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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 37 records · Page 2Linked to original sources

Uncertainty in predictions of the climate response to rising levels of greenhouse gases.

The range of possibilities for future climate evolution needs to be taken into account when planning climate change mitigation and adaptation strategies. This requires ensembles of multi-decadal simulations to assess both chaotic climate variability and model response uncertainty. Statistical estimates of model response uncertainty, based on observations of recent climate change, admit climate sensitivities--defined as the equilibrium response of global mean temperature to doubling levels of atmospheric carbon dioxide--substantially greater than 5 K. But such strong responses are not used in ranges for future climate change because they have not been seen in general circulation models. Here we present results from the 'climateprediction.net' experiment, the first multi-thousand-member grand ensemble of simulations using a general circulation model and thereby explicitly resolving regional details. We find model versions as realistic as other state-of-the-art climate models but with climate sensitivities ranging from less than 2 K to more than 11 K. Models with such extreme sensitivities are critical for the study of the full range of possible responses of the climate system to rising greenhouse gas levels, and for assessing the risks associated with specific targets for stabilizing these levels.

Journal Article↗

The exercise-induced enhancement of influenza immunity is mediated in part by improvements in psychosocial factors in older adults.

The primary goal of this study was to determine whether exercise-associated improvements of the immune response to influenza vaccination were mediated by improvements in psychosocial factors in older adults. At baseline, prior to the exercise intervention, older adult participants were immunized with influenza vaccine. Blood samples collected pre-immunization, 1, 4, and 12 weeks post-immunization were analyzed for anti-influenza antibody, whereas influenza-specific cytokine (IFNgamma) was evaluated at 1 week post-immunization. Depression and sense of coherence were measured pre-immunization. Four weeks post-immunization, participants were randomly assigned to either an aerobic exercise group (n=14) or a control group (n=14). After a 10-month exercise intervention, the immunization, blood collections, and psychosocial measures were repeated. At the post-intervention evaluation, exercise participants had improved scores on depression and sense of coherence. Also post-intervention, exercise participants had a greater increase in antibody and IFNgamma production. After controlling for the effect of both psychosocial measures, the exercise treatment remained significant with respect to antibody titer suggesting that the increases in antibody were not mediated by improvement in the psychosocial factors. In contrast, the enhancement of IFNgamma appeared to be mediated at least in part by the psychosocial factors. After controlling for psychosocial factors, exercise treatment was no longer significantly related to the change in IFNgamma. Taken together, our findings may suggest that the mechanism(s) of exercise-induced improvement in immunocompetence involve both physiological and psychological pathways.

Affect↗

[Value of fetal scalp lactate sampling during labour: a comparative study with scalp pH].

OBJECTIVE: To evaluate the validity and the feasibility of fetal scalp lactate sampling during labour in the assessment of non reassuring fetal status. PATIENTS AND METHOD: A prospective observational study was conducted on 129 fetal scalp blood samplings. Scalp lactate measurements were compared to scalp pH (gold standard procedure), neonatal cord blood gas (pH and lactates) and Apgar score. Pathological values taken were for scalp lactates>5 mmol/l, scalp pH<7.20, cord arterial pH<7.10, cord arterial lactates>6,35 mmol/l, and Apgar score<7 at one and five minutes. All measurements were performed using the Rapid Lab 860 device from Bayer. RESULTS: Scalp lactate correlated significantly with scalp pH (R=-0.54, P=0.001), with umbilical artery pH (R=-0.46, P=0,01), with umbilical artery lactate (P=0.49, P=0.01), but with neither Apgar score at one minute (R=-0.21, ns) nor at 5 minutes (R=-0.11, ns). Scalp lactate at a cut-off value of 5 mmol/l had the same predictive values than scalp pH at 7.20 to predict neonatal acidosis. Sampling failure with scalp lactate was inferior to 1 vs 18% for scalp pH. DISCUSSION AND CONCLUSION: The measurement of lactate in fetal blood scalp seems correlated to the fetal scalp pH. It may be an attractive alternative to pH analysis and a useful tool for monitoring fetal asphyxia, especially with the advent of handheld devices requiring small sample volumes.

Adolescent↗

Mapping bacterial glycolipid complexity using capillary electrophoresis and electrospray mass spectrometry.

This chapter presents the application of capillary electrophoresis coupled to electrospray mass spectrometry (CE-ES-MS) for the analysis of complex bacterial lipopolysaccharides (LPS) from pathogenic strains of Haemophilus influenzae and Neisseria meningitidis. A discussion is included of the development of electrophoretic conditions conducive to trace-level enrichment and separation of closely related glycoforms and isoforms, which provided sensitive detection of glycolipids from as little as five bacterial colonies. The chapter also describes the use of mixed MS scanning functions to aid the identification of specific functionalities and immunodeterminants of LPS, such as pyrophosphoethanolamine, phosphocholine, and N-acetyl neuraminic acid (Neu5Ac), which represent less than 2% of the overall LPS population. The combination of high-resolution capillary electrophoresis with sensitive tandem mass spectrometry (MS/MS) provides a unique analytical tool to probe the subtle structural changes resulting from oligosaccharide branching and location of substituted LPS isoforms. The ability to detect a diverse LPS population over a wide dynamic range of expression using CE-MS enables the correlation of structural changes between bacterial strains and isogenic mutants to assign functional gene relationship.

Acylation↗

Liver tumors in wild flatfish: a histopathological, proteomic, and metabolomic study.

Fish play host to viral, bacterial, and parasitic diseases in addition to non-infectious conditions such as cancer. The National Marine Monitoring Programme (NMMP) provides information to the U.K. Government on the health status of marine fish stocks. An aspect of this work relates to the presence of tumors and other pathologies in the liver of the offshore sentinel flatfish species, dab (Limanda limanda). Using internationally agreed quality assurance criteria, tumors and pre-tumors are diagnosed using histopathology. The current study has expanded upon this work by integrating these traditional diagnostic approaches with ones utilizing modern technologies for analysis of proteomic and metabolomic profiles of selected lesions. We have applied SELDI and FT-ICR technologies (for proteomic and metabolomic analyses, respectively) to tumor and non-tumor samples resected from the liver of dab. This combined approach has demonstrated how these technologies are able to identify protein and metabolite profiles that are specific to liver tumors. Using histopathology to classify "analysis groups" is key to the success of such an approach since it allows for elimination of spurious samples (e.g., those containing parasite infections) that may confuse interpretation of "omic" data. As such, the pathology laboratory plays a central role in collating information relating to particular specimens and in establishing sampling groups relative to specific diagnostic questions. In this study, we present pilot data, which illustrates that proteomics and metabolomics can be used to discriminate fish liver tumors and suggest future directions for work of this type.

Adenoma, Liver Cell↗

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.

Adult↗

Clinicopathologic profile of gastric carcinomas at the University Hospital of the West Indies.

The objective of this study was to examine the clinicopathologic features of gastric cancer seen at the University Hospital of the West Indies (UHWI) and to compare the findings with other studies. A retrospective study was conducted using data obtained from the surgical pathology reports of all gastrectomies and gastric biopsies during the period January 1993 and December 2002. Additional cases were identified from the Department of Surgery's audit database. Demographic, clinical and pathological features were analyzed. Two hundred and sixteen patients were identified, 126 males and 90 females. One hundred and thirty-six underwent biopsy procedures but no definitive surgery aimed at cancer eradication, while 70 had gastrectomy. The peak age prevalence in both males and females was the 70-79-year age group. While the antrum was the commonest site, there was an overall increase in tumours of the gastro-oesophageal junction and tumours of the entire stomach in the latter five-year period of the review especially in the 50-59-year age group. Epigastric pain and constitutional symptoms were the common presenting features, and the most common gross tumour characteristic was an ulcerating mass, while histologically, the intestinal variety was most common. Lymph node metastases were common. Helicobacter pylori (Hpylori) were present in 16.7% while chronic multifocal atrophic gastritis was present in 40%. This study indicates that the gastric cancer pattern is typical of developing countries. However, the low prevalence of H pylori in the resected specimens may indicate the importance of other risk factors for gastric cancer development in this population. This warrants further study.

Adult↗

Chronic kidney disease in the elderly; a silent epidemic.

Chronic kidney disease has been shown to be associated with significant increases in mortality and morbidity even in early stages. Despite this it is rarely diagnosed, actively investigated or managed in the elderly. We set out to establish the prevalence of CKD and identify causative factors in a consecutive series of referrals to a geriatric medical clinic. We calculated glomerular filtration rates (GFR) for 101 patients attending a geriatric medical clinic using the Cockroft and Gault formula, and collected data on medications and relevant past medical history. Mild CKD (GFR <60ml/min) was present in 80% of the group. Only 10% of these patients had serum creatinine >130(mmol/L. hypertension was present in 50% and only 9% were diabetic. Almost one third were on inappropriate drugs or dosages; most commonly non-steroidal anti-inflammatory drugs (99%). Chronic kidney disease is extremely common in older people attending a geriatric medical clinic and carries significant risks. CKD will not be detected by serum creatinine alone in 90% of cases. Routine calculation of GFR should be used to provide a more accurate measure of renal impairment and allow earlier intervention, risk factor reduction and improve prescribing practices.

Aged↗

Multicenter study of MTT and resazurin assays for testing susceptibility to first-line anti-tuberculosis drugs.

OBJECTIVE: A multicentre evaluation was performed to assess two rapid low-cost methods, MTT (3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide) and resazurin assays, for testing the susceptibility of Mycobacterium tuberculosis to the first-line anti-tuberculosis drugs rifampicin (RMP), isoniazid (INH), ethambutol (EMB) and streptomycin (SM). METHODS: Thirty coded M. tuberculosis strains were sent to seven laboratories located in Latin America, representing six countries. Each site performed the colorimetric assays, MTT and resazurin, blind for the first-line drugs RMP, INH, EMB and SM. The minimum inhibitory concentration results obtained were compared to the conventional proportion method on Lowenstein-Jensen medium. RESULTS: After establishing the breakpoint concentrations, excellent results were obtained for RMP, INH and EMB, with levels of specificity and sensitivity of between 96% and 99%. CONCLUSION: MTT and resazurin assays are promising, accessible new alternative methods for middle- and low-resource countries that need low-cost methods to perform rapid susceptibility testing of M. tuberculosis to key anti-tuberculosis drugs.

Antitubercular Agents↗

Two-dimensional viscous froth model for foam dynamics.

The two-dimensional viscous froth model is a simple tractable model for foam rheology and coarsening. It includes, but is not confined to, the quasistatic regime. Here we present a detailed analysis and implementation of the model, illustrated with various examples. With certain simplifying assumptions, it provides significant insight into strain-rate-dependent effects in foam rheology and elsewhere, particularly in relation to recent experiments.

Journal Article↗

Increased intestinal permeability in patients with inflammatory bowel disease.

Intestinal permeability can be measured by the sugar absorption test. This test is based on determining the ratio of the urinary excretion of a large and a small carbohydrate after oral administration. The aim of this study was to determine which combination of carbohydrates used in the test gives the highest correlation with disease activity in inflammatory bowel disease. 26 patients with Crohn's disease, 21 patients with ulcerative colitis and 27 healthy control subjects were included in the study. The patients with inflammatory bowel disease had either minimal or highly active disease or were in remission. Two disaccharides (lactulose: L, and cellobiose: C) and two smaller carbohydrates (rhamnose:R, and mannitol:M) were given orally and the urinary excretion was measured by high pressure liquid chromatography followed by pulsed amperometric electrochemical detection on a gold electrode. The ratios C/R, L/R, C/M and L/M were used as indicators for intestinal permeability. - There were no side effects of oral sugar administration. All patients tolerated the test well. Lactulose, rhamnose and cellobiose concentrations are easily be measured in the urine whereas mannitol measurement requires the use of an anion exchanger. This produced inconsistent results. Patients with Crohn's disease or with ulcerative colitis had increased permeability indices in comparison to healthy controls, even in remission. The L/R ratio gave a better differentiation between the healthy controls and patients with active disease than the other agents. Changes in disease activity are best reflected by use of cellobiose/rhamnose excretion quotient.

Adolescent↗

Effect of voluntary contraction intensity on the H-reflex and V-wave responses.

This study examined the evolution of H-reflex and V-wave responses of soleus muscle during maximal voluntary plantar-flexor contraction. We also investigated the relationship between the V response and force level and between V-wave during maximal voluntary contraction (MVC) and the maximal H reflex at rest. The H-reflex and the V-wave responses are measures of motoneuron excitability and also reflect the magnitude of presynaptic inhibition on Ia afferents and the magnitude of descending motor drive. Both may be influenced by postsynaptic inhibition. Twenty male subjects participated in the study and were assigned to one of two groups. The maximal M wave (Mmax) was evoked at rest in the 20 subjects, who then performed 10 maximal voluntary contraction. During MCV performance, a stimulus was delivered at supra-maximal intensity, which allowed us to record the superimposed M wave (Msup) and V wave of the soleus muscle. These parameters were also recorded during sub-maximal contractions (20, 40, 60, 80% of one MVC) in 10 subjects. The maximal H reflex (Hmax), was evoked at rest in the other 10 subjects. These subjects then performed 10 MVC and the Hsup (superimposed H, evoked by means of stimulus at Hmax intensity) was recorded. The results show that the amplitude of maximal M wave increased during MVC (gain 44.52 +/- 10.71%). No significant difference between Hmax/Mmax at rest and the Hsup/Msup ratios during MVC was observed, while an effect of force level on the V/Msup ratio was found. V/Msup and Hmax/Mmax were linearly correlated (r2 = 0.81), but V/Msup was significantly lower (P < 0.01) than Hmax/Mmax. In conclusion, the present study shows that maximal voluntary contractions potentiate some reflex responses. The V wave, which reflects motoneuron excitability presynaptic inhibition of Ia afferents and the magnitude of descending central motor drive to spinal motoneurons, may be a relatively simple method to analyse the modulation adaptive neural alterations at spinal and supraspinal level during voluntary contractions.

Adult↗

Assessment of low-frequency fatigue with two methods of electrical stimulation.

The aim of this study was to compare the use of transcutaneous vs. motor nerve stimulation in the evaluation of low-frequency fatigue. Nine female and eleven male subjects, all physically active, performed a 30-min downhill run on a motorized treadmill. Knee extensor muscle contractile characteristics were measured before, immediately after (Post), and 30 min after the fatiguing exercise (Post30) by using single twitches and 0.5-s tetani at 20 Hz (P20) and 80 Hz (P80). The P20-to-P80 ratio was calculated. Electrical stimulations were randomly applied either maximally to the femoral nerve or via large surface electrodes (ES) at an intensity sufficient to evoke 50% of maximal voluntary contraction (MVC) during a 80-Hz tetanus. Voluntary activation level was also determined during isometric MVC by the twitch-interpolation technique. Knee extensor MVC and voluntary activation level decreased at all points in time postexercise (P < 0.001). P20 and P80 displayed significant time x gender x stimulation method interactions (P < 0.05 and P < 0.001, respectively). Both stimulation methods detected significant torque reductions at Post and Post30. Overall, ES tended to detect a greater impairment at Post in male and a lesser one in female subjects at both Post and Post30. Interestingly, the P20-P80 ratio relative decrease did not differ between the two methods of stimulation. The low-to-high frequency ratio only demonstrated a significant time effect (P < 0.001). It can be concluded that low-frequency fatigue due to eccentric exercise appears to be accurately assessable by ES.

Adult↗

Neural activation of the triceps surae is impaired following 2 weeks of immobilization.

The purpose of this study was to investigate the effect of 2 weeks of ankle joint immobilization on triceps surae neural activation, with particular emphasis on the potential differences between the monoarticular soleus and the biarticular gastrocnemius muscles. Seventeen male volunteers were divided into the immobilized group (IG, n = 8) and the control group (CG, n = 9). Elastic adhesive bandages and an ankle stabilization orthosis were used to immobilize the ankle joint only. The plantar flexor torque obtained during maximal voluntary contractions (MVC) and after single, paired and tetanic stimuli applied at rest was measured. The associated EMG activity from the soleus and gastrocnemius muscles was also recorded, and their activation levels were estimated by means of the twitch interpolation technique. After immobilization, triceps surae maximal voluntary torque significantly decreased by 17% (P < 0.001). Strength losses were accompanied by a decrement in activation level (-6%, average of the three techniques used) and in maximal 100 Hz tetanic force (-11%). A significant decrease in the soleus (-22%, P < 0.05) but not in the gastrocnemius EMG activity, normalized to respective M-waves, was also found. It was concluded that the reduced voluntary torque output after immobilization could be attributed to both muscular and neural alterations. These latter selectively involved the monoarticular soleus muscle, while neural drive to the biarticular gastrocnemii, which had not been immobilized in their function as knee flexors, was preserved.

Adult↗

Electrocardiographic safety profile and monitoring guidelines in pediatric psychopharmacology.

A number of medications commonly used in pediatric psychopharmacology can prolong the QTc interval of the electrocardiogram. QTc prolongation can in turn predispose to torsades de pointes, a sometimes deadly arrhythmia. These considerations are clinically relevant given documented, if still controversial, reports of sudden deaths associated with the use of the tricyclic antidepressant (TCA) desipramine in children. While most reports of QTc prolongation have involved adult patients, this adverse effect can occur in children. After discussing the QTc parameter's derivation, accuracy, and limitations, this article reviews current knowledge about the propensity of the antipsychotics (both atypical and traditional), TCAs, and alpha agonists to prolong the QTc interval in young patients. Based on the literature reviewed, guidelines are provided for clinical and electrocardiographic monitoring in pediatric psychopharmacology.

Electrocardiography↗

Treatment of type II endoleaks after endovascular repair of abdominal aortic aneurysms: translumbar puncture and injection of thrombin into the aneurysm sac.

OBJECTIVES: The aim of this article is to report our experience in the use of a new technique for the treatment of type II endoleaks which appear after the endovascular treatment of abdominal aortic aneurysms. MATERIALS AND METHODS: In three patients with secondary type II endoleaks, we performed a translumbar puncture, introducing a 22-Gauge needle into the aneurysm sac under CT guidance. Once intrasac pressure had been registered, 1000U (2 ml) of human thrombin were slowly injected into the sac. RESULTS: Complete sealing of the endoleak was achieved in all three patients, confirmed by the lack of contrast filling of the sac in the CT scans performed 5 min and 24 h after the procedure. Initial intrasac pressure was equal to systolic arterial pressure in the three patients. After the procedure, the pressure decreased by 30-40 mmHg. There were no complications during the procedure, which lasted 45-90 min. No endoleak recurrence has been observed in any of the three cases 6 months later. CONCLUSIONS: We present an alternative method of treating type II endoleaks, which could become the treatment of choice if and when a wider experience confirms our initial good results.

Aortic Aneurysm, Abdominal↗