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R G Appel

Publications and source records attributed to R G Appel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Human immunodeficiency virus-associated nephropathy: current concepts.

A distinct form of renal disease has been described in patients at various stages of HIV infection that is becoming increasingly important as a cause of morbidity and mortality. Black race and intravenous drug abuse appear to predispose one to its development. The HIV-associated nephropathy is characterized by nephrotic-range proteinuria, rapid progression to end-stage renal disease, a diffuse sclerosing glomerulopathy with significant tubulo interstitial disease seen on light microscopy, and tubuloreticular inclusions seen via electron microscopy. The entity can be separated from heroin-associated nephropathy. The pathogenesis is unclear. Possibilities include direct invasion of the virus, effects of other viruses, genetic factors, immune factors, and multiple growth factors. Not all patients with HIV infection and renal disease have HIV-associated nephropathy. Because of prognostic and therapeutic implications, it is crucial to differentiate these lesions. Some reports suggest a possible beneficial effect of zidovudine therapy, but more study is required. Patient survival is dependent on the stage of HIV infection. Dialysis therapy does not appear to substantially prolong life in most patients with AIDS and irreversible renal failure. Therefore, a number of ethical issues have arisen that deal with medical futility.

AIDS-Associated Nephropathy↗
PubMed1994

Renal biopsy findings in presumed hypertensive nephrosclerosis.

The 'classic' descriptions of renal histologic abnormalities in patients with hypertensive nephrosclerosis were based upon specimens obtained at autopsy or sympathectomy and were evaluated by light microscopy, without the aid of immunofluorescence or electron microscopy. Patients with renal insufficiency accompanied by elevated blood pressure, hypertensive target organ damage (retinal disease and left-ventricular hypertrophy) and mild proteinuria are typically labelled as having hypertensive nephrosclerosis in the absence of renal biopsy material. Herein, we report the clinical summaries and renal pathology from 2 patients initially diagnosed with hypertensive nephrosclerosis. Glomeruli exhibiting focal and segmental sclerosis and interstitial scarring were present in both cases. The presence of primary renal disease in patients felt to have hypertensive nephrosclerosis is likely more common than currently appreciated. This may result from the lack of renal histologic material and the late presentation of these patients to nephrologists. Misclassification of hypertensive nephrosclerosis would impact greatly on the epidemiology of end-stage renal disease and the evaluation and treatment of patients with chronic renal insufficiency.

Biopsy↗
PubMed1994

Unexpected nonocclusive mesenteric infarction during continuous ambulatory peritoneal dialysis.

An unexpected case of nonocclusive mesenteric infarction in a patient on continuous ambulatory peritoneal dialysis is described. The common clinical finding in this entity is a low cardiac output state or even circulatory collapse. Nonocclusive mesenteric infarction has been reported very rarely during continuous ambulatory peritoneal dialysis, and only in the setting of cardiac dysfunction or prolonged hypotension. The current patient had none of the typical features commonly described in the clinical setting of nonocclusive mesenteric infarction; potential mechanisms, including the role of erythropoietin, in the genesis of this disorder are discussed.

Erythropoietin↗
PubMed1993

Renal duplex sonography after treatment of renovascular disease.

PURPOSE: To define the value of renal duplex sonography (RDS) to detect the presence of critical renal artery (RA) stenosis or occlusion after surgical repair or percutaneous transluminal balloon angioplasty (PTRA), we retrospectively reviewed our recent 71-month experience. METHODS: From January 1987 through November 1992, 272 patients underwent 279 operative RA repairs and 35 patients underwent PTRA. Three hundred twenty-five RDS examinations were performed in 176 patients after operative intervention or PTRA during the study period. Forty-one of these patients had conventional angiography providing 61 RA for RDS comparison, and these data form the basis of this analysis. Twenty-four women and 17 men (mean age 57 years) underwent 44 operative RA repairs or 17 PTRA for correction of atherosclerotic disease (51 arteries) or fibromuscular dysplasia (10 arteries). Before their renovascular procedure each patient had significant hypertension (mean 193/106 mm Hg). RDS after surgery or PTRA was technically complete for all 61 RA. RESULTS: Compared with angiography RDS correctly identified 47 of 48 repairs with less than 60% RA stenosis , 7 of 11 repairs with 60% to 99% stenosis, and 2 renal artery occlusions, providing a 69% sensitivity rate, 98% specificity rate, 90% positive predictive value, and a 92% negative predictive value. These results were adversely affected by branch RA disease, which accounted for three of four false-negative RDS study results. For 50 kidneys undergoing correction of main RA disease, RDS demonstrated an 89% sensitivity rate, 98% specificity rate, and 96% overall accuracy. RDS results were equivalent for both surgical and PTRA treatment. CONCLUSIONS: From this experience we conclude that RDS is useful for anatomic evaluation after surgical RA repair or PTRA. A negative RDS result excludes stenosis or occlusion of a main RA reconstruction but does not exclude significant branch level disease.

Adult↗
PubMed1992

Growth-regulatory properties of atrial natriuretic factor.

Recent evidence supports the notion that atrial natriuretic factor (ANF) has growth-regulatory properties. In the adrenal gland, ANF inhibits growth specifically in the zona glomerulosa. In the kidney, ANF causes an antimitogenic, antiproliferative effect in cultured glomerular mesangial cells. In vascular smooth muscle, ANF inhibits cell proliferation (hyperplasia) as well as cell growth (hypertrophy). ANF has growth-regulatory properties in a variety of other tissues such as brain, bone, myocytes, red blood cell precursors, and endothelial cells. The cellular mechanisms involved in the growth-regulatory actions of ANF are not totally clear. Evidence supports involvement of both biological and clearance receptors for ANF, guanosine 3',5'-cyclic monophosphate (cGMP) and cGMP-independent mechanisms, and protooncogene expression. For the most part, the actions reviewed in this report represent in vitro phenomena, and it is unclear whether these effects are relevant to normal physiology or pathophysiology. Nevertheless, an emerging hypothesis is developing which states that circulating and autocrine/paracrine factors such as ANF interact to regulate the vasomotor tone and cellular growth of a variety of tissues such as vascular smooth muscle and the glomerulus.

Adrenal Glands↗
PubMed1990

Mechanism of atrial natriuretic factor-induced inhibition of rat mesangial cell mitogenesis.

Recent observations suggest that atrial natriuretic factor (ANF) may have growth-inhibitory activity. The present studies were performed to further define this action in rat mesangial cells (which have both biological and clearance ANF receptors) and in 3T3 fibroblasts (which have only clearance ANF receptors). Both cell types were made quiescent by removal of serum and then reactivated by exposure to a serum-free defined medium. ANF inhibited [3H]thymidine uptake in a dose-dependent manner in mesangial cells (half-maximal response 10(-11) M; 47% maximal inhibitory effect) but had no effect in 3T3 fibroblasts. Exogenous 8-bromoguanosine 3',5'-cyclic monophosphate (0.1 mM) inhibited [3H]thymidine uptake by 33% in mesangial cells but had no effect in 3T3 fibroblasts. Counts in mesangial cells exposed to 0.1 mM sodium nitroprusside, which stimulates guanosine 3',5'-cyclic monophosphate (cGMP), were inhibited by 76%. However, this represented a toxic effect, because excessive trypan blue uptake was noted in this condition. Mesangial cell number after 3 days of logarithmic proliferation was reduced by 33% in cells incubated with 1.0 nM ANF compared with vehicle. Incubation of mesangial cell monolayers with ANF caused a concentration-dependent increase in intracellular cGMP accumulation. Threshold responses occurred at concentrations one order of magnitude greater than that resulting in the antimitogenic action. In 3T3 fibroblast monolayers exposed to ANF, cGMP accumulation occurred but was markedly attenuated compared with mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1988

Growth inhibitory activity of atrial natriuretic factor in rat glomerular mesangial cells.

Atrial natriuretic factor (ANF) binding sites, or ANF-induced cGMP accumulation, have been shown in numerous tissues that may not be intimately involved in volume homeostasis. In a series of experiments, we found that quiescent rat glomerular mesangial cells in culture could be reactivated to enter the cell cycle, and that ANF had potent inhibitory effects on proliferation of these cells. [3H]Thymidine incorporation increased by fivefold in reactivated compared to quiescent cells, and ANF in physiologic concentrations inhibited this incorporation by 48%. Thus, ANF appears to be a multifunctional peptide, consistent with a number of peptide growth factors.

Animals↗
PubMed1988

Papillary collecting tubule synthesis of prostaglandin E2 in Dahl rats.

Isolated kidneys of Dahl salt-sensitive rats (DS) excrete sodium less readily than those of Dahl salt-resistant rats (DR). The collecting tubule is an important source of papillary prostaglandin E2 and is a site of significant sodium reabsorption. We cultured renal papillary collecting tubule cells from 5-week-old, prehypertensive DS and DR on a low salt diet and also after 14 weeks of high salt feeding, and we measured prostaglandin E2 synthetic capacity. Unstimulated renal papillary collecting tubule cells from 5-week-old DS produced 62 +/- 5% less prostaglandin E2 than did comparable cells from DR (p less than 0.001). The cells from DS also synthesized less prostaglandin E2 after stimulation with the calcium ionophore A23187 (67 +/- 6% of control; p less than 0.001) or the addition of exogenous arachidonate (74 +/- 7% of control; p less than 0.01). Urinary prostaglandin E2 excretion was also diminished in the 5-week-old DS compared with their salt-resistant counterparts (18.1 +/- 1.3 vs 23.9 +/- 1.7 ng/24 hr; p less than 0.025). After high salt feeding, the DS became hypertensive but the DR remained normotensive. Renal papillary collecting tubule cells cultured from these DS continued to produce less prostaglandin E2 than those from control rats, both in the basal state (60 +/- 12% of control; p less than 0.09) and after stimulation with ionophore (62 +/- 2% of control; p less than 0.002). In these older animals, the DS continued to underexcrete prostaglandin E2 compared with the DR (29.7 +/- 3.2 vs 42.2 +/- 6.1 ng/24 hr; p less than 0.08). The underproduction of prostaglandin E2 in the papillary collecting tubule of DS may play a role in their inadequate renal natriuretic capacity and contribute to the onset and maintenance of salt-induced hypertension in this strain.

Animals↗
PubMed1987

Effect of atrial natriuretic factor on cytosolic free calcium in rat glomerular mesangial cells.

Since atrial natriuretic factor (ANF) inhibits angiotensin II (ANGII)-induced mesangial cell contraction, we studied its effect on cytosolic free calcium in fura-2-loaded monolayers. ANF lowered basal calcium from 117 +/- 5 to 89 +/- 2 nM, and also reduced the ANGII-induced calcium transient. The absolute level of cytosolic calcium after ANGII was lower in cells preincubated with ANF compared to buffer. In a few cell lines, ANF had no effect on cytosolic calcium, while in all cell lines ANF had inhibited contraction. Thus, while ANF has effects on cytosolic calcium in mesangial cells, the vasorelaxant effects of ANF may require additional physiologic interactions.

Animals↗
PubMed1987

Papillary collecting tubule responsiveness to atrial natriuretic factor in Dahl rats.

There is evidence that atrial natriuretic factor (ANF) has an action in the inner medullary collecting duct. In addition, the prehypertensive Dahl salt-sensitive (S) rat has an intrinsic tendency toward less natriuresis than the Dahl salt-resistant (R) rat has when challenged with ANF. To test the hypothesis that renal papillary collecting tubule cells from prehypertensive S rats might be genetically less responsive to ANF, S and R cells were grown in culture and studied for responsiveness to ANF by measurement of cyclic nucleotide responses. There was a concentration-dependent effect of ANF on renal papillary collecting tubule cell synthesis of intracellular cyclic guanosine 3',5'-monophosphate (cGMP) in both strains. However, the S cells were hyporesponsive compared with the R cells (p less than 0.002, by analysis of variance). Likewise, in response to Na nitroprusside, the S cells were hyporesponsive compared with the R cells as measured by intracellular cGMP accumulation (p less than 0.03, by analysis of variance). Arginine vasopressin stimulated intracellular cAMP equally in both strains. Also, ANF equally enhanced intracellular cGMP in glomerular mesangial cells from S and R rats, indicating possible specificity of the reduced responsiveness to ANF to the distal nephron of S rats. Plasma ANF levels had a slight tendency to be higher in prehypertensive S rats than in R rats (p = 0.088, by t test). These results suggest that the papillary collecting duct of Dahl S and R rats may differ in guanylate cyclase activity. This difference may partially explain the impaired natriuretic responses of S rats and could represent a factor contributing to the development of salt-sensitive hypertension.

Adenosine Monophosphate↗
PubMed1987

Vasopressin-resistant diabetes insipidus, liver dysfunction, hyperuricemia and decreased renal function. A case report.

A case of transient nephrogenic diabetes insipidus occurred in late pregnancy, the first associated with biopsy-proven hepatitis. Five previously reported cases occurred in pregnancy. All six patients demonstrated similar but transient signs, symptoms and laboratory abnormalities suggesting a syndrome peculiar to pregnancy. The characteristics of this syndrome are elevated liver function studies, decreased renal function, hyperuricemia and transient vasopressin-resistant diabetes insipidus.

Adult↗
PubMed1986

A mechanism by which atrial natriuretic factor mediates its glomerular actions.

Differential in vivo glomerular effects of atriopeptin I (AP I) and atriopeptin III (AP III) were studied in parallel with in vitro physiological and biochemical parameters. In anesthetized Sprague-Dawley rats, AP III, but not AP I, significantly increased glomerular filtration rate. Image analysis microscopy was used to assess the effect of AP I and AP III on angiotensin II (ANG II)-induced contraction of cultured rat glomerular mesangial cells. AP III, but not AP I, inhibited ANG II-induced mesangial cell contraction in a concentration-dependent manner. Additional inhibitory agents included exogenous DBcGMP, 8-BrcGMP, Na nitroprusside, and DBcAMP. AP III stimulated mesangial cell cGMP with a lower threshold and greater maximum stimulation than AP I. Neither agent stimulated cAMP accumulation. Since mesangial cell contractility may regulate the glomerular capillary surface area, these results suggest that AP III partially mediates its glomerular effects through inhibition of ANG II-induced mesangial cell contraction. Whereas cGMP is not clearly implicated as the mediator of this effect, it appears that both cGMP and cAMP may regulate the state of mesangial cell contractility.

Angiotensin II↗