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 Cooperativve 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 colonystimulating factor (rhGM-CSF) or placebo during the second cycle of MVP. The dose of rhGM-CSF was 125 g/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 (38°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.Institutions of the BI 71.018 Cooperative Study Group, National Cancer Center Research Institute (N. Saijo, Chairman): Douai Memorial Hospital (Y. Sano), Kanagawa Prefectural Cancer Center (K. Noda), Kantou Teishin Hospital (T. Uzawa), National Medical Center (J. Kabe), Shizuoka Prefectural General Hospital (H. Etou), Teikyo University (K. Mano), Tochigi Prefectural Cancer Center (Y. Saito), Tokyo Geriatric Medical Center (A. Kida), Tokyo Teishin Hospital (T. Morinari), Tokyo Metropolitan Komagome Hospital (S. Kudo), Tokyo Metropolitan Hiroo Hospital (A. Fujikawa), Toranomon Hospital (K. Nakada), Yokohama Municipal Hospital (K. Watanabe), National Cancer Center Central Hospital (K. Eguchi)     

DNA gyrase gyr A gene mutations in ofloxacin-resistant Staphylococcus aureus

A total of 106 clinical isolates of Staphylococcus aureus were classified into nine pattern types correlated with gyrA mutations. In 62 strains, mutations were found at a single codon (84, 85, 86 and 88), while 22 strains showed double mutations either at codons 84 and 85 or at codons 84 and 88. The double mutations led to the highest levels of ofloxacin resistance (MIC, >/= 128 mug/ml). All isolates with a single Ser-84--> Leu change had an ofloxacin MIC of 8-128 mug/ml, whereas others showed an MIC range of 8-16 mug/ml. Twenty-two wild type strains and one strain with a single mutation at codon 86 (silent mutation) were ofloxacin-susceptible. Thus, gyrA mutations seem to play a definite role in the high-level of resistance to ofloxacin.     

Surgical resection of intracardiac gastrinoma

There has been only one previous report of an intracardiac gastrinoma causing Zollinger-Ellison syndrome. In this communication we describe the successful surgical resection of a gastrinoma located in the interventricular septum using cardiopulmonary bypass, blood cardioplegia, and mild hypothermia. Preoperative evaluation and histologic examination of the resected tumor strongly suggest that this was a primary intracardiac gastrinoma.     

Bone Metastases from Soft Tissue Sarcomas

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.     

RhoN, a novel small GTP-binding protein expressed predominantly in neurons and hepatic stellate cells

A cDNA encoding a novel member of the small molecular weight GTP-binding protein (small G-protein) superfamily was cloned from rat spinal cord. The deduced amino acid sequence was highly homologous with those of so-far-known Rho proteins. Rho proteins were reported to alter many important cellular functions including formation of both actin stress fibers and focal adhesions. RNA blot hybridization and in situ hybridization analyses indicated that the novel small G-protein is expressed specifically in neurons in the brain and spinal cord and also in hepatic stellate cells. Based on the sequence similarity and neuron-specific expression in the brain, this protein was named RhoN. Unlike classical Rho proteins, RhoN was not susceptible to the ADP-ribosylation reaction by C3 botulinum toxin. Accordingly, RhoN seemed to be specifically involved in neuronal and hepatic functions as a C3 toxin-insensitive member of the Rho subfamily. Then, a mouse genomic DNA segment containing the RhoN gene was cloned. The locus was mapped on the mouse chromosome 11C-D. The sequence data showed that the protein-coding sequence for RhoN is divided by 4 introns, and that the defined 5 exons may encode intramolecular domains serving for different functions.     

Proliferation of intrahepatic bile-duct epithelium in biliary atresia

Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF) are considered as markers of cell proliferation. The expression of PCNA and TGF was evaluated immunohistochemically using anti-PCNA antibody and TGF in 31 patients with biliary atresia (BA) (15 jaundice-free and 16 with persistent jaundice) and 6 control infants. The labeling indices (LI) for PCNA- and TGF-positive bile-duct epithelium in BA were 14.1±14.0% and 51.4±33.7%, respectively, which was significantly higher than in the controls (P <0.01). In BA, the number of PCNA-immunoreactive cells was higher in the peripheral bile ductules than in the central bile ducts of the portal tract (P <0.01). LI was not related to patient age at the time of hepatic portoenterostomy in two groups divided at the age of 60 days. Patients in the persistent jaundice group had greater expression of PCNA and TGF (21.7±16.0% and 76.9±20.7%, respectively) compared to those in the jaundice-free group (6.0±2.7% and 24.3±20.9%, P <0.001). PCNA and TGF expression in the bile-duct epithelium of the portal tract was closely related to prognosis in BA patients, and thus could be useful as a prognostic marker.     

Use of YAG laser combined with mucosal suturing for the treatment of polypoid vocal cord]

To improve low-pitched voices in cases with polypoid vocal cords, YAG laser irradiation combined with a mucosal suturing technique was attempted in 9 female cases with severe polypoid changes in their vocal cords. A YAG laser beam (5 to 10 W) was used to irradiate the upper surface of the polypoid vocal cord. The polypoid content of the cord was gradually coagulated, and the free edge of the cord appeared to slide up toward the burned area. The polypoid content was then removed and squeezed through an open wound made in the burned area using a conventional method. Bleeding was successfully controlled using the laser. After the excessive mucosal margin was trimmed and the contour of the vocal cord was adjusted, the wound was closed by 7-0 monofilament absorbable suture. Suturing was relatively easy because the mucosal edge was also coagulated. Postoperative evaluations of voice quality revealed an improvement in the GRBAS scale of voice quality as well as an elevation in voice pitch and an upwards shift in the voice range in all cases.     

Treatment of ununited fracture of the hook of hamate by low-intensity pulsed ultrasound: a case report

A patient presented 4 months after sustaining a fracture of the hook of hamate. X-rays and computed tomography scanning of the carpal tunnel confirmed the presence of an ununited fracture. Low-intensity ultrasound was applied to the fracture site. After 4.5 months of exposure to ultrasound, union was confirmed by both x-rays and computed tomography scanning of the carpal tunnel. (J Hand Surg 2000; 25A:77-79.     

Pharmacological evidence that tetraethylammonium-sensitive,iberiotoxin-insensitive K+ channels function as a negative feedback element for sympathetic neurotransmission by suppressing ω-conotoxin-GVIA-insensitive Ca2+ channels in the relaxation of rabbit facial vein

Naunyn-Schmiedeberg's Archives of Pharmacology -