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In 2020, two mRNA-based vaccines, encoding the full length of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, have been introduced for control of the coronavirus disease (COVID-19) pandemic1,2. However, reactogenicity, such as fever, caused by innate immune responses to the vaccine formulation remains to be improved. Here, we optimized a lipid nanoparticle (LNP)-based mRNA vaccine candidate, encoding the SARS-CoV-2 spike protein receptor-binding domain (LNP-mRNA-RBD), which showed improved immunogenicity by removing reactogenic materials from the vaccine formulation and protective potential against SARS-CoV-2 infection in cynomolgus macaques. LNP-mRNA-RBD induced robust antigen-specific B cells and follicular helper T cells in the BALB/c strain but not in the C57BL/6 strain; the two strains have contrasting abilities to induce type I interferon production by dendritic cells. Removal of reactogenic materials from original synthesized mRNA by HPLC reduced type I interferon (IFN) production by dendritic cells, which improved immunogenicity. Immunization of cynomolgus macaques with an LNP encapsulating HPLC-purified mRNA induced robust anti-RBD IgG in the plasma and in various mucosal areas, including airways, thereby conferring protection against SARS-CoV-2 infection. Therefore, fine-tuning the balance between the immunogenic and reactogenic activity of mRNA-based vaccine formulations may offer safer and more efficacious outcomes.

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BACKGROUND: Although the clinicopathological significance of serum p53 antibodies (s-p53-Abs) in esophageal cancer have been evaluated previously, previous reports only analyzed around 100-200 patients. This study was a multi-institutional study promoted by the Japan Esophageal Society to evaluate the clinical significance of preoperative s-p53-Ab status and antibody titers in 1487 esophageal cancer patients without neoadjuvant therapy. METHODS: A total of 1487 patients with esophageal squamous cell carcinoma surgically treated between 2008 and 2016 in 15 hospitals in Japan were enrolled. The cut-off value to classify the patients into s-p53-Ab positive and negative groups was 1.30 U/ml. A receiver operating characteristic curve was constructed to assess the s-p53-Abs cut-off levels to differentiate poor prognosis among the s-p53-Ab positive group. Univariate and multivariate analyses were used to evaluate the clinicopathological and prognostic significance of s-p53-Ab status and titers. RESULTS: Although s-p53-Ab status was significantly associated with tumor depth (P = 0.002), nodal status (P = 0.027), and pathological stage (P = 0.002). The s-p53-Ab positive status was not significantly associated with poor overall survival (P = 0.699). Using 9.82 U/ml as a cut-off, the high s-p53-Ab titer group showed a significantly worse overall survival than the low s-p53-Ab titer group (P = 0.038). However, the difference was not significant in the multivariate analysis. CONCLUSION: The presence of s-p53-Abs was associated with tumor progression. Although high s-p53-Ab titers more than 9.82 U/ml, might be associated with poor prognosis for patients with esophageal squamous cell carcinoma, it was not an independent risk factor.

Asunto(s)

Proteínas de Unión al ADN , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Biomarcadores de Tumor/sangre , Proteínas de Unión al ADN/sangre , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/cirugía , Humanos , Pronóstico , Proteína p53 Supresora de Tumor/sangre

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Congenital toxoplasmosis (CT) and pregnancy malaria (PM) have been individually reported to cause severe negative outcomes in pregnancies but the diagnostic method is still debatable. This study sought to estimate the prevalence of PM and CT single and co-infections in pregnant women by using various specimens including plasma and placental tissues. Genomic DNA extracted from the placenta, cord blood or blood of mothers was tested by PCR. Conventional method of immunodiagnosis was done for CT. We tested 79 pregnant women aged 18-42 years (mean: 28±1.06). Prevalence of Plasmodium falciparum infection determined by PCR on mother's peripheral blood specimen was 6.3% whiles 57.3% was recorded for placental tissues (p<0.01). PCR testing for placental tissues showed 29.2% positive for Toxoplasma gondii, whiles 76.0% of mothers had serum IgG against T. gondii. It should be noted that 6.3% of the placental tissues showed PCR positive for SAG 3, a marker of active infection in T. gondii. Although there were no enhanced foetal disorders at birth in our study, there is a possibility of active transmission of T. gondii from mothers to foetuses even in immune mothers. Our study suggests that foetuses were exposed to P. falciparum and T. gondii in utero, and placenta is a better specimen for PCR in detecting such episodes. In cases of PCR-positive samples, clinical follow-up after birth may be important.

Asunto(s)

Malaria Falciparum/epidemiología , Complicaciones Parasitarias del Embarazo/diagnóstico , Complicaciones Parasitarias del Embarazo/epidemiología , Toxoplasmosis Congénita/diagnóstico , Toxoplasmosis Congénita/epidemiología , Adolescente , Adulto , Anticuerpos Antiprotozoarios/sangre , Coinfección , ADN Protozoario/análisis , Femenino , Humanos , Inmunoglobulina G/sangre , Recién Nacido , Malaria Falciparum/diagnóstico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Placenta/parasitología , Plasmodium falciparum/inmunología , Plasmodium falciparum/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Periodo Posparto , Embarazo , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Complicaciones Parasitarias del Embarazo/parasitología , Toxoplasma/inmunología , Toxoplasma/aislamiento & purificación , Toxoplasmosis Congénita/tratamiento farmacológico , Toxoplasmosis Congénita/parasitología , Adulto Joven

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Mosquito eggs laid within two hours are necessary for transgenic (injection) studies, because mosquito eggs become hard after that period. Thus, in order to have eggs available within this two-hour window, it is important to understand the ovipositional behavior of <i>Anopheles gambiae s.s.</i>. In the present study, the ovipositional behavior of <i>An. gambiae s.s.</i> (Kisumu) was investigated in several different conditions: age of mosquitoes, time post blood meal to access oviposition substrate, and light conditions. Two groups of mosquitoes, 3–5 days old and 9–11 days old were blood-fed. For those mosquito groups, an oviposition dish was set either at 48 hours or 72 hours after the blood meal either in a light condition or in an artificial dark condition. The number of laid eggs was compared among the different conditions. The 3–5 day-old mosquitoes apparently produced a higher number of eggs than 9–11 day-old mosquitoes, while there was no significant difference between the two groups. The number of laid eggs per one surviving blood-fed mosquito in the dark condition was significantly higher than that in the light condition (<i>p</i> = 0.03). Providing an oviposition dish at 72 hours after blood meal resulted in a significantly higher number of laid eggs per one surviving blood-fed mosquito than at 48 hours after blood meal (<i>p</i> = 0.03). In conclusion, the optimal condition to have readily available egg supply for transgenic analysis was as follows: 3–5 day-old mosquitoes with an oviposition dish placed at 72 hours after the blood meal in a dark environment.

RESUMEN

Mosquito eggs laid within two hours are necessary for transgenic (injection) studies, because mosquito eggs become hard after that period. Thus, in order to have eggs available within this two-hour window, it is important for transgenic studies to understand the ovipositional behavior of <i>Anopheles gambiae s.s.</i>. In the present study, the ovipositional behavior of <i>An. gambiae s.s.</i> (Kisumu) was investigated in several different conditions: age of mosquitoes, time post blood meal to access oviposition substrate, and light conditions. Two groups of mosquitoes, 3–5 day old and 9–11 day old mosquitoes were blood-fed. For those mosquito groups, an oviposition dish was set either at 48 hours or 72 hours after the blood meal either in a light condition or in an artificial dark condition. The number of laid eggs was compared among different conditions. The 3–5 day old mosquitoes apparently produced a higher number of eggs than 9–11 day old ones, while there was no significant difference between the 2 groups. The number of laid eggs per one surviving blood-fed mosquito in the dark condition was significantly higher than that in the light condition (<i>p</i> = 0.03). Providing an oviposition dish at 72 hours after blood meal resulted in a significantly higher number of laid eggs per one surviving blood-fed mosquito compared to providing an oviposition dish at 48 hours after blood meal (<i>p</i> = 0.03). In conclusion, the optimal condition to have readily available egg supply in the present study for transgenic analysis was as follows: 3–5 days old mosquitoes with an oviposition dish placed at 72 hours after the blood meal in a dark environment.

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The removal of aspiration objects is often required for aspiration, which takes place at the time of a video fluoroscopic examination of swallowing (VF) for the assessment of dysphagia rehabilitation. We report our approach against correspondence for aspiration at VF.　　As subjects for this report, we sampled 6 patients (average age: 78.3±3.0, four males and two females) from 19 patients, who had aspiration of barium sulfate or meal with barium contrast medium at the time of VF form October 1, 2009, to March 31, 2011. For the first step of correspondence for aspiration at VF, we dealt with coughing, huffing, suction and postural drainage under the guidance of a Speech-Language-Hearing Therapist and, depending on the case, a Physical Therapist who dealt with chest physical therapy. When expectoration was found impossible, we checked to see if it was necessary to perform biphasic cuirass ventilation with a clinical engineer. We assessed the chest X-ray films and existence or non-existence of expectoration immediately after aspiration, and fever, inflammatory response, respiratory symptoms and gastrointestinal symptoms one week after the examination, and retrospectively checked the influence of aspiration.　　As a result, three patients had residue as revealed on chest X-ray films, and the three remaining patients had none. For the former three patients, we intervened in a team approach and succeeded in removing the residue from two patients (one with initial correspondence, and the other with execution by the Physical Therapist). Though two patients had fever and inflammatory response one week later, It was hardly possible that aspiration at the time of VF became a direct cause. No patient had either the respiratory or gastrointestinal symptom.　　Correspondence for aspiration was attained by establishing a team approach system. Even if a patient had heavy aspiration, it was not reflected on chest X-ray films, depending on the case, and therefore deliberation was required for correspondence.

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Dengue virus is an arthropod-borne virus transmitted by <i>Aedes</i> mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essential for an understanding of dengue pathology. In addition, understanding the molecular mechanism(s) of virus entry is crucial for the development of effective new therapies to treat dengue patients. Binding of dengue virus to its receptor molecules is mediated through a viral envelope glycoprotein, termed E protein. We present a summary and describe the structures, binding properties, and pathological relevance of dengue virus receptor molecules proposed to date. In mammalian cells, there are many candidate molecules that may act as receptors, such as sulfated glycosaminoglycans (GAGs), lectins that recognize carbohydrates, glycosphingolipid (GSL), proteins with chaperone activity, laminin-binding proteins, and other uncharacterized proteins. There are also several lines of evidence for receptor molecules such as GSLs, proteins with chaperone activity, laminin-binding proteins, and other uncharacterized proteins in mosquito cells and organs. This review focuses on several molecules involved in carbohydrate-dependent binding of the virus.

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BACKGROUND: The number of adrenocortical tumors discovered incidentally has recently increased owing to the advent of imaging techniques. The most important diagnostic point in evaluation of resected specimens of these tumors is to discern malignancy to determine postoperative management of the patients. OBJECTIVE/METHODS: To determine what the effective methods of discerning malignancy in resected specimens of adrenocortical tumors are at this juncture. To provide relevant and practical information pertinent to those involved in the management of patients with adrenocortical tumors. CONCLUSION: Careful macroscopic evaluation, including the selection of the specimens submitted and application of the criteria of Weiss for histological diagnosis, is still considered the 'gold standard' for diagnosis of adrenocortical carcinoma. However, it is important to recognize its limitations in the diagnosis of adrenocortical oncocytoma and pediatric adrenocortical tumors. The auxiliary methods that may be of clinical relevance at this juncture include the analysis of the Ki67/MIB-1 labeling index and IGF-II expression in the tumors.

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<p><b>OBJECTIVES</b>To assess the validity of the criterion of overweight for Asian people that is recommended by Western Pacific Region of the World Health Organization.</p><p><b>METHODS</b>We carried out a cross-sectional analysis of the association between the criterion of overweight for ethnic Asian people--body mass indices (BMI) of 23.0-24.9 kg/m(2)--and the presence of obesity-related metabolic disorders among middle-aged Japanese men (n = 974, age range 51-59).</p><p><b>RESULTS</b>The odds ratios (95% confidence interval) of overweight to those with normal weight (BMI < 23.0 kg/m(2)) were 1.61 (1.11-2.33) for the presence of impaired glucose tolerance, 1.95 (1.30-2.93) for hypertension, 2.22 (1.63-3.03) for hypercholesterolemia, 2.83 (2.02-3.97) for hypertriglyceridemia, and 2.06 (1.06-4.00) for hyperuricemia. Overweight was not associated with the presence of type 2 diabetes or with high gamma-glutamyl transferase in the present study (odds ratios: 1.09 and 1.05, respectively). Adjustment for age, rank, and lifestyle factors affected the results only slightly.</p><p><b>CONCLUSIONS</b>Based on these results, we conclude that the Asian criterion of overweight appears to be rational in terms of its association with obesity-related metabolic disorders in male personnel of the Japan Self-Defense Forces in their fifties.</p>

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<p><b>OBJECTIVE</b>To elucidate the prevalence rate of metabolic disorders among subjects with asymptomatic colonic diverticulum.</p><p><b>METHODS</b>We carried out a cross-sectional analysis of the association between colonic diverticulum and selected metabolic disorders among the male personnel of the Self-Defense Forces who underwent total colonoscopy as part of their retirement check-up (age range, 51-59 years).</p><p><b>RESULTS</b>The prevalence rate of colonic diverticulum was 10.2% among the population studied. The scores of lifestyle factors including those of cigarette smoking and alcohol consumption were similar between the subjects with colonic diverticulum and those without it. Type 2 diabetes (21.6% vs 14.0%, P=0.047) and hypertension (30.9% vs 19.8%, P=0.011) were more prevalent among the subjects with colonic diverticulum than those without it. The prevalence rates of obesity, dyslipidemia, hyperuricemia, and impaired glucose tolerance were similar between the two groups.</p><p><b>CONCLUSION</b>The prevalence rates of type 2 diabetes and hypertension are elevated among the middle-aged male subjects with asymptomatic colonic diverticulum. The results may partly explain the reported association between colonic diverticulum and cardiovascular disease.</p>

RESUMEN

Objective: To elucidate the prevalence rate of metabolic disorders among subjects with asymptomatic colonic diverticulum. Methods: We carried out a cross-sectional analysis of the association between colonic diverticulum and selected metabolic disorders among the male personnel of the Self-Defense Forces who underwent total colonoscopy as part of their retirement check-up (age range, 51-59 years). Results: The prevalence rate of colonic diverticulum was 10.2% among the population studied. The scores of lifestyle factors including those of cigarette smoking and alcohol consumption were similar between the subjects with colonic diverticulum and those without it. Type 2 diabetes (21.6% vs 14.0%, P=0.047) and hypertension (30.9% vs 19.8%, P=0.011) were more prevalent among the subjects with colonic diverticulum than those without it. The prevalence rates of obesity, dyslipidemia, hyperuricemia, and impaired glucose tolerance were similar between the two groups. Conclusion: The prevalence rates of type 2 diabetes and hypertension are elevated among the middle-aged male subjects with asymptomatic colonic diverticulum. The results may partly explain the reported association between colonic diverticulum and cardiovascular disease.

Asunto(s)

Divertículo

RESUMEN

The decrease of balance capacity is considered as a high risk factor of fall accident, so it is important for the middle-aged and elderly people to keep balance capacity on a high level. In this study, we investigated the effects of aqua exercise on dynamic and static balance function. Thirty-two middle-aged women (56.6±8.1 years) participated a 60-min aqua exercise program three times per week for eight weeks. After exercise intervention, body weight, body mass index, grip strength, side step, shuttle stamina walking test were significantly improved (p<0.05-0.001). Functional reach (p<0.001) and total length of centroid shake with eye close condition (p<0.05) was significantly improved, but with eye open condition was not changed. However, when we evaluate the total length of centroid shake by T-score, static balance performance with eye open and close condition was significantly (p<0.05) improved in the below average groups. In addition, measurement value of functional reach was also improved in these groups. These results indicate that aqua exercise benefits not only physical muscle strength and endurance capacity, but also balance function in middle-aged women. Particularly aqua exercise is more effective for the subjects with lower static balance function before intervention.

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We investigated the relationship between body weight reduction and intensity of daily physical activities assessed with 3-dimensional accelerometer during a 3-month exercise program. Twenty-six middle-aged women (58.1±7.4 yrs.) participated in this study. Participants underwent a 90-min endurance exercise intervention once a week, and a 3-dimensionsal accelerometer was attached through the program. Body weight (BW), body mass index, fat mass and percent body fat were reduced significantly (p<0.001), while diastolic blood pressure (p<0.01) and shuttle stamina walking test (p<0.05) improved significantly after the exercise intervention. Moreover, a significant negative correlation was observed between the changes in BW and total activity time (TAT) per day of more than 3METs (TAT≥3METs)(r=−0.580, p<0.01) and TAT≥4METs (r=−0.627, p<0.001). To the contrary, the daily steps and the TAT≥2METs were not related to the changes in BW. After adjusting daily steps, TAT≥3METs (β=−0.630, p<0.01) and TAT≥4METs (β=−0.659, p<0.01) were still significantly related to the changes in BW. These results indicate that weight reduction has a much closer relationship with exercise intensity than daily steps. It is important to keep both quantity and intensity of exercise in the unsupervised exercise program aimed at weight reduction.

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[Case 1] At 37 weeks and 5 days, a 27-year old woman was admitted to our clinic due to spontaneous rupture of the membranes. Her first pregnancy had come to term in a cesarean section delivery, because of toxemia and the breech presentation. This time, she wanted to deliver spontaneously. She didn't go into spontaneous labor, however, 44 hours after rupture of her membranes. Past history included the cesarean section, so labor induction with oxytocin or prostaglandin was not attempted. Active labor was established after administered keishibukuryogan as a saiseito, and she delivered spontaneously at 38 weeks and 1 day.<br>[Case 2] At 39 weeks and 5 days, a 33-year old woman was admitted to our clinic, due to elective induction of labor. Her first pregnancy had come to term in a labor induction with oxytocin for the uterine inertia. In this pregnancy she wanted to deliver without the use of oxytocin. Active labor was established after administered Keishi-bukuryogan as a Saisei-to, and she delivered spontaneously at the same 39 weeks and 5 days.<br>The present cases suggest that keishibukuryogan may be effective for establishment of labor, not to say a labor inducer or stimulator such as oxytocin and prostaglandin.

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Aim:The usefulness of high-density barium, which was made to 150w/v% (MIX150), was examined to obtain better radiographs of the intestines. Methods: “MIX150” was compared with existing pharmaceutical “BAM100” to evaluate x-ray images (barium adhesion, dryness evaluation). MIX150 was used in 232 patients (mean age 56 years), while BAM 100 in 210 patients (mean age 55 years). Results: In terms of adhesion, MIX150 was excellent in the the cecum significantly and in dryness evaluation, in the entire region of the colon. Conclusion: High-density barium (150w/v%) was useful for enhancing the quality of radiographic images.

Asunto(s)

Rayos X , Bario

RESUMEN

The purpose of this study was to investigate the effect of constant endurance cycling exercise below Ventilatory Threshold (VT), under different pedal rate/torque regulations (PTR), on muscle oxygenation, as well as cardio-respiratory function and energy metabolism. Eight healthy male adults participated in the study for three tests. The first test was to examine the maximum oxygen uptake (VO₂max) using a ramp loading measurement of 60 rpm, 20 watt/min ; and an individual 80%VT load was obtained. The second and third tests (random) were to measure heart rate (HR), blood pressure (MAP), expired gas and NIRS data before, during and after 30 min 80%VT constant cycling exercise with low pedal rate/high torque (LPHT : 32 rpm, 23.3±6.0Nm) or high pedal rate/low torque (HPLT : 79rpm, 9.4±2.4Nm). As a result, HPLT showed higher values in HR (p<0.001), MAP (p<0.001), VO₂ (p<0.001), VCO₂ (p<0.001) and RER (p<0.05), than LPHT ; but LPHT showed a higher fat consumption rate than HPLT (p<0.05). Significant PTR effect were recognized for the parameters of the tissue hemoglobin index (THI) (p<0.001) and oxygenation hemoglobin (ΔO₂Hb) (p<0.01) ; and both indicated higher values for HPLT than LPHT ; but LPHT showed insignificantly (p=0.066) higher de-oxygenation hemoglobin (ΔHHb) than HPLT. Moreover, the significant time effects of THI and ΔO₂Hb were also recognized. In conclusion, this study indicated that during constant cycling exercise below VT, HPLT might result in greater muscle blood volume, higher muscle oxygenation concentration and higher HR and VO₂ compared with LPHT. These results suggest that, HPLT might be effective in alleviating the working load on lower limbs, as well as promoting muscle oxygenation, cardiorespiratory function (systemic oxygen supply) and energy metabolism. Therefore, HPLT constant cycling exercise below VT could be used in a rehabilitation program as a beneficial exercise for elderly people with decreasing muscle strength in their lower limbs.

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Coronary artery disease (CAD) was evaluated by noninvasive examination in abdominal aortic aneurysm (AAA) patients. A simultaneous operation or a 2-staged operation was performed depending on the seriousness of the condition when both diseases were combined. A total of 36 patients underwent elective repair of AAA between 1996 and 2001. Coronary angiography (CAG) was performed only in patients with suspected CAD by dipyridamole myocardial scintigraphy. Significant CAD was found in 8 patients. Simultaneous operation was performed in 4 patients, and off-pump coronary artery bypass grafting (OPCAB) was performed in all cases of simultaneous operation. In 4 patients receiving 2-staged operations, 1 standard coronary artery bypass grafting (CABG), 1 OPCAB and 2 percutaneous transluminal coronary angioplasties (PTCA) were performed prior to AAA surgery. Twenty-eight patients underwent only AAA operation. Though there were no incidents of perioperative myocardial infarction or cardiac related deaths in this group, 2 patients died due to other causes (hemorrhage and duodenal perforation). In the 8 patients associated with CAD, 1 patient died of MNMS after simultaneous operation. The other 7 patients revived their social function soon of the discharge. Dipyridamole cardiac scintigraphy was considered to be an effective examination for evaluation of CAD in AAA patients. There was no need to perform CAG in all AAA patients. The policy of choosing simultaneous operation or 2-staged operation according to the seriousness of the 2 diseases seemed to be appropriate.

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In dialysis cases complicated with ischemic heart disease, there are many problems, such as poor preoperative general condition, calcified aorta, water-electrolyte control, and the necessity for other simultaneous operations. Off-pump coronary artery bypass grafting (OPCAB) was considered very useful in coping with these problems. OPCAB, employed in five cases, was compared with conventional coronary artery bypass grafting with extracorporeal circulation (ECC group, 9 cases). Regarding preoperative coexisting diseases, collagen diseases, porcelain aorta, cerebral infarction, and others were recognized in the OPCAB group in 3 of 5 cases. Emergency operations were performed in 5 of 9 cases in the ECC group, and in 2 of 5 cases in the OPCAB group. The bypass number (3.2 vs. 2.0) and complete revascularization rate (7 of 9 vs. 2 of 5), tended to be higher in the ECC group. The OPCAP group was significantly superior in blood transfusion (6.7 vs. 3.0u), postoperative CK-MB (63 vs. 33u), and the postoperative usual hemodialysis commencing time (4.2 vs. 1.0 day). Concerning use of postoperative IABP (3 of 9 vs. 0 of 5), and postoperative ventilator weaning time (2.7 vs. 1.0 day), a good tendency was shown in the OPCAB group. Although a high mortality rate (2 of 5) was recognized in OPCAB group compared with ECC group (1 of 9), those were urgent cases who had a very poor preoperative condition, and both cases suffered non-cardiac deaths. Excluding special cases, such as an unstable hemodynamic state requiring assisted circulation, and poor coronary run off, OPCAB seems useful for the treatment of coronary artery disease in dialysis patients.

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Pulmonary vein isolation procedure was performed for atrial fibrillation associated with mitral valve disease in twelve patients. This simple procedure consisted of only isolation of the four pulmonary veins. Combined mitral valve surgery consisted of mitral valve plasty, mitral valve replacement with or without aortic valve replacement and tricuspid annuloplasty. Ten patients returned to a sinus rhythm. Two patients required DDD pacemaker implant for sick sinus syndrome. Left atrial contraction was detected in eight cases by trans-esophageal echography. Compared with the maze procedure, this operation was less invasive and preserved atrial appendage, helping to maintain normal secretion of atrial natriuretic peptide. This study suggests that the pulmonary vein isolation procedure may be an effective and simple maneuver for atrial fibrillation associated with mitral valvular disease.

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A 26-year-old woman visited our hospital complaining of infertility. Initially treatment was given based on clomiphene for induction of ovulation. However, she suffered from ovarian hyperstimulation syndrome (OHSS) due to the clomiphene, accompanied by abdominal pain. Unkei-to was decided on as the best mode of treatment since clomiphene could not be continued. The patient's basal body temperature (BBT) returned to its biphasic cycle. Three months later, natural pregnancy occurred that resulted in the birth of a healthy boy by normal delivery.<br>Unkei-to is frequently given for a variety of gynecological disorders, such as irregular menstruation, dysmenorrhea, discharge, climacteric disturbance, etc.<br>Although induction of ovulation is often a necessary and effective infertility therapy, multiple pregnancies and OHSS can be problematic. The present case suggests that Unkei-to may be effective for infertility involving clomiphene-induced OHSS