Large-scale identification of novel potential disease loci in mouse leukemia applying an improved strategy for cloning common virus integration sites

The identification of common virus integration sites (cVIS) in retrovirally induced tumors in mice provides a powerful strategy to isolate novel transforming genes. Applying virus LTR-specific inverse-PCR and RT-PCR combined with automated sequencing on CasBr-M Murine Leukemia Virus (MuLV) induced myeloid leukemias, 126 virus integration sites were cloned. Using locus- and LTR-specific primers, a nested-PCR/Southern-blotting procedure was developed on genomic DNA from a large panel of MuLV-induced leukemias, to analyse whether a particular virus insertion represented a cVIS. In fact 39 out of 41 integrations analysed this way appeared to represent a common virus integration. We recognized six previously cloned cVISs, i.e. Evi1, Hoxa7, c-Myb, Cb2/Evi11, Evi12, and His1 and 33 novel common insertions, designated Cas-Br Virus Integration Site (Casvis). Among this group we found integrations in or near genes encoding nuclear proteins, e.g. Dnmt-2, Nm23-M2, Ctbp1 or Erg, within receptor genes, e.g. Cb2 or mrc1, novel putative signaling or transporter genes, the ringfinger-protein gene Mid1 and a panel of genes encoding novel proteins with unknown function. The finding that 39 out of 41 integrations analysed represented a cVIS, suggests that the majority of the other virus insertions that were not yet analysed by the PCR/Southern-blotting method are located in a cVIS as well and may therefore also harbor novel disease genes.     

The value of serum Bcl-2 levels in advanced lung cancer patients

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.     

Supracricoid partial laryngectomy with cricohyoidopexy and cricohyoidoepiglottopexy: functional and oncological results

Sixty-eight patients who presented with glottic and glottosupraglottic squamous cell carcinoma and who were managed in this department with supracricoid partial laryngectomy (SCPL) with either cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP), were retrospectively reviewed. The authors analysed the functional and oncological results of the patients. The median follow-up period was 62 months. The average times until decannulation and nasogastric feeding tube removal were 27.7 and 26.4 days, respectively. All patients were successfully decannulated. All patients were able to swallow, but one patient was unable to swallow and had recurrent aspiration. Better functional results were achieved in patients managed with CHEP procedure than the patients managed with CHP procedure. The five-year absolute and cause-specific actuarial survival rates (Kaplan-Meier method) were 78.6 per cent and 93.9 per cent, respectively. The five-year actuarial local control and nodal control rates were 89.5 per cent and 90.4 per cent, respectively. Local recurrence was statistically more likely in patients with positive resection margins (p <0.006). Overall, local control and laryngeal preservation were achieved in 95.6 per cent and 89.7 per cent, respectively. Supracricoid partial laryngectomy procedures (CHEP and CHP) are possible alternatives to total laryngectomy in the treatment of selected advanced glottic and glottosupraglottic carcinomas.     

Effect of middle ear effusion on distortion product otoacoustic emission

OBJECTIVES: It is well documented that children, particularly between the ages of about 2 and 6 years, exhibit a high prevalence and incidence of otitis media. Distortion product otoacoustic emissions (DPOAEs) offer great potential for clinical testing of cochlear function in children. The aim of the present study was to determine the influence of middle ear effusion and physical properties of the effusion on the recording of DPOAE. METHODS: Nineteen children (38 ears) undergoing myringotomy and/or tympanostomy tube insertion for secretory otitis media were studied. Pre-operative and post-operative first day DPOAE signal to noise ratios were compared. The results were analyzed by paired samples test and ANOVA statistical methods. RESULTS: We were found significant differences between pre-operative and post-operative first day DPOAE signal to noise at 1, 1.5, 2 and 4kHz. In addition, comparison of the pre-operative DPOAE signal to noise ratio and per-operative middle ear findings are shown significant differences between glue (thick mucous) and the other three groups (mucous, serous and no-effusion groups) at 2 and 4kHz, and between glue and no effusion group at 8kHz. Also post-operative DPOAE signal to noise ratio in relation to per-operative middle ear findings were significantly different at 2, 4 and 8kHz. The most increase of emissions at the post-operative first day was seen in ears with glue effusion at 1 and 2kHz. CONCLUSIONS: Otitis media with effusion can be monitored by DPOAE measurement pre-operatively and post-operatively. In the pre-operative evaluation, glue effusion may cause a reduction in the emissions at 2, 4 and 8kHz more than the other kind effusions.     

Managerial implications of medical sales representative perceptions of job duties, job qualifications, and other performance-related issues

This study examined the perceptions of medical sales representatives of job related duties, job qualifications needed, and motivating factors and tested for differences based on gender, age, years of experience and education using prior research as a base. This study also explored issues that may arise between sales people and physicians. The authors surveyed 132 medical sales representatives from pharmaceutical firms located in Ankara, Turkey. The authors' findings highlight the need in Turkey for developing in-service training programs for medical sales representatives, especially in the areas related to technical aspects of the product, effective marketing and personal selling strategies, and consumer relations. Training in these areas will help salespeople to better manage the problems typically encountered in physician-sales representative relations. While the study was conducted in Turkey, the results are similar to findings in prior research conducted in other countries and therefore may be of interest to all sales managers.     

Serum bcl-2 and survivin levels in melanoma

This study was conducted to investigate the serum levels of bcl-2 and survivin in patients with melanoma and the relationship with tumour progression and known prognostic parameters. Forty-four patients with cutaneous melanoma were investigated. Serum samples were obtained on first admission before adjuvant and metastatic treatment were given and at follow-up. Serum bcl-2 and survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA). The baseline serum bcl-2 levels were significantly higher in patients with melanoma than in the control group (P=0.01). For the serum survivin levels, no difference was found (P=0.6). No significant correlations were found between the prognostic parameters analysed and the serum survivin concentrations. The same was true of the serum bcl-2 values, except for the age of the patient (P=0.025) and nodal involvement (P=0.003). No significant relationship was found between the serum levels of bcl-2 and survivin (r=-0.13, P=0.4). In node-positive patients (n=8) both of these anti-apoptotic substances were unchanged after interferon-alpha-2b therapy. However, serum survivin concentrations were significantly increased in 10 patients with metastatic melanoma who underwent dacarbazine (DTIC)-based cytotoxic chemotherapy (P=0.047). A similar finding was not determined for the serum bcl-2 levels. In conclusion, the results of this study suggest that decreased apoptosis is associated partly with an increase in serum bcl-2. However, much research continues in this field, and exciting new knowledge will ultimately emerge.     

Safety of paclitaxel in a patient with ovarian cancer and hyperbilirubinemia due to Rotor's syndrome

BACKGROUND: Rotor's syndrome is a rare congenital disorder characterized by functional hyperbilirubinemia. Treatment decision may be challenging in a cancer patient with Rotor's syndrome, since the majority of the antineoplastic agents are metabolized in the liver and excreted via the biliary system. We report the first case of paclitaxel administration in a patient with ovarian cancer and elevated bilirubin levels due to Rotor's syndrome. CASE: A 50-year-old woman with Rotor's syndrome had an exploratory laparotomy and was diagnosed to have stage IIIC epithelial ovarian cancer. The baseline serum bilirubin value was 15.3 mg/dL. She was started on a 50% dose of 87.5 mg/m(2) paclitaxel by 3-h infusion plus carboplatin AUC-6. The paclitaxel dose was increased by 25% at consecutive cycles until the standard dose of 175 mg/m(2)/3 h was achieved. Six cycles were administered without any metabolic derangement. The patient was rendered disease free with this treatment. CONCLUSION: Paclitaxel appears to be safe to administer to cancer patients with functional hyperbilirubinemia.     

Evaluation of pulmonary changes due to biomass fuels using high-resolution computed tomography

Biomass fuels are frequently used in rural areas of the world for cooking and heating frequently. It has been reported that the use of these fuels causes hazardous effects on the lungs. In this study, we evaluated the pulmonary changes due to the use of biomass fuels in a female population that lives in our territory by high-resolution computed tomography (HRCT). The study analyzed three groups of women. The first group comprised those subjects who were exposed to biomass without respiratory symptoms (group 1; n=32). The second group comprised those individuals that were exposed to biomass and showed respiratory symptoms, such as cough, sputum production, and dyspnea (group 2; n=30). The third group was composed of women who were not exposed to biomass and also had no respiratory symptoms (group 3; n=30). Women with a history of concomitant pulmonary diseases were excluded from the study. All groups were examined with HRCT. Groups 1 and 2 (individuals exposed to biomass fuels) had more pathologic findings than group 3 (not exposed to biomass fuels). Ground-glass appearance was seen in 71.9% in group 1, 23.3% in group 2, and 3.3% in group 3. The difference between the groups was statistically significant (p<0.05). Fibrotic bands were seen 50% in group 1, 63.3% in group 2, and only 6.7% in group 3 (p<0.001). Exposure to biomass fuels was the cause or predisposing factor for many pulmonary diseases, ranging from chronic bronchitis to diffuse lung diseases. We believe that these pathological changes due to biomass fuels can be detected earlier by HRCT and the diseases might be prevented or treated earlier.     

In vitro release studies of chlorpheniramine maleate from gels prepared by different cellulose derivatives

The objective of this study was to evaluate the in vitro and ex vivo percutaneous absorption of chlorpheniramine maleate (CPM) from different hydrogel formulations. Various concentrations of polymers, including hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) and methyl cellulose (MC) were used in the hydrogel formulations. All experiments were conducted using cellulose dialysis membrane. The passive permeation of CPM was affected by the polymer concentrations. The effect of each polymer on the release rate of CPM was found to be statistically different (P<0.05). The formulation which exhibited maximum drug release through cellulose membrane was then used with other membranes namely polyurethane membrane, rat skin and human skin. The release rate of CPM from different membranes was found to be statistically different (P<0.05). Within the different diffusional barriers rat skin was found to be best alternative to human skin. It seems suitable the use of cellulose derivatives for topical application of CPM to obtain high therapeutic concentration at the application site. The synthetic membranes can be used to assess product performance in quality assurance but give little indication of its performance ex vivo.