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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 325 records · Page 18Linked to original sources

In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors.

Cabergoline (CG) is a dopamine agonist that inhibits the secretion of prolactin (PRL) and growth hormone. In the present study, we evaluated the in vivo effect of CG on PRL secretion and the pituitary tumor induced by estrogen. Estrogen was administered by subcutaneous injection to 4-week-old Fischer 344 rats weekly for 10 weeks to induce tumors. On the last day of estrogen administration, doses of either CG or bromocriptine (BC), 0.6 mg/kg, were administered as a single oral route or chronically, given every third day. Sera and pituitary tumors were sampled on each treatment schedule. Serum levels of PRL were measured and the pituitary glands were weighed. Immunohistological evaluation was performed by optical and electron microscopy. A single dose of CG significantly inhibited the serum levels of PRL for 6 days. Following a single dose of BC, the PRL level was significantly inhibited only at 6 hours' postadministration. The continued oral administration of CG significantly reduced both the serum PRL level and the weight of the pituitary during 15 to 60 days of treatment as compared with BC. Morphologic studies revealed that CG reduced the size of the cells and of the granules, and increased the number of granules per unit area of the cytoplasm. These findings suggest that CG inhibits the maturation of PRL secretory granules and the secretion of PRL more than its synthesis. Thus, CG induced a prolonged lowering of PRL and had a good antitumor effect on rat pituitary tumors induced by estrogen.

Animals↗

Effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors: in vitro culture studies.

Cabergoline (CG) is a dopamine agonist that inhibits secretion of prolactin (PRL) and growth hormone. The purpose of this study was to investigate the PRL-lowering effect and antitumor effect of CG on estradiol-induced rat pituitary tumors in vitro and to elucidate these mechanisms. We compared the effects of CG with those of bromocriptine (BC) in terms of the inhibition of hormone secretion as well as antitumor effects on rat pituitary tumors. Primary cultures of dissociated pituitary tumor cells were used in these studies. A significant inhibition of prolactin (PRL) secretion was observed for both drugs within 12 h after treatment, and the inhibitory effects of CG and BC were antagonized by sulpiride or haloperidol. Inhibitory effect on PRL secretion after 12-h BC or CG pretreatment was more pronounced with CG than BC treatment at all time points. PRL secretion in group pretreated with CG was significantly suppressed at 72 h when compared to that of vehicle. Inhibition of de novo PRL synthesis was better demonstrated in the CG group. These findings suggest that CG has a higher affinity for the D2 receptor of pituitary cells as compared to BC and may preferentially inhibit PRL secretion rather than PRL production. An antitumor effect of CG has been confirmed at a lower dosage than that of BC.

Animals↗

Erythrocyte deformability of nonpregnant, pregnant, and fetal blood.

Erythrocyte deformability is an important determinant of microcirculation, of oxygen transport and release to the tissue. In an attempt to clarify the rheological peculiarity during pregnancy, erythrocyte deformability was measured in 10 nonpregnant controls and 10 pairs of mothers and newborns. When the hematocrit of the erythrocyte suspension in dextran solution was adjusted to 35%, the deformability of fetal erythrocytes was significantly higher than maternal blood (P < 0.05), and it was almost similar to that of nonpregnant controls. Erythrocyte deformability was dependent on the hematocrit, and there was an optimal hematocrit value at which the deformability was maximal. The hematocrit, where the deformability was maximal, was a lower value (32-35%) in maternal blood, conversely, a higher value (47-50%) in cord blood than that (40-43%) in the nonpregnant. Despite decreased deformability of maternal erythrocytes, it may be compensated by reducing the hematocrit (hemodilution), preserving effective peripheral circulation including uteroplacental perfusion. On the other hand, the deformability of fetal erythrocytes may be higher in vivo at the hematocrit of 47-50% to supply oxygen to the fetal tissue even in a low oxygen condition.

Adult↗

Choroid plexus carcinoma in the lateral ventricle--case report.

A 68-year-old male presented with choroid plexus carcinoma in the left lateral ventricle manifesting as dysarthria and gait disturbance. Magnetic resonance imaging showed a homogeneously enhanced mass in the trigone of the left lateral ventricle. Selective left posterior cerebral arteriography showed the tumor was fed by the left medial posterior choroidal artery. Detailed examinations found no evidence of an extraneural primary focus. He underwent partial removal of the tumor followed by local Lineac irradiation (50 Gy). After irradiation, the serum level of carcinoembryonic antigen decreased and the size of the residual tumor was reduced.

Adenocarcinoma↗

[A male case of primary Sjögren's syndrome with interstitial pneumonitis and interstitial tubulo-nephritis in the absence of dry eye and dry mouth: parotid gland MRI is a useful diagnostic method for Sjögren's syndrome].

Here we report a case of primary Sjögren's syndrome with hilar lymphadenopathy, interstitial pneumonitis and interstitial tubulo-nephritis. A 60-year old man was admitted to our hospital in May 1993 because of general fatigue and fever. He was noted to have hypergammaglobulinemia and had positive antibodies to nuclear antigens since 1990 in the absence of clinical manifestations. Since 9 months before admission, he presented with general fatigue, low grade fever and uveitis. On admission, chest X-ray and CT scan showed bilateral hilar lymphadenopathy and interstitial pneumonitis. The negative results for both serum angiotensin converting enzyme and histological findings of the cervical lymph node and the lung excluded the diagnosis of sarcoidosis. Serological examination exhibited marked elevation of polyclonal IgG level and anti-nuclear antibody, but neither anti-SS-A (Ro) nor anti-SS-B (La) antibody was detected. He did not have symptoms of xerophthalmia and xerostomia. Keratoconjunctivitis sicca was diagnosed by positive Schirmer's and rose bengal tests. His labial gland biopsy demonstrated severe mononuclear cell infiltration around the ducts. MRI findings of the parotid glands revealed heterogeneous and dotted high signal intensity similar to those in fat tissues in the T1- and T2-weighted images. These findings depicted that bilateral parotid gland was extensively destructed and was replaced by lipid tissue. Renal biopsy showed interstitial tubulo-nephritis. On the basis of the above findings, he was diagnosed to have primary Sjögren's syndrome and uveitis. Therefore, MR image of the parotid gland is considered to be a noninvasive and useful method for diagnosis of Sjögren's syndrome.

Humans↗

Intensive chemotherapy with cisplatin, doxorubicin, cyclophosphamide, etoposide and granulocyte colony-stimulating factor for advanced thymoma or thymic cancer: preliminary results.

A study was conducted to evaluate the impact of cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulating factor (G-CSF) on advanced thymoma or thymic cancer. Between August 1989 and December 1994, 14 patients with invasive, metastatic or recurrent thymoma or thymic cancer were treated with cisplatin (80 mg/m2, on day 1), doxorubicin (45 mg/m2, on day 1), cyclophosphamide (800 mg/m2, on day 1) and etoposide (80 mg/m2, on day 1-3) with G-CSF (90 micrograms/m2, on day 5-18) at the National Cancer Center Hospital, Tokyo. Courses were repeated every 3 or 4 weeks for a maximum of 4 cycles. Twelve patients were treated with 2 or more courses of PACE. Two patients were treated with only one course, one refused and another required emergency thoracic radiotherapy after one course of PACE. Six patients had partial responses (3 thymomas and 3 thymic cancers) but there were no complete remissions (response rates, 42.9%; 95% confidence interval, 17.7% to 71.1%). Moderate hematological toxicities were observed: grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopenia in 10, 13, 8 and 6 patients, respectively. Six patients developed infections that required antibiotics. Surgical resection or thoracic radiotherapy after PACE treatment was performed in 2 and 7 patients, respectively. The overall median survival time was 14.7 months (range, 5.9 to 59.7 months). For 9 patients who had received no prior treatment before chemotherapy, the median survival time was 8.9 months, and one patient survived for 4 years and is still alive. In conclusion, PACE with G-CSF frequently produces objective remissions in patients with advanced thymoma or thymic cancer. A large-scale intergroup study is necessary to determine the impact of this regimen on advanced thymoma and thymic cancer.

Adult↗

Tyrosine phosphorylation participates in peripheral T-cell activation and programmed cell death in vivo.

T-cell antigen receptor (TCR), which is not itself a protein tyrosine kinase (PTK), is thought to be associated with at least two SRC-like PTKs, P59fyn and ZAP-70. Activation of these PTKs is required for T-cell signal transduction. The aim of the present study was to determine the roles of PTKs in peripheral T-cell activation, induced by in vivo bacterial superantigen administration. We demonstrated that in vivo staphylococcal enterotoxin B (SEB) administration induced an enhanced tyrosine phosphorylation in peripheral spleen T cells undergoing a programmed cell death. In vitro immunecomplex kinase assay using antibody against P59fyn showed increased fyn kinase activity in SEB-stimulated spleen T cells. We examined the effect of PTK-specific inhibitors on DNA fragmentation and programmed cell death of V beta 8 positive T cells following in vitro culture of SEB-primed spleen T cells. Our results indicated that pretreatment of SEB-activated T cells with PTK inhibitors reduced DNA fragmentation and programmed cell death of V beta 8 positive T cells. These findings suggest that PTK plays an important role in activation and apoptosis of peripheral T cells induced by in vivo SEB administration.

Animals↗

[A case of dural arteriovenous malformation in the anterior fossa associated with an occlusion of the unilateral middle cerebral artery with moyamoya phenomenon].

The authors report a case of dural arteriovenous malformation (dAVM) in the anterior fossa that was associated with an occlusion of the unilateral middle cerebral artery with Moyamoya phenomenon. The patient was a 79-year-old man referred to our department with an episode of consciousness disturbance and headache. Computed tomography scan showed intracerebral hematoma in the left frontal lobe, combined with left frontal subdural hematoma and subarachnoid hemorrhage. Angiography revealed dAVM in the left anterior fossa, fed by the bilateral ethmoidal and the bilateral middle meningeal arteries, and draining into the superior and inferior sinuses through the pial veins with vascular sacs. While angiography revealed an occlusion of the right middle cerebral artery (M1 portion) good collaterals via leptomeningeal anastomosis had developed. T1-weighted magnetic resonance (MR) images showed an intracerebral hematoma as a low intensity area, and flow-void areas were indicative of vascular sacs. Time-of-flight MR angiography also clearly showed dAVM in the left anterior fossa. Co-existence of an occlusion of an intracranial major artery and dAVM in this location has not been reported previously and it was speculated that this association had occurred by chance.

Aged↗

[A case of pulmonary fibroma].

A 42-year-old man without symptoms was admitted to the hospital because of a well-circumscribed mass in his left upper lung field, which was found on a routine chest X-ray film. CT of the chest revealed a well-defined homogeneous mass in the left upper lobe. Bronchial biopsy yielded material unsatisfactory for diagnosis. On thoracotomy a tumor, entirely within the lung parenchyma, was found to occupy S3. Due to its size and location left upper lobectomy was done. Histologically, the tumor contained interlacing bundles of spindle cells compatible with fibroma, with no indicators of malignancy. Intrapulmonary fibromas are rare and only one report could be found in the Japanese literature.

Adult↗

[HTLV-I infection in primary Sjögren's syndrome--epidemiological, clinical and virological studies].

The HTLV-I seroprevalence rate among the patients with Sjögren's syndrome (SjS, 23.0%) was significantly higher than that among blood donors (3.4%). The age-adjusted summary odds ratio of HTLV-I infection among SjS patients as compared with blood donors was 3.1. The etiologic fraction, i.e., the proportion of SjS in the study population that are attributable to HTLV-I infection, was estimated to be 17.6%. Titers of serum antibodies to HTLV-I in the seropositive SjS patients were significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in sera of SjS patients. Salivary IgA class antibodies were common among seropositive SjS patients, but not in HAM patients or in healthy subjects. The findings strongly suggest that HTLV-I is involved in the pathogenesis of the disease in a subset of patients with SjS in endemic areas.

Adolescent↗

[Primary trabeculectomy for open-angle glaucoma with mitomycin C].

We examined the results of postoperative intraocular pressure (IOP) control and complications of trabeculectomy with mitomycin C in open angle glaucoma patients who had not undergone any other ocular surgery. The subjects were 80 eyes of 70 patients who underwent surgery with 0.04% mitomycin C as an adjunct for 3 minutes and were followed for 7-24 months (mean +/- standard deviation: 13 +/- 3.4). The preoperative IOP was 21-32 mmHg (mean +/- standard deviation: 24.6 +/- 4.3) in maximum tolerable medications. IOP control ratio, which was analysed with the Kaplan-Meier method at 24 months after surgery was 81.6% without any antiglaucoma medications, vs 92.0% with medications. These values were significantly higher (p < 0.05) than the results of trabeculectomy with 5-fluorouracil or without antimetabolic agents previously performed in our clinic. Shallow chamber in 18 eyes (23%), choroidal detachment in 14 eyes (18%), hypotonus maculopathy in 7 eyes (9%), and cataract progression in 5 eyes (7%) were recognised as complications. Although there are some complications to be conquered, trabeculectomy with mitomycin C seems to be effective in treating primary open angle glaucoma patients.

Adult↗

Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome.

There is accumulating evidence that human T-lymphotropic virus-1 (HTLV-1) infection contributes to the development of various inflammatory disorders. To elucidate the relation between the infection and Sjögren's syndrome, seroepidemiological and virological studies were conducted on patients with this syndrome in Nagasaki Prefecture, Japan, an area heavily endemic for HTLV-1. The HTLV-1 seroprevalence rate among the patients with Sjögren's syndrome (17/74, 23%) was significantly higher than that among blood donors (916/27,284, 3%), whereas the difference between patients with systemic lupus erythematosus and blood donors was insignificant. Moreover, among Sjögren's syndrome patients the seroprevalence was high irrespective of age, unlike that among blood donors, which rose with age. Titres of serum antibodies in the HTLV-1 seropositive patients with Sjögren's syndrome were similar to those among patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and significantly higher than those among healthy carriers. IgM class antibodies were commonly detected in the serum of patients with Sjögren's syndrome. However, unlike that in HAM/TSP patients, the viral load in peripheral-blood mononuclear cells was not necessarily high in the seropositive Sjögren syndrome group. Salivary IgA antibodies to HTLV-1 were common among seropositive patients with Sjögren's syndrome (5/7), which might be due to increased viral activity in the salivary glands. These antibodies were barely detectable in HAM/TSP patients (prevalence 1/10) or in healthy carriers (0/11). The findings strongly suggest that HTLV-1 is involved in the pathogenesis of the disease in a subset of patients with Sjögren's syndrome in endemic areas.

Adolescent↗

Prevention of anti-CD3 monoclonal antibody-induced thymic apoptosis by protein tyrosine kinase inhibitors.

The thymus gland is crucial for the formation of thymocytes of diverse TCR specificity. Recent studies have demonstrated that deletion (negative selection) of autoreactive thymocytes occurs through the process of apoptosis in which TCR activates cell death by DNA fragmentation. In addition, in vitro stimulation of thymocytes with anti-CD3 mAb, calcium ionophore, or glucocorticoids results in DNA fragmentation followed by cell death. The availability of various substances capable of inhibiting activation-induced programmed cell death of thymocytes may be used as a tool to help identify several important events occurring during the process of apoptosis. We investigated the effect of protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, on thymocyte apoptosis induced by stimulation of anti-CD3 mAb or glucocorticoid. Anti-CD3 mAb stimulation resulted in removal of CD4+CD8+ thymocytes by DNA fragmentation. However, in PTK inhibitor-pretreated thymocytes, there was a minimal deletion of double positive thymocytes. In contrast, PTK inhibitors did not prevent glucocorticoid-induced thymic apoptosis. Our results suggest that anti-CD3 mAb-induced thymic apoptosis depends on PTK activation via TCR, and that glucocorticoid-induced thymic apoptosis is PTK-independent.

Animals↗

Transactivation of the human interleukin-6 gene by human T-lymphotropic virus type 1 Tax protein.

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates both humoral and cellular immune responses. Accumulating evidence suggests that the infection of T cells and other cell types with human T-lymphotropic virus type 1 (HTLV-1) results in the constitutive expression of IL-6. However, the underlying molecular mechanisms are little understood. When a reporter plasmid, pIL6-CAT-E3, in which the human IL-6 enhancer/promoter region from -630 to +14 was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, was transfected, HTLV-1-infected but not -uninfected T-cell lines activated the IL-6 promoter. This indicated the presence of a factor transactivating the IL-6 gene in the infected cells. To evaluate the involvement of the HTLV-1-encoded transacting factor (Tax) in this transactivation, we examined the effect of transient cotransfection with the Tax-expression plasmid, pMAX-Neo, on the transcription from the IL-6 promoter by use of COS1 cells. The cotransfected COS1 has about six-times greater the CAT activity than that transfected with pIL6-CAT-E3 alone. The analysis of a series of deletions of the IL-6 promoter suggested that the region (-105/-47) containing a NF kappa B site was crucial for the Tax responsiveness. We further examined the effect of Tax on endogenous IL-6 gene expression using the Jurkat clone, JPX-9, stably transfected with pMAX-Neo. JPX-9 accumulated steady state transcripts of the endogenous IL-6 gene in response to the induction of Tax expression. Our findings indicate an important role of the Tax protein in the expression of IL-6 in cells infected with HTLV-1.

Animals↗

HTLV-I proviral DNA in umbilical cord blood of babies born to carrier mothers.

Human T-lymphotropic virus type I (HTLV-I) in cord blood raises the possibility of intrauterine transmission as an alternative pathway to transmission via breast milk. However, none of 7 children with HTLV-I proviral DNA positive cord blood had seroconverted by 24-48 months. Contamination of cord blood by maternal blood was precluded on the basis of viral load and IgA concentration. Thus cord blood proviral DNA is not a hallmark of intrauterine infection. Moreover, none of the cord blood samples of 9 formula-fed children later confirmed to be infected was positive for HTLV-I, indicating that intrauterine infection is not a likely candidate as an alternative pathway.

Breast Feeding↗

Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer.

Irinotecan hydrochloride (CPT-11), a semisynthetic derivative of camptothecin, has been demonstrated to be active against solid tumors such as non-small cell lung cancer and colorectal cancer. Two combination phase I trials were undertaken to determine the maximum tolerated dose of CPT-11 in combination with cisplatin and vindesine in patients with advanced non-small cell lung cancer. All 46 patients (age 32-73 years) entered into these trials had a good performance status (Eastern Cooperative Oncology Group score, 0-1) and had received no prior chemotherapy or radiotherapy. In the first trial, 14 stage IV and 2 stage IIIb patients were studied; in the second trial 30 patients with stage IV disease were accrued. In the first trial, CPT-11 was given as a 90-min i.v. infusion on days 1 and 8 in combination with a fixed dose of cisplatin (100 mg/m2, i.v., on day 1) and vindesine (3 mg/m2, i.v., on days 1 and 8), every 4 weeks. The starting dose of CPT-11 was 25 mg/m2, and the dose was increased in increments of 25 mg/m2. In the second trial, the doses of either CPT-11 (days 1 and 8) or cisplatin (day 1) were escalated with a fixed dose of vindesine (same dose as the first study) given in a 4-week cycle. The starting doses of CPT-11 and cisplatin were 20 and 60 mg/m2, respectively, and the dose of either CPT-11 or cisplatin was increased in increments of 20 mg/m2. At least 3 patients were entered at each dose level in both trials. Use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was not permitted in this trial. In the first trial, grade 4 granulocytopenia and grade > or = 3 diarrhea were dose limiting at 50 mg/m2 CPT-11, which represented the maximum tolerated dose. At the subsequent dose of CPT-11, 7 new patients were requited at the 50% reduced dose level of 37.5 mg/m2 on days 1 and 8. Nine patients were evaluated for response, and 4 of them achieved a partial response. In spite of a low dose of CPT-11 (25-37.5 mg/m2), the maximum concentration in plasma of CPT-11 (> 0.4 micrograms/ml) reached > 10-fold the in vitro concentration of CPT-11 required for 50% inhibition of growth. In the second trial, the dose-limiting toxicities were grade 4 granulocytopenia lasting for > or = 7 days and grade > or = 3 diarrhea.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

7-Ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin: mechanism of resistance and clinical trials.

The camptothecin derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy camptothecin (CPT-11) has attracted the attention of clinicians because of its high antitumor activity against refractory solid cancers. We established two CPT-11-resistant cell lines, a non-small-cell lung-cancer cell line (PC-7/CPT-11) from the parental PC-7 line and an ovarian cancer cell line (HAC-2/CPT-11) from the parental HAC-2 line. The mechanisms of resistance to CPT-11 in PC-7/CPT-11 cells were reduced conversion of CPT-11 to its active metabolite SN-38 and point mutation topoisomerase I. Those in HAC-2/CPT-11 cells were reduction of topoisomerase I activity and decreased sensitivity of topoisomerase to topoisomerase I inhibitors. No point mutation of the topoisomerase was observed in HAC-2/CPT-11 cells. We conducted two phase I trials using CPT-11 in combination with other anticancer agents. One was a phase I trial of CPT-11 and cisplatin given with a fixed dose of vindesine to patients with advanced non-small-cell lung-cancer and the other was a phase I study on a topoisomerase-targeting combination of CPT-11 and etoposide (VP-16) in patients with various malignant solid tumors. The results of the first trial indicated that the recommended dose of CPT-11 for phase II studies was 80 mg/m2 combined with 3 mg/m2 vindesine on days 1 and 8 and 60 mg/m2 cisplatin on day 1. In the second trial, the recommended dose of CPT-11/VP-16 given with recombinant granulocyte colony-stimulating factor (on days 4-17) was found to be 60/60 mg/m2. In both trials, diarrhea and granulocytopenia were considered to be dose-limiting toxicities.

Amino Acid Sequence↗

Efficacy of recombinant human granulocyte-macrophage colony-stimulating factor for chemotherapy-induced leukopenia in patients with non-small-cell lung cancer.

To assess the feasibility and efficacy of rhGM-CSF in ameliorating chemotherapy-induced leukopenia in patients with advanced non-small-cell lung cancer, we conducted a double-blind placebo controlled phase III study in a multicenter setting. Patients were eligible if they had cytologically or histologically proven cancer, no prior chemotherapy, stage IIIB or IV disease, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, an age of less than 76 years, and no symptomatic brain metastasis, disseminated bone metastasis, or previous vertebral/pelvic irradiation. The chemotherapy regimen consisted of mitomycin given at 8 mg/m2 on day 1, cisplatin given at 100 mg/m2 on day 1, and vindesine given at 3 mg/m2 i.v. on days 1 and 8 (MVP). If the granulocyte nadir count recorded after the first cycle of MVP was less than 1,000/mm3, patients were randomly assigned to receive recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo during the second cycle of MVP. The dose of rhGM-CSF was 125 micrograms/m2 given daily s.c. for 14 consecutive days starting on day 2. Of the 52 patients enrolled, 45 were evaluable. The nadir of granulocytes was significantly lower in the placebo group (P = 0.007). The period during which the granulocyte count was less than 1,000/mm3 was significantly longer in the placebo group (median, 6 vs 10 days; P = 0.04). The incidence of adverse effects related to rhGM-CSF, such as fever (> or = 38 degrees C) and skin rash, was significantly higher in the rhGM-CSF group (P = 0.011). The rate of response to chemotherapy did not significantly differ between the two groups. In conclusion, rhGM-CSF reduced the duration of chemotherapy-induced granulocytopenia. The clinical usefulness of this agent may be deminished because of the adverse effects encountered when it is used in combination with a moderately myelotoxic chemotherapy regimen.

Adult↗