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Biomedical subjects

P Murphy

Publications and source records attributed to P Murphy.

At least 127 records · Page 7Linked to original sources

Differential diagnoses of influenza A virus, influenza B virus, and respiratory syncytial virus infections by direct immunofluorescence using mixtures of monoclonal antibodies of different isotypes.

Differences between isotypes of monoclonal antibodies were employed to detect influenza A and B viruses and respiratory syncytial virus by direct immunofluorescence using fluorescein isothiocyanate or Texas Red conjugates. Examination of 56 specimens for influenza A and B viruses and 112 specimens for influenza A virus and respiratory syncytial virus showed the mixed-isotype test to be comparable to the conventional procedure.

Antibodies, Monoclonal↗

Correlation between apoptosis, proliferation and bcl-2 expression in malignant non-Hodgkin's lymphoma.

Aim-To investigate whether clinical features of non-Hodgkin's lymphomas, at the time of first biopsy, correlate with studies of cell proliferation and cell death as well as with the level of bcl-2 expression.Methods-Bcl-2 expression, determined by immunocytochemistry, was compared with cell proliferation, measured using in situ hybridisation for histone mRNA, and cell death by apoptosis, measured using in situ end labelling for DNA cleavage.Results-Histone mRNA staining gave a labelling index of 30% of cells for reactive germinal centres, 5.2-13.5% of cells for low grade non-Hodgkin's lymphoma and 12.1-50.5% of cells for high grade non-Hodgkin's lymphoma. In situ end labelling gave a labelling index of 5.0-10.0% of cells for reactive germinal centres, 1.0-3.7% of cells for low grade non-Hodgkin's lymphoma and 4.7-13.5% of cells for high grade non-Hodgkin's lymphoma. There was a positive correlation between apoptotic index and proliferation index. More cases of low grade than high grade non-Hodgkin's lymphoma expressed bcl-2. There was no correlation between apoptotic index and bcl-2 expression for high grade non-Hodgkin's lymphoma.Conclusions-The molecular mechanisms controlling cell proliferation and death in non-Hodgkin's lymphoma are complex, probably involving a range of genes, including bcl-2. A better understanding of resistance to cell death is needed if the clinical goal of tailoring cancer treatment to individual tumours is to be achieved.

Journal Article↗

Linkage study of the D5 dopamine receptor gene (DRD5) in multiplex Icelandic and English schizophrenia pedigrees.

OBJECTIVE: The authors investigated the possibility that genetic variation or mutation of the dopamine D5 receptor gene might modify susceptibility to schizophrenia. METHOD: Twenty-three Icelandic and English pedigrees containing multiple cases of schizophrenia were genotyped by using a highly informative microsatellite for the D5 dopamine receptor gene DRD5. RESULTS: By means of three different affection models, negative lod scores were obtained under assumptions of autosomal dominant and recessive inheritance. There was no evidence for locus heterogeneity. Nonparametric extended relative pair analysis also produced negative results. CONCLUSIONS: These data indicate that mutations of the D5 dopamine receptor gene are not a major cause of schizophrenia in these pedigrees. Because of the probable existence of locus heterogeneity, the D5 receptor gene may be of etiologic importance in other families with schizophrenia.

Base Sequence↗

Lack of evidence for close linkage of the glutamate GluR6 receptor gene with schizophrenia.

OBJECTIVE: Previous research has consistently implicated genetic factors in the pathogenesis of schizophrenia. It has been hypothesized that an abnormality in glutamatergic function is of etiologic importance in schizophrenia, and therefore the glutamate receptor family of genes are potential susceptibility loci for schizophrenia. To test this hypothesis the authors sought to detect linkage between the GluR6 glutamate receptor gene and schizophrenia. METHOD: Twenty-three English and Icelandic families containing multiple cases of schizophrenia were genotyped with a microsatellite trinucleotide repeat polymorphism localized at the GluR6 glutamate receptor locus. Lod scores, model-free linkage analysis, and extended relative pair analysis were used to test for linkage. RESULTS: No statistically significant evidence of linkage between GluR6 and schizophrenia was found. CONCLUSIONS: The results do not support the hypothesis that GluR6 allelic variants provide a major gene contribution to the etiology of schizophrenia in a large proportion of these pedigrees.

Alleles↗

Further tests for linkage of bipolar affective disorder to the tyrosine hydroxylase gene locus on chromosome 11p15 in a new series of multiplex British affective disorder pedigrees.

OBJECTIVE: This study was undertaken to confirm or refute previous reports that link bipolar affective disorder to polymorphic DNA markers at or near the gene for tyrosine hydroxylase. METHOD: A previous linkage analysis, which used a tetranucleotide repeat polymorphism at the tyrosine hydroxylase locus, of six Icelandic families was extended to include a new series of 17 multiply affected British families. RESULTS: Overall lod scores under the assumption of locus heterogeneity were between 1.20 and 1.40 at zero recombination with tyrosine hydroxylase, and these scores persisted across three affective disorder models. CONCLUSIONS: These results provide some support for linking affective disorder to this genetic region and suggest that additional linkage and association studies should be conducted to determine whether tyrosine hydroxylase or a nearby locus contributes to susceptibility to bipolar affective disorder in some families.

Alleles↗

Ectopic pregnancy loss during fertility management.

Using qualitative techniques, data were obtained from seven women who experienced an ectopic pregnancy loss while undergoing fertility management. Ectopic pregnancy is a risk factor associated with fertility management, but unlike early miscarriage in fertility management, an ectopic pregnancy has additional potential negative sequelae for the women, including risk for severe hemorrhage and death and threat to future fertility. The purpose of this study was to describe women's experiences of loss following diagnosis and treatment of an ectopic pregnancy while undergoing fertility management. A thematic analysis of the data derived from semistructured interviews was conducted. Themes emerging from the women's discussion of their pregnancy loss and fertility plans included physical pain and shutdown, emotional protection, grief, and pressure, endpoints, and decision making. For women continuing fertility management, both the life-threatening risks of future ectopics and time allowances for grieving were minimized.

Abortion, Spontaneous↗

The regulation of Krox-20 expression reveals important steps in the control of peripheral glial cell development.

The zinc finger transcription factor gene Krox-20 is expressed in Schwann cells and is required for the myelination of peripheral nerves. We show that the regulation of Krox-20 expression in peripheral glial cells reveals three important steps in the development and differentiation of these cells. (i) Expression of Krox-20 in Schwann cells requires continuous neuronal signalling via direct axonal contact. Therefore Krox-20 appears to be a key component of the transduction cascade linking axonal signalling to myelination. (ii) Krox-20 inducibility is acquired by Schwann cells at the time that they are formed from their precursors. Diffusible factor(s) synthesised by the neural tube can mediate this transition and can be mimicked by NDFbeta or a combination of CNTF and bFGF. Furthermore, the neural tube activity is blocked by a hybrid protein containing the NDF-binding domain of the ErbB4 receptor, strongly implicating NDF in the physiological transition. (iii) In sensory ganglia, the microenvironment is capable of negatively regulating Krox-20, presumably by preventing the conversion of satellite glial cells toward a Schwann cell-like phenotype.

Animals↗

Genetic counseling in hereditary nonpolyposis colorectal cancer: an extended family with MSH2 mutation.

OBJECTIVES: Molecular genetic advances have increased the demand for DNA testing. We describe DNA based genetic counseling in a hereditary nonpolyposis colorectal cancer (HNPCC) family. METHODS: This extended HNPCC family was found to harbor the MSH2 germline mutation. Family history, medical, and pathology documents enabled us to secure a high degree of verification that the kindred qualified as HNPCC. DNA testing revealed the MSH2 germline mutation that was verified independently in two laboratories. Genetic counseling was provided before DNA testing and disclosure of MSH2 findings. RESULTS: Genetic counseling revealed a variety of findings characterized by emotional stress in MSH2 germline mutation carriers. Concerns centered around reproductive issues, potential transmission of the deleterious gene to their progeny, and discrimination by insurance carriers and employers. More than one-half of the patients found to harbor the MSH2 mutation considered the option of prophylactic subtotal colectomy. CONCLUSION: DNA testing should be restricted to well-verified candidate families in which genetic counseling should be mandatory. HNPCC family members sought genetic risk assessment for their own health and that of their children. Contrasting emotional responses took place when told of their gene testing status and this required a sensitive empathetic listening ear. Patients have many concerns about their lifetime cancer destiny when told that they harbor the culprit MSH2 germline mutation.

Adult↗

Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer.

OBJECTIVE: To evaluate measurement of serum prostate specific antigen as a potential screening test for future clinical prostate cancer among healthy men. DESIGN: Nested case-control study with stored serum samples collected from 49,261 men with follow up using national death and cancer registration systems. SUBJECTS: 265 asymptomatic men who subsequently developed clinical prostate cancer and 1055 controls matched for age, study centre, and duration of storage of samples. MAIN OUTCOME MEASURES: Distribution of concentrations of the antigen in men who developed prostate cancer and in controls. RESULTS: Prostate specific antigen concentrations were significantly higher in men who subsequently developed prostate cancer than in controls. In the first three years after blood collection the median concentration was 23 times greater in cases than in controls of the same age at the same centre (that is, 23 multiples of the median). A smaller difference persisted thereafter; 4.0 multiples of the median 3-6 years after blood collection, 3.6 6-10 years, and 1.8 after 10 years. In the first three years the proportion of men who developed prostate cancer and had raised levels of the antigen (> or = 12 multiples of the median) (detection rate or sensitivity) was 81% (95% confidence interval 54% to 96%). The proportion of men who did not develop prostate cancer but had levels this high (false positive rate) was only 0.5%. CONCLUSION: Prostate specific antigen measurement is a highly discriminatory screening test for prostate cancer among healthy men. In the general population, 60-74 year old men who had > or = 12 times the normal median level would have about a 50% chance of developing clinical prostate cancer in the next three years. Measurement of this antigen is a good enough screening test to justify a randomised controlled trial to determine any reduction in mortality from prostate cancer.

Aged↗

UKCCCR multicentre randomised controlled trial of one and two view mammography in breast cancer screening.

OBJECTIVE: To compare one view (oblique) and two view (oblique and craniocaudal) mammography in breast cancer screening. DESIGN: Randomised controlled trial. SETTING: Nine breast screening centres in England. SUBJECTS: 40,163 women aged 50-64 attending their first breast screening examination. INTERVENTIONS: Women were randomised to have one view mammography, two view mammography, or two view mammography in which one view was read by one reader and both views were read by another. MAIN OUTCOME MEASURES: Prevalence of cancer detected, recall rates, cost per cancer detected, and marginal cost per extra cancer detected. RESULTS: Two view mammography detected 24% more women with breast cancer (95% confidence interval 16% to 31%) than one view mammography. Prevalence of detected cancer was 6.84 with two view mammography and 5.52 per 1000 women with one view. The proportion of women recalled for assessment was 15% lower (95% confidence interval 6% to 23%) with two view (6.97%) than with one view (8.16%) mammography. The cost of two view screening was higher (26.46 pounds compared with 22.00 pounds per examination) but the average cost per cancer detected was similar (5330 pounds compared with 5310 pounds) and the marginal cost per extra cancer detected with two views was similar to the average cost (5400 pounds). CONCLUSION: Two view mammography is medically more effective than one view; it detects more cancers and reduces recall rates; it is also similarly cost effective financially.

Breast Neoplasms↗

Linkage analysis of chromosome 22q12-13 in a United Kingdom/Icelandic sample of 23 multiplex schizophrenia families.

A possible linkage to a genetic subtype of schizophrenia and related disorders has been reported on the long arm of chromosome 22 at q12-13. (Pulver et al., 1994: Am J Med Genet 54:36-43; Coon et al., 1994: Am J Med Genet 54:72-79; Pulver et al., 1994: Am J Med Genet 54:44-50). However formal statistical tests in a combined sample could not reject homogeneity and prove that there was a linked subgroup of families. We have studied 23 schizophrenia pedigrees to test whether some multiplex schizophrenia families may be linked to the microsatellite markers D22S274 and D22S283 which span the 22q12-13 region. Two point followed by multipoint lod and non-parametric linkage analyses under the assumption of heterogeneity provided no evidence for linkage over the relevant region.

Chromosomes, Human, Pair 22↗

Time-quantified fetal movement detection with two-transducer data fusion.

OBJECTIVE: Our purpose was to develop an automated ultrasound-based fetal movement detection system to better define fetal movements. STUDY DESIGN: One hundred one patients had fetal movements recorded over a 20-minute period. Results of movement detection by a single-transducer system (Russell 1) and a two-transducer fusion system (Russell 2) were compared with those of Hewlett-Packard (HP-M-1350-A), maternal perception, and expert ultrasonography review. RESULTS: A total of 86,592 seconds of videotape was scored for fetal movement. Russell 2 had a second-per-second sensitivity of 57.21% compared with Russell 1 at 40.95%, the HP-M-1350-A at 31.44%, and maternal perception at 30.80%. Russell 2 detected 67.57% of discrete movements compared with 57.52%, 41.98%, and 37.92%, respectively, in other systems. CONCLUSION: Russell 2 represents a significant improvement over existing systems in detection of fetal movements on a second-per-second basis.

Adolescent↗

Colour duplex in assessing the infrainguinal arteries in patients with claudication.

Non-invasive assessment of the lower-limb vasculature may avoid unnecessary arteriography. Colour duplex scanning of the femoral and popliteal arteries was performed in claudicants who were potential candidates for endoluminal therapy. This was compared with the findings of biplanar conventional arteriography and intra-arterial digital subtraction angiography. In 112 lower limbs duplex gave the following results compared with angiography: the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for occlusions (n = 48), stenoses (n = 31), atheromatous vessel (n = 21) and disease-free (n = 12) were all greater or equal to 94%. The lengths of the occlusions were accurately identified by duplex. Clinical examination and spectral analysis at the common femoral artery failed to identify two patients who had an iliac lesion. Colour duplex examination is the investigation of choice in assessing the major infrainguinal arteries in patients with claudication.

Adult↗

Complications of day-case angiography using 5F catheters.

Questionnaires were sent retrospectively to patients who had undergone day-case angiography at a British teaching hospital to evaluate the complications suffered after leaving hospital. In 1992, 5F catheters were used in 61 day-case patients. On analysis of the responses and detailed follow-up in areas of concern, no unexpected complication was found. It is concluded that day-case angiography using 5F catheters is associated with low morbidity after discharge home.

Ambulatory Care↗

The role of thrombolysis in the management of thromboembolic disorders: a four-year review.

OBJECTIVE: To examine the role of thrombolysis alone, or in conjunction with surgery and angioplasty, in the treatment of thromboembolic disorders. DESIGN: A retrospective review of 70 patients, who received thrombolysis on 73 occasions between 1990 and 1993. PATIENTS AND METHODS: Four groups were defined: (1) thrombolysis alone (40%); (2) thrombolysis followed by angioplasty (23%); (3) thrombolysis followed by surgery (13%) and (4) thrombolysis after failed angioplasty (24%). RESULTS: Twenty-eight patients (40%) received thrombolysis alone of which 13 were successful. In 25 cases (36%) thrombolysis was initially successful in that it permitted further angioplasty or surgical reconstruction. This adjunctive treatment was successful in 16 cases. Overall, when used as a first-line treatment, thrombolysis was successful in 72% of cases. Success in this context includes those in which a further procedure was possible after thrombolysis. These groups included 20 occluded grafts in which thrombolysis played an important part in unblocking 13 (65%) of them. In a separate group of 17 patients (24%) thrombolysis was given after failed angioplasty and was successful on 15 (88%) occasions. Local complications occurred in 17 patients. There were three deaths. There were no intra-cerebral haemorrhages. CONCLUSIONS: Thrombolysis alone can be used successfully. There is a large group in which thrombolysis can help to increase the success rate of interventional radiology.

Adult↗