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Biomedical subjects

C Costello

Publications and source records attributed to C Costello.

At least 37 records · Page 2Linked to original sources

Aneuploidy analysis in fibroblasts of human premature aging syndromes by FISH during in vitro cellular aging.

Cultured cells from human premature aging syndromes show premature replicative senescence and as such might serve as models for genetic studies of cellular replicative senescence/aging. To date, no systematic study on chromosome-specific aneuploidy in premature aging syndromes has been carried out using molecular-cytogenetic techniques. We, therefore, have performed a comparative analysis of chromosome-specific aneuploidy levels at both interphase and metaphase in earlier (younger) and later (older) passage fibroblasts from two normal male and female versus six male and female premature aging syndromes (Cockayne, Hutchinson-Gilford and Werner) by FISH. We have used seven chromosome-specific DNA probes (nos. 1, 4, 6, 8, 10, 15, X) and four DNA probes (nos. 1, 4, 6, X) for females and males, respectively. Our data on total aneuploidy of each chromosome in all cell cultures indicated that significantly higher percentages of aneuploid cells were detectable at interphase than at metaphase. Also, the interphase aneuploidy levels of all chromosomes under study were significantly higher in cells from the syndromes as compared to these of the normal controls at both earlier and later passages. In general, the interphase aneuploidy level of each of the chromosomes in both the control and experimental cell cultures increased with in vitro proliferation and aging, although to a much lesser extent in the controls. The aneuploidy levels, however, varied widely from chromosome to chromosome in each case. Since adequate numbers of mitotic cells were not always available in some later passage cells of various premature aging syndromes, metaphase chromosome analysis for all chromosomes under study was not always possible at this stage, but interphase cytogenetics was very informative in all cases. No consistent pattern of chromosome-specific aneuploidy was detected in the earlier passage cells (younger cells) of the syndromes. However, the later passage cells (older cells) from all three female syndromes consistently showed the highest aneuploidy levels for the X chromosome at interphase.

Adolescent↗

Benign cutaneous Degos' disease.

We report the case of a 44-year-old woman with Degos' disease who also had a lupus anticoagulant. Electron microscopy of the mature lesions showed interwoven tubular structures within the endothelial cells, as have been observed in previous cases of Degos' disease. Four years after her first cutaneous lesions, there is no evidence of involvement of other organs. Aspirin (300 mg daily) has arrested the cutaneous disease.

Adult↗

CD5 positive breast carcinoma in a patient with untreated chronic lymphocytic leukaemia: molecular studies of chromosome 13q.

A 67 year old woman presented with a right breast lump which proved to be a grade 2 invasive ductal carcinoma with axillary lymph node metastasis. She had a five year history of CD5 positive chronic lymphocytic leukaemia, which never required treatment. Immunoperoxidase stains for CD5, using the monoclonal antibody NCL-CD-54C7, showed that there was extensive infiltration of axillary lymph nodes with CD5 positive B lymphocytes. Strong staining for CD5 was also seen in the carcinoma cells within the breast and lymph node metastases. It has recently been suggested that there is a tumour suppresser locus in chronic lymphocytic leukaemia at 13q12.3 near or at the BRCA2 locus. Deletion of regions on chromosome 13q containing the BRCA2 and RB1 genes has also been reported in sporadic breast cancers. These observations suggest that there may be a link between these two diseases acting through chromosome 13, but amplification of several microsatellite repeat markers failed to show any loss of heterozygosity or repeat instability at either these or several other loci on chromosome 13. Examination of additional such cases is needed to perform a more comprehensive study of the significance of positive CD5 staining of breast carcinoma.

Aged↗

Neutrophil adhesion molecule surface expression and responsiveness in cystic fibrosis.

The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.

Acute Disease↗

Helmets, injuries and cultural definitions: motorcycle injury in urban Indonesia.

This paper examines motorcycle helmet use and injuries in a developing country with a helmet law. Data were collected by systematic street observations and interviews with motorcyclists and supplemented with motorcycle injury data from a 1 month study of all patients coming to emergency departments in Yogyakarta, Indonesia. Observations show that 89% of motorcycle drivers (N = 9242) wore helmets; only 20% of the passengers (N = 3541) did. However, only 55% of the drivers wore helmets correctly (e.g. with chin strap buckled). Differences in time and place were noted in interviews when motorcyclists reported wearing helmets least at night and when no police were around; various reasons for not wearing helmets included physical discomfort and absence of police surveillance. Data from emergency departments found that motorcycles were involved in 64% of all traffic accident injuries, comprising 33% of total trauma patients presenting to emergency departments. Injury Severity Scores were calculated for the 26% of motorcycle injuries which were admitted to the hospital, with 60% having scores of 1-8, 27% 9-15, and 9% > 15. We conclude that although motorcycle drivers appear to comply with the motorcycle helmet law, it is a "token compliance." Less than 50% of riders were maximally protected by helmets and very little safety consciousness was found among drivers. Suggestions for improving helmet use that take cultural definitions of wearing helmets into account are presented for future research.

Accidents, Traffic↗

Cutaneous lymphocytic vasculitis in acute myeloid leukaemia.

We report a 63-year-old woman who presented with an 8-week history of widespread indurated, purpuric lesions associated with weight loss of 7 kg and several episodes of epistaxis. A skin biopsy demonstrated a lymphocytic vasculitis with haemorrhage and parakeratosis. A blood film and bone marrow examination showed features of a myelodysplastic syndrome in transformation to acute myeloid leukaemia. Leucocytoclastic vasculitis and polyarteritis nodosa occur in association with acute myeloid leukaemia, but the association with lymphocytic vasculitis is new.

Acute Disease↗

Serum vitamin B12 and transcobalamin levels in early HIV disease.

A cohort of asymptomatic human immunodeficiency virus (HIV) seropositive patients was followed over a 2 1/2-year period, to establish changes in serum vitamin B12 (B12) concentrations. Serum B12, CD4 count, and clinical progression to acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were measured. The unsaturated B12 binding capacities of the transcobalamins were also determined at the start of the study and compared to those from a homosexual HIV seronegative control group. The geometric mean of serum B12 in 218 asymptomatic HIV seropositive patients was significantly lower than of a homosexual HIV seronegative control group (P = 0.02) and the unsaturated B12 binding capacities of transcobalamins I and II were significantly higher in the asymptomatic patients compared with the same control group (P < 0.03, P < 0.0001, respectively). Fifty-nine of the asymptomatic HIV seropositive patients were followed over a 2 1/2-year period during which most had falling serum B12 levels (64%). Twelve patients progressed clinically to ARC or AIDS, of which nine had repeat serum B12 estimation prior to progression. All nine patients had or developed falling serum B12 levels without any evidence of an HIV-related bowel disorder. All patients progressing had falling CD4 counts. Subnormal serum B12 levels are common in HIV disease and occur at an early stage. B12 levels fall in most patients with time and may help predict those patients whose disease will progress the most rapidly.

Acquired Immunodeficiency Syndrome↗

Evidence for adenoma-carcinoma sequence in the duodenum of patients with familial adenomatous polyposis. The Leeds Castle Polyposis Group (Upper Gastrointestinal Committee).

AIMS: To explore the association between duodenal adenoma and carcinoma in patients with familial adenomatous polyposis (FAP). METHODS: A multicentre survey of 1262 patients with FAP yielded 47 cases of duodenal cancer. The association between adenoma and cancer was assessed in these cases. RESULTS: Adenomatous tissue was found within duodenal cancer in 29 of 44 (66%) patients with FAP and in mucosa adjacent to duodenal cancer in 31 of 42 (73%) such patients. Adenomas were found as a component of, or adjacent to, duodenal cancer in 38 of 45 (84%) patients. CONCLUSIONS: These observations support the existence of the adenomacarcinoma sequence in the duodenum of patients with FAP. Factors associated with malignant change included villous histology, moderate or severe dysplasia, and the presence of stage IV duodenal polyposis.

Adenoma↗

Water preparation practices in south Kalimantan, Indonesia.

This study investigated water preparation practices, water sources, and sanitation measures in 400 households in four villages in Banjar district of South Kalimantan, Indonesia. A survey of randomly selected households in each of the four villages was undertaken during the season of low prevalence of diarrhoeal disease (February-March 1989). A follow-up survey of the same households was conducted 6 months later to measure prevalence during the peak season. Twenty-three in-depth interviews were carried out with key persons in local villages. Observations on behaviour in the local food stalls were recorded. The results of the study indicate that 97% of the households report that they regularly boil their drinking water. However, 37% of the households regularly or occasionally mix boiled with unboiled water for drinking, or use unboiled water alone. The mixing of boiled with unboiled water is particularly frequent in the preparation of 'cold tea', a popular drink in households and food stalls. The occasional or regular use of unboiled water varies by ethnicity, education and literacy, and economic status. The use of unboiled water is associated with higher rates of childhood diarrhoeas in the households studied.

Adult↗

Chemical contrast in X-ray microscopy and spatially resolved XANES spectroscopy of organic specimens.

The scanning transmission x-ray microscope at the National Synchrotron Light Source has been used to record x-ray absorption near-edge structure (XANES) spectra from 0.01-square-micrometer regions of organic specimens. The spectral features observed reflect the molecular structure of the dominant absorbing atoms and provide the contrast mechanism for high-resolution imaging with chemical sensitivity. This technique was used with x-ray energies near the carbon K absorption edge to identify and map separate phases in various polymer blends and to map the DNA distribution in chromosomes with a spatial resolution of 55 nanometers.

Acrylic Resins↗

Rectal cancer risk in patients treated for familial adenomatous polyposis. The Leeds Castle Polyposis Group.

Total colectomy with ileorectal anastomosis (IRA) in familial adenomatous polyposis (FAP) leaves patients at risk for rectal cancer. To assess this risk, the rectal cancer incidence in 297 patients with FAP undergoing IRA since 1951 was determined in the population-based registers of Denmark, Finland and Sweden. At the same time, detailed data on 50 patients with FAP and invasive rectal cancer were obtained from 11 international polyposis registries. The cumulative incidence of rectal cancer was 13.1 per cent at 25 years. The 5-year survival rate of patients with FAP developing rectal cancer was 71 per cent. Combining both studies, the risk of dying from rectal cancer after IRA was 2.0 per cent at 15 years of follow-up. These results justify IRA as primary treatment for most patients; restorative proctocolectomy is preferred for some subgroups. The high all-cause mortality rate observed in this relatively young population necessitates lifelong surveillance of patients with FAP.

Adenomatous Polyposis Coli↗

Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.

Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.

Adult↗

Public health nutrition practices to prevent low birth weight in eight southeastern states.

This study was conducted to identify current public health nutrition practices for the prevention and treatment of low-birth-weight (LBW) infants in eight southeastern states. Nutrition personnel (n = 1,054) were mailed a 51-item questionnaire with three parts that sought information on the respondents' professional backgrounds and employment status and on practice and standards of care for women before and during pregnancy and of LBW infants. Results based on a 62% response rate indicated 73% had worked in public health nutrition for 2 to 9 years, 56% were direct care providers, and 51% had bachelor's degrees. Only 40% of respondents indicated that their agencies had prepregnancy nutrition intervention protocols, whereas 89% indicated that they had high-risk pregnancy screening protocols and 91% indicated that they had high-risk treatment protocols. More than 91% indicated that their treatment protocols included guidelines for weight gain, preparation of nutrition care plans, and assessment of dietary and biochemical factors, health behavior, and obstetric history. Only 73% indicated inclusion of assessment of educational level. Nutritionists saw high-risk pregnant women (or those at risk for preterm labor) slightly more frequently during pregnancy than they saw low-risk women; however, the range (0.9 to 3.8 vs 0.5 to 2.3) and average (2.0 vs 1.2) number of visits for both groups differed only slightly. Nutritionists counseled women and charted in the medical record more frequently than they used nutrition care plans. To reduce LBW, nutritionists should implement treatment protocols and monitor high-risk women closely. The relationship between pre-pregnancy nutrition interventions and birth weight should be investigated.

Birth Weight↗