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Biomedical subjects

J Molloy

Publications and source records attributed to J Molloy.

At least 19 recordsLinked to original sources

Epidemiology of injuries and illnesses in America's Cup yacht racing.

OBJECTIVES: To determine the incidence and severity of injuries and illnesses incurred by a professional America's Cup yacht racing crew during the preparation for and participation in the challenge for the 2003 America's Cup. METHODS: A prospective study design was used over 74 weeks of sailing and training. All injuries and illnesses sustained by the 35 professional male crew members requiring medical treatment were recorded, including the diagnosis, nature, location, and mechanism of injury. The volume of sailing and training were recorded, and the severity of incidents were determined by the number of days absent from both sailing and training. RESULTS: In total, 220 injuries and 119 illnesses were recorded, with an overall incidence of 8.8 incidents/1000 sailing and training hours (injuries, 5.7; illnesses, 3.1). The upper limb was the most commonly injured body segment (40%), followed by the spine and neck (30%). The most common injuries were joint/ligament sprains (27%) and tendinopathies (20%). The incidence of injury was significantly higher in training (8.6) than sailing (2.2). The most common activity or mechanism of injury was non-specific overuse (24%), followed by impact with boat hardware (15%) and weight training (13%). "Grinders" had the highest overall injury incidence (7.7), and "bowmen" had the highest incidence of sailing injuries (3.2). Most of the illnesses were upper respiratory tract infections (40%). CONCLUSIONS: The data from this study suggest that America's Cup crew members are at a similar risk of injury to athletes in other non-collision team sports. Prudent allocation of preventive and therapeutic resources, such as comprehensive health and medical care, well designed conditioning and nutritional programmes, and appropriate management of recovery should be adopted by America's Cup teams in order to reduce the risk of injury and illness.

Adult↗

Molecular and serological detection of A. centrale- and A. marginale-infected cattle grazing within an endemic area.

A reverse line blot hybridization (RLB) one-stage nested PCR (nPCR) for Anaplasma centrale and a nested PCR for Anaplasma marginale were used to detect infected cattle grazing within an endemic region in Israel. A novel set of PCR primers and oligonucleotide probes based on a 16S ribosomal RNA gene was designed for RLB detection of both Anaplasma species, and the performance of the molecular assays compared. The immunofluorescent antibody test (IFA) was used to detect antibodies to both Anaplasma species, whereas, a highly sensitive and specific competitive enzyme-linked immunosorbent assay (cELISA) was used to detect antibodies in A. centrale-vaccinated cattle. The RLB and the nested PCR procedures showed bacteremia with sensitivity of 50 infected erythrocytes per milliliter. Up to 93% of the A. centrale vaccinates carried specific antibodies that were detected by cELISA, and up to 71% of the vaccinated cattle were found to be naturally infected with A. marginale according to the PCR and the RLB assays. Nevertheless, no severe outbreaks of A. marginale infection occurred among vaccinated herds in this endemic region. It appears that both, molecular tools and serology are useful for evaluation of the vaccine efficacy. In the light of wide natural field infection with A. marginale, strong recommendations to continue the A. centrale vaccination program regime will continue until a new generation of non-blood-based vaccine will be developed.

Anaplasma centrale↗

Postpartum pituitary hypophysitis.

The case of a young woman who developed lymphocytic hypophysitis 2 weeks after delivery of a healthy baby is reported. The patient presented with clinical features suggestive of a pituitary mass lesion, but surgery was avoided when other clinical and radiologic features were considered. The patient recovered with steroid treatment only. We review the literature on this increasingly recognized condition and argue that medical management may be more suitable than previously thought.

Adult↗

Public health and the role of the nurse: the need for greater clarity.

There is evidence that public health is currently taking centre stage in the challenge to improve the population's health. This represents a change from the 1980s and 1990s where health promotion was the dominant concept among community nurses. Public health means different things to different people and while nurses have a role to play, there is a need to be more precise about their specific contribution. The creation of public health nursing posts across the UK is contribution to this confusion, as there is little emerging consensus as to what professionals in these posts should do. At present, there does not appear to be a dominant strategy or model of working. A preliminary analysis of job advertisements for public health nursing posts indicates a requirement for a 'supercharged' health visitor to work in a specific area to provide a link between the professional and lay communities. The emphasis is on community development with little on population health. Government policy on public health clearly highlights the important role of nurses in contributing to the public health agenda. The current role and function of public health nursing posts may not allow them to be classed as specialist public health nurses/nursing and to provide educational opportunities for nurses to develop the knowledge and skills which will enable them to work alongside medical and other healthcare colleagues in the pursuit of specialist public health practitioner status.

Community Health Nursing↗

Asymptomatic embolization predicts stroke and TIA risk in patients with carotid artery stenosis.

BACKGROUND AND PURPOSE: Improved methods of identifying patients at high risk of thromboembolism would allow improved targeting of therapy. One such situation is carotid artery stenosis. This is associated with an increased risk of stroke, which can be reduced by carotid endarterectomy. However, the risk-benefit ratio is low in patients with tight asymptomatic stenosis and moderate symptomatic stenosis. Most stroke in patients with carotid stenosis is believed to be embolic. Therefore, the detection of asymptomatic cerebral emboli using Doppler ultrasound may allow identification of a high-risk group. METHODS: Transcranial Doppler ultrasound was used to record for 1 hour the ipsilateral middle cerebral artery in 111 patients with >60% carotid artery stenosis (69 symptomatic, 42 asymptomatic). The Doppler audio signal was recorded onto digital audio tape for later analysis for embolic signals (ES) by an individual blinded to clinical details. In 67 subjects the relationship between ES and angiographically determined plaque ulceration was investigated. All subjects were followed up prospectively, and the relationship between ES and risk of future ipsilateral carotid artery territory ischemic events (TIA and stroke) was determined. RESULTS: ES were detected in 41(36.9%) subjects. In symptomatic patients there was a significant inverse relationship between the number of ES per hour and time elapsed since last symptoms (Spearman's rho=-0.2558, P=0.034). ES were more common in subjects with plaque ulceration, with a relative risk of 4. 94 (95% CI, 1.23 to 19.84; P=0.025) after controlling for both symptomatic status and degree of stenosis. The presence of ES at entry was predictive of TIA and stroke risk during follow up in both symptomatic (P=0.02) and asymptomatic patients (P=0.007). Considering all 111 patients, the presence of asymptomatic embolization was predictive of a further ischemic event, with an adjusted OR of 8.10 (95% CI, 1.58 to 41.57; P=0.01) after controlling for other cardiovascular risk factors, degree of stenosis, symptomatic status, and aspirin or warfarin use. CONCLUSIONS: Asymptomatic embolization in patients with carotid artery stenosis correlates with known markers of increased stroke risk and is an independent predictor of future stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. It may allow identification of a high-risk group of patients who will particularly benefit from carotid endarterectomy. A large multicenter study is now required to confirm these findings.

Adult↗

Changing values for nursing and health promotion: exploring the policy context of professional ethics.

In this article we illustrate, and argue for, the importance of researching the social context of health professionals' ethical agendas and concerns. We draw upon qualitative interview data from 20 nurses working in two occupational health sites, and our discussion focuses mainly upon aspects of the shifting 'ethical context' for those nurses with a health promotion remit who are working in the British National Health Service. Within this discussion we also raise a number of potentially substantive issues, including the risks of colluding in 'double standards', and the tensions between the practitioner and managerial roles in nursing. Overall, we hope to pose questions about the best ways to understand the ethical agency and responsibilities of health professionals.

Attitude of Health Personnel↗

S-nitrosoglutathione reduces the rate of embolization in humans.

BACKGROUND: Antiplatelet agents presently used in the secondary prevention of cardiovascular disease fail to prevent the majority of cases of recurrent stroke and systemic embolization. An evaluation of the efficacy of new agents is hampered by a lack of in vivo models in humans. Asymptomatic cerebral embolic signals (ES) may be detected with the use of transcranial Doppler ultrasonography. These signals are particularly common after carotid endarterectomy, and this provides a situation in which new antiplatelet agents can be evaluated. With this model, we determined the effectiveness of S-nitrosoglutathione (GSNO), a nitric oxide donor with relative platelet specificity, in reducing cerebral embolization. METHODS AND RESULTS: Transcranial Doppler ultrasound recordings from the ipsilateral middle cerebral artery were made after carotid endarterectomy in 12 control patients and 12 patients receiving intravenous GSNO from the induction of anesthesia until 2 hours after skin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hours after skin closure. The Doppler signal was recorded onto tape, and analysis for ES was performed, with the investigators blinded to treatment group. All patients received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery. The median (range) number of ES detected during the initial 3-hour postoperative recording was markedly reduced in the GSNO group compared with the control group: 7.5 (0 to 61) versus 38.5 (1 to 219) (P=0.018). This difference persisted until 6 hours after surgery. CONCLUSIONS: Despite the administration of aspirin and heparin, frequent embolization occurred and was markedly reduced after the administration of GSNO. This demonstrates the potential use of platelet-specific nitric oxide donors in the treatment of thromboembolic disease. This model of cerebral embolism may allow determination of the effectiveness of new antiplatelet agents in humans.

Aged↗

Temporal variability of asymptomatic embolization in carotid artery stenosis and optimal recording protocols.

BACKGROUND AND PURPOSE: Although asymptomatic embolization can be detected in patients with carotid artery stenosis, its temporal variability is unclear. An understanding of this is important in designing optimal recording protocols for future prospective studies of the predictive value of embolic signals (ES). We determined the effect of repeating and extending recording times in patients with symptomatic and asymptomatic carotid stenosis. METHODS: In 20 asymptomatic and 20 symptomatic subjects with > 60% carotid stenosis, we used transcranial Doppler ultrasound to record for ES in the ipsilateral middle cerebral artery. Three 1-hour recordings were performed on three separate days, and on one occasion (not necessarily the first) the recording was extended to 2 hours. The recordings were saved onto digital tape for subsequent blinded analysis. RESULTS: Marked temporal variability was seen in symptomatic patients in whom the cumulative proportion of subjects with ES increased from 10 (50%) after a single hour of recording to 12 (60%) and 15 (75%) after two and three recordings, respectively. Extending the recording to 2 hours increased the yield of ES-positive patients from 6 (30%) to 8 (40%). In symptomatic patients there was excellent agreement between whether patients were positive for ES during each of two consecutive 1-hour recordings (kappa = 0.78, P = 0.0003) but poor agreement between the results of two single-hour recordings performed on different days (kappa = 0.22, P = 0.27). In asymptomatic patients, 4 (20%) were ES positive during the first hour; this increased to 5 (25%) after the recording was repeated once, with no further increase after the third recording. Extending the recording to 2 hours increased the yield from 3 (15%) to 7 (35%). In contrast to symptomatic stenoses, in patients with asymptomatic stenoses there was fair agreement between whether patients were ES positive on two consecutive 1-hour recordings (kappa = 0.49, P = 0.01) or two single-hour recordings performed on different days (kappa = 0.48, P = 0.02). Symptomatic subjects were more likely to have ES (when all 1-hour recordings were considered, 24/60 versus 10/60; P = 0.0046). ES in symptomatic subjects had a higher relative intensity increase than in asymptomatic subjects (P = 0.01). CONCLUSIONS: The temporal variability of ES needs to be taken into account in the design of optimal recording protocols and comparisons of results from different studies. Extending the duration of recording beyond an hour in symptomatic stenoses is of less value, but repeating the recording on a different day will often identify additional subjects with ES. In intervention studies in symptomatic patients, the time since last symptoms must be considered. In asymptomatic stenosis, extending the duration of recording beyond an hour will increase the proportion of patients positive for ES.

Adult↗

Use of a decibel threshold in detecting Doppler embolic signals.

BACKGROUND AND PURPOSE: To improve reproducibility and reliability in the identification of embolic signals detected with the use of Doppler ultrasound, many studies have used an intensity threshold. However, variable thresholds between 3 and 12 dB have been used, and often the method of measurement of intensity is not stated. Potentially different methods of measurement could result in different intensity measurements for the same embolic signal. We determined the effect of these differences using commercial transcranial Doppler systems. METHODS: We analyzed 81 embolic signals recorded from the middle cerebral arteries of patients with carotid artery disease using three different methods of measuring intensity that had been previously used in research studies. In method 1 individual time frames of the frequency spectra were analyzed, in method 2 a color-coded intensity scale was used, and in method 3 automated software was used. RESULTS: There was a highly significant correlation between measurements made by the different techniques (method 1 versus method 2: r = .68, P < .0001; method 1 versus method 3: r = .66, P < .0001; method 2 versus method 3: r = .70, P < .0001). However, the absolute values of intensity for the same embolic signals varied markedly for the different methods. For example, a 4-dB threshold according to method 1 was equivalent to an approximately 7-dB threshold measured by method 2. These differences had major effects on the proportion of embolic signals detected with the use of the same decibel threshold but with intensity measured in the different ways. For example, using a threshold of 7 dB would result in only 4.9% of signals being missed by method 2 but 42.2% and 51.4% being missed by methods 1 and 3, respectively. CONCLUSIONS: Our results demonstrate that the intensities of the same embolic signals, recorded with the same parameters, are markedly different when analyzed in the different ways used in previous studies. This has important implications when a decibel threshold is used and emphasizes that criteria developed by one investigator on one machine cannot be used by another investigator without initial reevaluation. This could account for some of the differences in frequencies of embolic signals reported in previous clinical studies.

Differential Threshold↗

A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: A common polymorphism (T/t) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) enzyme has been associated with elevated serum homocysteine, itself a risk factor for stroke. Some studies have reported an association with ischemic heart disease, but no published studies have examined its relationship with stroke. METHODS: We determined the TT genotype frequency and T allele frequency in 345 patients with ischemic cerebrovascular disease (CVD) and 161 control subjects. In a subgroup we also determined serum homocysteine and folate concentrations. RESULTS: In the patient group there was a significant relationship between TT genotype and homocysteine concentration after we controlled for other risk factors. Controlling for serum folate weakened this relationship, and folate itself was independently related to serum homocysteine. There was no difference between patients and control subjects in either TT genotype frequency (10.7% versus 13.7%; P = .34) or T allele frequency (0.68 versus 0.67; P = .67). There was no association when analysis was limited to individuals deficient in folate (serum folate < 25th centile) or to younger individuals (< 65 years). There was no association between TT genotype and any stroke subtype or with degree of carotid stenosis. CONCLUSIONS: In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.

Aged↗

High speed centrifugal separator for rapid on-line sample clarification in biotechnology.

Sample clarification is a common operation in biochemical analytical methods for removing interfering or unwanted particulates from an analyte sample. Filtration provides one option for removal of particulates. However, in many cases the loss of soluble protein due to filter adsorption is unacceptable and an alternative must be sought. In this paper a microcentrifuge designed to automatically sample, spin, deliver supernatant to an analyser and wash out solids from the bowl is described. The performance of the system is assessed in terms of its clarification efficiency and the time required to achieve satisfactory clarification. Additionally, the effects of different protein precipitating agents on yeast homogenate samples separated using the microcentrifuge are studied where the system is used to deliver supernatant to a flow injection analyser. The paper demonstrates that the microcentrifuge may be used to separate rapidly such samples on a time scale between 10-60 s depending upon the type and size of sample and be successfully used as a component of an at-line monitoring system.

Biotechnology↗

Multigated Doppler ultrasound in the detection of emboli in a flow model and embolic signals in patients.

BACKGROUND AND PURPOSE: The ability to detect asymptomatic circulating cerebral emboli may contribute to the management of patients with stroke, but its clinical usefulness will depend on effective systems for automatically detecting embolic signals (ES) and differentiating them from artifact. A new method involves the use of a multidepth probe that allows recording from both distal and proximal sample volumes along the same vessel. Theoretically, an embolus should appear sequentially, with a time delay, between the two channels, whereas an artifact should appear simultaneously in the two channels. METHODS: We evaluated this method in an in vitro flow model and in patients. In an in vitro model, with a flow pattern mimicking intracerebral flow, 181 air bubbles and 193 thrombus emboli were compared with the signals resulting from 368 episodes of artifact; a sample volume of 5 mm and a channel separation of 10 mm were used. ES from two groups of patients-those with carotid artery stenosis (141 ES) and those with mechanical prosthetic cardiac valves (125 ES)-were studied and compared with 222 episodes of artifact produced in the same patients. RESULTS: In the model the mean (SD) time delay was 17.32 (9.94) ms for air emboli and 17.78 (10.66) ms for thrombus emboli compared with -0.01 (0.39) ms for artifact (air and thrombus emboli versus artifact, P < .0001). A sensitivity of 100% and specificity of 100% were obtained when a cutoff of > 2 ms was used for an embolus. The method allowed equally good detection of those air emboli that resulted in receiver overload and aliasing. In patients the mean (SD) time delay was 29.6 (28.2) ms for valve ES and 14.9 (15.42) for carotid ES compared with 0.00 (0.46) for artifact (carotid and valve ES versus artifact, P < .0001). Considering only those signals that were visible in both Doppler time domains resulted in a sensitivity for valve ES of 98.9% and for carotid ES of 94.0%, with a specificity of 99.0%. However, in one patient in the valve group some ES were visible only in the proximal channel, possibly because of passage of emboli down branch vessels between the two sample volumes. In addition, for the less intense carotid ES some signals were unclear or absent in one or both of the time domain signals at either depth, although visible in the post-fast Fourier transform spectra. Including those ES visible in only one channel reduced the sensitivity to 75.2% for valve ES and 92.6% for carotid ES. CONCLUSIONS: The multigated technique offers a new method of detecting ES and differentiating them from artifact and is the first reliable method for differentiating intense ES resulting in receiver overload from artifact. Occasionally its sensitivity is reduced when ES do not appear in the distal channel, probably because they pass down a side branch; this may be reduced by reducing gate separation. Some less intense carotid ES can be difficult to detect if the amplitude increase is small compared with the amplitude of the background Doppler signal.

Aged↗

Functional recovery of troponin I in a Drosophila heldup mutant after a second site mutation.

To identify proteins that interact in vivo with muscle components we have used a genetic approach based on the isolation of suppressors of mutant alleles of known muscle components. We have applied this system to the case of troponin I (TnI) in Drosophila and its mutant allele heldup2 (hdp2). This mutation causes an alanine to valine substitution at position 116 after a single nucleotide change in a constitutive exon. Among the isolated suppressors, one of them results from a second site mutation at the TnI gene itself. Muscles endowed with TnI mutated at both sites support nearly normal myofibrillar structure, perform notably well in wing beating and flight tests, and isolated muscle fibers produce active force. We show that the structural and functional recovery in this suppressor does not result from a change in the stoichiometric ratio of TnI isoforms. The second site suppression is due to a leucine to phenylalanine change within a heptameric leucine string motif adjacent to the actin binding domain of TnI. These data evidence a structural and functional role for the heptameric leucine string that is most noticeable, if not specific, in the indirect flight muscle.

Alleles↗

Effects of tropomyosin deficiency in flight muscle of Drosophila melanogaster.

We have studied the structure and function of muscle fibers in which tropomyosin stoichiometry has been reduced by genetic mutation. We used a Drosophila melanogaster flightless mutant Ifm(3)3 and a genetic cross of this mutant with wild type flies to achieve a gradation of tropomyosin gene dosage. We measured the flight ability and wingbeat frequency of the live insects and the ultrastructure and mechanochemistry of isolated single flight muscle fibers. Flight ability is impaired when tropomyosin gene dosage is reduced. Wingbeat frequency also depends upon gene dosage as well as the severity of myofilament lattice disruption and the number of myofilaments in the organized core of the myofibrils. A reduction in number of myofilaments appears to result in a reduction in active muscle stiffness without resulting in an appreciable change in kinetics of force production. Ifm(3)3 is trapped in a relaxed state and cannot generate active force. However, tight-binding rigor cross-bridges are able to form; in the absence of ATP, Ifm(3)3 muscle fibers have high stiffness and force.

Actin Cytoskeleton↗

Myosin light chain-2 mutation affects flight, wing beat frequency, and indirect flight muscle contraction kinetics in Drosophila.

We have used a combination of classical genetic, molecular genetic, histological, biochemical, and biophysical techniques to identify and characterize a null mutation of the myosin light chain-2 (MLC-2) locus of Drosophila melanogaster. Mlc2E38 is a null mutation of the MLC-2 gene resulting from a nonsense mutation at the tenth codon position. Mlc2E38 confers dominant flightless behavior that is associated with reduced wing beat frequency. Mlc2E38 heterozygotes exhibit a 50% reduction of MLC-2 mRNA concentration in adult thoracic musculature, which results in a commensurate reduction of MLC-2 protein in the indirect flight muscles. Indirect flight muscle myofibrils from Mlc2E38 heterozygotes are aberrant, exhibiting myofilaments in disarray at the periphery. Calcium-activated Triton X-100-treated single fiber segments exhibit slower contraction kinetics than wild type. Introduction of a transformed copy of the wild type MLC-2 gene rescues the dominant flightless behavior of Mlc2E38 heterozygotes. Wing beat frequency and single fiber contraction kinetics of a representative rescued line are not significantly different from those of wild type. Together, these results indicate that wild type MLC-2 stoichiometry is required for normal indirect flight muscle assembly and function. Furthermore, these results suggest that the reduced wing beat frequency and possibly the flightless behavior conferred by Mlc2E38 is due in part to slower contraction kinetics of sarcomeric regions devoid or partly deficient in MLC-2.

Allosteric Regulation↗

Functional and ultrastructural effects of a missense mutation in the indirect flight muscle-specific actin gene of Drosophila melanogaster.

A single-site mutation of the flight-muscle-specific actin gene of Drosophila melanogaster causes a substitution of glutamic acid 93 by lysine in all the actin encoded in the indirect flight muscle (IFM). In these Act88FE93K mutants, myofibrillar bundles of thick and thin filaments are present but lack Z-discs and all sarcomeric repeats. Dense filament bundles, which are probably aberrant Z-discs, are seen in myofibrils of pupal flies, but early in adult life these move to the periphery of the fibrils and are not seen in skinned adult fibres. Consistent with this observation, alpha-actinin and other high molecular weight proteins, possibly associated with Z-discs, are not detected on SDS/polyacrylamide gels or Western blots of skinned adult IFM. The mutation lies at the beginning of a loop in the small domain of actin, near the myosin binding region. However, that the mutant actin binds myosin heads is shown by (1) rigor crossbridges in electron micrographs, (2) the appropriate rise in stiffness when ATP is withdrawn in mechanical experiments, and (3) equal protection against tryptic digestion provided by rigor binding between actin and myosin in both wild-type and mutant fibres. Reversal of rigor chevron angle along some thin filaments reflects reversal of thin-filament polarity due to lattice disorder. The absence of Z-discs, alpha-actinin and two high molecular weight proteins, and binding studies by others, suggest that the substitution at residue 93 affects the binding of the mutant actin to a protein, possibly alpha-actinin, which is necessary for Z-disc assembly or maintenance.

Actins↗