Phase I/II study of vinorelbine, mitomycin, and cisplatin for stage IIIB or IV non-small-cell lung cancer.

PURPOSE: To determine the maximum-tolerated doses (MTDs) of vinorelbine (VRB), mitomycin (MMC), and cisplatin (P), given in two courses every 28 days to previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: At least three or four patients were entered at each dose level. The starting dose was 20 mg/m(2) for VRB on days 1 and 8 and 4 mg/m(2) for MMC on day 1, with a fixed dose of P 80 mg/m(2) on day 1 every 4 weeks. MMC was increased to 6 mg/m(2) at dose level 2 and subsequently to 8 mg/m(2) at dose level 4. At dose level 3, VRB was increased to 25 mg/m(2). Twenty-five patients were entered onto the phase I study and 19 patients were entered onto phase II study. RESULTS: Nadir leukocyte and platelet counts decreased at each dose level. At dose levels 1 and 2, the dose-limiting toxicity (DLT) was not seen, but at dose levels 3 and 4, DLT was encountered in two patients. Nearly half the patients at dose level 4 had dose reduction due to grade 4 leukopenia. A mathematic model of all toxicity suggested that dose level 4 (VRB 25 mg/m(2) on days 1 and 8 and MMC 8 mg/m(2) and P 80 mg/m(2) on day 1, every 4 weeks) would be the recommended dose for phase II study at which grade 4 toxicity is expected in 相似文献   

A surgically recovered case of spontaneous rupture of the esophagus. —The significance of preoperative esophagoscopy for direct sture—

A 65-year-old man with spontaneous rupture of the esophagus survived with a direct suture of the esophagus 15 hours after the onset of symptoms. Endoscopic examination of the esophagus was especially of great help in determining the surgical procedure in this patient, and we want to stress the importance of prompt diagnosis and immediate surgery for this disease.     

The complementary role of indium-111 labeled leukocyte imaging,ultrasonography and computed tomography in the evaluation of postoperative infection or abscess

We report our experiences with the combined use of indium-111 labeled leukocyte imaging (In-III WBC scan.), computed tomography (CT) and ultrasonography (US) for evaluation of suspected postoperative infection or abscess, and discuss the complementary roles of these modalities. Postoperative abscesses or infections were diagnosed in 9 of 20 patients. All patients were correctly diagnosed by In-111 WBC imaging and 4 patients could not be diagnosed by US because of bowel gas. One false-positive CT examination and another artifact on CT images due to respiratory movements were obtained. The three modalities were found to be complementary: CT and US were efficient imaging methods for diagnosis and treatment of abscess. In-111 WBC imaging could estimate the activity of inflammation.     

Mechanisms involved in aggravation of ethanol-induced gastric mucosal lesions in adrenalectomized rats

Effects of adrenalectomy (AD) on ethanol-induced gastric injury and prostaglandin (PG) protection on the damage were investigated in rats and compared with those of N-ethylmaleimide (NEM), a sulfhydryl (SH) blocker, and diethyl maleate (DEM), a SH depletor. Oral administration of 100% ethanol (1 ml) induced elongated bands of hemorrhagic lesions in the corpus mucosa of sham operated rats, and these lesions were significantly prevented by 16,16-dimethyl PGE2 (dmPGE2, 10 micrograms/kg, s.c.). AD markedly enhanced the mucosal ulcerogenic responses caused by ethanol and abolished the protective effect of dmPGE2; this agent rather worsened the lesions, which appeared throughout the corpus mucosa. AD by itself enhanced the microvascular permeability in the gastric mucosa without any effect on SH contents. These alterations caused by AD were significantly reverted by hydrocortisone treatment (10 mg/kg/day for 2 weeks, s.c.). On the other hand, a single injection of NEM (10 mg/kg, s.c.) similarly enhanced the vascular permeability, worsened the ethanol-induced lesion, and mitigated the protective effect of dmPGE2 without altering mucosal SH contents, while DEM (1 ml/kg, s.c.) significantly reduced the mucosal SH levels and the lesions. These results suggest that AD worsened the mucosal lesions induced by ethanol, probably by enhancing the microvascular permeability, and this action may be due to a lack of steroid secretion but is not directly related to a mucosal SH deficiency.     

A diary form quality of life questionnaire for Japanese patients with lung cancer and summarization techniques for longitudinal assessment

The aim of this study was to confirm the validity and reliability of a new diary-type quality of life (QOL) self-rating questionnaire tailored for use by Japanese inpatients with lung cancer receiving chemotherapy. Two kinds of summary statistics were tested in QOL analysis. The questionnaire has a four-scale structure; physical, psychological, daily activity and global scales. Fifty-three patients were enrolled to test the reliability and validity. Summary statistics were assessed using indices of the area under the curve (AUC) and the maximum fluctuations of QOL scores (Dif max) in patients receiving cisplatin or carboplatin. The questionnaire had satisfactory reliability and validity. The physical, psychological and global scales scores changed to the worst levels after treatment, continuing for 1 week in the cisplatin group, whereas those of the carboplatin group began to worsen from day 3, but returned to prechemotherapy levels by day 9. The cisplatin group showed significant decrease of QOL compared with the carboplatin group in the AUC of psychological and two global scales, in the Dif max of psychological and linear analogue global scales. These results suggested that this questionnaire reflects differences in the influence of chemotherapy, and that AUC and Dif max may be useful indices for the analysis of QOL as measures to assess multidimensional QOL.     

MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

Mutations in the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of secreted proteases cause diseases linked to ECM abnormalities. However, the mechanisms by which these enzymes modulate the ECM during development are mostly unexplored. The Caenorhabditis elegans MIG-17/ADAMTS protein is secreted from body wall muscle cells and localizes to the basement membrane (BM) of the developing gonad where it controls directional migration of gonadal leader cells. Here we show that specific amino acid changes in the ECM proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the requirement for MIG-17 activity in gonadal leader cell migration in a nidogen (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and LET-2 activities are required for proper accumulation of NID-1 at the gonadal BM. However, mutant FBL-1C or LET-2 in the absence of MIG-17 promotes NID-1 localization. Furthermore, overexpression of NID-1 in mig-17 mutants substantially rescues leader cell migration defects. These results suggest that functional interactions among BM molecules are important for MIG-17 control of gonadal leader cell migration. We propose that FBL-1C and LET-2 act downstream of MIG-17-dependent proteolysis to recruit NID-1 and that LET-2 also activates a NID-1-independent pathway, thereby inducing the remodeling of the BM required for directional control of leader cell migration.     

Interference of a ventricular assist device with magnetic navigation during insertion of Sherlock 3CG™, a bedside peripherally inserted central catheter

Journal of Artificial Organs - Recently, the Sherlock 3CG™ Tip Confirmation System, including a magnetic tracking system and an intracavitary electrocardiography guidance system, has been...     

Neuroleptic malignant syndrome during haloperidol treatment in a cancer patient

A case of neuroleptic malignant syndrome (NMS) in a 64-year-old man with cancer of the soft palate is reported. During haloperidol treatment for delirium, the patient showed consciousness disturbance with extrapyramidal signs. With discontinuation of haloperidol and replacement by dantrolene and bromocriptine, the patient recovered completely. Although major tranquilizers are widely used in clinical oncology to manage symptoms, NMS has been rarely reported in cancer patients, presumably because of lack of awareness. Early recognition of NMS and prompt treatment may improve the potentially fatal outcome.     

Clinical,autoimmune, and genetic characteristics of adult-onset diabetic patients with GAD autoantibodies in Japan (Ehime Study)

OBJECTIVE: To characterize the clinical, autoimmune, and genetic features in Japanese adult-onset diabetic patients with GAD autoantibodies. RESEARCH DESIGN AND METHODS: GAD autoantibodies (GADab) were screened in 4,980 diabetic patients with age of onset >20 years in the hospital-based Ehime Study, and the GADab-positive (GADab(+)) patients were then divided into two groups according to their insulin secretion and compared with nondiabetic subjects. The insulin-deficient state was defined as <0.33 nmol/l serum C-peptide (CPR) at 2 h postprandial or 6 min after a 1-mg glucagon load. RESULTS: GADab was detected in 188 (3.8%) of the 4,980 diabetic patients tested. Of these patients, 72 (38.3%) were classified as insulin deficient, 97 (51.6%) were classified as non-insulin deficient, and 19 (10.1%) were unclassified. The GADab(+) insulin-deficient patients were characterized by young age at onset of diabetes, low BMI, low maximum BMI, and high levels of HbA(1c). The prevalence of IA-2 autoantibodies and thyrogastric autoantibodies in the GADab(+) insulin-deficient patients were significantly higher than those in the GADab(+) non-insulin-deficient patients (P < 0.05). GADab(+) patients with insulin deficiency had increased frequencies of HLA DRB1*0405-DQB1*0401, *0802-*0302, and *0901-*0303 haplotypes, whereas the frequency of only HLA DRB1*0405-DQB1*0401 was increased in the case of GADab(+) non-insulin-deficient patients. Of note is the fact that the GADab(+) non-insulin-deficient group did not differ from healthy control subjects with respect to type 1 diabetes protective haplotype HLA DRB1*1502-DQB1*0601. A total of 13% of the GADab(+) patients with diabetes had genotypes comprising the DRB1*1501-DQB1*0602 or *1502-*0601 and were characterized by old age at onset of diabetes, high BMI, resistance to the insulin-deficient state, low titer of GADab, and low frequency of other organ-specific autoantibodies. CONCLUSIONS: We conclude that GADab(+) non-insulin-deficient patients differ from GADab(+) patients with insulin deficiency with respect to clinical characteristics, humoral autoimmunity to other organ-specific autoantibodies, as well as HLA class II genes.