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Biomedical subjects

M F Murphy

Publications and source records attributed to M F Murphy.

At least 91 records · Page 5Linked to original sources

Severe fetomaternal alloimmune thrombocytopenia presenting with fetal hydrocephalus.

We report two patients where the finding of isolated fetal hydrocephalus led to the detection of severe fetal thrombocytopenia, using fetal blood sampling. Serological investigation led to the diagnosis of fetomaternal alloimmune thrombocytopenia (FMAIT) due to anti-HPA-1a. Both women had had previous unsuccessful pregnancies probably due to FMAIT; one had had four miscarriages at 17-18 weeks' gestation. The other had had one previous pregnancy complicated by severe fetal anaemia, and eventually hydrocephalus developed and the fetus died without the diagnosis of FMAIT being considered. Subsequent pregnancies in the two women were also affected by FMAIT, but prenatal treatment, predominantly with serial fetal platelet transfusions, resulted in a successful outcome in both cases. These observations suggest that FMAIT should be suspected if there is isolated fetal hydrocephalus, unexplained fetal anaemia, or recurrent miscarriages. The accurate diagnosis of FMAIT is important because recent advances in prenatal management can improve the outcome of subsequently affected pregnancies.

Abortion, Habitual↗

Sedation.

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Procedural Sedation↗

State of the art in platelet transfusion therapy.

Platelet transfusions are established as effective treatment for thrombocytopenic bleeding, and are commonly used prophylactically to prevent bleeding in thrombocytopenic patients. However, many issues in platelet supportive care remain to be resolved, including the optimal methods for the preparation of platelet concentrates, the best means for the prevention of complications such as platelet refractoriness, transfusion reactions and the transmission of infection, and the precise clinical indications for their use. The demand for platelet concentrates continues to rise, mainly due to the increasing number of patients undergoing myeloablative therapy. This is leading to considerable interest in the coming availability of recombinant thrombopoietin for clinical use.

Humans↗

Breast cancer in Swedish women before age 50: evidence of a dual effect of completed pregnancy.

We set out to detect a transient increase in risk of breast cancer following childbirth, the existence of which has been postulated, but for which empirical evidence is contradictory. Breast cancers and births occurring among the cohort of Swedish women born after 1939 were linked, yielding 3,439 cases and 25,140 age-matched controls with at least two children. Within three years of their last childbirth, women had an estimated rate of breast cancer of 1.21 (95 percent confidence interval [CI] = 1.02-1.44) times that of women whose last birth was 10 or more years earlier, after adjustment for parity and age at first birth. Further analyses suggested that this effect reflected, in part, a small transient increase in breast cancer risk that lasts for about three years following completed pregnancy. The effect of age at first birth on breast cancer risk appears to be confounded by time since last birth; the parity-adjusted rate ratio for having a first birth at age 35 years or more compared with under 20 years is reduced from 1.72 (CI = 1.14-2.58) to 1.36 (CI = 0.88-2.09) on additional adjustment for time since last birth. A transient increase in breast cancer risk after childbirth appears thus appears to account for part of the effect of age at first birth on breast cancer risk.

Adult↗

Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support in patients with haematological malignancy.

BACKGROUND: Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support is increasingly being used in patients with haematological malignancy considered to be at high risk for recurrence. The results of this approach, in comparison with the previous experience at St. Bartholomew's Hospital (SBH) using autologous bone marrow transplantation form the basis of this report. PATIENTS AND METHODS: 42 patients (age range 18-63 years, median 42 years), deemed to have a poor prognosis with conventional therapy received myelo-ablative therapy with PBPC support. Diagnoses comprised: non-Hodgkin's lymphoma (NHL): 16 patients, Hodgkin's disease (HD): 9, Multiple Myeloma (MM): 12, and solid tumours (ST): 5. PBPC were mobilised using adriamycin: 35 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 orally, days 1-5, followed by G-CSF: 5 micrograms/kg, subcutaneously, for a median of 7 days (range 6-9 days). RESULTS: A total of 67 PBPC collections were performed, 1 being 'sufficient' (i.e. mononuclear cells > or = 1.5 x 10(8)/kg and CD34+ cells > or = 1 x 10(6)/kg) in 21 of the 42 patients. The median time to haematological recovery following reinfusion of PBPC was 13 days for both neutrophils > 0.5 x 10(9)/l and platelets > 20 x 10(9)/l (ranges: 8-27, and 8-48 days, respectively) which is significantly shorter than for patients in the historical control group. Supportive care requirements were also significantly reduced, as was the duration of hospital stay i.e., median 19 days (range 12-73 days) compared with 29 days (range 9-180 days). CONCLUSION: These results confirm rapid blood count recovery following myelo-ablative therapy with PBPC support and the feasibility of this approach.

Adolescent↗

Antenatal screening for fetal alloimmune thrombocytopenia: the results of a pilot study.

Feto-maternal incompatibility for the human platelet antigen HPA-1a is an important cause of severe fetal thrombocytopenia. The incidence is 1 in 1000-2000 pregnancies, which is more common than other conditions for which screening is presently carried out. Antenatal diagnosis and management are now available, but only for subsequent siblings following diagnosis of a previously affected infant. This study describes a pilot prospective screening programme for the antenatal detection of fetomaternal alloimmune thrombocytopenia (FMAIT) due to HPA-1a incompatibility. 3473 women were typed for HPA-1a using a method designed for large-scale typing. 71 women found to be HPA-1a negative were further tested for HLA-DR52a as a risk factor for alloimmunization. All women were monitored for the development of anti-HPA-1a throughout pregnancy and a cord full blood count was taken at delivery. Two affected pregnancies were found and treated: a singleton pregnancy was treated antenatally and a twin pregnancy after delivery. The study showed that screening for FMAIT could be established within the pre-existing antenatal red cell serology programme. It was concluded that screening should be based on platelet typing and offered regardless of parity. Further stratification, combining DR52a typing and HPA-1a antibody screening, although focusing on the group of women at greater risk, may not identify all affected pregnancies. Confirmation of the diagnosis and severity of FMAIT continues to depend on fetal blood sampling during pregnancy or cord blood samples after birth.

Adult↗

A single temperature amplification technique applied to the detection of citrus tristeza viral RNA in plant nucleic acid extracts.

A procedure for the successful detection of citrus tristeza virus (CTV) RNA in total crude nucleic acid extracts of infected citrus whole leaves and bark is described. The method requires the isolation and precipitation of total nucleic acids from either infected whole leaf or bark tissue. The CTV viral RNA is then specifically amplified using a single temperature RNA Self-Sustained Sequence Replication technique (3SR) performed at 42 degrees C for 60 minutes. The amplified negative-sense viral RNA product can subsequently be detected by fixing a portion of the reaction mixture onto a nylon membrane and hybridizing with positive sense tristeza specific DNA oligonucleotide probes. Central California isolates of CTV were readily detected by this method. Denatured viral specific dsRNA was also a suitable template for the specific detection of CTV.

Base Sequence↗

A simplified method for large-scale HPA-1a phenotyping for antenatal screening.

A simplified method for large-scale HPA-1a phenotyping of platelets was developed for use in an antenatal screening programme for fetomaternal alloimmune thrombocytopenia (FMAIT). The test was based on the MAIPA assay, which was modified for antigen-typing with a well-characterized anti-HPA-1a reagent. The resulting assay gave reliable results, was inexpensive and allowed testing of large batches using semiautomated equipment.

Antibodies, Monoclonal↗

Antenatal management of fetomaternal alloimmune thrombocytopenia--report of 15 affected pregnancies.

The recognition that spontaneous intracranial haemorrhage (ICH) may occur in utero in fetomaternal alloimmune thrombocytopenia (FMAIT) led us to attempt to prevent this in 15 pregnancies of 11 women who had previously affected infants with FMAIT due to anti-HPA-1a. The antenatal management included fetal platelet transfusions and maternal steroids and/or high-dose intravenous immunoglobulin (IVIgG). In the first pregnancy, ICH occurred between 32 and 35 weeks' gestation before any treatment had been given, emphasizing the need for earlier intervention. Five of the 14 subsequent pregnancies in this study were considered to be severely affected (severe haemorrhagic complications in a previous infant and initial fetal platelet count < 20 x 10(9)/L in this study); four were managed successfully with weekly fetal platelet transfusions started between 18 and 29 weeks and continued until delivery at 33-35 weeks, and one severely affected case who was referred at 36 weeks was managed successfully with a single platelet transfusion prior to delivery. Five pregnancies were considered to be mildly affected (previous infants were unaffected by severe bleeding and initial fetal platelet count > 50 x 10(9)/L in this study). The platelet counts were maintained in one case with steroids and in three with IVIgG without the need for repeated platelet transfusions, but in the fifth the fetal platelet count fell despite steroids and IVIgG and serial platelet transfusions were required. Four pregnancies were unsuccessful; two pregnancies were terminated after severe ICH occurred at an early stage before fetal blood sampling had been carried out, one fetus died after the mother had a severe fall despite the successful initiation of fetal platelet transfusions and one died due to a cord haematoma which occurred at the time of the initial fetal blood sampling. The optimal management of FMAIT to reduce the risk of antenatal ICH remains uncertain. Steroids and IVIgG may be effective in some mildly affected cases but serial fetal platelet transfusions are the preferred therapy for those who are severely affected.

Antigens, Human Platelet↗

Relative importance of immune and non-immune causes of platelet refractoriness.

In this prospective study, 26 consecutive patients being treated for haematological malignancies receiving standard (i.e. non-leucocyte-depleted) blood components were observed for the development of refractoriness to platelet transfusions. One hundred and sixteen of the 266 (44%) platelet transfusions failed to produce a satisfactory response. In 102/116 (88%), the poor response was in the presence of non-immune factors known to be associated with platelet refractoriness. Non-immune factors were present alone in 78/116 (67%), and in combination with immune factors in a further 24/116 (21%). Immune factors (HLA and platelet-specific antibodies) were present during 29/116 (25%) of unsuccessful platelet transfusions. Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of non-immune factors. The non-immune factors associated with refractoriness were often multiple, most frequently a combination of fever, infection and antibiotic therapy. This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied. It also suggests that measures for the prevention of HLA alloimmunisation, such as leucocyte depletion, may have a limited impact in reducing the incidence of refractoriness to platelet transfusions.

Acute Disease↗

Clinical aspects of platelet transfusion therapy.

Platelet transfusions are established as effective treatment for thrombocytopenic bleeding. However, the indications for prophylactic platelet transfusions are being reconsidered because of the greatly increased demand for platelet concentrates. Platelet refractoriness is the main clinical problem associated with repeated platelet transfusions. This is most frequently due to HLA alloimmunisation or non-immune platelet consumption associated with clinical factors such as septicaemia. The initial management of refractory alloimmunised patients is to use HLA-matched platelet transfusions. If there is no improvement with HLA-matched platelet transfusions, platelet crossmatching may identify the cause of the problem and help with the selection of compatible donors. Other measures used to improve responses to platelet transfusions are usually ineffective. There has been considerable interest in methods to prevent HLA alloimmunisation and platelet refractoriness and particularly in leucocyte depletion of blood components. The use of leucocyte-depleted blood components has other benefits for multitransfused patients, but further studies are needed before the routine use of leucocyte-depleted blood components can be recommended for patients likely to receive repeated platelet transfusions.

Antigens, Human Platelet↗

Application of polymerase chain reaction to detect animals latently infected with agents of malignant catarrhal fever.

Oligonucleotide primers derived from alcelaphine herpesvirus 1 (AHV-1) isolate WC11 DNA, the first identified agent of malignant catarrhal fever (MCF), were used to assay blood lymphocyte DNA using the polymerase chain reaction (PCR). Multiple species of exotic ruminants were examined to determine the suitability of this technique for detecting animals that may be latently infected. To correlate the PCR results with those of serology, serum samples were obtained from each animal concurrently with lymphocyte collection and subjected to an AHV-1 virus-neutralization assay (VNA). A total of 86 MCF-susceptible animals were tested, and the results of the VNA and PCR assays were compared. PCR results were positive for 44 animals. Of these, 13 were positive by VNA. Animals positive by both VNA and PCR were all wildebeest, the asymptomatic carriers of AHV-1, confirming the ability of the primers to amplify AHV-1 sequence. Positive PCR results from species other than wildebeest may represent sequence amplified from viruses related to AHV-1, which may not induce antibodies capable of neutralizing the WC11 isolate used in the VNA. This study demonstrates that PCR is capable of detecting the presence of MCF agents in various populations of captive ruminants prior to the appearance of clinical MCF so that the sources of infection can be more reliably ascertained.

Animals↗

Diagnosis of malignant catarrhal fever by polymerase chain reaction amplification of alcelaphine herpesvirus 1 sequence.

We derived sequence information from cloned HindIII fragment "D" of alcelaphine herpesvirus 1 strain WC11, an agent of malignant catarrhal fever (MCF). Based on this sequence, oligonucleotide primers were selected and synthesized for use in a polymerase chain reaction amplification assay. These primers were used to test samples of total nucleic acids isolated from multiple tissues taken from an Indian gaur (Bos guarus gaurus) at the San Diego Wild Animal Park in San Diego, California (USA) which had clinical signs of a natural infection of MCF. Six of eight tissue samples examined had amplifiable sequences present. A nucleic acid probe complementary to the sequence of the original clone between the primer sites also was synthesized and used to confirm the identity of the amplified viral sequences, thus providing a diagnosis of MCF at the molecular level.

Animals↗