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Biomedical subjects

G B Appel

Publications and source records attributed to G B Appel.

At least 55 records · Page 3Linked to original sources
PubMed1990

Acute deterioration of renal function associated with enteric hyperoxaluria.

Enteric hyperoxaluria due to malabsorption syndromes has been well documented to cause renal calculi and chronic tubulointerstitial renal damage. Rarely, in the setting of intestinal bypass operations for morbid obesity, enteric hyperoxaluria has produced acute renal failure. We report two patients who suffered acute deterioration of renal function associated with increased intestinal absorption and renal excretion of oxalate associated with steatorrhea. One patient had a large portion of his small bowel resected many years prior to the onset of the renal failure and the second patient had chronic pancreatitis causing steatorrhea. Both patients had renal biopsy documentation of the acute nature of the tubular damage produced by oxalate deposition. The mechanisms of their deterioration of renal function may relate to sudden increases in steatorrhea in association with episodes of volume depletion. Enteric hyperoxaluria may be an easily overlooked and potentially preventable etiology of acute renal dysfunction.

Acute Kidney Injury↗
PubMed1989

Course and prognosis of human immunodeficiency virus-associated nephropathy.

PURPOSE: Patients infected with the human immunodeficiency virus (HIV) have been described to have an unusual form of renal disease known as HIV-associated nephropathy. This condition is characterized by severe proteinuria, rapid progression to renal insufficiency, and a morphologic pattern of focal segmental glomerulosclerosis (FSGS) on renal biopsy. Despite increasing awareness of this entity, the epidemiology and clinical course of HIV-associated nephropathy are not yet well defined. We therefore decided to study HIV-infected patients with this biopsy-proven pattern of focal sclerosis. PATIENTS AND METHODS: Using life-table analysis, we evaluated the clinical features and course of 26 patients with HIV infection and biopsy-proven FSGS and compared them with those in 24 subjects with HIV infection who had no glomerular disease at autopsy. RESULTS: The group with FSGS had a higher percentage of blacks (96% versus 46%) and intravenous drug abusers (42% versus 17%), and had a higher mean serum creatinine level (5.4 mg/dL versus 1.0 mg/dL) than the group of HIV-infected subjects without glomerular disease. At the time of diagnosis of FSGS, six patients had clinical acquired immunodeficiency syndrome (AIDS), eight had AIDS-related complex (ARC), and 12 patients had no evidence of AIDS or ARC. The progression to end-stage renal disease for all patients was rapid, with a median time to dialysis of 10.9 weeks. Duration of patient survival was dependent upon the stage of HIV infection at the time of diagnosis of renal disease. Patients who presented with AIDS had a median survival of 1.9 months, compared to a median survival of 3.6 months for those with ARC and 9.7 months for initially asymptomatic HIV carriers (p less than 0.05). Fifteen patients either presented with or developed AIDS during the course of the study, and all died as a consequence of their immunodeficiency. Survival curves from the diagnosis of AIDS to death were similar in the group with HIV-associated nephropathy (7.3 weeks) compared to the control AIDS group without renal disease (6.9 weeks). CONCLUSION: Our data indicate that FSGS associated with HIV infection can occur before other manifestations of AIDS, is more common in blacks and in intravenous drug abusers, and is rapidly progressive to uremia. Patient survival is dependent upon the stage of HIV infection. These findings may prove useful in devising more effective strategies for the care of this growing patient population.

AIDS-Related Complex↗
PubMed1989

The hyperlipidemia of the nephrotic syndrome.

Lipid abnormalities in patients with the nephrotic syndrome have long been recognized. However, the significance of these lipid abnormalities, the mechanisms producing them, and their potential treatment have all been a cause of debate. Recent data have helped clarify each of these areas of controversy. Studies of the lipoprotein abnormalities of patients with the uncomplicated nephrotic syndrome have shown that many will have elevated levels of total and low-density lipoprotein cholesterol, whereas only a few will have elevated levels of high-density lipoprotein cholesterol. If these lipid abnormalities have the same significance in this population as in other populations studied, then some patients with unremitting nephrotic syndrome will be at high risk for cardiovascular disease. The elevated cholesterol levels noted in the nephrotic syndrome are caused primarily by enhanced hepatic synthesis, with lesser contributions by decreased clearance and altered enzyme activities. The signal for enhanced hepatic lipogenesis may relate to changes in plasma albumin concentration, plasma oncotic pressure, a local effect of viscosity at the hepatic sinusoidal level, or a loss of urinary proteins or other liporegulatory substances. Recently, a number of short-term studies in nephrotic patients have documented the safety and efficacy of lipid-lowering drugs such as the bile acid-binding resins, probucol, and the HMGCoA (hydroxymethylglutaryl coenzyme A) reductase inhibitors.

Animals↗
PubMed1989

Interstitial nephritis related to nonsteroidal anti-inflammatory agents and beta-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies.

Acute interstitial nephritis (AIN) is a common pattern of renal injury induced by therapeutic agents. In order to characterize the types of mononuclear leukocytes infiltrating the kidney in drug-induced interstitial nephritis, a panel of monoclonal antibodies (Leu1, Leu3a, OKT8, OKM1, Leu14, OKT17, IL-2) was applied to cryostat sections of 13 renal biopsies (five non-steroidal anti-inflammatory agents (NSAID) (Group I); five beta-lactam antibiotics (Group II), 3 miscellaneous (Group III]. The majority of infiltrating mononuclear leukocytes were Leu1-positive T cells (71.7 +/- 18.7%), followed by monocytes (15.2 +/- 7.7%) and B cells (7.4 +/- 9.1%). Leu3a/OKT8 ratio was 0.954 +/- 0.341. Rare cells reacted with antibody to the interleukin-2 receptor (1.4 +/- 1.2%). No statistically significant differences could be found in the percentages of T lymphocytes, B lymphocytes, monocytes, activated (IL-2+) T cells or Leu3a/OKT8 (helper/suppressor) ratios in the three groups. In Group II, the following pathologic correlations were seen: Leu3a/OKT8 versus interstitial inflammation (R = -0.848), percent Leu3a versus interstitial inflammation (R = -0.818), percent OKT17 versus tubulitis (R = 0.785), percent Leu14 versus tubular atrophy (R = -0.891), and interstitial edema (R = 0.965). Our findings support a role for cellular immune mechanisms in the pathogenesis of AIN related to both NSAIDs and beta-lactam antibiotics.

Adult↗
PubMed1988

Determination of acquired immunodeficiency syndrome (AIDS) after renal transplantation.

Diagnosing the acquired immunodeficiency syndrome (AIDS) in transplant recipients can be difficult due to the patient's medication-induced immunosuppressed state. We report two renal allograft recipients who acquired HIV infection at the time of transplantation and later went on to develop multiple opportunistic infections. Careful documentation of HIV antibody status of the donor and recipient, when available, the nature of immunosuppressive therapy used, the type of infections and their timing after transplantation, as well as the patient's absolute T4 lymphocyte count, T cell ratio, and B cell humoral response to infection were used as factors to distinguish between infection related to immunosuppressive therapy and that seen in HIV-induced immunodeficiency. Reduction in immunosuppressive therapy because of the HIV-related immunodeficiency state did not result in allograft rejection. Both patients died of their multiple infections. The determination of AIDS in the transplant recipient has both therapeutic and prognostic significance. This diagnosis should be considered when transplant patients develop unusual infections in relationship to their posttransplant course.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Sulfadiazine-associated obstructive nephropathy occurring in a patient with the acquired immunodeficiency syndrome.

A 45-year-old man with the Acquired Immunodeficiency Syndrome (AIDS) and CNS toxoplasmosis presented with acute renal failure, hematuria, and renal colic shortly after starting treatment with sulfadiazine. Ultrasound examination of his kidneys was suggestive of intraparenchymal crystallization of sulfadiazine. His renal failure and ultrasound findings rapidly resolved with alkaline hydration. On rechallenge with sulfadiazine, he again developed renal insufficiency and ultrasonic findings consistent with stones. The use of sulfadiazine in the treatment of CNS toxoplasmosis in AIDS patients should be monitored carefully with the recognition that this form of crystalline-induced acute renal failure can occur in a dehydrated patient.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization.

The long-term course of 56 patients with systemic lupus erythematosus who had precisely defined renal histology and carefully assessed clinical status at the time of their initial renal biopsy prior to 1976 was evaluated and analyzed by life-table analysis. The average length of follow-up has now been greater than 10 years since initial biopsy. Patients with mesangial lesions (World Health Organization [WHO] classes IIA and IIB) had a more favorable renal and patient survival at five and 10 years than did patients in the other WHO classes (III, IV, and V). Individual renal histologic features of activity and chronicity when combined into an activity index and a chronicity index did not significantly predict renal survival in this population, nor did the presence of hypertension or renal dysfunction at the time of the initial renal biopsy significantly influence renal or patient survival. Patients with the nephrotic syndrome at initial biopsy had a poorer renal survival than did patients without the nephrotic syndrome. However, patients who experienced a remission of the nephrotic syndrome fared better in terms of both renal and patient survival than did those patients without a remission. By life-table analysis, patient survival was significantly better for patients in whom biopsy was performed after 1973 than for those in whom biopsy was performed prior to that time despite similar clinical features and WHO histology in each group interval. Our data suggest that improved survival for patients in recent studies may relate to better supportive care and more selective use of immunosuppressive therapy in patients with milder forms of lupus nephritis.

Actuarial Analysis↗
PubMed1986

Treatment of the hyperlipidemia of the nephrotic syndrome: a controlled trial.

The hyperlipidemia of the nephrotic syndrome is often associated with elevated total and low-density lipoprotein (LDL) cholesterol levels and low or normal high-density lipoprotein (HDL) cholesterol levels. This pattern of hyperlipidemia has been associated with an increased risk of accelerated atherosclerosis in other populations. Despite extensive studies of diet and drug therapy in other populations, few such therapeutic studies exist in patients with the nephrotic syndrome. To investigate the effect of diet and lipid-lowering drugs on the lipoprotein-lipid profile of patients with unremitting nephrotic syndrome and marked hyperlipidemia, we conducted a controlled trial using two such drugs: colestipol and probucol. Colestipol lowered the mean total fasting plasma cholesterol of seven patients from 397 +/- 27 to 317 +/- 37 mg/dL, a 20.2% decrease, and lowered the LDL cholesterol from 398 +/- 28 to 203 +/- 18 mg/dL, a 31.9% decrease. It did not affect the HDL cholesterol level, and thus lowered the LDL-to-HDL cholesterol ratio. Probucol lowered the mean total cholesterol from 439 +/- 72 to 339 +/- 60 mg/dL, a 22.6% decrease, and the LDL cholesterol from 282 +/- 43 to 215 +/- 26 mg/dL, a 23.8% decrease. Although the HDL cholesterol was lowered from 49 +/- 9 to 43 +/- 7 mg/dL by probucol, a 12.2% decrease, the LDL-to-HDL cholesterol ratio still declined. Both drugs were well tolerated and proved safe in this short-term trial. Antihyperlipidemic therapy may well be indicated in certain patients with unremitting nephrotic syndrome.

Adult↗
PubMed1986

Monoclonal antibody identification of infiltrating mononuclear leukocytes in lupus nephritis.

Populations of mononuclear inflammatory cells infiltrating the renal interstitium in LN were studied by means of an avidin-biotin immunoperoxidase technique applied to cryostat sections of 26 renal biopsies (3 WHO class IIb; 4 class III; 8 class IV; 4 class V; 4 class III and V; and 3 class IV and V). The majority of interstitial leukocytes were T cells (mean 65.7 +/- 14.1). The number of cells reactive with OKT8 (47.3 +/- 11.0) exceeded the number of OKT4 positive cells (32.5 +/- 11.3) in 22 of 26 biopsies. Cells reactive with antimonocyte antibodies OKM1 and OKM5 (6.7 +/- 5.9 and 7.9 +/- 5.9, respectively) and B lymphocytes (OKB2 3.9 +/- 3.5) were a minor component of the interstitial infiltrates. Monocytes were the predominant cell type among stained cells in glomerular tufts and crescents. Tissue T4/T8 ratios varied widely (range 0.31 to 1.81), and were less than 1 in 22 of 26 patients. There was no correlation between tissue T4/T8 ratios and simultaneous peripheral blood T4/T8 ratios. Using stepwise multivariate linear regression, tissue T4/T8 ratio was found to correlate highly with renal histologic activity (P less than 0.001) but was not independently predictive of any other histopathologic or clinical variable studied. Mean tissue T4/T8 ratio in LN was significantly lower than that of other glomerular and interstitial diseases studied (P less than 0.001), a finding which may reflect differences in the pathogenesis of renal injury. These findings suggest that local cellular immune mechanisms may be important in the modulation of disease activity in LN.

Adolescent↗
PubMed1986

Tubulointerstitial disease in lupus nephritis: relationship to immune deposits, interstitial inflammation, glomerular changes, renal function, and prognosis.

The interrelationships between tubulointerstitial immune deposits (TID), interstitial inflammation, glomerular changes, renal function, and prognosis were assessed in the renal biopsies from 93 patients with lupus nephritis. The prevalence of TID was 33% by immunofluorescence and 23% by electron microscopy. Although predominantly detected along and within tubular basement membranes, extraglomerular immune deposits were also present in the wall of renal interstitial capillaries and small arteries as well as in Bowman's capsule. The prevalence of TID correlated with the activity of glomerular lesions and, to a lesser extent, with the severity of proliferative lupus nephritis (WHO classes II-IV). TID were much less common in the membranous form (WHO class V). The severity of interstitial inflammation correlated with the degree of renal insufficiency and was an accurate prognostic indicator of progressive deterioration of renal function. However, there was no correlation between prevalence of TID and prevalence and severity of interstitial inflammation, suggesting that the latter is not necessarily secondary to the presence of immune complexes and that other pathogenetic mechanisms may be involved.

Antibodies, Anti-Idiotypic↗
PubMed1985

The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity.

Although hyperlipidemia is a common feature of the nephrotic syndrome, the distribution of cholesterol among the plasma lipoproteins and the mechanism of the enhanced hepatic synthesis of lipoprotein lipids are not well understood. We studied the distribution of cholesterol among the plasma lipoproteins, as well as the relation between total cholesterol and plasma albumin concentration, oncotic pressure, and viscosity in 20 consecutive adult patients with uncomplicated nephrotic syndrome. The total plasma cholesterol (mean +/- S.D., 302 +/- 100 mg per deciliter [7.8 +/- 2.6 mmol per liter]) and low-density-lipoprotein cholesterol concentrations (215 +/- 89 mg per deciliter [5.6 +/- 2.3 mmol per liter]) were elevated in most patients, but the high-density-lipoprotein cholesterol level was normal or low (46 +/- 18 mg per deciliter [1.2 +/- 0.5 mmol per liter]) in 95 per cent of the patients. Thus, many hypercholesterolemic patients with unremitting nephrotic syndrome may be at increased risk for atherosclerotic heart disease. A significant inverse correlation was found between the total plasma cholesterol concentration and both the plasma albumin concentration (r = -0.528) and the plasma oncotic pressure (r = -0.674), but not the plasma viscosity (r = +0.319). Enhanced hepatic synthesis of lipoprotein lipids may be stimulated by a decreased plasma albumin concentration or oncotic pressure but does not appear to be due to changes in plasma viscosity.

Adult↗
PubMed1985

Thrombotic thrombocytopenic purpura syndrome in systemic lupus erythematosus: treatment with plasma infusion.

Two patients with well documented systemic lupus erythematosus developed a syndrome resembling thrombotic thrombocytopenic purpura. Both had severe thrombocytopenia, microangiopathic hemolytic anemia, seizures, and renal dysfunction. Prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen levels were normal; fibrin degradation products were minimally elevated. Histologic evaluation of renal biopsies in both patients confirmed the impression of intravascular thrombosis. Therapy with corticosteroids, other immunosuppressive drugs and splenectomy (in one case) proved unsuccessful. The infusion of fresh frozen plasma, with or without plasmapheresis, reversed the syndrome. This report indicates that patients with systemic lupus may develop a thrombotic thrombocytopenic purpura like syndrome which responds to fresh plasma infusion.

Adrenal Cortex Hormones↗
PubMed1984

Acute renal failure in patients with multiple myeloma.

In the past, patients with multiple myeloma and acute renal failure have had a poor prognosis. Few patients recovered renal function and fewer still survived for prolonged time periods. This report describes the course of 10 patients with multiple myeloma and true acute renal failure treated during the decade 1970 to 1980, and reviews recent reports concerning this association. The use of radiographic contrast agents is no longer the primary predisposing factor to acute renal failure in the myeloma population. Rather, infection, hypercalcemia, and dehydration in the presence of light chain excretion are the major conditions precipitating the renal failure. Despite severe renal failure requiring dialysis, many patients may regain good renal function. Factors associated with a good or poor prognosis in this population are reviewed. The prognosis in patients with myeloma and acute renal failure has greatly improved in recent years, and prolonged survival may occur.

Acute Kidney Injury↗
PubMed1984

Nephrotic syndrome associated with use of the nonsteroidal anti-inflammatory drugs. Case report and review of the literature.

Although acute interstitial nephritis associated with the use of nonsteroidal anti-inflammatory drugs has long been recognized, only recently has its association with 'minimal change' nephrotic syndrome been reported. We report here a case of this pattern of nephrotic syndrome without concurrent interstitial nephritis associated with the use of tolmetin. The clinical picture, laboratory data, course, and relevant histopathologic findings of previous cases in the literature of nephrotic syndrome related to the use of the nonsteroidal anti-inflammatory drugs are reviewed and discussed.

Aged↗
PubMed1983

Nephrotic syndrome and immune complex glomerulonephritis associated with chlorpropamide therapy.

Therapeutic drugs are well-recognized as a cause of the nephrotic syndrome in humans. However, documentation of the renal histopathologic features is lacking or incomplete in many cases. Even when accurate histopathologic information is available, there is little evidence to support a specific pathogenetic mechanism of renal injury in the vast majority of cases. We describe a patient with diabetes who had hepatitis and dermatitis in association with the use of chlorpropamide. In addition to these well-described toxic reactions to this drug, the nephrotic syndrome developed. Renal biopsy revealed the presence of a proliferative glomerulonephritis that was shown to be of an immune complex nature on immunofluorescence and electronmicroscopic study. Serial serum complement levels and circulating immune complex levels were consistent with an immunologically mediated reaction. Repeated renal biopsy documented resolution of the renal changes. Thus, in this patient, a drug-induced nephrotic syndrome was associated with a proliferative glomerulonephritis, probably due to the formation of immune complexes.

Chlorpropamide↗