Congenital anomalies induced by triamcinolone acetonide in murine embryos.

INTRODUCTION: We have studied the morphogenesis of anorectal malformations in mice using retinoids. Several investigators have reported an interaction between glucocorticoids and retinoids. It was supposed that glucocorticoids had some effects on the morphogenesis of murine embryos similar to retinoids. Therefore, we investigated alterations in the morphogenesis of murine embryos after triamcinolone acetonide (TAC) administration. MATERIAL AND METHODS: TAC was administered in a single dose (15 mg/kg or 30 mg/kg body weight) to pregnant ICR-SLC mice on embryonic day 7 (E7), 8, 9, and 10. They were sacrificed on E18, and fetuses were examined for internal and external malformations. Randomly chosen fetuses were embedded in paraffin for immunohistochemical staining of the glucocorticoid receptor (GR). RESULTS: The groups given 15 mg/kg TAC had one peak in the incidence of cleft palate on E9 (100 %) and the groups given 30 mg/kg TAC showed a biphasic pattern in the incidence of cleft palate on E7 and E10. No other anomalies were found. GR expression was marked in the subepithelial layer of palatal processes in the treated specimens. CONCLUSION: The group given 15 mg/kg TAC on E9 provided a good model of cleft palate in ICR-SLC mice, and cleft palate was probably induced by various factors including disturbance of the bone morphogenetic protein (BMP) signaling pathway, shown by GR overexpression.

Increased plasma fibrinopeptide A levels during attacks induced by hyperventilation in patients with coronary vasospastic angina.

Plasma fibrinopeptide A levels, beta-thromboglobulin levels and platelet factor 4 levels were estimated by enzyme-linked immunosorbent assay before and after hyperventilation in 12 patients with coronary vasospastic angina and in 12 control subjects matched for age and gender. In all 12 study patients, anginal attacks accompanied by electrocardiographic (ECG) changes (ST elevation in 11 patients and ST depression in 1 patient) were induced by hyperventilation. Coronary angiography was performed on 11 of the 12 patients, and coronary artery spasm with the same ECG changes was induced by intracoronary injection of acetylcholine in all 11. The plasma fibrinopeptide A levels increased significantly from 2.0 +/- 0.4 to 10.0 +/- 2.4 ng/ml during the attack (p less than 0.001) in the study patients, but remained unchanged before and after hyperventilation in the control subjects. The plasma levels of beta-thromboglobulin and platelet factor 4 remained unchanged after hyperventilation in both groups. Our data indicate that coronary artery spasm may induce thrombin generation and trigger thrombus formation in the coronary artery.

Hyperventilation-induced simultaneous multivessel coronary spasm in patients with variant angina: an echocardiographic and arteriographic study.

Left ventricular wall motion abnormalities during an attack of coronary spasm induced by hyperventilation were examined with use of two-dimensional echocardiography in 27 patients with variant angina. Transient abnormal wall motion (asynergy) confined to one coronary artery region was found in 18 of the 27 patients and transient abnormal motion extending over more than one coronary artery region in the remaining 9 patients. Spasm of more than one major coronary artery was demonstrated separately by coronary arteriography during an attack induced by injection of acetylcholine or ergonovine in seven of the nine patients who manifested asynergy in more than one coronary artery region. In one patient, spasm was demonstrated in one major coronary artery, and the other coronary arteries were severely stenosed or occluded organically. In the remaining patient, acetylcholine was not injected into both arteries; however, the attack was sometimes associated with ST segment elevation in the anterior leads and at other times in the inferior leads. Therefore, simultaneous multivessel coronary spasm seems to have occurred in eight of the nine patients who exhibited asynergy in more than one coronary artery region. The 8 patients with simultaneous multivessel coronary spasm had a higher degree and longer duration of ST segment elevation and a higher incidence of arrhythmias during the attack induced by hyperventilation than did the 19 patients with single vessel coronary spasm, and all of them had no significant organic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity and specificity of intracoronary injection of acetylcholine for the induction of coronary artery spasm.

Intracoronary injection of acetylcholine has been shown to induce coronary spasm in patients with variant angina. To examine its sensitivity and specificity, incremental doses of acetylcholine (20, 50 and 100 micrograms into the left coronary artery and 20 and 50 micrograms into the right coronary artery) were injected into the coronary artery or arteries in 70 patients with variant angina (Group 1) (mean age 57 years) and 93 patients without variant angina or angina at rest (Group 2) (mean age 54 years). Forty patients of the latter group had atypical chest pain, 16 cardiomyopathy, 14 arrhythmia, 11 valvular disease, 7 stable effort angina due to advanced coronary artery disease, 3 congenital heart disease and 2 hypertension. A temporary cardiac pacemaker set at 40 to 50 beats/min was positioned in the right ventricle. Coronary spasm was defined as total occlusion or severe vasoconstriction associated with chest pain or ischemic ST changes on the electrocardiogram or both. In Group 1, acetylcholine induced spasm in 63 (90%) of the 70 patients in the artery or arteries predicted to be responsible for spontaneous attacks. In Group 2, acetylcholine induced coronary spasm only in one patient with effort angina and advanced coronary artery disease although lesser degrees of vasoconstriction (less than or equal to 75% of the luminal diameter) occurred in most patients after acetylcholine (specificity of acetylcholine thus was 99%). In conclusion, intracoronary injection of acetylcholine is sensitive and reliable for the induction of coronary spasm.

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina.

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.

Mediastinoscopic extended thymectomy for pediatric patients with myasthenia gravis.

BACKGROUND: Extended thymectomy is indicated for children with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for mediastinoscopic extended thymectomy (MET) on children with MG. METHOD: A total of 14 children underwent MET at Kanagawa Children's Medical Center between 2005 and 2013. A mediastinal operation field was made by a V-shaped hook infrasternally to extirpate the thymus with adipose tissue around the thymus. RESULTS: The operation time and the amount of blood loss were 182±44 minutes and 34±43 ml, respectively. Postoperative complications, in the form of transient paralysis of the right recurrent nerve, occurred in 2 patients. The median length of postoperative hospital stay was 4.5 days. After MET, 6 patients achieved complete remission and 7 patients achieved steroid dose reduction, but no improvement was seen in 1 patient. CONCLUSIONS: This procedure offers the advantage of good surgical access for dissection around the bilateral phrenic nerves in extended total thymectomy, while achieving good cosmetic results.

Entrainment of idiopathic ventricular tachycardia of left ventricular origin with evidence for reentry with an area of slow conduction and effect of verapamil.

Recurrent sustained ventricular tachycardia (VT) with QRS morphology of the right bundle branch block and left axis deviation was studied in 4 patients without any underlying heart diseases. The mean VT rate was 155 beats/min and the endocardial catheter mapping during VT showed the earliest activation site at the left ventricular lateral wall near the apex. In all patients, rapid pacing from the right ventricular outflow tract during VT resulted in constant fusion beats except for the last entrained beat (thus VT was entrained), while pacing from the right ventricular apex and from the earliest activation site failed to demonstrate entrainment. During entrainment from the right ventricular outflow tract (mean pacing rate 168 beats/min), conduction intervals from the pacing site to the earliest activation site (St-A interval) and to the right ventricular apex (St-B interval) were measured in 3 patients. The St-A intervals were 400, 410 and 440 ms and the St-B intervals were 80, 70 and 90 ms, respectively. A small dose of verapamil (1.0 mg) was administered during VT, which resulted in a decrease of VT rate by a mean of 23 beats/min. During entrainment from the right ventricular outflow tract the St-A interval was prolonged in all 3 patients while the St-B interval remained the same. In conclusion, the mechanism of this VT was best explained by reentry with an area of slow conduction. Verapamil slowed the rate of VT by prolonging conduction within the area of slow conduction. Tachycardia entrainment makes possible a selective examination of antiarrhythmic drug effect on the area of slow conduction within the reentry circuit of VT.

Magnesium deficiency detected by intravenous loading test in variant angina pectoris.

To study whether magnesium (Mg) deficiency is present in patients with variant angina, 24-hour Mg retention of low dose Mg (0.2 mEq/kg lean body weight) administered intravenously over 4 hours in 20 patients with variant angina was examined. No patient had received calcium antagonists before or during the study. All had attacks of chest pain associated with ST elevation on electrocardiograms. Twenty-one subjects without ischemic heart disease were studied as control subjects. Ten patients with variant angina were restudied 10 to 529 days (mean 235 +/- 30) after the treatment with calcium antagonists (diltiazem 120 to 240 or nifedipine 40 to 80 mg/day), which resulted in complete suppression of anginal attacks. The mean serum Mg concentrations in the patients with variant angina and the control subjects were 2.1 +/- 0.05 and 2.1 +/- 0.03 mg/dl, respectively (difference not significant). However, 24-hour Mg retention in the patients with variant angina was 60 +/- 5%, while that in the control subjects was 36 +/- 3% (p less than 0.001), suggesting that Mg deficiency is present in at least some patients with variant angina. The mean serum Mg concentrations before and after calcium antagonist treatment in 10 patients with variant angina were 2.1 +/- 0.09 and 2.1 +/- 0.07 mg/dl, respectively (difference not significant). However, 24-hour Mg retention decreased significantly (p less than 0.01) from 60 +/- 6 to 34 +/- 7% after the treatment. There is Mg deficiency in many patients with variant angina and it is corrected after treatment with calcium antagonists.

Purification of haemorrhagic proteinase from the venom of Agkistrodon caliginosus (Kankoku-Mamushi).

A haemorrhagic proteinase was purified from A. caliginosus venom by ion-exchange chromatography on CM-Sephadex C-50, DEAE-Sephadex A-50, S-Sepharose Fast Flow and Q-Sepharose Fast Flow, and gel-filtration on a Sephadex G-100 column. By this procedure, about 17.6 mg of the enzyme were obtained from 4 g of the venom. The enzyme showed a single band on polyacrylamide gel electrophoresis at pH 8.3 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme had weak caseinolytic and potent haemorrhagic activities, and the minimum haemorrhagic dose of the enzyme was about 0.04 microg. The haemorrhagic activity of the enzyme was only suppressed by treatment with ethylenediamine tetraacetic acid-disodium or o-phenanthroline. The enzyme is composed of a single polypeptide chain with a molecular weight of about 70 kDa and is a glycoprotein. These results indicate that the enzyme is a metalloproteinase as are haemorrhagic proteinases from other snake venoms.

Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study.

We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina.

[A case report of miliary tuberculosis with acute respiratory failure diagnosed by polymerase chain reaction method].

A 51-year-old male was admitted because of cough and high fever. His chest X-ray and CT revealed miliary shadows, he was administered some antibiotics. But on the 8th day, his chest X-ray revealed ground glass shadows and he was under severe hypoxemia. We suspected miliary tuberculosis with acute respiratory failure due to his clinical course. The intensive therapy with antituberculosis drugs, hydrocortisone (1 g/day) was started and intubation was performed. The smear of the clinical samples did not show acid-fast bacilli on admission. However, by the polymerase chain reaction amplification method specific DNA fragments of Mycobacterium tuberculosis complex were detected from BALF and bone marrow. He was extubated after the 13th day and he recovered. It is difficult to separate and identify tubercle bacilli rapidly, but PCR is available for early diagnosis.

[A case of tubercular liver and splenic abscesses].

A 34-years male was admitted to our hospital with a hypochondria pain and low grade fever. Abdominal CT revealed an encapsulated 8 x 3 cm low density lesion on the surface of the liver (S5, S8) and multiple low density lesions of the spleen. The patient had already been treated with anti-tuberculous drugs for the past 7 months after being diagnosed as tuberculous pleuritis. Although echo-guided percutaneous needle biopsy was tried for the hepatic lesion, no special finding was obtained. Therefore a diagnostic laparotomy was performed and the hepatic lesion was resected. Abscess formation of the resected lesion was noted. Histopathology of the lesion revealed epithelioid granuloma, but microscopy, culture and PCR for tuberculosis revealed negative results. Abdominal CT, 3 weeks after surgery, revealed enlargement of the splenic lesion. Splenectomy was carried out to avoid splenic rupture. Multiple abscess of the resected spleen was noted. Pathological finding, Ziehl-Neelsen stain and PCR for tuberculosis confirmed the diagnosis of tubercular splenic and liver abscess. Although tubercular liver and splenic abscess are very rare recently, it should be included in the differential diagnosis of unknown hepatic and splenic lesions.

[Adoptive immunotherapy for pulmonary tuberculosis caused by multi-resistant bacteria using autologous peripheral blood leucocytes sensitized with killed Mycobacterium tuberculosis bacteria].

A patient with pulmonary tuberculosis caused by bacteria resistant to various anti-microbial agents was treated with adoptively transferred autologous peripheral blood leucocytes (PBL) sensitized with killed Mycobacterium tuberculosis organisms in vitro. The 32-year-old man was admitted to our hospital from National Sanitarium Okinawa Hospital with weight loss, high fever, and rapid aggravation on chest X-ray. Patient's PBL obtained by leukapheresis and separated with Ficoll-Hypaque solution were cultured with killed Mycobacterium tuberculosis bacteria of 0.4 microgram per ml at 1 x 10(6) cells per ml for 7 days in media containing 0.5 U recombinant 1L-2 per ml. After incubation, PBL were layered and centrifuged on Ficoll-Hypaque solution and washed three times with saline. PBL (1-3 x 10(8)) were combined and concentrated for infusion in 20 to 30 ml saline. After injection, patient displayed fever and transitory drop of PaO2. Although the patient did not have an improved on chest X-ray, his fever was alleviated, weight was increased, accelerated ESR was slightly improved, and the number of organisms in sputum (Number of Gaffky) temporarily decreased. Adoptive immunotherapy using the autologous PBL which were sensitized with killed bacteria may be an effective anti-tuberculous immunotherapy.

[Three-channeled aortic dissection; report of a case].

The formation of 2 adjacent lumens is rarely observed in aortic dissection. We report herein a case of ruptured 3-channeled aortic dissection in a short time of hospitalization. A 58-year-old man who had been followed up for aortic dissection (Stanford type B) was admitted to Kumamoto National Hospital with an abdominal pain and a lumbago. A computed tomography (CT) revealed that a 3-channeled aortic dissection from the aortic arch to the right common iliac artery. An intramural hematoma was generated in the abdominal aorta and the left kidney was not enhanced. We initially adopted conservative therapies. But on the next day, he suddenly complained a severe back pain and died. At autopsy, the thoracic aorta was found to have ruptured into the mediastinum, and massive hematoma was formed.

Irreducible indirect inguinal hernia containing uterus, ovaries, and Fallopian tubes.

An indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes is extremely rare in pediatrics. The present report describes the very rare case of a 1-month-old girl with an irreducible indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes, and the successful surgical treatment of simple herniorraphy. We review the literature on this type of relationship between indirect inguinal hernia and hernial visceras of the uterus, ovaries, and Fallopian tubes and discuss the clinical features of this complication. Furthermore, the possible cause of indirect inguinal hernia containing the uterus, ovaries, and Fallopian tubes was explored.

Activation of OASIS family, ER stress transducers, is dependent on its stabilization.

Endoplasmic reticulum (ER) stress transducers transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins accumulate in the ER. BBF2 human homolog on chromosome 7 (BBF2H7) and old astrocyte specifically induced substance (OASIS), ER-resident transmembrane proteins, have recently been identified as novel ER stress transducers that have roles in chondrogenesis and osteogenesis, respectively. However, the molecular mechanisms that regulate the activation of BBF2H7 and OASIS under ER stress conditions remain unresolved. Here, we showed that BBF2H7 and OASIS are notably unstable proteins that are easily degraded via the ubiquitin-proteasome pathway under normal conditions. ER stress conditions enhanced the stability of BBF2H7 and OASIS, and promoted transcription of their target genes. HMG-CoA reductase degradation 1 (HRD1), an ER-resident E3 ubiquitin ligase, ubiquitinated BBF2H7 and OASIS under normal conditions, whereas ER stress conditions dissociated the interaction between HRD1 and BBF2H7 or OASIS. The stabilization of OASIS in Hrd1(-/-) cells enhanced the expression of collagen fibers during osteoblast differentiation, whereas a knockdown of OASIS in Hrd1(-/-) cells suppressed the production of collagen fibers. These findings suggest that ER stress stabilizes OASIS family members and this is a novel molecular mechanism for the activation of ER stress transducers.

Therapeutic value of selective salpingography for infertile women with patent fallopian tubes: the impact on pregnancy rate.

OBJECTIVE: To determine the therapeutic value of selective salpingography (SSG) for infertile women with patent fallopian tubes. DESIGN: Retrospective, case-control analysis. SETTING: University Hospital, infertility clinic. PATIENTS: Infertile cases with patent tubes documented by hysterosalpingography (HSG) or by HSG followed by laparoscopic examination (n = 80). INTERVENTION(S): Hysteroscopic SSG. MAIN OUTCOME MEASURE(S): Patency rate of tubes by SSG. Pregnancy rate following SSG. RESULT(S): Eighty cases were divided into the study group (SSG performed, 37 cases) and the case-control group (SSG not performed, 43 cases). Successful SSG of at least one tube was obtained in all of 37 cases (100%) in whom SSG was attempted. A patency rate of 95.9% was documented in the 73 cannulated tubes of these cases. The total subsequent pregnancy rate (48.6%) within 12 months of follow-up after SSG was significantly higher than that (11.6%) obtained in the control group (p < 0.001). The cumulative pregnancy rate in the study group was also significantly higher than that in the control group (p < 0.001). CONCLUSION(S): The findings of the present study encourage the application of SSG to infertile women, either as a sole therapeutic approach or in association with other methods of assisted reproductive technology, even if their fallopian tubes are shown to be patent by HSG.

Augmentation of temporal area by insertion of silicone plate under the temporal fascia.

The Japanese are mesocephalic and their faces tend to look broad when viewed from the front. The main reason for this appearance is the prominent zygoma. The temporal area is closely related to the zygoma, and when this portion of the face is excessively concave, the zygoma stands out and causes the face to appear seedy or older than the actual age. To cure this condition, there have been three conventional operations performed in Japan, which are not without shortcomings. The authors have improved on these methods and have succeeded in solving most of the problems in 21 cases by devising a method in which a soft silicone plate is inserted under the temporal muscle fascia.