The Two Different States of Hepatitis B Virus DNA in Asymptomatic Carriers (HBe-Antigen-Positive versus Anti-HBe-Positive Asymptomatic Carriers)

During the course of hepatitis B virus (HBV)infection, there exists a long period of normal liverfunction tests with different states of HBeAg/Ab. As thestate of HBV in asymptomatic carriers was not well characterized, we quantitatively andqualitatively examined HBV in both HBeAg-positive andanti-HBe-positive asymptomatic carriers. Sera from 10HBeAg-positive and 27 anti-HBe-positive asymptomatic carriers were analyzed. The amount of HBV DNAwas determined by dot-blot hybridization and polymerasechain reaction. The mutations in precore and coreregions, spanning 636 nucleotides, of hepatitis B virus were examined by directly sequencing theamplified HBV DNA. HBV DNA was detected in all 10 HBeAg-positive cases, whereas it was found in only 7 of 27(26%) anti-HBe-positive cases by the nested PCR method. The mean amount of HBV DNA inHBeAg-positive cases was 10^9.1±0.7copies/ml, while that in anti-HBe-positive cases was10^1.0±1.5 copies/ml. There were no 0.7missense mutations in the entire precore and core genes of HBV DNA taken fromHBeAg-positive asymptomatic carriers. In contrast, manymutations (mean 9.0 ± 3.3, range 6-14) weredetected in the core gene of seven anti-HBe-positiveasymptomatic carriers including two cases with increments of themutations. Analysis of the precore region revealed threewild-type and four mutant-type (including one coexistingwith wild-type) cases. These data suggest that HBV exists in quite different ways inasymptomatic carriers; in the HBeAg-positive phase HBV probably coexists with the host andremains as the wild type, whereas in theanti-HBe-positive phase a drastically reduced amount of HBV with many mutationsremains, probably as a consequence of the long-lastinginteraction with the host. Nevertheless, such smallamount of virus could cause fulminant hepatic failure. It is important to make further clinical andvirological investigations in order to understand thestate of asymptomatic carrier.     

Effect of Three Different Modes of Alcohol Administration on the Activity of the Rat Hypothalamic-Pituitary-Adrenal Axis

The present study compared the effect of different modes of alcohol administration on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. In a first series of studies, we investigated the influence of the intraperitoneal (ip) and intragastric (ig) effect of acutely administered alcohol. Over a 3–hr period, alcohol induced dose-related increases in adrenocorticotropic hormone (ACTH) and alcohol levels in the circulation. There was a good correlation between blood ACTH and alcohol levels (ip treatment, R = 0.84; ig treatment, R = 0.79). Measurement of steady-state mRNA of the immediate early gene NGFI-B, taken as an index of neuronal activation in the paraventricu-lar nucleus (PVN) of the hypothalamus of rats administered 3 g of alcohollkg, indicated significant (p < 0.01) increases between 60 and 180 min after both ip and ig alcohol injection, with peak stimulation at 1 and 2 hr, respectively. Although NGFI-6 mRNA levels had returned to control level in the parvicellular portion of the PVN of animals administered the drug ip 4 hr earlier, they were still significantly (p < 0.01) elevated 4 hr after ig treatment. A second series of studies used rats fed an alcohol diet containing 6.4% alcohol (w/v), or pair-fed. The rats were tested during the 4th or 6th night of treatment. Despite blood alcohol levels ranging between 0.060 and 0.140% w/v, there was no significant rise in plasma ACTHlcorticosterone levels in animals fed the drug, and no detectable NGFI-B mRNA in their PVN. Collectively, these results indicate that both the ip and the ig acute injection of alcohol induced dose-related increases in plasma ACTH levels. PVN neuronal activation was also observed. In contrast, the alcohol diet had no effect on HPA hormone levels or PVN expression Of NGFI-B.     

口服阿苯达唑脂质体大鼠体内药物动力学的研究

通过Wistar大鼠口服阿苯达唑脂质体的体内药物动力学实验,建立和考察了高效液相色谱法（HPLC）测定生物样品中阿苯达唑及其代谢产物的浓度的方法;用药动学软件包进行体内模型拟合,获取药动学参数和比较阿苯在唑脂质体的相对生物利用度。结果显示;测定阿苯达唑及其代谢产物的HPLC方法回收率较高,可满足汪同生物样品的测定;口服阿苯达唑脂质符合一级吸收二室动力学模型。与阿苯达唑片剂粉末相比,具有较高有生物利用度并有一定的肝脏靶向性。     

Proliferative Response of Different Exocrine Pancreatic Cell Types to Hormonal Stimuli: II. Effects of Long-Term Secretin Administration

The effect of graded doses of secretin on exocrine pancreatic growth and cell proliferation was studied in a long-term experiment. After 16.5 and 150μg/kg/24h of secretin, each administered as two subcutaneous injections daily for 14 days, the pancreatic wet weight decreased, whereas the protein and DN A content of the gland was uninfluenced. When administered as described above for 14 days, 16.5, 50, 150, and 450μg/kg/24 h of secretin did not affect the proliferation rate of ductal, acinar, or centroacinar cells as measured by a labeling index after 7 days of continuous ³H-thymidine administration. In the control groups a higher labeling index was found for ductal cells (19.9%) than for acinar cells (11.0%). During the 7 days of ³H-thymidine administration 80–90% of ductal and acinar cells remained in the GO phase. There was a significantly higher labeling index in interlobular than in intralobular duct cells.     

Effect of Oral Contrast Administration for Abdominal Computed Tomography in the Evaluation of Acute Blunt Trauma

Study objective: To determine how frequently oral contrast medium (OC) is essential for computed tomography (CT) diagnosis of blunt intraabdominal injury and to quantify the delay associated with OC administration and the incidence of adverse effects. Methods: This retrospective chart review, with prospective reevaluation of CT scans for diagnostic value of OC, took place in a university teaching hospital and Level I trauma center. Participants were blunt-trauma victims admitted between June 1, 1988, and November 1, 1993, who had abdominal CT as part of their initial evaluation. Trauma registry records were used to identify study patients. Available charts and CTs were reviewed for all patients with intestinal/mesenteric and pancreatic injuries. Randomly selected cases of liver injury, spleen injury, and no intraabdominal injury were also reviewed. Blinded CT scans were reevaluated for quality of bowel opacification and value of OC to diagnostic impression. Results: During the study period, 2,162 blunt-trauma patients had an abdominal CT; 297 intraabdominal injuries were diagnosed in 248 patients. Full review was done on 124 charts, and 70 CT scans were reevaluated. Thirty-one (100%) of 31 liver and spleen injuries were diagnosed on CT, and OC was considered essential in none of these studies. One (4.5%) of 22 intestinal and mesenteric injuries was seen on CT, but this was the only such injury treated nonoperatively. None of 21 surgically confirmed intestinal/mesenteric injuries was seen on CT. Free air or free OC was seen in none of 7 cases of intestinal perforation. OC was judged essential in none of 20 scans in patients without intraabdominal injury. On 2 scans, OC was considered essential for the radiographic diagnosis. One of these was a normal pancreas at exploration (radiographic false-positive result). The only pancreatic injury requiring specific surgical treatment was missed on CT. Twenty-one percent of patients required placement of a nasogastric tube for contrast administration after failing oral administration, and 23% vomited OC. One of 124 had documented aspiration of OC. Average additional time incurred in the ED for administration of OC was 144 minutes. Conclusion: OC is rarely essential for CT diagnosis of intraabdominal injury. It may improve sensitivity for pancreatic injury, but it does not help identify injuries requiring surgical treatment. Even with OC, CT is insensitive for intestinal injury. Vomiting and aspiration are significant risks. Use of OC adds a significant amount of time to ED evaluation. Adverse effects of OC administration, in this setting, may outweigh its benefits. [Tsang BD, Panacek EA, Brant WE, Wisner DH: Effect of oral contrast administration for abdominal computed tomography in the evaluation of acute blunt trauma. Ann Emerg Med July 1997;30:7-13.]     

Effect of Vitamin E Deficiency on Inhibition of Liver Regeneration by Long-Term Administration of Alcohol

The effects of vitamin E (VE) deficiency on liver regeneration suppressed by long-term administration of alcohol were studied. Male rats were divided into two groups: the alcohol group and the control group. In addition, each group was subdivided into two groups according to the presence or not of VE. Altogether, four groups were provided: a group maintained on the VE-deficient alcohol diet (group EA), a group maintained on the VE-deficient control diet (group EC), a group maintained on the ordinary alcohol diet (group A), and a group maintained on the ordinary control diet (group C). After pair-feeding for 6 weeks, partial hepatectomy was performed to determine the ornithine decarboxylase (ODC) activity, polyamine levels, lipid peroxide levels, and DNA synthesis. DNA synthesis at 24 hr after partial hepatectomy was suppressed significantly in the alcohol administration group, regardless of the presence or not of VE. DNA synthesis at 48 hr after partial hepatectomy tended to show low values in group EA, compared with group A. As for the hepatic ODC activity, group EA showed the lowest value at 4 hr after partial hepatectomy. Of polyamines, the putrescine level in group EA at 4 hr after partial hepatectomy was significantly low, compared with the other three groups. The levels of spermidine and spermine decreased by long-term administration of alcohol, but the effect of VE deficiency was not found. The lipid peroxide level increased significantly in the VE-deficient diet administration group, but the effect of alcohol administration was not found. These results suggested that the decrease in putrescine after ODC suppression by VE deficiency in addition to the decrease in spermidine and spermine caused by long-term alcohol administration were concerned with suppression of DNA synthesis later.     

The Evaluation of Dysphagia Following Radical Surgery for Oral and Pharyngeal Carcinomas by Cine-Magnetic Resonance Imaging (Cine-MRI)

Cine-magnetic resonance imaging (cine-MRI) creates moving pictures by a video system and turbo-flash method that allow for high-speed MRI. This report describes our experience using this new technique for dynamic imaging using the fast spoiled GRASS (SPGR) sequence to study swallowing in patients with dysphagia following radical surgery for oral cancer. We defined two new parameters, laryngeal elevation and the angle of the epiglottis, to quantify swallowing ability by cine-MRI. These variables were markedly different in patients with dysphagia than they were in healthy controls. Cine-MRI not only provides dynamic images of swallowing but can generate objective measures of swallowing ability as well.     

The site of action of aβ 2-receptor stimulating drug (Fenoterol) on antigen-induced bronchoconstriction

The influence of Fenoterol administered to the upper and lower area of the air conducting system on antigen-induced bronchoconstriction was studied in 60 dogs. In small doses, Fenoterol administered to the upper airways blocked bronchoconstriction by antigen applied to upper but not to lower airways. The intravenous administration of the same dose was without effect. In large doses, Fenoterol blocked bronchoconstriction induced at both sites. Application of both doses of Fenoterol to lower airways blocked bronchoconstriction induced at both sites and was more effective than intravenous treatment. We concluded that there is an important local effect of Fenoterol on the upper respiratory tract in antigen-induced bronchoconstriction from this site as well as on the lower airways.     

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.     

Evaluation of constipation in older adults: Radioopaque markers (ROMs) versus wireless motility capsule (WMC)

There is scarce information regarding assessment of constipation in older subjects. We examined regional and whole-gut transit time (WGTT) with wireless motility capsule (WMC) and compared this with radioopaque markers (ROM) transit. 39 constipated and 11 healthy older subjects (≥65 years) ingested a ROM capsule and WMC, wore a data receiver and kept stool diaries for 5 days. WMC recordings were analyzed for colonic transit time (CTT), WGTT and gastric emptying time (GET). Radiographs obtained on day 5 assessed ROM transit. Results for each device were compared. The CTT (p=<0.0001), WGTT (p=<0.001) and GET (p=<0.04) as measured by WMC were all slower in constipated subjects compared to healthy subjects. ROM colonic transit was also slower (p=<0.007) in constipated compared to healthy subjects. The diagnostic utility for identifying subjects with constipation as assessed by receiver operating characteristics were similar; 0.85 (WMC) versus 0.73 (ROM). Device agreement for slow colonic transit was 88% with good correlation between WMC and ROM (CTT r=0.718, p=0.0001, WGTT r=0.693, p=0.0001). Slow transit constipation was identified in 28% with ROM and 32% with WMC. No adverse events were recorded. WMC is a safe and useful device that provides objective diagnosis of delayed colonic and whole gut transit in older constipated adults. It is a radiation-free, physiologic and ambulatory technique that provides additional diagnostic information than ROM.     

Huge Amoebic Liver Abscess in the Left Lobe Treated by Oral Administration of Metronidazole

A man in his 60s visited a clinic with chief complaints of a fever and general malaise. Suspecting a liver abscess in the left lobe with infiltration into the subcutaneous fat tissue under the rectus abdominis muscle based on computed tomography findings, we performed fine-needle aspiration. An amoebic liver abscess was diagnosed. Remission was achieved by the oral administration of metronidazole alone without placement of a drainage tube. The results obtained in this case suggest that the first line of treatment should be a non-invasive approach with oral administration alone. Invasive intervention should then be considered depending on subsequent progress.     

Factor VIII Clotting Antigen (VIIICAg) in Haemophilia Measured by Two Immunoradiometric Assays (IRMA) using Different Antibodies, and the Measurement of Inhibitors to Procoagulant Factor VIII (VIIIC) by IRMA

Factor VIII clotting antigen (VIIICAg) was measured by immunoradiometric assay (IRMA) using two different antibodies. Both antibodies arose in polytransfused severe haemophiliacs and had similar titres against VIIIC. In 12 normal plasmas there was no significant difference in VIIICAg values obtained (VIIICAg (AbI) = VIIICAg (AbII)). In the majority of 15 severe haemophiliacs tested VIIICAg was undetectable by both antibodies. In 28 mild to moderate haemophiliacs VIIICAg (AbII) was significantly greater than VIIICAg (AbI) ( P < 0·01) suggesting different antigenic determinants. The difference, however, was small and does not affect diagnosis of haemophilia. A modified IRMA has been used to measure and VIIIC inhibitors by competition of the inhibitor with ¹²⁵I labelled VIIICAg antibodies for common antigenic determinants. Using an inhibitor of 225 Bethesda units as a standard, results by IRMA of inhibitors in severe haemophiliacs have been similar to those obtained by clotting assay, but with a sensitivity of 0·01 u/ml suggesting the possible use in the detection of weak inhibitors.     

Evaluation of fluticasone (flixonase) nasal spray versus beclomethasone (beconase) nasal spray in the treatment of allergic rhinitis

Although response to intranasal steroid therapy has been reported in patients with allergic rhinitis, efficacy of some nasal steroids is noteworthy.This study was undertaken to evaluate the efficacy of a two-week course of Fluticasone (Flixonase) nasal spray vs. Beclomethasone (beconase) nasal spray in patients with symptoms of allergic rhinitis referred to our clinic. This study reviewed sixty randomized studies with symptoms of allergic rhinitis which supported common aeroallergens with skin prick test. Patients received a total daily dose of nasal spray of Fluticasone (Flixonase) 100 mcg bid (N=30) compared with patients with allergic rhinitis who received a total daily dose of Beclomethasone (Beconase) 50mcg 2 puffs bid (N=30). Patients were visited before and after therapy, and efficacy of Flixonase and Beconase was evaluated by the change in nasal symptoms including: nasal discharge, nasal obstruction, nasal itching, and sneezing. After two weeks of treatment nasal symptoms of blockage, discharge, sneezing and itching were significantly better in the group treated with Fluticasone nasal spray (65%, 82%, 67%, 79% respectively (p<0.001) but after treatment with beconase nasal spray lower benefits in the nasal symptoms includes: 50%, 71%, 51%, 57% respectively. After two weeks of treatment no deleterious changes consequent to therapy were observed in nasal symptoms. 100 mcg bid Flixonase (Fluticasone) intranasal spray is more effective than 50 mcg 2 puffs bid Beconase (Beclomethasone) intranasal spray. Like asthma, allergic rhinitis is an inflammatory disease and should be managed with anti-inflammatory medication.