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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1996

A multicenter inspection of the swirling phenomenon in platelet concentrates prepared in routine practice. Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion.

BACKGROUND: In a previous multicenter study, the absence of the swirling phenomenon correlated well with platelet disc-to-sphere transformation, a morphology feature associated in the past with poor platelet viability. STUDY DESIGN AND METHODS: In 13 centers, 5366 platelet concentrates (PCs) were prepared and stored under routine conditions and evaluated for the presence of swirling. PCs found not to have swirling were evaluated for pH and platelet and white cell counts in parallel with an equal number of PCs with swirling that were studied as controls. RESULTS: In 13 participating centers, swirling was reported to be absent after 3 and 5 days of storage in 0 to 3.8 percent and in 0 to 18 percent of PCs, respectively. In 94 percent of units with swirling, pH was 6.7 to 7.5; this is a range of values associated with adequate in vivo survival. In 69 percent of PCs without swirling, pH was lower than 6.4 or higher than 7.6; these values are associated with reduced platelet viability. Three-quarters of the cases in which the absence of swirling was associated with pH values between 6.7 and 7.5 were reported from 2 out of the 13 participating centers. CONCLUSION: In PCs prepared and stored under routine conditions, the presence of swirling correlated well with pH values associated with adequate platelet in vivo viability. In about 20 percent of PCs without swirling, this was not due to a low or high pH value, and it would be useful to investigate whether this lack of swirling is associated with poor platelet viability. These data support the possibility that the evaluation of swirling by visual inspection might replace invasive and more cumbersome assays currently used for routine PC quality control.

Blood Platelets↗
PubMed1996

An investigation into the physical stability of a neonatal parenteral nutrition formulation.

The physical stability of a neonatal parenteral nutrition formulation has been examined using differential interference contrast (DIC) microscopy. In vitro studies indicated that particle size increases occur immediately after mixing the Intralipid emulsion with the amino acid/glucose solution, while simulation of clinical administration indicated that larger droplets were observed at the end of the catheter approximately 1 h after administration commenced. Microscopic observation of adjacent droplets of the two fluids showed reversible aggregation occurring almost immediately. It was concluded that the current method of administering this neonatal emulsion does not prevent droplet coalescence.

Drug Stability↗
PubMed1996

General practitioners' immediate management of men presenting with urethral symptoms.

OBJECTIVES: To describe the immediate reported management, by general practitioners (GPs), of men presenting with symptoms of urethral discharge, or dysuria only. SUBJECTS: All 692 GPs in practice in Brent, Harrow, Ealing, Hammersmith, and Hounslow (UK). METHOD: Data were collected using a GP completed questionnaire concerning the management of the last male patient seen, aged less than 40 years, complaining of urethral discharge, and the last male patient under 40 years complaining of dysuria only. RESULTS: The response rate among GPs was 52%. Fifty three per cent of men with urethral symptoms, 86% of men with a urethral discharge and 24% with dysuria only, were identified by GPs and referred without investigation or treatment to a genitourinary medicine clinic. Of men with dysuria only, 93% of investigations by GPs were reported to include a mid-stream urine (MSU) specimen for bacteriology, and 19% a urethral swab for chlamydia. Seventy eight per cent of GPs reported using treatments with a broad spectrum antibiotic, 53% with trimethoprim, whilst 14% of GPs reported using a tetracycline in common use to treat non-gonococcal urethritis. Urine specimens were reported to be "culture positive" in 41% of men who had an MSU specimen tested, and 15% of men who had a urethral swab tested were reported to be chlamydia positive. CONCLUSION: The GPs included in this study were not a full sample, or representative of all the GPs, and the data are retrospective. Nevertheless, we found a large difference in GPs reported management for men with urethral symptoms according to whether or not urethral discharge was a reported complaint. Reported management is likely to be, at least, indicative of actual management. Therefore, the results suggest that assessment by GPs of men presenting with dysuria should be explored and more appropriate management strategies defined.

Adolescent↗
PubMed1996

The Nottingham Study of Neurotic Disorder: influence of cognitive therapists on outcome.

BACKGROUND: In previously published papers from the Nottingham Study of Neurotic Disorder a short treatment package of cognitive-behaviour therapy was no more effective than placebo drug treatment after 10 weeks' assessment in a cohort of 210 patients with neurotic disorders. This paper examines the outcome over two years of the patients treated by cognitive-behaviour therapy separated into two therapist groups, those who were competent in administering treatment and those of uncertain competence. METHOD: The therapists (mainly community psychiatric nurses) of 70 patients with an original DSM-III diagnosis of either dysthymic, panic or generalised anxiety disorder were separated into two groups on the basis of their perceived competence by their supervisor (DK). Ratings of psychopathology were made at regular intervals over two years by assessors blind to knowledge of treatment or therapist. RESULTS: The patients treated by competent therapists (n = 30) generally showed greater improvement than those allocated to therapists of uncertain competence (n = 40), mainly with respect to depressive symptoms, and the difference persisted over two years, long after the cognitive-behaviour therapy had been completed. CONCLUSIONS: Cognitive-behaviour therapy given by competent therapists over a 10 week period is of lasting benefit in neurotic disorder.

Adult↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1996

Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a pediatric oncology group study.

PURPOSE: In an effort to improve outcome for children with advanced B-cell malignancies, a treatment plan based on a published regimen that consists of four courses of fractionated cyclophosphamide (cyclo) given with doxorubicin (doxo) and vincristine (VCR) was intensified by alternating with sequential high-dose methotrexate (MTX) and cytarabine (Ara-C), given in conjunction with intrathecal (IT) MTX and Ara-C. PATIENTS AND METHODS: From October 1986 to October 1992, 133 eligible patients were enrolled: 74 with B-cell (surface immunoglobulin-positive [Slg+] acute lymphoblastic leukemia (B-ALL) and 59 with stage IV small noncleaved-cell lymphoma (SNCCL). The median age was 8 years; there were 103 males and 30 females. Abdominal tumor masses were prominent in 63 cases (33 B-ALL and 30 stage IV SNCCL). RESULTS: Complete remission (CR) was achieved in 66 B-ALL and 57 stage IV patients (93% overall). At 4 years, the estimated event-free survival (EFS) rate is 65% +/- 8% for patients with B-ALL and 79% +/- 9% for those with stage IV SNCCL. Among patients with CNS involvement, 23 of 36 remain in CR (4-year EFS rate, 64% +/- 13%). Relapses occurred early; only 3 patients relapsed after completion of therapy. Thirteen relapses occurred in the marrow, three in the CNS, and six in other sites. Of 11 CNS-positive patients who relapsed, only two recurred primarily in the CNS. CONCLUSION: The results of this study indicate that with intensified chemotherapy an increasing potential for cure exists for patients with B-ALL and stage IV SNCCL.

Adolescent↗
PubMed1996

Deep breathing in children with severe malaria: indicator of metabolic acidosis and poor outcome.

Despite the frequent association of respiratory symptoms and signs with malarial morbidity and mortality in sub-Saharan Africa, the value of individual symptoms and signs has rarely been assessed. We have prospectively examined the association of individual clinical findings with the summary diagnosis of respiratory distress, outcome, and the presence of metabolic acidosis in children admitted with severe malaria to a Kenyan district hospital. Respiratory distress was present in 119 of the 350 children included in the study and in 23 of the 30 deaths (relative risk = 6.5, 95% confidence interval = 2.8-14.4). The features of a history of dyspnea, nasal flaring, and indrawing or deep breathing (Kussmaul's respiration) were individually most closely associated with the summary diagnosis of respiratory distress. Of these, deep breathing, which was sensitive (91%) and specific (83%) for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress. Therefore, it warrants further prospective evaluation in different clinical settings and areas of different malaria endemicity.

Acidosis↗
PubMed1996

Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops.

OBJECTIVE: The development of bronchopulmonary dysplasia (BPD) often has been attributed to injury from mechanical ventilation and supplemental oxygen. Early lung inflammation in infants with BPD has been thought to be secondary to these factors. The purpose of this study was to evaluate whether preexisting (prenatal) inflammation may be a primary causative factor in the development of BPD. METHODS: Intubated newborns of less than 2,000 g birth weight were prospectively enrolled. The presence or absence of chorioamnionitis was documented. Lung inflammation was evaluated on days 1, 2, and 4 of intubation by assaying concentrations of interleukin 1 beta (IL-1 beta), thromboxane B2, leukotriene B4, and prostaglandin E2 in tracheal lavages. Infants in whom BPD developed were compared with those in whom it did not using these measures. RESULTS: Fifty-three infants were enrolled; 41 survived. Thirty-eight had respiratory distress syndrome; 15 were intubated for other diagnoses. Infants prenatally exposed to chorioamnionitis were less likely to present with respiratory distress syndrome; however, chorioamnionitis was significantly associated with both the presence of IL-1 beta from the first day of intubation and the development of BPD. Tracheal lavage concentrations of IL-1 beta were higher in infants in whom BPD developed. Thromboxane B2 concentrations were similar on day 1 but were higher on days 2 and 4 in infants in whom BPD developed. CONCLUSIONS: In this study, intubated infants weighing less than 2,000 g at birth in whom BPD developed had increased exposure to inflammation prenatally (chorioamnionitis) and evidence of increased lung inflammation from the first postnatal day. We speculate that chorioamnionitis may accelerate lung maturation but that it also causes lung inflammation and subsequent lung injury in intubated infants, fostering the development of BPD.

Bronchoalveolar Lavage↗
PubMed1996

Using HL7 and the World Wide Web for unifying patient data from remote databases.

W3-EMRS is an architecture designed to access clinical data from remote heterogeneous electronic medical record system (EMRS) databases. We describe the technologies used in an experimental implementation of W3-EMRS that concurrently collects data from several sources and presents them in an integrated set of views. After describing some of the organizational constraints, the architectural decision, implementation methodology, and operation of the completed project are discussed.

Computer Communication Networks↗
PubMed1996

Haemagglutination properties of Moraxella (Branhamella) catarrhalis.

The ability of 30 isolates of Moraxella (Branhamella) catarrhalis to haemagglutinate erythrocytes of five species was examined. Two haemagglutination phenotypes of M. catarrhalis were observed: phenotype I isolates (n = 10) agglutinated human erythrocytes, while phenotype II isolates (n = 7) agglutinated both human and rabbit erythrocytes. No haemagglutination was observed with chick, sheep or horse erythrocytes. Haemagglutination by both phenotype I and II isolates was abolished following treatment of these isolates with pronase and trypsin, while heat treatment at 70 degrees C markedly reduced the level of haemagglutination by both sets of isolates. Haemagglutination by phenotype II isolates was inhibited by galactose, whereas haemagglutination by phenotype I isolates was not inhibited by this carbohydrate. Transmission electron microscopy (TEM) studies showed that very close cell-surface interactions occurred when both phenotypes of M. catarrhalis adhered to the human erythrocyte. Fimbrial attachment was not apparent. Haemagglutinating isolates of both phenotypes had a trypsin-sensitive outer fibrillar coat when examined by TEM.

Animals↗
PubMed1995

Platelet storage for transfusion in synthetic media: further optimization of ingredients and definition of their roles.

Currently, most platelet concentrates (PC) are stored for transfusion at 20 degrees C to 24 degrees C in autologous plasma. There are potential advantages in replacing some of this plasma with a synthetic medium. In this study, our major goals were to define the optimal ingredients and their concentrations in such a medium and to gain insight into the mechanism by which each ingredient confers benefit. In addition, we wished to validate a new polyvinyl chloride container plasticized with di-n-decyl phthalate (DnDP) for PC storage. PC derived from donations of whole blood were stored for 7 days in autologous plasma or a basic synthetic medium (BSM) containing 15 mmol/L glucose, 21 mmol/L citrate, and physiologic concentrations of salts other than bicarbonate within either the DnDP container or a licensed polyolefin container, PL-732. Metabolic events were characterized and a panel of in vitro tests were used to monitor platelet quality as systematic changes in the BSM were made. Platelet quality was as least as good, if not better, after storage in DnDP in comparison to PL-732. pH consistently decreased to less than 6.0 because of inadequate buffering of lactic acid in BSM alone. However, pH and the in vitro tests were well maintained by either the serial addition of bicarbonate (BSM + B) or the addition of at least 15 mmol/L acetate and 10 mmol/L phosphate (BSM + AP). The benefits of BSM + AP were traced to a decrease in lactic acid production by 33% and 19% relative to plasma and BSM + B, respectively, and the vigorous oxidation of acetate (0.66 +/- 0.09 mmol/d/10(12 platelets). The rates of lactate production and acetate consumption were similar and the pH during storage correlated with difference between the two rates, suggesting that acetate oxidation has an alkalinizing effect equivalent on a molar basis to the acidifying effect of production of lactate and a hydrogen ion. When pyruvate replaced acetate, it was also metabolized vigorously (0.52 +/- 0.06 mmol/d/10(12) platelets). Its presence suppressed lactic acid production by 44% relative to BSM + B and allowed maintenance of pH and platelet quality similar to what is achieved with acetate. The results strongly suggest that the benefit from acetate (or pyruvate) is derived from its oxidation and the use of a hydrogen ion during that oxidation. For reasons that are not yet clear, the omission of phosphate resulted in pH decrease to less than 6.0 in 3 of 9 PC even with acetate present.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1995

Functional redundancy of promoter elements ensures efficient transcription of the human 7SK gene in vivo.

Deletion and mutation studies of the human 7SK gene transfected into HeLa cells have identified three functional regions of the promoter corresponding to the TATA box at -25, the proximal sequence element (PSE) between -49 and -65 and the distal sequence element (DSE) between -243 and -210. These elements show sequence homology to equivalent regions in other snRNA genes and are functionally analogous. Unlike the DSEs of many snRNA genes however, the 7SK DSE does not contain a consensus binding site for the transcription factor Oct-1 but rather, contains two non-consensus Oct-1 binding sites that can function independently of one another to enhance transcription. Unusually, the 7SK PSE can retain function even after extensive mutation and removal of the conserved TGACC of the PSE has little effect in the context of the whole promoter. However, the same mutation abolishes transcription in the absence of the DSE suggesting that protein/protein interactions between DSE and PSE binding factors can compensate for a mutant PSE. Mutation of the 7SK TATA box allows snRNA type transcription by RNA polymerase II to occur and this is enhanced by the DSE, indicating that both the DSE and the PSE can also function with pol II. In addition, mutation of the TATA box does not abolish pol III dependent transcription, suggesting that other sequence elements may also play a role in the determination of polymerase specificity. Although the human 7SK gene is transcribed efficiently in Xenopus oocytes, analysis of the 7SK wild-type gene and mutants in Xenopus oocytes gives significantly different results from the analysis in HeLa cells indicating that the recognition of functional elements is not the same in the two systems.

Amino Acid Sequence↗
PubMed1995

Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus.

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks after infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for expression of three pleiotropic cytokines, TNF-alpha, IL-1 beta, and IL-6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen. The data show that all three cytokines and iNOS are expressed by astrocytes in chronically infected spinal cords. These activated astrocytes are localized to areas of virus infection and demyelination, although most of the astrocytes expressing these proteins are not MHV-infected. MHC class I and II antigen can be detected in these spinal cords as well, but not in cells with the typical morphology of astrocytes. TNF-alpha, IL-6, and iNOS are also evident in the brains of mice with MHV-induced acute encephalitis, but in marked contrast to the results obtained with the chronically infected mice, most of the cells expressing these cytokines or iNOS had the morphology of macrophages or other mononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spinal cords of mice with chronic demyelination. These results are consistent with a role for both viral infection of glial cells and high localized levels of proinflammatory cytokines and nitric oxide in the demyelinating process in mice infected with MHV-JHM. They also show that analogously to the human demyelinating disease, multiple sclerosis, astrocytes are a major cellular source for these cytokines in mice with chronic, but not acute disease.

Acute Disease↗
PubMed1995

Factor VNew Brunswick: Ala221-to-Val substitution results in reduced cofactor activity.

We have characterized the factor V protein and cDNA of a patient displaying factor V deficiency (parahemophilia) and correlated the reduced activity with a missense mutation of Ala221-to-Val. Plasma from the subject individual (C1) presented reduced factor V antigen (39% of normal) that displayed reduced activity (approximately 26% of normal). Factor V purified from this individual by standard techniques shows normal migration on sodium dodecyl sulfate gels and a normal pattern of activation by thrombin. Purified antigen from sibling C2 gives a much reduced specific activity of 263 U/mg (17% of normal). Sibling C3, the mother, and the father have antigen within the normal range (57% to 200%) that has approximately normal specific activity. The cDNA encoding the factor Va heavy and light chains of the subject individual was polymerase chain reaction-amplified and sequenced and revealed an A-to-G substitution at position 3 of codon 51 (silent mutation), a C-to-T substitution in position 2 of codon 221 (Ala221-Val), a T-to-C substitution at position 3 of codon 708 (silent mutation), and a G-to-A substitution at position 1 of codon 2185 (Thr2185-Ala). The latter mutation was also observed in control individuals and is proposed to be a possible polymorphism. Restriction analyses demonstrated the presence of one mutant and one normal allele in the father. The subject individual (C1) and sibling C2 carry only the mutant allele. The mother and sibling C3 carry only the normal allele. The inheritance pattern suggests the presence of a missing or nonexpressed allele in the mother that is passed on to all the siblings. Expression of only the mutant allele by the subject individual (C1) and sibling C2 is consistent with reduced factor V antigen and activity in these patients. We have designated this mutant as Factor VNew Brunswick.

Adolescent↗
PubMed1995

Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.

The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1.

Animals↗