HLA typing of a Hong Kong Chinese family with intermediate uveitis.
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Adolescent↗
Biomedical subjects
N Collins
Publications and source records attributed to N Collins.
End of life in ICU--care of the dying or 'pulling the plug'?
This study, a modified subsection of the European ETHICUS study on End-of-Life (EOL) Decision Making in the Intensive Care Unit (ICU), examines the pattern of limiting futile life-sustaining therapies in an Irish ICU including the practice of withdrawing mechanical ventilation in anticipation of death. 1146 patients were admitted to the Mater Hospital, Dublin ICU from 1/9/1999 to 30/6/2000 and all 126 patients who died in ICU were included. EOL categories were prospectively defined (by Ethicus methodology) as cardiopulmonary resuscitation (CPR); brain death; withholding (WH); withdrawing (WD) life sustaining therapy and active shortening of the dying process (SDP). Complete data were obtained for 122 of the 126 patients who died during this period. 45 patients (36%) had therapy withheld, 40 (33%) had therapy withdrawn, 26 (21%) had unsuccessful CPR and 11 (10%) were Brain Dead. SDP was not performed. In total, 85 patients had a limitation of life sustaining therapy. CPR was the main therapy withheld (96% of WH/WD patients). Inotropic infusions were limited (WH or WD) in 40/85 (47%) of patients. Fluids, feeding and oxygen were rarely withdrawn (2.4%, 6%, 4.8% respectively). Twenty-two patients had two or more EOL decisions. Tracheal extubation or withdrawal of ventilation was less frequent (16.4%) but more common if a second EOL decision was made. No patient had sedation withdrawn or decreased. Eight patients of 85 (9%) had sedation increased. The study demonstrates that EOL decision making is common (69% of deaths and 7.4% of ICU admissions) in Ireland and demonstrates that the pattern of treatment limitation relates primarily to cardiovascular and other treatments and less to respiratory life sustaining treatment. Artificial nutrition and hydration were rarely withdrawn.
Adult↗
Proton pump inhibitors: a survey of prescribing in an Irish general hospital.
Prescription rates and attendant costs of proton pump inhibitors (PPIs) continue to rise. The aim of this study was to assess the extent and appropriateness of PPI prescribing in an Irish general hospital. Using a structured pro forma, we conducted a 1-day comprehensive survey of the prescription charts of all inpatients. Of the 157 inpatients, 48 (30.6%) were on PPI therapy and omeprazole was the most widely prescribed PPI. Rabeprazole, the least expensive PPI, was the least prescribed. Prescription of PPI therapy was for an approved indication in 32 patients (66.6%) but was for an unapproved or unknown indication in 16 (33.3%). Prescribing had been initiated in hospital in 34 patients (70.8%) but only one-third of the patients on PPI therapy had undergone endoscopy. Over 90% of patients were on additional, often multiple, prescribed medications. Our results suggest that PPIs are overprescribed in hospital practice, and there is scope to improve the quality and cost-effectiveness of PPI prescribing.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Subcutaneous fibrous hamartoma in a foal.
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Animals↗
Decision-making about hormone replacement therapy by women in England and Scotland.
OBJECTIVE: The aim of this study was to explore women's decision-making about the balance of risks and benefits of taking hormone replacement therapy (HRT) based on the latest evidence from the Women's Health Initiative (WHI) trial of combined HRT. METHODS: Women aged 50-69 years, who were eligible for the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) trial, were invited to participate in one of eight focus groups. Participants were asked to discuss their views about taking HRT based on the latest international evidence. RESULTS AND CONCLUSIONS: Eighty-two women participated overall. Qualitative content analysis was applied to the discussion transcripts. Women regarded the decisions they make about taking HRT as highly personal, and, for women currently taking HRT, the overwhelming reason for continuation was perceived improvement in quality of life regardless of either the risks or the benefits in the longer term.
Aged↗
Benefits of multidisciplinary case conferencing using audiovisual compared with telephone communication: a randomized controlled trial.
Multidisciplinary case conferencing using a video-link was compared with multidisciplinary case conferencing by telephone. One hundred patients were randomized to either videoconferencing (intervention group, 50 patients) or audioconferencing (control group, 50 patients). The effectiveness of the intervention compared with the control was evaluated in terms of: the number of conferences per patient, average length of conference, length of treatment, number of occasions of service, degree of multidisciplinary team involvement, recorded level of communication, quality of the management plan (in terms of the number of points contained in it) and staff satisfaction. The intervention and control groups showed significant differences on only two of the outcome measures: the mean number of case conferences per patient was less for the intervention group, and the intervention group had a shorter length of treatment (6 days) than the control group (10 days). The study did not demonstrate any significant differences in occasions of service or time commitment, which might have resulted in lower costs. However, the introduction of case conferencing by video-link was accompanied by a high level of satisfaction on the part of the 14 team members who were interviewed.
Attitude of Health Personnel↗
Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic.
PURPOSE: Data from the Breast Cancer Linkage Consortium suggest that the proportion of familial breast and ovarian cancers linked to BRCA1 or BRCA2 may be as high as 98% depending on the characteristics of the families, suggesting that mutations in BRCA1 or BRCA2 may entirely account for hereditary breast and ovarian cancer families. We sought to determine what proportion of families with both breast and ovarian cancers seen in a breast cancer risk evaluation clinic are accounted for by coding region germline mutations in BRCA1 and BRCA2 as compared to a linkage study group. We also evaluated what clinical parameters were predictive of mutation status. PATIENTS AND METHODS: Affected women from 100 families with at least one case of breast cancer and at least one case of ovarian cancer in the same lineage were screened for germline mutations in the entire coding regions of BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis, a polymerase chain reaction-based heteroduplex analysis, or direct sequencing. RESULTS: Unequivocal deleterious mutations were found in 55% (55 of 100) of the families studied. Mutations in BRCA1 and BRCA2 accounted for 80% and 20% of the mutations overall, respectively. Using multivariate analysis, the strongest predictors of detecting a mutation in BRCA1 or BRCA2 in this study group were the presence of a single family member with both breast and ovarian cancer (P <.0009; odds ratio [OR], 5.68; 95% confidence interval [CI], 2.04 to 15.76) and a young average age at breast cancer diagnosis in the family (P <.0016; OR, 1.69; 95% CI, 1.23 to 2.38). CONCLUSION: These results suggest that at least half of breast/ovarian families evaluated in a high-risk cancer evaluation clinic may have germline mutations in BRCA1 or BRCA2. Whether the remaining families have mutations in noncoding regions in BRCA1, mutations in other, as-yet-unidentified, low-penetrance susceptibility genes, or represent chance clustering remains to be determined.
Adult↗
Resistance gene analogs in barley and their relationship to rust resistance genes.
Regions of amino acid conservation in the NBS domain of NBS-LRR resistance proteins facilitated the PCR isolation of eight resistance gene analog (RGA) sequences from genomic DNA of rice, barley, and Aegilops tauschii. These clones and other RGAs previously isolated from maize, rice, and wheat were assigned to 13 classes by DNA-sequence comparison and by their patterns of hybridisation to restricted barley DNA. Using a doubled-haploid mapping population, probes from 12 RGA classes were used to map 17 loci in the barley genome. Many of these probes have been used for mapping in wheat, and the collective data indicate that the positions of orthologous RGAs are conserved between barley and wheat. RGA loci were identified in the vicinity of barley leaf rust resistance loci Rph4, Rph7, and Rph10. Recombinants were identified between RGA loci and Rph7 and Rph10, while a cluster of RGA sequences detected by probe 5.2 cosegregated with Rph4 in 55 F2 lines.
Blotting, Southern↗
Factors associated with frequent admission to hospital for patients with chronic airflow limitation.
BACKGROUND: Chronic airflow limitation (CAL) is a common cause of admission and readmission to hospital. This study has explored associated factors with repeat hospital admission in patients with CAL. METHOD: A retrospective file review of patients admitted more than once to hospital during the 1999 calendar year, with a diagnosis of CAL. RESULTS: Two hundred and two patients admitted with CAL accounted for 284 admissions and 1815 bed days. Of these, 46 patients were admitted more than once accounting for 115 (40.5%) admissions and 730 (39.8%) bed days. The study found evidence of general practice involvement in 35 (30.5%) admissions immediately before presentation at the hospital emergency department (ED). The discharge summary following that admission revealed only 67 (54%) were referred back to their general practitioners for follow up. The number of admissions attending the ED between the hours of 9.00 am and 5.00 pm were 62 (53.9%) and 96 (83.5%) between the hours of 7.00 am and 10.00 pm. CONCLUSION: Treatments given in hospital were similar, in most cases, to what could be provided at home with appropriate community based support. General practitioners were involved in approximately one-third of those patients requiring admission or re-admission to hospital.
Female↗
Urban stress and mental health among African-American youth: assessing the link between exposure to violence, problem behavior, and coping strategies.
This project examines gender differences in exposure to violence, coping strategies and problem behavior among 306 African-American middle and high school students in the state of Virginia. Gender differences in problem behaviors among youth exposed to violence as either victims or witnesses are examined in addition to variations in coping strategies. Relying on recent research examining violent behavior and victimization events, the study focuses on the internalizing and externalizing behavioral characteristics (i.e., academic achievement, anxiety, depression, negative self-esteem, and delinquency) of urban students exposed to violence and the extent to which coping strategies differ. Results show specific gender differences with regard to problem behavior and coping strategy among African-American youth exposed to violence. For adolescent males, exposure to violence and victimization is strongly associated with externalizing problem behaviors such as delinquency, while adolescent females exposed to violence and victimization are more likely to exhibit internalizing symptoms indicative of post-traumatic stress disorder. Among students exposed to violence and victimization, females are more likely to use problem-focused coping (i.e., social support) as an adaptive strategy in comparison to males. Implications for intervention and future research are discussed.
Adaptation, Psychological↗
Rapid detection of DNA sequence variants by conformation-sensitive capillary electrophoresis.
The identification of novel sequence variants, which may be either disease-causing mutations or silent polymorphisms, in large numbers of samples is becoming the rate-limiting step in associating diseases with specific genes. This is particularly true in light of the imminent arrival of the complete reference sequence of the human genome. A number of techniques have been developed to analyze DNA samples for sequence variants rapidly. We describe a new technique, capillary-based conformation-sensitive gel electrophoresis (capillary CSGE) that transfers mutation detection from acrylamide gel to capillary electrophoresis. Capillary CSGE was able to detect 7/7 short insertion/deletions and 16/22 base substitutions in a series of random single-nucleotide polymorphisms and known variants in the lipoprotein lipase and BRCA2 genes. This technique has the potential to screen many megabases of DNA in a single day.
BRCA2 Protein↗
Microsequence heterogeneity and expression of the LSU rRNA genes within the two single copy ribosomal transcription units of Theileria parva.
The nucleotide sequences of the large subunit ribosomal RNA coding genes within the two single copy ribosomal DNA transcription units of a cloned Theileria parva isolate from a buffalo were determined. The two LSU rRNA coding units differed by 11 nucleotide substitutions and two deletions of 1 and 6 bp, all located in the 5' end of the LSU coding region. We also observed microsequence heterogeneity between the two buffalo parasite LSU sequences and the previously determined LSU rRNA gene of a T. parva parasite isolated from cattle. At all positions which were variable between the two LSU rRNA coding sequences of the buffalo-derived parasite, either unit 1 or unit 2 matched the LSU rRNA coding sequence of the cattle-derived T. parva parasite in a mosaic pattern. Synthetic oligonucleotides specific for LSU units 1 and 2 of the buffalo T. parva were developed, and used to assay expression of the two units. Both units were expressed in the intra-lymphocytic schizont stage of T. parva. A 2.5-10-fold excess of rRNA derived from LSU unit 1, compared with unit 2, was observed in the schizont stage, the difference being attributable to variation in the level of expression of unit 2. Theileria represents the third genus of Sporozoan protozoa, in addition to Plasmodium and Babesia, exhibiting rRNA coding genes, which are divergent in sequence between different transcription units.
Animals↗
A novel approach to studying the migratory morphology of embryonic mesenchymal cells.
A polarized morphology, defined by extension of an anterior pseudopod, is essential for the amoeboid migration of embryonic mesenchymal cells. Leukocytes adopt a similar morphology immediately following suspension in simple buffers containing chemotactic factors. Polarization in suspension therefore provides a rapid and sensitive screening assay for putative regulators of leukocyte migration. The aim of the present study was to investigate whether this assay might also be used to study the motile behaviour of embryonic mesenchymal cells. Primary cultures of mesenchymal cells were established from explants of stage 28 chick embryo corneal-limbal stroma. Serum-starved, subconfluent cultures were harvested using ethylene-diamine tetra-acetic acid and resuspended in Hanks' solution for up to 15 min at 37 degrees C. A variety of cell shapes, including spherical cells, blebbed cells, and cells with either non-polarized or polarized pseudopodia were observed. The proportions of cells with pseudopodia increased significantly over time. Treatment of cells with the chemotactic mitogen platelet derived growth factor-BB (PDGF-BB, homodimer isoform) suppressed blebbing and increased both pseudopod formation and polarization. Optimal polarization occurred in concentrations of PDGF-BB that are similar to those required for optimal chemotaxis (10 ng x mL(-1)). The polarization observed in the absence of PDGF-BB suggests that the migration of cells examined in this study might be controlled at least in part by some intrinsic mechanism. In addition, the strong polarization response to PDGF-BB confirms the role for this growth factor during corneal development. Observations of mesenchymal cell morphology in suspension, therefore provide novel data regarding the motile behaviour of embryonic cells.
Animals↗
Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts.
We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.
Child, Preschool↗
Modulation of paclitaxel resistance by annexin IV in human cancer cell lines.
A recurring problem with cancer therapies is the development of drug resistance. While investigating the protein profile of cells resistant to a novel antimitotic compound (A204197), we discovered an increase in annexin IV expression. When we examined the annexin IV protein expression level in a paclitaxel-resistant cell line (H460/T800), we found that annexin IV was also overexpressed. Interestingly a closely related protein, annexin II, was not overexpressed in H460/T800 cells. Immunostaining with either annexin II or IV antibody revealed that annexin IV was primarily located in the nucleus of paclitaxel-resistant H460/T800 cells. Short-term treatment of H460 cells with 10 nM paclitaxel for up to 4 days resulted in induction of annexin IV, but not annexin II expression. In addition, there was an increase in annexin IV staining in the nucleus starting at day 1. Furthermore, cells pretreated with 10 nM paclitaxel for 4 days resulted in cells becoming approximately fivefold more resistant to paclitaxel. Transfection of annexin IV cDNA into 293T cells revealed that there was a threefold increase in paclitaxel resistance. Thus our results indicate that annexin IV plays a role in paclitaxel resistance in this cell line and it is among one of the earliest proteins that is induced in cells in response to cytotoxic stress such as antimitotic drug treatment.
Annexin A4↗
BRCA1 and BRCA2 mutations in breast cancer families with multiple primary cancers.
Ninety-eight women ascertained from high-risk breast/ovarian cancer clinics with breast cancer reporting at least one other primary cancer in themselves or in a relative with breast cancer were compared with 99 women with breast cancer who reported a family history of breast cancer only. All DNA was screened for coding region mutations in BRCA1 and BRCA2 using heteroduplex analysis, followed by direct sequencing. Our data indicate that 42.9% of families reporting breast and any second nonbreast type of primary cancer in the same individual had a BRCA1 or BRCA2 mutation, as compared with the 12.1% of families reporting breast cancer only (P < 0.001). Among the 66 women reporting breast cancer and a nonovarian second primary cancer, 15 (22.7%) had mutations in BRCA1 or BRCA2 (P = 0.04). Among the 32 families where ovarian cancer was the second primary cancer, 27 (84.4%) had a mutation in BRCA1 or BRCA2 (P < 0.001). BRCA1 and BRCA2 mutations were twice as common in the presence of a reported second nonovarian cancer. These data suggest that the presence of multiple primary cancer of any kind may predict for an increased likelihood of finding a BRCA1 or BRCA2 mutation and supports previous studies suggesting that BRCA1 and BRCA2 mutations may be associated with an increased susceptibility to cancers other than breast and ovarian cancer.
BRCA2 Protein↗
Androgen receptor polymorphisms: association with prostate cancer risk, relapse and overall survival.
Several reports have suggested that one or both of the trinucleotide repeat polymorphisms in the human androgen receptor (hAR) gene, (CAG)n coding for polyglutamine and (GGC)n coding for polyglycine, may be associated with prostate cancer risk; but no study has investigated their association with disease progression. We present here a study of both hAR trinucleotide repeat polymorphisms not only as they relate to the initial diagnosis but also as they are associated with disease progression after therapy. Lymphocyte DNA samples from 178 British Caucasian prostate cancer patients and 195 control individuals were genotyped by PCR for the (CAG)n and (GGC)n polymorphisms in hAR. Univariate Cox proportional hazard analysis indicated that stage, grade and GGC repeat length were individually significant factors associated with disease-free survival (DFS) and overall survival (OS). The relative risk (RR) of relapse for men with more than 16 GGC repeats was 1.74 (95% CI 1. 08-2.79) and of dying from any cause, 1.98 (1.13-3.45). Adjusting for stage and grade, GGC effects remained but were not significant (RR(DFS)= 1.60, p = 0.052; RR(OS)= 1.65, p = 0.088). The greatest effects were in stage T1-T2 (RR(DFS)= 3.56, 95% CI 1.13-11.21) and grade 1 (RR(DFS)= 6.47, 95% CI 0.57-72.8) tumours. No differences between patient and control allele distributions were found by odds-ratio analysis, nor were trends with stage or grade evident in the proportion of short CAG alleles. Non-significant trends with stage and grade were found in the proportion of short GGC alleles. The (GGC)n polymorphism in this population is a significant predictor of disease outcome. Since the (GGC)(n) effect is strongest in early-stage tumours, this marker may help forecast aggressive behaviour and could be used to identify those patients meriting more radical treatment.
Aged↗