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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 19 recordsLinked to original sources

Estimating the long-term impact of a prophylactic human papillomavirus 16/18 vaccine on the burden of cervical cancer in the UK.

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites.

Calibration↗

Preclinical and post-treatment changes in the HCC-associated serum proteome.

SELDI-based proteomic profiling of body fluids is currently in widespread use for cancer biomarker discovery. We have successfully used this technology for the diagnosis of hepatocellular carcinoma (HCC) in hepatitis C patients and now report its application to serial serum samples from 37 hepatitis C patients before development of HCC, with HCC and following radiofrequency ablation of the tumour. As with alpha-fetoprotein, an accepted biomarker for HCC, we hypothesised that HCC-associated proteomic features would 'return to normal' following successful treatment and the primary aim of our study was to test this hypothesis. Several SELDI peaks that changed significantly during HCC development were detected but they did not reverse following treatment. These data may be interpreted to suggest that the characteristic SELDI profile is not linearly related to tumour burden but may result from the progression of underlying liver disease or from the emergence of precancerous lesions. beta2-Microglobulin, a protein previously reported to be markedly elevated in patients with HCV related HCC, was also the most significantly HCC associated proteomic feature (m/z 11720) in this study.

Aged↗

Identification of serum biomarkers for colon cancer by proteomic analysis.

Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. Early detection greatly improves prognosis; however, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their applicability. No serum-based test is currently of sufficient sensitivity or specificity for widespread use. In the best currently available blood test, carcinoembryonic antigen exhibits low sensitivity and specificity particularly in the setting of early disease. Hence, there is great need for new biomarkers for early detection of CRC. We have used surface-enhanced laser desorbtion/ionisation (SELDI) to investigate the serum proteome of 62 CRC patients and 31 noncancer subjects. We have identified proteins (complement C3a des-arg, alpha1-antitrypsin and transferrin) with diagnostic potential. Artificial neural networks trained using only the intensities of the SELDI peaks corresponding to identified proteins were able to classify the patients used in this study with 95% sensitivity and 91% specificity.

Adenocarcinoma↗

Transfusion of autologous blood from reinfusion systems in total knee arthroplasty.

After total knee arthroplasty (TKA) the technique of wound management is not standardised. In this prospective study the efficacy of autologous blood reinfusion from the wound was investigated. One hundred patients (100 TKAs) were enrolled in this sequential cohort study. In one-half of the operations, a reinfusion system with suction and in the other half one wound drain without suction were used. Blood loss, transfusion requirements, range of motion, Insall scores and the incidence of complications were studied. The use of a reinfusion system did not decrease the homologous transfusion requirements. The blood loss in the group with a suction drainage system was significantly higher. Our experiences since May 2002 with one drain without suction in 787 consecutive TKAs confirm all findings of the current study.

Aged↗

Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study.

Abacavir therapy is associated with significant drug hypersensitivity in approximately 8% of recipients, with retrospective studies indicating a strong genetic association with the HLA-B*5701 allele. In this prospective study, involving 260 abacavir-naive individuals (7.7% of whom were positive for HLA-B*5701), we confirm the usefulness of genetic risk stratification, with no cases of abacavir hypersensitivity among 148 HLA-B*5701-negative recipients.

Adult↗

Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis.

Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a 'blind' test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73-99%) and 86% specificity (95% CI 65-95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (P<0.001) and were identified as kappa and lambda immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC.

Amino Acid Sequence↗

Morphological, yield, cytological and molecular characterization of a bread wheat x tritordeum F1 hybrid.

The morphological, yield, cytological and molecular characteristics of bread wheat x tritordeum F(1) hybrids (2n = 6x = 42; AABBDH(ch)) and their parents were analysed. Morphologically, these hybrids resembled the wheat parent. They were slightly bigger than both parents, had more spikelets per spike, and tillered more profusely. The hybrids are self-fertile but a reduction of average values of yield parameters was observed. For the cytological approach we used a double-target fluorescence in situ hybridization performed with total genomic DNA from Hordeum chilense L. and the ribosomal sequence pTa71. This technique allowed us to confirm the hybrid nature and to analyse chromosome pairing in this material. Our results showed that the expected complete homologous pairing (14 bivalents plus 14 univalents) was only observed in 9.59% of the pollen mother cells (PMCs) analysed. Some PMCs presented autosyndetic pairing of H(ch) and A, B or D chromosomes. The average number of univalents was higher in the wheat genome (6.8) than in the H(ch) genome (5.4). The maximum number of univalents per PMC was 20. We only observed wheat multivalents (one per PMC) but the frequency of trivalents (0.08) was higher than that of quadrivalents (0.058). We amplified 50 RAPD bands polymorphic between the F(1) hybrid and one of its parents, and 31 ISSR polymorphic bands. Both sets of markers proved to be reliable for DNA fingerprinting. The complementary use of morphological and yield analysis, molecular cytogenetic techniques and molecular markers allowed a more accurate evaluation and characterization of the hybrids analysed here.

Breeding↗

Pulmonary toxicity associated with sirolimus treatment in kidney transplantation.

INTRODUCTION: An important side effect of sirolimus, a drug often used in organ transplantation, is pulmonary toxicity. MATERIALS AND METHODS: We present five kidney transplant patients who developed this toxicity associated with sirolimus. All underwent chest radiography computed tomography, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), microbiological studies of the bronchial aspirate, blood, and sputum, and cytomegalovirus (CMV) polymerase chain reaction (PCR) in blood as well as two had transbronchial biopsies. RESULTS: All five were men of mean age 54.8 +/- 10.3 years. In two sirolimus formed part of de novo therapy, and three were converted from calcineurin inhibitors. The mean treatment time was 16.6 +/- 13.7 months, with trough levels of 11.3 +/- 3 ng/mL. The patients presented with fever, cough, dyspnea, anemia, and dyslipidemia. The radiological pattern was diffuse alveolointerstitial (n = 2), or bilateral basal interstitial (n = 2), or bilateral basal alveolar (n = 1). The cell count in the BAL was 95% to 99% macrophages. In two patients cultures for bacteria were positive: Hemophilus and Pseudomonas. Tests for fungi, mycobacteria, pneumocystis, and legionella, as well as PCR for CMV were all negative. Transbronchial biopsy yielded insufficient material in one patient and a deposit of fibrinoid material and nonnecrotizing granuloma in the other. Antibacterial therapy was started, three with cotrimoxazole and two with ganciclovir, with no response. The respiratory symptoms improved after withdrawal of sirolimus (mean, 2.4 +/- 1.5 days). The mean hospital stay was 19.8 +/- 14.1 days. CONCLUSION: Pulmonary toxicity due to sirolimus should be included in the differential diagnosis of kidney transplant patients who display signs of interstitial pneumonia. Its diagnosis is difficult requiring exclusion of other pulmonary diseases. Resolution of the symptoms was quick after suspension of the drug.

Adult↗

[Prenatal diagnosis and management of a case of rapidly involuting congenital hemangioma. Review of literature].

Rapidly involuting congenital hemangioma (RICH) is a rare vascular lesion, identified in 1996, of elective localization in the dermal-hypodermic tissue. Its name comes from its particular natural course: it is fully developed at birth and then completely involutes, usually in the first year. We present a case of a RICH of the scalp discovered with a screening ultrasonography in the 31st week of gestation. We list the differential diagnoses. After birth, positive diagnosis lies preferably on pathology examination of a biopsy specimen in order to eliminate the hypothesis of a less favorable vascular lesion, teratoma or malignant tumor.

Adult↗

Plantar flexion torque as a function of time of day.

The possible peripheral and/or central origin in the mechanisms responsible for day-time fluctuation in maximal torque of the triceps surae muscle were investigated with a special emphasis on antagonist muscle coactivation. Eleven healthy male subjects (physical education students) took part in this investigation. The electromechanical properties of the plantar flexor muscles were recorded at two different times of day: between 06:00 h and 08:00 h in the morning and between 17:00 h and 19:00 h in the evening. To investigate peripheral mechanisms, the posterior tibial nerve was stimulated at rest, using percutaneous electrical stimuli, to evoke single twitch, double twitch, and maximal tetanic contraction (100 Hz). Maximal voluntary contraction of the plantar flexors was also assessed by means of the relative electromyographic activity of respective agonist and antagonist muscles (soleus, gastrocnemius medialis, gastrocnemius lateralis, and tibialis anterior). A double twitch was delivered during maximal voluntary plantar flexion to record muscle activation (i.e., interpolated twitch technique). The coactivation level of the tibialis anterior muscle during plantar flexion was calculated. The results indicated a significant decrease in maximal voluntary muscle torque of triceps surae in the evening as compared with the morning (-7.0 %; p < 0.05). Concerning the central command, when extrapolated by the twitch interpolation technique, the decrease in mean activation level of -6.8 % was consistent with the fluctuation in torque (-7.0 %). Soleus muscle electromyographic activity (normalized to the M-wave) showed a significant decline (21.6 %; p < 0.001). Moreover, individual changes in MVC percentage were significantly related to those of normalized electromyographic activity of the soleus muscle (r = 0.688; p < 0.01). Thus, it indicated that the subject's capacity to activate the soleus muscle was affected by the time of day. The coactivation level in the tibialis anterior muscle during plantar flexion did not change significantly in the evening. Concerning peripheral mechanisms, we observed a decrease in maximal M-wave amplitude for soleus and gastrocnemii, associated with unchanged single twitch and tetanus torque. To conclude, impairment in soleus muscle central command seemed to be the mechanism in the origin of torque failure. Such information would be of importance in the investigation of day-time fluctuations in complex motor task performances implicating the triceps surae muscle.

Adult↗

Comparison of redox and D29 phage methods for detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis.

Rapid, accurate and inexpensive methods are essential to detect drug-resistant Mycobacterium tuberculosis and allow timely application of effective treatment and precautions to prevent transmission. The proportion method, the MTT and Alamar Blue redox methods, and the D29 mycobacteriophage assay, were compared for their ability to detect resistance to isoniazid and rifampicin. When tested against a panel of known M. tuberculosis strains, the redox methods and the D29 assay showed good sensitivity and specificity compared to the proportion method, suggesting that they could be useful alternatives for identifying multidrug resistance in M. tuberculosis.

Antitubercular Agents↗

Transglutaminase-catalyzed reactions responsible for the pathogenesis of celiac disease and neurodegenerative diseases: from basic biochemistry to clinic.

Transglutaminases (TGases) are enzymes which catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate with the formation of an N-gamma-(epsilon-L-glutamyl)-L-lysine [GGEL] cross link (isopeptidic bond) and the concomitant release of ammonia. Such cross-linked proteins are often highly insoluble. The TGases are closely related enzymes and can also catalyze other important reactions for cell life. Recently, several findings concerning the relationships between the biochemical activities of the TGases and the basic molecular mechanisms responsible for some human diseases, have been reported. For example, some neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), supranuclear palsy, etc., are characterized in part by aberrant cerebral TGase activity and by increased cross-linked proteins in affected brains. Our article describes the biochemistry and the physio-pathological roles of the TGase enzymes, with particular reference to human pathologies in which the molecular mechanism of disease can be due to biochemical activities of the tissue TGase enzyme (tTGase, type 2), such as in a very common human disease, Celiac Disease (CD), and also in certain neuropsychiatric disorders.

Brain↗

Evaluation of a rapid culture method for tuberculosis diagnosis: a Latin American multi-center study.

SETTINGS: Tuberculosis (TB) diagnostic laboratories in Latin America. OBJECTIVES: Evaluation of thin-layer agar (TLA) compared to Löwenstein-Jensen (LJ) culture for the diagnosis of TB. DESIGN: Phase II prospective study in six laboratories. Samples included sputum and extra-pulmonary specimens from patients with a clinical diagnosis of TB. Respiratory samples were decontaminated using NaOH/ NALC; all samples were centrifuged, stained with Ziehl-Neelsen for acid-fast bacilli (AFB), cultured on LJ and TLA and identified according to recommended procedures. Sensitivity and likelihood ratios (LR), growth detection time and contamination rate were calculated for both media. RESULTS: A total of 1118 clinical specimens were studied. Cultures detected Mycobacterium tuberculosis in all AFB-positive samples, whereas for AFB-negative specimens LJ detected 3.2% and TLA 4.4%. Sensitivity was 92.6% (95%CI 87.9-95.9) and 84.7% (95%CI 78.8-89.0) for TLA and LJ, respectively. Positive and negative LRs were similar. Contamination was 5.1% for TLA and 3.0% for LJ. Median time to detection of a positive culture was 11.5 days (95%CI 9.3-15.0) for TLA and 30.5 days (95%CI 26.9-39.0) for LJ (P < 0.0001). CONCLUSION: Difference in the characteristics of the participating laboratories, the disease prevalence and the number and type of specimens processed did not affect the overall performance of TLA as compared to LJ, supporting the robustness of the method and its feasibility in different laboratory settings.

Agar↗

Evaluation of the resazurin microtiter assay for rapid detection of ofloxacin resistance in M. tuberculosis.

OBJECTIVE: To evaluate the performance of the colorimetric resazurin microtiter assay (REMA) method for the detection of ofloxacin resistance. METHODS: A panel of 120 multidrug-resistant Mycobacterium tuberculosis strains was tested blindly by the REMA method and compared with the results obtained using the BACTEC 460 method. RESULT: A very good correlation was observed between the two methods. CONCLUSION: The REMA method is simple, rapid and can be an inexpensive alternative procedure for the rapid detection of anti-tuberculosis drug resistance in laboratories with limited resources.

Anti-Bacterial Agents↗

Role of dislocation loops on the elastic constants of lyotropic lamellar phases.

We study the role of dislocation loops defects on the elasticity of lamellar phases by investigating the variation of the lamellar elastic constants, B and K, induced by the proliferation of these defects. We focus our interest on one particular lamellar phase made up of a mixture of C(12)E(5) and DMPC in water, which is already well-characterised. This lamellar phase undergoes a second-order (or weakly first-order) lamellar-to-nematic phase transition at about 19 degrees C and dislocation loops are seen to proliferate within the lamellar structure when temperature is decreased below 30 degrees C. The values of both elastic constants of this given lamellar phase are measured as a function of temperature, approaching the lamellar-to-nematic transition, with the help of Quasi-Elastic Light Scattering (QELS) on oriented lamellar phases. Very surprisingly we observe a strong and rapid increase in both Band K as the lamellar-to-nematic transition temperature is approached. These increases are seen to start as soon as dislocation loops can be observed in the lamellar phase. We interpret our results as being the consequence of the appearance and proliferation of dislocation loops within the lamellar structure. According to a simple model we developed we show that B and K are proportional to the density of dislocation loops in the lamellar phase.

Colloids↗

MRI in guiding and assessing intramyocardial therapy.

Cardiovascular intervention, using MRI guidance, is challenging for clinical applications. Real-time imaging sequences with high spatial resolution are needed for monitoring intramyocardial delivery of drug, gene, or stem cell therapies. New generation MR scanners make local intramyocardial and vascular wall therapies feasible. Contrast-enhanced MRI is used for assessing myocardial ischemia, infarction, and scar tissue. Active (microcoils) and passive (T1 and T2* mechanisms) tracking methods have been used for visualization of endovascular catheters. Safety issues related to potential heating of endovascular devices is still a major obstacle for MRI-guided interventions. Fabrication of MRI-compatible interventional devices is limited. Noninvasive imaging strategies will be critical in defining spatial and temporal characteristics of angiogenesis and myocardial repair as well as in assessing the efficacy of new therapies in ischemic heart disease. MRI contrast media improve the capability of MRI by delineating the target and vascular tree. Labeling stem cells enables MRI to trace distribution, differentiation, and survival in myocardium and vascular wall. In the long term, MRI in guiding and assessing intramyocardial therapy may circumvent the limitations of peripherally administered cell therapy, X-ray angiography, and nuclear imaging. MRI represents a highly attractive discipline whose systematic development will foster the implementation of new cardiac and vascular therapies.

Cardiomyopathies↗