Biomedical subjects
Publications and source records attributed to F Dumler.
In our case of gross hematuria in a renal transplant recipient, the source of bleeding was identified as the patient's own right ureteral remnant. We have discussed the significance of autologous ureteral hemorrhage in regard to diagnosis, clinical implications, and management.
Primary metabolic alkalosis is a disorder caused by both precipitating and perpetuating mechanisms. Correction of the abnormality requires intervention at both levels. Diuretic therapy and prolonged nasogastric suctioning are the major precipitating events, while volume depletion is the most common aggravating factor. Treatment is directed toward correction of dehydration and removal of the precipitating cause when possible. If this does not suffice, hemodialysis with a high chloride dialysate, with or without hydrochloric acid infusion, is the treatment of choice.
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UTP, CTP, and RNA synthesis were studied in the renal cortex of diabetic and control rats in vivo. The incorporation of UTP into RNA (nmol/h DNA) was used as estimate of RNA synthesis rate. Two to three days after streptozotocin injection, UTP and CTP ppol size and orotate incorporation into UTP and RNA were greater in diabetic animals than in controls. In addition, RNA content and RNA synthesis rate were increased. These changes were corrected by insulin infusion. In diabetic animals, additional increases in UTP pool, RNA content, and RNA synthesis rate followed contralateral nephrectomy. This increase in RNA content was greater than in uninephrectomized controls. The changes in the diabetic renal cortex were not accompanied by increased plasma concentrations of growth hormone. The increase in RNA content in the diabetic renal cortex is probably due to increased RNA synthesis. Increased synthesis of pyrimidines and expansion of the UTP pool may make this substrate more readily available for the synthesis of UDP sugars and may facilitate the synthesis of basement membrane in diabetes.
Glomerular uracil nucleotide metabolism was studied in vivo in control and diabetic rats 48 h after the injection of streptozotocin. The animals were infused for 2 h with 3H-orotate and the fraction of infused dpm incorporated into glomerular uracil nucleotides and RNA/mg of glomerular DNA was calculated. Diabetic glomeruli showed an increase in RNA/DNA compared to controls (p less than 0.05) and a greater incorporation of 3H-orotate into uracil nucleotides and RNA. These changes were reversed by insulin therapy. In separate experiments the renal cortical uracil nucleotide pool was expanded by feeding chow supplemented with 0.5% orotate to rats for 6 months. Normal animals fed orotate developed significant glomerular basement membrane thickening (p less than 0.01) when compared to age-matched controls, which was morphologically indistinguishable from that of diabetics. Orotate feeding also produced further basement membrane thickening in diabetic rats. These results suggest that early diabetes is characterized by an increase in glomerular uracil nucleotides, and that chronic expansion of the uracil nucleotide pool is associated with glomerular basement membrane thickening.
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A patient with scleroderma and severe renal failure was initially treated with hemodialysis and minoxidil (Loniten) without any improvement in her skin involvement. At a later date bilateral nephrectomy and a successful cadaveric renal transplant were performed. Her cutaneous manifestations have improved remarkably during the four years since transplantation. Because these patients do not tolerate hemodialysis very well, renal transplantation appears to be the most effective form of treatment, with the possible added benefit of cutaneous improvement.
The possibility of compartmentation of UTP in vivo was investigated in the renal cortex of unanaesthetized rats. In addition, liver and spleen were studied in order to compare tissues with different utilization of precursors for pyrimidine nucleotide synthesis. After continuous 2h infusions of [(3)H]uridine or [(3)H]orotate, their incorporation into UTP, UDP-sugars and RNA was quantified. Rates of RNA synthesis were calculated by dividing the incorporation of precursor into RNA by the average specific radioactivity of the UTP pool. Although similar RNA-synthesis rates might have been expected with the two precursors, higher rates were found with uridine than with orotate. The relative incorporation into UDP-sugars of these precursors was also different. Similar results were obtained in the liver. In the spleen, equal amounts of both precursors were incorporated into UTP, but [(3)H]orotate incorporation did not lead to labelling of RNA. To evaluate the heterogeneity of cells with respect to the metabolism of pyrimidines, precursor incorporation was studied in isolated glomeruli and by radioautography. Incorporation into glomeruli was qualitatively similar to but quantitatively different from results in the renal cortex. Although there is obvious tissue heterogeneity, compartmentation of UTP pools is the most credible explanation for the results obtained with the renal cortex and liver. Consequently RNA and UDP-sugars may originate from two different UTP pools. Tissue heterogeneity is the likely explanation for the results obtained in the spleen. Studies of synthesis of pyrimidine and RNA, particularly in relation to growth and regeneration, must take into consideration the precursor used, the apparent existence of UTP compartmentation and the degree of cellular heterogeneity.
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Hemodialysis-induced hypoxemia has been attributed to membrane-related complement activation leading to pulmonary leukostasis and to hypoventilation secondary to carbon dioxide losses via the dialyzer. We have separately assessed the role of membrane- and dialysis-related factors by using different dialyzers and sequential ultrafiltration and hemodialysis with first-use cellulose dialyzers produced both leukopenia and hypoxemia. With reused cellulose and polyacrylonitrile dialyzers, hypoxemia still occurred, but without leukopenia. Ultrafiltration produced leukopenia and no changes in Pao2; during the subsequent hemodialysis, hypoxemia developed as the leukocyte count increased by 50%. Our data indicate that leukopenia and hypoxemia are unrelated effects of hemodialysis, and favor hypoventilation as the major determinant of hypoxemia during hemodialysis.
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Osteonecrosis of the femoral head results in an increased uptake of 18F due to a reparative reaction in the necrotic area and its surroundings. Twenty hemodialysis and twenty-seven post-transplant patients were studied serially. In the hemodialysis group, nine patients had positive scintigraphs and eleven had negative studies. All were asymptomatic. In the transplant group, twelve were positive and fifteen were negative. Four patients with positive scans later developed unequivocal clinical and radiographic evidence of osteonecrosis. Patients with negative scans have been asymptomatic and without radiological abnormalities. Age, sex, duration of dialysis, bone mineral densitometry, total steroid dose, duration of hospitalization after transplantation, and serum chemistries were not different in positive and negative patients. All patients on alternate-day steroids have negative scans. A positive 18F scintigraph antedates the occurrence of clinical and radiological findings of osteonecrosis.
The effect of continuous arteriovenous hemofiltration on the clearance of either tobramycin or gentamicin (mean dose, 1.65 +/- 0.36 mg/kg) was studied in eight critically ill patients. Mean aminoglycoside clearance by hemofiltration was 3.47 +/- 1.93 mL/min and total body clearance was 11.92 +/- 3.51 mL/min. Hemofiltration clearance (HFCL) was directly correlated with hemofiltration flow rate (HFQR): HFCL (mL/min) = 1.03 HFQR (mL/min)-0.88 (R = .89). Mean volume of distribution was 0.31 +/- 0.08 L/kg, and the elimination rate constant was 0.020 +/- 0.01 hr-1. Continuous arteriovenous hemofiltration was responsible for the removal of between 3% and 36% of each aminoglycoside dose in 24 hours. In critically ill patients with changing hemofiltration flow rates, measurement of multiple serum aminoglycoside concentrations is necessary to accurately assess dosing requirements and avoid ototoxicity and nephrotoxicity.
An 84-year-old woman was admitted to the hospital for progressive edema and decreased urine output. She had been taking nabumetone for 6 months, but had discontinued the agent 2 weeks before admission due to progressive edema. On admission she had 2-3+ pitting edema. Her serum electrolytes were sodium 122 mEq/L, potassium 5.9 mEq/L, chloride 93 mEq/L, and carbon dioxide 19 mEq/L. A urinalysis was significant for protein 3061 mg/dl, ketones 15 mg/dl, blood 2+, leukocytes 26-50/high-power field, and a protein:creatinine ratio 24.9. The serum creatinine and blood urea nitrogen concentrations were 2.7 mg/dl and 70 mg/dl, respectively. Throughout hospitalization the patient underwent aggressive diuresis. She developed congestive heart failure, and hemodialysis was initiated. A renal biopsy specimen on hospital day 9 showed tubular damage with minimal glomerular changes consistent with a diagnosis of nonsteroidal agent-induced nephropathy. On day 13, a 24-hour urine collection had a protein excretion of 3151 mg. Although the patient recovered from her renal failure (creatinine clearance 43 ml/min), the nephrotic syndrome persisted (13 g protein/day). The patient developed infectious complications and died on hospital day 32.
A two-point model has been developed that uses actual predialysis (C0) and postdialysis (C1) blood urea nitrogen (BUN) values, and calculates the third value (C2) by forcing a solution for urea generation (Gurea) and urea volume of distribution (Vurea) that results in a predialysis BUN value a week later (C7) similar to C0. This two-point model was evaluated in 64 patients (mean age: 59 +/- 17 years) undergoing thrice weekly chronic hemodialysis, with mean predialysis (C0) and postdialysis (C1) midweek BUN values of 70 +/- 16 and 28 +/- 10 mg/dl, respectively. Compared to the standard three-point, single pool, variable volume standard, the two-point model accurately predicted Kt/V (1.08 +/- 0.22 versus 1.08 +/- 0.23, respectively) and Vurea (48.1 +/- 14.1 versus 48.1 +/- 13.9 L, respectively). The model also approximated C2 concentrations within an 11% range (66 +/- 20 versus 69 +/- 16 mg/dl for modeled and actual, respectively; p = 0.007) that allowed useful estimates of Gurea (6.64 +/- 1.87 versus 6.71 +/- 2.47 g/min for model and actual, respectively) and normalized protein catabolic rate (0.94 +/- 0.19 versus 0.94 +/- 0.26 for modeled and actual, respectively; p = ns). It is concluded that the two-point model described may be used for calculation of Kt/V and normalized protein catabolic rate in the clinical setting when a third BUN value is not available.
Infections are a common problem in dialysis patients. As hospital stay shortens, many require outpatient antibiotic therapy. Parenteral administration may pose considerable logistic and financial burdens, whereas daily intraperitoneal dosing increases the risk of contamination. Ceftazidime, with its long half-life, may provide adequate dosing when administered intraperitoneally thrice weekly. The authors therefore studied the kinetics of a 2 g loading dose followed by a 1.5 g dose every 48 hr in seven stable chronic peritoneal dialysis patients. In vitro stability at 4 degrees C (measured by high performance liquid chromatography) was 91% at 120 hr. Peak serum concentration (60 +/- 22 microg/ml) was reached at 4.9 +/- 2.2 hr. Serum values were 25 +/- 9 and 8 +/- 3 microg/ml at 24 and 48 hr, respectively. However, median trough levels at 48 hr in dialysate were significantly lower than in serum (2.8 vs 8.5 microg/ml, respectively; p = 0.0425). Pharmacokinetic parameters were as follows: bioavailability (F), 88% +/- 8%; volume of distribution at steady state (VDss), 20 +/- 8 L; absorption half-life (T1/2(abs)), 1.8 +/- 1.3 hr; elimination half-life (T1/2(el)), 11.4 +/- 4.5 hr; and clearance (CL), 22 +/- 10 ml/min. Intraperitoneal ceftazidime every 48 hr is a practical alternative to parenteral therapy of nonperitoneal infections. In peritonitis, whether increased permeability results in improved dialysate levels remains to be defined.
Experimental evidence suggests that acidosis may have a deleterious effect on protein metabolism. We evaluated 124 chronic dialysis patients (59 +/- 17 years) and defined acidosis as an anion gap >18 meq/L. A direct correlation (p < 0.0001 was found between anion gap and serum albumin (R = 0.402), BUN (R = 0.488), and serum creatinine (R = 0.473) concentrations. Acidotic patients (43%), when compared with nonacidotic patients, had greater serum albumin concentrations (3.95 +/- 0.50 vs. 3.60 +/- 0.48 g/dl, p = 0.0001, respectively), higher normalized protein catabolic rates (1.12 +/- 0.27 vs. 0.96 +/- 0.26 g/kg/d, respectively; p = 0.0004), and higher BUN (70 +/- 19 vs. 55 +/- 17 mg/dl, p = 0.0001) and serum creatinine (11.1 +/- 3.4 vs. 8.3 +/- 3.2, p = 0.0001 mg/dl) concentrations. However, no differences in midarm muscle circumference, fat free mass, or body cell mass were noted between groups when assessed by dialysis modality or acidosis status. In conclusion, mild chronic metabolic acidosis, likely caused by increased dietary protein intake, does not independently and adversely impact nutritional status in chronic dialysis patients.