The renal response to infection.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
C C Nast
Publications and source records attributed to C C Nast.
Regulation of eicosanoid production in rabbit colon by interleukin-1.
Prostaglandins and thromboxanes are increased in human and experimental colitis, but the factors that regulate this enhanced production are unclear. The present studies evaluate the effects of the monokines, interleukin-1 alpha and beta on eicosanoid production in rabbit colon. In tissue incubations the peak dose response of eicosanoid release to human recombinant interleukin-1 is 50 ng/ml. Interleukin-1 alpha increases prostaglandin E2 (PGE2) by 4.5 +/- 1.9 ng/g tissue, 6-keto PGF1 alpha by 6.2 +/- 2.7 ng/g, and thromboxane B2 by 2.1 +/- 0.3 ng/g compared to placebo. In isolated rabbit colons perfused with Krebs' solution, 10-h infusion of interleukin-1 alpha (50 ng/ml) progressively increases production of PGE2, 6-keto PGF1 alpha, and thromboxane B2. Bolus injections of bradykinin increase production of PGE2, but not 6-keto PGF1 alpha and thromboxane B2, and these responses are markedly augmented by interleukin-1 alpha: at 10 h bradykinin-stimulated PGE2 production is 518 +/- 104 vs. 95 +/- 18 ng/5 min (p less than 0.005), 6-keto PGF1 alpha is 172 +/- 88 vs. 8 +/- 2 ng/5 min (p less than 0.02), and thromboxane B2 is 60 +/- 14 vs. 13 +/- 4 ng/5 min (p less than 0.02) for interleukin-treated colons vs. placebo-treated colons, respectively. The response is greater with interleukin-1 alpha than interleukin-1 beta. This study demonstrates that interleukin-1 stimulates prostaglandin and thromboxane production in normal colon tissue. These data are consistent with the concept that interleukin-1 production by inflammatory cells may augment prostaglandin and thromboxane production in colitis.
6-Ketoprostaglandin F1 alpha↗
Oxygen-dependent differences in exopolysaccharide production and aminoglycoside inhibitory-bactericidal interactions with Pseudomonas aeruginosa--implications for endocarditis.
Antibiotic-induced growth inhibition and killing of a non-mucoid strain of Pseudomonas aeruginosa (PA-96) in vitro and ex vivo were studied at oxygen tensions approximating those of the right and left cardiac ventricles in vivo (pO2 = 40 VS. 80 mm Hg). This pseudomonal strain grew equally at the two oxygen tensions, yet only bacteria exposed to pO2 80 mm Hg revealed significant exopolysaccharide production as shown by PAS and ruthenium red staining. Similarly, scanning electron microscopy of pseudomonal cells within aortic (but not tricuspid) vegetations revealed surface excrescenses compatible with surrounding exopolysaccharide (glycocalyx). Amikacin at 10 x MIC caused significantly less in-vitro killing of pseudomonal cells at pO2 80 VS. 40 mm Hg. In vitro and ex vivo (within experimental aortic and tricuspid vegetations), post-antibiotic effect durations were about 50% shorter for cells exposed to amikacin at pO2 80 mm Hg than 40 mm Hg. These data demonstrate suboptimal aminoglycoside-induced growth inhibition and killing, as well as enhanced exopolysaccharide production of a non-mucoid P. aeruginosa strain at oxygen tensions reflective of the left side of the heart. These findings may in part explain the better results seen in aminoglycoside-treated right compared to left-sided pseudomonal endocarditis in man.
Amikacin↗
Clinical utility of kidney biopsies in the diagnosis and management of renal disease.
A prospective study was undertaken to assess the utility of the renal biopsy as a tool in the clinical practice of nephrology. Nephrologists performing this procedure were surveyed concerning prebiopsy diagnosis, plans for therapy and estimation of prognosis, before and after biopsy results were disclosed. On the basis of 108 specimens from both academic centers and community hospitals, clinical and pathological diagnoses differed in 63% and therapeutic approach was altered in 34% of the cases. These results were greatest for nephrotic syndrome and for renal failure of rapid onset. The change in treatment was frequently of major consequence: decisions for the use of corticosteroids, cytotoxic agents and/or plasma exchange were altered based upon biopsy diagnoses. There were no differences either in diagnostic acumen or therapeutic approach between academic and community nephrologists. We conclude that renal biopsies are an important and frequently used part of the nephrologists' approach to patient care.
Acute Kidney Injury↗
Pathogenic effects of monocytopenia, granulocytopenia and dexamethasone on the course of experimental Pseudomonas aeruginosa endocarditis in rabbits.
Intravegetation host inflammatory cell function may play a role in the more salutary clinical outcomes in human right- vs. left-sided endocarditis. To study this in vivo, 90 rabbits with tricuspid Pseudomonas aeruginosa endocarditis received either no therapy (controls), nitrogen mustard (HN2) to induce combined granulocytopenia + monocytopenia, etoposide (VP-16-213) to induce selective monocytopenia, or dexamethasone. Intravegetation inflammatory cell influxes were scored on a semiquantitative histopathologic scale. In VP-16-213 and dexamethasone recipients and tricuspid endocarditis controls, gradual decreases in mean intravegetation bacterial densities were observed over a 13-day infection period; in contrast, HN2 treatment was associated with a significant increase in intravegetation bacterial densities by day 13 of infection (p less than 0.001 vs. other tricuspid endocarditis groups). Histopathologically, vegetations from untreated controls and dexamethasone recipients showed granulocyte influxes during infection, while HN2 treatment resulted in predominantly granulocyte depletion within infected tricuspid vegetations; VP-16-213 caused mononuclear cell depletion at this site. This study supports the concept that the granulocyte plays a critical role in modulating spontaneous endocardial clearances of bacteria in experimental tricuspid endocarditis.
Animals↗
Evaluation of cyclosporine nephrotoxicity by renal transplant fine needle aspiration.
Fine needle aspiration is a relatively safe, minimally invasive technique for morphologic evaluation of intragraft events in renal transplant recipients. We assessed the usefulness of this technique in the diagnosis of acute cyclosporine nephrotoxicity (NT). Two aspirate features considered indicative of NT were examined; tubular cell cytoplasmic isometric vacuolization (IV) and isolated graft lymphocytosis. Fifty-six adequate aspirates from 22 patients receiving cyclosporine were evaluated by the method of Hayry and von Willebrand. Retrospectively, four groups were identified for the purpose of this study: A, greater than 50% tubular cell population with IV (N = 11); B, less than 50% tubular cell population with IV (N = 15); C, graft lymphocytosis without IV (N = 15); D, normal aspirates (N = 15). A retrospective clinical diagnosis of cyclosporine NT was present at the time of ten aspirations in Group A (91%) and one each in Groups B (7%) and C (7%, P less than 0.001). No patients with aspirates in Group D had NT. The remaining aspirates were from patients with multiple clinical diagnoses. Plasma cyclosporine levels did not correlate with IV or graft lymphocytosis. Serum creatinine levels were higher in patients from Group A as compared with Group D (P less than 0.03). We conclude that not all patients treated with cyclosporine or diagnosed with clinical cyclosporine NT demonstrate IV or lymphocytosis in graft aspirates. However, when isometric vacuolization occurs in greater than 50% of tubular cells, acute cyclosporine NT must be considered strongly. Isolated graft lymphocytosis is a nonspecific finding.
Biopsy, Needle↗
Sex vulnerability in the subtotal nephrectomy model of glomerulosclerosis in the rat.
Unilateral nephrectomy and contralateral ligation of two thirds of the renal arterial circulation were performed on male (N x M, n = 6) and female (N x F, n = 7) Sprague-Dawley rats. Sham nephrectomies were performed in 16 male and female control rats (SN x M, n = 8; SN x F, n = 8). Creatinine clearance corrected for body weight and systolic arterial blood pressure were equal in both nephrectomized groups after 1, 3, and 5 weeks. The appearance of proteinuria was delayed in N x F and was still significantly less than N x M after 5 weeks (79 +/- 22 vs 30 +/- 12 mg per 24 hours, p less than 0.05). Glomerular visceral epithelial cell protein reabsorption droplets and vacuolization were equal in N x M and N x F. N x F exhibited one fifteenth of the glomerulosclerosis seen in N x M (p less than 0.01). In addition, there was one fourth of the mesangial expansion, but this trend did not reach statistical significance (p greater than 0.05). Mean glomerular volume was similar in male and female sham-operated (p greater than 0.05) and nephrectomized rats (p greater than 0.05), and nephrectomy resulted in hypertrophy in both groups (p less than 0.01). Glomerular procollagen alpha 1(IV) mRNA levels were higher in N x M than in all other groups (p less than 0.05) and correlated with mesangial expansion and glomerular sclerosis (p less than 0.01) but not with systemic hypertension, proteinuria, or epithelial cell changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Cystosarcoma phyllodes metastatic to the mandible.
Cystosarcoma phyllodes of the breast appears to encompass a diverse group of tumors with variable clinical behaviors. Although the tumor can behave in a malignant fashion, metastases to the head and neck region are distinctly uncommon. A case is presented of a solitary metastasis to the mandible appearing 1 year after mastectomy and in the absence of widespread disease. The metastatic potential of this neoplasm is discussed and involvement of the head and neck region is reviewed.
Breast Neoplasms↗
Chemotactic peptides. Mechanisms, functions, and possible role in inflammatory bowel disease.
An important component of host defenses is the ability of inflammatory cells to detect and respond to minute concentrations of chemoattractant substances. Chemotactic peptides elaborated by both bacteria and leukocytes are the focus of this review. These peptides induce directed migration of inflammatory cells towards their targets, and stimulate biological functions including degranulation, release of oxygen radicals, phagocytosis, and eicosanoid production. Among the released eicosanoids, leukotriene B4 potentiates the leukocyte response. As with other chemotactic factors, these functions are regulated partially through differential coupling to high- and low-affinity receptors and via calcium as the second messenger. Some chemotactic peptides are elaborated by normal colonic luminal bacteria. Recent evidence demonstrates that these peptides can produce mucosal inflammation in vivo. A possible mechanism for this effect involves abnormal colonic permeability in susceptible individuals that allows bacterial chemotactic peptides access to the mucosa where they may induce inflammation. Remaining questions include the mechanism by which the mucosal barrier is breached and the role of leukotrienes in the potentiation of colonic inflammation.
Animals↗
Effects of 16,16-dimethyl prostaglandin E2 and indomethacin on leukotriene B4 and inflammation in rabbit colitis.
The role of increased prostaglandin production and the effects of exogenous prostaglandins on inflammation of colitis are not established. We administered intramuscular 16,16-dimethyl prostaglandin E2 (DiM-PGE2) and indomethacin to rabbits with formalin immune-complex colitis and measured leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and severity of inflammation. DiM-PGE2 (100 micrograms/kg/BID) reduced LTB4 production (from 401 +/- 108 to 216 +/- 58 pg/ml) and infiltration of neutrophils, mucosal necrosis, inflammatory exudate and edema (all P less than 0.05). Other studies determined that parenteral DiM-PGE2 did not reduce the initial chemical damage induced by formalin, suggesting that cytoprotection of chemical insult was not the mechanism of suppressed inflammation in the immune colitis model. Indomethacin (10 mg/kg/d) reduced endogenous PGE2 by 80%, but did not reduce leukotriene production or inflammation. Exogenous prostaglandins cause a dose-dependent suppression of inflammation in experimental colitis, by a mechanism other than cytoprotection of chemical-induced mucosal injury.
Animals↗
HIV-associated nephropathy. A unique combined glomerular, tubular, and interstitial lesion.
Although a variety of renal lesions may occur in acquired immune deficiency syndrome (AIDS), a rare but aggressive form of focal and segmental glomerulosclerosis with capillary collapse has been considered a possible component of this disorder. It is manifested by heavy proteinuria and progression to renal failure in a short time. We studied renal biopsies from nine patients with HIV infection and the above clinical features and compared the renal tissues to biopsies from HIV-positive individuals with immune complex glomerulonephritis and to biopsies from patients with heroin abuse nephropathy. The HIV-associated nephropathy was characterized by a combination of lesions: focal and segmental glomerulosclerosis, often in an early stage of evolution and with prominent degenerative changes of visceral epithelium; tubular necrosis without identifiable nephrotoxic or hemodynamic etiology; interstitial edema; large plasma protein-containing tubular casts in all segments of the nephron associated with marked tubular dilatation; and widespread tubuloreticular structures in vascular endothelium. In contrast, neither the sclerosing glomerular changes nor the tubulointerstitial abnormalities were present in HIV-infected patients with immune complex glomerulonephritis. Similarly, the tubular and interstitial changes and widespread tubuloreticular structures were absent in heroin-abuse nephropathy. The lesions of HIV-associated nephropathy occurred in patients with AIDS, AIDS-related complex, and in individuals clinically asymptomatic for HIV infection. Their morphological features in asymptomatic patients are sufficiently specific to allow for accurate diagnosis of HIV infection.
Acquired Immunodeficiency Syndrome↗
In vivo production of leukotriene B4 and leukotriene C4 in rabbit colitis. Relationship to inflammation.
Leukotriene B4, a proinflammatory compound, recently has been identified as the major metabolite of arachidonic acid in tissue incubations of human and animal colitis. To determine the relationship of inflammation to the in vivo production of leukotrienes, rabbit colitis was induced by formalin enema followed by intravenous infusion of immune complexes, and serial samples were collected by rectal dialysis. Leukotrienes B4 and C4 were measured by radioimmunoassay after high-pressure liquid chromatography. Prostaglandin E2 was assayed after Sephadex chromatography. Leukotrienes were not detected in control animals. Eicosanoid production progressively increased during development of inflammation and correlated with severity of inflammatory cell infiltration (p less than 0.01). Methylprednisolone decreased prostaglandin E2 but did not significantly reduce leukotrienes or inflammation. These data demonstrate that in vivo production of leukotrienes B4 and C4 correlates with indices of inflammation, consistent with the concept that these eicosanoids contribute to the inflammation of colitis.
Animals↗
Recurrent Henoch-Schönlein purpura following renal transplantation.
A 20-year-old patient with Henoch-Schönlein purpura leading to end-stage renal failure received a living-related renal transplant. She was treated with conventional immunosuppressive therapy. Following a quiescent period of 18 months pretransplant, at 3 months after engraftment there was recurrence of purpuric lesions with subsequent abdominal pain and glomerulonephritis. Renal and skin biopsies confirmed the immunopathologic changes of Henoch-Schönlein purpura. This case represents the second report of an adult with multiorgan recurrence of Henoch-Schönlein purpura following transplantation.
Adolescent↗
In vivo production of leukotrienes in experimental colitis.
Explore the source record for details and available documents.
Animals↗
Splenic immune deposits in bacterial endocarditis.
Splenic and renal tissues from a 61-year-old man with subacute bacterial endocarditis and acute renal failure were studied. Immune complex deposits were found both within glomeruli and splenic venous sinus basement membranes, substantiating the systemic nature of the immune injury in this disorder. The splenic deposits may, in part, be responsible for the splenomegaly often present in endocarditis.
Antigen-Antibody Complex↗
Renal cholesterol granulomas: identification and morphological pattern of development.
Cholesterol granulomas are infrequent and rarely described renal lesions occurring usually in the interstitium, characterized by clusters of foreign body giant cells containing ingested cholesterol crystals. Over a seven-year period, we observed them in 5 of 789 (0.6%) renal biopsies from patients with nephrotic syndrome of varying glomerulopathies. Four patients had renal insufficiency at the time of biopsy, while the fifth developed it within three months. To define the lesions we studied the morphogenesis of cholesterol granulomas by light and electron microscopy. Initially small cholesterol crystals formed in tubular epithelium; the crystals enlarged and were released into tubular lumina where they elongated or were passed in the urine. Further luminal growth caused the crystals to become lodged at some point in the nephron, distort and destroy tubule cells, and pierce through basement membranes with subsequent exposure to interstitial monocytes and formation of granulomas. It is likely these morphological abnormalities evolve from lipid disturbances in the nephrotic syndrome.
Adult↗
Immunohistochemical distribution of renal prostaglandin endoperoxide synthase and prostacyclin synthase: diminished endoperoxide synthase in the hepatorenal syndrome.
To evaluate possible causes of the diminished prostaglandin production in advanced hepatorenal syndrome, prostaglandin endoperoxide synthase and prostacyclin synthase were localized and semiquantitated by immunofluorescence in postmortem, biopsy and nephrectomy renal tissues. In normal kidneys, antiprostacyclin synthase serum caused intense staining in peritubular capillaries, in the adjacent renal interstitial cells and in glomerular mesangial regions. Antiprostaglandin endoperoxide synthase serum caused staining of collecting duct epithelial cells, cells of the thin ascending limb and possibly glomerular mesangial cells. Prostacyclin synthase-positive staining was graded 5+ (scale of 0+ to 5+) in all kidney samples. Medullary collecting tubule prostaglandin endoperoxide synthase-positive staining was graded 4+ or 5+ in kidney samples from patients with acute tubular necrosis or acute tubulointerstitial nephritis and from patients with liver failure without the hepatorenal syndrome. However, prostaglandin endoperoxide synthase-positive staining was markedly diminished or absent (average 1+) in patients with the hepatorenal syndrome. These data suggest that loss of the medullary prostaglandin endoperoxide synthase is the cause of diminished urinary prostaglandin E2 excretion in the hepatorenal syndrome.
Adult↗