Essential hyperhidrosis is a well recognized dermatologic and neurologic disorder, characterized by excessive sweating of the eccrine sweat glands. It is also associated with cardiac autonomic dysfunction because sympathetic fibers to eccrine glands of palms of the hand arise from stellate and upper thoracic ganglia, which also innervate the heart. In this study, we investigated cardiac function in patients with essential hyperhidrosis by conventional and tissue Doppler imaging methods. Eighteen subjects with essential hyperhidrosis and eighteen control subjects were included in this study. Pulsed-wave Doppler parameters of the left and right ventricles, which represent diastolic filling abnormalities, were obtained by conventional Doppler and tissue Doppler imaging. Isovolumetric relaxation time, isovolumetric contraction time, ejection time and myocardial performance index were also calculated. Mitral inflow peak early (EM) and late (AM) velocities and EM/AM ratio, which represent diastolic filling of left ventricle, were significantly lower in hyperhidrotic subjects than in controls. Also, mitral lateral annulus early and late velocities and early/late velocity ratio, reflecting diastolic filling of left ventricle, were significantly lower in hyperhidrotic subjects than those of controls. However, there were no differences between hyperhidrotic subjects and control subjects with regard to the other echocardiographic indices of left and right ventricle diastolic functions. In conclusion, decreased mitral inflow suggests left ventricle diastolic dysfunction in patients with essential hyperhidrosis. This indicates that hyperactivity of sympathetic nervous system in patient with hyperhidrosis may alter cardiac function in long term.
Systemic embolization is a potential complication in patients with thrombi situated in the left atrium and particularly, in the left atrial appendage (LAA). Reduced LAA contraction velocities, determined by the transesophageal echocardiography (TEE), are associated with increased risk of LAA spontaneous echocontrast and thrombus formation, and a history of systemic embolism. However, TEE remains a semi-invasive procedure, limiting its serial application as a screening tool. Therefore, it is desirable to obtain information regarding LAA function by transthoracic echocardiography in patients having cardioembolic stroke. The present study was designed to investigate various echocardiographic variables for patients with stroke to predict LAA dysfunction, reflected as reduced LAA contraction velocity. We studied a total of 61 patients with newly diagnosed acute embolic stroke (42 patients) and transient ischemic attack (19 patients). Computerized tomographic scanning was performed for the diagnosis of embolic stroke. Left atrial functional parameters determined by transthoracic echocardiography, such as left atrial active emptying fraction and acceleration slope of mitral inflow A wave, had significant correlations with the LAA contraction velocity (r = 0.57, p < 0.001; r = 0.54, p < 0.001, respectively). Left atrial volume index, left atrial active emptying volume and left atrial fractional shortening were also correlated with LAA contraction velocity (r = −0.44, p < 0.001; r = 0.38, p = 0.003; r = 0.37, p = 0.004, respectively). In conclusion, transthoracic echocardiography can provide valuable and reliable information about the LAA contraction velocity in stroke patients with sinus rhythm. This finding gives new insights for the appropriate strategy in the evaluation of an acute ischemic stroke.
Acute esophageal toxicity (AET) is a common complication and dose-limiting toxicity in thoracic radiotherapy. Previous studies demonstrated several clinical and dosimetric parameters of AET in patients with lung cancer. However, there are few reports dealing with these variables in intra-thoracic malignancies, including lung cancer and other thoracic malignancy. The purpose of this study was to evaluate the clinical and dosimetric factors associated with AET in patients with intra-thoracic malignancies. We examined 61 patients with intra-thoracic malignancies treated with radiotherapy: 34 patients with non-small-cell lung cancer (55%), 9 cases with small-cell lung cancer (15%), 7 cases with thymic cancer (11%), 4 thymomas (7%), 2 malignant lymphomas (3%), one seminoma (2%), one liposarcoma (2%), and 3 cases of other malignancies (5%). Radiotherapy was performed with a median dose of 60 Gray (Gy) (range 40-67 Gy). AET was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. The following parameters were analyzed with respect to associations with AET by univariate and multivariate analyses: age, gender, thoracic surgery before radiotherapy, concurrent chemotherapy, duration of radiotherapy, maximum esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving from 10 Gy (V10) to 65 Gy (V65), in 5-Gy increments. 43 patients (70%) developed AET: 36 patients (59%) with AET of RTOG Grade 1, 7 patients (11%) with Grade 2, and no patients (0%) with Grade 3 or worse. On multivariate analysis, V35 > 30% was the most statistically significant factor associated with mild AET (p = 0.013). Our findings provide a better understanding of the factors related to AET, and might be useful in designing a treatment plan to prevent severe esophageal toxicity.
It is not fully clear whether intramuscular oxidative metabolism contributes to total adenosine triphosphate (ATP) production during forearm isometric exercise at varying intensities. We tested hypothesis that oxidative metabolism with intramuscular O2 contributes to lessen the dependence on anaerobic metabolism, in particular phosphocreatine (PCr) breakdown. Seven male subjects were tested for changes in muscle oxygenation (MO2) and high-energy phosphates in forearm flexor muscles at rest and during exercise under arterial occlusion by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and near infrared spectroscopy (NIRS). Isometric wrist flexion exercise was performed for 1 min or until exhaustion at intensities corresponding to 30%, 50% and 70% of maximal voluntary contraction (MVC) under intramuscular O2 (Intramuscular O2-Ex) and anaerobic (Anaero-Ex) conditions. Oxidative ATP production in Intramuscular O2-Ex was calculated as 0.05 ± 0.01 mM/s for 30%MVC, 0.08 ± 0.01 mM/s for 50%MVC and 0.11 ± 0.01 mM/s for 70%MVC. At a lower intensity (30%MVC), PCr breakdown rate (0.17 ± 0.02 mM/s) of Anaero-Ex was significantly higher than the rate (0.13 ± 0.01 mM/s) of Intramuscular O2-Ex (p < 0.05). There was no significant difference in ATP production rates through PCr breakdown and glycolysis between Intramuscular O2-Ex and Anaero-Ex at the higher intensities (50% and 70%MVC). In conclusion, intramuscular oxidative metabolism plays a significant role in reducing the dependence on PCr breakdown during isometric exercise at a lower intensity (30%MVC).
Acupuncture has been introduced as one of the available therapies widely used in alternative medicine, but it has not achieved widespread acceptance with scientific evidence. Furthermore there are still many unanswered questions about the basic mechanisms of acupuncture. To investigate the neuropharmacological mechanisms of oriental acupuncture, we studied the acupuncture-induced changes of in vivo monoamine release in the rat brain. A microdialysis guide cannula was implanted into the nucleus accumbens (ACC), which plays an important role in the brain reward system. Acupuncture treatment at the unilateral or bilateral Shenshu (bladder urinary channel 23) acupoints, located on the both sides of the spinous processes on the lower back, was carried out for 60 min in freely moving rats, and the dopamine (DA) and serotonin (5-HT) contents of the microdialysates in the ACC were measured simultaneously. In rats subjected to acupuncture at bilateral Shenshu acupoints, increases of 5-HT release in the ACC were observed at 20 min of acupuncture treatment and continued until 40 min after acupuncture was ended. Acupuncture at a unilateral Shenshu acupoint increased the release of 5-HT at 20 min compared with that in the sham-control group. Five-HT release returned to the baseline level at 120 min. The effects of acupuncture at bilateral Shenshu acupoints on the release of 5-HT in the ACC were greater than that of unilateral acupuncture treatment. In contrast, DA release in the ACC was not changed following acupuncture treatment. Effective acupuncture increased and prolonged the activity of serotonergic neurons in the reward system pathway of the brain. This suggests that oriental acupuncture therapy may be effective for the treatment of emotional disorders, drug abuse and alcoholism.
An increased seroprevalence of Helicobacter pylori (H. pylori), especially high virulent cytotoxin-associated gene-A (CagA) positive strains, has been found in many extragastrointestinal disorders. Moreover, it has been reported that the risk of chronic bronchitis may be increased in H. pylori infected patients. However, until now there are no data regarding the relationship between H. pylori infection and chronic bronchitis among Chinese population. Therefore the aim of the present study was to assess the seroprevalence of H. pylori and in particular of CagA positive virulent strains in patients with chronic bronchitis among Chinese population. We evaluated 46 patients with chronic bronchitis, 48 age- and sex-matched patients with peptic ulcer and 48 healthy control subjects. All enrolled subjects underwent a serologic test for H. pylori IgG and CagA by enzyme linked-immunosorbent assay (ELISA). There was no significant difference in the seropositivity for these parameters between chronic bronchitis and peptic ulcer groups (86.9% vs 89.6% for anti-H. pylori IgG and 67.4% vs 72.9% for anti-H. pylori-CagA IgG). However, these serological parameters were significantly higher in the patients with chronic bronchitis or peptic ulcer than those in control group, who showed 60.4% for anti-H. pylori IgG seropositivity and 20.8% for anti-H. pylori-CagA IgG seropositivity. Among the patients with chronic bronchitis, no significant difference was found in these serological parameters between the current cigarette smokers and never smokers. This is the first report of a high seroprevalence of H. pylori infection in chronic bronchitis among Chinese population.
Morpholino oligonucleotides (MO) can induce gene silencing by binding to a target mRNA and inhibiting its translation, and this technique has been especially successful in studies of embryonic development in various vertebrates. But in mice MO-induced downregulation of target genes has not been widely reported. In this study, we examined whether MO delivery using ethoxylated polyethylenimine (EPEI) delivery reagent is useful for silencing gene expression in the mouse preimplantation embryo, by targeting endogenous gene Oct4. To optimize the conditions for MO delivery, we examined the MO concentration, the EPEI concentration, the treatment time, and the number of MO treatments. The MO treatment was performed at the 2-cell, the morula, the blastocyst, and the hatched blastocyst stage. We first determined the optimal conditions for MO delivery into the nucleus using fluorescein isothiocianate (FITC)-labeled MO, and demonstrated that treatment with a combination of 20 μM MO and 0.56 μM EPEI for 3 hrs produced effective MO delivery. MO-induced downregulation of Oct4 was then examined. Two-step MO treatment at the 2-cell and blastocyst stages successfully suppressed Oct4 expression. This MO treatment resulted in marked reduction of Oct4 protein at the blastocyst stage. After cultivation of blastocysts for further 4 days, derivatives of embryos either differentiated to trophoblastic cells or showed developmental arrest at the blastocyst. This phenocopy is similar to Oct4-deficient embryos. Overall, our results indicate that MO delivery with EPEI is an effective tool for analyzing gene function in mouse preimplantation embryos.
Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic disease generally characterized by café-au-lait spots and neurofibromas. Malignant tumors of the nervous system, such as malignant schwannomas, gliomas, or astrocytomas, have been well known to coexist with neurofibromatosis. However, occurrence of malignant tumors unrelated to the nervous system is rare. We report an unusual case of a 29-year-old NF1 female suffering from malignant peripheral nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal femur. Osteosarcoma is the most common high-grade malignant bone tumor in which the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent excision of MPNST in the left posterior thigh. No osteosarcomatous portion was identified in these specimens. The patient underwent postoperative chemotherapy. At 29, left proximal thigh pain and swelling appeared. Computed tomography demonstrated cortical bone destruction in the left proximal femur where MPNST occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor. Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip disarticulation was performed. The removed tumor was composed of highly anaplastic cells. Lace-like irregular osteoid formation was observed among the tumor cells. MPNST component was totally absent. The tumor was diagnosed as osteoblastic type osteosarcoma. Two months after disarticulation the patient died of bilateral pulmonary metastasis. The correlation between the histogenesis of osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated, but the finding of osteosarcomatous transformation in this case suggests the divergent cellular differentiation to mesenchymal malignant tumors of neuroectodermal tissue in NF1 patients.
Here we describe a case of idiopathic pulmonary alveolar proteinosis (I-PAP), in which anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibody and high level of KL-6 were found in the serum. Anti-GM-CSF antibody is responsible for I-PAP, and KL-6 is a serum marker for the activity of diffuse interstitial lung disease. A 38-year-old woman, who had no symptoms, was found to have an abnormal shadow on chest radiograph 5 years previously at a health check up. Chest radiograph showed a patchy shadow in the left lower lung field. Thoracoscopic biopsy was performed because the shadow had gradually expanded during the 5 years. Histological examination revealed proteinous material filling the alveoli and positive staining by the PAS method, suggesting PAP. Anti-GM-CSF antibody and a high level of KL-6 were detected in the serum at the time of diagnosis. Three years later, the shadow disappeared spontaneously. During this period, the level of KL-6 dramatically decreased, although that of GM-CSF antibody remained unchanged. The present case suggests that the serum level of the anti-GM-CSF antibody represents a useful marker for the diagnosis but not for follow-up of the clinical course. On the contrary, KL-6 is an excellent marker for the assessment of the clinical course of I-PAP.
Intermittent intravenous cyclophosphamide pulse therapy (IVCY) has been reported to be effective for the treatment of refractory systemic lupus erythematosus (SLE). However, there is a proportion of patients with SLE, who are IVCY-resistant and need a long-term therapy to sustain the remission. We report here a case of a 6-year-old Japanese girl with SLE refractory to IVCY. She suffered from persistent hypocomplementemia and recurrent flares despite receiving methylprednisolone pulse, mizoribine pulse and IVCY therapy. Administration of cyclosporine A (CsA) was, therefore, initiated. Within 2 months of the start of CsA administration, the serum levels of C3, C4 and complement hemolytic activity began to increase rapidly, and finally returned to the normal levels. The serum anti-dsDNA antibody titer was decreased significantly after the initiation of this treatment. The prednisolone dose could be successfully tapered without precipitation of any flares. No adverse effects of CsA were observed. Based on these clinical observations, we suggest that CsA might be an effective treatment option for selected cases of refractory SLE.