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Biomedical subjects

P G Martin

Publications and source records attributed to P G Martin.

At least 19 recordsLinked to original sources
PubMed2007

Muscle fatigue changes cutaneous suppression of propriospinal drive to human upper limb muscles.

Some voluntary drive reaches human upper limb muscles via cervical propriospinal premotoneurones. Stimulation of the superficial radial nerve can inhibit these premotoneurones selectively and the resultant suppression of voluntary drive to motoneurones changes on-going electromyographic (EMG) activity. We investigated whether muscle fatigue changes this cutaneous-induced suppression of propriospinal drive to motoneurones of upper limb muscles. EMG was recorded from the extensors and flexors of the wrist and elbow. In the first study (n = 10 subjects), single stimuli (2 x perception threshold; 2PT) to the superficial radial nerve were delivered during contraction of the wrist extensors, before and after sustained fatiguing contractions of wrist extensors. In the second study (n = 10), similar stimuli were applied during elbow extension, before and during fatigue of elbow extensors. In the final study (n = 10), trains of three stimuli (2PT) were delivered during contractions of wrist extensors, before and while they were fatigued. With fatigue of either the wrist or elbow extensors, EMG suppression to single cutaneous stimuli increased significantly (by approximately 75%) for the fatigued muscle (P < 0.05). Conversely, in the other muscles, which were coactivated but not principally involved in the task, inhibition decreased or facilitation increased. Trains of stimuli produced greater suppression of on-going wrist extensor EMG than single stimuli and this difference persisted with fatigue. A control study of the H reflex in extensor carpi radialis showed that the mechanism responsible for the altered EMG suppression in fatigue was not at a motoneurone level. The findings suggest that the proportion of descending drive mediated via the disynaptic propriospinal pathway or the excitability of inhibitory interneurones projecting to propriospinal neurones increases substantially to fatigued muscles, but decreases to other active muscles. This pattern of changes may maintain coordination during multimuscle movements when one group of muscles is fatigued.

Adult↗
PubMed2006

Theta burst stimulation does not reliably depress all regions of the human motor cortex.

OBJECTIVE: The excitability of the human motor cortex projecting to hand muscles can be reduced by theta burst transcranial magnetic repetitive stimulation (TBS). This study compared the magnitude and variability of changes evoked by TBS for a distal and proximal arm muscle. METHODS: Eight subjects participated in three studies. In each study, electromyographic responses (MEPs) to single-pulse transcranial magnetic stimulation assessed cortical excitability before and after 40s of TBS. In the first two studies, TBS (intensity, 80% active motor threshold) was delivered to the optimal locations for biceps or first dorsal interosseous (FDI). In the final study, weaker intensity TBS was delivered over the biceps representation. RESULTS: TBS targeting biceps produced highly variable results among subjects. For the group, MEPs were not significantly depressed. Repeat studies in individual subjects highlighted the variability of responses. For FDI, MEPs were significantly depressed 5min after TBS and remained depressed for >30min (p<0.05). No significant changes in biceps MEPs occurred with weaker TBS. CONCLUSIONS: The magnitude and reliability of TBS depends on the region of the cortex targeted. SIGNIFICANCE: Results obtained for the hand should not be considered indicative of changes that will occur in other regions of the motor cortex or the brain.

Adult↗
PubMed2006

Output of human motoneuron pools to corticospinal inputs during voluntary contractions.

This study investigated transmission of corticospinal output through motoneurons over a wide range of voluntary contraction strengths in humans. During voluntary contraction of biceps brachii, motor evoked potentials (MEPs) to transcranial magnetic stimulation of the motor cortex grow up to about 50% maximal force and then decrease. To determine whether the decrease reflects events at a cortical or spinal level, responses to stimulation of the cortex and corticospinal tract (cervicomedullary motor evoked potentials, CMEPs) as well as maximal M-waves (M(max)) were recorded during strong contractions at 50 to 100% maximum. In biceps and brachioradialis, MEPs and CMEPs (normalized to M(max)) evoked by strong stimuli decreased during strong elbow flexions. Responses were largest during contractions at 75% maximum and both potentials decreased by about 25% M(max) during maximal efforts (P < 0.001). Reductions were smaller with weaker stimuli, but again similar for MEPs and CMEPs. Thus the reduction in MEPs during strong voluntary contractions can be accounted for by reduced responsiveness of the motoneuron pool to stimulation. During strong contractions of the first dorsal interosseous, a muscle that increases voluntary force largely by frequency modulation, MEPs declined more than in either elbow flexor muscle (35% M(max), P < 0.001). This suggests that motoneuron firing rates are important determinants of evoked output from the motoneuron pool. However, motor cortical output does not appear to be limited at high contraction strengths.

Action Potentials↗
PubMed2002

Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service.

BACKGROUND: Invasive procedures to obtain fetal DNA for prenatal blood grouping present a risk to the fetus. During pregnancy, cell-free fetal DNA is present in maternal blood. The detection of RHD sequences in maternal plasma has been used to predict fetal D status, based on the assumption that RHD is absent in D- genomes. STUDY DESIGN AND METHODS: Real-time PCR assays were designed to distinguish RHD from RHDpsi (possessed by the majority of D- black Africans). Plasma-derived DNA from 137 D- women was subjected to real-time PCR to detect fetal RHD and Y chromosome-associated SRY sequences. The accuracy of RHD genotyping from maternal plasma was investigated by comparing results with those obtained by conventional RHD genotyping from fetal tissue or serologic tests on the infant's RBCs. The quantity of fetal DNA in maternal plasma was investigated in 94 pregnancies. RESULTS: Fetal D status was predicted with 100-percent accuracy from maternal plasma. The number of copies of fetal DNA in maternal plasma was found to increase with gestation. CONCLUSION: Combination of the sensitivity of real-time PCR with an improved RHD typing assay to distinguish RHD from RHDpsi enables highly accurate prediction of fetal D status from maternal plasma. This has resulted in the implementation of a clinical noninvasive fetal RHD genotyping service.

DNA↗
PubMed2000

The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype.

Antigens of the Rh blood group system are encoded by 2 homologous genes, RHD and RHCE, that produce 2 red cell membrane proteins. The D-negative phenotype is considered to result, almost invariably, from homozygosity for a complete deletion of RHD. The basis of all PCR tests for predicting fetal D phenotype from DNA obtained from amniocytes or maternal plasma is detection of the presence of RHD. These tests are used in order to ascertain the risk of hemolytic disease of the newborn. We have identified an RHD pseudogene (RHD psi) in Rh D-negative Africans. RHDpsi contains a 37 base pair (bp) insert in exon 4, which may introduce a stop codon at position 210. The insert is a sequence duplication across the boundary of intron 3 and exon 4. RHDpsi contains another stop codon in exon 6. The frequency of RHDpsi in black South Africans is approximately 0.0714. Of 82 D-negative black Africans, 66% had RHDpsi, 15% had the RHD-CE-D hybrid gene associated with the VS+ V- phenotype, and only 18% completely lacked RHD. RHDpsi is present in about 24% of D-negative African Americans and 17% of D-negative South Africans of mixed race. No RHD transcript could be detected in D-negative individuals with RHDpsi, probably as a result of nonsense-mediated mRNA decay. Existing PCR-based methods for predicting D phenotype from DNA are not suitable for testing Africans or any population containing a substantial proportion of people with African ethnicity. Consequently, we have developed a new test that detects the 37 bp insert in exon 4 of RHDpsi. (Blood. 2000; 95:12-18)

Amino Acid Sequence↗
PubMed2000

Injury trends of passenger car drivers in frontal crashes in the USA.

Injuries trends of passenger car drivers in head-on collisions are identified based on crash data extracted from the National Automotive Sampling System. Annual injury incidence levels are estimated for years 1990-2007. Over that period, the number of crashes is predicted to rise by 71%. However, the number of serious injuries to drivers is expected to rise by only 41% and driver fatalities are anticipated to decrease by 9%. Meantime, the types of injuries suffered by drivers are changing. Year-to-year shifts in injury patterns result from changes in vehicle size classes within the US vehicle fleet population and increases in seat belt use and air bag availability. The effectiveness of air bags in saving lives is estimated to be 30%, and with more air bag-equipped cars on the road, the probability of sustaining a life-threatening head or a torso injury is reduced. Air bags, however, are not as effective in preventing upper and lower extremity injuries, and thus arm and leg injuries will become more prevalent in years to come.

Accidents, Traffic↗
PubMed2000

Evaluation of the von Willebrand factor antigen (vWF-Ag) assay using an immuno-turbidimetric method (STA Liatest vWF) automated on the MDA 180 coagulometer.

The standard enzyme-linked immunosorbent assay (ELISA) test for von Willebrand factor antigen (vWF-Ag), though sensitive and specific, does not deliver the flexibility to handle single sample assessments economically or provide rapid, emergency testing capability. The present study examined the performance characteristics of an immuno-turbidimetric assay kit (STA Liatest) modified for automation on the MDA(R)180 coagulation analyser using a supplied protocol. One hundred and sixteen patient samples were assessed by both the standard and the modified method. The correlation coefficient was 0.98 across the range of values 1-487 IU/dl. Above 200 IU/dl, where specimen dilution was indicated, there was greater diversity (r = 0.86) between the techniques. Plotting the difference between methods against the mean of both showed excellent agreement between methods below 100 IU/dl vWF. The intra-assay and interassay coefficients of variation were less than 3% at both low and normal range levels. The MDA(R)180 automated vWF assay merits consideration as an alternative to ELISA testing that provides random access and result availability within 30 min.

Antigens↗
PubMed2000

Hypoglycaemia induced by exogenous insulin--'human' and animal insulin compared.

AIMS: A systematic review of the literature was carried out to examine whether published evidence suggests a difference in the frequency and awareness of hypoglycaemia induced by 'human' and animal insulin. METHODS: The review identified randomized controlled trials and studies of other designs including observational comparisons, case series and case reports in which the use of 'human' insulin was compared to animal insulin in people with diabetes. These were identified from bibliographic databases and hand-searches of key journals. The main outcome measures were frequency, severity, awareness and symptoms of insulin induced hypoglycaemia. RESULTS: Fifty-two randomized controlled trials, 37 of double-blind design, were identified which included one or more of the relevant outcome measures. Of these, 21 specifically investigated hypoglycaemic frequency and awareness as primary outcomes (six in people with previously reported reduced hypoglycaemic awareness). The remainder of the identified trials reported hypoglycaemic outcomes as a secondary or incidental outcome during comparative investigations of efficacy or immunogenicity. Seven of the double-blind studies reported differences in frequency of hypoglycaemia or awareness of symptoms, although none of the studies which selected subjects on the basis of previously reported impaired awareness demonstrated significant differences between insulin species. Four of the unblinded trials reported differences in hypoglycaemia. This reached statistical significance in two of the studies. A further 56 studies of other designs and case reports were considered. In addition to the 10 case reports describing individuals with impaired hypoglycaemic awareness, nine studies reported differences in the incidence and manifestation of hypoglycaemia during 'human' insulin treatment. Notably, none of the four population time trend studies found any relationship between the increasing use of 'human' insulin and hospital admission for hypoglycaemia or unexplained death among those with diabetes. The largest case series could find no support for the hypothesis that an influence of treatment with 'human' insulin on hypoglycaemia had contributed to any of the 50 deaths investigated. When all types of studies considered are ranked in order of rigour (according to the accepted 'hierarchy of evidence'), it is the least rigorous which lend most support to the notion that treatment with 'human' insulin has an effect on the frequency, severity or symptoms of hypoglycaemia. CONCLUSIONS: Evidence does not support the contention that treatment with 'human' insulin per se affects the frequency, severity or symptoms of hypoglycaemia. However, a number of studies, mainly those of less rigorous design, describe an effect when people are transferred from animal insulin to 'human' insulin. It is not possible to state how common this is or whether the phenomenon is specific to 'human' insulin or an effect resulting from stricter glycaemic control (perhaps compounded, in some cases, by neurological complications in long-standing diabetes). This remaining uncertainty makes it essential that insulin from animal sources continues to be available so that clinicians and patients may retain this choice of treatment.

Animals↗
PubMed2000

Prenatal determination of fetal blood group status.

BACKGROUND AND OBJECTIVES: The prenatal determination of fetal blood group status by molecular techniques has been used in the clinical management of alloimmunised pregnancies for seven years, in particular for the definition of fetal Rh D, c and E, K, Fya and Jka status. This has arisen in response to the definition of the molecular bases of human blood group polymorphism. MATERIALS AND METHODS: PCR-based amplification assays have been designed to define fetal blood group status, where the source of template DNA is normally derived from amniotic fluid or chorionic villus. Recently, non-invasive methods have been explored to obtain fetal DNA from maternal peripheral blood. RESULTS: PCR-based tests are now available to screen for all fetal medicine significant blood group antigens. The Rh system is the most complex, and assays to define Rh genotype have been modified in response to our increased understanding of the molecular biology of this blood group system. CONCLUSION: Prenatal diagnosis of fetal blood group status is now in widespread use in the clinical management of HDN. Non-invasive testing, if applied in the clinical setting may invoke a dramatic increase in the numbers of pregnancies that may be analysed prenatally.

Blood Group Antigens↗
PubMed1999

Evaluation of a novel ELISA screening test for detection of factor VIII inhibitory antibodies in haemophiliacs.

Treatment of patients with haemophilia A with coagulation factor concentrates may result in the development of inhibitory antibodies directed against factor VIII (FVIII). In this study, a previously unpublished ELISA test for FVIII inhibitor screening (Genetic Testing Institute [GTI] FVIII inhibitor, Brookfield, WI, USA) was evaluated in 131 blood samples (124 samples from patients with haemophilia A, and seven serial samples from one patient with an acquired FVIII inhibitor). Comparisons were made with the routine screening assay (based on recovery of FVIII) and confirmed where positive (< 90% recovery) with the New Oxford assay. The ELISA kit had a sensitivity of 97.7% and specificity of 78.4%. The high negative predictive value of this new test (98.6%) suggests it may be useful as a reliable, rapid (< 2 h) and flexible (microwell strip format) tool for inhibitor screening of samples from both patients with haemophilia A and those with suspected acquired FVIII inhibitors.

Antibodies↗
PubMed1998

Lower limb response and injury in frontal crashes.

This article examines two observational and two experimental data sets that emphasize lower limb injuries in passenger car crashes. Statistics show that 60% of moderate-to-severe below-knee injuries sustained by front seat occupants in head-on crashes occur with > 3 cm of footwell intrusion. Moreover, crash tests and computer simulations of car-to-car frontal offset collisions show no causal relationship between the magnitude of footwell intrusion and the axial load measured in the dummy leg. This article correlates below-knee injuries with several factors that influence their frequency and severity, such as the vehicle change in velocity, the magnitude of footwell intrusion, the rate and timing of the intrusion and the size of the vehicle. The vehicle change in velocity and the intrusion rate and timing had the greatest influence on the risk of lower limb injury, while the other factors had much less of an effect.

Accidents, Traffic↗
PubMed1998

Inflammatory mediators in adults undergoing cardiopulmonary bypass: comparison of centrifugal and roller pumps.

BACKGROUND: The nonocclusive centrifugal pump is used for cardiopulmonary bypass (CPB) and mechanical cardiac assistance. This study examined its impact on proinflammatory cytokine release. METHODS: Forty-one patients undergoing elective coronary artery bypass grafting were randomized prospectively to either a standard roller pump group (n = 21) or a centrifugal vortex pump group (n = 20) for CPB. The two groups were well matched in age, sex, severity of disease, and duration of CPB and aortic cross-clamping. Plasma levels of the cytokines tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8, as well as terminal complement, neutrophil counts, and leukocyte elastase, were analyzed before, during, and after CPB. RESULTS: In both groups, traces of tumor necrosis factor-alpha were observed infrequently and interleukin-1beta was not detected. Plasma levels of interleukin-6 and interleukin-8 increased during and after CPB, reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours. The release of interleukin-6 was significantly greater in the centrifugal group (p < 0.05), whereas the interleukin-8 concentration did not differ between the groups throughout the study period. Levels of terminal complement increased in both groups perioperatively, reaching a peak 30 minutes after protamine administration, whereas neutrophil counts and elastase peaked 2 hours after protamine administration. Plasma terminal complement, neutrophil counts, and elastase release were significantly higher in the centrifugal group (p < 0.05). Peak terminal complement correlated (r = 0.64, p < 0.01) with peak elastase in the centrifugal group only. CONCLUSIONS: This study confirms the proinflammatory nature of CPB in adults and demonstrates that use of the centrifugal pump induces a greater systemic inflammatory response than use of the standard roller pump.

Adult↗
PubMed1998

Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary bypass.

The relative contribution of full-dose aprotinin, used with heparin-bonded surfaces, to contact activation during cardiopulmonary bypass was examined. In vitro Carmeda-bonded cardiopulmonary bypass circuits were perfused with whole blood anticoagulated with heparin (3.3 U/ml). Aprotinin (300 kIU/ml) was added to the circuits of one set of experiments. Samples were taken prior to perfusion and at 30, 60, 120 and 360 min. The activated coagulation time was extended in the aprotinin experiments, significantly at 30 min (P=0.003) and 120 min (P=0.001). Thrombin-antithrombin complexes and prothrombin fragment F1+2 were both higher in the non-aprotinin experiments at 120 min (P=0.02 each) and 360 min (P=0.005 and 0.001, respectively). Plasma leucocyte elastase was raised in the non-aprotinin experiments in comparison to the aprotinin experiments at each timepoint (30 min, P=0.04; 60 min, P=0.006; 120 min, P=0.001; 360 min, P=0.0001), as was interleukin-8 at 120 min (P=0.05) and 360 min (P=0.0001). No differences were found for the platelet activation marker P-selectin. Platelet and white blood cell counts fell significantly in the non-aprotinin experiments compared with the aprotinin experiments at 360 min (P=0.05 and 0.03, respectively). It would appear that the use of aprotinin has additional haemostatic beneficial effects to those found with heparin-bonded circuits in terms of effects on contact activation and inflammation.

Anticoagulants↗
PubMed1997

Evidence of genetic diversity underlying Rh D-, weak D (Du), and partial D phenotypes as determined by multiplex polymerase chain reaction analysis of the RHD gene.

The human blood group Rh antigens are expressed by proteins encoded by a pair of highly homologous genes located at chromosome 1p34-36. One of the genes (RHCE) encodes Rh CcEe antigens, while the other (RHD) the D antigen. Point mutations in the RHCE gene generate the C/c and E/e polymorphisms, while it has been shown that an RHD gene deletion can generate the D-negative phenotype. We have analyzed intron 4 of the RHCE and RHD genes and have defined the site of an RHD-specific deletion located in this intron. Using a multiplex RHD typing assay, which combines a reverse polymerase chain reaction (PCR) primer, which straddles this RHD-specific sequence, and a pair of primers located in exon 10 of the RHD gene, we have analyzed 357 different genomic DNA samples derived from individuals expressing D+, D-, weak D, and partial D phenotypes. Of these, we have noted a significant discordance with our multiplex PCR assay in the D- phenotypes dCcee and dccEe (which have been previously described) and weak D phenotypes. Our results suggest that in five serologically D- individuals we have identified an apparently intact RHD gene. Sequence analysis of transcripts obtained from one of these individuals (of phenotype dCCee) illustrates the presence of full-length RHD transcripts, which have a point mutation at nucleotide 121 (C --> T), which generates an in-frame stop codon (Gln41Stop). Thus, we describe a different molecular basis for generating the D- phenotype to the complete RHD gene deletion described previously. We also show that there are discordances with serotype and the multiplex assay in weak D and partial D phenotypes, indicating that the underlying molecular basis can be heterogeneous. Existing Rh D PCR assays assume the complete absence of the RHD gene in D- phenotypes. We describe a different molecular basis for generating the D- phenotype to the complete RHD gene deletion described previously.

Amino Acid Sequence↗
PubMed1997

"Low-dose" aprotinin modifies hemostasis but not proinflammatory cytokine release.

BACKGROUND: Cytokines are implicated in the pathogenesis of the "whole-body inflammatory response" that may complicate the period after cardiopulmonary bypass (CPB). Low-Dose aprotinin in the pump during CPB has been shown to improve postoperative hemostasis and platelet preservation. We tested the hypothesis that low-dose aprotinin influences the inflammatory reaction (in terms of cytokine release) after CPB. METHODS: In a prospective, randomized study, 36 patients undergoing elective coronary artery bypass grafting were investigated. Nineteen patients received low-dose aprotinin (2 x 10(6) KIU (280 mg] in the pump), and a control group of 19 did not. Complement activation, cytokine production, leukocyte elastase release. D-dimer level, full blood count, postoperative blood loss, and transfusion requirements were analyzed before, during, and after after CPB. RESULTS: Interleukin-1 beta was not detected in either group, whereas traces of tumor necrosis factor-alpha were infrequently observed. Plasma elastase, interleukin-6, interleukin-8, and neutrophil count increased (p < 0.001) during and after CPB compared with the baseline levels, reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours. Proinflammatory cytokine markers did not differ significantly (p > 0.1) between the groups throughout the study period. The C5b-9 level increased (p < 0.001) in both groups perioperatively, reaching its peak 15 minutes after protamine. Twenty-four-hour postoperative blood loss was significantly (p < 0.001) reduced in the aprotinin group in association with markedly reduced D-dimer levels (p < 0.001). Patients in the aprotinin group also received significantly less banked blood postoperatively than the control group (p < 0.01). CONCLUSIONS: Low-dose aprotinin fails to modify proinflammatory cytokine release, yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting.

Aged↗