Radiofrequency catheter ablation for sinoatrial node reentrant tachycardia: electrophysiologic features of ablation sites

The aim of this study was to investigate catheter ablation of sino-atrial reentrant tachycardia (SART) and the electrophysiologic characteristics of the ablation sites. From January 1990 to October 1997, 651 patients with supraventricular tachycardia were referred and 11 patients were found to have SART. Ablation was successful in all cases with a mean number of 3.3 radiofrequency (RF) current pulses. SART terminated during 22 of 36 RF pulses. In spite of prompt termination, tachycardia could be re-induced in 3 of 11 patients with its earliest activation site shifted. At effective ablation sites, the electrograms during tachycardia were characterized as fractionated (75+/-17 ms), and 38+/-16 ms prior to surface P wave, and 42+/-18 ms prior to the high right atrium. Unipolar electrograms revealed a sharp negative unipolar deflection, so called QS pattern, in 15 of 20 sites during SART and 15 of 15 sites during sinus rhythm. During effective applications, atrial premature beats (APB) with activation sequences identical to sinus rhythm appeared in 14 of 22 cases. Effective ablation sites of SART showed fractionated electrograms during tachycardia and sinus rhythm. Unipolar electrogram with a QS pattern and APB during energy application could be an indicator of the optimal ablation sites.     

Sodium nuclear magnetic resonance imaging of acute cardiac rejection in heterotopic heart transplantation

Nuclear magnetic resonance (NMR) imaging was used to measure tissue sodium-23 in the myocardium undergoing cardiac rejection. In six dogs, the donor heart was heterotopically transplanted into the recipient's chest cavity. The dogs were then killed and sodium-23 images of the excised hearts were obtained using a high field (1.5 Tesla) NMR imaging system. Proton NMR imaging of each excised heart was also performed and T1, T2 relaxation times were calculated. Subsequently, these data were correlated with pathological findings of mild, moderate and severe rejection. The correlation coefficients between the rejection score and the T1, T2 relaxation times and sodium NMR signal intensity were 0.79, 0.70 and 0.84, respectively. Severely rejected areas of the myocardium were visualised by increased sodium NMR signals. These findings suggest that an increase of sodium NMR intensity is mainly caused by an increase of intracellular sodium content due to irreversible myocardial necrosis. Sodium NMR allows evaluation of the location and extent of rejection of myocardium after heart transplantation.     

IL‐28B (IFN‐λ3) and IFN‐α synergistically inhibit HCV replication

Genetic variation in the IL‐28B (interleukin‐28B; interferon lambda 3) region has been associated with sustained virological response (SVR) rates in patients with chronic hepatitis C treated with peginterferon‐α and ribavirin. However, the mechanisms by which polymorphisms in the IL‐28B gene region affect host antiviral responses are not well understood. Using the HCV 1b and 2a replicon system, we compared the effects of IFN‐λs and IFN‐α on HCV RNA replication. The anti‐HCV effect of IFN‐λ3 and IFN‐α in combination was also assessed. Changes in gene expression induced by IFN‐λ3 and IFN‐α were compared using cDNA microarray analysis. IFN‐λs at concentrations of 1 ng/mL or more exhibited concentration‐ and time‐dependent HCV inhibition. In combination, IFN‐λ3 and IFN‐α had a synergistic anti‐HCV effect; however , no synergistic enhancement was observed for interferon‐stimulated response element (ISRE) activity or upregulation of interferon ‐ stimulated genes (ISGs). With respect to the time course of ISG upregulation, the peak of IFN‐λ3‐induced gene expression occurred later and lasted longer than that induced by IFN‐α. In addition, although the genes upregulated by IFN‐α and IFN‐λ3 were similar to microarray analysis, interferon‐stimulated gene expression appeared early and was prolonged by combined administration of these two IFNs. In conclusion, IFN‐α and IFN‐λ3 in combination showed synergistic anti‐HCV activity in vitro. Differences in time‐dependent upregulation of these genes might contribute to the synergistic antiviral activity.     

Elucidation of genomic origin of synchronous endometrial and ovarian cancer (SEO) by genomic and microsatellite analysis

ObjectiveElucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs).MethodsWe reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes.ResultsSixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease.ConclusionMost SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.     

Ocular injury caused by an air bag for a driver wearing eyeglasses.

BACKGROUND: Although air bags have been shown to reduce the number of fatalities and serious injuries caused by motor vehicle accidents, there have been many reports of air bag-related ocular injuries. We recently treated air bag-related corneal laceration in a patient wearing eyeglasses at the time of a motor accident. CASE: A 38-year-old Japanese man was driving a car at approximately 40 km per hour when he struck a stopped 2-ton truck. He was wearing a three-point lap-shoulder seat belt. At impact, the driver's-side air bag deployed and struck the man on the left side of his face. He was wearing eyeglasses with glass lenses, and the air bag broke the left lens of his eyeglasses, and glass fragments lacerated his cornea. OBSERVATIONS: External examination showed multiple superficial abrasions of the skin and ecchymosis of the left side of his face. Slit-lamp examination of his left eye showed corneal laceration and hyphema. The lens had opacities and was covered with fibrin membrane. Repair of the corneal laceration and phacoemulsification of the lens were performed. Six months later, his best corrected visual acuity was 20/20 in the left eye. CONCLUSIONS: As cars are increasingly equipped with air bags, reports of air bag-related eye injuries have increased. To our knowledge, this is the first reported case of corneal laceration caused by a shattered lens in an air bag-related injury. Ophthalmologists should caution patients about the danger of eye injuries in air bag-equipped cars, and thought should be given to improving the materials for eyeglasses.     

Auditory brain stem responses in relation to the clinical symptoms of schizophrenia

Auditory brain stem responses (ABSR) were examined systematically both in normal and schizophrenic subjects. All ABSR wave forms were evoked by click stimuli, which were delivered binaurally through headphones both to normal subjects and to a nondeteriorated group of schizophrenics. However, in the group of schizophrenics with marked deterioration of personality, not all wave forms were elicited, and the amplitudes were low. The characteristics of the ABSR wave forms correlated well with the clinical symptoms of the schizophrenic illness. The cause of these ABSR wave form changes in schizophrenics is discussed.     

A case of advanced gastric cancer resistant to S-1 successfully treated with weekly administration of paclitaxel

A 62-year-old female was diagnosed with type 2 advanced gastric cancer in May 2003. Pathological examination showed a poorly differentiated carcinoma. Computed tomography (CT) revealed paraaortic lymph node metastasis, duodenal metastasis and ascites due to peritoneal dissemination. Chemotherapy with CDDP+S-1 was started and continued. After the chemotherapy, there were progressive diseases. Therefore, paclitaxel (PTX) was administered at a dose of 80 mg/m2/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and CT scan revealed metastatic lymph nodes were reduced after 4 cycles. After 13 cycles, MRI revealed a solitary brain mass was detected. She was resected for a right temporal-occipital brain metastatic tumor, and local cerebral irradiation was performed. After this operation, she was diagnosed with brain metastasis from advanced gastric cancer. The procedure was interrupted for about 6 months. After rehabilitation, PTX treatment was restarted as 14th cycle. She has survived without recurrence more than 30 cycles after the resection. A weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1 resistant recurrent gastric cancer.     

Nonviable Burkholderia mallei induces a mixed Th1- and Th2-like cytokine response in BALB/c mice

Nonviable cell preparations of Burkholderia mallei, the causative agent of glanders, were evaluated as potential vaccine candidates in a BALB/c murine model. Three different B. mallei cell preparations plus Alhydrogel were evaluated: a heat-killed preparation, an irradiation-inactivated preparation, and a preparation of a capsule-negative mutant strain which had been irradiation inactivated. BALB/c mice were vaccinated twice with the different B. mallei preparations, and spleens and sera were collected to determine their cellular and humoral immune responses. All three bacterial cell preparations had essentially the same results in two cellular immune response assays. In a splenocyte proliferation assay, the amount of cell proliferation in response to the homologous immunogen, concanavalin A, or lipopolysaccharide was similar for all the cell preparations. Also, splenocytes from the inoculated mice expressed interleukin 2 (IL-2), gamma interferon, and small amounts of IL-4 and IL-5, and more IL-10 cytokine in the presence of the homologous antigen. When the immunoglobulin subclasses from these mice were examined, they all produced higher levels of IgG1 than IgG2a subclasses. The higher ratio of IgG1 to IgG2a was not due to the amount of the immunogen or the adjuvant (Alhydrogel) used in the BALB/c mice. The cell preparations did not protect the vaccinated mice from a live challenge (>300 50% lethal doses). Our results suggest that in BALB/c mice, a mixed T-helper-cell-like response to nonviable B. mallei is obtained, as demonstrated by a Th1- and Th2-like cytokine response and a Th2-like subclass immunoglobulin response. This may be the reason for the inability of the B. mallei cells that were examined as candidate vaccines to protect the mice from a live challenge.     

Differential effects of background noise of various intensities on neuronal activation associated with arousal and stress response in a maze task

Background noise (BGN) can affect performance of various tasks as a function of its intensity. Such effects may involve modulation of arousal level during task performance, though the neural mechanisms responsible for the intensity-dependence of effects of BGN are still unclear in detail. We examined the effects of BGN (white noise) of various intensities (control, < 40 dB without BGN; 70 dB; 100 dB) during maze task on neuronal activity related to arousal and stress responses using c-Fos immunohistochemistry in rats. Performance (number of errors, time to goal, and number of rearings) during the maze task under 70 dB-BGN, but not 100 dB-BGN, was improved compared with the control condition. In addition, 70 dB-BGN increased c-Fos expression in brain areas responsible for arousal, including mesopontine tegmentum, basal forebrain (BF), locus coeruleus (LC), and cortex, whereas 100 dB-BGN markedly activated neurons in stress-related nuclei, such as the hypothalamic paraventricular nucleus, central nucleus and basolateral nucleus of the amygdala, as well as BF cholinergic neurons, LC neurons, and cortex. These findings suggest that BGN during maze task can induce differential neuronal activation depending on the intensity of BGN in the brain areas relating to arousal and stress responses, which might be involved in maze performance.     

Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro.

We examined 35 primary human ovarian adenocarcinomas for the presence of epidermal growth factor (EGF) receptor (EGFR) in plasma membranes from cancer tissues by using 125I-EGF as a ligand. Specific 125I-EGF bindings were observed in 20 (57%) of these 35 cases. Scatchard analysis showed a class of high affinity EGF receptor: Kd 5.0 +/- 1.0 x 10(-10) M; Bmax, 83.3 +/- 12.1 fmol/mg protein (mean +/- SE, n = 20). Northern analysis in polyadenylated RNA from 15 EGFR(+) cancers using pretransforming growth factor alpha (pre-TGF alpha), prepro-EGF complementary DNA, and pE7, a complementary DNA clone of human EGFR, as probes revealed that pre-TGF alpha and EGFR mRNAs but not prepro-EGF mRNA were expressed in all cases examined. Immunocytochemical studies using monoclonal antibodies (mAbs) against TGF alpha, EGF, and EGFR showed that TGF alpha and EGFR but not EGF proteins were present on ovarian cancer cells in all cases. These data suggested a possible TGF alpha/EGFR autocrine mechanism in EGFR(+) ovarian cancers. We, therefore, examined the biological significance of this autocrine mechanism by using primary monolayer cell cultures. In primary cultures from EGFR (+) cancers, TGF alpha added to the culture medium stimulated the [3H]thymidine incorporation dose dependently. Moreover, the addition of mAbs against TGF alpha and EGFR but not EGF inhibited [3H]thymidine incorporation dose dependently in EGFR(+) cancer cells. On the other hand, in primary cultures from EGFR(-) cancers, TGF alpha and anti-TGF alpha, -EGFR, and -EGF mAbs did not show any effects on [3H]thymidine incorporation. All these results suggested the possible crucial role of a TGF alpha/EGFR autocrine growth mechanism in primary human ovarian cancers which express EGFR.