Search

The aim of this study was to non-invasively investigate euploid embryos using methods other than pre-implantation genetic testing for aneuploidy. The study focused on direct cleavage (DC) observed during early embryo development. We also investigated the relationship between the mode of early embryo division and embryo ploidy. Embryos were divided into the normal cleavage (NC) and DC groups, and the DC group was further subdivided into the DC-First (DC-F) and DC-Second (DC-S) groups, depending on whether DC was observed at the first or second cleavage, respectively. The acquisition rates of euploid embryos and embryos appropriate for transfer were compared between the groups. Our results revealed that the timing of the first division did not differ between blastocyst grades or in embryos with varying degrees of ploidy. Further, the timing of the first cleavage did not affect the acquisition rate of embryos appropriate for transfer and euploid embryo formation rate did not significantly differ between the DC and NC groups. We also noted that for embryos appropriate for transfer, euploidy acquisition rate did not differ significantly between the DC and NC groups. Further, the euploidy acquisition rate of embryos did not differ between the DC-F and DC-S groups. However, the acquisition rate of embryos appropriate for transfer, including those with low mosaicism, was significantly higher in the DC-S group than in the DC-F group. These findings indicated that the number of good-quality blastocysts formed was significantly higher in the NC group than in the DC group and the acquisition rate of embryos appropriate for transfer, including those with low mosaicism, was significantly higher in the DC-S group than in the DC-F group.

Research Question: Is there a relationship between the pronuclear axis and the first cleavage plane formation in human pronuclear-stage embryos, and what are the effects on ploidy and clinical pregnancy rates?, Design: Transferred embryos were followed up until their prognoses. A total of 762 embryos formed two cells and reached the blastocyst stage after normal fertilization in a time-lapse incubator. Embryos were classified into three groups: group A: embryos in which the first plane of division was formed parallel to the axis of the pronucleus; group B: embryos in which cases of oblique formation were observed; and group C: embryos in which cases of perpendicular formation were observed., Results: The euploidy rate was significantly higher in groups A and B than those in group C (P < 0.01), whereas the aneuploidy rate was significantly higher in group C (P < 0.01) than in groups A and B. No differences were found between the three groups in frequency of positive HCG-based pregnancy tests, frequency of clinical pregnancies, miscarriage rates or delivery rates., Conclusions: The formation pattern of the first plane of division relative to the pronuclear axis was a predictor of embryonic ploidy, with a reduced rate of euploidy and a high probability of aneuploidy observed when the first plane of division was perpendicular to the pronuclear axis., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: In preimplantation genetic testing for aneuploidy, opinions regarding the handling of mosaic embryos vary. In this study, we aimed to investigate the effects of freeze-thawing, the number of cells obtained, and the number of laser irradiation cycles on the degree of embryonic mosaicism., Study Design: This study was conducted in three parts. First, we classified specimens into the normal biopsy (control) (119 patients, 304 blastocysts) and thawed-biopsy (TB group) (26 patients, 72 blastocysts)) groups. The control and TB groups were then classified into three categories (euploidy, mosaic and aneuploidy) according to next-generation sequencing (NGS) results, and the number of cells collected and laser irradiation cycles were compared for each category. Subsequently, the effects of differences in the number of cells collected and laser irradiation cycles on NGS results were investigated in the control and TB groups. Finally, data on cell collection and laser irradiation cycles and NGS analysis results for the groups were compared., Results: The TB group had a significantly higher incidence of chromosomal mosaicism than the control group. Neither the number of cells collected nor the laser irradiation cycles affected the percentage of chromosomal mosaicism. However, the freeze-thaw process increased the occurrence of mosaicism., Conclusions: This study showed that repeated freeze-thaw cycles increase the incidence of mosaicism, but the embryos are not aneuploid and are therefore suitable for transfer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on whether it is also effective for patients with poor-quality embryos and low rates of good blastocyst formation. Specifically, the effectiveness of delayed-start gonadotropin-releasing hormone antagonists with progesterone has not been adequately investigated. Therefore, we compared the efficacy of the original delayed-start gonadotropin-releasing hormone antagonist protocol using medroxyprogesterone acetate (MPA) and high-dose gonadotropin in patients with poor ovarian response., Methods: Overall, 156 patients with recurrent assisted reproductive technology failure who underwent the original protocol were included. They received cetrorelix acetate (3 mg) and MPA (10 mg) on cycle day 3, and high-dose gonadotropin was initiated on day 11. When the leading follicle reached 14 mm, ganirelix acetate (0.25 mg) was administered until the trigger day. The number of oocytes retrieved, metaphase II (MII) oocytes, two pronuclear (2PN) zygotes, and good blastocysts and live birth rates were compared between the previous (Cycle A) and original (Cycle B) cycles in three groups (Group A, all patients; Group B, poor responders; and Group C, patients with poor-quality embryos)., Results: In Group A (n=156), the number of MII oocytes (3.6 ± 3.3 versus 4.5 ± 3.6), 2PN zygotes (2.8 ± 2.9 versus 3.8 ± 3.1), good blastocysts (0.5 ± 0.9 versus 1.2 ± 1.6), and live birth rates (0.6 versus 24.4) significantly increased in Cycle B. Similar results were obtained in Group B (n=83; 2PN zygotes [1.7 ± 1.7 versus 2.3 ± 1.8], good blastocysts [0.4 ± 0.7 versus 0.9 ± 1.3], live birth rates [0 versus 18.1]) and Group C (n=73; MII oocytes [5.1 ± 3.8 versus 6.6 ± 4.0], 2PN zygotes [4.0 ± 3.4 versus 5.4 ± 3.4], good blastocysts [0.7 ± 1.1 versus 1.6 ± 1.9], and live birth rates [1.4 versus 31.5])., Conclusion: This original protocol increased the number of MII oocytes retrieved, 2PN zygotes, good blastocysts, and live birth rates in both poor responders and in patients with poor-quality embryos., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Takeuchi, Orita, Iwakawa, Kuwatsuru, Kuroki, Fukumoto, Mizobe, Tokudome and Moewaki.)

Purpose: We examined the impacts of the smooth endoplasmic reticulum cluster (sERC) presence on embryonic development and blastocyst ploidy., Methods: Patients who underwent oocyte retrieval from January 2019 to November 2021 were included in the study. We classified the oocytes into three groups: normal oocytes in the sERC ( -) cycle, normal oocytes in the sERC ( +) cycle, and sERC ( +) oocytes. Next, the levels of serum estradiol, progesterone, anti-Mullerian hormone, follicle-stimulating hormone, and human menopausal gonadotropin were compared between the groups. Moreover, fertilization, degeneration, and abnormal fertilization rates were compared between groups. To investigate developmental outcomes, the blastocyst and good-quality blastocyst rates after intracytoplasmic sperm injection were compared. The quality of the transferred blastocysts was evaluated at follow-up. Additionally, embryos were submitted for next-generation sequencing analysis to examine the effect of sERC presence on ploidy., Results: The sERC ( +) group had significantly higher serum estradiol, serum progesterone, and serum anti-Mullerian hormone concentrations compared to those in the sERC ( -) group (P < 0.01). The abnormal fertilization rate was higher in the sERC ( +) cycle-sERC ( +) oocyte group (16.1%; 37/230) than in the sERC ( +) cycle-normal oocyte (6.2%; 63/971) and sERC ( -) cycle-normal oocyte groups (7.1%; 174/2467) (P < 0.01). After embryo transfer, nine women gave birth, and no confirmed congenital anomalies were observed. There was no significant difference in ploidy between the sERC ( +) and sERC ( -) groups., Conclusion: The occurrence rates of embryos with euploidy were similar between the sERC ( +) and sERC ( -) groups., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To examine how differences in trophectoderm biopsy techniques affect the frequency of mosaic embryos and sequencing results., Methods: We examined differences in next-generation sequencing (NGS) analysis results among operators or according to biopsy technique. Additionally, we determined the cut-off for the number of collected cells to predict the occurrence of mosaicism. We collected cells according to the cut-off value and examined whether there was a difference in the NGS analysis results between the pulling and flicking methods., Results: There was no difference in the NGS analysis results among the operators. Regarding re-biopsy, changes in the mosaic were observed in all specimens. The cut-off value for the number of collected cells was five, and when more than five cells were collected, there was no difference in the NGS analysis results between the two methods., Conclusions: We demonstrated that if trophectoderm biopsy techniques and NGS are stable, the cell collection location has a greater effect on NGS results than the biopsy technique., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Purpose: This study was conducted to assess the effectiveness of a new trophectoderm (TE) biopsy method that does not require prior opening of the zona pellucida at the blastocyst stage., Methods: TE biopsy was conducted using a modified extrusion method for embryos during the cleavage stage. In this method, culture medium was injected into the perivitelline space to help extrude TE cells from the zona pellucida before TE biopsy., Results: Our extrusion method preserves the embryo culture environment until immediately before biopsy because it does not require opening of the zona pellucida prior to TE biopsy. Furthermore, this method does not require a waiting time for blastocyst hatching after laser irradiation, thereby minimizing damage to the embryos and maintaining the time schedule of culture operations., Conclusions: TE biopsy using this novel extrusion method may be useful in various applications, including the collection of TE cells for next-generation sequencing analysis., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Purpose: To compare the clinical outcomes of embryo transfers that were cryopreserved and thawed two or three times with those cryopreserved and thawed once by CryoTip., Methods: Data for 388 single cryopreserved-thawed blastocyst transfer cycles, performed from April 2012 to March 2014, were assessed. The blastocysts were classified into three groups: blastocysts (A) cryopreserved once, (B) cryopreserved twice, and (C) cryopreserved three times., Results: The pregnancy rate was 43.8% (134/306) in group A and 46.3% (38/82) in group B, while the miscarriage rate was 29.1% (39/134) in group A and 23.7% (9/38) in group B. The rate of improvement/maintenance of blastocyst grade was 84.0% (257/306) in group A and 80.5% (66/82) in group B. The pregnancy and miscarriage rates of the blastocysts that showed improvement/maintenance in the grade were 45.9% (118/257) and 29.7% (35/118) in group A and 48.5% (32/66) and 21.9% (7/32) in group B, respectively. The pregnancy rate was 33.3% (2/6), while the miscarriage rate was 0.0% (0/2) in group C., Conclusions: Pregnancy rates achieved with re-cryopreserved and rethawed blastocyst transfer were comparable to those achieved with single cryopreserved-thawed blastocyst transfer., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest. Human rights statements and informed consent and Animal studies: All the procedures were followed in accordance with the ethical standard of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all the patients in the study., (© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Central post-stroke pain (CPSP) including thalamic pain is one of the most troublesome sequelae that can occur after a cerebrovascular accident. Although the prevalence of CPSP among stroke patients is relatively low, the persistent, often treatment-refractory, painful sensations can be a major problem and decrease the affected patient's quality of life. To better understand of the pathophysiological basis of CPSP, we developed and characterized a new mouse model of thalamic CPSP. This model is based on a hemorrhagic stroke lesion with collagenase in the ventral posterolateral nucleus of the thalamus. Histopathological analysis indicated that the thalamic hemorrhage produced a relatively confined lesion that destroys the tissue within the initial bleed, and also showed the presence of activated microglia adjacent to the core of hemorrhagic lesions. Behavioral analysis demonstrated that the animals displayed diclofenac-, morphine- or pregabalin-resistant mechanical allodynia and thermal hyperalgesia of the hind paw contralateral to the lesion for over 112 days. However, we found that minocycline, a microglial inhibitor, significantly ameliorated mechanical allodynia and thermal hyperalgesia. These results suggest that this model might be proved as a useful animal model for studying the neuropathology of thalamic syndrome, and developing improved therapeutics for CPSP., (Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Many vestibular schwannomas (VS) manifest intratumoral microhemorrhages whose underlying mechanisms are not fully understood. Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes the thrombin-mediated formation of activated protein C that inhibits thrombus formation. We investigated the existence of TM in VS and its potential role in the development of microhemorrhages. We used immunohistochemical staining to study the expression of TM in tissues derived from 25 patients with VS. Hemosiderin deposition was examined by Berlin blue staining and compared with the expression of TM. Vascular endothelial cells in all 25 VS tissues expressed TM. The TM-positive vessel ratio, calculated by dividing the number of TM-positive by the number of CD34-positive lumens, was significantly higher in hemosiderin-laden than hemosiderin-negative tissues (0.71 ± 0.17 vs. 0.53 ± 0.31, p = 0.049, Mann-Whitney U test). Our findings suggest a close relationship between the expression of TM and microhemorrhage in VS.

We determined distribution of plasma cells and IgG4/IgG index and factors associated with the index in intracranial inflammatory lesions. Specimens of nine patients were analyzed immunohistochemically using antibodies against CD45, CD68, CD3, CD4, CD8, CD20, CD138, lambda chain, kappa chain, IgG, IgG4, IL-1α, IL-6, IL-18, toll-like receptor (TLR) 2, TLR4, high-mobility group box 1 (HMGB1), tumor necrosis factor-alpha (TNF-α), myeloid differentiation factor 88 (MyD88), and anaplastic lymphoma kinase (ALK). The relationship between all the factors was assessed using Spearman's rank correlation coefficient (ρ). Negative ALK staining was observed in all the patients. Plasma cells were detected in eight patients with varying degrees. The highest number of neutrophils, but no plasma cells, was observed in a patient with the shortest history of inflammation. IgG4/IgG index was independent of the number of plasma cells. The index was relatively highly correlated with IL-6 (ρ = 0.7271) and TLR4 expression (ρ = 0.7246). IL-6 expression was highly correlated with TLR4 expression (ρ = 0.8042). IL-18 was maximally expressed in all the patients. TLR4 expression was strong, but TRL2 expression was weak. Positive HMGB1 staining was observed in all the patients, predominantly in the nuclei, but also in the cytoplasm in four patients. The cytoplasmic expression strongly correlated with IL-1α expression (ρ = 0.9583). The cytoplasmic colocalization of HMGB1 and IL-1α was histologically confirmed in cells with collapsing nuclei by the double-staining method. The IgG4/IgG indexes varied case by case. IL-6 and TLR4 expressions may influence IgG4/IgG index. The nuclei of cells with both IL-1α and HMGB1 expressions in the cytoplasm collapse in the cell death stage. The cooperative high expression of TLR4, IL-6, IL-18, MyD88 and HMGB1 suggest their critical roles in the inflammation circuit., (© 2012 Japanese Society of Neuropathology.)

The spontaneously epileptic rat (SER) begins to exhibit both tonic convulsions and absence seizures from 6 weeks of age and SERs have stable seizures after 10 weeks of age. Low-dose administrations of levetiracetam (LEV) for 4- to 5-weeks-old SERs which did not show spontaneous seizures reduced both seizures 5 weeks after termination of administration. The hippocampus of SER exhibited decreased CA3 neurons, sprouting of mossy fibers, and hyperexpression of the brain-derived neurotrophic factor (BDNF). We attempted prophylactic LEV administrations in preseizure-manifesting SERs to evaluate if such a treatment regimen would protect the hippocampal sclerosis-like changes observed in SERs. The osmotic mini-pump administered LEV dissolved in saline to 4-weeks-old SERs for 4 weeks at 2.5 μl/h. LEV was administered at 420 mg/ml for 4 weeks in Group A. In Group B, LEV was given at 420 mg/ml for the first 2 weeks followed by doubling the dosage (840 mg/ml) in the following 2 weeks. LEV administrations in preseizure-manifesting SERs reduced the decrease of CA3 neurons and mossy fibers sprouting at 10-11 weeks of age in both group A and B. LEV attenuated BDNF expression in inner molecular layers of the dentate gyrus, striatum radiatum, and CA3 in 10- to 11- and 14- to 15-weeks-old SERs. In group B, LEV decreased BDNF expression in hilus and CA1 of 10- to 11- weeks-old SER. The present results suggest that prophylactic treatment with LEV in preseizure-manifesting SERs inhibits hippocampal sclerosis-like neuronal degeneration and/or regeneration., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Wnts are secreted ligands that consist of 19 members in humans, regulate cell proliferation, differentiation, motility and fate in many stages including the embryonic stage and tumorigenesis. Wnts bind to cell surface receptors named Frizzleds and LRPs, and transduce their signals through β-catenin-dependent and -independent intracellular pathways. Gliomas are one of the most common intracranial tumors. Gliomas exhibit a progression associated with widespread infiltration into surrounding neuronal tissues. However, the molecular mechanisms that stimulate the invasion of glioma cells are not fully understood. We established two cell lines from human glioma cases and analyzed the expression of all Wnt and Frizzled members in these cell lines and other well-known glioma cell lines by real-time PCR study. The mRNA of Wnt-5a and -7b and Frizzled-2, -6 and -7 were overexpressed in glioma cells. The elevation of Wnt-5a expression was most remarkable. Although Wnt-5a is reported to have oncogenic and antioncogenic activity in several cancers, the role of Wnt-5a signaling in human glioma cells remains unclear. Immunohistochemical study also revealed high expression of Wnt-5a in 26 (79%) of 33 human glioma cases. The positivity of Wnt-5a expression was correlated with the clinical grade. Knockdown of Wnt-5a expression suppressed migration, invasion and expression of matrix metalloproteinase-2 of glioma cells. Reciprocally, treatment with purified Wnt-5a ligand resulted in stimulation of cell migration and invasion. MMP-2 inhibitor suppressed the Wnt-5a-dependent invasion of U251 cells. These results suggested that Wnt-5a is not only a prognostic factor but also a therapeutic target molecule in gliomas for preventing tumor cell infiltration., (© 2011 Japanese Cancer Association.)

Spontaneously epileptic rats (SER) are double mutants with both tonic convulsion and absence-like seizures from the age of 8 weeks. Hippocampal CA3 neurons in SER display a long-lasting depolarizing shift accompanied by repetitive firing (attributed to abnormalities of the Ca(2+) channels) with a single stimulation of the mossy fibers. In the present investigation, we examined if the seizure discharges of SER were correlated with the hippocampal abnormality of SER using electrophysiological and histological methods. In CA1 neurons of seizure-susceptible mature SER, higher-voltage (<8-11 V) stimulations induced a long depolarization shift (in 25% of neurons) with repetitive firing (in 12.5% of neurons). However, the tremor rat, one of the parent strains of SER, did not exhibit such abnormal firing in the CA3 region of the hippocampus. The number of CA3 neurons in SER was significantly (p<0.01) lower than that in tremor rats and Wistar rats, although no significant difference was established in the hilus. Sprouting of mossy fiber was observed in the dentate of mature SER; however, negligible staining was spotted in the dentate of both mature tremor and Wistar rats. Interestingly, expression of the brain-derived neurotrophic factor was higher in the hilus, CA3, and granular cell layer of dentate gyrus in SER than normal Wistar rats. The expression levels of TUNEL, bax, and Caspase-3 did not show significant changes between the SER and Wistar rats. SER exhibited hippocampal sclerosis-like changes which did not have enough potential for epileptogenesis. Repetitive tonic seizures and vulnerable CA3 neurons of SER could be involved in the induction of sclerosis-like changes in the hippocampus., (Copyright 2010 Elsevier B.V. All rights reserved.)

The present study was undertaken to analyze the acute and chronic effects of exercise on insulin sensitivity in elder diabetic patients using a horseback riding therapeutic equipment (Joba). The acute effects of exercise were examined by means of a single session of Joba riding that lasted for 30 min. The average glucose infusion rates (GIR) before and during exercise were regarded as an index of the insulin action in peripheral tissues by the euglycemic clamp. The chronic effects of exercise were studied by training the elder diabetic patients for 12 weeks using the Joba apparatus. The insulin sensitivity was determined pre- and post-training by a 90 min euglycemic clamp. In the acute study, average GIR during exercise was significantly higher than pre-exercise (7.8+/-0.4 versus 5.2+/-0.3 mg kg(-1)min(-1), P<0.01) and average GIR during recovery decreased to almost the same levels of pre-exercise (5.0+/-0.4 mg kg(-1)min(-1); P<0.01). The 12-week training resulted in a significant increase in the steady-state GIR (from 5.2+/-0.3 to 7.4+/-0.8 mg kg(-1)min(-1); P<0.05). The steady-state GIR after 12 weeks of detraining returned to pre-training levels (5.3+/-0.5 mg kg(-1)min(-1); P<0.05). In elder diabetic patients, mechanical horseback riding enhances the insulin-induced glucose uptake.

We investigated the effects of Goshajinkigan (GJG), a Chinese herbal medicine, on insulin sensitivity in patients with type 2 diabetes using the homeostasis model assessment of insulin resistance (HOMA-R) and the euglycemic insulin clamp procedure. Daily oral administration of GJG (7.5 g/day) was performed for 1 month in 71 type 2 diabetes patients: the GJG treatment group. HOMA-Rs were calculated before and after 1 month of GJG treatment and compared with those of 44 controls who were matched in terms of sex, age, body mass index (BMI) and HbA1c levels with the experimental group. In 64 patients out of the GJG treatment group, HOMA-R was calculated 1 month after discontinuation of treatment. In addition, euglycemic clamp was conducted in eight patients before and after the GJG treatment. HOMA-R was 4.78+/-0.37 (means+/-S.E.) before GJG treatment and significantly decreased to 4.02+/-0.25 after GJG treatment (P=0.019). No significant change was observed in the control group. HOMA-R returned to the pre-treatment level (P=0.018) 1 month after GJG treatment discontinuation. Glucose infusion rates and metabolic clearance rates determined by the high-dose euglycemic clamp increased after 1 month of GJG treatment (from 9.6+/-1.1 to 11.1+/-0.7 mg/kg/min, P=0.045 and from 7.9+/-0.8 to 9.1+/-0.8 ml/kg/min, P=0.046, respectively). These results indicate that GJG administration might be useful for improving insulin resistance in patients with type 2 diabetes.

Background: Anthropometric characteristics, lifestyle, and baseline biological markers of Japanese non-professional ultra-marathon runners have not been fully assessed., Methods: We evaluated anthropometric characteristics, lifestyle, and baseline biological markers of 180 Japanese amateur ultra-marathon runners (144 males [mean age: 50.5 +/- 9.4 (standard deviation) years] and 36 females [48.9 +/- 6.9]), and compared them with those of participants in a community heath check-up program and with the figures in the literature. We furthermore evaluated baseline blood indices according to monthly running distance with analysis of variance adjusted for age, body mass index, smoking and alcohol drinking habits., Results: The ultra-marathon runners demonstrated more favorable values for body mass index and bone density, and the proportion of smoking, and undertaking physical activity (for both sexes), eating breakfast (for males), and having daily bowel movements (for females), while greater proportion of alcohol drinking habit (for both sexes), than the comparison group. Average monthly running distances and standard deviations (km) were 257.2 +/- 128.9 for males and 209.0 +/- 86.2 for females. Male runners possessed beneficial markers, including lowered triglyceride and elevated high-density lipoprotein cholesterol, and their values showed hockey-stick (or inverse hockey-stick) patterns depending on their monthly running distance. Some subjects running more than 300 km/month exhibited signs of an over-reaching/training syndrome, including somewhat lowered hemoglobin, ferritin and white blood cell count, and elevated creatine kinase and lactate dehydrogenase., Conclusions: Together with a desirable lifestyle, Japanese non-professional ultra-marathon runners with vigorous exercise habit demonstrated a preferable health status according to biological indices.

Pulmonary actinomycosis is a rather rare chronic pulmonary infection. Its diagnosis may be difficult without biopsy, because its culture from sputum or bronchial secretion is rarely successful. We report a case of pulmonary actinomycosis diagnosed by means of TBLB. A 57-year-old man was admitted to our hospital because of hemosputum. The chest radiograph at the first visit revealed a nodular lesion in the right middle lobe. The biopsy examination showed sulfur granules of which PAS-positive mycelium was arranged in a radiating pattern. On the basis of these findings, we diagnosed pulmonary actinomycosis. So far, there have been only 4 reported cases of pulmonary actinomycosis diagnosed by TBLB in Japan. TBLB is worth trying in the diagnosis of pulmonary actinomycosis, because it can avoid surgical procedures, if successful.

To counteract insulin resistance, it is necessary to increase the utilization rate of fatty acids in blood and adipose tissue. The aim of the present study was to determine the relation between metabolic responses and exercise duration from changes in the respiratory exchange ratio (RER). The mean RER during 30 minutes of moderate exercise (mean pulse 115 beats/min) was 0.89 +/- 0.02, indicating no major change. Significant changes were observed in the levels of plasma glucose (PG), plasma free fatty acid (FFA), and plasma immunoreactive insulin (IRI) before and after exercise, demonstrating a decrease in PG and IRI, and an increase in FFA levels. However, the RER value indicated that carbohydrate was the dominant metabolic substrate; therefore, prolonged or repetitive brief and mild to moderate exercise is necessary to increase the utilization of fatty acids.

We report two patients with out-of-hospital cardiac arrest who recovered after hypothermia therapy. A 25-year-old man and a 16-year-old boy were transferred to our hospital after cardiopulmonary arrest due to idiopathic ventricular fibrillation and hypertrophic cardiomyopathy, respectively. We carried out hypothermia therapy using cooling blankets, and the patients were maintained at 32-33 degrees C for 96 and 36 h, respectively. After slow rewarming, they regained consciousness and recovered. During hypothermia, hypokalemia and arrhythmia occurred. Their arrest times (no spontaneous circulation and no CPR) were 10 min and 8 min, and CPR times (no spontaneous circulation while CPR was being performed) were 24 min and 20 min, respectively. In cases where the duration of ischemia is prolonged, the prognosis is expected to be poor. Therefore, we believe that hypothermia therapy is beneficial for such patients.

Cardiac function at the time of ventricular premature contractions (VPC) is influenced by the coupling interval or the site of those origin. Clinical and experimental studies of the effects of VPC on intracardiac pressure dynamics have been performed; however, little is known about left ventricular blood flow dynamics. This study was attempted to determine the characteristics of blood flow dynamics in respect to the site of origin of VPC using pulsed Doppler echocardiography. The subjects consisted of 18 cases with VPC but without apparent organic heart disease. Seven cases had VPCs with a left bundle branch block pattern suggesting possible origin in the right ventricle. The other 11 cases had VPCs with a right bundle branch block pattern indicating the left ventricular origin. With the probe in the apical position, the blood flow patterns of the left ventricular outflow, central and inflow tracts were examined. The results were as follows; 1. Except for one case with shortened coupling interval, all six cases with VPCs originated from the right ventricle showed preservation of left ventricular ejection flow. 2. In two of the three cases with VPC which originated from the left ventricle and with left axis deviation, systolic flow in the left ventricular central area showed "back flow" to the apex. Ejection flow at the outflow tract was markedly diminished or disappeared in all three cases. 3. In all eight cases with VPC which originated from the left ventricle and with right axis deviation, ejection flow was slightly disturbed both in the left ventricular outflow and in the central area. 4. Ejection flow volume assessed by velocity integral indicated similar dynamics as did the ejection flow velocity. 5. In left ventriculography, asynchrony due to dyskinetic motion of the anteroapical wall was observed at the times of VPCs with left axis deviation. In conclusion, the patterns of left ventricular ejection flow dynamics depend on the site of origin of VPCs. This disturbed flow is more apparent in VPCs originating from the left ventricle compared to the right ventricle. This is especially true in cases with left axis deviation, in which VPCs arise from the posterior site of the left ventricle.