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Biomedical subjects

G B Appel

Publications and source records attributed to G B Appel.

At least 19 recordsLinked to original sources

Cyclosporine: nephrotoxic effects and guidelines for safe use in patients with rheumatoid arthritis.

Renal abnormalities occur frequently in patients with rheumatoid arthritis; they may be complications of the rheumatoid disease process itself (amyloidosis) or may result from various therapies including gold compounds, D-penicillamine, analgesics such as aspirin or phenacetin used long term, and nonsteroidal anti-inflammatory drugs. Cyclosporine, a highly effective immunosuppressive agent currently under investigation as a treatment for RA, is also known to produce renal dysfunction. Some forms of functional and structural tubular changes appear readily reversible. Others associated with renal vasculopathy and interstitial fibrosis can lead to irreversible nephrotoxicity. A clear understanding of the pharmacology, drug interactions, and types of renal side effects encountered with cyclosporine can lead to a reduction of adverse renal reactions. Similarly, an understanding of which patients are at high risk for renal dysfunction can lead to safer and more efficacious use of this potent immunosuppressive agent.

Arthritis, Rheumatoid

Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia.

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester transfer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome displayed increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CE/triglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in patients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r = 0.69, P = 0.004) and with plasma apoB concentration (r = 0.68, P = 0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hypertriglyceridemic nephrotic syndrome patients (r = -0.67, P = 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are unusually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrichment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.

Adult

Intravenous "pulse" cyclophosphamide therapy of crescentic glomerulonephritis.

Pulse steroids and monthly intravenous cyclophosphamide with a rapid steroid taper were used to treat seven patients with crescentic glomerulonephritis. Despite major impairment of renal function, all patients had a marked improvement in GFR by six months and improvement in proteinuria occurred in six of the seven patients. Two patients were able to discontinue dialysis. The doses of steroids and cyclophosphamide used were less than in comparable studies and side-effects of therapy were minimal. Repeat renal biopsies at over one year demonstrated marked glomerulosclerosis despite relatively stable renal function. Histologic analysis of total glomerular involvement indices on serial biopsies suggested no recruitment of new glomeruli into the crescenteric process once treatment had been initiated. Thus, intravenous pulse cyclophosphamide with pulse steroid therapy appears to be a safe and effective initial therapy for some patients with RPGN. Significant glomerulosclerosis on repeat biopsies suggests that glomerulosclerosis may be predetermined by the initial degree of irreversible glomerular damage and that the long-term course of the disease remains guarded.

Adult

Kinetics of intravenous amoxicillin in patients on long-term dialysis.

The kinetics of intravenous amoxicillin was studied in 8 patients with creatinine clearances of less than 7 ml/min who were on long-term hemodialysis. Kinetic parameters were determined using a 2-compartment linear model. The serum half-life (t1/2) of amoxicillin in these patients ranged from 7.5 to 21 hr. The t1/2 fell to 2.84 +/- 0.45 hr during dialysis. Approximately 30% of the dose was recovered in the dialysate during 4 hr of dialysis and there was a 25% reduction per hour in serum concentration. We present a dosage schedule for intravenous amoxicillin in patients with reduced renal function who are undergoing hemodialysis.

Adolescent

Kinetics of intravenous mezlocillin in chronic hemodialysis patients.

The kinetics of intravenous mezlocillin was studied in 8 patients with creatinine clearances under 7 ml/min who were undergoing chronic hemodialysis. Kinetic parameters were determined using a 2-compartment linear model. The mezlocillin serum half-life (t 1/2) in these patients ranged from 2.9 to 7.8 hr (mean, 5.4). The t 1/2 decreased to 1.57 +/- 0.09 hr during dialysis. Approximately 18% of the dose was recovered in the dialysate in 4 hr of dialysis. There was a 30% reduction per hour in serum concentration. The kinetics of mezlocillin, due to removal by nonrenal mechanisms, more closely resemble the kinetics of penicillin G and ampicillin than of carbenicillin and ticarcillin. A dosage schedule for use of intravenous mezlocillin in patients undergoing hemodialysis is presented.

Adult

Pharmacokinetics of intravenous piperacillin in patients undergoing chronic hemodialysis.

The pharmacokinetic properties of piperacillin, a piperazine derivative of ampicillin, were determined in seven patients with creatinine clearances less than 7 ml/min who were undergoing chronic, intermittent hemodialysis. A two-compartment linear model was used to analyze the data. Mean elimination half-life was 1.26 +/- 0.1 h; the mean elimination constant was 0.95 +/- 0.08 h-1; the mean volume of distribution was 0.16 +/- 0.02 liters/kg of body weight; the mean volume of the central compartment was 0.10 +/- 0.01 liters/kg of body weight; and the mean clearance was 0.09 +/- 0.01 liters/h per kg of body weight. Mean elimination half-life while off dialysis of 2.1 h.

Adult

Amyloidosis in chronic heroin addicts with the nephrotic syndrome.

Four chronic heroin addicts had renal amyloidosis and the nephrotic syndrome. Amyloidosis had the secondary type of tissue distribution and developed after many years of addiction. That chronic immunologic stimulation by one or more exogenous antigens or multiple acute inflammatory episodes were important factors in the pathogenesis of amyloidosis in these patients is postulated. Amyloidosis, although uncommon, must be considered among the different types of renal involvement that are known to occur in drug addicts, especially those with the nephrotic syndrome, and amyloid should be specifically searched for in their renal biopsies.

Adult

Gentamicin in 1978.

For a decade gentamicin has been used extensively because of its antimicrobial efficacy and the relatively low prevalence of clinical toxicity. Recently the more frequent appearance of resistant organisms, reports of increased nephrotoxicity and ototoxicity, and the development of newer aminoglycoside antibiotics have raised doubts about the continued use of this agent. This paper reassesses the role of gentamicin. It is clear that an appreciation of the pharmacokinetics and the clinical use of gentamicin as well as an understanding of the patterns of toxicity in animals and humans can lead to more efficient treatment with this antimicrobial agent. Despite ample competition from a number of newer aminoglycoside antibiotics, gentamicin will probably continue to be used widely in the near future.

Amikacin

Acute interstitial nephritis associated with carbenicillin therapy.

Although acute interstitial nephritis has been documented during therapy with many antibiotics of the penicillin class, it has not previously been reported in association with carbenicillin therapy. We report here the case of a patient who developed the characteristic clinical features of this form of injury while receiving prolonged large doses of carbenicillin. Histologic examination confirmed the presence of a striking interstitial nephritis. Carbenicillin should be considered a potential cause of renal damage in patients who develop rash, eosinophilia, and microscopic hematuria in association with deterioration of renal function.

Acute Disease

The anion gap in asymptomatic plasma cell dyscrasias.

The presence of a low anion gap in patients with multiple myeloma has recently been emphasized. This has been related to the retention of chloride and bicarbonate anions to offset the cationic charge of the monoclonal immunoglobulins. We now report the presence of a low anion gap in 50 patients with asymptomatic plasma cell dyscrasias. No correlation was found between the size of the anion gap and the height of the paraprotein "spike" or the size of the anion gap and an index of the net cationic charge of the monoclonal immunoglobulins.

Anions