Expression of HER2neu (c-erbB-2) and epidermal growth factor receptor in cervical cancer: prognostic correlation with clinical characteristics, and comparison of manual and automated imaging analysis

OBJECTIVES: To evaluate HER2neu and epidermal growth factor receptor (EGFR) expression with respect to overall survival and disease-free survival (DFS), and correlate expression with pretreatment factors. Comparative evaluations of manual and automated immunohistochemical imaging systems for HER2neu and EGFR expression were made. METHODS: Fifty-five patients with stages I-IVA carcinoma of the cervix were treated with definitive radiation therapy. Immunohistochemistry was performed for HER2neu and EGFR, and scored by both manual and automated methods. Univariate and multivariate analyses were performed with disease-free survival (DFS) and overall survival (OS) as primary endpoints, and biomarkers were evaluated for correlation between prognostic factors. RESULTS: Strong correlations in HER2neu and EGFR protein expression were observed between digitally and manually analyzed staining (P <== 0.0001). Increased FIGO stage and decreased HER2neu expression were significant for reduced DFS on univariate analysis (P <== 0.001 and P = 0.03, respectively). Increased FIGO stage, decreased HER2neu expression, and increased membranous staining of EGFR were significant for diminished OS on univariate analysis (P <== 0.0001, P = 0.002, and P = 0.043, respectively). Multivariate analysis revealed only increased membranous staining of EGFR associated with diminished DFS and OS (P = 0.046 and P = 0.012, respectively). Overexpression of HER2neu correlated significantly with adenocarcinoma, and overexpression of EGFR correlated significantly with squamous cell carcinoma histology (P = 0.038 and P = 0.035). Inverse correlations were observed between HER2neu expression and clinical stage, EGFR membranous staining, and EGFR distribution (P = 0.007, P = 0.006, and P = 0.034, respectively). CONCLUSIONS: Increased expression of HER2neu and decreased EGFR membranous staining identified patients with improved DFS and OS on univariate analysis, although only decreased EGFR membranous staining was significant on multivariate analysis. We also found strong correlation of results between manually and automated imaging methods.     

Intratympanic perfusion for the treatment of tinnitus

Intratympanic treatment of tinnitus with corticosteroids or gentamicin should be considered as an option of treatment in selected tinnitus patients, alone or in combination with standard modalities of management such as tinnitus retraining therapy, masking, and hearing aid amplification. Review of the literature and the authors' experience suggest the following points regarding intratympanic treatment for tinnitus: 1. Lidocaine, although effective in decreasing tinnitus, has been largely abandoned because of its severe side-effect profile and need for inpatient administration. 2. Corticosteroids have been associated with few if any side effects. 3. The good results reported in the literature with intratympanic steroids for treating tinnitus of various causes should be viewed with caution,because most are retrospective and uncontrolled studies. 4. Some Meniere's disease patients with tinnitus may experience tinnitus improvement following intratympanic steroids. This treatment may be considered in such patients, especially for those with good hearing. 5. Gentamicin is effective in eliminating or reducing tinnitus in a significant number of patients with Meniere's disease and may be considered especially for those with nonserviceable hearing. 6. Further prospective, randomized, and controlled studies to evaluate the effect of intratympanic perfusion for the treatment of tinnitus are warranted.     

Lung function,asthma symptoms,and quality of life for children in public housing in Boston: a case-series analysis

Background  

Children in urban public housing are at high risk for asthma, given elevated environmental and social exposures and suboptimal medical care. For a multifactorial disease like asthma, design of intervention studies can be influenced by the relative prevalence of key risk factors. To better understand risk factors for asthma morbidity in the context of an environmental intervention study, we conducted a detailed baseline evaluation of 78 children (aged 4–17 years) from three public housing developments in Boston.     

Evaluation of the size and type of free particulates collected from unused asbestos-containing brake components as related to potential for respirability

BACKGROUND: Chrysotile asbestos has found multiple applications in the production of friction products. At one point it comprised 40-50% of the composition of brake linings thus generating the potential for the development of asbestos related diseases in millions of workers involved in vehicle repairs. While some attention has been given to the health status of workers involved in the handling of worn components, little has been given to the potential for exposure during the handling and fitting of new (unused) components as replacement parts. METHODS: Unused brake linings or brake shoes with attached linings from four different sources were gently rinsed with prefiltered water that was then collected on filters for analysis by Analytical Transmission Electron Microscope. RESULTS: Large numbers of chrysotile asbestos containing structures, the majority of respirable size, were present in each sample. CONCLUSIONS: We conclude that any manipulation of new asbestos containing brake components would be expected to yield free dust containing chrysotile asbestos of respirable size. That the vast majority of these fibers and particulates would not be counted as regulated fibers rendering assessment of potential exposures in the work place, based on data of Permissible Exposure Limits or Regulated Fibers, questionable.     

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05.These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.     

Quantitative analysis of asbestos burden in women with mesothelioma

BACKGROUND: Lung tissue from 15 women who died from mesothelioma was evaluated for tissue burden of ferruginous bodies and uncoated asbestos fibers. The group contained individuals who had occupational exposure to asbestos and others had family members whose work history included vocations where contact with asbestos containing materials occurred. METHODS: Tissue samples from tumor free lung were digested and filtered and then investigated for ferruginous bodies by light microscopy and asbestos and non-asbestos fibers by analytical transmission electron microscopy (ATEM). Size and type of fibers were also analyzed. RESULTS: Asbestos bodies were found in 13 of the 15 samples and asbestos fibers were found in all cases. The most commonly found uncoated asbestos fiber in these individuals was amosite whereas tremolite was the second most commonly found form. The asbestos fiber burden in these females was often of mixed types. CONCLUSIONS: The asbestos body and fiber burden in these cases show variation in tissue burden. Some cases in this study had appreciable burden, which was attributed to secondhand exposure from occupationally exposed family members. Mesothelioma can occur also in individuals with comparatively low tissue burdens of asbestos.     

Impact of an endovascular program on the operative experience of abdominal aortic aneurysm in vascular fellowship and general surgery residency

BACKGROUND: This study was performed to determine the impact of an endovascular program (EVP) on open and endovascular abdominal aortic aneurysm (AAA) operations in a residency training institution. METHODS: Over an 8-year period ending in September 2001, hospital records of all patients undergoing open or endovascular AAA repair were retrospectively reviewed. Data were analyzed to determine the changing patterns of case volume, type of operative repair, and complexity of open repair with regards to the training of both general surgical chief residents and vascular fellows. RESULTS: A total of 849 AAA operations were performed during the study period. The initiation of the EVP in 1997 resulted in a steady increase in the total annual AAA cases (P < 0.05), due in part to an increase in endovascular AAA operations despite a decrease in the annual open AAA volume. EVP had a positive impact on the overall operative experience of vascular fellows owing to the large increase in their endovascular AAA experience (annual mean pre-EVP 3 +/- 0.8 versus post-EVP 47 +/- 9.6, P < 0.01). A significant reduction occurred in the vascular fellows' open AAA experience (annual mean pre-EVP 40 +/- 12.7 versus post-EVP 19 +/- 9.4, P < 0.05). EVP did not affect the endovascular AAA experience of general surgery chief residents (annual mean pre-EVP 1 +/- 0.8 versus post-EVP 3 +/- 1.5, not significant). A significant reduction occurred in chief residents' open AAA experience (annual mean pre-EVP 39 +/- 9.7 versus post-EVP 18 +/- 7.4, P < 0.05). EVP did not affect the operative experience of complex open AAA operations in either vascular fellows or general surgery residents. CONCLUSIONS: An endovascular program has a positive impact on the aortic aneurysm practice in an academic institution, as evidenced by the significant increase in annual endovascular AAA cases despite a decrease in open AAA operations. Although vascular fellows continued to maintain sufficient experience in both open and endovascular AAA operations, general surgery chief residents suffered a significant decrease in their open AAA experience. Further evaluation of the residency system is warranted to better optimize the training paradigm of both vascular fellowship and general surgery residency.