Plasmapheresis in the treatment of an acute pancreatitis due to protease inhibitor-induced hypertriglyceridemia.

The use of protease inhibitors such as ritonavir to treat HIV-infected individuals has been associated with lipodystrophy, combined hyperlipidemias, and hypertriglyceridemia-induced pancreatitis. We report here on the treatment by plasmapheresis of a HIV-patient who presented with a rapid onset of severe ritonavir-induced hypertriglyceridemia complicated with an acute pancreatitis. A 35-year-old HIV-1 positive male following 3 weeks of ritonavir treatment presented with nausea, abdominal pain, a distended abdomen, and the following laboratory values: amylase (238 U/L), lipase (864 U/L), total cholesterol (27.1 mmol/L), and triglycerides (62.9 mmol/L). Following two plasmaphereses, the levels of total cholesterol, triglycerides, lipase, and amylase declined drastically and the patient was discharged home after 4 days with lipid and pancreatic enzyme levels within the reference range. To our knowledge, this is the first case of pancreatitis due to a PI-induced hyperlipidemia in a HIV-patient treated with plasmapheresis in an acute setting.

Different properties of the bradycardia produced by neostigmine and edrophonium in the cat.

PURPOSE: The bradycardia produced by neostigmine and edrophonium was examined according to its relation to cholinesterase inhibition and to its sensitivity to block by muscarinic receptor antagonists. For comparison, the ability of muscarinic antagonists to block the bradycardia produced by electrical stimulation of the vagus nerve was determined. METHODS: Cats were anaesthetized, vagotomized and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. The right vagus nerve was isolated for electrical stimulation. The muscarinic antagonists used were atropine, glycopyrrolate, pancuronium, gallamine, and AFDX-116. RESULTS: Neostigmine produced a dose-dependent decrease in cholinesterase activity which reached a plateau at a cumulative dose of 0.16 mg.kg-1 (ED50 0.009 +/- 0.003 mg.kg-1). Neostigmine produced a dose-dependent decrease in heart rate with the dose-response relationship (ED50 0.1 +/- 0.01 mg.kg-1; P = 0.0006) shifted to the right of that for the inhibition of cholinesterase activity. In contrast to the anticholinesterase effect, the bradycardic effect did not reach a plateau and continued to increase even at doses at which the cholinesterase inhibition was maximal. The maximal decrease in heart rate when the heart was still in sinus rhythm was by 81 +/- 13 bpm (49 +/- 7% of baseline), which was produced by a dose of 0.32 mg.kg-1. Edrophonium produced dose-dependent decreases in cholinesterase activity and heart rate, which were highly correlated (correlation coefficient r = 0.99, P < 0.0001). The ED50 of the reduction in heart rate (0.9 +/- 0.18 mg.kg-1) and cholinesterase activity (0.89 +/- 0.12 mg.kg-1) produced by edrophonium were similar. Moreover, the reduction in heart rate and cholinesterase activity produced by edrophonium reached a plateau at the same dose (6.4 mg.kg-1). At this dose, heart rate decreased by 22 +/- 2 bpm (14.6 +/- 0.9% of baseline). Compared to the bradycardia produced by stimulation of the vagus nerve, that produced by neostigmine was blocked by muscarinic antagonists at significantly lower doses while that produced by edrophonium was blocked at similar doses. CONCLUSIONS: The neostigmine-induced bradycardia is poorly correlated with cholinesterase inhibition compared to that produced by edrophonium, and has a higher sensitivity to muscarinic receptor antagonists compared to that produced by edrophonium or vagus nerve stimulation. These results are consistent with the hypothesis that the neostigmine-induced bradycardia is, in part, the result of neostigmine directly activating cholinergic receptors within the cardiac parasympathetic pathway. The bradycardia produced by edrophonium may be accounted for solely by an anticholinesterase action.

Erythrocyte electrolytes in psychiatric illness.

Erythrocyte sodium and potassium were measured in 71 patients with a variety of psychiatric disorders and 39 normal controls. Alterations in red cell sodium and potassium occurred in association with changes with mood state in affective illness. However, alterations in erythrocyte potassium may be a non-specific finding in all psychiatric illness. The methodological limitations of our study are discussed. Our data suggest that further study is required to clarify the role of intracellular electrolyte disturbances in psychiatric illness, particularly affective disorders.

A model for assessing interference.

Most studies of analytical interference indicate the magnitude but not the type of interference. We developed a model for interference that assesses the magnitude of the following types of interference: independent of analyte concentration, dependent on analyte concentration, and a combination of the two. The experimental design for the model is an orthogonally arranged matrix with progressively increasing concentrations of analyte and interfering agent. Multiple regression with these independent variables (concentration of analyte, concentration of interfering agent, and the product of the two) is used to determine the magnitude, direction, and significance of each type of interference. Applying the model to study interference by hemoglobin with determinations of creatinine, direct bilirubin, and total bilirubin showed that hemoglobin interferes with determination of creatinine independent of the analyte concentration, interferes with total bilirubin dependent on the analyte concentration, and interferes with direct bilirubin by a combination of these two.

The method of determination must be considered in interpreting blood cholesterol levels.

Based on the results of recent clinical trials, physicians have been encouraged to screen and treat patients for hypercholesterolemia. Since the data from the Lipid Research Clinics (LRC) have been used to define the patient population that should be treated, a comparison of LRC cholesterol results with those obtained with two commonly used clinical laboratory instruments was performed. Both the Technicon SMAC and the Du Pont aca had positive bias compared with the LRC method. Therefore, many patients with cholesterol concentrations greater than 265 mg/dL (6.85 mmol/L) as determined by these routinely used methods have markedly lower levels determined by LRC methods. These findings not only indicate that rigorous interlaboratory standardization is required to conform to LRC reference values, but they also suggest that the clinician should be aware of these methodological considerations when the decision to treat hypercholesterolemia is made.

Erythrocyte sodium and potassium in affective illness.

In a preliminary study, erythrocyte sodium and potassium were measured in 24 affectively ill patients and 24 normal controls. Erythrocyte sodium was significantly lower and erythrocyte potassium was significantly higher in the euthymic and affective depressed patients as compared with controls.

Automated determination of urinary creatinine without sample dilution: theory and practice.

The rate of the Jaffé reaction depends on the concentration of sodium hydroxide; the pseudo-first-order rate constant of the reaction, at 37 degrees C in 10 mmol/L picrate solution, is 0.004 mmol/L. We formulated an automated method to determine urinary creatinine directly without manual sample dilution. The conditions are as follows: 10 mmol/L picrate and 60 mmol/L sodium hydroxide (final concentrations); ratio of sample to final volume, 1:41; temperature, 37 degrees C; wavelengths of measurement, 500 or 510 nm; interval of measurement, 30 to 90 s; and mode of measurement, kinetic. Determinations of creatinine in patients' samples by the new method compared favorably with those obtained with the AutoAnalyzer and aca. The run-to-run CVs were 3.6% or less, and the method was accurate for concentrations of creatinine up to 3000 mg/L. We recommend this method as a good replacement for the AutoAnalyzer or aca methods.

Hemoglobin interference from in vivo hemolysis.

Laboratory values for specimens from a case of intravascular hemolysis showed that hemoglobin was significantly increased and thus could interfere with the determination of other analytes. We studied this problem by adding increasing amounts of purified hemoglobin (to a maximum concentration of 19.3 mg/L) to aliquots of pooled serum samples. The hemoglobin significantly interfered with the determination of only five analytes: albumin, aspartate aminotransferase, direct bilirubin, and total protein on the SMAC, and creatinine on the Astra. We propose that for cases of proven intravascular hemolysis, values for only the analytes not affected by hemoglobin should be reported. We find lactate dehydrogenase activity useful in assessing the components of in vivo hemolysis; the differences between serum and plasma values for potassium, lactate dehydrogenase, and hemoglobin are related to in vitro hemolysis. Criteria for specimen collection and assessment of type of hemolysis are proposed.

Acute renal failure and seizures associated with chlorambucil overdose.

A case of chlorambucil overdose is presented. The clinical manifestations were acute renal failure and seizures. We are not aware of this combination of clinical features being previously reported with chlorambucil overdose.

Ketone interference in estimation of urinary creatinine; effect on creatinine clearance in diabetic ketoacidosis.

Acetoacetate is known to spuriously raise serum creatinine concentration in patients with diabetic ketoacidosis. Its effect on urinary creatinine has not been studied. Since the renal threshold for ketoacids is low, large amounts of acetoacetate may be present in the urine of uncontrolled diabetics. We investigated this interference using three different automated analysers. We found that +3 or +4 reactions with Ketostix, equivalent to greater than 10 - 15 mmol/L of acetoacetate caused significant interference with the Abbott VP and Beckman Astra instruments. This could cause errors in the calculation of creatinine clearance especially when serum creatinine is close to a normal level. We recommend that measurement of creatinine clearance be delayed until better diabetic control is achieved or the creatinine be measured by a method which is free from ketone interference, e.g., by the Dupont aca.