Experimental Bacteroides fragilis endocarditis in rabbits

A serum-resistant strain of Bacterioides fragilis that did not produce heparinase was used to study the characteristics of B. fragilis endocarditis in the rabbit experimental model. The infective dose required to produce endocarditis in 50% of rabbits was significantly lower for rabbits with left-sided intracardiac catheters (log10 6.3 colony-forming units +/- 0.6/ml) as compared with right-sided intracardiac catheters (log10 7.7 colony-forming units +/- 0.8/ml). After 3 days of infection, bacterial titers of the tricuspid vegetations were significantly lower than titers of aortic vegetations (P less than 0.01), although at 5 days the titers were similar (P greater than 0.05). The weights of tricuspid vegetations, although similar at 3 days (P less than 0.05). There were no spontaneous deaths during 12 days of infection. In rabbits with the catheter removed before infection, bacterial titers were similar to those titers in rabbits with the catheter continuously in place. This model will permit study of various drug regimens for treatment of this disease.     

Prevalence of fascioliasis in humans, horses, pigs, and wild rabbits in 3 Chilean provinces

This study sought to estimate for the first time the prevalence of fascioliasis among the rural population in the Chilean provinces of Curico, Talca, and Linares, while also determining the disease's prevalence among horses and wild rabbits in Curico and Talca and among pigs in Talca. From January 1986 to December 1990 a randomly selected sample of 5,861 persons in the three provinces was given intradermal, complement-fixation, double-diffusion, and immunoelectrophoresis tests to detect antibody to Fasciola hepatica. In addition, the ELISA test was used in Talca and Linares. Fecal specimens from horses and pigs were inspected for eggs, and the liver and bile ducts of rabbits were examined histopathologically. The overall prevalence of infection among the human subjects was 0.70%, with rates of 0.6% in Curico, 0.75% in Talca, and 0.71% in Linares. The prevalences of infection in horses, rabbits, and pigs were 13.5%, 6.1%, and 20.6%, respectively. It is estimated that some 2,000 people are infected in the study area. It is recommended that rabbits be taken into account in all control programs for this zoonosis.     

Human fascioliasis: comparison of a fasciolicidal effect of bithionol and praziquantel

BACKGROUND: The frequency of gliadin antibody (GA) positivity has been found to be increased among patients with chronic liver disease, as has that of coeliac disease (CD). CD has also been found to be increased among patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). METHODS: To investigate these relationships further, a micro-enzyme-linked immunosorbent assay and immunofluorescence tests for GAs and endomysial antibodies (EMAs) were performed in large subgroups of patients representing various chronic liver diseases and in healthy blood donors. RESULTS: As compared with blood donors (among whom it was 5%) the frequency of IgA GA positivity was higher in all patient subgroups: alcoholic liver disease, 20% (22 of 110, P < 0.001); PBC, 16% (16 of 101, P < 0.001); PSC, 24% (19 of 80, P < 0.001); chronic hepatitis, 19% (13 of 70, P < 0.001); and hepatitis C virus infection, 11% (11 of 104, P < 0.01). Two patients with autoimmune chronic hepatitis were EMA-positive, and in both cases the presence of CD was verified by small-bowel biopsy. CONCLUSIONS: IgA GA positivity generally occurs at increased frequency among patients with chronic liver disease and may represent non-specific immune activation. In liver disease GA testing is not useful in screening for CD, whereas the EMA test seems to be highly specific. CD is more prevalent than expected among patients with autoimmune chronic hepatitis but not among those with PBC or PSC.     

Experimental study on growth of epiphysial plate: free graft in rabbits

The growth potential of a free graft of an epiphysial plate was investigated in rabbits. Two epiphysial plate grafts were harvested from each iliac crest. One was grafted to the head (onto bone) and the other to the ear (onto cartilage). Both of the epiphysial plates enlarged to a maximum height of 1.4 cm and became similar to iliac crests. Enchondral ossification was observed up till approximately 28 weeks of age. We conclude that an epiphysial plate has growth potential after free heterotopic transplantation.     

Experimental erbium: YAG laser photoablation of trabecular meshwork in rabbits: an in-vivo study

Photoablative laser trabecular surgery has been proposed as an outflow-enhancing treatment for open-angle glaucoma. The aim of the study was to investigate the time course of repair response following low-thermal Erbium: YAG laser trabecular ablation. In 20 anaesthetized rabbits gonioscopically controlled ab-interno photoablation of the ligamenta pectinata and underlying trabecular meshwork (TM) was performed with a single-pulsed (200 microseconds) Erbium: YAG (2.94 microns) laser. The right eye received 12-15 single laser pulses (2 mJ) delivered through an articulated zirconium fluoride fiberoptic and a 200 microns (core diameter) quartz fiber tip, the left unoperated eye served as control. At time intervals of 30 minutes, 2, 10, 30, and 60 days after laser treatment, eyes were processed for light- and scanning electron microscopy. The applied energy density of 6-4 J cm-2 resulted in visible dissection of the ligamenta pectinata and reproducible microperforations of the TM exposing scleral tissue accompanied by blood reflux from the aqueous plexus. The initial ablation zones measured 154 +/- 36 microns in depth and 45 +/- 6 microns in width. Collateral thermal damage zones were 22 +/- 8 microns. At two days post-operative, ablation craters were still blood- and fibrin-filled. The inner surface of the craters were covered with granulocytes. No cellular infiltration of the collateral thermal damage zone was observed. At 10 days post-operative, progressive fibroblastic proliferation was observed, resulting in dense scar tissue formation with anterior synechiae, proliferating capillaries and loss of intertrabecular spaces inside the range of former laser treatment at 60 days post-operative. Trabecular microperforations were closed 60 days after laser treatment in all rabbits. IOP in treated and contralateral eyes did not significantly change its level during whole period of observation. Low-thermal infrared laser energy with minimal thermal damage to collateral structures could not effectively prevent early scarring of trabecular surgery in rabbits.     

Experimental and clinical correlation in acute pancreatitis pathogenesis

Pathological aspects in 100 cases of operated A.P. different in severity are not strictly related to aetiological conditions. Clinical observations have suggested some components of pathogenesis: obstruction of bilio-pancreatic inflow in duodenum at the beginning of the attack, bilio-pancreatic reflux on cholangiograms, strong secretory digestive stimulation before attack. Some experimental animals models (dogs) which can mimic pathogenic mechanism (obstruction of pancreatic flow, common bilio-pancreatic duct, closed duodenal loop, acute cholecystitis) have revealed characteristic pathological changes depending on the initiating process. Our conclusion that severity of pathological changes in A.P. are determined by the initiating mechanisms which may differ in some aetiological condition or may be common for different ones.     

Experimental seizure-induced brain damage: electrophysiological, metabolic and pathological correlation

We have studied IL-6 gene expression and production by in vitro stimulated peripheral blood mononuclear cells (PBMC) isolated from common variable immunodeficiency (CVI) patients. A strong hybridization signal for the IL-6 probe was observed in mRNA extracted from phytohaemagglutinin (PHA)- and PHA/phorbol myristate acetate (PMA)-stimulated PBMC from most of 12 CVI patients analysed. IL-6 production by PHA-stimulated PBMC from 28 CVI patients was evaluated in ELISA and found to be significantly (P < 0.0001) higher than in normal controls. IL-6 production, however, did not correlate with the lymphocyte populations examined, nor with the absolute number of monocytes. We have also showed that IL-6 was able to increase IgM secretion by several Epstein-Barr virus (EBV)-transformed cell lines derived from both normal donors and CVI patients, but it failed to modify substantially the amounts of IgM and IgG produced in vitro by PBMC derived from CVI patients and activated with pokeweed mitogen (PWM) or anti-IgM. Our data indicate that IL-6 gene expression and production is increased in CVI, but CVI cells do not respond to IL-6 with increased production of immunoglobulin.     

Therapeutic endoscopy of the hepatobiliary and pancreatic system: a Vietnamese experience

We studied the effect of the selective serotonin reuptake inhibitor (SSRI), paroxetine, on basal plasma prolactin concentrations in 11 healthy subjects. Subjects were tested before paroxetine, and after 1 and 3 weeks of treatment (20 mg daily). On each test occasion prolactin levels were sampled before and following administration of a placebo capsule, for a total of 4 h. After 3 weeks paroxetine treatment plasma prolactin levels were significantly higher than those seen either pre-treatment or after 1 week of treatment. In contrast, 1 week of paroxetine treatment did not significantly increase prolactin concentrations over pre-treatment values. Plasma concentrations of paroxetine did not differ between 1 and 3 weeks of treatment. The secretion of plasma prolactin is, in part, under the tonic regulation of serotonergic pathways and the present results therefore support animal experimental data suggesting that SSRIs produce a delayed increase in some aspects of brain serotonin neurotransmission.     

Aphasia outcome in stroke: a clinical neuroradiological correlation

Fourteen aphasic patients with acute onset of thromboembolic cerebrovascular insults demonstrable by angiography or radioscintigrams who were available for long-term follow-up have been studied. Their aphasia evolution was compared with acute angiographical and radioisotopic findings, and the lesions shown by follow-up computerized axial tomography (CT). Angiographical site of occlusion, evidence of early reopening of occluded vessels, and radioisotopic flow asymmetries including the "hot-stroke" luxury perfusion failed to correlate with aphasia outcome. Radioisotopic static images were more helpful by depicting lesion location and number but lacked the definition seen on the CT scan. The long-term CT scan by showing the size, location and number of lesions had a good correlation with aphasia outcome. Those patients with large dominant hemisphere involvements, either one large or many smaller lesions, fared poorly while those with lesser lesions did better. Bilateral lesions, at times evasive clinically, helped to account for significant aphasia residuals.     

Interventional radiology in children with hepatobiliary rhabdomyosarcoma

A patient presented with severe bactrim-induced neutropenia with a reversed CD4+/CD8+ lymphocyte ratio. R-metHUG-CSF at 300 micrograms daily produced a dramatic neutrophil response and the therapy was discontinued after 2 weeks.     

Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis

Gene expression in the pharyngeal muscles of Caenorhabditis elegans is controlled in part by organ-specific signals, which in the myo-2 gene target a short DNA sequence termed the C subelement. To identify genes contributing to these signals, we performed a yeast one-hybrid screen for cDNAs encoding factors that bind the C subelement. One clone recovered was from daf-3, which encodes a Smad most closely related to vertebrate Smad4. We demonstrated that DAF-3 binds C subelement DNA directly and specifically using gel mobility shift and DNase1 protection assays. Mutation of any base in the sequence GTCTG interfered with binding in the gel mobility shift assay, demonstrating that this pentanucleotide is a core recognition sequence for DAF-3 binding. daf-3 is known to promote formation of dauer larvae and this activity is negatively regulated by TGFbeta-like signaling. To determine how daf-3 affects C subelement enhancer activity in vivo, we examined expression a gfp reporter controlled by a concatenated C subelement oligonucleotide in daf-3 mutants and other mutants affecting the TGFbeta-like signaling pathway controlling dauer formation. Our results demonstrate that wild-type daf-3 can repress C subelement enhancer activity during larval development and, like its dauer-promoting activity, daf-3's repressor activity is negatively regulated by TGFbeta-like signaling. We have examined expression of this gfp reporter in dauer larvae and have observed no daf-3-dependent repression of C activity. These results suggest daf-3 directly regulates pharyngeal gene expression during non-dauer development.     

Long-term effects of transduodenal sphincterotomy: symptoms and hepatobiliary function

BACKGROUND/AIMS: Endoscopic sphincterotomy is widely used in treating common bile duct stones, but the long-term effects of destroying the sphincter of Oddi are not known. This study investigated the long-term (15-20 years) effects of transduodenal sphincterotomy on gastrointestinal symptoms and hepatobiliary function in a retrospective controlled study. METHODOLOGY: Between 1974 and 1977, choledocholithotomy was performed in 131 patients either transduodenally (60 patients) or via choledochotomy (71 patients). For the retrospective part of the study, all hospital records, death certificates and autopsy reports were reviewed. Twenty-seven patients who could be reached and volunteered to participate (12 and 15, respectively) were re-examined. In the re-examination part of the study, a standard questionnaire interview, laboratory tests, quantitative cholescintigraphy and ultrasonography were performed. RESULTS: The hospital mortality for the primary operations was 0.8%, 0% for the transduodenal sphinterotomies and 2% for the choledochotomies; the difference was not significant. During the follow-up period, no significant differences could be seen in the death rate or in the causes of death between the study groups. During re-examination, flatulence was found to be more common in the choledochotomy subgroup (7/15 vs 2/12, p<0.05). In the laboratory tests, conjugated bilirubin and serum aspartate amino transferase levels were higher in the transduodenal subgroup than in the choledochotomy subgroup (3.3 umol/L, SD 0.4 vs 2.2 umol/L, SD 0.2, p<0.02; and 25 U/L, SD 12.6 vs 18.6 U/L, SD 5.0, p<0.05, respectively). Furthermore, 6/12 (50%) of the transduodenal subgroup had elevated serum alanine aminotransferase, aspartate aminotransferase or amylase levels, as compared to 1/15 (7%) in the choledochotomy subgroup (p<0.02). In terms of ultrasonography, in the choledochotomy subgroup, the common bile duct diameter was larger than 8 mm in 8/15 (53%) patients, as compared to 1/12 (8%) in the transduodenal subgroup (p<0.02). In terms of quantitative cholescintigraphy, in 9/12 (75%) patients of the transduodenal subgroup, the hilum-duodenum transit time was less than 10 minutes, as compared to 4/12 (47%) of the choledochotomy subgroup. CONCLUSIONS: Transduodenal sphincterotomy results in decreased flatulence and enhanced common bile duct drainage, even in the long-term period, but slightly higher serum liver funtion tests, when compared to supraduodenal choledochotomy.     

The role of hepatobiliary scintigraphy in cystic fibrosis

This was a prospective open study that examined the quantitative and qualitative analysis of hepatobiliary scintigraphy (DISIDA) in detecting liver involvement in cystic fibrosis (CF). Forty-four adult and pediatric patients (median age, 12.1 years; range, 1.1-36.3 years) were divided into three groups: group 1, no evidence of liver involvement (n = 8); group 2, biochemical evidence of liver involvement on two or more occasions (n = 26); and group 3, clinical evidence of liver disease (n = 10). In groups 1 and 2, the most common qualitative scintigraphic finding was focal intrahepatic retention of tracer (26/34 patients, 12 of whom had normal findings on ultrasonography). This finding corresponds to focal cholestasis and may warrant treatment with the choleretic agent ursodeoxycholic acid (UDCA). In the group 3 patients, the abnormal qualitative scintigraphic appearances (heterogeneous uptake of tracer and nodular liver outline) added little to the findings on ultrasonography; however, these patients had a prolonged mean hepatic clearance time compared with those in groups 1 and 2 (one-way ANOVA; P < .015). It is proposed that scintigraphy with DISIDA has a role in the detection of early liver involvement in cystic fibrosis.     

Drug-induced proteolysis: a correlation with oedema-reducing ability

A very strong correlation has been shown to exist between acid and neutral protease activity levels in the skin, the acid protease activity level of the oedema fluid, and the oedema-reducing ability of the benzo-pyrones and related drugs. Macrophages, which are believed to be the main cells affected by the drugs, are very common in thermally injured tissues. Their lysosomal enzymes work at an acid pH. Since the main acid protease is cathepsin D, the overall acid protease levels are representative of changes in cathepsin D levels. Elevated levels are concomitant with more complete and rapid digestion of accumulated protein. The resulting fragments then can rapidly leave the injured tissues, freeing the oedema fluid. This form of proteolysis is very much different from that which is used by pharmacologists as a measure of inflammation. Normal proteolysis in inflammation represents an estimate of tissue derangement, but the proteolysis induced by drugs such as the benzo-pyrones represents a means of lessening some of the more injurious effects of this derangement. The results presented here strongly confirm this.     

Hepatic imaging with iodinated nanoparticles: a comparison with iohexol in rabbits

RATIONALE AND OBJECTIVES: We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease. METHODS: Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration. Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents. RESULTS: EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration. CONCLUSION: EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for liver CT scanning.     

The therapeutic use of a phosphatide food concentrate in diseases of the hepatobiliary system

Our studies on phosphatide, a food concentrate, produced as a by-product during the extraction of an edible oil in the oil-extraction plants, showed its high efficacy in patients (n = 52) with abnormalities of the hepatobiliary system. The drug having more than 40 weight percent of phosphorus-containing lipids appeared to be efficacious not only in respect of the subjective status of the patients but also the functional state of the liver and paraments characterizing lipid metabolism.