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Biomedical subjects

L Sweeney

Publications and source records attributed to L Sweeney.

At least 19 recordsLinked to original sources
PubMed2001

Distinctive patterns of Her-2/neu, c-myc, and cyclin D1 gene amplification by fluorescence in situ hybridization in primary human breast cancers.

BACKGROUND: Human solid tumors undergo clonal evolution as they progress, but evidence for specific sequences of genetic changes that occur in individual tumors and are recapitulated in other tumors is difficult to obtain. METHODS: Patterns of amplification of Her-2/neu, c-myc, and cyclin D1 were determined by fluorescence in situ hybridization (FISH) in relation to the presence of p53 dysfunction and ploidy in 60 primary human breast cancers. RESULTS: We show that there are clusters of genophenotypic abnormalities that distinguish lobular breast cancers from nonlobular tumors; that cyclin D1 amplification occurs prior to the divergence of lobular breast cancers from nonlobular cancers; that p53 dysfunction, Her-2/neu amplification, and c-myc amplification are characteristic features of nonlobular breast cancers, but not of lobular breast cancers; and that the frequencies of amplification of all three oncogenes examined increase progressively with increasing aneuploidy, but that each gene exhibits a different profile of increasing amplification in relation to tumor progression. Early amplification of c-myc appears to be an especially prominent feature of hypertetraploid/hypertetrasomic tumors. CONCLUSIONS: The data suggest that in tumors containing multiple abnormalities, these abnormalities often accumulate in the same cells within each tumor. Furthermore, the same patterns of accumulation of multiple genophenotypic abnormalities are recapitulated in different tumors.

Alleles↗
PubMed2000

Correlations among p53, Her-2/neu, and ras overexpression and aneuploidy by multiparameter flow cytometry in human breast cancer: evidence for a common phenotypic evolutionary pattern in infiltrating ductal carcinomas.

Human solid tumors develop multiple genetic abnormalities that accumulate progressively in individual cells during the course of tumor evolution. We sought to determine whether there are specific sequences of occurrence of these progressive evolutionary changes in human breast cancers by performing correlated cell-by-cell measurements of cell DNA content, p53 protein, Her-2/neu protein, and ras protein by multiparameter flow cytometry in 56 primary tumor samples obtained at surgery. In addition, p53 allelic loss and Her-2/neu gene amplification were determined by fluorescence in situ hybridization in cells from the same samples. We reasoned that if there is a specific order in which genetic changes occur, the same early changes would be found consistently in the cells with the fewest abnormalities. We reasoned further that late-developing abnormalities would not occur alone in individual cells but would almost always be found together with the early changes inherited by the same cells. By these criteria, abnormalities involving p53 generally occurred early in the course of development of invasive breast cancers, whereas ras protein overexpression was found to be a late-occurring phenomenon. Within individual tumors, cellular p53 overexpression was often observed alone in individual cells, whereas ras protein overexpression was rarely observed in the absence of p53 overexpression and/or Her-2/neu overexpression in the same cells. Furthermore, the intracellular level of each abnormally expressed protein was found to increase progressively as new abnormalities were acquired. Infiltrating ductal carcinomas exhibited characteristic phenotypic patterns in which p53 allelic loss and/or p53 protein overexpression, Her-2/neu amplification and/or overexpression, aneuploidy, and ras overexpression accumulated within individual cells. However, this pattern was not a prominent feature of lobular breast cancers. All six lobular breast cancers studied were diploid. p53 allelic loss and/or early p53 overexpression, and late ras cooverexpression in the same cells were less common in lobular breast cancers than in infiltrating ductal carcinomas. Although Her-21neu overexpression was a common finding in lobular breast cancers, Her-2/neu amplification was not observed in these tumors.

Aneuploidy↗
PubMed2000

Determining the identifiability of DNA database entries.

CleanGene is a software program that helps determine the identifiability of sequenced DNA, independent of any explicit demographics or identifiers maintained with the DNA. The program computes the likelihood that the release of DNA database entries could be related to specific individuals that are the subjects of the data. The engine within CleanGene relies on publicly available health care data and on knowledge of particular diseases to help relate identified individuals to DNA entries. Over 20 diseases, ranging over ataxias, blood diseases, and sex-linked mutations are accounted for, with 98-100% of individuals found identifiable. We assume the genetic material is released in a linear sequencing format from an individual's genome. CleanGene and its related experiments are useful tools for any institution seeking to provide anonymous genetic material for research purposes.

Confidentiality↗
PubMed1999

Genetic evolutionary staging of early non-small cell lung cancer: the P53 --> HER-2/NEU --> ras sequence.

INTRODUCTION: The sequence of genetic evolutionary abnormalities that have occurred in a given lung cancer tumor before tumor sampling can be inferred from patterns of intracellular co-occurrence of these abnormalities in tumor cell subpopulations at the time of sampling. The same evolutionary sequences that are present within each lung cancer were evident in intertumor comparisons. METHODS: Correlated cell by cell measurements of cell DNA content, p53, Her-2/neu, and ras proteins were obtained by multiparameter flow cytometry on 46 surgically resected stage I-III primary non-small cell lung cancers. Early evolutionary changes were identified by the fact that they could appear alone in individual cells. Later appearing abnormalities were identified by the fact that they were accompanied by early abnormalities in the same cells. Patients were followed prospectively. Evolutionary patterns observed in individual tumors were correlated with subsequent clinical outcome of patients undergoing surgical resection. RESULTS: Three common patterns were identified: (I) a diploid DNA pathway consisting of the sequence p53 overexpression --> Her-2/neu overexpression --> ras overexpression, (II) an aneuploid DNA pathway with the same p53 --> Her-2/neu --> ras sequence, and (III) a pathway in which none of the intracellular protein measurements made here were abnormal. Fourteen tumors recurred after 11.5 months' median study time. Nine of 12 recurrences in pathways I and II occurred in patients whose tumors were far advanced along these molecular genetic pathways. CONCLUSIONS: Multiparameter cell-based genetic evolutionary studies may be a promising approach for identifying patients with stage I-III non-small cell lung cancer at high risk for recurrence.

Adult↗
PubMed1999

The diagnostic value, parental and patient acceptability of micturating cysto-urethrography in children.

OBJECTIVES: To evaluate the medical indications and outcome including psychological and physical consequences of micturating cysto urethrography. METHODS: A prospective study of 165 consecutive children undergoing MCUG during a 3 month period. Medical data, including outcome was recorded. The distress of the child was recorded by the radiographer at the time of the examinations. Postal questionnaires were sent to parents one week after the test to obtain information on their own and their child's perception of the test, and any physical and/or behavioural changes. RESULTS: Age distribution for first and subsequent MCUG. [table: see text] 73% of first MCUG's were requested because of urinary tract infection. 52% of first MCUG's in infants were abnormal compared with 13% in older children aged 1 to 4 years. 29 children aged 4 and over underwent a second or subsequent MCUG (53% abnormal). These children would be suitable for indirect cystography. One quarter of children experienced difficulty in passing urine following the test, haematuria was experienced by four. Radiographers recorded severe distress in 27% of children and 27% of parents also recorded distress. CONCLUSIONS: A high incidence of distress was detected for both parent and child. Units should establish special guidelines for the use of this invasive procedure. A clear explanation of the investigation to parents and children should be standard practice. Routine employment of sedation for patients may be advisable. Alternative methods of imaging should be considered and evaluated, and indirect isotope cystography employed where appropriate.

Anxiety↗
PubMed1998

Oral ciprofloxacin in the treatment of pseudomonas exacerbations of paediatric cystic fibrosis: clinical efficacy and safety evaluation using magnetic resonance image scanning.

Ciprofloxacin is effective for treating pulmonary infection in adult cystic fibrosis patients, and demonstrates excellent efficacy against Pseudomonas aeruginosa, but its use in paediatric cystic fibrosis patients has been limited because quinolone-induced cartilage toxicity has been observed in juvenile animals and has been considered a potential risk for children. Children with cystic fibrosis (n = 26; aged 6-16 years), with proven P. aeruginosa colonization of their sputum, were enrolled into a 14-day, open, non-comparative study. Patients were assigned to twice-daily treatment with oral ciprofloxacin 250 mg, 500 mg or 750 mg, depending on their body weight. None of the patients exhibited any signs or symptoms of arthropathy, as assessed by magnetic resonance imaging of the right knee, during or immediately after treatment, or at the 3-month post-therapy assessment. Cough, sputum production and sputum purulence were improved in more than 70% of patients. Patients showed a mean weight increase of 0.4 kg (95% confidence interval 0.1 to 0.7 kg) over the study period. Only one patient required a repeat chest radiograph, which showed no resolution of the abnormal radiographic appearances. Three patients reported adverse events during the trial, none of which were considered to be related to the study treatment.

Administration, Oral↗
PubMed1998

Three computational systems for disclosing medical data in the year 1999.

Today most organizations release and receive medical data with all explicit identifiers, such as name, address, and phone number, removed in the incorrect belief that patient confidentiality is maintained because the resulting data look anonymous. We examine three computer programs that do maintain patient confidentiality when disclosing electronic medical records: the Scrub System which locates personally-identifying information in letters between doctors and notes written by clinicians; the Datafly System which generalizes data within the record based on a profile of the recipient at the time of access; and, the mu-Argus System which is becoming a European standard for disclosing public use data. The techniques presented in these systems help protect confidentiality in the face of a changing globally-networked society with immediate access to volumes of personal data.

Computer Communication Networks↗
PubMed1998

Intracellular coexpression of epidermal growth factor receptor, Her-2/neu, and p21ras in human breast cancers: evidence for the existence of distinctive patterns of genetic evolution that are common to tumors from different patients.

Multiparameter flow cytometry studies were performed on cells from the primary tumors of 94 patients with breast cancer. Correlated cellular measurements of cell DNA content, Her-2/neu, epidermal growth factor receptor (EGFR), and p21ras levels were performed on each of 5,000 to 100,000 cells from each tumor. When criteria for positivity were matched with those in common use for immunohistochemical studies, 28 of 94 (30%) breast cancers were classified as positive for Her-2/neu overexpression. When similar criteria were applied to the EGFR measurements, 23 of 94 (24%) cases were classified as positive for EGFR overexpression. Similarly, 23 of 94 (24%) cases were classified as positive for p21ras overexpression. By conventional flow cytometric criteria for DNA ploidy, 24 cases were diploid, 28 were tetraploid, and 42 were aneuploid. When the measurements were treated as separate sets of data, the only statistically significant correlations noted were the high frequency of diploid tumors, which did not overexpress any of the three oncogenes studied (P < 0.05), and an association between Her-2/neu overexpression and aneuploidy (P < 0.03). When the data were treated as correlated intracellular measurements, 90 of the 94 tumors studied contained a population of cells in which the intracellular levels of Her-2/neu expression were directly correlated with the levels of EGFR expression in the same cells. The ratio of Her-2/neu molecules to EGFR molecules in the same cells exceeded 1 in the majority of tetraploid and aneuploid cases and was close to or less than 1 in the majority of diploid cases. In nearly all tumors, p21ras overexpression was observed only in cells that overexpressed Her-2/neu, EGFR, or both, and p21ras levels per cell were more closely correlated with levels of EGFR per cell in the same cells than with Her-2/neu levels per cell. The data are consistent with a model in which heterodimerization of Her-2/neu and EGFR in individual cells is achieved by one of several genetic evolutionary pathways, all of which commonly lead to p21ras overexpression. The two major genetic evolutionary pathways identified in this study are an aneuploid, Her-2/neu overexpression-driven pathway seen in 59 of 94 tumors, and a diploid, EGFR overexpression-driven pathway seen in 19 of 94 tumors. All tumors with Her-2/neu:EGFR ratios greater than 2 contained an infiltrating ductal carcinoma component, whereas all infiltrating pure lobular carcinomas had Her-2/ neu:EGFR ratios that were less than 2. All of the genetic evolutionary pathways identified in this study were represented among the 11 tumors from patients who experienced early tumor recurrences.

Analysis of Variance↗
PubMed1997

Brief treatment of mild-to-moderate child depression using primary and secondary control enhancement training.

Elementary school children with mild-to-moderate depressive symptoms were randomly assigned to a control group or an 8-session Primary and Secondary Control Enhancement Training program. The program focused on (a) primary control (changing objective conditions to fit one's wishes; e.g., through activity selection and goal attainment) and (b) secondary control (changing oneself to buffer the impact of objective conditions; e.g., altering depressogenic thinking, practicing mood-enhancing cognitions). At immediate posttreatment and 9-month follow-up, the treatment group showed greater reductions than the control group in depressive symptomatology on the Children's Depression Inventory and the Revised Children's Depression Rating Scale, and treated children, more than controls, shifted from above to within the normal range on both measures. Future research is needed to test treatment effects with severely depressed youths.

Analysis of Variance↗
PubMed1997

Guaranteeing anonymity when sharing medical data, the Datafly System.

We present a computer program named Datafly that maintains anonymity in medical data by automatically generalizing, substituting, and removing information as appropriate without losing many of the details found within the data. Decisions are made at the field and record level at the time of database access, so the approach can be used on the fly in role-based security within an institution, and in batch mode for exporting data from an institution. Often organizations release and receive medical data with all explicit identifiers, such as name, address and phone number, removed in the incorrect belief that patient confidentiality is maintained because the resulting data look anonymous; however, we show the remaining data can often be used to re-identify individuals by linking or matching the data to other databases or by looking at unique characteristics found in the fields and records of the database itself. When these less apparent aspects are taken into account, each released record can be made to ambiguously map to many possible people, providing a level of anonymity determined by the user.

Confidentiality↗
PubMed1996

Lymphangioma circumscriptum associated with paravesical cystic retroperitoneal lymphangioma.

A boy with long-standing congenital cutaneous lymphangioma circumscriptum (LC), presented at the age of 6 years with an episode of painless haematuria, subsequently attributed to bladder wall involvement of a paravesical cystic retroperitoneal lymphangioma. Magnetic resonance imaging demonstrated this lymphangioma to be in communication with the cutaneous lesions. Deep lymphatic and visceral involvement is an extremely unusual occurrence in association with LC. This is the first report of an association between LC and cystic retroperitoneal lymphangioma. LC occasionally heralds a deeper, more clinically significant lymphangioma which may not become apparent until many years after the initial dermatological presentation. We report this case to raise awareness of this potential association and to demonstrate the usefulness of magnetic resonance imaging in the assessment of the deep component of cutaneous lymphangiomas.

Child↗
PubMed1996

Replacing personally-identifying information in medical records, the Scrub system.

We define a new approach to locating and replacing personally-identifying information in medical records that extends beyond straight search-and-replace procedures, and we provide techniques for minimizing risk to patient confidentiality. The straightforward approach of global search and replace properly located no more than 30-60% of all personally-identifying information that appeared explicitly in our sample database. On the other hand, our Scrub system found 99-100% of these references. Scrub uses detection algorithms that employ templates and specialized knowledge of what constitutes a name, address, phone number and so forth.

Algorithms↗
PubMed1993

Control-related beliefs and self-reported depressive symptoms in late childhood.

Research thus far links depressive symptoms in children to one type of control-related belief: low levels of perceived personal competence. However, child research, unlike adult research, has not supported a linkage between depressive symptoms and another theoretically important control-related belief: perceived noncontingency of outcomes. Here we reexamined the issue, adjusting for limitations in previous methodology by using (a) psychometrically stronger measures of control beliefs, and (b) a general population sample rather than children being treated in mental health clinics. In contrast to previous results, we found that both perceived incompetence and perceived noncontingency were strongly related to children's depression, together accounting for 40% of the variance in Child Depression Inventory scores. We also found, as in previous research, that depressive symptoms were correlated with uncertainty as to the causes of outcomes, especially successes. The findings suggest that children may be susceptible to both "personal helplessness" and "universal helplessness" forms of depression.

Child↗