Economic and clinical impact of a pharmacy-based filgrastim protocol in oncology patients.

The effects of a clinical protocol for filgrastim use in oncology patients were studied. A chart review was conducted for every fourth oncology inpatient who received filgrastim at a community hospital between January and June 1996 to determine how filgrastim was being used in the hospital's oncology patients. The results were presented to the oncology committee, and a filgrastim protocol was implemented. The protocol stated that filgrastim would be discontinued when the absolute neutrophil count (ANC) was > or =1500 cells/mm3 for two days after the neutrophil nadir. Six months after the protocol was implemented, a follow-up evaluation was conducted by reviewing the chart for every fourth oncology patient who received filgrastim between November 1996 and April 1997. Twenty-one patient charts were reviewed before the protocol was implemented, and 34 charts were reviewed after implementation. The results showed there was compliance with the protocol for 19 (76%) of the 25 patients evaluable for compliance. Sixty-seven percent of patients were febrile before the protocol was implemented, and 56% were febrile afterward. Ten percent of patients had documented infections before implementation, compared with 12% afterward. The average ANC at which filgrastim was discontinued before and after the protocol was implemented was 6839 and 5538 cells/mm3, respectively. Filgrastim was discontinued by a pharmacist in 32% of cases. A $22,416 cost saving was achieved in the first six months after protocol implementation, with no compromise in clinical efficacy. A pharmacy-based protocol for discontinuing filgrastim therapy in oncology patients saved a community hospital more than $22,000 in the first six months withno adverse impact on the drug's effectiveness.

Interaction of itraconazole and digoxin.

A 69-year-old man who had been taking digoxin for 2.5 years developed an elevated serum concentration of digoxin in association with digoxin toxicity (characterized by nausea and vomiting) 9 days after the addition of itraconazole to his regimen for the treatment of sternal osteomyelitis. Coadministration of itraconazole resulted in a statistically significant increase in the half-life of digoxin that necessitated a reduction of the digoxin dose by almost 60%. We thus recommend that patients receiving itraconazole and digoxin concomitantly have serum levels of digoxin monitored frequently. In addition, these patients should be carefully questioned about nonspecific gastrointestinal symptoms, which may indicate early digoxin toxicity.

Carbamylcholine and phorbol esters desensitize muscarinic receptors by different mechanisms in rat pancreatic acini.

Pretreatment of rat pancreatic acini with phorbol 12-myristate, 13-acetate (PMA), a protein kinase C (PK-C) activator, caused the desensitization of carbamylcholine (CBC)-induced amylase release in a concentration- and time-dependent fashion. The less potent phorbol-12, 13-dibutyrate (PDBu) also provoked a desensitization, but the inactive 4-alpha-phorbol-12,13-didecanoate had no effect. PMA or PDBu also significantly reduced subsequent amylase release induced by caerulein or secretin in contrast to CBC, which only reduced amylase release induced by CBC or secretin. Preincubation of acini with PMA did not lead to a decrease in PMA or A23187-stimulated amylase release. A 3 h resting period did not restore the desensitization induced by PMA or PDBu. Pretreatment with PMA did not cause changes in muscarinic receptor high- and low-affinity populations as observed with CBC pretreatment. The PK-C inhibitor H-7 completely prevented the desensitization induced by PDBu but not that induced by CBC. TMB-8, another PK-C inhibitor, also completely prevented the desensitization induced by PDBu but only partially that induced by CBC. These results suggest that phorbol esters can induce desensitization of muscarinic receptor-stimulated amylase release by a different mechanism than that involved in muscarinic agonist-induced desensitization.

Serotonin, 5-hydroxyindoleacetic acid and substance P content of discrete brain nuclei in rats made hypo- or hyperthyroid in the neonatal period: effect of growth hormone treatment.

In order to determine the role of growth hormone (GH) in the therapeutic effect of thyroxine (T4), we measured the content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and substance P in discrete brain nuclei of neonatally-induced hypothyroid rats and in neonatally-induced hypothyroid rats subsequently maintained on bovine growth hormone (b-GH) injections. Substance P was measured by radioimmunoassay whilst 5-HT and 5-HIAA levels were determined by HPLC with electrochemical detection. In neonatal hypothyroid rats, substance P concentration increased in 5 out of 11 brain nuclei dissected while 5-HT and 5-HIAA level increased in 7 out of 19 brain nuclei selected. Although b-GH-replacement therapy abolished the hypothyroid-induced accumulation of 5-HT and 5-HIAA in brain nuclei with exception of the substantia nigra zona reticulata, it did not influence the substance P accumulation. This suggests that the abnormal brain development observed during hypothyroidism may, in part, result from absence of growth hormone. We also observed that neonatal hyperthyroidism induced very little modification of 5-HT, 5-HIAA and substance P concentrations in discrete nuclei of the rat brain.

Influences of both thyroid and bovine growth hormones on substance P, thyrotropin-releasing hormone, serotonin and 5-hydroxyindoleacetic acid contents in the lumbar spinal cord of developing rats.

Neonatal hypothyroidism was induced by injection of 131I on the first living day whilst neonatal hyperthyroidism was induced by daily administration of high doses of thyroxine (T4). Following decapitation, segments of the lumbar spinal cord were microdissected by a punch technique. We measured serotonin and 5-hydroxyindoleacetic acid (5-HIAA) contents by high performance liquid chromatography and both substance P and thyrotropin-releasing hormone (TRH) levels by radioimmunoassay. We demonstrated that: (1) neonatal hyperthyroidism decreased substance P and TRH levels in the dorsal and ventral horns respectively, without modifying serotonin and 5-HIAA contents; (2) neonatal hypothyroidism increased the concentration of substance P in dorsal horn, of TRH in ventral horn (confirming our previous work), of serotonin in ventral horn, and of 5-HIAA in both ventral and dorsal horns; (3) T4-replacement therapy abolishes hypothyroid effects on substance P, TRH, and 5-HIAA, but not on 5-HT accumulation; and (4) bovine growth hormone-replacement therapy has no therapeutic action on the hypothyroid-induced accumulation of substance P, TRH, serotonin and 5-HIAA.