Local tissue reaction to intravenous fluorouracil and leucovorin.

Fluorouracil alone can cause a variety of dermatologic adverse effects; however, it is not considered to be a chemical vesicant. We report a case of apparent enhanced local skin reaction from the combination of intravenous fluorouracil and leucovorin. The reaction occurred in the patient's other hand on rechallenge.

Correlation of free phenytoin to serum albumin in cancer patients.

The objectives of this study were to compare the total and free phenytoin serum concentrations of cancer patients with hypoalbuminemia with those of cancer patients with normal serum albumin and to correlate the percentage of free phenytoin with the albumin concentration. A total of 22 patients were studied, 13 with normal albumin concentration and 9 with low albumin. The mean free phenytoin in the normal albumin group was 9.9 (+/- 1.3) percent and 17.6 (+/- 4.6) percent in the low albumin group. With the groups combined, the mean free phenytoin was 13.1 percent (range 8.3-22.2) with the albumin range of 20-45 g/L. There was a significant negative correlation (r = -0.9, p less than 0.001) between the percentage of free phenytoin and the measured serum albumin. In cancer patients, the serum albumin concentration appears to be the key factor that determines the percentage of free phenytoin. In cancer patients with low serum albumin concentration, the total and free phenytoin concentration should be measured for adequate assessment of phenytoin therapy.

Phenytoin hepatotoxicity: a review of the literature.

Phenytoin hepatotoxicity is a serious idiosyncratic reaction that occurs in less than one percent of patients. The onset of symptoms occurs early in therapy, usually within the first six weeks. Presenting symptoms often include fever, rash, lymphadenopathy, hepatomegaly, anorexia, and myalgias or arthralgias. Other significant findings that may develop throughout hospitalization are jaundice, periorbital or facial edema, and splenomegaly. The following alterations in liver function tests are associated with phenytoin hepatotoxicity: elevations in serum aminotransferases, lactic dehydrogenase, alkaline phosphatase, bilirubin, and prothrombin time. Rechallenges, lymphocyte stimulation test, and liver biopsy have been used to aid in the diagnosis. Rechallenge is the most definitive diagnostic approach; however, its use is limited by the potential of a fatal reaction. Although the exact mechanism of phenytoin hepatotoxicity is unknown, the majority of literature supports a hypersensitivity mechanism. The severity of this adverse effect ranges from self-limiting to fatal. Since 1965 six fatal cases have been reported. To date, sufficient evidence is not available to establish treatment guidelines. Discontinuation of phenytoin therapy is warranted.

Erythromycin ototoxicity and acute psychotic reaction in cancer patients with hepatic dysfunction.

Two cases of severe hearing loss due to intravenous administration of erythromycin lactobionate are described. Documented, bilateral sensorineuronal hearing loss developed in both patients and gradually improved when the dose of erythromycin was decreased. Neither patient had severe renal dysfunction (documented clearances of 25 to 30 mL/min), but both had hepatic dysfunction with elevated bilirubin levels. Additionally, both were receiving other ototoxic drugs concurrently. Both patients also had an acute psychotic reaction that was temporally related to the ototoxicity and high-dose erythromycin therapy.

Tobramycin blood levels from an indwelling right atrial catheter.

Indwelling right atrial catheters provide continuous access to the venous circulation for the purpose of long-term alimentation and blood collection. Two types of central venous systems are the Broviac and Hickman catheters. In general, the Hickman is more versatile, allowing easy blood sample collection, in addition to continuous intravenous fluid and drug administration. Two cases are presented where apparent erroneous tobramycin blood samples were collected through one of these catheter systems. One case compares Hickman tobramycin blood levels with standard peripheral venicollection. Possible ramifications and solutions to the problem are discussed.

Sexual dysfunction due to antihypertensive agents.

A review of sexual dysfunction due to antihypertensive agents is presented. Sexual dysfunction is a relatively common complication of antihypertensive drug therapy and has been associated with nearly all of the antihypertensive agents. The physiology of the normal sexual response, proposed mechanisms of sexual dysfunction, and the types of disorders and relative incidence rates associated with individual agents are discussed. Since a disturbance in sexual function may lead to poor compliance with the drug regimen, it is important that the clinician be familiar with this topic. Information on the detection of antihypertensive-agent-induced sexual dysfunction, patient counseling, and therapeutic alternatives, should a disorder in sexual function occur, also is provided.

Salivary phenytoin concentrations in geriatric patients.

The concentrations of phenytoin in saliva (Csal) and serum (C) in geriatric patients were compared. Salivary and venous blood samples were collected from 13 patients over 55 years old who were taking oral phenytoin for at least one week. The data of 10 patients were suitable for analysis. Phenytoin concentrations were determined with an immunoassay. Phenytoin Csal/C ratios were calculated. Based on previously reported Csal/C ratios of approximately 0.1 for general patient samples, an expected Csal for each patient was calculated as (C)(0.1). A Student's t test for paired data was used to test for differences between the expected and measured salivary concentrations. The mean Csal/C ratio was 0.098 (S.D. = 0.03, range 0.041-0.152). The correlation between the measured Csal and C was 0.96. There was no significant difference between the expected and measured salivary phenytoin concentrations (p greater than 0.6). This study suggests that age does not affect the ratio of salivary to serum phenytoin concentrations. The wide range of ratios observed, however, indicates that more research is needed before salivary phenytoin concentrations should be used clinically in geriatric patients.

Phenytoin concentrations in venous versus capillary blood of geriatric patients.

In 15 elderly patients who had seizure disorders, venous blood (standard venipuncture) was compared with capillary blood (finger lancet puncture) as the source of the specimen for determination of serum phenytoin concentration. The values obtained by the two procedures were similar (r = 0.99). The mean serum phenytoin levels in the venous samples was 17.3 micrograms/ml, and in the capillary samples 17.0 micrograms/ml; the paired t test showed no statistical difference. Either method provides an adequate blood sample for determination of phenytoin, and both may be used interchangeably. Capillary samples may be preferable for aged patients in whom venipuncture proves difficult or painful.

Comparison of theophylline concentrations in venous blood and capillary blood in asthmatic children.

Twenty children, five to 16 years old, diagnosed as having asthma, were studied to compare the serum concentrations of theophylline obtained by standard venipuncture with capillary concentrations obtained by finger lancet. The mean theophylline concentration in venous samples was 9.27 mg/L and in capillary samples was 9.26 mg/L. Comparison by the paired t-test showed no statistical difference between kinds of samples. When surveyed as to their preference, nine patients preferred the venous method, five the capillary method, and six had no preference.