Dosing guidelines for foscarnet and trimetrexate.

The P & T Committee at Trinity Lutheran Hospital, a 320-bed, community/teaching hospital in Kansas City, MO, has developed dosing and monitoring guidelines for foscarnet sodium (Foscavir) and trimetrexate glucuronate (Neutrexin)--two drugs used to treat patients with opportunistic infections associated with the human immunodeficiency virus (HIV). Presented in this Experience Brief is a short discussion of these drugs, the rationale for guideline development, and the actual dosing and monitoring protocols devised.

Species variation in hepatic metallothionein.

Metallothionein (MT) is a low-molecular-weight protein involved in the homeostasis of endogenous metals and in the detoxication of heavy metals. In humans, the levels of hepatic MT have been shown to be up to 100 times the levels found in rat and mouse liver. In order to further investigate this species difference in hepatic MT levels, hepatic MT was quantified in 15 species (human, monkey, dog, cat, cow, pig, sheep, goat, rabbit, chicken, hamster, rat, mice, guinea pig, and frog). Fresh liver was obtained from each species and MT was quantified by 2 different metal-saturation assays. Results from the Cd-heme and Ag-heme assays showed that human, dog, cat, pig, and goat had the highest hepatic MT levels (400-700 micrograms/g liver). Monkey, cow, and sheep had moderate hepatic MT levels (about 200 micrograms/g liver), while rodents (mouse, rat, hamster, guinea pig, and rabbit) had low hepatic MT levels (2-10 micrograms/g liver). Hepatic MT levels in non-mammals (chick and frog) were slightly higher than rodents (about 20 micrograms/g liver). Sephadex G-75 column elution volumes ranged from 1.7 to 1.8, which implies that MT from all species had approximately the same molecular weight and similar structure. Copper and zinc concentration in the cytosols were measured by atomic absorption spectrophotometry. Dog and cat had the highest levels of Cu (86 and 50 micrograms/g liver, respectively), and pig and hamster were lowest (about 10 micrograms/g liver). Human, dog, cat, and goat had the highest levels of zinc (approximately 40-50 micrograms/g liver) while hamster and guinea pig were lowest (approximately 15 micrograms/g liver). The results show that there is a marked species difference in hepatic MT concentrations with dog, cat, and human having the highest levels.

Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase chain reaction.

OBJECTIVE: To identify and prospectively follow patients with suspected human ehrlichiosis regarding clinical manifestations, laboratory variables, methods for confirming the diagnosis, and complications. DESIGN: Prospective case study. SETTING: University and Veterans Affairs hospital and clinics. PATIENTS: Observations in 30 adult patients with acute febrile illness or with unexplained fevers and cytopenias or abnormal liver profiles or both. MEASUREMENTS: Serial clinical examinations, hematologic profiles, liver profiles, electrolyte determinations, chest radiographs, and response to therapy; other studies appropriate for patient care. INTERVENTION: Therapy with doxycycline. RESULTS: Thirty cases of ehrlichiosis were identified between 1989 and 1992. Tick exposure was strongly associated with the illness (P = 0.0001). Symptoms were nonspecific; fever, chills, and headache predominated but many other symptoms also occurred. Fever and skin rashes with various morphologic characteristics were the most common physical findings. Laboratory investigations indicate that the hematologic, hepatic, and central nervous systems are commonly involved in human ehrlichiosis. Twenty of 23 patients (87%) tested by the polymerase chain reaction using Ehrlichia chaffeensis sequences and whole blood samples were positive for E. chaffeensis. CONCLUSIONS: The syndrome of human ehrlichiosis is not commonly recognized by physicians. Ehrlichiosis should be considered in the differential diagnosis of patients with febrile illness after known or possible tick exposure, particularly if accompanying cytopenias or abnormal liver profiles or both are present. The therapeutic response to doxycycline is prompt, and complications are uncommon in promptly treated patients. The polymerase chain reaction applied to whole blood samples is a promising test for rapid confirmation of the diagnosis within 24 to 48 hours.

Vascular amyloid in a patient with multiple myeloma.

A patient developed nodules on the scalp in the distribution of blood vessels and was found to have multiple myeloma. Biopsy of a nodule and of muscle demonstrated amyloid in the vasculature. Clinical manifestations of vascular amyloid are discussed. Cutaneous nodules along the course of vessels and symptoms of peripheral vascular disease may be presenting signs of systemic amyloidosis.