Development of progressive glomerulosclerosis in experimental chronic serum sickness

A rat model of chronic serum sickness was used to study the pathogenesis of progressive glomerulosclerosis complicating experimental immune-complex glomerulonephritis. Chronic serum sickness was induced by immunising rats with bovine serum albumin followed by intraperitoneal administration of the antigen. Early lesions consisted of mesangial deposits of rat immunoglobulins, followed later by transient subendothelial and persistent subepithelial immune aggregates. On the basis of the peak level of proteinuria around day 80, three groups of rats were distinguished: I physiological proteinuria; II 50-500 mg/24 h; and III greater than 500 mg/24 h. The animals were killed at day 220 and the presence of mesangial proliferation, epithelial proliferation, and synechiae, as well as focal glomerulosclerosis was scored. It appeared that all and only proteinuric animals developed progressive glomerulosclerosis, although all three groups of animals passed through a phase with mesangial and subendothelial immune deposits. A strong correlation was found between the degree of proteinuria and the proportion of glomeruli affected. We conclude that the combination of mesangial and subendothelial deposits on the one hand and subepithelial deposits associated with increased protein loss on the other constitute a conditio sine qua non for the development of progressive glomerulosclerosis in this model. The use of specific antibodies to investigate the composition of the sclerotic lesions showed the presence of laminin and type IV collagen, but not of types I and III collagen in sclerotic areas of glomeruli. This indicates that the development of progressive glomerulosclerosis in this model is due to an increased production of glomerular basement membrane components by presumably solely glomerular cells after the occurrence of immunological glomerular injury.     

Amelioration of hypertrophic cardiomyopathy using nonsurgical septal ablation in a cirrhotic patient prior to liver transplantation.

A 53-year-old male with hepatitis C cirrhosis, who had been refused liver transplantation because of hypertrophic cardiomyopathy (HC), underwent nonsurgical septal ablation using alcohol with resolution of his ventricular outflow obstruction. This patient was able to subsequently undergo a successful deceased donor liver transplantation. This is the first reported case of alcohol induced septal ablation being performed in a cirrhotic patient with HC. Such nonsurgical procedures may be attractive in cirrhotic patients who are refused access to liver transplantation because of high surgical risk.     

How Frequent Are Asthma Exacerbations in a Pediatric Primary Care Setting and Do Written Asthma Action Plans Help in Their Management?

Purpose. In the National Heart, Lung, and Blood Institute Guidelines for the Diagnosis and Management of Asthma, the expert panel recommends that a written asthma action plan be provided for all patients with asthma. Studies evaluating the usefulness of the asthma action plan in children are limited. We aim to determine exacerbation frequency and usefulness of the asthma action plan in managing exacerbations that occur in a pediatric primary care setting. Methods. Caretakers of asthmatic children attending the general pediatric clinic in an inner-city hospital completed a one-page questionnaire covering topics such as asthma severity, frequency of exacerbations, and possession/usefulness of an asthma action plan. Although controversy exists over the definition of yellow and red zone exacerbations, we defined the yellow zone as symptoms that require albuterol more than three times a day or more than two nights in succession. The red zone was defined as symptoms requiring systemic corticosteroids and/or an urgent physician visit. Results. Seventy of 75 subjects completed the survey. Almost 80% of respondents carried the diagnosis of persistent asthma, whereas the remainder had intermittent asthma. Exacerbation frequency over a 3-month period was determined. Approximately 80% of children experienced at least one yellow zone episode: 42% had one or two yellow zone episodes, and 39.6% had between three and five episodes. Sixty-three percent of patients did not experience a single red zone exacerbation. Almost 75% (44 of 59) of subjects possessed an asthma action plan. Ninety percent (37 of 41) of respondents with action plans found the plan to be useful in managing exacerbations. Conclusion. Approximately four of every five asthmatic children seen in this primary care setting experienced a yellow zone exacerbation at least once during a 3-month period. One third experienced at least one red zone episode. Nine of every 10 caretakers with an action plan reported the asthma action plan to be of value in managing exacerbations.     

Quantitative analysis of 8-isoprostane and hydrogen peroxide in exhaled breath condensate.

Exhaled breath condensate (EBC) provides a noninvasive means of sampling the lower respiratory tract. Collection of EBC might be useful in the assessment of airway oxidative stress in smokers. The aim of this study was to determine 8-isoprostane and hydrogen peroxide levels in EBC, and, in addition, to investigate the reproducibility of these measurements. EBC samples were collected from 12 healthy male smokers at three time points within 1 week. 8-isoprostane and H2O2 were measured in nonconcentrated EBC using immunochemical and colorimetric assays, respectively. 8-isoprostane and H2O2 were detected in only 36 and 47% of all EBC samples, respectively. It was not possible to calculate the within-subject variation in a reliable manner since only three of the 12 smokers exhibited detectable 8-isoprostane concentrations on all three occasions (mean 4.6 pg x mL(-1); range 3.9-7.7 pg x mL(-1)), whereas H2O2 could not be detected on all three occasions in any of the smokers. Spiking experiments revealed a recovery of 83.5-109.5% for 8-isoprostane and 69.9-129.0%, for H2O2 in fresh EBC samples. It was concluded that levels of 8-isoprostane and hydrogen peroxide cannot be reproducibly assessed in exhaled breath condensate from healthy smokers because of their low concentration and/or the lack of sensitivity of the available assays.     

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.     

The partogram's result and neonatal outcome.

The aim was to investigate to what extent low Apgar scores are linked to the partogram's result and, more specifically, if the action line should be set 3 rather than 4 h parallel and right to the alert line. Some 24.0% of all labours evolved left to the alert line and 26.3% of the labours right to the alert line crossed the 4-h action line. An Apgar score of 相似文献