Radiation dose during fluoroscopically guided central venous access device insertion: retrospective observational study. / Dosis de radiación durante la inserción guiada por fluoroscopia de un dispositivo de acceso venoso central: un estudio observacional retrospectivo.

INTRODUCTION: Central venous access devices (CVAD) are used to deliver intravenous therapy to the bloodstream. CVAD insertion is sometimes fluoroscopically guided and thus associated with radiation dose to both the patient and the staff members within the room. The objective of this study is to assess the radiation dose to the patient through a retrospective audit and directly measure the exposure to staff members in simulated procedures. A secondary objective is to evaluate the radiation exposure to the staff and patients when utilising fluoroscopic pulse rate of 7.5 pps and 4 pps. MATERIAL AND METHODS: A retrospective audit of patients undergoing Permcath and Hickman line insertions was conducted. The patients were grouped by the pulse rate used for the duration of the study; 4 pulses per second (pps) (n=24) and 7.5 pps (n=33). A STEP OD-2 monitor and PMMA was used in a simulated environment to estimate the radiation exposure to locations that a Radiologist, Nurse and Radiographer would be standing during the procedures using the average procedure details collected in the retrospective audit. Measurements were conducted at heights to reflect a whole body estimate and an estimate to the lens of the eye. RESULTS: The results show that the median dose area product (DAP) for CVAD insertion is 0.7Gy.cm2 and 0.3Gy.cm2 for procedures done at 7.5 pps and 4 pps, respectively. This corresponded to an effective dose of 0.22 mSv and 0.1 mSv. The radiologist, nurse and radiographer were exposed to a whole-body shielded dose of 0.36µSv, 0.1µSv and 0.05µSv when 7.5 pps was utilised and 0.13µSv, 0.03µSv and 0.02µSv when 4 pps was used. The exposure to the head of radiologist, nurse and radiographer was 2.1µSv, 1.4µSv, and 0.6µSv in the 7.5 pps studies and 0.7µSv, 0.5µSv, and 0.2µSv when 4pps was used. CONCLUSION: The patient effective dose was estimated to be 0.1-0.22 mSv depending on the fluoroscopic pulse rate utilised during CVAD insertions. Additionally, The radiologist, nurse and radiographer whole body and lens exposure was estimated in a simulated setting. In all cases, there was a statistically significant dose reduction when the lower fluoroscopic pulse rate was used. Thus, where possible, consideration should be given to utilising a lower pulse rate during CVAD insertions to reduce the exposure to both staff and patients.

Characterization of the structure and properties of authentic and counterfeit polypropylene surgical meshes.

A counterfeit version of the Ethicon Prolene polypropylene mesh was distributed to hospitals and clinics and unintentionally implanted into patients undergoing tension-free hernia repair. On December 19, 2003, the Food and Drug Administration (FDA) issued a public health web notification indicating that the counterfeit mesh was not sterile or safe to use. To develop safety recommendations for patients with the counterfeit mesh implant, we compared the counterfeit's structural, physical, chemical and mechanical properties with polypropylene meshes previously cleared by FDA. The mesh fibers for all the products tested were found to have similar chemical and physical properties. The mechanical properties were directly related to the knitted structure (loop size, repeat distance, fabric tightness) and the porosity. Extracts from the counterfeit mesh passed cytotoxicity screening tests. The FDA further recommended that if the mesh had been inadvertently implanted, then those patients should be monitored as would be the practice for any patient with an implanted surgical mesh.

Altered surface expression and increased turnover of the alpha6beta4 integrin in an undifferentiated carcinoma.

The integrin alpha6beta4, predominantly expressed on tissues of epithelial origin, is known to be variably expressed on carcinomas. The biochemical changes resulting in altered expression during tumor progression are unknown. We have analyzed the expression of alpha6beta4 in a multi-step mouse model of skin carcinogenesis representing normal keratinocyte, benign papilloma and malignant undifferentiated carcinoma. All cell lines expressed the alpha6 integrin exclusively as the alpha6beta4 integrin heterodimer. Analysis of this integrin by flow cytometry and immunoprecipitation of surface labeled proteins revealed that the undifferentiated carcinoma cells have an approximately 75% reduction in surface expression of the integrin as compared with the keratinocyte and papilloma cell lines. The alpha6beta4 integrin which remains expressed on the carcinoma cells is diffusely distributed in the membrane and has an approximately 2.5-fold increased biological turnover as compared with normal keratinocytes. The decreased biological half-life and the loss of polarized expression of alpha6beta4 on the carcinoma cells suggests an altered functional role for the alpha6beta4 integrin on carcinoma cells during tumor progression. These factors may contribute to the known supression of hemidesmosome structures and the increased migration phenotype associated with some epithelial carcinomas.

Characterization of integrin subunits, cellular adhesion and tumorgenicity of four human prostate cell lines.

Cellular adhesion to extracellular matrix proteins via integrin molecules is a major factor in the process of invasion and metastasis of human tumor cells. Four human prostate cell lines were characterized according to the presence and quantity of integrin subunits, the ability of the cells to attach to extracellular substrates and the capacity of the cells to form tumors in severe combined immunodeficient (SCID) mice. All four human prostate cell lines expressed three to five integrins on their cell surfaces. The DU145, PC3 and 431P cells expressed primarily alpha 3, alpha 5, and alpha 6 integrin at similar levels. These cell lines expressed the subunits beta 1, beta 3, and beta 4 with beta 1 predominant. The DU145 cells preferred attachment to fibronectin, followed by laminin and vitronectin. Approximately 50%-60% of the binding of DU145 cells to fibronectin and laminin was dependent on the function of alpha 5 beta 1 and alpha 6 respectively. The cell line LNCaP differed in its low expression of the alpha 3 subunit, 95% of cellular adhesion to fibronectin and laminin being integrin-dependent and its inability to attach to vitronectin, in spite of surface expression of alpha v beta 3. All the cell lines except for LNCaP readily formed tumors within SCID mice and the expression of alpha 3, alpha 6, beta 1 and beta 4 integrin subunits was preserved in the resulting tumor tissue. The altered adhesion properties of the LNCaP cells may explain their altered tumorigenicity.

Development and utilization of a somatic cell hybrid mapping panel to assign NotI linking probes to the long arm of human chromosome 6.

A somatic cell hybrid mapping panel that defines seven regions of the long arm and one region of the short arm of human chromosome 6 has been developed. Utilizing this panel, 17 NotI boundary clones from a NotI linking library were regionally assigned to the long arm of chromosome 6. The majority of these clones (11) were found to localize within band regions 6q24-q27. The nonuniform distribution of NotI sites may indicate a cluster of HTF islands and likely represents a coincidence of coding sequences in this region of chromosome 6. Cross-hybridization of these linking clones to DNA from other species (zoo blots) provides further evidence for transcribed sequences in 7 of the NotI clones. These NotI clones were also used to identify corresponding NotI fragments using pulsed-field gel electrophoresis, facilitating further physical mapping of this region. Finally, regional assignment of five polymorphic probes to the long arm of chromosome 6 is also presented. These hybrids and probes should facilitate the construction of a physical and genetic linkage map to assist in the identification of disease loci along chromosome 6.

Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma.

Malignant melanoma has been documented to display recurring abnormalities of chromosome 6, particularly the long arm (6q). Restriction fragment length polymorphism analysis was used as a molecular genetic approach to examine loci on chromosome 6q for loss of constitutional heterozygosity (LOH). Five DNA markers that recognize restriction fragment length polymorphisms along 6q and one polymorphic DNA marker for 6p were used to screen 20 autologous pairs of tumor DNA and normal DNA to determine the tumor and constitutional genotypes of each patient. LOH on chromosome 6q was identified at 21 of 53 informative loci (40%). Five patients with more than one informative locus had allele losses consistent with the loss of the entire long arm (or of an entire copy) of chromosome 6, while four other patients demonstrated terminal deletions of 6q. The chromosomal region bearing the highest frequency of 6q allelic loss (60%) is defined by the marker loci c-MYB and ESR (6q22-23 and 6q24-27). In contrast to the frequency of 6q loss, LOH was observed at loci on four other chromosomes (1, 11, 16, 17) in only 5% of cases. These results have led us to conclude that the loss of sequences from the long arm of chromosome 6 is a nonrandom and possibly biologically relevant event in human malignant melanoma.

Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6.

Chromosome banding analysis of human malignant melanoma has documented the nonrandom alteration of chromosome 6. To determine the relevance of chromosome 6 abnormalities in melanoma, a normal chromosome 6 was directly introduced into melanoma cell lines. The resulting (+6) microcell hybrids were significantly altered in their phenotypic properties in culture and lost their ability to form tumors in nude mice. The loss of the chromosome 6 from melanoma microcell hybrids resulted in the reversion to tumorigenicity of these cells in mice. The introduction of the selectable marker (psv2neo) alone into melanoma cell lines had no effect on tumorigenicity. These results support the idea that one or more genes on chromosome 6 may control the malignant expression of human melanoma.

Molecular mapping of the oncogene MYB and rearrangements in malignant melanoma.

The human cellular oncogene MYB has been mapped to 6q22-q23. Deletions and translocations involving this region of the long arm of chromosome 6 occur frequently in human malignant melanoma, and there are anecdotal reports of MYB gene rearrangements in this cancer. In the current study, Southern blotting and pulsed field gel electrophoresis (PFGE) have been performed to determine whether MYB or its flanking regions are commonly altered in malignant melanoma. Southern blotting failed to document obvious rearrangement of the MYB gene in 15 cases studied. To extend analysis of the MYB region, a long-range restriction map was established by PFGE. This map was then linked to the known restriction map of frequent cutting enzymes. Based on the mapping data and analysis of the MYB region in melanomas, ClaI tissue-specific variation due to methylation was demonstrated. Also, two melanomas (containing alterations in band 6q13) also demonstrated by PFGE a unique restriction fragment for the MYB gene. These results extend significantly the physical map surrounding the MYB locus and provide further evidence for the rearrangement of chromosome 6 in malignant melanoma.

The psychological and behavioral considerations of orthognathic surgery on identical (monozygotic) twins.

The psychologic and behavioral changes that may occur with the impact of orthognathic surgery on the physical appearance of an identical twin set have been addressed. This unique situation has not been discussed in the literature with respect to reconstructive or cosmetic facial surgery. A report on elective orthognathic surgery performed on identical twins and the subsequent impact on the twin relationship due to alterations of "self-image phenomenon" is given. Such an impact was a consideration in this case. Further collective study in this area is needed but is difficult to obtain because of the rarity of occurrence of this type of case.