Biomedical subjects
Publications and source records attributed to D J Leehey.
We report a woman with hypercalcemia and hypophosphatemia due to primary hyperparathyroidism. Hemodialysis using a phosphorus-enriched, conventional, calcium-containing dialysis solution resulted in the simultaneous correction of hypercalcemia and hypophosphatemia, resulting in a marked improvement of the patient's impaired mental status.
A phosphorus-enriched dialysate was used to intensively hemodialyze two non-uremic and non-hyperphosphatemic patients poisoned with ethylene glycol. As a consequence of the use of such a dialysate, we were able to prevent a fall in plasma inorganic phosphorus levels in these patients in spite of the intensive dialytic therapy.
The effect of vascular access recirculation (AR) on the modeled urea distribution volume (V) is not straightforward. When blood is sampled properly so that it is not admixed with recirculated blood, AR will cause an unexplained increase in V in cases in which AR is present throughout the dialysis session (when AR is limited to the terminal portion of a dialysis session it will cause little or no change in the modeled V). On the other hand, when blood is sampled from the arterial line after simply stopping the pump, postdialysis blood urea nitrogen (BUN) represents arterial line BUN and does not always reflect the BUN in the patient's blood. Under these conditions, when AR is present throughout the dialysis session the modeled V usually shows an unexplained decrease, but V may be unchanged, depending on the urea reduction ratio (URR). We performed a mathematical analysis to predict when V would be decreased and when it would be unchanged when the postdialysis BUN is contaminated with admixed blood. The analysis revealed that when AR is present uniformly throughout the dialysis session, the modeled V should be underestimated when the URR is < or = O.70. When the URR is greater than 0.70, even severe degrees of AR may not be reflected by a change in V. When AR is limited to the terminal part of the dialysis session or when AR increases during the dialysis session, and when V is based on admixed postdialysis blood, underestimation of V will occur in almost all circumstances. In a cross-sectional comparison of modeled to anthropometric volume ratios in eight patients with severe AR and in 11 controls, and in sequential modeling studies in a single patient in whom severe AR developed gradually over time, the volume ratio was low in most, but not all instances when modeled V was based on an admixed postdialysis BUN sample.
An elderly man with end-stage renal disease required intensive hemodialysis therapy because of sepsis-induced hypercatabolism. We were able to prevent the occurrence of hypophosphatemia by using a phosphorus-enriched dialysate during hemodialysis treatments.
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Three patients with acute massive swelling of the left lower extremity occurring soon after placement of a renal allograft in the left iliac fossa are described. In each patient, obstruction to venous outflow from the left lower limb was documented by venography. We surmise that venous obstruction resulted principally from a combination of extrinsic compression of the left iliac vein by the right common iliac artery or by the allograft, and enhanced venous return from the allograft.
A normophosphatemic patient suffering from lithium intoxication was hemodialyzed with a phosphorus-enriched, bicarbonate-based dialysis solution. A post-dialysis fall in plasma phosphorus level was prevented.
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Abnormalities in extracellular matrix degradation may play a pathogenetic role in diabetic nephropathy. Cultured renal mesangial cells are known to synthesize increased amounts of matrix proteins when incubated in high glucose media (e.g., 30 mmol/l). However, the effect of glucose loading on degradative enzymes is unknown. Primary cultures of rat mesangial cells were grown until confluent in the presence of fetal calf serum (FCS) and insulin (0.67 U/ml). Cells were then cultured for 7 days in plastic wells in either 10 or 30 mmol/l glucose media containing neither FCS nor insulin. Collagenase activity in media were determined by zymography and quantitative spectrofluorometry. Cathepsin B and D activities in cell extracts were measured by spectrofluorometry (using the fluorescent substrate Z-Arg-Arg-7-amido-4-methylcoumarin) and 125I-labeled hemoglobin digestion, respectively. Gelatin-degrading activity of live mesangial cells was also determined. mRNA levels for collagenase IV, cathepsin B, and cathepsin D were determined by Northern analysis. A major band of collagenase activity with a molecular size of 72 kDa was observed in all mesangial cell media. Exposure of cells to high glucose media resulted in significant reductions in collagenase and cathepsin B activities as well as impairment in gelatin-degrading activity. Collagenase IV and cathepsin B and D mRNA levels were also decreased by glucose loading. To exclude the possibility that glucose loading was injurious to cells, 3H-leucine uptake (as a measure of protein synthesis) and membrane alkaline phosphatase activity (as a biochemical marker of viability) were not affected by the high glucose condition.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: Previous studies have shown a decrease in serum magnesium (Mg) concentration when continuous ambulatory peritoneal dialysis (CAPD) patients previously maintained on a 1.0-1.2 mEq/L Mg peritoneal dialysis solution (PDS) were dialyzed with a 0.5 mEq/L Mg PDS. However, the prevalence of hypomagnesemia in CAPD patients dialyzed with low-Mg PDS is unknown. DESIGN: A retrospective study to determine the prevalence of hypomagnesemia and the factors associated with its occurrence in CAPD patients dialyzed using a 0.5 mEq/L Mg PDS. SETTING: A CAPD unit in a large Veterans Affairs Hospital. PATIENTS: All our CAPD patients (33) enrolled over a 52-month period. RESULTS: All patients had serum magnesium levels higher than 1.25 mEq/L prior to use of low-Mg PDS. Hypomagnesemia (serum Mg < 1.25 mEq/L) developed in 21/33 patients (64%) when a 0.5 mEq/L Mg PDS was employed. Hypomagnesemia developed a mean of 8.2 months after beginning treatments. The duration of dialysis and the number of episodes of peritonitis did not differ between patients with and those without hypomagnesemia. Serum albumin levels were significantly lower in patients with hypomagnesemia (2.5 +/- 0.12 g/dL vs 3.2 +/- 0.12, p < 0.01). Magnesium supplements were given to 13 patients; following this therapy, serum magnesium values became normal. CONCLUSIONS: CAPD patients dialyzed with a 0.5 mEq/L Mg PDS may develop a considerable fall in serum magnesium level and may require magnesium supplements in order to restore normal serum values.
Diabetes mellitus is now the most common cause of end-stage renal disease (ESRD) in the U.S., and the percentage of ESRD patients with diabetes is increasing yearly. One-year survival in such patients is poorer than in those with other etiologies of ESRD but has improved from 64% to 74% over the past decade. However, overall 5-year survival on dialysis is still less than 20% in this population. It is controversial whether hemodialysis or peritoneal dialysis (CAPD, CCPD) is the best choice. Advantages of hemodialysis include its ready availability and convenience for patients, who are frequently incapacitated by blindness, cerebrovascular disease, and/or amputations. However, patients may tolerate dialytic ultrafiltration poorly due to autonomic neuropathy. Maintenance of vascular access is difficult, which may contribute to inadequate dialysis in some patients. Cardiovascular disease remains the most common cause of death. Management of coronary artery disease is difficult because of the high prevalence of silent ischemia. Control of blood pressure is of paramount importance in preventing cardiovascular complications. Improved survival in diabetics who were dialyzed in a more intensive than usual fashion has been reported recently. In addition, much of the difference in survival rates between diabetics and nondiabetics can be accounted for by the poorer nutritional status in the former group. Thus attention to the dose of dialysis administered and assurance of adequate nutrition should result in improved survival of the diabetic patient on hemodialysis.
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A new sample preparation technique, solid-phase extraction employing the ion-pair reagent octyl sodium sulfate (OSS), was developed for the selective isolation of nanogram quantities of naloxone from human plasma. Plasma samples containing naloxone, OSS, buffer, and naltrexone (internal standard) were applied to octyldecylsilane (C18) cartridges, and the opiates were eluted with 100% methanol. An extraction efficiency of 90% was achieved. Extracts were then examined by reversed-phase high-performance liquid chromatography with electrochemical detection, with mobile phase composition adjusted to optimize separation and quantitation. An oxidizing potential of +0.93 V resulted in an assay sensitivity of 1.0 ng. Thus, plasma naloxone levels of ca. 20 ng/ml could be readily detected and quantified. The intra-assay coefficient of variation at plasma levels of 80 ng/ml was 7.2%. Plasma naloxone values obtained during a 5-h infusion of the drug (0.24 mg/min) in two normal human subjects were stable and reproducible. Thus, the method herein described is applicable to human studies employing naloxone infusion.
1. Decreased pressor sensitivity to angiotensin II occurs in cirrhosis, but the mechanism remains unclear. 2. Angiotensin II dose-response studies were performed in conscious, chronically instrumented cirrhotic and control rats, and angiotensin II concentration-response studies were performed in isolated blood vessels obtained from similar groups of animals. 3. Cirrhotic rats demonstrated a significantly decreased pressor response to angiotensin II (5-80 ng/kg intravenously). However, angiotensin II-generated tension in thoracic aortic rings isolated from cirrhotic rats and studied in vitro was not impaired. These findings are consistent with the concept that circulating vasodilator substances in cirrhosis rather than an abnormality intrinsic to vascular smooth muscle cells are responsible for the decreased pressor sensitivity to angiotensin II in vivo. 4. Pretreatment with the cyclo-oxygenase inhibitor indomethacin (3 mg/kg intravenously) restored pressor sensitivity to angiotensin II to normal, suggesting that cyclo-oxygenase products, possibly vasodilator prostaglandins, may be involved in mediating pressor resistance to this hormone in vivo.
A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups. However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively). Similarly, severity of toxicity was not affected by the dosing intervention. Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease. After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy.
Skin necrosis similar to that induced by warfarin was seen in a patient who had never received the drug but who was vitamin K-deficient due to malnutrition and prolonged treatment with broad-spectrum antibiotics. He also had end-stage renal failure and was receiving prophylactic subcutaneous heparin therapy because of immobilization. His plasma protein C antigen level and, disproportionately, his plasma protein C functional activity were decreased. Both protein C values improved after vitamin K therapy, discontinuation of heparin, and initiation of hemodialysis. We surmise that skin necrosis occurred as a result of protein C deficiency caused by vitamin K depletion. Production of abnormal (descarboxy) protein C/protein S due to vitamin K deficiency and increased protein C inhibitory activity associated with renal failure and/or heparin administration may have contributed to the clinical picture. This rare but serious complication of a relatively common disorder, viz., vitamin K deficiency, reinforces the importance of vitamin K supplementation in malnourished patients who receive long-term antibiotic maintenance therapy.
Several extracorporeal techniques have been used to remove N-acetylprocainamide (NAPA), the major metabolite of procainamide, in patients intoxicated with this substance. We report a patient with life-threatening NAPA intoxication who was rapidly and successfully treated with combined high-efficiency hemodialysis and charcoal hemoperfusion. The hemodialyzer and hemoperfusion cartridge were placed in series such that the patient's blood was dialyzed before reaching the cartridge. Overall clearance of NAPA was 153 mL/min, with clearance due to hemodialysis averaging 102 mL/min and that due to hemoperfusion averaging 88 mL/min. Thus, addition of the hemoperfusion cartridge into the extracorporeal circuit resulted in a 50% increase in clearance over that obtainable by high-efficiency hemodialysis alone. In comparison to other modalities, this technique is more effective than either hemodialysis or charcoal hemoperfusion alone and can achieve a more rapid reduction of serum NAPA levels than that observed with slow continuous hemofiltration or hemodiafiltration.