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M F Murphy

Publications and source records attributed to M F Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2001

Technical optimization of RhD zygosity determination by real-time quantitative polymerase chain reaction: implication for fetal RhD status determination by maternal plasma.

We have recently reported the development of a multiplex, real-time quantitative polymerase chain reaction (PCR) assay for RhD zygosity determination based on the coamplification and quantification of RHD-specific sequences in relation to a reference gene, albumin. This paper discusses the optimization procedure and technical parameters of this multiplex assay.

Albumins↗
PubMed2001

Determination of RhD zygosity: comparison of a double amplification refractory mutation system approach and a multiplex real-time quantitative PCR approach.

BACKGROUND: Rh isoimmunization and hemolytic disease of the newborn still occur despite the availability of Rh immunoglobulin. For the prenatal investigation of sensitized RhD-negative pregnant women, determination of the zygosity of the RhD-positive father has important implications. The currently available molecular methods for RhD zygosity assessment, in general, are technically demanding and labor-intensive. Therefore, at present, rhesus genotype assessment is most commonly inferred from results of serological tests. The recent elucidation of the genetic structure of the prevalent RHD deletion in Caucasians, as well as the development of real-time PCR, allowed us to explore two new approaches for the molecular determination of RhD zygosity. METHODS: Two methods for RhD zygosity determination were developed. The first was based on the double Amplification Refractory Mutation System (double ARMS). The second was based on multiplex real-time quantitative PCR. For the double ARMS assay, allele-specific primers were designed to directly amplify the most prevalent RHD deletion found in RhD-negative individuals in the Caucasian population. The multiplex real-time quantitative PCR assay, on the other hand, involved coamplification and quantification of RHD-specific sequences in relation to a reference gene, albumin, in a single PCR reaction. A ratio, DeltaCt, based on the threshold cycle, was then determined and reflects the RHD gene dosage. RESULTS: The allele-specific primers of the double ARMS assay reliably amplified the RHD-deleted allele and therefore accurately distinguished homozygous from heterozygous RhD-positive samples. The results were in complete concordance with serological testing. For the multiplex real-time quantitative PCR assay, the DeltaCt values clearly segregated into two distinct populations according to the RHD gene dosage, with mean values of 1.70 (SD, 0.17) and 2.62 (SD, 0.29) for the homozygous and heterozygous samples, respectively (P: <0.001, t-test). The results were in complete concordance with the results of serological testing as well as with the double ARMS assay. CONCLUSION: Double ARMS and real-time quantitative PCR are alternative robust assays for the determination of RhD zygosity.

Albumins↗
PubMed2000

Multiple births and risk of epithelial ovarian cancer.

BACKGROUND AND METHODS: Prevailing hypotheses about the causes of ovarian carcinogenesis predict that women with a history of multiple births (twins, triplets, etc.) should be at increased risk of epithelial ovarian cancer. However, the scant available evidence suggests that they may actually be at lower risk. To resolve this issue, we pooled data from eight studies involving 2859 parous women with epithelial ovarian cancer (case patients) and 7434 parous women without ovarian cancer (control women). In addition to assessing their history of multiple births (and the sex of the children, where available), we obtained information on age, parity, oral contraceptive use, and other reproductive factors for each woman. Details of tumor histology were available for all case patients. We estimated the relative risks of various histologic types of ovarian cancers associated with multiple births by using multivariable logistic regression analysis, adjusting for matching and confounding variables. RESULTS: Among these parous women, 73 case patients (2. 6%) and 257 control women (3.5%) had a history of multiple births. The adjusted summary odds ratio (OR) for developing all types of epithelial ovarian cancer that are associated with multiple births was 0.81 (95% confidence interval [CI] = 0.61-1.08). We found no evidence that risks associated with multiple births differed among women with borderline or invasive tumors and among women with same-sex and opposite-sex offspring from multiple births. The risk reductions appeared specific for nonmucinous tumors (n = 2453; summary adjusted OR = 0.71 [95% CI = 0.52-0.98]); in contrast, associations with mucinous tumors (n = 406) were heterogeneous across studies. CONCLUSIONS: Parous women with nonmucinous ovarian cancer are no more likely to have a history of multiple births than other parous women, counter to the predictions of current hypotheses for causes of ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed2000

Prevention of worsening of severe thrombocytopenia after red cell transfusions by the use of leucocyte-depleted blood.

Platelet counts were measured before and after red cell transfusions in 30 patients with anaemia and severe thrombocytopenia resulting from haematological diseases. There was a mean reduction of 1.1 x 109/l (P = 0.43) in the platelet count after transfusions of 2-3 units of leucocyte-depleted red cell concentrates (20 patients). However, there was a mean reduction of 2.7 x 109/l (P = 0.03), approximately 10%, in the platelet count after transfusions of non-leucocyte-depleted red cell concentrates (10 patients). The findings suggest that the forthcoming introduction of universal leucocyte depletion of red cell concentrates will minimize the worsening of thrombocytopenia that occurs in severely thrombocytopenic patients receiving standard non-leucocyte-depleted red cell concentrates.

Adult↗
PubMed2000

Severe haemolysis after an ABO unmatched kidney transplant - a nonsecretor transplanted from a donor with high anti-A titre.

A case of severe haemolysis following an ABO unmatched renal transplant is reported in a group A nonsecretor who received a kidney from a group O living related donor. Following the haemolytic episode, group A donor units were incompatible and the patient was transfused with group O blood. Serological investigation of the recipient revealed anti-A present in the serum and on the red cells. Investigation of the donor revealed the presence of high-titre anti-A. The association of such high-titre donor antibody with haemolysis in ABO unmatched grafts has not been reported before. We discuss the risk factors for developing haemolysis in an ABO unmatched organ transplant and explore the possible relevance of such high donor antibody titre to recipients who are nonsecretors.

ABO Blood-Group System↗
PubMed2000

Preparation and storage characteristics of white cell-reduced high-concentration platelet concentrates collected by anapheresis system for transfusions in utero.

BACKGROUND: Important concerns with regard to in utero platelet transfusions are avoidance of volume overload and the immunomodulatory effects of residual white cells (WBCs). This study evaluated a modification of a leukocyte-reduction system (LRS, Spectra, COBE BCT) for apheresis, which collects high-concentration WBC-reduced platelets (HCPs) for in utero transfusion. STUDY DESIGN AND METHODS: The LRS procedure was modified by running the platelet collection pump at specified low flow rates (Q(col)) for the first part of the procedure, collecting HCPs by gently purging them from the LRS chamber into a designated collection bag and then restoring the original LRS procedure settings to collect a second standard apheresis platelet concentrate (PC). Two centers carried out 32 procedures. Platelet yield, residual WBCs, and in vitro platelet function studies were evaluated. RESULTS: Platelet concentrations in 60 mL of HCPs were predictable according to Q(col) (r(2) = 0.735). HCP yields varied from 0.9 to 3.2 x 10(11), depending on the desired final platelet concentrations in 60 mL, with an overall average of 1. 92 x 10(11) (n = 32). Apheresis PCs had a mean platelet yield of 2.9 x 10(11) (1.3-4.4 x 10(11), n = 20) and 3.9 x 10(11) (2.2-5.8 x 10(11), n = 12) at concentrations of 1.3 x 10(12) per L for single-needle and dual- needle procedures, respectively. Median WBC counts were 5.6 x 10(3) for HCPs and 2.0 x 10(4) for apheresis PCs, with >99 percent expected to be less than 1 x 10(6). HCP in vitro characteristics were equivalent to those of apheresis PCs at 24 hours after collection. In vitro performance declined over storage as a function of HCP yield. HCP pH at 22(o)C was maintained at a level of >6.2 for more than 3 days for yields >1.6 x 10(11), less than 2 days for yields 1.6 to 2.2 x 10(11), and less than 24 hours for yields >2.2 x 10(11). HCPs showed good in vitro characteristics and could be stored for 1 to 3 days, depending on the total number of platelets collected. CONCLUSION: A standard apheresis PC and an HCP requiring no secondary processing can be collected with the Spectra LRS. The platelet concentration may be determined by clinical need. HCPs meet the requirements for components that are transfused in utero.

Blood Platelets↗
PubMed2000

Breast cancer risk in male twins: joint analyses of four twin cohorts in Denmark, Finland, Sweden and the United States.

To test the hypothesis that in utero exposure to high levels of oestrogen increases the risk of male breast cancer, we followed 115 235 male twins for more than 3.5 million person-years at risk. We observed 11 cases of male breast cancer versus 16.16 expected based on national rates (standardized rate ratio 0.68, 95% confidence interval 0.34-1.22) and conclude that any adverse influence of in utero oestrogen exposure is likely to be small.

Breast Neoplasms, Male↗
PubMed2000

Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder.

OBJECTIVE: To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD). DESIGN: Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study. SETTING: Outpatient clinic. PATIENTS: One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup. METHODS: After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring. RESULTS: An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design. CONCLUSIONS: The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.

Adult↗
PubMed2000

Is it necessary to administer anti-D to prevent RhD immunization after the transfusion of RhD-positive platelet concentrates?

Serology for the presence of anti-D after RhD-incompatible platelet transfusions was performed in 24 RhD-negative patients with haematological disease and 59 RhD-negative patients with non-haematological disease. None of the patients were given prophylaxis with anti-D to prevent RhD immunization. Eight out of 59 (13.5%) non-haematology patients developed detectable anti-D, whereas 0 out of 24 (0%) of the haematology patients formed anti-D (P = 0.06). The risk of alloimmunization after RhD-incompatible platelet transfusions using platelet concentrates prepared by modern technical methods appears to be small in patients with haematological disease, but is significant in non-immunocompromised patients.

Adolescent↗
PubMed1999

Clinical guidelines and hospital discharges of children with acute urinary tract infections.

In order to evaluate the effect of the introduction of recent similar guidelines on the treatment of acute urinary tract infection (UTI) in children, and possible changes in its epidemiology, we analyzed the records of hospital discharge for acute UTI under the age of 15 years in England and Wales between 1979 and 1993 and in Finland between 1978 and 1994. Cases were defined by the ICD9 diagnostic codes 590.1 (acute pyelonephritis) and 599.0 (UTI, site not specified) for males and females according to three age groups (0-4, 5-9, and 10-14 years). We also compared the registry data on kidney transplants due to end-stage renal disease caused by recurrent pyelonephritis in the United Kingdom and Finland. In England the rate of attack of symptomatic UTI per 1,000 girls under 15 years increased from 0.74 (95% confidence interval 0.71-0.76) in 1987 to 1.32 (1.29-1.35) in 1993 (P < 0.001, test for trend). The respective figures for Finnish girls were 1.74 (1.62-1.86) in 1987 and 1.62 (1.51-1.74) in 1993 (P = 0.72). In English boys, the increase in the attack rate was from 0.38 (0.36-0.40) in 1987 to 0.70 (0.68-0.73) in 1993 (P < 0.001). In Finnish boys the respective figures were 0.74 (0.66-0.82) in 1987 and 0.88 (0.80-0.97) in 1993 (P < 0.02). The observed increases in the attack rates of UTI most probably relate to increased referral of acute UTI patients to hospitals for the recommended imaging studies rather than changing occurrence. Publication of guidelines for treatment of UTI in children, consolidating more-general awareness, may have contributed to this. The mean annual numbers of kidney transplants in the United Kingdom and Finland during 1989-1995 due to end-stage renal disease caused by pyelonephritis were of similar magnitude, i.e., 1.9 (1.6-2.3) transplants per million inhabitants in the United Kingdom and 2.8 (1.5-4.7) transplants per million inhabitants in Finland. The decreasing trend in these figures in both countries, although statistically significant only in the United Kingdom (P < 0.05, test for trend), suggests improved longterm outcome of these patients induced by better diagnosis and treatment of pyelonephritis and the diseases related to it, such as congenital malformations. According to our data, valid clinical guidelines are effective in changing clinical practice.

Acute Disease↗