New complexities for BRCA1 and BRCA2.
A large number of diverse functions have been attributed to the BRCA1 and BRCA2 breast cancer susceptibility genes. Here we review recent progress in the field.
BRCA1 Protein↗
Biomedical subjects
P Kerr
Publications and source records attributed to P Kerr.
Genetic variation in Australian isolates of myxoma virus: an evolutionary and epidemiological study.
Myxoma virus and the European rabbit have been coevolving in Australia since the introduction of the Standard Laboratory Strain (SLS) of myxoma virus as a biological control agent for rabbits in 1950. To examine the degree of genetic variation that has occurred in the virus between 1950 and 1995 and to find genetic markers to use for epidemiological studies, we have examined 37 recent field isolates of myxoma virus for restriction fragment length polymorphisms (RFLPs) by comparision with the progenitor SLS released in 1950. Fifteen RFLPs in Australian isolates have been identified and characterized by mapping and partial DNA sequence analysis. The RFLPs that are most common are deletion and insertion events in regions of tandem repeats. Some of these RFLPs have been investigated by using polymerase chain reaction to identify them in archival tissue samples. In epidemiological studies we characterized two polymorphisms which occur in the Lausanne strain of myxoma virus (widely introduced into Australia from the 1970s) but not in SLS and showed that all of the viruses we isolated were derived from the SLS.
Amino Acid Sequence↗
Fixation location effects on fixation durations during reading: an inverted optimal viewing position effect.
Previous research has found that words are identified most quickly when the eyes are near their center (the Optimal Viewing Position effect). A study was conducted to determine whether this same phenomenon is observed during reading, as revealed by a relationship between fixation position in a word and the duration of the fixation. An analysis of three large existing corpora of eye movement data, two from adults and one from children, showed a surprising inverted Optimal Viewing Position curve: mean fixation duration is greatest, rather than lowest, when the eyes were at the centers of words. From this phenomenon, we suggest an alternative explanation to the fixation duration trade-off effect in word refixations [O'Regan & Lévy-Schoen, Attention and performance XII: the psychology of reading (1987)]; the phenomenon also contradicts expectations of both oculomotor and cognitive theories of eye movement control. Attempts to test alternative explanations led to the discovery of another phenomenon, the Saccade Distance effect: mean fixation durations vary with the distance of the prior fixation from the currently-fixated word, being longer with greater distances. The durations of fixations in reading are complexly determined, with influences both from language and perceptual/oculomotor levels.
Adult↗
Development of a monoclonal sandwich ELISA for the detection of animal and human Escherichia coli O157 strains.
AIMS: Production of a monoclonal antibody (MAb) to Escherichia coli O157 to develop a rapid test using a sandwich ELISA (sELISA) format. METHODS AND RESULTS: A MAb (7A6) was developed to the long-chain lipopolysaccharide of E. coli O157. A sELISA developed with the MAb reacted with 28 bovine and seven human enterohaemorrhagic E. coli (EHEC) O157 strains and also with two enterotoxigenic E. coli O157 strains. Cross-reaction to a rabbit diarrhoeal E.coli O15, Citrobacter freundii, Salmonella urbana and Vibrio cholerae O1 Inaba was detected. CONCLUSION: A MAb-based sELISA to detect E. coli O157 was produced. Its application to field samples is required to fully determine its prospective use for the detection of EHEC O157, to evaluate the non-specific interference of the cross-reacting strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The assay produced is not wholly specific to EHEC O157, but has the potential to be used as a rapid method for screening large numbers of samples for E. coli O157.
Animals↗
A comparison of a monoclonal antibody-based sandwich ELISA and immunomagnetic bead selective enrichment for the detection of Escherichia coli O157 from bovine faeces.
AIMS: To compare a recently developed monoclonal antibody (MAb) based sandwich ELISA (sELISA) with an immunomagnetic separation (IMS) method for the detection of Escherichia coli O157 in bovine faeces. METHODS AND RESULTS: Faecal samples from 345 cattle were obtained from eight farms in Northern Ireland, in which human disease due to E. coli O157 had occurred. Both assays detected E. coli O157 on five of the farms and the phage-type of the majority of the bovine strains were the same as the corresponding human isolates. Similar numbers of the organism were detected by the two methods, 59 by the sELISA and 53 by the IMS procedure, 39 of the positive samples being common to both. Twenty samples were sELISA positive/IMS negative. CONCLUSIONS: If the IMS is regarded as the gold standard, then the sELISA is less sensitive and less specific, but under the conditions used sELISA positive results were obtained from all positive farms, and the sELISA gave a presumptive positive a day earlier than the IMS method. SIGNIFICANCE AND IMPACT OF THE STUDY: The sELISA has the potential to be used as a rapid method for screening large numbers of samples for E. coli O157, but further work is required to determine its specificity.
Animals↗
A cost-minimization analysis of the societal costs of realtime teledermatology compared with conventional care: results from a randomized controlled trial in New Zealand.
A randomized controlled trial was carried out to measure the societal costs of realtime teledermatology compared with those of conventional hospital care in New Zealand. Two rural health centres were linked to a specialist hospital via ISDN at 128 kbit/s. Over 10 months, 203 patients were referred for a specialist dermatological consultation and 26 were followed up, giving a total of 229 consultations. Fifty-four per cent were randomized to the teledermatology consultation and 46% to the conventional hospital consultation. A cost-minimization analysis was used to calculate the total costs of both types of dermatological consultation. The total cost of the 123 teledermatology consultations was NZ$34,346 and the total cost of the 106 conventional hospital consultations was NZ$30,081. The average societal cost of the teledermatology consultation was therefore NZ$279.23 compared with NZ$283.79 for the conventional hospital consultation. The marginal cost of seeing an additional patient was NZ$135 via teledermatology and NZ$284 via conventional hospital appointment. From a societal viewpoint, and assuming an equal outcome, teledermatology was a more cost-efficient use of resources than conventional hospital care.
Cost Savings↗
Radiofrequency tissue reduction of the palate in patients with moderate sleep-disordered breathing.
OBJECTIVE: Radiofrequency volumetric reduction of the palate has been advocated as a treatment for mild sleep-disordered breathing (SDB). Our study examines the efficacy of this procedure on patients with mostly moderate SDB. DESIGN: Prospective, nonrandomized, consecutive series. SETTING: St. Boniface Hospital, Sleep Disorders Centre, University of Manitoba, Winnipeg. METHOD: Twelve patients with polysomnographically proven moderate SDB were given a total of 2400 to 3600 joules of radiofrequency energy to their soft palate over two to three treatments. Follow-up examined the effect of treatment on subjective and objective parameters including the Epworth Sleepiness Scale, loudness of snoring, Apnea-Hypopnea Index (AHI), and Arousal Index. RESULTS: Two of 12 patients had a good objective response to treatment in that their AHI dropped by more than 50% and to a value of less than 20. However, none of the patients claimed to have a satisfactory subjective response. There was a slight reduction in the mean AHI from 31.2+/-5.1 to 25.3+/-4.2 (p < .05), but no clinically significant difference was found between pre- and post-treatment groups with respect to other sleep parameters. There was no improvement in daytime sleepiness or snoring. CONCLUSIONS: Radiofrequency tissue ablation of redundant soft palate tissues lacks clinical efficacy in patients with moderate SDB.
Adult↗
Carotid artery intima-medial thickness is increased in chronic renal failure.
1. Chronic renal failure (CRF) is associated with rapidly progressive atherosclerotic vascular disease. In the present study, carotid arterial intima-medial thickness (IMT) was assessed in a large cohort of patients with CRF and matched controls and related to risk factors. 2. A total of 159 subjects with CRF (serum creatinine > or =0.40 mmol/L) aged > 50 years (mean (+/-SD) 63.8+/-7.7 years) and 159 healthy controls matched for age, sex and smoking status were studied. 3. The IMT was determined using B-mode ultrasound measurements of the far wall of both common carotid arteries and presented as the mean IMT. Fasting plasma homocysteine (tHcy) was measured in the CRF group. 4. Intima-medial thickness was significantly greater in CRF patients than controls (0.89+/-0.17 vs 0.73+/-0.13 mm, respectively) after matching for age, sex and smoking status. Heart rate and pulse pressure were also significantly increased. The tHcy was increased two-fold in the CRF group (27.7+/-11.3 micromol/L; normal < 13.0 micromol/L) and did not correlate with carotid IMT. 5. Compared with controls after adjusting for traditional risk factors, patients with CRF exhibit significantly increased IMT.
Blood Pressure↗
Patient cost-benefits of realtime teledermatology--a comparison of data from Northern Ireland and New Zealand.
As part of a randomized controlled trial of the costs and benefits of realtime teledermatology in comparison with conventional face-to-face appointments, patients were asked to complete a questionnaire at the end of their consultation. One hundred and nine patients took part in an initial teledermatology consultation and 94 in a face-to-face consultation. The proportion of patients followed up by the dermatologist was almost the same after teledermatology (24%) as after a hospital appointment (26%) and for similar reasons. Two hundred and three questionnaires were completed after the first visit and a further 20 after subsequent visits. Patients seen by teledermatology at their own health centre travelled an average of 12 km, whereas those who attended a conventional clinic travelled an average of 271 km. The telemedicine group spent an average of 51 min attending the appointment compared with 4.3 h for those seen at the hospital. The results of the present study, as in a similar study conducted in Northern Ireland, show that the economic benefits of teledermatology favour the patient rather than the health-care system.
Computer Systems↗
Family-focused case management: a case study of an innovative demonstration program.
Using results from a formative evaluation, the paper describes family-focused case management (FFCM). FFCM is an innovative community mental health service designed to support both consumers/survivors and their families. The formative evaluation used a multi-informant, multi-method approach to describe FFCM services and assess their quality. Focus groups with program stakeholders produced a "program-logic model" and identified minimum standards for FFCM. Service activities and outcomes defined in the program-logic model were typical of those offered to consumers/survivors in intensive case management programs, but were supplemented with support being offered to their families. Monitoring of service activities showed that the case manager had regular contact with families and offered them a mix of direct and indirect services that corresponded, in most cases, to defined program standards. Interviews with 14 family members and 8 consumers/survivors receiving FFCM services revealed high levels of satisfaction with most aspects of the program. Overall, evaluation findings suggest that intensive case management can be expanded to include providing support to families. Future directions for developing FFCM are discussed.
Case Management↗
An intrinsic timer that controls cell-cycle withdrawal in cultured cardiac myocytes.
Developing cardiac myocytes divide a limited number of times before they stop and terminally differentiate, but the mechanism that stops their division is unknown. To help study the stopping mechanism, we defined conditions under which embryonic rat cardiac myocytes cultured in serum-free medium proliferate and exit the cell cycle on a schedule that closely resembles that seen in vivo. The culture medium contains FGF-1 and FGF-2, which stimulate cell proliferation, and thyroid hormone, which seems to be necessary for stable cell-cycle exit. Time-lapse video recording shows that the cells within a clone tend to divide a similar number of times before they stop, whereas cells in different clones divide a variable number of times before they stop. Cells cultured at 33 degrees C divide more slowly but stop dividing at around the same time as cells cultured at 37 degrees C, having undergone fewer divisions. Together, these findings suggest that an intrinsic timer helps control when cardiac myocytes withdraw from the cell cycle and that the timer does not operate by simply counting cell divisions. We provide evidence that the cyclin-dependent kinase inhibitors p18 and p27 may be part of the timer and that thyroid hormone may help developing cardiac myocytes stably withdraw from the cell cycle.
Animals↗
Use of a monoclonal antibody against an Escherichia coli O26 surface protein for detection of enteropathogenic and enterohemorrhagic strains.
A monoclonal antibody (MAb) was obtained from a mouse immunized with solubilized outer membrane proteins extracted from a bovine enterohemorrhagic strain of Escherichia coli (EHEC), O26. The MAb produced a strong immunoblot reaction at approximately 21 kDa for an O26 strain containing the intimin gene (eae) and verocytotoxin (VT), but not with an O26 eae- and VT-negative strain, or O157 eae- and VT-positive strains. The MAb was used in a sandwich enzyme-linked immunosorbent assay (ELISA) format to screen strains from animal and human sources, and all reactive strains were characterized for the presence of eae and the gene encoding VT factors by PCR. The antigen was detected in a group of strains containing a high proportion of O26, the majority of which were eae positive with or without VT; these were isolated mostly from animal enteritis cases but included a small number of human enteric isolates. Nonreactors included eae-positive (with or without VT) O157 strains and one O26 strain. In a survey of mixed cultures from both animal and human enteric disease, ELISA-positive reactions were obtained from 7.1 to 11.2% of samples from bovine, porcine, ovine, and human sources. The two human O8 and ten animal O26 ELISA-reactive pure strains obtained from these samples contained six eae- and/or VT-positive strains; the other six strains lost their ELISA positivity following storage at -70 degrees C, after which none were found to contain either eae or VT factors. The association of the antigen detected by the MAb with significant enteropathogenic E. coli and EHEC virulence factors in isolates from both animal and human enteric infections indicates a diagnostic potential for the assay developed.
Animals↗
Use of patient-specific estimates in patient evaluation and rehabilitation.
For a number of years we have been using open-ended questionnaires in the assessment of hearing disability and handicap, tinnitus complaint behaviour together with shortcomings and benefits of various rehabilitative interventions. More recently we have applied this approach to positive experiences reported by adults who have developed a hearing impairment and to the use of silence or social withdrawal as a communication tactic. In addition, we have asked individuals to rate the magnitude of each of their listed disabilities, handicaps, shortcomings, etc., on a scale to provide a qualitative assessment of each of these elements important to the individual. Such a procedure can be repeated after the intervention to measure changes in such estimates. This approach can thus highlight for the therapist, those elements of the patients' problems which are being well or poorly addressed and hence help them to concentrate their effort on the latter. Results obtained using this technique are presented and discussed.
Aged↗
Progress towards using recombinant myxoma virus as a vector for fertility control in rabbits.
The history of myxoma virus, its use in Australia as a mortality agent and the development of the virus as a vector for controlling fertility in wild rabbit populations in Australia is reviewed. Myxoma virus recombinants have been constructed to express model antigens. Four potential insertion sites in the genome have been identified and two have been used to construct single and double recombinant viruses expressing Escherichia coli enzymes beta-galactosidase and beta-glucuronidase. Another recombinant expressing an influenza virus haemagglutinin gene (A/PR8/34) induced high and sustained antibody responses following intradermal inoculation in rabbits. To demonstrate the potential of introducing a recombinant virus into wild rabbit populations, a virus containing a natural deletion was released at four field locations. Preliminary analysis of the data has shown that the introduced virus spread well on 3 of the 4 locations. The steps being taken to address the ethical and safety implications of the introduction of a recombinant virus into the field are discussed.
Animals↗
Ocular manifestations of autosomal recessive Alport syndrome.
Ocular abnormalities are common in X-linked Alport syndrome, but they have not been studied in patients with the rarer autosomal recessive disease. We have examined the eyes of a family with autosomal recessive Alport syndrome. Four of the eight offspring of a consanguineous marriage had renal failure and deafness by the age of 20 years. The diagnosis of Alport syndrome was confirmed on the ultrastructural demonstration of a lamellated glomerular basement membrane (GBM) in one affected family member. Autosomal recessive inheritance was suggested by the lack of linkage to the COL4A5/COL4A6 locus, and by linkage to the COL4A3/COL4A4 locus. All four affected family members had anterior lenticonus (or had had a lens replacement for this) and the three who were examined had a dot-and-fleck retinopathy. Neither of the two unaffected offspring who were examined nor the father had these abnormalities. The ocular manifestations of autosomal recessive Alport syndrome are probably identical to those for the X-linked form. Although the mutations in these diseases affect genes for different type IV collagen chains, these chains occur together in the basement membranes of the kidney, eye and ear, and abnormalities in any one may result in the same clinical phenotype.
Adult↗
Effect of severe gastroesophageal reflux on sleep stage in patients with aperistaltic esophagus.
Polysomnography and esophageal pH studies were conducted in 13 patients with an aperistaltic esophagus; seven of these had scleroderma and six were patients treated for achalasia. The percentage total time of pH<4.0 when recumbent exceeded 30% for both groups. There was a total of 51 reflux events for both groups. There were 22 reflux events recorded for both groups that were less than 5 min in length and 29 events greater than 5 min. In 26 of 32 (81%) instances, patients either began awake and went to sleep during a reflux event or did not awake during a reflux event. Only six of 32 (19%) reflux events caused sleep disruption. We conclude that even the severe reflux demonstrated in this subset of patients does not always disrupt sleep. Patients may have severe prolonged reflux and not arouse.
Acute Disease↗
Long-stay patients with mental health problems and learning difficulties: selection and preparation for community living.
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Activities of Daily Living↗
Treatment outcome of squamous cell carcinoma of the oral tongue.
Treatment outcome was retrospectively assessed in 106 patients with squamous cell carcinoma of the oral tongue registered in the population-based Manitoba Cancer Registry between January 1979 and December 1992. Twenty-six percent were diagnosed with stage I lesions, while 33%, 16%, and 24% were stage II, III, and IV, respectively. Most patients with stage I and II disease were treated with either surgery alone (57%) or in combination with radiotherapy (29%). Advanced lesions were generally treated with radiotherapy alone (37%) or in combination with surgery (35%). Actuarial survival at 5 years was 44% for all patients, and 64%, 46%, 42%, and 16% for stages I to IV, respectively. Over 90% of the 35 treatment failures occurred within 24 months. The initial sites of recurrence were the neck in 22 patients, the primary site in 16 patients, and distant metastases in 5 patients. At the time of death, disease was present above the clavicles in 62%, and metastases were identified in 22%. Locoregional control remains a significant problem in oral cancer. Elective treatment of the neck, resection of the primary with negative surgical margins, and the use of combined modality treatment in advanced stages of disease may help reduce treatment failure.
Adult↗