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Effect of corticosteroid therapy on human immunodeficiency virus-associated nephropathy.

PURPOSE: Human immunodeficiency virus-associated nephropathy (HIV-AN) occurs predominantly in blacks and is characterized histologically by focal segmental glomerulosclerosis or mesangial proliferation and a lymphohistiocytic tubulointerstitial infiltrate. Patients manifest heavy proteinuria and, once azotemia occurs, progress rapidly to end-stage renal disease within 2 to 6 months. No treatment has been shown to be useful for HIV-AN. The purpose of this study was to determine the effect of corticosteroid agents on the progression of HIV-AN. PATIENTS AND METHODS: Four consecutive HIV-infected adults with fewer than 200 CD4 cells/microL, moderate to severe renal insufficiency, proteinuria greater than 2 g per 24 hours, and HIV-AN demonstrated by renal biopsy were treated with 60 mg of prednisone daily for 2 to 6 weeks. Patients were followed with respect to serum creatinine level, 24-hour protein excretion, adverse drug reactions, and the occurrence of opportunistic infections. RESULTS: CD4 counts ranged from 30 to 80 cells/microL before therapy with steroids. The mean (+/- SD) pretreatment serum creatine concentration was 9.1 +/- 5.7 mg/dL and decreased to 3.3 +/- 1.8 mg/dL (P < 0.05) after 2 to 6 weeks of corticosteroid therapy. Twenty-four hour protein excretion did not change (5.2 +/- 2.4 g pretreatment versus 4.6 +/- 4.1 g posttreatment). One patient was able to discontinue dialysis after 10 days. Two patients developed Mycobacterium avium-complex infections and steroid-associated psychosis. One of these patients developed a recurrence of genital herpes, and the other developed dermatomal zoster. None of the four required dialysis during a 1.5- to 5.5-month period of follow-up after cessation of steroid treatment. CONCLUSION: In selected patients with HIV-AN, short-term treatment with corticosteroid agents improves renal function and prevents the development of end-stage renal disease during a 1.5- to 5.5-month period of observation, but may be associated with an increased risk of opportunistic infection.

Adult↗

Comparative group study between patients surviving five or more years after portacaval shunt procedure and those surviving less than one year.

The classic criteria utilizing preoperative clinical evaluations and laboratory tests for predicting risk and long-term survival in cirrhotic patients under-going portacaval shunting still appear to be the most useful. Analysis of the factors that could be determinant in separating patients who are going to survive a portacaval shunt for five or more years from the short-term survivors revealed the former group had a lesser incidence of preoperative encephalopathy, ascites, malnutrition, and hypoalbuminemia. None of the intraoperative factors were found to be decisive. However, the prompt and uncomplicated postshunt recovery was an accurate prediction for long-term survival. This could be explained by the assumption that these patients had a better hepatic functional reserve at the time of portal-systemic shunting. The early appearance in the postoperative period, of fluid retention, azotemia, oliguria, inability to eat, and the early appearance of the symptoms of portal encephalopathy were premonitory of short-term survival. Return to alcohol ingestion was also associated with short-term survival. The hepatorenal syndrome was usually the cause of death in the short-term survivors whereas nonhepatic disease was the cause of demise in the long-term survivors. The operative mortality for all patients undergoing portacaval shunting during an eight year period was 10.7 per cent. Of the patients who left the hospital alive, 16.1 per cent died within the subsequent twelve months, 53 per cent survived from thirteen to fifty-nine months after their operation, and 19.6 per cent survived sixty or more months.

Adult↗

Major surgery in patients with chronic renal failure.

To determine the risks of performing major surgical procedures on patients with chronic renal failure, the charts of twenty-nine hemodialysis patients who underwent thirty-eight elective and nine emergency operations were reviewed. Preoperative preparation included adequate hemodialysis of the patients, 88 per cent of whom were dialyzed within 24 hours of surgery. Azotemia was well controlled prior to administration of anesthesia. The average preoperative hematocrit was 26 per cent, and only one patient was hyperkalemic preoperatively. There were no intraoperative complications attributable to the patients' impaired renal function. Postoperative complications were frequent and are discussed in detail. Hemodialysis was done immediately postoperatively in five patients and on the first postoperative day in twenty-three additional patients with no problems. There were only two deaths (4.3 per cent) in the series. With careful monitoring during the perioperative period, major surgical procedures can safely be performed on patients with chronic renal failure.

Adolescent↗

Synergistic effect of acute renal failure and respiratory failure in the surgical intensive care unit.

A retrospective evaluation of the effect of renal and respiratory failure on mortality in our surgical intensive care unit was undertaken. The coexistence of combined renal and respiratory failure had a synergistic adverse effect on survival. Combined pulmonary and kidney failure appeared to develop simultaneously. A subset of patients with severe prerenal azotemia but without uremia had the highest mortality. These results are not consistent with the simple combination of single systems failure but rather suggest that renal and respiratory failure are makers of a generalized underlying defect.

Acute Kidney Injury↗

Clinical usefulness of high-pressure liquid chromatographic determination of serum pentamidine in AIDS patients.

We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy.

Acquired Immunodeficiency Syndrome↗

Triphasic waves: a reassessment of their significance.

Electroencephalograms and case histories of 50 patients with triphasic waves were reviewed. EEGs were studied for slowed dominant activity, anteriorly dominant triphasic waves, anterior-posterior lag time and bursts of triphasic waves. Etiologies of triphasic waves were: hepatic (28), azotemia (10), anoxia (10) and hyperosmolarity (2). Sixteen hepatic and two azotemic patients showed all of these characteristic EEG features. Triphasic waves demonstrating all of these features are highly characteristic of but are not pathognomonic for hepatic encephalopathy. Prognosis correlated best with the type of hepatic injury and deteriorating renal function. We postulate that triphasic waves are generated by the same thalamocortical volleys which normally induce spindles.

Brain↗

Metabolic studies of postischemic acute renal failure in the rat.

Postischemic acute renal failure was induced by 1 hr of clamping of the renal vasculature. Adenine nucleotide (ATP, ADP, AMP) and lactate (Lac) levels were measured after 0, 0.25, 1, 6, 24, and 48 hr of reflow to determine the time necessary for recovery to control levels. After 1 hr of ischemia with no reflow, [ATP] was 18% and [Lac] was 10-fold control levels. Control levels were restored after 24 hr of reflow. Variable ischemic times (5, 15, 30, 60, 90, and 120 min) followed by (1) no reflow or (2) 24 hr of reflow were also studied. [ATP] decreased to 25 and 13% of controls after 5 and 120 min of ischemia, respectively, and [Lac] increased to 5- and 13-fold controls after 5 and 120 min. Five to ninety minutes of ischemia followed by 24 hr of reflow resulted in a trend toward restoration of ATP and Lac levels; whereas, 120 min of ischemia followed by 24 hr of reflow resulted in death. The results indicate that: (1) In vivo ischemia results in a drastic and rapid shift in the ATP-ADP-AMP equilibrium; (2) the absolute concentration of ATP is not a reliable criterion of cell viability, but the ability to resynthesize ATP may be determinant in the reversibility of the lesion; (3) 1 hr of ischemia is reversible with respect to restoration of [ATP] and [Lac], but 24 hr of reflow are needed for restoration; and (4) ischemia for 90 min results in a metabolic derangement which is partially reversible in that metabolite levels are partially restored after 24 hr of reflow. However, 90 min of vascular clamping is not functionally reversible since the majority of animals exhibit severe azotemia and do not survive.

Acute Kidney Injury↗

Significance of megamitochondria in alcoholic liver disease.

The significance of megamitochondria in the alcoholic liver injury of humans was investigated as part of a large Veterans Administration cooperative study of the natural history of alcoholic hepatitis. Two hundred twenty patients were clinically stratified into the following three groups according to disease severity using serum bilirubin and prothrombin time as indicators: Group 1 (mild disease), serum bilirubin levels less than 5 mg/dl and prothrombin time prolonged for less than 4 s; group 2 (moderate disease), serum bilirubin levels greater than 5 mg/dl but prothrombin time prolonged for less than 4 s; and group 3 (severe disease), serum bilirubin levels greater than 5 mg/dl and prothrombin time prolonged for greater than 4 s. Megamitochondria were observed in 20% of the patients (45 of 220). Of these, 43 patients were in groups 1 and 2 of severity and only 1 patient belonged in group 3. The association of megamitochondria with cirrhosis was infrequent (33%, 15 of 45 patients). The differences in severity correlated with the differences in mortality: in patients with megamitochondria, only 1 had died at 6 mo compared with 40 deaths in patients without megamitochondria. By 12 mo, there were two deaths in patients with megamitochondria versus 51 deaths in those patients without. No complications were present in 72% of patients with megamitochondria versus 39% for those without. Infection, gastrointestinal bleeding, pancreatitis, hyperglycemia, azotemia, delirium tremens, seizures, and hepatic encephalopathy were all more common in patients without megamitochondria. The patients with megamitochondria appear to represent a subcategory of alcoholic hepatitis with a milder degree of clinical severity, lower incidence of cirrhosis, fewer complications, and good long-term survival.

Biopsy, Needle↗

Candida-associated diarrhea in hospitalized patients.

Ten hospitalized patients with severe diarrhea associated with intestinal Candida overgrowth are reported. Candida-associated diarrhea is predominantly of the secretory type, characterized by frequent watery stools, usually without blood, mucus, tenesmus, or abdominal pain. The patients were elderly, malnourished, and critically ill, or suffered from chronic debilitating illness. Their hospital stays were prolonged, and the majority were being treated with multiple antibiotics or chemotherapeutic agents. Diarrhea often led to dehydration, prerenal azotemia, hyperchloremic metabolic acidosis, and electrolyte imbalance. Stool culture most frequently isolated Cand. albicans in association with decreased normal flora. Colonoscopy showed no evidence of colitis. Diagnosis was made based on the absence of diarrhea-producing medications, the continuation of diarrhea despite fasting, the exclusion of other infections, inflammatory conditions and other causes of secretory diarrhea, and a dramatic response to a short course of nystatin.

Aged↗

Histopathology of cocaine hepatotoxicity. Report of four patients.

Although cocaine is believed to be hepatotoxic for humans, the hepatic histopathology has been reported in only 1 patient. That patient had zone-1 necrosis. We have encountered 4 patients with liver injury secondary to cocaine use, 1 of whom died. The biopsies from two patients showed well-demarcated zone-3 necrosis identical to that seen with acetaminophen toxicity. The patient who died had necrosis of almost all hepatocytes as found at biopsy and autopsy. Biopsy was performed on another patient after resolution of the illness, and showed hyperplastic endoplastic reticulum but no necrosis. All patients had mild large- and small-droplet steatosis in surviving hepatocytes. Inflammation was mild. Drug screenings performed on all patients showed the presence of a cocaine metabolite and the absence of acetaminophen, alcohol, and other potential toxins. Patients typically had early marked increase and rapid decrease of serum aminotransferases, mild-to-moderate increase in prothrombin time, myoglobinuria, and moderate azotemia. The predominant pattern of zone-3 necrosis is similar to that reported of mice given cocaine.

Adult↗

Nutritional, hepatic, and metabolic effects of cachectin/tumor necrosis factor in rats receiving total parenteral nutrition.

BACKGROUND: In orally fed animals, infusion of cachectin/tumor necrosis factor (TNF) caused weight loss and muscular wasting, accompanied by anorexia. Despite muscle wasting, there were gains in weight and protein and DNA contents of the viscera, but no significant metabolic abnormalities. METHODS: To observe the effect of cachectin/TNF on the nutritional-metabolic status, and without the confounding effect of anorexia, cachectin/TNF was infused into rats receiving total parenteral nutrition in sufficient amounts to induce weight gain in controls at the same rate as in orally fed rats. RESULTS: TPN prevented loss of body weight, but cachectin-treated animals had reduced nitrogen retention and carcass weight. By contrast, there were gains in visceral protein levels, which in the liver was due to a marked proliferation of biliary epithelium. In addition, cachectin-treated animals receiving TPN developed hyperglycemia, hyperosmolality, diuresis, and dehydration. They also had azotemia and cholestasis. CONCLUSIONS: In the absence of the effects of anorexia, cachectin reduced nitrogen retention and caused metabolic and multisystem dysfunction, comparable with the effects of clinical sepsis.

Animal Nutritional Physiological Phenomena↗

Retroperitoneal fibrosis: a two decade experience and gynecologic manifestations.

A 20-year experience with idiopathic retroperitoneal fibrosis (RPF) is presented (6 cases). Its gynecologic manifestations with the simulation of pelvic malignancy is discussed. Three of the patients presented with pelvic masses, one of these a para-vaginal mass. In one patient, RPF followed or was concurrent with invasive squamous cell carcinoma of the cervix, of which this is the first reported case. The subject of RPF is reviewed with the modes of management and evidence for an autoimmune etiology. Thrombocytopenia, a previously unreported finding with RPF, was noted in three of the six patients. The reversal of the A/G ratio in these patients is discussed, correlating this finding with the progression of azotemia.

Adult↗

An evaluation of a new patient compliance index using plasma propranolol levels.

Propranolol levels in plasma were studied in relation to dose prescribed in order to assess poor compliance with antihypertensive treatment. Fifty consecutive ambulatory patients (36-81 years) having hypertension, including 19 with azotemia, were investigated. Patient interviews using questionnaires and chart reviews were used to evaluate compliance. A composite Compliance Index was calculated for each patient. Individual oral doses of propranolol ranged from 20 to 160 mg. Subsequent plasma levels were determined by high performance liquid chromatography. Good correlation between last oral dose (mg) per body weight (kg) and log plasma propranolol levels were observed in patients whose compliance indices were above the mean for this sample (r = 0.74, p less than 0.01), when blood pressure control was satisfactory (r = 0.66) or excellent (r = 0.78), and when serum creatinines were greater than or equal to 1.4 (r = 0.76, p less than 0.001). Poor correlations between dose and propranolol levels suggest poor compliance with treatment.

Adult↗

Protein and energy tolerance by stressed geriatric patients.

Nutritional support of stressed geriatric patients remains empiric and has classically been limited by tolerance. Although the hypermetabolic response is known to increase protein and calorie demands, tolerance to increased loads of delivered nutrients in older patients has been questioned. We compared tolerance to nutrient delivery and nitrogen metabolism in 38 stressed surgical patients over age 65 to 38 Injury Severity Score or disease matched younger controls. Twenty-seven of the 31 geriatric patients (87%) who maintained normal renal function (serum creatinine less than 2.0 mg/dl) became azotemic (BUN greater than 30) while receiving 1.5 to 2.0 g of protein per kilogram of ideal body weight compared to only 21% of controls. This phenomenon led to inaccuracies in 17% of geriatric nitrogen balance studies because of unaccounted for serum accumulation of urea nitrogen (compared to only 6% in the control group). When calculated protein requirements were administered to the geriatric group, the mean nitrogen balance was -1.6. Resting energy expenditure as measured by indirect calorimetry demonstrated a strong correlation between actual calorie expenditures and calculated needs based on the Harris-Benedict basal energy expenditure (BEE) multiplied by an activity factor of 1.2 and a stress factor of 1.75 for trauma (r = 0.86, P less than 0.05) or 1.5 for general surgery patients (r = 0.72, P less than 0.05). In summary, energy requirements by stressed geriatric patients can be closely defined by calculation of the Harris-Benedict BEE in conjunction with appropriate activity and stress factors. However, attempts to deliver traditional levels of protein lead to azotemia and are frequently unsuccessful in achieving positive nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of refractory oral candidiasis with fluconazole. A case report.

We describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin, clotrimazole, and ketoconazole. In vitro resistance to clotrimazole was demonstrated as well. The patient received temporary relief with intravenous amphotericin B therapy, but this was associated with serious adverse effects, including transfusion-requiring anemia, azotemia, and severe thrombophlebitis. Despite two courses of intravenous amphotericin B therapy, the patient's highly symptomatic, recurrent oral and esophageal candidiasis continued. The patient was then treated with fluconazole and obtained immediate relief without associated adverse effects.

Acquired Immunodeficiency Syndrome↗

Acute renal failure and glucosuria induced by ferric nitrilotriacetate in rats.

Nitrilotriacetate (NTA), an effective metal-chelating agent, has been used as a substitute for polyphosphates in household laundry detergents. Nephrotoxicity and renal tumorigenicity have been reported in experimental animals that received high doses of NTA po for 4 weeks to 2 years. Since NTA exists in water as a variety of NTA-metal complexes, it was important to investigate the biological effects of NTA in a complexed form. In this study, acute and subchronic toxicity of a ferric iron chelate of NTA (Fe-NTA) was investigated in rats. When Fe-NTA was given ip, acute tubular necrosis and renal failure occurred following a single injection of 15 mg iron/kg. Repeated injections of sublethal doses produced degeneration and necrosis of the proximal tubular epithelium and was associated with polyuria, glucosuria, aminoaciduria, and azotemia. After 9 days of treatment, regeneration of the tubular epithelium with atypical cells was observed. Except for a parenchymal iron deposit, no marked changes were observed in other organs. None of these effects were observed in animals given noncomplexed NTA. In conclusion, the toxicity observed following high doses of NTA given po may be the result of an absorbed metal-NTA chelate.

Acute Kidney Injury↗

Pharmacologic probing of amphotericin B-induced renal dysfunction in the neonatal rat.

Acetazolamide, furosemide, chlorothiazide, and amiloride are pharmacologic agents that act primarily in the proximal tubule, loop of Henle, early distal tubule and late distal tubule and collecting duct, respectively. In order to investigate the renal pathophysiology induced by amphotericin B, these diuretic agents were used as probes of discrete segments of the nephron in the neonatal rat. Six-day-old rats were treated with amphotericin B (20 mg/kg, sc) or the vehicle. Twenty-four hours later, when evidence of amphotericin B-induced renal pathophysiology is detectable, the responses to the diuretic agents were assessed in a 2-hr clearance test, during which creatinine clearance (CCr) and the fractional excretion (FE) of water and various components of the filtrate were determined. Amphotericin B induced alterations in basal function including azotemia, hypostenuria, increases FE water and electrolytes, and a decreased FE urea (although CCr was normal). The diuretic responses to furosemide, chlorothiazide, and amiloride were not altered, indicating that the functional viability of the respective tubular segments was not affected by amphotericin B treatment. Although the maximal response to acetazolamide also remained unchanged in amphotericin B-treated pups, there was an attenuation in the half-maximal response, reflecting an apparent shift in the sensitivity to acetazolamide. All of the diuretic agents elicited an increase in urea excretion in amphotericin B-treated pups such that FE urea approached control values. Additionally, the magnitude of this increase was proportional to the magnitude of the increase in water excretion induced by each diuretic agent. These results indicate a disruption of urea recycling in the nephron and support the hypothesis that amphotericin B acts to increase the permeability of the distal tubule to urea. Thus, results from this study demonstrate the usefulness of pharmacologic agents as functional probes in the characterization of specific components of renal pathophysiology.

Amphotericin B↗

Risk indicators after envenomation in humans by Echis coloratus (mid-east saw scaled viper).

To determine the frequency, severity and predictors of bleeding and azotemia after envenomation in humans by Echis coloratus, a retrospective survey of 68 cases in Israel between 1970 and 1989 was carried out. We used univariate and multivariate analyses of clinical variables on admission for the outcome variables of bleeding, hemoglobin and platelet levels, and blood urea. Within hours or days after envenomation, a major bleeding episode occurred in 18% of the victims, a drop in hemoglobin to 10 g/dliter or less in 14%, and an increase in blood urea to 9 mmole/liter or more in 15%. These complications correlated with time interval between envenomation and hospital admission, and the following admission variables: degree of bleeding, hemoglobin level, platelet and white blood cell counts, blood urea and proteinuria. Complications were unlikely in patients who were presented with all of the following: a hemoglobin level of 13 g/dliter or more, a platelet count of 100,000/mm3 or more, a blood urea level of 7 mmole/liter or less, no proteinuria and no bleeding. Treatment on admission with a specific monovalent antiserum was associated with a shorter duration of hemostatic failure and a reduced incidence of anemia and thrombopenia. Infusion of fresh frozen plasma on admission did not appear to be effective in preventing complications.

Adult↗