Medical imaging and telemedicine - from medical data production, to processing, storing, and sharing: a short outlook.
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Database Management Systems↗
Biomedical subjects
John Clark
Publications and source records attributed to John Clark.
National survey of dietary supplement policies in acute care facilities.
PURPOSE: Policies on the use of dietary supplements in acute care facilities were studied. METHODS: A national online survey was conducted in 2004 to determine institutional policies and practices related to the use of dietary supplements. Directors of pharmacy in acute care settings were asked about the role of the pharmacy and therapeutics committee, the use of a nonformulary request process, the use of informed consent, requirements for written orders, mechanisms to identify dietary supplements, recording of supplement use in the pharmacy database, recording of supplement use in the medication administration record, prohibitions on dietary supplement use, storage of dietary supplements, reporting of adverse events, and the use of published references. RESULTS: Usable responses were received from 302 (25.4%) of 1189 pharmacy directors. Policies on dietary supplements were developed and implemented in 62% of facilities, with 38% of respondents indicating that no such policy existed. Policies most commonly required a written order by an authorized prescriber, documentation of use in the medication administration record, and a mechanism for identification of dietary supplements by a health care practitioner prior to use. Thirty percent of respondents with policies reported that they prohibited dietary supplement use, and 9% of those without policies prohibited use in practice. Most institutions allowed the use of a patient's own supply of supplements if ordered by an authorized prescriber. Supplements were most commonly stored at the nurses' station or in a patient drawer. The most commonly used reference was the Internet. Pharmacists had concerns about the consistency of dietary supplement formulations, the lack of FDA review of supplements, and the difficulty of identifying supplements and distinguishing reputable manufacturers. CONCLUSION: A survey of pharmacy directors in acute care facilities revealed that many had no formal policy regarding dietary supplements and had not implemented planning for such a policy.
Data Collection↗
Design, synthesis, and structure-activity relationships of tetrahydroquinoline-based farnesyltransferase inhibitors.
Tetrahydroquinoline-based small molecule inhibitors of farnesyltransferase (FT) have been identified. Lead compounds were shown to have nanomolar to sub-nanomolar activity in biochemical assays with excellent potency in a Ras-mutated cellular reversion assay. BMS-316810 (9e), a 0.7 nM FT inhibitor, was orally-active in a nude mouse tumor allograft efficacy study.
Alkyl and Aryl Transferases↗
Accuracy of intraoperative imprint cytology for sentinel lymph node evaluation in the treatment of breast carcinoma.
BACKGROUND: The current report provides results from a large retrospective analysis of intraoperative imprint cytology performed on axillary sentinel lymph nodes (IIC(N)) removed over the course of 2137 breast surgeries (4905 lymph nodes). It is hoped that these results may serve as benchmarks for those interested in using this technique. METHODS: The current study included 2078 patients with T1-2 invasive breast carcinoma who underwent sentinel lymph node biopsy (SLNB) and IIC(N). Lymph nodes were bivalved, imprinted, stained with Diff-Quik (Baxter Diagnostics, McGaw Park, IL), and reviewed by a cytopathologist. A positive intraoperative diagnosis led to immediate complete axillary lymph node dissection (CALND). On final pathology, lymph nodes found to be negative on hematoxylin and eosin staining were submitted for cytokeratin staining. RESULTS: Of the 2137 cases for which SLNB was performed, 673 were found to have positive lymph node status on final pathology. Of these 673 cases, 359 were identified by IIC(N), resulting in a sensitivity rate of 53.3%. The specificity and overall accuracy rates for this technique were 99.5% and 85.0%, respectively. In IDC cases, IIC(N) had a sensitivity rate of 55.5%, compared with 38.7% in ILC cases. Based on these results, the reoperative CALND rate was calculated to be approximately 14.7%, with 54.5% of these reoperative procedures being performed for cases in which lymph nodes positive only for micrometastases were found. Macrometastasis-positive lymph nodes that went undetected by IIC(N) were present in only 154 of the 2137 cases examined (7.2%). CONCLUSIONS: IIC(N) accurately predicts final lymph node status in 85.0% of patients. Although the accuracy of this technique varies with tumor size and type, IIC(N) remains a time-efficient and cost-effective adjunct to SLNB.
Adult↗
Novel techniques in sentinel lymph node mapping and localization of nonpalpable breast lesions: the Moffitt experience.
The concept of lymphatic mapping has helped to redefine the clinical significance of lymph nodes with respect to breast cancer. The combination technique using both blue dye and radiocolloid is the most effective method of lymphatic mapping. The data in the literature support the concept that all patients undergoing lumpectomy or especially mastectomy should undergo lymphatic mapping if a diagnosis of invasive cancer is remotely possible. The low morbidity, high sensitivity, and specificity of mapping indicate its use for increasing numbers of patients thought initially not to be candidates for the procedure.
Breast Neoplasms↗
Clinical considerations in breast cancer sentinel lymph node mapping: a Moffitt review.
Lymphatic mapping redefined the clinical significance of axillary lymph nodes in the treatment of breast cancer. Current literature supports the concept that any patient diagnosed with invasive breast cancer should in fact have their sentinel lymph nodes evaluated. However, there are many cases of " special situations in lymphatic mapping " . These special situations mark an important point that should be considered: When and who should undergo lymphatic mapping? A summary of these considerations/cases will be the focus of this report.
Breast Neoplasms↗
Characterization of a mutation in the lens-specific CP49 in the 129 strain of mouse.
PURPOSE: The 129 strain of mouse carries a mutation in the gene for CP49 (phakinin), an intermediate filament protein thus far demonstrated only in the lens fiber cell. As such, these mice represent naturally occurring mutants of interest in the study of the lens cytoskeleton. However, this strain of mouse is also widely used as a source of embryonic stem cells in gene-targeting studies. The presence of a mutation in a lens-specific gene can confound interpretation of studies in which lens genes have been knocked out. In the present study, both the genotype and phenotype of these mice were characterized, to permit an evaluation of the biological impact of this mutation and to facilitate the discrimination between wild-type and mutant animals that have been derived from this strain in gene-targeting studies. METHODS: The CP49 cDNA and, when relevant, the genomic DNA sequences were determined for the 129/SvJ and C57BL/6J mice and from a commercially available 129/OLa P1 genomic clone. PCR primers were screened for their capacity to discriminate between the mutant and wild-type CP49 genes. Northern blot analysis was used to assess mRNA levels for CP49, filensin, and gammaS-crystallin (control). Western blot analysis was used to identify changes in protein size and abundance. The impact of the mutation on lens architecture was evaluated at the light-microscope level. Lens fiber cell ghosts from mutant and wild-type mice were examined in the electron microscope for the presence of beaded filaments. Lens clarity was assessed by slit lamp. RESULTS: The 129 strain of mice exhibited a 6303-bp deletion from the end of intron B, and the beginning of exon 2. This deletion results in the loss of the exon 2 splice acceptor site, absence of exon 2 from the CP49 mRNA, and dramatically reduced levels of CP49 mRNA. The CP49 protein was undetectable by Western blot analysis. Messenger RNA levels for filensin, CP49's assembly partner, were normal, but protein levels were sharply reduced. Light microscopy established that the initial differentiation and elongation of the fiber cells proceeded normally. Electron microscopy showed the absence of beaded filaments, whereas slit lamp microscopy showed a slowly emerging and progressive loss of optical clarity. CONCLUSIONS: The 129/SvJ and 129/OLa strains of mice harbor a mutation that sharply reduces CP49 mRNA levels and essentially eliminates both CP49 and the beaded filament. These lenses exhibited a slow but progressive loss of optical clarity with age. Thus, the 129 strain of mouse behaves as a functional CP49 knockout. The loss of clarity in the lenses of these animals and the absence of beaded filaments (and any attendant interactions that may exist between beaded filaments and other lens proteins/structures) suggest that gene-targeting studies of lens proteins in which the 129 strain was used as a source of embryonic stem cells may need reevaluation.
Amino Acid Sequence↗
Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells.
The transcription factor Oct-4 is a marker of pluripotency in mouse and human embryonic stem (ES) cells. Previous studies using a tetracycline-regulated Oct-4 transgene in the ZHBTc4 cell line demonstrated that downregulation of Oct-4 expression induced dedifferentiation into trophoblast, a lineage mouse ES cells do not normally generate. We found that transfection of Oct-4-specific short interfering RNA significantly reduced expression and functional activity of Oct-4 in mouse and human ES cells, enabling its role to be compared in both cell types. In mouse ES cells, Oct-4 knockdown produced a pattern of morphological differentiation and increase in expression of the trophoblast-associated transcription factor Cdx2, similar to that triggered by suppressing the Oct-4 transgene in the ZHBTc4 cell line. In addition, downregulation of Oct-4 was accompanied by increased expression of the endoderm-associated genes Gata6 and alpha-fetoprotein, and a gene trap associated with primitive liver/yolk sac differentiation. In human ES cells, Oct-4 knockdown also induced morphological differentiation coincident with the upregulation of Gata6. The induction of Cdx2 and other trophoblast-associated genes, however, was dependent on the culture conditions. These results establish the general requirement for Oct-4 in maintaining pluripotency in ES cells. Moreover, the upregulation of endoderm-associated markers in both mouse and human ES cells points to overlap between development of trophoblast and endoderm differentiation.
Animals↗
Expression by transgenesis of a constitutively active mutant form of the prolactin receptor induces premature abnormal development of the mouse mammary gland and lactation failure.
Prolactin (PRL) initiates signal transduction by inducing homodimerization of PRL receptor (PRL-R). We have previously developed a mutant form of the PRL-R in which a part of the extracellular domain is deleted. This receptor constitutively activates protein gene transcription. We examined the oligomerization of the mutant PRL-R using two differently epitope-tagged receptors in a coimmunoprecipitation assay. It was shown that mutant receptor dimers were formed in a ligand-independent manner, which may explain the constitutive activity on milk protein gene expression. To study the biological activity of this mutant PRL-R on mammary gland development, we generated two lines of transgenic mice expressing the corresponding cDNA specifically in the mammary epithelial cells. For both transgenic lines, the mammary gland of 8-wk-old virgin mice was overdeveloped with numerous dilated ductal and alveolar structures, whereas only a limited duct network was present in wild-type animals at the same age. During pregnancy, the ducts and alveoli of transgenic mice were more developed than those of control animals. At parturition, the transgenic animals failed to lactate and nourish their offspring, and the involution of the mammary gland was strongly delayed. In conclusion, the expression of a constitutively active PRL-R by transgenesis induces a premature and abnormal mammary development and impairs terminal differentiation and milk production at the end of pregnancy.
Animals↗
The clinical relevance of positive sentinel nodes only versus positive nonsentinel lymph nodes in breast cancer patients.
BACKGROUND: The purpose of this study was to determine the difference in clinical outcomes for patients with histologically positive sentinel lymph nodes (SLN+) compared with patients with histologically positive nonsentinel second echelon lymph nodes (NSLN+). METHODS: Eight hundred thirteen node positive patients from a prospectively accrued database of 3200 patients who underwent sentinel node mapping were evaluated. In all, 506 of the 813 patients (62%) were SLN+ only and 307 of the 813 patients (38%) were SLN+ plus at least one NSLN+. Patients' overall survival and disease-free survival were obtained and statistical analyses performed comparing the two groups. RESULTS: As the number of NSLN+ increased, there was a significant difference in disease-free survival (P = 0.001) and overall survival (P = 0.003) between those patients who had 0 to 4 NSLN+ and those who had 5 or more NSLN+. The SLN+ only patients did not show significant differences with respect to survival, based on the number of SLN+ (overall survival, disease-free survival; P = 0.742). CONCLUSIONS: The survival (overall survival, disease-free survival) for patients with 3 or more SLN+ was not statistically different than for patients with 1 or 2 SLN+ (P = 0.742). However, an alteration of biologic behavior was observed when multiple NSLN+ contain metastatic breast cancer. Involvement of 5 or more NSLN+ portends a significantly (P = 0.001) worse prognosis, regardless of the number of SLN+.
Breast Neoplasms↗
Effect of 0.5 Tesla magnetic resonance imaging on the surgical management of breast cancer patients.
BACKGROUND: This trial examines the utility of breast magnetic resonance imaging (MRI) for detection of occult breast disease and its effect on surgical treatment. METHODS: Between October 2000 and March 2002, 76 of 1289 patients underwent bilateral breast MRI within 4 months of a mammogram. The MRI scan, mammogram, pathology reports, and physicians' notes were reviewed to determine impact of MRI on surgical treatment. RESULTS: Magnetic resonance imaging detected 23 additional lesions in 19 patients not detected by mammogram. Cancer occult to mammography was detected by MRI in 6 women, constituting 7.9%. Magnetic resonance imaging impacted surgical treatment plans in 10 of 76 (13.2%) patients. CONCLUSIONS: Magnetic resonance imaging is effective at identifying new subclinical breast disease not seen on mammography. Ten of 76 patients (13.2%) who underwent MRI had their surgical management altered due to MRI findings. Specific criteria should be studied to know which subgroups would benefit most from breast MRI.
Adult↗
A future for transgenic livestock.
The techniques that are used to generate transgenic livestock are inefficient and expensive. This, coupled with the fact that most agriculturally relevant traits are complex and controlled by more than one gene, has restricted the use of transgenic technology. New methods for modifying the genome will underpin a resurgence of research using transgenic livestock. This will not only increase our understanding of basic biology in commercial species, but might also lead to the generation of animals that are more resistant to infectious disease.
Animals↗
Targeted deletion of the lens fiber cell-specific intermediate filament protein filensin.
PURPOSE: To determine the function of the lens fiber cell-specific cytoskeletal protein, filensin, in lens biology. METHODS: Targeted genomic deletion was used to delete exon 1 and the transcriptional start site of the filensin gene. Resultant chimeric animals were bred to homozygosity for the mutant allele. These animals were outbred to mice bearing the wild-type CP49 alleles to eliminate the mutant CP49 gene carried by the 129 strain of mice. Animals homozygous for the mutated filensin gene and wild-type CP49 gene were compared with wild-type and heterozygous animals by Northern and Western blot analyses, light and electron microscopy, and slit lamp microscopy. RESULTS: Disruption of the filensin gene successfully blocked production of filensin mRNA, reduced levels of filensin's assembly partner CP49, and prevented the assembly of beaded filaments. Despite the absence of beaded filaments, lenses did not show obvious changes in fetal development, nor in the differentiation of epithelial cells into mature fiber cells, as judged by light microscopic analysis. Filensin knockouts began to show evidence of light-scattering by 2 months and worsened with age. Heterozygous animals exhibited an intermediate phenotype, showing a reduction in filensin transcript and moderate light-scattering at 5 months. CONCLUSIONS: The lens fiber cell-specific intermediate filament protein filensin is essential for beaded filament assembly. However, although beaded filaments are not needed for normal lens fetal development or fiber cell differentiation, they appear to be necessary for the long-term maintenance of optical clarity. The mechanism by which the absence of filensin and the beaded filament affects optical clarity has yet to be defined.
Animals↗
Radioactive seed localization breast biopsy and lumpectomy: can specimen radiographs be eliminated?
BACKGROUND: Wire localization (WL) is the current standard for surgical diagnosis of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with radioactive seed localization (RSL). This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL. METHODS: A total of 134 women were entered onto an institutional review board-approved study. RSL was performed by placing a titanium seed containing.29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The surgeon used a handheld gamma detector to locate and excise the iodine-125 seed and the lesion. RESULTS: Specimen radiographs were eliminated in 98 (79%) of 124 patients. Surgical seed retrieval was 100% in 124 patients. No seed migration occurred after correct radiographical placement. A total of 26 (21%) of 124 patients required a specimen radiograph; 22 (85%) of these 26 were performed for microcalcifications. CONCLUSIONS: After surgical removal, RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion. If small microcalcifications are noted before surgery, then specimen radiographs may be necessary. RSL reduced requirements for specimen radiographs, decreased OR time, improved incision placement, and improved resections to clear margins.
Adult↗
Measurement of brain tissue oxygenation performed using positron emission tomography scanning to validate a novel monitoring method.
OBJECT: The benefits of measuring cerebral oxygenation in patients with brain injury are well accepted; however, jugular bulb oximetry, which is currently the most popular monitoring technique used has several shortcomings. The goal of this study was to validate the use of a new multiparameter sensor that measures brain tissue oxygenation and metabolism (Neurotrend) by comparing it with positron emission tomography (PET) scanning. METHODS: A Neurotrend sensor was inserted into the frontal region of the brain in 19 patients admitted to the neurointensive care unit. After a period of stabilization, the patients were transferred to the PET scanner suite where C15O, 15O2, and H2(15)O PET scans were obtained to facilitate calculation of regional cerebral blood volume, O2 metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm Hg) and the same sequence of PET scans was repeated. For each scanning sequence, end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three patients the sensor was inserted into areas of contusion and these patients were eliminated from the analysis. In the subset of 16 patients in whom the sensor was placed in healthy brain, no correlation was found between the absolute values of PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained between the change in PbO2 (deltaPbO2) and the change in PvO2 (deltaPvO2) produced by hyperventilation in a 20-mm region of interest around the sensor (p = 0.78, p = 0.0035). CONCLUSIONS: The lack of correlation between the absolute values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for PvO2. Nevertheless, the positive correlation between deltaPbO2 and deltaPvO2 when the sensor had been inserted into healthy brain suggests that tissue PO2 monitoring may provide a useful tool to assess the effect of therapeutic interventions in brain injury.
Adult↗
Management development of clinicians in Indonesia.
This paper evaluates an open learning and applied learning programme for health professionals delivered by the authors in Indonesia. It also highlights the importance of the active involvement of Indonesian health professionals in the delivery and the need for the programme to be contextualised. The background is a pilot programme for the management development of clinicians in Indonesia. As a country facing huge political, economic and social problems there is an urgent need to improve the health status of the population, for example, by reducing the maternal mortality rate. The objectives of the Indonesian Health Referral and Hospital Programme in the 6th Five Year Development Strategy includes not only this type of health improvement target but also the need for improvement in the management of resources.
Journal Article↗
Dropped gallstones post laparoscopic cholecystectomy mimicking peritoneal seeding: CT and ultrasound features.
PURPOSE: The purpose of this work was to investigate the ultrasound (US) and CT features of dropped gallstones mimicking peritoneal seeding in patients after laparoscopic cholecystectomy (LCC). METHOD: We describe the US and CT features of dropped gallstones mimicking peritoneal seeding in eight patients who underwent LCC. We also conducted a retrospective study of consecutive LCC patients who subsequently had CT to determine the prevalence of this condition. RESULTS AND CONCLUSION: The density of dropped gallstones on CT ranged from hypodense to partially or completely calcified nodules. Some stones did not have visible surrounding reaction, whereas others showed an enhancing halo. All stones were echogenic and demonstrated shadowing on US. The stones were located mostly on the right side of the abdomen, and the majority were around the liver. The prevalence of dropped gallstones post laparoscopic cholecystectomy was 4.2%.
Adult↗