The state of several indices of non-specific immunity in rats with nephrotoxic glomerulonephritis

Changes in the interferon reaction of leukocytes, bactericidal property of the blood serum against the E. coli and streptococcus, the activity of beta-lysins in experimental nephrotoxic glomerulonephritis reproducible with the aid of heterogenous nephrotoxic serum in mongrel male rats were studied. This model permitted to trace the changes in the nonspecific protection mechanisms depending on the pathological process in the kidneys. In nephrotoxic glomerulonephritis the most pronounced changes were seen in the interferon reaction of leukocytes: it decreased up to 90% in comparison with the normal depending on the duration of the disease. In difference from this the changes in the anti-bacterial immunity indices were observed at the period of marked nephrotic process activity.     

Attenuation of contractions to acetylcholine in canine bronchi by an endogenous nitric oxide-like substance

1. The involvement was assessed of an endogenous nitric oxide-like substance in contractions of canine bronchi to acetylcholine. 2. Canine third order bronchial rings, in some of which the epithelium was removed mechanically, were suspended in organ chambers and isometric tension was recorded. In some experiments, the content of guanosine 3',5'-cyclic monophosphate (cyclic GMP) of the bronchi was also measured. 3. Acetylcholine induced concentration-dependent contractions. The contractions were potentiated by nitro-L-arginine (an inhibitor of the synthesis of nitric oxide), oxyhaemoglobin (a scavenger of nitric oxide), and methylene blue (an inhibitor of soluble guanylate cyclase). The magnitude of the potentiation to acetylcholine-induced contractions by these inhibitors were not significantly different between tissues with and without epithelium. 4. Acetylcholine induced a concentration-dependent increase in intracellular content of cyclic GMP, which was similar in bronchi with and without epithelium. These increases were abolished by nitro-L-arginine and methylene blue. 5. During contractions to acetylcholine, exogenous nitric oxide relaxed the canine bronchi. The relaxations were not affected by nitro-L-arginine, but were augmented by superoxide dismutase plus catalase, and were abolished by methylene blue. 6. These observations suggest that, during contraction evoked by acetylcholine, the production of an endogenous nitric oxide-like substance increases and in turn attenuates the response of the airways to the muscarinic agonist. However, the endogenous nitric oxide-like substance does not play a major role in the epithelium-dependent attenuation of the contraction to acetylcholine in canine bronchi.     

Toxicology studies with cytembena (NSC-104801), an antineoplastic agent with a multispecies nephrotoxic effect

The toxic effects of cytembena in beagle dogs and rhesus monkeys were investigated with the drug given as single or daily iv injections in doses ranging from 12.5 to 200 mg/kg/day to dogs and 6.25 to 50 mg/kg/day to monkeys. Renal tubular damage was a major drug- and dose-related finding in both species and was clinically indicated by an accompanying uremia, elevated serum creatinine, and proteinuria. In the kidney, the primary lesion was cellular necrosis and desquamation of the distal tubular epithelium in animals given the lowest toxic doses. More severe but similar histologic changes produced by this drug were further characterized by single dose studies in mice which showed renal mitochondrial swelling and disruption plus generalized cell swelling as progressive, subcellular developments which were well established 24 hours after treatment. Cellular regeneration in the renal tubular epithelium was found in dogs and monkeys retained 6 weeks for observation after treatment, although functional recovery was inconsistent. A toxic effect to lymphoid tissue was an additional finding which is described.     

Prevalence of autoantibodies associated with glomerulonephritis, unaffected after extracorporeal shock wave lithotripsy for renal calculi, in a three-year follow-up

A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.     

Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model

To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H2O2, MPO and immunoglobulin (Ig)G localized transiently along the GMB. At the time of maximal inflammation, at 4 and 10 d after perfusion, MPO, IgG, and C3 could not be detected anymore. MPO-immunized rats perfused with the lysosomal enzyme extract and H2O2, in contrast to control-immunized and/or control-perfused rats, developed a proliferative GN characterized by intra- and extracapillary cell proliferation, ruptured Bowman's capsule, periglomerular granulomatous inflammation, and formation of giant cells. Monocytes, polymorphonuclear leukocytes (PMN), and to a far lesser extent T cells were found in the glomeruli. Interstitial infiltrates consisted of monocytes, PMN, and T cells. Granulomatous vasculitis of small vessels was found at 10 d after perfusion. The proliferative NCGN in this rat model closely resembles human anti-MPO-associated pauci-immune NCGN, and enables the study of the pathophysiology of anti-MPO-associated NCGN.     

Study of an anti-human transthyretin immunoadsorbent. Influence of coupling chemistry on binding capacity and ligand leakage

The pig has been reported to present with a stronger hypoxic pulmonary vasoconstriction than many other species, including the dog, but it is not known whether this is associated with a different longitudinal partitioning of pulmonary vascular resistance (PVR). We investigated the relationships between cardiac output (Q) and mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao), and effective pulmonary capillary pressure (Pc') minus Ppao, in seven minipigs and in seven dogs in hyperoxia (FI(O2) 0.4) and hypoxia (FI(O2) 0.1), first without, then with the inhalation of 80 ppm nitric oxide (NO) to inhibit any reversible component of PVR. Pc' was estimated from the Ppa decay curve following pulmonary artery balloon occlusion. In hyperoxia, minipigs compared to dogs had (Ppa - Ppao)/Q and (Pc' - Ppao)/Q plots shifted to higher pressures. Hypoxia at each level of Q increased Ppa - Ppao in minipigs more than in dogs, and Pc' - Ppao in minipigs only. Inhaled NO reversed hypoxia-induced changes in (Ppa - Ppao)/(Q and (Pc' - Ppao)/Q plots. We conclude that the minipig, compared to the dog, presents with higher PVR and reactivity including vessels downstream to the site of Pc' as determined by the arterial occlusion technique.     

Acute pancreatitis with hyperlipemia: studies with an isolated perfused canine pancreas

Clinical evidence suggests that in many settings hypertriglyceridemia can initiate an episode of acute pancreatitis. Hydrolysis of triglycerides by pancreatic lipase with the local release of large quantities of free fatty acids (FFAs) has been proposed as the pathogenetic mechanism. To gather information to evaluate this mechanism an isolated, ex vivo, perfused pancreatic preparation was used. Control preparations remained normal in gross appearance, gained little weight (18 gm), extracted oxygen and glucose and released carbon dioxide, and continued to secrete during a 4 hour perfusion period. Serum amylase remained normal (972 CU/100 ml) as did FFAs (1.11 mEq/liter). When triglycerides were added to the perfusate to increase the serum triglycerides to 1,600 mg%, the glands became edematous, hemorrhagic, and gained considerable weight (52 gm) during the 4 hour perfusion period. Serum amylase became markedly elevated (2,624 CU/100 ml), as did the serum FFA (29.19 mEq/liter). When FFAs were added directly to the perfusate, the glands became edematous, hemorrhagic, and gained weight (90 gm), but did so much more rapidly than when triglycerides were added. These studies add support to the concept that hypertriglyceridemia can initiate pancreatic injury. Furthermore, they suggest that the mechanism may be through the release of FFAs.     

Subsidence of an uncemented canine femoral stem

Factors contributing to subsidence were analyzed by radiographic evaluation and mechanical testing of 36 canine cadaver femora during and after insertion of an uncemented porous-coated femoral stem and by radiographic evaluation of 35 canine total hip arthroplasties. Mean percentage of canal fill in immediate postoperative radiographs, and percentage of canal fill at midimplant and distal implant locations, were accurate predictors of subsidence. Force required to implant the femoral stem was strongly correlated with force required for implant subsidence. Femoral morphology and percentage of canal fill at the middle and distal sites were accurate predictors of subsidence. Implants in femora with a stovepipe morphology (canal flare index less than or equal to 1.8) were six times more likely to subside than implants in femora that had a normal appearance (canal flare index 1.8 to 2.5), and 72 times more likely to subside than implants in champagne-fluted femora (canal flare index greater than or equal to 2.5). Femora with more than 85% mean, middle, or distal canal fill were less likely to subside.     

Bullous pemphigoid associated with acute glomerulonephritis

We report an 82-year-old man who presented with bullous pemphigoid and who later developed an acute glomerulonephritis with the histopathological and immunofluorescence pattern of a postinfectious glomerulonephritis. Antibodies directed against 230 and 180 kDa bullous pemphigoid antigens were detected in the patient's serum by means of the immunoprecipitation technique. Staphylococcus aureus and methicillin-resistant S. aureus were isolated from the patient's skin. We consider that in this particular patient the cutaneous infection played a part in the development of the kidney complication.     

Attenuation of experimental autoimmune neuritis in the Lewis rat by treatment with an antibody to L-selectin

The leukocyte adhesion molecule L-selectin plays a key role in the initial steps of transendothelial migration of T cells and monocytes. In this study we investigated the role of L-selectin in the pathogenesis of experimental autoimmune neuritis (EAN) an animal model of the Guillain-Barré syndrome. EAN was induced in Lewis rats by sensitization with peripheral nerve myelin. Treatment with HRL3, a monoclonal antibody to L-selectin, efficiently suppressed clinical signs of EAN. Histological examination of the peripheral nervous system (PNS) revealed a marked reduction of inflammatory infiltrates and demyelination during treatment with HRL3. We conclude that L-selectin-dependent mechanisms are of pathophysiological relevance in EAN. Modulation of L-selectin in vivo could be a novel therapeutic approach to autoimmune diseases of the PNS.     

Modeling Natural Attenuation of Fuels with Bioplume III

A natural attenuation model that simulates the aerobic and anaerobic biodegradation of fuel hydrocarbons was developed. The resulting model, BIOPLUME III, demonstrates the importance of biodegradation in reducing contaminant concentrations in ground water. In hypothetical simulations, aerobic biodegradation limited further plume expansion and accounted for approximately 30% of the overall contaminant reduction. Anaerobic biodegradation, in comparison, accounted for more than 65% of the mass loss and concentration declines and caused a shrinking of plume dimensions through time. Application of the model to Site ST-29 at Patrick Air Force Base demonstrated the viability of natural attenuation as a remedy for the existing fuel hydrocarbon plume at the site. Model simulations indicated that a stable plume will be established within 30–40 years and that the plume extent will likely stabilize to <170 m (500 ft) downgradient from the source area.     

Therapy of rapidly progressive glomerulonephritis with immunosuppressive agents

Rapidly progressive glomerulonephritis is a kidney disease leading to sudden and definitive damages of the renal parenchyma and progressive impairment of its function until the complete failure. Histological findings of the changes are characterized with dominant glomerular lesions with crescentic formations. Early and intensive immunosuppressive therapy with pulse doses of steroids (Solumedrol 1.5 to 2.5 g), followed by Prednisolone 1 mg/kg every other day and cytostatic drugs (cyclophosphamide 1-2 mg-kg/every other day) discontinues the processes of specific and non-specific inflammation in the kidney and could enable regeneration of the kidney tissues with favorable outcome of the disease. Immunosuppressive therapy should be gradually lowered after two months, and applied for at least three to six months.     

Arterial hypertension in patients with primary glomerulonephritis

Arterial hypertension is a state of blood pressure permanently higher than 160/90 mm Hg (21.3/12.6 kPa). The renal cause of hypertension occurs in about 10% of all cases. The aim of this article was to establish the frequency, the level, and the connection of the hypertension in different types of primary glomerulonephritis. In this study 90 patients with primary glomerulonephritis were observed. Hypertension was present in 45 patients (50%) and different frequency were noticed in different types of glomerulonephritis. The smallest frequency was recorded in the group with minimal changes and IgA nephritis. In the group with mesangioproliferative glomerulonephritis 52% of patients had hypertension and in the group with focal segmental sclerosis 78%. The most frequent hypertension was observed in the group with rapidly progressive glomerulonephritis. Renal failure was more frequent in patients with hypertension. Different frequencies of hypertension was established in different types of glomerulonephritis. It was not severe and was well controlled by remedies. In most cases it suggest a severe glomerular lesions and fast progression of the disease.     

Treatment of glomerulonephritis

Issuing from the importance of the glomerulonephritis and the different spontaneous course of the certain morphological forms of glomerulonephritis recommendations are given for the indication of a therapy of glomerulonephritis. For the prednisone, indomethazin, azathioprin and cyclophosphamide treatment therapeutic schemata proved in practice are recommended. The results of the therapy of 32 cases of glomerulonephritis treated with prednisone and of 125 cases treated with indomethazin are described. Two observations of a five-year-course in a rapid progressive glomerulonephritis and in a Goodpasture syndrome refer to a probably favourable therapeutic effect of azathioprin. Finally it is referred to the advantages of an additional immunofluorescence-histological examination of the renal tissue in 50 cases of glomerulonephritis observed during the course.     

Treatment of pancreatic stones with extracorporeal lithotripsy with sonographic localization

BACKGROUND: Pancreatic stones may be treated by endoscopic extraction or by surgery. Extracorporeal shock wave lithotripsy increased possibility of noninvasive steps to their elimination. The aim of this study was to describe our first experience with this method. METHOD AND RESULTS: 10 patients (6 men and 4 women) in average age 47 years (between 19 to 72 years) were treated. The lithotriptor MEDILIT with sonographic targeting was used for fragmentation of pancreatic stones. Fragmentation was achieved in 8 patients, in 4 cases we observed spontaneous disappearnace, in 3 cases an endoscopic extraction of fragments was necessary. In one case good fragmentation was observed at control ECRP, but the repeated Wirsungography showed a big pseudocyst which had not been diagnosed at the first examination and surgery was necessary. In 2 cases no fragmentation was achieved and in these cases surgery was also indicated. No serious side effects were observed, nor elevation of amylase values compared with the situation before the shock wave treatment. CONCLUSIONS: Extracorporeal shock wave lithotripsy of pancreatic stones revealed good fragmentation and disappearance stone from ductus Wirsungi without serious side effects on clinical course and surrounding soft tissues.