Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Gefitinib is active and well tolerated in patients with advanced non-small cell lung cancer (NSCLC); however, its role in patients with brain metastases has not been clearly defined. We had conducted a prospective study to give gefitinib to NSCLC patients irrespective of their performance status (PS), number of prior treatment regimens and the presence of brain metastases. A total of 76 patients were enrolled. Fifty-seven patients had measurable lesions and the objective response rate was 33.3% (95% confidence interval [95% CI], 20.7-46.0%). For all enrolled patients, the disease control rate was 63.2% (95% CI, 52.1-74.3%) with a median progression-free survival of 5.0 months (95% CI, 3.6-6.5 months) and median overall survival 9.9 months (95% CI, 4.9-14.8 months). Twenty-one patients had simultaneously assessable intracranial lesions (ICLs) and extracranial lesions (ECLs), 17 of them (81.0%) showed comparable tumor response. There was no survival difference between the patients with and without metastatic brain disease. Most drug-related adverse events were mild. Intolerable toxicities happened in five patients, four of them were interstitial pneumonia (5.8%). Severity of skin toxicity was tightly associated with tumor response and patient survival (P = 0.007 and <0.001) and the association was consistent in the analysis using early toxicity profile (P = 0.033 and 0.001). In conclusion, gefitinib is active in patients with brain metastasis from NSCLC and tumor response is related to skin toxicity. It is feasible to conduct randomized trials to identify the role of gefitinib alone or in combination with other modality for treatment of NSCLC patients who have metastatic brain lesion(s).     

A viral model for corneal scarring and neovascularization following ocular infection of rabbits with a herpes simplex virus type 1 (HSV-1) mutant

PURPOSE: Herpes simplex virus type 1 (HSV-1) remains a major cause of corneal scarring and visual loss. Although efforts have been made, no reproducible animal model is available to examine recurrent corneal disease. Here we propose a rabbit ocular model to study recurrent corneal disease using an HSV-1 mutant that reactivates with high efficiency. METHODS: Rabbits were ocularly infected with 2 x 10 PFU/eye of the parental McKrae, dLAT2903 (a LAT-null virus with a low-reactivation phenotype), or CJLAT (a high-reactivation virus). Acute ocular disease [days 2, 4, 7, and 10 postinfection (pi)], recurrent ocular disease, and neovascularization (days 30 to 58 pi) were monitored. RESULTS: All acute ocular disease symptoms, including conjunctivitis and corneal disease, were similar with all 3 viruses. No corneal scarring was detected in any eyes up to day 30 pi. Between days 35 and 58 pi, corneal scarring was observed in 11/14 (experiment 1) and 18/22 (experiment 2) eyes of CJLAT-infected rabbits. Significantly less corneal scarring was seen in eyes of rabbits infected with McKrae (0/18 and 0/16) or dLAT2903 (0/16 and 3/24) (P < 0.0001). Many of the eyes with corneal scarring developed obvious, measurable neovascularization. CONCLUSIONS: Rabbits infected with CJLAT developed corneal scarring and neovascularization similar to that of clinical ocular HSV-1 recurrent disease. Because this occurred well after the acute infection had resolved, the corneal scarring and neovascularization appeared to be recurrent disease. Thus, CJLAT ocular infection of rabbits may provide a good and reproducible animal model to study factors involved in corneal scarring and neovascularization from recurrent ocular HSV-1.     

The role of TH1 and TH2 cytokines in HSV-1-induced corneal scarring

Objective: The study was to evaluate the diagnostic efficacy of nested polymerase chain reaction (nPCR) using primers targeting B1 gene of Toxoplasma gondii (T. gondii) with Witmer Desmonts coefficient (WDC) technique in intraocular fluids of clinically suspected toxoplasma retino choroiditis (TRC) patients. Materials and Methods: Two hundred and seventy eight specimens from 189 patients (25 TRC patients and 164 controls) consisting of 189 serum samples and 89 intraocular fluids were included in the study. The clinical specimens were categorized into TRC patients (typical TRC lesion-group I &; atypical TRC lesion-group II) and controls (voluntary blood donors-group III, patients undergoing uncomplicated cataract surgery-group IV, ocular inflammation of nontoxoplasma origin-group V). Detection of anti T. gondii IgG and IgM antibodies in serum samples and intraocular fluids were performed and WDC was calculated by the standard method. The standardized nPCR was applied on the 89 intraocular fluids. Results: Clinical diagnosis of TRC based on fundus examination was considered to be the “gold standard.” Anti T. gondii IgG/IgM antibodies were detected in serum by ELISA in 95.6% of 25 clinically suspected TRC patients (gp I and II), 28% of gp III, 40.4% of gp IV, and in 58.3% of gpV. Witmer Desmont's coefficient was positive in 72.7% (16/22) and nPCR in 59.1% (13/22) of TRC patients (gp I and II). Both WDC and nPCR were negative in all the controls. The difference in sensitivity of WDC and nPCR was not statistically significant (p = 0.5247). Conclusions: Though both WDC and nPCR were reliable diagnostic techniques for ocular toxoplasmosis, nPCR is more acceptable because of the amount of specimen(s) required, rapidity, cost effectiveness, and direct evidence of T. gondii DNA in the intraocular fluids.     

Role of intravenous omeprazole in patients with high-risk peptic ulcer bleeding after successful endoscopic epinephrine injection: a prospective randomized comparative trial

BACKGROUND: Epinephrine injection is the most common endoscopic therapy for peptic ulcer bleeding. Controversy exists concerning the optimal dose of proton pump inhibitors (PPI) for patients with bleeding peptic ulcers after successful endoscopic therapy. The objective of this study was to determine the optimal dose of PPI after successful endoscopic epinephrine injection in patients with bleeding peptic ulcers. METHODS: A total of 200 peptic ulcer patients with active bleeding or nonbleeding visible vessels (NBVV) who had obtained initial hemostasis with endoscopic injection of epinephrine were randomized to receive omeprazole 40 mg infusion every 6 h, omeprazole 40 mg infusion every 12 h or cimetidine (CIM) 400 mg infusion every 12 h. Outcomes were checked at 14 days after enrollment. RESULTS: Rebleeding episodes were fewer in the group with omeprazole 40 mg infusion every 6 h (6/67, 9%) as compared with that of the CIM infusion group (22/67, 32.8%, p < 0.01). The volume of blood transfusion was less in the group with omeprazole 40 mg every 6 h than in those groups with omepraole 40 mg infusion every 12 h (p= 0.001) and CIM 400 mg infusion every 12 h (p < 0.001). The hospital stay, number of patients requiring urgent operation, and death rate were not statistically different among the three groups. CONCLUSION: A combination of endoscopic epinephrine injection and a large dose of omeprazole infusion is superior to combined endoscopic epinephrine injection with CIM infusion for preventing recurrent bleeding from peptic ulcers with active bleeding or NBVV.     

Budesonide/formoterol Combination as a Maintenance and Rescue Therapy

Background. To investigate the rationale of clinicians when treating asthmatics with combined budesonide/formoterol in a single inhaler as a maintenance and rescue therapy (BFMRT). Methods. A questionnaire was used to investigate, from the perspective of outpatient clinic physicians, why, how, and for whom BFMRT should be prescribed. Participants (N = 274) were employed in medical centers, regional hospitals, district hospitals, and private clinics; the majority of the clinicians were pulmonologists (75.5%). Results. Most participants (84.9%) prescribed BFMRT primarily because of its convenience; 60.4% prescribed 1 puff (budesonide/formoterol, 160/4.5 μg/puff) twice daily and as needed and 38.5% 2 puffs twice daily and as needed; 70.4% did not insist that patients use budesonide/formoterol as a rescue treatment. There was no agreement on the dose (1 or 2 puffs as needed) or interval (5, 10, or 20 min) required for rescue treatment. Almost half (48.2%) of the physicians reported that they would not prescribe BFMRT because of patients' lack of understanding of the treatment. Further analysis showed that physicians practicing in medical centers, those specializing in chest medicine, and those working in higher socioeconomic regions may appreciate the benefits of BFMRT more than non-pulmonologists, those working in settings other than medical centers, and those employed in lower socioeconomic areas. Conclusions. More effort needs to be expended in the education of physicians responsible for asthma management, non-pulmonologists, those working outside of medical centers, and those practicing in rural areas in new treatment concepts to achieve optimal asthma control throughout the country.     

Culturing adult human bone marrow stem cells on gelatin scaffold with pNIPAAm as transplanted grafts for skin regeneration

Skin tissue engineering is a possible solution for the treatment of extensive skin defect. The ultimate goal of skin tissue engineering is to restore the complete functions of native skin, but until now the structures and functions of skins are only partially restored. By negative immunoselection (CD45 and glycophorin A), we isolated and cultivated adult human bone marrow stem cells (hBMSCs) that are of multilineage differentiation potential. In this study, we first demonstrated that by using gelatin/thermo-sensitive poly N-isopropylacrylamide (pNIPAAm) and the immunocompromised mice model, the hBMSCs possess the differentiation potential of epidermis and the capability of healing skin wounds. The in vitro observations and the results of the scanning electron microscope showed that the hBMSCs can attach and proliferate in the gelatin/thermo-sensitive pNIPAAm. To further monitor the in vivo growth effect of the hBMSCs in the skin-defected nude mice, the green fluorescence protein (GFP) gene was transduced into the hBMSCs by the murine stem cell viral vector. The results showed that the rates of cell growth and wound recovery in the hBMSC-treated group were significantly higher than those in the control group, which was only treated with the gelatin/pNIPAAm (p < 0.01). More importantly, the re-epithelialization markers of human pan-cytokeratin and E-cadherin were significantly increased on day 7, day 14, and day 21 after the hBMSC-scaffold with the pNIPAAM in the mice with skin defects (p < 0.05). Moreover, the stem cell markers of human CD13 and CD105 were gradually decreased during the period of wound healing. In sum, this novel method provides a transferring system for cell therapies and maintains its temperature-sensitive property of easy-peeling by lower-temperature treatment. In addition, the in vitro and in vivo GFP imaging systems provide a new imaging modality for understanding the differentiation process and the effective expression of stem cells in wound healing.