Furthermore, non-small cell lung cancer cases with high expression and intermediate expression of phosphorylated tyrosine-containing proteins had a significantly shorter disease-free postoperative survival than those with low expression of phosphorylated tyrosine-containing proteins using log-rank analysis (P((Low, Int)) <0.0028; P((Low, High))=0.0002). Furthermore, phosphorylated tyrosine-containing proteins expression level statistically contributed to disease-free survival in Cox's proportional hazard model. Therefore, phosphorylated tyrosine-containing proteins in non-small cell lung cancer tissues seem to reflect its biological malignancy, and this evaluation may be valuable for constructing the most appropriate therapeutic strategy.

Aged↗
PubMed2002

Bandgap modulation of carbon nanotubes by encapsulated metallofullerenes.

Motivated by the technical and economic difficulties in further miniaturizing silicon-based transistors with the present fabrication technologies, there is a strong effort to develop alternative electronic devices, based, for example, on single molecules. Recently, carbon nanotubes have been successfully used for nanometre-sized devices such as diodes, transistors, and random access memory cells. Such nanotube devices are usually very long compared to silicon-based transistors. Here we report a method for dividing a semiconductor nanotube into multiple quantum dots with lengths of about 10nm by inserting Gd@C82 endohedral fullerenes. The spatial modulation of the nanotube electronic bandgap is observed with a low-temperature scanning tunnelling microscope. We find that a bandgap of approximately 0.5eV is narrowed down to approximately 0.1eV at sites where endohedral metallofullerenes are inserted. This change in bandgap can be explained by local elastic strain and charge transfer at metallofullerene sites. This technique for fabricating an array of quantum dots could be used for nano-electronics and nano-optoelectronics.

Journal Article↗
PubMed2002

Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

Adolescent↗
PubMed2002

Optimisation of illumination for photodynamic therapy with mTHPC on normal colon and a transplantable tumour in rats.

Recent reports suggest that the effect of photodynamic therapy (PDT) can be enhanced by fractionating the light dose or reducing the light fluence rate. We assessed these options on two tissues in rats (normal colon and a transplanted fibrosarcoma) using the photosensitiser meta-tetrahydroxyphenylchlorin (mTHPC). Animals were sensitised with 0.3 mg/kg mTHPC, 3 days prior to illumination with red light (652 nm) using a single fibre touching the target tissue and killed 1-3 days later for quantitative measurement of the extent of PDT necrosis. Results were similar for both tissues, although the differences between illumination regimens were less marked in tumour tissue. Using continuous illumination and a fixed low energy in colon, the extent of necrosis was up to almost three times larger with 5 mW than with 100 mW, although the maximum attainable necrosis was independent of power. The long treatment time using 5 mW could be halved without loss of effect by increasing the power during treatment. Dividing the light into two equal fractions at 100 mW increased the lesion size by up to 20% in colon (independent of the timing of the dark interval), but by only 10% in tumour and had no effect at 20 mW. Previous studies using 5-aminolaevulinic acid (ALA) showed a much larger effect of fractionation that was critically dependent on the timing of the dark interval. We postulate that enhancement of PDT by fractionation is due to improved oxygen supply to the treated area which may be due to reversal of temporary vascular occlusion (more likely with ALA) or less rapid photochemical consumption of oxygen (more likely with mTHPC). At lower fluence rates, the oxygen consumption rate is not fast enough to be improved by fractionation. We conclude that fractionated or low power light delivery can enhance PDT with mTHPC. Although the effects are not large, this may be of value for interstitial treatment of solid tumours when multiple sites are treated simultaneously.

Animals↗