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Biomedical subjects

M Warren

Publications and source records attributed to M Warren.

At least 19 recordsLinked to original sources
PubMed1999

In vivo and in situ ischemic tissue characterization using electrical impedance spectroscopy.

The investigation of processes of ischemia in different organ tissues is very important for the development of methods of protection and preservation during surgical procedures. Electrical impedance spectroscopy was used to distinguish between different tissues and their degree of ischemia. We describe mathematical methods used to adjust experimental data to Cole-Cole models for one-circle and two-circle impedance loci and a study of the main parameters for representing the behavior of ischemia in time. In vivo and in situ postmortem measurements of different tissues from pigs are shown in the 100 Hz to 1 MHz range. The Cole parameters that best characterize the ischemia are R0 and fc.

Animals↗
PubMed1999

Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin signaling pathways.

We have shown that estrogen elicits a selective enhancement of the growth and differentiation of axons and dendrites (neurites) in the developing CNS. We subsequently demonstrated widespread colocalization of estrogen and neurotrophin receptors (trk) within developing forebrain neurons and reciprocal transcriptional regulation of these receptors by their ligands. Using organotypic explants of the cerebral cortex, we tested the hypothesis that estrogen/neurotrophin receptor coexpression also may result in convergence or cross-coupling of their signaling pathways. Estradiol elicited rapid (within 5-15 min) tyrosine phosphorylation/activation of the mitogen-activated protein (MAP) kinases, ERK1 and ERK2, that persisted for at least 2 hr. This extracellular signal-regulated protein kinase (ERK) activation was inhibited successfully by the MEK1 inhibitor PD98059, but not by the estrogen receptor (ER) antagonist ICI 182,780, and did not appear to result from estradiol-induced activation of trk. Furthermore, we also found that estradiol elicited an increase in B-Raf kinase activity. The latter and subsequent downstream events leading to ERK activation may be a consequence of our documentation of a multimeric complex consisting of, at least, the ER, hsp90, and B-Raf. These novel findings provide an alternative mechanism for some of the estrogen actions in the developing CNS and could explain not only some of the very rapid effects of estrogen but also the ability of estrogen and neurotrophins to regulate the same broad array of cytoskeletal and growth-associated genes involved in neurite growth and differentiation.

Animals↗
PubMed1999

Psychobiological markers of stress in pregnancy: 6-sulfatoxymelatonin--a longitudinal study.

Maternal stress, physical and psychological, has been associated with adverse pregnancy outcome. The pineal gland is a physiological transducer that reflects adrenergic input. In a recent pilot study, we found urinary 6-sulfatoxymelatonin, the melatonin metabolite, to be elevated after a women spent a day at work compared to levels after a day off work, a leisure day. To evaluate the value of melatonin as a marker of stress, we evaluate melatonin metabolite levels in 121 women, along with perceived anxiety levels and urinary cortisol. Urinary cortisol and maternal anxiety levels each were significantly higher after a work day compared to a leisure day p = .03 and p = .001, respectively. 6-Sulfatoxymelatonin was not significantly different between work and leisure. Changes in cortisol levels were correlated with changes in melatonin metabolite levels (r = .62, p = .001). There was no correlation between changes in anxiety between work and leisure and changes in 6-sulfastoxymelatonin. We found no correlation with 28 week 6-sulfatoxymelatonin or 28-week cortisol and birth weight or gestational age at delivery. Results of this study suggest that melatonin secretion may not be a valuable marker for stress in pregnancy.

Adult↗
PubMed1999

Differences in urinary excretion patterns of the hLH beta core fragment in premenopausal, perimenopausal, and postmenopausal women.

OBJECTIVE: The heterodimeric luteinizing hormone beta core fragment (hLH beta cf) is a highly stable urinary analyte reflective of circulating hLH. It is measured easily because of its high molar content and has none of the multiple isoforms and subunit dissociation problems of LH urinary measurements. As part of a long-term effort to develop new biochemical assays to stage women during the perimenopausal transition, we have examined the patterns of urinary excretion of this metabolite of hLH in premenopausal, perimenopausal, and postmenopausal women. DESIGN: We measured the concentration of the hLH beta cf in 10 consecutive first morning void urine specimens from premenopausal, perimenopausal, and postmenopausal women. Day 1 of collection was the first day of menses in the cycling women. RESULTS: Postmenopausal women exhibited a widely fluctuating pattern of LH beta core fragment excretion, which is not correlated with hLH measured by immunofluorometric assay or with follicle-stimulating hormone measured by immunofluorometric assay. The postmenopausal group was easily distinguished from premenopausal women on the basis of an area-under-the-curve concentration function. Perimenopausal women displayed intermediate hLH beta cf concentrations; some clearly were in postmenopausal ranges, and others were in the premenopausal ranges. CONCLUSIONS: The pattern of excretion and concentrations of the hLH beta cf is significantly different between premenopausal and postmenopausal women. Perimenopausal women exhibited intermediate changes. The capability to measure this type of stable urinary metabolite as a reflection of changes in dynamics of its parent circulating hormone offers new possibilities in the development and application of large-scale testing that does not require blood sampling.

Adult↗
PubMed1999

Studies on infections with the Berok strain of Plasmodium cynomolgi in monkeys and mosquitoes.

Infections with the Berok strain of Plasmodium cynomolgi were induced in Macaca mulatta, Macaca fascicularis, Macaca nemestrina, Aotus lemurinus griseimembra, Aotus azarae boliviensis, and Saimiri boliviensis monkeys. Transmission was obtained with sporozoites developing in Anopheles peditaeniatus, Anopheles maculatus, Anopheles quadrimaculatus, Anopheles culicifacies, and Anopheles dirus mosquitoes. This strain of P. cynomolgi offers significant potential for a number of experimental studies. The parasite induces high-density parasite counts in both Old World and New World monkeys; rhesus monkeys readily support the development of gametocytes infectious to different anopheline mosquitoes routinely maintained in the laboratory; the gametocytes are infective to laboratory-maintained Anopheles albimanus, a vector rarely susceptible to plasmodia of Old World monkeys; encapsulated oocysts are produced in An. culicifacies as well as in Anopheles gambiae; and the parasite has been adapted to long-term in vitro culture.

Animals↗
PubMed1998

Differential uptake of myocardial perfusion radiotracers in normal, infarcted, and acutely ischemic peri-infarction myocardium.

OBJECTIVES: We measured the uptake of technetium-99m tetrofosmin (99m Tc) and thallium-201 (201 TI) in areas of healed transmural myocardial infarction and in the regions of acute peri-infarction ischemia. METHODS: Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left anterior descending (LAD) coronary artery below the first branch underwent one hour of proximal LAD occlusion followed by injection of 99m Tc-tetrofosmin and 201TI either in the left atrium (GI, n= 19) or in the jugular vein (GII, n = 6). Twelve other pigs (GIII) with similar acute peri-infarction ischemia received 99m Tc-tetrofosmin and 201Tl into the left ventricle during cardiocirculatory arrest to rule out the effect of coronary collaterals. Radiotracer counting was determined in samples from normal, acute ischemic and necrotic regions. RESULTS: Uptake of 99m Tc-tetrofosmin and 201 Tl was greater in the infarct scar (median % of normal tissue: 20 for 99m Tc and 8.6 for 201 Tl in GI; 22 and 15 in GII) than in acute ischemic myocardium (3.2 and 2.5 in GI; 6.4 and 3.3 in GII). Radiotracer injection in arrested hearts (GIII) depicted a similar pattern (median % of injected dose: 6.2 for 99m Tc and 10 for 201Tl in the scar; 2.3 and 4.0 in acute ischemia; 2.9 and 3.5 in normal tissue). The infarcted region showed connective tissue and lack of viable myocardium. CONCLUSION: A 1-month old infarct scar with no viable myocardial tissue can take up significant fractions of 99mTc-tetrofosmin and 201Tl even in the absence of coronary collateral perfusion. Data suggest that the infarct scar can extract these radiotracers from the intraventricular blood.

Animals↗
PubMed1998

Passive transmission of ischemic ST segment changes in low electrical resistance myocardial infarct scar in the pig.

OBJECTIVES: To analyze the passive electrical properties of a healed infarction and assess their role on transmission of contiguous ischemic ST segment potential changes. METHODS: We measured tissue resistivity (omega cm) at 1 kHz and the epicardial ST segment during 1 h of proximal reocclusion of the left anterior descending (LAD) coronary artery in 12 anesthetized pigs with one-month-old transmural infarction elicited by LAD ligature below the first branch. The impedance spectrum (1 to 1000 kHz) of normal and infarcted myocardium was measured in seven other pigs with similar infarctions. Electrical transmission of current pulses (30 microA) in infarcted tissue and in test solutions was also investigated. RESULTS: The infarct scar has a lower than normal resistivity (110 +/- 30 omega cm vs. 235 +/- 60 omega cm, p < 0.0001) and, unlike the normal myocardium, resistivity and phase angle of the scar did not change at increasing current frequencies, reflecting no capacitative response. LAD reocclusion induced a resistivity rise (510 +/- 135 omega cm, p < 0.01) and a ST segment elevation (0.6 +/- 0.7 to 9.5 +/- 5.1 mV, p = 0.002) in the ischemic peri-infarction zone, whereas the infarcted area showed ST segment elevation (0.5 +/- 0.5 to 3.8 +/- 2.6 mV, p = 0.03) with no resistivity changes. Potential decay of both ST segment and current pulses in the scar and in 0.9% NaCl solution was less than 1 mV/mm. Transmural deposition of connective tissue was seen in the center of the infarction. CONCLUSIONS: A one-month-old transmural infarction is a low resistance, noncapacitative medium that allows a good transmission of current pulses and of ST segment potential changes generated by contiguous peri-infarction ischemia.

Animals↗
PubMed1998

Nonneutral evolution and differential mutation rate of gender-associated mitochondrial DNA lineages in the marine mussel Mytilus.

Mussels have two types of mitochondrial DNA (mtDNA). The M type is transmitted paternally, and the F type is transmitted maternally. To test hypotheses of the molecular evolution of both mtDNA genomes, 50 nucleotide sequences were obtained for 396 bp of the COIII gene of European populations of Mytilus edulis and the Atlantic and Mediterranean forms of M. galloprovincialis. Analysis based on the proportion of synonymous and nonsynonymous substitutions indicate that mtDNA is evolving in a non-neutral and complex fashion. Previous studies on American mussels demonstrated that the F genome experiences a higher purifying selection and that the M genome evolves faster. Here we show that these patterns also hold in European populations. However, in contrast to American populations, where an excess of replacement substitution between F and M lineages has been reported, a significant excess of replacement polymorphism within mtDNA lineages is observed in European populations of M. galloprovincialis. European populations also show an excess of replacement polymorphism within the F but not within the M genome with respect to American M. trossulus, as well as a consistent pattern of excess of rare variants in both F and M genomes. These results are consistent with a nearly neutral model of molecular evolution and a recent relaxation of selective constraints on European mtDNA. Levels of diversity are significantly higher for the M than F genome, and the M genome also accumulates synonymous and nonsynonymous substitutions at a higher rate, in contrast with earlier reports where no difference for the synonymous rate was observed. It is suggested that a subtle balance between relaxed selection and a higher mutation rate explains the faster evolutionary rate of the M lineage.

Animals↗
PubMed1998

Rehabilitation of visuomotor skills in poststroke patients using the Dynavision apparatus.

The Dynavision is a new apparatus that may help address some of the limitations inherent in conventional approaches to rehabilitation of visual skills of persons suffering from neurological dysfunction. Here the basic features of the apparatus are described, an overview of preliminary experimental evidence for its effectiveness in rehabilitation presented and application in the training of compensatory scanning strategies for visual inattention and visual-field deficits and in the increasing of oculomotor control outlined.

Attention↗
PubMed1998

Methods of responding to healthcare security incidents.

This paper considers the increasing requirement for security in healthcare IT systems and, in particular, identifies the need for appropriate means by which healthcare establishments (HCEs) may respond to incidents. The main discussion focuses upon two significant initiatives that have been established in order to improve understanding and awareness of healthcare security issues. The first is the establishment of a dedicated Incident Reporting Scheme (IRS) for HCEs, enabling the level and types of security incidents faced within the healthcare community to be monitored and advice appropriately targeted. The second aspect presents a description of healthcare security World Wide Web service, which provides a comprehensive source of advice and guidance for establishments when trying to address and prevent IT security breaches. The discussion is based upon work that is currently being undertaken with the ISHTAR (Implementing Secure Healthcare Telematics Applications in Europe) project, as part of the Telematics Applications for Health programme of the European Commission.

Computer Security↗
PubMed1998

Studies on infections with two strains of Plasmodium inui from Taiwan in rhesus monkeys and different anopheline mosquitoes.

Rhesus monkeys infected with the Taiwan strains of Plasmodium inui could be appropriate models for understanding host-parasite relationships during long-term chronic infection. Two strains of P. inui originally from Taiwan were studied in rhesus monkeys and different anopheline mosquitoes. Maximum parasite counts for 13 intact animals infected with the Taiwan I strain ranged from 22,215 to 760,000/microl (median maximum parasite count = 242,800/microl). Following splenectomy, the maximum parasite count for the 9 animals ranged from 160,000 to 2,360,000/microl (median = 1,160,000/microl). Sporozoite transmission was demonstrated via the bites of infected Anopheles dirus mosquitoes and by the intravenous inoculation of sporozoites harvested from the guts of infected Anopheles maculatus. Prepatent periods were 12 and 20 days, respectively. With monkeys infected with the Taiwan II strain, the parasite counts when intact were from 40,882 to 223,686/microl. After splenectomy, maximum parasite counts ranged from 96,750 to 1,960,000/microl (median maximum parasite count for 8 splenectomized animals = 840,000/microl). Two transmissions were obtained via the bites of infected An. dirus mosquitoes; prepatent periods were 10 days. Limited studies with progressively increasing doses of pyrimethamine resulted in parasites more resistant to treatment.

Animals↗
PubMed1997

Changes in myocardial electrical impedance induced by coronary artery occlusion in pigs with and without preconditioning: correlation with local ST-segment potential and ventricular arrhythmias.

BACKGROUND: Myocardial ischemia increases tissue electrical resistivity leading to cell-to-cell uncoupling, and this effect is delayed by ischemic preconditioning in isolated myocardium. Alterations in myocardial resistivity elicited by ischemia in vivo may influence arrhythmogenesis and local ST-segment changes, but this is not well known. METHODS AND RESULTS: Myocardial impedance (resistivity [omega x cm] and phase angle [degrees]), epicardial ST segment, and ventricular arrhythmias were analyzed during 4 hours of coronary artery occlusion in 11 anesthetized open-chest pigs; these were compared with 13 other pigs submitted to a similar coronary occlusion preceded by ischemic preconditioning. Myocardial resistivity rose slowly during the first 34+/-7 minutes of occlusion (237+/-41 to 359+/-59 omega x cm), increased rapidly to 488+/-100 omega x cm at 60 minutes, and reached a plateau value (718+/-266 omega x cm, ANOVA; P<.01) at 150+/-69 minutes. By contrast, phase-angle changes began after 17 minutes of ischemia (-3.0+/-1.6 degrees to -4.2+/-1.2 degrees at 29+/-8 minutes) and evolved faster thereafter (-12.5+/-5.3 degrees at 144+/-56 minutes). Marked changes in myocardial impedance were observed during the reversion of ST-segment elevation that occurred 1 to 4 hours after occlusion, but impedance changes were less apparent during the early ST-segment recovery seen at 15 to 35 minutes of ischemia. The second arrhythmia peak (30+/-5 minutes) coincided with the fast change in tissue impedance, and both were delayed (P<.05) by ischemic preconditioning. CONCLUSIONS: A rapid impairment of myocardial impedance occurs after 30 minutes of coronary occlusion, and its onset is better defined by shift in phase angle than by rise in tissue resistivity. Phase 1b arrhythmias are associated with marked impedance changes, and both are delayed by preconditioning. Reversion of ST-segment elevation is partially associated with impairment of myocardial impedance, but other factors play a role as well.

Animals↗
PubMed1997

Crystallization of 5-aminolaevulinic acid dehydratase from Escherichia coli and Saccharomyces cerevisiae and preliminary X-ray characterization of the crystals.

5-Aminolaevulinic acid dehydratase (ALAD) catalyzes the formation of porphobilinogen from two molecules of 5-aminolaevulinic acid. Both Escherichia coli and Saccharomyces cerevisiae ALADs are homo-octameric enzymes which depend on Zn2+ for catalytic activity and are potently inhibited by lead ions. The E. coli enzyme crystallized in space group I422 (unit cell dimensions a = b = 130.7 A, c = 142.4 A). The best crystals were obtained in the presence of the covalently bound inhibitor laevulinic acid. The yeast enzyme (expressed in E. coli) crystallized in the same space group (I422) but with a smaller unit cell volume (a = b = 103.7 A, c = 167.7 A). High resolution synchrotron data sets were obtained from both E. coli and yeast ALAD crystals by cryocooling to 100 K.

Crystallography, X-Ray↗
PubMed1997

Transverse vaginal septum: case report and review of the literature.

A case of perforated complete transverse vaginal septum in the upper third of the vagina in a patient presenting at 19 years of age for evaluation of primary infertility. Diagnosis was made by hysterosalpingography. The patient was treated surgically and conceived 2 months after the procedure. The finding of transverse vaginal septum in an asymptomatic infertility patient is highly unusual. We reviewed the literature since 1966 and summarized 73 cases. The review confirms the benign characteristics of this rare anomaly and supports the embryonic origin of the transverse septum from the vaginal plate.

Adult↗
PubMed1997

Safety, functionality and acceptability of a prototype polyurethane condom.

Male condoms made from synthetic materials offer an alternative to latex condoms that may be more acceptable to users, thereby potentially resulting in more protected acts of intercourse. A prospective, noncomparative clinical study was conducted to evaluate the safety of using certain polyurethane materials to make condoms. Fifty-one healthy, contracepting, mutually monogamous couples were recruited between June 30 and November 24, 1993 to use a prototype roll-on polyurethane condom developed by Family Health International. Couples were to use the condoms for 10 consecutive acts of vaginal intercourse over a 4-week period. Baseline and postexposure genital examinations, including colposcopy for female participants, were performed. Fifty couples completed the study requirements and 517 acts of intercourse occurred using the condoms. Two adverse events were reported: irritation of introitus in a female participant and a small irritated erythematous lesion on a male participant's penis. Neither event was considered to be serious and both were resolved without treatment. Breakage and slippage rates were similar to those reported for latex condoms. These results suggest that polyurethane condoms represent a safe, functional and acceptable alternative to latex condoms.

Adult↗
PubMed1997

Local repolarization abnormalities induced by transcatheter radiofrequency ablation in pigs.

Radiofrequency (RF) ablation alters action potential repolarization of myocardial cells and, theoretically, this should induce ST-T segment changes in the ECG. Since these ECG abnormalities have been rarely reported in patients submitted to RF ablation we assess the ability of the procedure to cause ST-T segment changes in local electrograms. Epicardial ECG mapping was performed in 17 anesthetized open chest pigs submitted to endocardial (n = 9) or to epicardial (n = 8) unipolar radiofrequency ablation (500 kHz, 20 W for 5-10 s). To characterize the cellular electrophysiological alterations induced by RF ablation transmembrane action potentials were recorded at various distances from the ablation lesion; these were compared with seven control pigs. Endocardial RF ablation induced a transient (< 5 min) change of 6.1 +/- 2.4 mV in T wave amplitude (baseline: 12.8 +/- 5.6 mV, P < 0.001) in 141 out of 269 epicardial electrodes. T wave changes were associated with shortening in local activation time (20.1 +/- 2.3 ms at baseline vs 18.5 +/- 2.5 ms at 60 s after ablation, P = 0.03). RF current caused persistent St segment elevation at the center of the ablation lesion with no transmural expansion. Intracellular potentials along a 2-6 mm wide myocardial band bordering the RF lesion lower amplitude (101 +/- 7.0 mV vs 71 +/- 23 mV, P < 0.01) and shorter duration (254 +/- 44 ms vs 156 +/- 29 ms, P < 0.01) than control hearts. The center of the ablation lesion was electrically unexcitable. We concluded that RF ablation alters cellular electrophysiology in small areas surrounding the ablation lesion and this causes short-lasting transmural changes in T 3 wave amplitude and nontransmural ST segment elevation.

Action Potentials↗
PubMed1997

Addressing information security training and awareness within the European healthcare community.

This paper discusses the need to promote information security issues within modern healthcare establishments and the consequent need for appropriate training and awareness initiatives. Security is an area of extreme significance in healthcare information systems but, whilst the need is generally recognised, many personnel are not familiar with even basic concepts and procedures. As such, adequate promotion of security through training and awareness initiatives is viewed as a vital first step. The paper highlights a series of basic factors that healthcare establishments (HCEs) should consider in setting up a training and awareness framework. The discussion then examines a number of ways in which relevant information may be disseminated to staff, including security guidelines, training seminars and world-wide web based services. The paper is largely based upon work that is currently being conducted as part of the Health Telematics ISHTAR (Implementing Secure Healthcare Telematics Applications in euRope) project.

Awareness↗