Secondary infections related to neutropenia and functional defects of phagocytes are common consequences in patients treated for cancer. The hematopoietic colony-stimulating factors (CSF) have been introduced into clinical practice as additional supportive measures that can reduce the incidence of infectious complications in patients with cancer and neutropenia.
The aim of this study was to determine the role of granuolcyte/macrophage(GM)-CSF and granulocyte(G)-CSF in enhancing in vivo human neutrophil function. A luminol-dependent chemiluminescence assay was developed to evaluate whether the repair in neutropenia accompanies the ability of neutrophils to function. A dose of 5 microg G-CSF kg(-1) day(-1) [recombinant human (rHu) G-CSF; filgrastim] or 250 microg GM-CSF m(-2) day(-1) (rHu GM-CSF; molgramostim) was administered subcutaneously once daily to 12 metastatic cancer patients being treated with different cytotoxic regimens.
All injections of CSF were given after the initiation of neutropenia and continued until the occurrence of an absolute neutrophil recovery. rHu GM-CSF and rHu G-CSF, administered once daily at the 250 microg m(-2) day(-1) and 5 microg kg(-1) day(-1) level, were effective in increasing the absolute neutrophil count and neutrophil function, as measured by an automated chemiluminescence system.
rhugm brucells
Materials and Methods
Study population. Patients were included if they (1) presented with a clinical and radiological picture compatible with active pulmonary TB, and had strongly positive smears (3 plus), according to the acid-fast-bacilli (AFB) method in two consecutive sputum smears; (2) were between 18 and 50 years old; (3) had no history of previous TB treatment; and (4) had leukocyte counts below 25,000/mm3 at entry. Patients were excluded if they (1) presented with any serious concomitant diseases, such as severe pulmonary dysfunction, renal, cardiac, hematological or hepatic diseases; (2) had severe dermatological lesions above grade 3 on the WHO score system; (3) were pregnant or lactating women; (4) had a history of alcohol abuse, had diabetes mellitus, mental disorders, were HIV or HTLV-I/II positive; (5) were receiving immunosuppressive treatments; or (6) could not provide informed consent or be followed after the hospitalization period. Administration of previous or concomitant medications such as antimycobacterial drugs, other than those initially scheduled, was not permitted during the study period.
All patients gave written informed consent prior to entering the study.
Randomization and study treatment. After diagnosis of tuberculosis, the patients who met all entrance criteria were hospitalized, for at least the first two weeks to allow better clinical evaluation of tolerability. Patients were randomized to take either rhu-GM-CSF 125 µg/M2/dose) subcutaneously twice a week for four weeks, or a placebo, both supplied by Immunex Corporation. Neither the physician nor the patient were aware of which drug they were taking. In addition to the challenge treatment, all patients who weighed more than 45 kg were scheduled to take daily Rifampin (600mg/day) + Isoniazid (400mg/day) for six months, and Pyrazinamide (2000mg/day) for the initial two months. Patients below 45 kg were scheduled to take 450mg/day Rifampin + 300mg/day Isoniazid for six months, and 1500mg/day Pyrazinamide for the initial two months.
Colony-stimulating factors (CSFs) are secreted glycoproteins that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate and differentiate into a specific kind of blood cell (usually white blood cells).
Description: Can be used for various studies in the realm of gene expression, both normal and pathological. It is an excellent control and suitable for educational purposes.
