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Biomedical subjects

C E Pippenger

Publications and source records attributed to C E Pippenger.

At least 37 records · Page 2Linked to original sources

Comparison of whole-blood cyclosporine levels and the frequency of endomyocardial lymphocytic infiltrates (the Quilty lesion) in cardiac transplantation.

Endomyocardial lymphocytic infiltrates (ELI), or "Quilty" lesions are morphologically and immunohistochemically distinct and are thought to be due in part to Cyclosporine therapy. In order to evaluate the relationship of ELI to CsA therapy, we compared the whole-blood CsA levels (WBCsA) with the frequency of ELI in our cardiac transplant patients. From January 1, 1987 to January 1, 1988, 364 concurrent endomyocardial biopsies and WBCsA were performed on 43 cardiac transplant patients. All biopsies were evaluated for acute rejection. ELI were recognized as well-circumscribed, flat or pedunculated lesions within the endomyocardium composed of mature T lymphocytes with pockets of B lymphocytes and occasional macrophages and plasma cells. All WBCsA were trough levels and were determined by high-pressure liquid chromatography. Results were evaluated using a logistic regression model for clustered data. ELI were observed in 17.9% (65/364) biopsies, and 60.5% (26/43) of patients had at least one ELI during the study period. The mean WBCsA was 155.2 ng/ml (SD = 62.9) in the ELI-positive group, and 190.2 ng/ml (SD = 97.0) in the ELI-negative group. Applying the regression model revealed a statistically significant negative correlation between WBCsA and the presence of ELI (P = 0.033)--that is, a lower WBCsA was associated with an increased probability of ELI. The frequency of clinically significant rejection was lower in the ELI-positive biopsies, and this correlation approached statistical significant (P = 0.053). These data suggest that ELI are unrelated to increased WBCsA and may represent an idiosyncratic reaction to CsA, or be related to factors other than CsA therapy.

Adolescent↗

Treatment of a potentially lethal dose isoniazid ingestion.

A seven-year-old boy ingested 3,000 mg (125 mg/kg) of isoniazid. Initial blood levels of isoniazid were 250 micrograms/mL approximately six hours after ingestion. Despite IV treatment in the emergency department with 3,000 mg pyridoxine and a repeat of the same antidote one hour later in the intensive care unit, the high isoniazid blood levels and persistent metabolic acidosis and coma prompted a decision to increase drug clearance by hemodialysis. Clearance data confirmed the effectiveness of hemodialysis in removing the poison, and the clinical response was dramatic.

Acidosis↗

The pediatric acute care laboratory.

The acute care laboratory service is an integral part of the total care required by the critically ill pediatric patient. Successful laboratory support for the intensive care unit requires optimal location, and sample collection, analysis, and reporting. These needs may be met with proper commitment on the part of laboratory staff and by application of the analytical technology now available. Testing support must reflect the special medical needs of pediatric patients in terms of sample size, test menu, instrumentation, and results interpretation.

Blood Gas Analysis↗

Clinically significant carbamazepine drug interactions: an overview.

Knowledge of the principles of drug action and distribution contributes to an understanding of the occurrence of drug interactions. The pharmacologic action of most drugs is postulated to occur by the formation of a drug-receptor complex at the site of action that is capable of altering the physiologic response of the target system. The therapeutic response observed depends on the sum of the numerous factors that can affect the disposition pattern of a drug. In an individual, the response to a given drug dose remains relatively constant, but in a large population, a fixed dose can produce a range of plasma concentrations and therefore varied clinical responses. For most drugs, there is a linear relationship between the total dose and the plasma concentration achieved at steady state. Saturation, or zero-order, kinetics accounts for nonlinear increases in drug concentration with dosage increase. Drug-drug interactions with carbamazepine include several types. (1) Autoinduction of carbamazepine metabolism increases the carbamazepine clearance rate, decreases the half-life, and decreases serum concentrations; the clinician must reevaluate a patient's serum levels at 4 to 6 weeks after initiation of therapy. (2) Carbamazepine induces the metabolism of other antiepileptic drugs, enhancing the clearance of phenytoin, primidone, valproic acid, clonazepam, and ethosuximide. (3) Other drugs added to the epileptic patient's drug regimen may induce the metabolism of carbamazepine, causing increased serum concentrations. (4) Inhibition of carbamazepine metabolism by other drugs can also occur; symptoms of drug intoxication rapidly follow. Interactions occur between carbamazepine and macrolide antibiotics, cimetidine, propoxyphene, and isoniazid. Drug-drug interactions are preventable.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbamazepine↗

Choosing an antiepileptic drug. The case for individualized treatment.

The range of drugs available for seizure control is broad, but selection of the drug and the dosage most likely to be effective for an individual patient is complex. In general, drug choice is determined by type of seizures involved and total daily dosage is based on milligrams per kilogram, so that plasma levels for all patients can be easily interpreted. Optimal seizure control is often possible with use of a single drug; in fact, in most patients with epilepsy, single-drug therapy is more effective than multiple-drug therapy and more desirable.

Adolescent↗

Enhanced gastrointestinal excretion of phenytoin in a patient with Crohn's disease.

A patient with Crohn's disease and generalized seizures who lacked the distal small bowel and ascending colon required 600 mg of intravenous phenytoin daily (11 mg/kg/24 h) to maintain her plasma phenytoin levels in the 12-24 micrograms/ml range. She received no oral phenytoin. Stool volumes ranged from 1,125 to 1,875 ml/24 h, and stool fraction phenytoin levels from 15 to 41 micrograms/ml. Urinary 5-(p-hydroxyphenyl)-5-phenylhydantoin and phenytoin levels in three 24-h samples were sufficient to account for 26, 46, and 57% of the administered drug, compared with the expected 70-90%. This was most likely due to an alteration of the normal cycle of absorption and reexcretion between the intestinal lumen and the blood resulting in net excretion of phenytoin into the bowel.

Adult↗

High-dose monotherapy in treatment of intractable seizures.

We evaluated the therapeutic efficacy and toxicity of high-dose monotherapy, using carbamazepine or phenytoin, in patients with previously uncontrolled seizures. Treatment with a single drug was equal to or better than polypharmacy, but only a few patients became free of seizures. Toxicity was mild and associated with higher total plasma levels after polypharmacy. Free fractions ranged from 0.14 to 0.30 for carbamazepine and from 0.60 to 0.13 for phenytoin. Toxicity was associated with free phenytoin levels above 3 micrograms/ml; there was no clear relationship between free carbamazepine level and toxicity.

Adult↗