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.     

Spontaneous conception in the presence of stage IIIC endometrioid ovarian cancer

OBJECTIVE: To describe a rare case of spontaneous conception in a patient with a preexisting metastatic ovarian cancer. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 39-year-old Asian woman who conceived while undergoing an evaluation for primary infertility and newly detected bilateral adnexal masses. INTERVENTION(S): Staging laparotomy and total abdominal hysterectomy and bilateral salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Anatomic pathology diagnosis. RESULT(S): Blighted ovum and stage IIIC endometrioid adenocarcinoma of ovary. CONCLUSION(S): Metastatic ovarian cancer does not prevent either spontaneous ovulation or spontaneous conception.     

Validation and reproducibility of computerised cell-viability analysis of tissue slices

Background

The identification of live cells using membrane integrity dyes has become a frequently used technique, especially with articular cartilage and chondrocytes in situ where tissue slices are used to assess cell recovery as a function of location. The development of a reproducible computerised method of cell evaluation would eliminate many variables associated with manual counting and significantly reduce the amount of time required to evaluate experimental results.

Methods

To validate a custom computerised counting program, intra-person and inter-person cell counts of nine human evaluators (three groups – unskilled, novice, and experienced) were compared with repeated pixel counts of the custom program on 15 digitised images (in triplicate) of chondrocytes in situ stained with fluorescent dyes.

Results

Results indicated increased reproducibility with increased experience within evaluators [Intraclass Correlation Coefficient (ICC) range = 0.67 (unskilled) to 0.99 (experienced)] and between evaluators [ICC = 0.47 (unskilled), 0.85 (novice), 0.93 (experienced)]. The computer program had perfect reproducibility (ICC = 1.0). There was a significant relationship between the average of the experienced evaluators results and the custom program results (ICC = 0.77).

Conclusions

This study demonstrated that increased experience in cell counting resulted in increased reproducibility both within and between human evaluators but confirmed that the computer program was the most reproducible. There was a good correlation between the intact cell recovery determined by the computer program and the experienced human evaluators. The results of this study showed that the computer counting program was a reproducible tool to evaluate intact cell recovery after use of membrane integrity dyes on chondrocytes in situ. This and the significant decrease in the time used to count the cells by the computer program advocate its use in future studies because it has significant advantages.

     

Rosai Dorfman disease presenting as synchronous nasal and intracranial masses

A 56-year-old woman with vertex headaches, new-onset seizure disorder, nasal obstruction, and hyposmia was found to have a dural-based intracranial mass as well as bilateral masses arising from the inferior turbinates and extending into the nasopharynx. The patient underwent endoscopic resection of the involved portions of the inferior turbinates, including the sizable nasopharyngeal component. Craniotomy was performed at a later date. Both pathologic specimens were consistent with extranodal Rosai-Dorfman disease. The patient showed resolution of all symptoms after surgery. Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, is a rare entity usually presenting as cervical nodal disease. When extranodal disease of the head and neck is present, prompt recognition and conservative surgical management is the treatment of choice for this benign pseudolymphomatous entity.     

An unusual case of mixed-dust exposure involving a "noncommercial" asbestos

Our health center evaluated an individual for suspected pneumoconiosis, which had resulted from exposures in a foundry/metal reclamation facility. Appropriate consent forms were obtained for the procedures. Historically, individuals who work in foundries have been exposed to various types of dusts. The clinical findings in this case were consistent with silicosis with a suspicion of asbestos-induced changes as well. A sample from this individual, analyzed by electron microscopy, showed both classical and atypical ferruginous bodies. The uncoated fiber burden in this individual indicated an appreciable number of anthophyllite asbestos fibers. This finding, coupled with analysis of cores from ferruginous bodies and the presence of ferruginous bodies in areas of interstitial fibrosis, pathologically supported the diagnosis of asbestos-related disease. The unique factor associated with this case is that unlike in some settings in Finland where anthophyllite was mined and used commercially, this mineral fiber is not commonly found in commercially used asbestos products in the United States. Although the actual source of the asbestos exposure in this case is still being sought, it should be recognized that anthophyllite is a contaminant of many other minerals used in workplace environments, including foundries. The fiber burden indicates a unique type of exposure, differing from that usually construed as typical in occupational settings in the United States.     

Malignant mesothelioma from neighborhood exposure to anthophyllite asbestos

BACKGROUND: Anthophyllite asbestos has been reported to cause asbestosis, lung cancer, mesothelioma, and pleural plaques in occupationally exposed workers. Anthophyllite has also been associated with pleural plaques in Finland and Japan among those who live near mines and mills and have neighborhood or environmental exposure. METHODS: We evaluated a 38-year-old patient with pleural mesothelioma who lived, attended school, and delivered newspapers near a manufacturing facility that used exclusively anthophyllite asbestos fiber from ages 8-17 years. He had no work exposure to asbestos. RESULTS: The pleural mesothelioma was an epithelial type with tubulopapillary structures and was treated with an extrapleural pneumonectomy followed by radiation therapy. The malignant cells were positive by immunohistochemistry for cytokeratin but negative for carcinoembryonic antigen, S100, B72.3, and leu M1 antigen. Anthophyllite fibers were > 5 microm in length in lung tissue compared to 3 microm from a general population study. CONCLUSIONS: Anthophyllite asbestos has been associated with neighborhood environmental exposure and pleural plaques; we now report a neighborhood exposure and pleural mesothelioma.