We screened for mutations of the glucocorticoid receptor (GR) gene in patients with systemic lupus erythematosus (SLE), a typical autoimmune disease. Polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) revealed a single mutation in exon 9 of the GR gene in 11/132 (8.3%) among 66 patients with SLE. No mutations were detected in 52 healthy individuals (0/104, 0.0%), but the same mutation was detected in other autoimmne diseases (4/108, 3.7%). DNA sequencing showed a T to C substitution at codon 766 (position 2430) of the GR gene, which does not alter the amino acid sequence of the GR. Further analysis using a LightCycler generated different melting curves indicates that the pattern with this mutation is different from that of wild type. The identified mutation of the GR gene may represent a polymorphism associated with SLE.
In immuno-light and -electron microscopy, brain-type fatty acid binding protein (B-FABP) is localized in the sustentacular cells enclosing the chromaffin cells in the adrenal medulla. This represents another new feature commonly shared by the sustentacular cells and ganglionic satellite cells, the latter of which has already been reported to localize this molecule, and suggests a common feature in lipid metabolism shared by the two cells enclosing peripheral neurons and paraneurons. On the other hand, epidermal-type fatty acid binding protein (E-FABP) is localized in two discrete cells in the adrenal gland: the one is a subpopulation of intra-adrenal macrophages which are intensely immunoreactive for F4/80, a marker of macrophages, and are rich in pleomorphic lysosomes. Because of their direct apposition to adjacent cortical endocrine cells and medullary chromaffin cells, the macrophages may be involved not only in phagocytosis of degenerating adrenal cells but also in exertion of some yet unknown effects on the endocrine function of the cortical and medullary cells via humoral factors such as cytokines which have recently been known to be secreted by macrophages. The other is a population of cells having scanty perikaryal cytoplasm poor in organneles and several thinny extended processes in the cortex and exhibiting weak immunoreactivity for E-FABP. The possible natures of these cells immunoreactive for E-FABP are discussed in view of a subpopulation of endothelial cells or the dendritic cells of antigen-presenting property.
There have been no previous reports whether long-term bile diversion enhances pancreatic exocrine secretion. The aim of this study was to elucidate the effect of long-term bile diversion on pancreatic exocrine secretion. Four mongrel dogs were prepared for chronic gastric and pancreatic fistulas and received intraduodenal sodium oleate infusion (controls). These dogs, then underwent diversion of bile from the intestines by ligating the common bile duct and interposing a segment of jejunum between the gallbladder and the urinary bladder (total biliary diversion [TBD]). After three weeks, the dogs received an identical sodium oleate infusion. TBD augmented basal pancreatic exocrine secretion compared with controls (4.4-fold increase in basal flow volume; 9.0-fold increase in bicarbonate output; and 3.3-fold increase in protein output). Likewise, TBD augmented oleate-stimulated exocrine secretion (2.0-fold increase in cumulative flow volume; 2.6-fold increase in bicarbonate output; and 1.4-fold increase in protein output). TBD also augmented basal and oleate-stimulated plasma cholecystokinin levels. Administration of a Cholecystokinin-A receptor antagonist (loxiglumide) after TBD reduced the flow volume and bicarbonate output to the control levels, and the protein output to less than a half of the control level. Long-term bile diversion enhances basal and oleate-stimulated pancreatic exocrine secretion, at least partly via increased cholecystokinin secretion.
We examined the defecatory conditions in a population of Japanese subjects and analyzed the measured parameters as a means for self-evaluation of defecation. Subjects (n=1195) were residents of northern Japan and were all aged over 40 years. The state of defecation and fecal characteristics were assessed with regard to nine parameters including “self-reported bowel habit” and “bowel movement frequency.” Logistic regression analysis was carried out to analyze the association between the complaint of constipation and other eight parameters. A higher tendency for constipation was noted in women than in men. The highest value of the odds ratio was “bowel movement frequency”; especially the value “once per three days or more” was noted in both genders (odds ratio: 13.38 and 42.46 in men and women, respectively). In addition, “stool appearance”, “length of time for bowel movement”, “straining after bowel movement”, “alternating diarrhea/constipation/disorder” and “travel-related changes in bowel movements” were significantly related with the complaint of constipation (“self-reported bowel habits”) in both genders. In conclusion, the study elucidated that personal and subjective evaluation of bowel habits in normal subjects consisted of various factors under the heading of “bowel movement frequency”.
Physicians’ not entering their patients can jeopardize the success of a randomized controlled trial (RCT). We used a survey to investigate the possible reasons why physicians who initially agreed to collaborate did not recruit any patients for an RCT being conducted in Japan. A total of 167 questionnaires were sent out and 122 responses were received. Main reasons for not entering patients were: concern about the detrimental effects on the doctor-patient relationship (51.8%), patients’ refusal (47.5%), complicated registration and follow-up procedures (34.9%), and not feeling comfortable recruiting their own patients (32.4%). Multivariate logistic regression made it clear that physicians who thought that registering their own patients would damage the doctor-patient relationship and who expected the RCT would fail were more likely to be uncomfortable entering their own patients. Moreover, physicians aged 50 years or older, who felt uncomfortable recruiting their own patients, and saw no advantage in participating in the trial, were more likely to view the enrolment and follow-up procedures as cumbersome. We conclude that training and a manual for obtaining informed consent and a face-to-face demonstration of patient registration/follow-up procedures for the potential participants are prerequisites for increasing physician participation in RCTs in Japan.
Tachycardia accompanies the preload reduction. Our aim is to assess the effect of the heart rate change on wall motion in ischemic heart. In 8 dogs with occlusion of left anterior descending artery, we changed the heart rate (heart rate 90, 120, and 150 beats/minute) after using UL-FS49, a selective bradycardic agent, with atrial pacing. Preload was changed by inferior vena caval occlusion at a heart rate of 90 beats/minute. With either an increase in heart rate or an inferior vena caval occlusion, the end-diastolic length was decreased, but the end-diastolic length relationships between the non-ischemic and the ischemic region made different lines from those of the heart rate change and inferior vena caval occlusion. When increasing the heart rate, isovolumetric shortening was unchanged in the non-ischemic region with more expansion in the ischemic region. While inferior vena caval occlusion at a heart rate of 90 beats/minute, isovolumetric shortening was increased in the non-ischemic region, with more expansion in the ischemic region. Both in tachycardia and by the inferior vena caval occlusion, ejectional shortenings decreased in the non-ischemic and ischemic regions. Our results suggest that, in ischemic heart, tachycardia changes both in the end-diastolic length relationship between the non-ischemic and the ischemic region and at the isovolumetric contraction phase. The changes seem to be not only due to the inferior vena caval occlusion, but also due to tachycardia itself.
The aim of the present study was to evaluate the basic life support skills of doctors in a hospital resuscitation team and to identify potential factors affecting those skills. Twelve anesthesiology residents were induced in this study. Each doctor was asked to perform mouth-to-mouth ventilation for 10 minutes and then chest compression for another 10 minutes on a Laerdal Skillmeter Resusci-Anne manikin during the day (10 am) and at night (10 pm). The rates of correct ventilation, correct chest compression, ventilation errors (i.e., excessive inflation, stomach insufflation, insufficient ventilation), and compression errors (i.e., insufficient chest compression/decompression, excessive chest compression, incorrect hand placement) were determined for each 2-min interval up to 10 min. In addition, effects of sex, seniority, CPR duration, and time of day (day vs night) on those skills were assessed. The mean rates of correct ventilation were 53.3±23.9% (day) and 60.4±16% (night); the mean rates of correct chest compression, 76.9±15% (day) and 76.5±14.7% (night). During the first 2-minutes period of testing at night, men doctors more frequently achieved correct ventilation than did women doctors (p<0.05). Overall, the practical CPR skills of the study participants were not influenced by sex, seniority, CPR duration, or time of day; however, the participants’ skills were poor. This suggests that all medical staff, especially members of in-hospital resuscitation teams, should undergo regular, periodic CPR training.
We present a case report of encephalopathy associated with Salmonella urbana infection in a child. A 5-year-old boy was admitted to our clinic with convulsions and coma. Cerebrospinal fluid (CSF) interleukin-6 (IL-6) and IL-8 were elevated at onset and were decreased within normal limit on the fifth day. Residual neurological deficits included severe mental deficits and spastic tetraplegia. High levels of CSF proinflammatory cytokines might be related to central nervous system (CNS) disease activity. Although encephalopathy is a rare complication of non-typhi Salmonella infection, it should be borne in mind as an occasionally serious and potentially lethal disease.
We report three cases of intracranial aspergillosis originating in the sphenoid sinus in immunocompetent patients. The patients presented with an orbital apex syndrome in that a unilateral loss of vision and cranial nerve III palsy were seen in all cases and a contralateral involvement was also seen in one case. Despite the initial treatment with a conventional dose of itraconazole (ITCZ, 200 mg/day), the neurological deficits failed to improve and the granulomatous inflammation was not suppressed. Therefore, we treated with a combination of a high dose of ITCZ at 500-1000 mg/day (16-24 mg/kg/day) and amphotericin B (AMPH-B) at 0.5 mg/kg/day, in conjunction with a pulse dose of methylprednisolone at 1000 mg/day. Two cases responded favorably in that the ocular movements completely recovered, and their maximum serum concentrations of the hydroxy ITCZ were 7816 ng/ml and 5370 ng/ml. However, the other case worsened, despite ITCZ treatment at 16 mg/kg/day, and the serum concentration of the hydroxy ITCZ was 3863 ng/ml. The surgical decompression of the cavernous sinus via an extradural approach was performed, and the dose of ITCZ was increased to 24 mg/kg/day. The resulting serum concentration of the hydroxy ITCZ was 4753 ng/ml, and the outcome of this case has been favorable. These results suggest that a high blood level of the hydroxy ITCZ (more than 4500 ng/ml) is a prerequisite for the successful treatment of intracranial aspergillosis and that the combination treatment of ITCZ with AMPH-B would be preferred. The concomitant use of steroid and/or surgical decompression should be considered, if the invasiveness is not well-controlled in spite of intensive medical therapy.
We report a case of branch retinal artery occlusion (BRAO) in a patient with iron-deficiency anemia. Various ophthalmological and laboratory studies were performed. A 32-year-old man had a sudden decrease of vision in his left eye to counting fingers at 30 cm two days ago. The left fundus showed a cherry-red spot and milky-white edema, except for the upper temporal region of the macula, and an optic disc malformation. Fluorescein angiography revealed leakage from the disc and a slightly delayed filling time in the left eye but an arterial filling defect was not noted. The differential diagnosis in this young patient includes polycythemia, hypercoagulopathy, coagulation abnormalities, trauma, hypertension, and autoimmune diseases such as systemic lupus erythematosus. Laboratory examinations revealed no abnormalities except for iron-deficiency anemia. The patient was treated with stellate ganglion block, hyperbaric oxygen, and ferrous sulfate. His visual acuity never recovered to better than 0.08. He had a coincidental rectal carcinoid and the tumor was excised surgically. No metastasis was observed. BRAO can be a complication of anemic retinopathy and can lead to severe visual loss without early medication.