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Biomedical subjects

J Haynes

Publications and source records attributed to J Haynes.

At least 19 recordsLinked to original sources

Use of recombinant activated factor VII in massive obstetric haemorrhage.

Massive obstetric haemorrhage is a life-threatening emergency that remains a major cause of maternal mortality. Conventional management is aimed at optimising uterine tone, replacing circulating volume and blood products, and surgery to achieve haemostasis. Recently there have been numerous reports of the (unlicensed) use of recombinant activated factor VII in the management of major obstetric haemorrhage. We report our experience of using it in the treatment of major post-partum haemorrhage in four previously healthy parturients. The published reports of recombinant activated factor VII use in post-partum haemorrhage (unrelated to pre-existing coagulopathies) are compared.

Adult↗

Autoinflation for hearing loss associated with otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) or 'glue ear' is an accumulation of fluid in the middle ear, in the absence of acute inflammation or infection. It is the commonest cause of acquired hearing loss in childhood and the usual reason for insertion of 'grommets'. Potential treatments include decongestants, mucolytics, steroids, antihistamines and antibiotics. Autoinflation devices have been proposed as a simple mechanical means of improving 'glue ear'. OBJECTIVES: To determine the effects of autoinflation in adults and children with otitis media with effusion. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, CENTRAL (The Cochrane Library Issue 1, 2006), MEDLINE (1951 to 2006), EMBASE (1974 to 2006) and twelve other databases, using the Cochrane Ear, Nose and Throat Disorders Group search strategy. SELECTION CRITERIA: We selected randomised controlled trials that compared any form of autoinflation to no autoinflation in individuals with 'glue ear'. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed quality and extracted data from included studies. MAIN RESULTS: Six studies met the inclusion criteria. Improvement occurred for the composite measure of tympanogram or audiometry at less than one month (Relative Risk of Improvement (RRI) 2.47, 95% confidence interval (CI) 0.93 to 6.58) and at more than one month (RRI 2.20, 95% CI 1.71 to 2.82). Subgroup analysis based on the type of intervention showed a significant effect using a Politzer device under one month (RRI 7.07, 95% CI 3.70 to 13.51) and over one month (RRI 2.25, 95% CI 1.67 to 3.04). Pooled estimates showed non-significant change in tympanometry (type C2 and B) at less than one month (RRI 1.65, 95% CI 0.49 to 5.56) and non-significant improvement in tympanometry at greater than one month (RRI 1.89, 95% CI 0.77 to 4.67). Non-significant improvements occurred for discrete pure tone audiometry (RRI 0.80, 95% CI 0.22 to 2.88) and non-discrete audiometry (WMD 6.95 dB, 95% CI 21.03 to 7.13). None of the studies demonstrated a significant difference in the incidence of side effects between interventions. AUTHORS' CONCLUSIONS: All of the studies were small, of limited treatment duration and short follow up. However, because of the low cost and absence of adverse effects it is reasonable to consider autoinflation whilst awaiting natural resolution of otitis media with effusion. Further research should consider the duration of treatment and the long-term impact of autoinflation on developmental outcomes in children.

Adult↗

Wess-Zumino current and the structure of the decay tau- -->K- pi- K+ nu tau.

We present the first study of the vector (Wess-Zumino) current in tau(-)-->K-pi-K+nu(tau) decay using data collected with the CLEO III detector at the Cornell Electron Storage Ring. We determine the quantitative contributions to the decay width from the vector and axial vector currents. Within the framework of a model by Kühn and Mirkes, we identify the quantitative contributions to the total decay rate from the intermediate states omegapi, rho(')pi, and K*K.

Journal Article↗

Observation of eta'c production in gammagamma fusion at CLEO.

We report on the observation of the eta(')(c)(2(1)S0), the radial excitation of the eta(c)(1(1)S0) ground state of charmonium, in the two-photon fusion reaction gammagamma-->eta(')(c)-->K(0)(S)K+/-pi(-/+) in 13.6 fb(-1) of CLEO II/II.V data and 13.1 fb(-1) of CLEO III data. We obtain M(eta(')(c))=3642.9+/-3.1(stat)+/-1.5(syst) MeV and M(eta(c))=2981.8+/-1.3(stat)+/-1.5(syst) MeV. The corresponding values of hyperfine splittings between 1S0 and 3S1 states are DeltaM(hf)(1S)=115.1+/-2.0 MeV and DeltaM(hf)(2S)=43.1+/-3.4 MeV. Assuming that the eta(c) and eta(')(c) have equal branching fractions to K(S)Kpi, we obtain Gamma(gammagamma)(eta(')(c))=1.3+/-0.6 keV.

Journal Article↗

Phagosomal maturation and intracellular survival of Mycobacterium avium subspecies paratuberculosis in J774 cells.

The mechanisms by which Mycobacterium avium subspecies paratuberculosis (M. a. ptb) survives within macrophages are not well characterized. One strategy for intracellular survival developed by Mycobacterium tuberculosis is inhibition of phagosomal maturation. In this study it was hypothesized that M. a. ptb is capable of survival within macrophages by residing within a phagosomal compartment that does not mature into a functional phagolysosome. To test this hypothesis the following objectives were determined. Phagosomal maturation was evaluated by comparison of stage specific markers on the membranes of phagosomes containing live M. a. ptb with those containing killed M. a. ptb, Mycobacterium smegmatis, and zymosan A using immunofluorescent labeling and confocal microscopy. Intracellular survival of live M. a. ptb within J774 macrophages was compared to that of M. smegmatis by direct determination of bacterial viability by differential live/dead staining. The results of this study show that the phagosomes containing live M. a. ptb had increased levels of an early marker (transferrin receptor [TFR]) and decreased levels of a late maturation marker (lysosome associated membrane protein one [Lamp-1]), relative to those containing killed M. a. ptb, M. smegmatis, and zymosan A. Additionally, compared to M. smegmatis, M. a. ptb has enhanced ability to survive within cultured macrophages. These data indicate that M. a. ptb resists intracellular killing by residing within a phagosomal compartment that retains the characteristics of early phagosomes and resists maturation into functional phagolysosome.

Animals↗

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion.

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

Adult↗

Fading of nipple-areolar reconstructions: the last hurdle in breast reconstruction?

Fading of nipple-areolar reconstructions is commonly reported, but there are few formal studies of this phenomenon. The purpose of this study was to determine whether deficiencies in nipple-areolar reconstruction and pigmentation were perceived by patients, their partners and independent observers, and whether a technique could be developed to measure nipple-areolar colour reliably. A total of 57 patients, 32 partners and four independent observers completed questionnaires about the appearance of the patients' breast reconstructions in general and specifically about their nipple-areolar reconstructions. Scores for the general attributes of the breast reconstruction were used as internal controls for the scores of the nipple-areolar reconstruction. A computer software package was developed to analyse colour in photographs of the reconstructions. Independent observers thought that nipple-areolar reconstruction improved the appearance of a breast reconstruction 81% of the time. Considerably fewer patients were happy with their nipple-areolar colour than were happy with the more general attributes of the breast reconstruction (P < 0.005). Colour analysis objectively demonstrated measurable mismatch between normal and reconstructed nipple-areolar skin, which was positively correlated with time since surgery due to fading of the nipple-areolar reconstruction. In our patients, the quality of nipple-areolar reconstruction, in particular its pigmentation, is seen as inferior to that of the rest of the breast reconstruction in the eyes of patients, their partners and independent observers. The poor colour match and fading of reconstructed nipple-areolar skin are phenomena that can be measured using colour analysis.

Adult↗

A ComGA-dependent checkpoint limits growth during the escape from competence.

In Bacillus subtilis, competence for transformation develops in 5-10% of the cells in a stationary phase culture. These cells exhibit a prolonged lag in the resumption of growth and cell division during the escape from competence. To better understand the basis of this lag, we have characterized competent cultures microscopically. To distinguish the minority of competent cells, a translational fusion between ComK, the competence transcription factor, and the green fluorescent protein (GFP) was used as a marker. Only 5-10% of the cells in a competent culture were fluorescent, indicating that ComK synthesis is an all or nothing event. To validate the identification of competent cells, we demonstrated the coincident expression of comEA, a late competence gene, and comK-gfp. Competent cells resemble stationary phase cells; the majority are single (not in chains), contain single nucleoids, and rarely contain FtsZ rings. Upon dilution into fresh medium, competent cells maintain this appearance for about 2 h. In contrast, the majority of non-competent cells rapidly resume growth, exhibiting chaining, nuclear division and FtsZ-ring formation. The late competence protein ComGA is required for the competence-related block in chromosome replication and cell division. In the competent cells of a comGA mutant culture, chromosomal replication and FtsZ-ring formation were no longer blocked, although competent comGA mutant cells were abnormal in appearance. It is likely that one role for ComGA is to prevent growth, chromosome replication and cell division until ComK can be eliminated by degradation. A mutation in the ATP-binding site of comGA inactivated the protein for transformation but did not prevent it from inhibiting DNA replication and cell division. The buoyant density difference between competent and non-competent cells depends on the competence-specific growth arrest.

Bacillus subtilis↗

The relationship of the number of Meissner's corpuscles to dermatoglyphic characters and finger size.

This study investigated the relationships between the density of Meissner's corpuscles and the dermatoglyphic characteristics of human fingers. Dermatoglyphic prints and tissue samples were collected from the index (II) and ring (IV) fingers of 28 cadavers from the Medical School, University of Adelaide. Pattern types, pattern intensity, total ridge count and ridge breadth, were determined for each sample and the density of Meissner's corpuscles established by recording the mean number of Meissner's corpuscles underlying a 10 mm long line on the skin surface. No relationship was found between the density of Meissner's corpuscles and pattern type, pattern intensity or total ridge count. Negative correlations were found for the density of Meissner's corpuscles with both ridge width and size of fingers. Males were found to have significantly larger fingers, larger ridge breadth, and a lower density of Meissner's corpuscles per 10 mm compared with females. However, there was no difference between the total number of Meissner's corpuscles per finger in males and females. No significant differences were found in either the density of Meissner's corpuscles between antimeres or between the index and ring fingers. These results suggest that for both the left and right hand in males and females, there is a similar number of Meissner's corpuscles for both the index and ring fingers.

Aged↗

Nurses' attitudes and practices in sickle cell pain management.

Professional objectivity should be the primary focus of patient care. Health care professionals are at times reluctant to give opioids out of fear that patients may become addicted, which would result in the undertreatment of pain. The influence of nurses' attitudes on the management of sickle cell pain was studied. The variables of age, education, area of practice, and years of active experience were considered. Of the respondents, 63% believed addiction was prevalent, and 30% were hesitant to administer high-dose opioids. Study findings suggest that nurses would benefit from additional education on sickle cell disease, pain assessment and management, and addiction. Educational recommendations are discussed.

Adult↗

Transcriptional coregulation by the cell integrity mitogen-activated protein kinase Slt2 and the cell cycle regulator Swi4.

In Saccharomyces cerevisiae, the heterodimeric transcription factor SBF (for SCB binding factor) is composed of Swi4 and Swi6 and activates gene expression at the G(1)/S-phase transition of the mitotic cell cycle. Cell cycle commitment is associated not only with major alterations in gene expression but also with highly polarized cell growth; the mitogen-activated protein kinase (MAPK) Slt2 is required to maintain cell wall integrity during periods of polarized growth and cell wall stress. We describe experiments aimed at defining the regulatory pathway involving the cell cycle transcription factor SBF and Slt2-MAPK. Gene expression assays and chromatin immunoprecipitation experiments revealed Slt2-dependent recruitment of SBF to the promoters of the G(1) cyclins PCL1 and PCL2 after activation of the Slt2-MAPK pathway. We performed DNA microarray analysis and identified other genes whose expression was reduced in both SLT2 and SWI4 deletion strains. Genes that are sensitive to both Slt2 and Swi4 appear to be uniquely regulated and reveal a role for Swi4, the DNA-binding component of SBF, which is independent of the regulatory subunit Swi6. Some of the Swi4- and Slt2-dependent genes do not require Swi6 for either their expression or for Swi4 localization to their promoters. Consistent with these results, we found a direct interaction between Swi4 and Slt2. Our results establish a new Slt2-dependent mode of Swi4 regulation and suggest roles for Swi4 beyond its prominent role in controlling cell cycle transcription.

Cyclins↗

Patient-initiated hospital follow-up for rheumatoid arthritis.

OBJECTIVES: To evaluate the clinical efficacy, cost and acceptability of a shared care system of patient- or general practitioner (GP)-initiated hospital review in rheumatoid arthritis (RA). METHODS: A 2-yr randomized controlled trial of routine rheumatologist-initiated review was compared with a shared care system. Shared care patients had no routine follow-up but patients or GPs initiated access to rapid review by the multidisciplinary team via a nurse-run helpline. Control patients had a rheumatologist-initiated medical review at intervals of 3-6 months. Clinical and psychological status, resource use, and patient and GP satisfaction and confidence were assessed. Three-monthly clinical data were assessed (blind) for safety monitoring, with failure set at a 20% increase in pain, disability or disease activity. RESULTS: Two hundred and nine established RA patients participated, of whom 182 were evaluable. Safety-net failures were not different between groups. Shared care patients had less pain (24 months, 3.9 cm on a 10-cm visual analogue scale vs 4.8 cm for controls; P: < 0.05), a smaller increase in pain over 2 yr (+ 0.4 cm vs +1.6 cm for controls; P: < 0.01), greater self-efficacy (6, 15, 18, 21 months, P: < 0.05), used 33.5% less resources (208 ponds sterling per patient per year vs 313 pound sterling for controls; P: < 0.001) and were more confident in the system (6, 9, 12, 18, 21, 24 months, P: < 0.01 to P: < 0.001). CONCLUSIONS: A patient-initiated system for hospital review over 2 yr offers some clinical benefit compared with the traditional system, using fewer resources and attracting greater patient confidence. Longer-term assessment of the system would be appropriate.

Aged↗

5-(N-ethylcarboxamido)adenosine desensitizes the A2b-adenosine receptor in lung circulation.

The adenosine agonist 5-(N-ethylcarboxamido)adenosine (NECA) induces vasodilation in the pulmonary circulation via A2-adenosine-receptor activation. We addressed whether prolonged treatment with NECA desensitizes in A2-adenosine- receptor function in isolated lung and pulmonary artery smooth muscle cells (PASMC). In lung microcirculation preconstricted with a hypoxic gas, initial administration of NECA caused a 57% vasodilatory response after 3-4 min. Readministration of NECA after 45 min resulted in minimal vasodilation. The highest accumulation of PASMC cAMP occurred 3-5 min after NECA, coincident with NECA-induced vasodilation. In PASMCs treated with NECA for 45 min, cAMP did not increase. Isoproterenol- and indolidan-induced vasodilation remained intact in NECA-desensitized lungs. In NECA-desensitized PASMCs, isoproterenol-induced cAMP accumulation was decreased, suggesting a common mechanism of desensitization. cAMP accumulation was decreased in cholera toxin-treated NECA-desensitized PASMCs compared with cholera toxin-treated control PASMCs, demonstrating that Gsalpha-adenylyl cyclase signaling contributes to desensitization. The A2a-adenosine-receptor agonist CGS-21680C neither increased cAMP accumulation in PASMCs nor attenuated NECA-induced vasodilation. These data support that the A2b-adenosine receptor is responsible for pulmonary vasodilation and desensitization through mechanisms(s) involving Gsalpha-adenylyl cyclase signaling.

Adenosine↗

Beyond the call.

Explore the source record for details and available documents.

Humans↗

Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge.

Naked DNA vaccines expressing the prM and E genes of two tick-borne flaviviruses, Russian spring summer encephalitis (RSSE) virus and Central European encephalitis (CEE) virus were evaluated in mice. The vaccines were administered by particle bombardment of DNA-coated gold beads by Accell gene gun inoculation. Two immunizations of 0.5 to 1 microg of RSSE or CEE constructs/dose, delivered at 4-week intervals, elicited cross-reactive antibodies detectable by enzyme-linked immunosorbent assay and high-titer neutralizing antibodies to CEE virus. Cross-challenge experiments demonstrated that either vaccine induced protective immunity to homologous or heterologous RSSE or CEE virus challenge. The absence of antibody titer increases after challenge and the presence of antibodies to E and prM, but not NS1, both before and after challenge suggest that the vaccines prevented productive replication of the challenge virus. One vaccination with 0.5 microg of CEE virus DNA provided protective immunity for at least 2 months, and two vaccinations protected mice from challenge with CEE virus for at least 6 months.

Animals↗

Chimeric potyvirus-like particles as vaccine carriers.

Presentation of subunit vaccines in a highly ordered aggregate form can result in enhanced immune responses. Coat protein (CP) monomers of a potyvirus (Johnsongrass mosaic virus) when produced in heterologous host expression systems (Escherichia coli, yeast and insect cells) self-polymerized to produce potyvirus-like particles (PVLPs). The N- and C-terminal regions of potyvirus CP are surface-exposed and are not required for assembly. Hybrid CP monomers containing short peptides fused to their N- and/or C-termini, or large target antigens fused to the N-terminus or replacing most of the N- or C-terminal exposed regions retained the ability to assemble into hybrid PVLPs. Such chimeric PVLPs were highly immunogenic in mice and rabbits even in the absence of any adjuvant. Potyvirus CP is highly versatile in accommodating peptides or large antigens and is able to present antigens exposed on the surface of virus-like particles. This, combined with the efficiency of high level bacterial and insect cell expression systems, makes PVLPs an attractive non-pathogenic and non-replicative vaccine carrier.

Animals↗