Biomedical subjects

Michael J Walsh

Publications and source records attributed to Michael J Walsh.

9 recordsLinked to original sources

PubMed2006

ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.

Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA-LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm(-1) - 950 cm(-1) consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (approximately 1650 cm(-1)) and II (approximately 1530 cm(-1)) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.

Female↗

PubMed2006

Low-dose treatment with polybrominated diphenyl ethers (PBDEs) induce altered characteristics in MCF-7 cells.

Polybrominated diphenyl ethers (PBDEs) are hydrophobic and persistent additive flame retardants that seemingly transfer into environmental compartments where they bioaccumulate i.e. in human biota. We examined the micronucleus-forming activities of low-dose PBDEs (congeners 47, 99, 153, 183 or 209) in MCF-7 cells along with their ability to modulate growth, cell biochemistry [by infrared (IR) microspectroscopy], clonogenic survival or quantitative expression of cytochrome P450 isoenzymes (CYP1A1, CYP1A2 and CYP1B1), cyclin-dependent kinase inhibitor 1A [CDKN1A (P21(WAF1/CIP1))], B-cell leukaemia/lymphoma-2 (BCL-2) and Bcl-2-associated X (BAX). Elevations in micronucleus formation were observed following treatment with 10(-12) to 10(-9) M PBDE concentrations despite the fact that less than one-fourth of the concentration of each test agent administered partitioned out of the media and into the incubating cells. However, low-dose treatment levels remained within the range of reported concentrations measured in UK serum samples collected in 2003. Clonogenic survival and gene expression was unaltered following 10(-12) to 10(-9) M PBDE treatment but significant (P < 0.05) elevations in growth kinetics were observed. Significant alterations in IR cell spectra were associated with treatments, and plotted clusters following principal component analysis highlighted these changes. Whether such in vitro effects point to an underlying ability of PBDEs to initiate and drive target-cell alterations in vivo now needs to be addressed.

Cell Line, Tumor↗

PubMed2006

IR microspectroscopy: potential applications in cervical cancer screening.

Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3-5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated 'biochemical-cell fingerprint' of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.

Female↗

PubMed2005

Trends in gamma-hydroxybutyrate (GHB) and related drug intoxication: 1999 to 2003.

STUDY OBJECTIVE: To analyze changes in gamma-hydroxybutyrate (GHB) case reporting, we review GHB or congener drug cases reported to the California Poison Control System, comparing these to other data sets. METHODS: We identified cases from the California Poison Control System computerized database using standardized codes and key terms for GHB and congener drugs ("gamma butyrolactone," "1,4-butanediol," "gamma valerolactone"). We noted California Poison Control System date, caller and exposure site, patient age and sex, reported coingestions, and outcomes. We compared California Poison Control System data to case incidence from American Association of Poison Control Centers and Drug Abuse Warning Network data and drug use prevalence from National Institute for Drug Abuse survey data. RESULTS: A total of 1,331 patients were included over the 5-year period (1999-2003). California Poison Control System-reported GHB exposures decreased by 76% from baseline (n=426) to the final study year (n=101). The absolute decrease was present across all case types, although there was a significant proportional decrease in routine drug abuse cases and an increase in malicious events, including GHB-facilitated sexual assault (P=.002). American Association of Poison Control Centers data showed a similar decrease from 2001 to 2003. Drug Abuse Warning Network incidence flattened from 2001 to 2002 and decreased sharply in 2003. National Institute for Drug Abuse survey time trends were inconsistent across age groups. CONCLUSION: Based on the precipitous decrease in California Poison Control System case incidence for GHB during 5 years, the parallel trend in American Association of Poison Control Centers data, and a more recent decrease in Drug Abuse Warning Network cases, a true decrease in case incidence is likely. This could be due to decreased abuse rates or because fewer abusers seek emergency medical care. Case reporting may account for part of the decrease in the incidence of poison center contacts involving GHB.

Adolescent↗

PubMed2005

Inflammatory markers are not associated with outcomes following elective external cardioversion.

BACKGROUND: Electrical cardioversion is a common modality of therapy for persistent atrial fibrillation. Unfortunately even if the cardioversion is initially successful many patients revert to atrial fibrillation. It has been proposed that there may be an inflammatory component to this arrhythmia. It is interesting to speculate that this may have a role in determining the outcome following elective cardioversion. METHODS: The study group consisted of 81 patients with persistent atrial fibrillation undergoing elective external cardioversion. Blood samples were taken immediately prior to the procedure. Soluble E-Selectin, P-Selectin, intra-cellular adhesion molecule and vascular cell adhesion molecule were assayed using a commercially available enzyme linked immunosorbent assay technique (R&D systems) and high sensitivity C reactive protein was measured by rate nephelometry. Patients were reviewed at 8 weeks and bloods were taken at this time. RESULTS: At baseline patients who had an unsuccessful cardioversion (n=15) were compared to those who had a successful cardioversion (n=66). Thirty-two patients of the 66 initially successful patients reverted to atrial fibrillation during the follow-up period. There was no difference in the levels of baseline serum inflammatory markers measured between those with an unsuccessful cardioversion and those who were successful. When the group who reverted to atrial fibrillation were compared to those who remained in sinus rhythm again there was no difference in the levels of serum markers measured at baseline. CONCLUSION: There was no association between maintenance of sinus rhythm following cardioversion and serum inflammatory markers.

Atrial Fibrillation↗

PubMed2004

Surface electromyographic activity in total laryngectomy patients following laryngeal nerve transfer to neck strap muscles.

Hands-free triggering and pitch control would improve electrolarynx devices, which are inconvenient to use and sound unnatural. The present study tested the strategy of salvaging voice-related neural signals for hands-free electrolarynx control either by transferring cut recurrent laryngeal nerves (RLNs) to denervated neck strap muscles or by preserving strap muscles with their normal innervation. An RLN nerve transfer was performed at the time of total laryngectomy in 8 individuals, and in 5 of these subjects, strap muscles with intact ansa cervicalis innervation were also preserved for comparison. Neck surface electromyography performed over the strap muscles was used periodically for more than 1 year on phonatory and nonphonatory tasks. Signals were eventually obtained in all subjects from both RLN-innervated and ansa-innervated strap muscles that correlated with speech production. After 1 year, RLN-driven signals were larger than ansa-driven signals in magnitude, and their timing appeared better correlated with intended phonation. The results show that neck surface electromyography is an effective control source for hands-free electrolarynx activation, and that RLN transfer may provide the best approach for obtaining phonation-related activity.

Electromyography↗

PubMed2003

Early diastolic filling dynamics in diastolic dysfunction.

BACKGROUND: The aim of the study was to determine the relationship between the rate of peak early mitral inflow velocity and the peak early diastolic mitral annular tissue velocities in normal controls and to compare them with subjects with diastolic dysfunction. METHODS: The relationship between early passive diastolic transmitral flow and peak early mitral annular velocity in the normal and in diastolic dysfunction was studied. Two groups comprising 22 normal controls and 25 patients with diastolic dysfunction were studied. RESULTS: Compared with the normal group, those with diastolic dysfunction had a lower E/A ratio (0.7 +/- 0.2 vs. 1.9 +/- 0.5, p < 0.001), a higher time-velocity integral of the atrial component (11.7 +/- 3.2 cm vs. 5.5 +/- 2.1 cm, p < 0.0001), a longer isovolumic relaxation time 73 +/- 12 ms vs. 94 +/- 6 ms, p < 0.01 and a lower rate of acceleration of blood across the mitral valve (549.2 +/- 151.9 cm/sec2 vs. 871 +/- 128.1 cm/sec2, p < 0.001). They also had a lower mitral annular relaxation velocity (Ea) (6.08 +/- 1.6 cm/sec vs 12.8 +/- 0.67 cm/sec, p < 0.001), which was positively correlated to the acceleration of early diastolic filling (R = 0.66), p < 0.05. CONCLUSIONS: This investigation provides information on the acceleration of early diastolic filling and its relationship to mitral annular peak tissue velocity (Ea) recorded by Doppler tissue imaging. It supports not only the premise that recoil is an important mechanism for rapid early diastolic filling but also the existence of an early diastolic mechanism in normal.

Adult↗

PubMed2003

Reciprocal activation of leukocyte-endothelial adhesion molecules in acute coronary syndromes.

BACKGROUND: The acute coronary syndromes are associated with an intense inflammatory response and sustained leukocyte activation. This inflammatory state has been correlated with an adverse prognosis, but the source of this inflammation remains controversial, with evidence that it may arise either from the coronary vasculature or from the systemic endothelium. METHODS: Levels of soluble cell adhesion molecules, and of their respective monocyte cell surface ligands, were measured in the peripheral serum of 21 patients presenting with acute coronary syndromes. Soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were measured by enzyme linked immunosorbent assay and expression of the monocyte integrins CD11b (Mac-1) and CD49d (VLA-4) was measured by direct immunofluorescence using flow cytometry. RESULTS: High levels of the monocyte receptor CD11b (531 vs. 345 MFI, P<0.01), and its soluble intercellular adhesion molecule-1 (329 vs. 232 ng/ml, P<0.01), were noted in patients with acute coronary syndromes compared to healthy controls. CONCLUSIONS: Reciprocal activation of monocyte receptor ligands and endothelial adhesion molecules was found in the peripheral blood of patients with acute coronary syndromes. This may indicate a coordinated state of pro-inflammatory upregulation with widespread activation of both leukocytes and endothelium and suggests a systemic rather than local source for inflammation in acute coronary disease.

Aged↗

PubMed2002

Endothelial inflammation and thrombolysis resistance in acute myocardial infarction.

BACKGROUND: Despite recent refinements to thrombolysis for acute myocardial infarction, a significant minority of patients still fail to reperfuse. There is no reliable predictor of this state of "thrombolysis resistance", but platelet and endothelial factors are believed to be important. Cell adhesion molecules are expressed by the endothelium when activated and their shed or soluble portion can be quantified in the peripheral serum, where they may be taken as a measure of endothelial activation. We sought to find a link between markers of endothelial inflammation at time of infarction and failure to reperfuse as measured by vessel occlusion at angiography. METHODS: Patients presenting with their first acute myocardial infarction had levels of soluble adhesion molecules, C-reactive protein and monocyte chemotactic protein-1 measured prior to thrombolysis. An angiogram on day five after admission was performed to establish patency of the index vessel. RESULTS: Levels of soluble vascular adhesion molecule-1 (sVCAM-1) taken prethrombolysis were significantly elevated compared to those with a patent vessel (620+/-90 vs. 418+/-28 ng/ml, P<0.03. The positive predictive value of sVCAM-1 for vessel patency was 88%. CONCLUSIONS: We found elevated serum levels of the adhesion molecule soluble vascular adhesion molecule-1 (sVCAM-1) at presentation in patients with acute myocardial infarction who did not respond to thrombolysis. Endothelial activation may be important in thrombolysis resistance.

Acute Disease↗