Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org

BackgroundTIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.⁵ We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients.MethodsThe patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke.ResultsCurrent smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption.ConclusionsThe two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.     

SALVAGE THERAPY IN PATIENTS WITH UNRESECTABLE HILAR CHOLANGIOCARCINOMA

We describe our methods and outcomes of multidisciplinary treatments in patients with unresectable hilar cholangiocarcinoma. Fifty‐seven patients with a known outcome were enrolled. Thirty‐four of 57 patients were treated and evaluated by salvage therapy. For salvage therapy, we used internal and external radiotherapy, photodynamic therapy, YAG laser therapy and microwave coagulation therapy. The median survival time was 548 days for the group receiving salvage therapy and 198 days for the group not receiving this treatment. In conclusion, although no randomization of the patients was performed in this retrospective study, our present data provide convincing evidence that salvage therapy is a useful therapeutic approach for unresectable hilar cholangiocarcinomas.     

Subarachnoid hemorrhage in systemic lupus erythematosus in Japan: two case reports and a review of the literature

We report 51- and 43-year-old Japanese female patients with systemic lupus erythematosus (SLE) associated with subarachnoid hemorrhage (SAH) due to rupture of intracranial saccular aneurysms. We also review the literature of Japanese SLE patients with SAH. SAH in Japanese SLE patients is more frequent than in patients from Western countries, has different features from the general population, and can occur regardless of SLE disease activity. Clinicians must pay attention to SAH in all SLE patients.     

Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.     

Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.

OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK). Materials and Methods: BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression. RESULTS: RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.     

The prognostic significance of nuclear DNA content in non-small-cell lung carcinoma

The nuclear DNA content of paraffin-embedded specimens of primary non-small-cell lung carcinomas was analysed using flow cytometry in 210 patients (80 squamous cell carcinomas, 99 adenocarcinomas, 19 large cell carcinomas and 15 others). The relationship between nuclear DNA content and prognostic factors was studied using multivariate analysis with Cox's proportional hazard model. 1) The frequency of DNA aneuploidy was 77.3% among 210 patients, and it significantly (p less than 0.05) increased with advanced stage and the presence of lymph node metastasis. 2) The patients with DNA aneuploid tumors had a significantly (p less than 0.001) less favorable prognosis than those with DNA diploid tumors among 179 patients with non-small-cell lung carcinomas. Similar results were demonstrated in 79 patients with stage I carcinomas and in 85 patients who underwent absolute curative resection. 3) Multivariate analysis using Cox's proportional hazard model showed that DNA ploidy was an independent prognostic factor for survival. Especially in the patients with absolute curative resection, DNA ploidy was the most important prognostic factor. In conclusion, flow cytometric nuclear DNA content analysis provided useful biological information, and DNA ploidy was an important and major independent prognostic factor in non-small-cell lung carcinoma.     

Clinical and pathological evaluations of methotrexate, vinblastine, Adriamycin and cisplatin chemotherapy for advanced urothelial cancers

We have treated advanced transitional-cell carcinoma of the urothelial tract with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since July of 1985. We analyzed the effect of that chemotherapy in 26 patients with advanced urothelial cancer who were treated in our hospital and followed up. They were divided into two groups. Group 1 consisted of 15 patients with distant metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for metastatic lesions after surgical removal of the primary lesion, and the remaining 4 patients were not operable since they had very advanced-stage tumors; they received only M-VAC chemotherapy. Group 2 contained 11 patients who received M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1% and the mean duration of response was 12.6 months. In the 11 patients who had received M-VAC as adjuvant therapy after surgical removal of the primary tumor, the mean duration of response was 14.1 months. After M-VAC chemotherapy, six patients underwent surgical resection of metastatic lesions and restaging was done pathologically in these cases. The clinical response coincided with the pathological response in all six cases. In group 2,5 of 11 patients experienced histological downstaging of the resected bladder. M-VAC chemotherapy combined with surgical resection of residual tumors has proved to be an effective option against advanced urothelial cancer.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

Identification of secretin diastereoisomers produced during synthesis

The byproducts P-1 and P-2, which were produced during the synthesis of porcine secretin, were isolated in pure form from the crude secretin by HPLC. These were identified by a combination of amino acid analysis, enzymatic digestion, and isocratic or linear gradient reversed-phase (RP)-HPLC. The amino acid compositions of P1 and P2, determined by amino acid analysis after acid hydrolysis, were found to be the same as those of porcine secretin without distinction between L-and D-amino acids. But, HPLC of their digestive fragments with trypsin and alpha-chymotrypsin differed from that of secretin. The fragments, S7-12 of P-1 and S13-21 of P-2 were determined to be different from the corresponding fragments obtained from secretin by HPLC analysis of their digestive fragments. The amino acid composition of each acid hydrolysate, following digestion with D-amino acid oxidase, was found to have less leucine or alanine content than secretin. The HPLC analysis of the fragments from P-1 and P-2 by tryptic and alpha-chymotryptic digestion showed that they are the same as those from synthetic D-Leu10 secretin or D-Ala17 secretin, respectively. Consequently, P-1 and P-2 are concluded to be the secretin diastereoisomers, D-Leu10 and D-Ala17 secretin, respectively.