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Biomedical subjects

K J Lavelle

Publications and source records attributed to K J Lavelle.

At least 19 recordsLinked to original sources

Effect of prostaglandins on immune complex interaction with glomerular cells in vitro.

Previous studies demonstrated that prostaglandins of the E1 (PGE1) series reduced immune complex (IC) accumulation and inflammation in murine glomeruli in IC glomerulonephritis (GN). This study examines the effect of PGE1 on IC interaction with cultured rabbit glomerular cells and heparan sulfate synthesis by the cells. IC were formed with antigen chemically modified to produce a cationic (CAT) charge or left unmodified (UM). CAT IC binding to cells was greater than UM IC in the absence of PGE1. CAT IC binding to cells was increased by PGE1 while UM IC interaction was not affected. Prolonged exposure of cells to PGE1 enhanced CAT IC binding. Heparan sulfate synthesis by the cells was not affected by the concentrations of PGE1 employed. The findings suggest the benefit provided by PGE1 in murine IC GN may not be due to a direct effect on glomerular cells which reduces glomerular IC accumulation.

Alprostadil↗

Effect of indomethacin and benoxaprofen on immune complex interaction with cultured glomerular cells.

Prostaglandins of the E series (PGE) increased immune complex (IC) interaction with cultured glomerular cells in a previous study. The present study examines the effect of indomethacin (IND) and benoxaprofen (BEN) on interaction of IC with cultured cells and their effect on PGE enhanced cell-IC interaction. IC were formed with antigen modified to produce a cationic (CAT) charge or left unmodified (UM). IND increased cell interaction with IC formed with CAT antigen (CAT IC). BEN had no effect on the interaction of IC formed with either antigen. The combined use of IND and PGE increased CAT IC interaction to the same degree as when each was used alone. BEN prevented the increased CAT IC interaction produced by IND or PGE when used in combination. Protamine sulfate prevented the enhanced CAT IC interaction produced by IND or PGE while sodium heparin had no effect. The results indicate IND and PGE increase cell IC interaction, the increase is not additive when they are combined, the effects of both are blocked by BEN, and protamine sulfate inhibits the effects of both compounds.

Animals↗

Effect of antigen charge on immune complex interaction with glomerular cells in culture.

The effect of antigen charge on immune complex (IC) interaction with glomerular cells was evaluated using cultured rabbit glomerular cells. Rat albumin (Alb) was modified to produce a cationic charge; isoelectric point (pI) 7.4-8.0; anionic charge, pI 4.0-4.2; or left unmodified, pI 6.2-6.4. I125-IC (100 micrograms Alb in complex) was incubated with cells for 44 hr. Cationic Alb IC (CAT IC) interaction was 7 and 10 times greater than unmodified (UM) and anionic (AN) IC, 7596 +/- 613 vs 1016 +/- 176 and 746 +/- 106 pg I125-Alb/micrograms cell protein, mean +/- SE (P less than 0.01). A 10-fold excess of unlabeled CAT Alb decreased CAT IC interaction (6342 +/- 432 vs 1246 +/- 296 pg I125-Alb/micrograms cell protein, P less than 0.01) increased UM IC (981 +/- 186 vs 3994 +/- 394 pg I125-Alb/micrograms cell protein, P less than 0.01), and had no effect on AN IC. A 10-fold excess unlabeled CAT IC increased interaction of both CAT IC (7067 +/- 514 vs 37,416 +/- 3026 pg I125-Alb/micrograms cell protein) and UM IC (994 +/- 123 vs 12,922 +/- 566 pg I125-Alb/micrograms cell protein) but not of AN IC. Incubation of cells with CAT, UM, or AN Alb followed by specific antibody demonstrated increased antibody interaction with cells exposed to CAT Alb (15,212 +/- 676 vs 3866 +/- 406 and 1785 +/- 206 pg I125-IgG/microgram cell protein for UM and AN Alb, respectively).

Albumins↗

Nephrotoxicity of radiocontrast media in ischemic renal failure in rabbits.

Ischemic renal failure was produced in rabbits by occluding the renal arteries for 90 min. Group 1 (n = 8) received radiocontrast media at the time of occlusion, group 2 (n = 8) 24 h after occlusion, and group 3 (n = 8) 3 days after occlusion. Group 4 (n = 12) was subjected to ischemic injury alone, group 5 (n = 4) served as sham-operated controls and group 6 (n = 4) did not undergo surgery but received radiocontrast media. Serum creatinine concentration in group 1 increased to a greater degree (p less than 0.001) than all other groups and did not return to normal during the 8-day observation period. Creatinine concentration in groups 2, 3, 4, and 6 were comparable and significantly increased compared to sham-operated group (p less than 0.05). Urinary excretion of alanine aminopeptidase and N-acetyl-beta-glucosaminidase in group 1 was significantly greater than all other groups (p less than 0.05). Microscopic analysis indicated tubular necrosis was more prominent in group 1. Radiocontrast media is nephrotoxic and in the setting of ischemic injury may prevent recovery of renal function. Toxicity was dependent on the time of administration since functional impairment was not increased if dye was given 1 or 3 days after ischemic injury.

Acetylglucosaminidase↗

Interaction of immune complexes with cultured rabbit glomerular cells.

Rabbit glomerular cell cultures were established from adolescent and mature rabbits in the absence of antibiotics. Fibroblast growth factor was added to half the cultures. Immune complexes (IC) formed with 125I bovine albumin and rabbit antibody were incubated with 10-day-old cultures for 44 h. Cell-IC interaction was observed in all samples but was increased in cultures without growth factor: the effect was not age dependent. Cells cultured without growth factor had increased surface accumulation of fibronectin. Addition of antifibronectin antibody to cell cultures did not inhibit cell complex interaction. The presence of unlabeled IC reduced labeled IC binding in cultures without growth factor. Binding of IC made with F(ab')2 fragments exceeded that of IC made with intact IgG. The results suggest IC bind with cultured glomerular cells and the degree of interaction is influenced by the presence of growth factors which alter cell membrane composition.

Animals↗

Management of amikacin overdose.

A woman with subarachnoid hemorrhage inadvertently received 18 g of amikacin over a 4-hr period, 20 times the recommended total daily dose. Intravenous fluids were administered to expedite renal excretion of the amikacin, and a peritoneal dialysis was performed to augment drug elimination. Drug levels were measured sequentially in serum, urine, and peritoneal dialysate. Renal clearance of the drug was increased compared to clearance following a standard dose and the drug was rapidly excreted in the urine. Amikacin was not detected in the peritoneal dialysate. There were no apparent toxic effects from the overdose. A patient with normal renal function who receives a potentially toxic dose of amikacin can be appropriately managed by careful hydration and maintenance of a generous diuresis.

Adult↗

Mezlocillin enteral absorption in rabbits.

To determine the role of enterohepatic recirculation on its nonlinear elimination, we studied the enteral absorption of mezlocillin in rabbits. Mezlocillin was not substantially absorbed from the stomach or duodenum. We conclude that enterohepatic recirculation does not cause the dose-dependent elimination kinetics of mezlocillin.

Animals↗

The effect of antimacrophage antiserum on immune complex glomerulonephritis.

The effect of anti-M IgG on acute IC GN was assessed in rabbits. Nephritis was induced in sensitized animals with BSA. Anti-M IgG and the other immunoglobulins given to the various groups were administered by intra-aortic injection at the orifice of the left renal artery to avoid pulmonary sequestration of the antibodies. The animals were nephrectomized on the right to permit unilateral renal perfusion. The immunoglobulins were given to the study groups every 8 hr for 4 days, which corresponded to the period of IC formation and deposition in this model. Renal arteria perfusion with anti-M IgG reduced glomerular cellularity and preserved renal function. The groups given the other immunoglobulins were not afforded the same protection.

Animals↗

Renal hyperconcentration of 99mTc-HEDP in experimental acute tubular necrosis.

The effect of transient renal ischemia on renal concentration and distribution of 99mTc-HEDP, 99mTc-DMSA, and 99mTc-DTPA was compared in rabbits with acute tubular necrosis. Scintigrams were obtained after injection in normal rabbits or ones with unilateral or bilateral ischemia. 99mTc-HEDP concentration in ischemic tissue was 8 to 18 times normal 1--4 hours after injection, and the resulting images delineated the morphological changes in the ischemic kidneys more accurately than those obtained with DMSA or DTPA. Calcium concentration in the ischemic kidneys increased sixfold. 99mTc-HEDP may be useful in evaluation of renal failure secondary to tubular injury.

Acute Kidney Injury↗

Ferritin- and apoferritin-induced immune complex glomerulonephritis in mice.

In order to study the effects of the protein moiety independent of the protein-iron complex in the development of ferritin-induced glomerulonephritis, we compared the effects of ferritin, equimolar amounts of apoferritin, and equimolar amounts of iron dextran in Swiss albino mice. The results were compared to both saline-injected and non-injected controls. Ferritin resulted in a glomerulonephritis associated with predominantly mesangial deposition of immune complexes. Tubulo-interstitial changes occurred as well. Iron dextran resulted in similar but less severe tubulo-interstitial changes and evoked no glomerular alterations. Apoferritin resulted in an immune complex glomerulonephritis usually associated with membranous deposits. No tubular or interstitial changes occurred. Proteinuria developed in animals receiving apoferritin. Since the protein-iron complex caused tubular and interstitial damage, apoferritin may provide a more suitable model of immune-complex-mediated glomerulonephritis.

Animals↗

The influence of selective thrombocytopenia on immune complex glomerulonephritis.

Anticoagulation in experimental GN has not uniformly reduced inflammation and prevented functional impairment. The observation that platelet thrombi are occasionally present in nephritic kidneys prompted the suggestions that platelet aggregation may play a fundamental role and that inhibition of aggregation may be of therapeutic value. To test this hypothesis, the effect of selective platelet depletion on acute IC GN in the rabbit was evaluated. IC GN was induced with bovine albumin, and platelet depletion with APS. Platelet depletion preceded proteinuria by more than 36 hr and was sustained for 5 days. Platelet accumulation within the nephritic kidney was quantitated with chromium-labeled platelets. The hemodynamic effect of parenteral administration of APS on the evolution of IC GN was assessed by comparing IV with IP administration. Thrombocytopenia in the absence of hypotension had no inhibitory effect on IC GN, nor was there platelet accumulation within the nephritic kidneys of the platelet-depleted animals. These results indicate that platelet aggregation is not essential in the pathogenesis of IC GN and that inhibition of platelet aggregation may be of little value.

Animals↗

Surgical treatment of infective endocarditis in hemodialysis patients.

Congestive heart failure following infective endocarditis in hemodialysis patients has been uniformly fatal in patients treated with antibiotics alone. Thirteen patients on chronic hemodialysis have undergone replacement of the infected valve with an overall survival of 61%. The aortic valve was involved in 10 patients and Staphylococcus aureus the responsible organism in nine. Recurrent bacteremia occurred in two of the eight long-term survivors and was successfully treated with antibiotics in one patient and replacement of the prosthesis in the other. The surgical treatment of infective endocarditis in the hemodialysis patient is an acceptable mode of therapy and its application should not be hindered by reservations concerning operative feasibility or postoperative longevity. As in non-dialysis patients with infective endocarditis and congestive heart failure early operative intervention may substantially improve survival.

Adult↗