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.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

Software compensation improves the analysis of heterogeneous tumor samples stained for multiparameter DNA flow cytometry

Background: High concentrations of propidium iodide (PI), in combination with fluorescein isothiocyanate (FITC) and R-phycoerythrin (RPE) used for multiparameter DNA flow cytometry (FCM), cause spectral cross-talk into the green fluorescence channel (FL1). We have evaluated the use of post-acquisition software compensation (N-Color Compensation) in order to correct this spectral cross-talk caused by PI. Method: Cell mixtures were prepared consisting of keratin 8/18 FITC labeled, keratin 8/18 RPE labeled, and unlabeled MCF-7 breast carcinoma cells. DNA was stained with PI (100 μM). Post-acquisition software compensation was applied to correct the spectral cross-talk of PI fluorescence. Secondly, the distribution of the Ki-67 (FITC) protein during the cell cycle (PI) of SiHa cervical carcinoma cells (no software compensation) was compared to the Ki-67 expression pattern of SiHa cells, simultaneously stained for keratin 8 (RPE), after applying software compensation. Finally, software compensation was used to compare the relative levels of PCNA and p53 expression in two clinical ovarian cancer ascites specimens, stained for PCNA or p53 (FITC), keratin 8/18 (RPE), and DNA (PI), with a known p53 status (positive and negative, respectively). Results: The Ki-67 cell cycle-dependent pattern of a triply stained sample (Ki-67 (FITC), keratin 8 (RPE), and DNA (PI)) is restored after software compensation and the results are comparable to the Ki-67 distribution of a sample stained solely for Ki-67 and DNA. P53 expression could only be resolved after using software compensation in the p53 positive ovarian ascites (OA) sample. Conclusions: We conclude that software compensation is a robust and reliable post-acquisition method for the correction of RPE/PI spectral cross-talk, permitting better identification of weakly expressed proteins in heterogeneous clinical tumor samples stained for multiple cellular antigens and DNA using PI.     

The Scimitar syndrome: CT findings in partial anomalous pulmonary venous return

An anomalous pulmonary vein draining into the subdiaphragmatic inferior vena cava was initially demonstrated on computed tomographic (CT) scans. The diagnosis of scimitar syndrome was confirmed with digital subtraction angiography. In retrospect, the anomalous vein and dextroposition of the heart were shown on chest radiographs.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean ± SD of total stool output (g kg⁻¹) was 532 ± 476 vs 479 ± 354 and the duration (h) of diarrhoea was 108 ± 68 vs 103 ± 53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

Basic isoferritin and hypercalcaemia in renal cell carcinoma

A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a “basic isoferritin”. The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.