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Biomedical subjects

D M Walsh

Publications and source records attributed to D M Walsh.

At least 55 records · Page 3Linked to original sources
PubMed1998

Incidence of urinary incontinence and constipation during pregnancy and postpartum: survey of current findings at the Rotunda Lying-In Hospital.

OBJECTIVE: To assess the impact of pregnancy upon continence and constipation. DESIGN: A questionnaire survey. SETTING: Maternity wards in the Rotunda Lying In Hospital, Dublin, Republic of Ireland. POPULATION: 7771 women who were delivered of liveborn infants. METHODS: Questionnaires were delivered and collected by physiotherapy staff as part of routine postnatal care. RESULTS: Analysis of data using chi2 tests showed significant differences between three parity groups [primigravidae, multigravidae (2-4) and multigravidae (5+)] for symptoms of both urinary incontinence (chi2 = 119.54, df = 2, P = 0.000) and constipation (chi2 = 12.53, df = 3, P = 0.002); the incidence of both constipation and urinary incontinence increased with parity. CONCLUSION: The results of this survey have emphasised the relation between parity and postpartum incontinence which stresses the importance of early diagnosis and intervention.

Constipation↗
PubMed1997

Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate.

Fibrillogenesis of the amyloid beta-protein (Abeta) is a seminal pathogenetic event in Alzheimer's disease. Inhibiting fibrillogenesis is thus one approach toward disease therapy. Rational design of fibrillogenesis inhibitors requires elucidation of the stages and kinetics of Abeta fibrillogenesis. We report results of studies designed to examine the initial stages of Abeta oligomerization. Size exclusion chromatography, quasielastic light scattering spectroscopy, and electron microscopy were used to characterize fibrillogenesis intermediates. After dissolution in 0.1 M Tris-HCl, pH 7.4, and removal of pre-existent seeds, Abeta chromatographed almost exclusively as a single peak. The molecules composing the peak had average hydrodynamic radii of 1.8 +/- 0.2 nm, consistent with the predicted size of dimeric Abeta. Over time, an additional peak, with a molecular weight >100,000, appeared. This peak contained predominantly curved fibrils, 6-8 nm in diameter and <200 nm in length, which we have termed "protofibrils." The kinetics of protofibril formation and disappearance are consistent with protofibrils being intermediates in the evolution of amyloid fibers. Protofibrils appeared during the polymerization of Abeta-(1-40), Abeta-(1-42), and Abeta-(1-40)-Gln22, peptides associated with both sporadic and inherited forms of Alzheimer's disease, suggesting that protofibril formation may be a general phenomenon in Abeta fibrillogenesis. If so, protofibrils could be attractive targets for fibrillogenesis inhibitors.

Alzheimer Disease↗
PubMed1997

Failure to demonstrate any hypoalgesic effect of low intensity laser irradiation (830nm) of Erb's point upon experimental ischaemic pain in humans.

BACKGROUND AND OBJECTIVE: This study assessed the putative analgesic effect of low intensity, near-infrared laser irradiation (830nm; 1.5 & 9.0J/cm2; continuous wave). STUDY DESIGN/MATERIALS AND METHODS: The current study was completed under double-blind conditions using a standardised form of the submaximal effort tourniquet technique. Healthy naive female volunteers (n = 48) attended on two occasions for pain induction in the non-dominant upper limb, the first during which baseline data were obtained and on a second occasion during which subjects were randomly allocated to either control, placebo, or one of two treatment groups. In the treatment groups, irradiation was applied to ten points on the ipsilateral Erb's point immediately prior to the pain induction procedure at the parameters stated: For the placebo condition, sham "irradiation" was delivered by applying the laser unit without activating the probe. Pain was measured using computerised visual analogue scales and McGill Pain Questionnaires to assess "current pain intensity" and "worst pain experience," respectively. RESULTS: Whereas analysis of variance and appropriate posthoc tests showed a trend toward hypoalgesia at a radiant exposure of 1.5J/cm2, no significant effects of laser therapy were found. CONCLUSIONS: These results do not provide convincing evidence for the clinical potential of low intensity laser irradiation as a pain relieving modality, at least at the parameters used. Further work is thus necessary to provide objective quantifiable data on the putative clinical efficacy of this modality and the relevance (if any) of irradiation parameters.

Analgesia↗
PubMed1996

Lack of effect of transcutaneous electrical nerve stimulation upon experimentally induced delayed onset muscle soreness in humans.

The aim of the current study, for which ethical approval was obtained, was to assess the hypoalgesic efficacy of transcutaneous electrical nerve stimulation (TENS) upon acute stage (72 h) experimentally induced delayed onset muscle soreness (DOMS). TENS naive subjects (n = 48; 24 male and 24 female) were recruited, screened for relevant pathology and randomly allocated to one of four experimental groups: control, placebo, low TENS (200 microseconds; 4 Hz) or high TENS group (200 microseconds; 110 Hz). DOMS was induced in a standardised fashion in the non-dominant elbow flexors of all subjects by repeated eccentric exercise. Subjects attended on three consecutive days for treatment and measurement of elbow flexion, extension and resting angle (Universal goniometer), Mechanical Pain Threshold/tenderness (algometer) and pain (Visual Analogue Scale (VAS)) on a daily basis, plus McGill Pain Questionnaire on the third day only. Measurements were taken before and after treatment under controlled double blinded conditions. Analysis of results using repeated measures analysis of variance (ANOVA) and post hoc tests showed some inconsistent isolated effects of high TENS (110 Hz) compared to the other conditions upon resting angle and flexion scores; no significant effects were found for any of the other variables. These results provide no convincing evidence for any measurable hypoalgesic effects of TENS upon DOMS-associated pain at the stimulation parameters used here.

Adult↗
PubMed1996

Aggregation and metal-binding properties of mutant forms of the amyloid A beta peptide of Alzheimer's disease.

The fibrillogenic properties of Alzheimer's A beta peptides corresponding to residues 1-40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37 degrees C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal A beta, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to beta sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20x the concentration of Zn2+, Cu2+ displaced > 95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 microM was obtained for the binding of Zn2+ to A beta but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon.

Alzheimer Disease↗
PubMed1996

Delayed-onset muscle soreness: lack of effect of combined phototherapy/low-intensity laser therapy at low pulse repetition rates.

A double-blind, placebo-controlled study using male subjects (n = 60), was conducted to investigate the efficacy of three different frequencies of combined phototherapy/low-intensity laser therapy (CLILT) in alleviating the signs and symptoms of delayed-onset muscle soreness (DOMS). The study was approved by the University's ethical committee. After screening for relevant pathologies, recent analgesic or steroid drug usage, current pain, diabetes, or current involvement in regular weight-training activities, subjects were randomly allocated to one of five experimental groups: Control, Placebo, or 2.5-Hz, 5-Hz, or 20-Hz CLILT groups (660-950 nm; 31.7 J/cm2; pulsed at the given frequencies for a duration of 12 min; n = 12 all groups). Once baseline measurements were obtained, DOMS was induced in the nondominant arm, which was exercised in a standardized fashion until exhaustion, using repeated eccentric contractions of the elbow flexors. The procedure was repeated twice more to ensure exhaustion was achieved, after which subjects were treated according to group allocation. In the CLILT/placebo groups, the treatment head was applied directly to the affected arm at the level of the musculotendinous junction. Subjects returned on two consecutive days for further treatment and assessment. The range of variables used to assess DOMS included range of movement (universal goniometer), mechanical pain threshold/tenderness (algometer) and pain (visual analogue scale and McGill Pain Questionnaire). Measurements were taken before and after treatment on each day, except for the McGill Pain questionnaire, which was completed at the end of the study. Analysis of results using repeated measures and one-factor analysis of variance with relevant post hoc tests showed significant changes in ranges of movement accompanied by increases in subjective pain and tenderness for all groups over time (p = 0.0001); however, such analysis failed to show any significant differences between groups on any of the days. These results thus provide no convincing evidence for any putative hypoalgesic effect of CLILT upon DOMS at the parameters used here.

Adult↗
PubMed1996

Manipulation of transcutaneous electrical nerve stimulation variables has no effect on two models of experimental pain in humans.

Two separate studies investigated the hypoalgesic effect of manipulation of Transcutaneous Electrical Nerve Stimulation (TENS) parameters on two models of experimental pain: the Submaximal Effort Tourniquet Technique and cold-pressor pain. For the first study, 32 healthy subjects (16 male and 16 female) attended once for the purpose of cold-pressor pain induction that involved immersion of the nondominant hand in a water bath at 0 degree C. Subjects were allocated to Control, Placebo, or 1 of 2 treatment groups (110 or 4-Hz TENS). Pain threshold measurements (time to withdrawal of hand in seconds) were obtained over six standardised cold pain cycles (i.e., two before stimulation onset, three during stimulation, and one cycle after stimulation). In the second study, 48 healthy volunteers (24 male and 24 female) attended on two occasions, 48 h apart, for the purposes of ischaemic pain induction. On the first attendance, baseline data were obtained and on the second, subjects were randomly allocated to Control, Placebo, or one of four treatment groups with different combinations of stimulation frequencies and pulse durations (4 or 110 Hz and 50 or 200 microseconds). Measurements of "current pain intensity" and "worst pain experienced" were obtained via the Visual Analogue Scale (VAS) and the McGill Pain Questionnaire (MPQ), respectively. Analysis of variance performed on both sets of collected data revealed no significant differences between any of the groups, thus indicating no apparent relevance of manipulation of TENS parameters using these models of pain. Several hypotheses are suggested to explain these findings.

Adult↗
PubMed1996

The effect of H-wave therapy upon conduction in the human superficial radial nerve in vivo.

This study was designed to investigate the putative neurophysiological effects of so-called 'H-wave therapy' (HWT), a form of electrical stimulation, upon conduction latencies in the human superficial radial nerve. Antidromic compound action potentials were recorded from the superficial radial nerve in the dominant forearms of thirty-two healthy human volunteers, who were randomly assigned to a control or one. of three HWT groups (2, 16 or 60 Hz). HWT was applied under double-blind conditions for three consecutive 5 min periods. Action potentials were recorded pre-HWT and immediately after each period of stimulation, i.e. at 5, 10 and 15 min. Analysis of results showed significant increases in negative and positive peak latencies in the 16 Hz and, to a greater extent, in the 60 Hz groups when compared with controls. No changes in conduction latency were observed in the low frequency 2 Hz group. The results of this study demonstrate that HWT applied at frequencies of 16 and 60 Hz may produce a direct, localized effect upon conduction in underlying peripheral nerves.

Adolescent↗
PubMed1995

The activity of 5-HT1D receptor ligands at cloned human 5-HT1D alpha and 5-HT1D beta receptors.

The present study has examined the functional activity of the 5-HT1D receptor agonist, sumatriptan, and antagonists, GR127935 (2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxyl ic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide), GR55562 (3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl] benzamide), metergoline and methiothepin in HeLa cells, stably transfected with either 5-HT1D alpha or 5-HT1D beta receptor subtypes. Sumatriptan, GR127935 and metergoline (each 0.01-1 microM) behaved as agonists, producing a concentration-dependent inhibition of forskolin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production at both 5-HT1D alpha and 5-HT1D beta receptor subtypes (mean pIC50 values of 8.4 and 8.3 for sumatriptan, 7.9 and 8.0 for GR127935, and 7.9 and 8.3 for metergoline, respectively). In contrast, GR55562 and methiothepin behaved as competitive 5-HT1D receptor antagonists and were devoid of any agonist activity. GR55562 (10 microM) caused a rightward displacement of the GR127935 and metergoline concentration-response curves. The agonist activity of GR127935 and metergoline, observed in the present study, contrasts with their recognised 5-HT1D receptor antagonist profiles in animal isolated tissue and behavioural models. Unlike GR127935, GR55562 behaved as a silent antagonist at the cloned human 5-HT1D alpha and 5-HT1D beta receptors in the study.

Cyclic AMP↗
PubMed1995

GR159897, a potent non-peptide antagonist at tachykinin NK2 receptors.

GR159897 ((R)-1-[2-(5-fluoro-1H-indol-3-yl)ethyl]-4-methoxy-4- [(phenylsulfinyl)methyl]piperidine) is a novel, highly potent and selective non-peptide antagonist at tachykinin NK2 receptors. GR159897 inhibited binding of the NK2 receptor antagonist radioligand [3H]cyclohexylcarbonyl-Gly-Ala-(D)Trp-Phe-NMe2 ([3H]GR100679) to human ileum NK2 receptors transfected into Chinese hamster ovary cells (pKi 9.5) and to rat colon membranes (pKi 10.0). GR159897 was a competitive antagonist of contractions induced by the NK2 receptor agonist [Lys3,Gly8-R-gamma-lactam-Leu9]neurokinin A-(3-10) (GR64349) in guinea-pig trachea (pA2 8.7), and had negligible activity at human NK1 receptors transfected into Chinese hamster ovary cells (pKi 5.3), NK1 receptors in guinea-pig trachea (pKB < 5) or NK3 receptors in guinea-pig cerebral cortex (pKi < 5). In vivo, in the anaesthetised guinea-pig, GR159897 (0.12 mg.kg-1 i.v.) potently antagonised bronchoconstriction induced by GR64349 (dose-ratio = 28), with a long duration of action (3 h). GR159897 should be a useful tool for studying the physiological and pathophysiological role of tachykinin NK2 receptor activation.

Animals↗
PubMed1995

Double-blind, placebo-controlled investigation of the effect of combined phototherapy/low intensity laser therapy upon experimental ischaemic pain in humans.

BACKGROUND AND OBJECTIVE: This study assessed the putative analgesic effect of combined monochromatic light/laser irradiation at low intensity (660-950 nm; 31.9 J/cm2; pulsed at 16 or 73 Hz). STUDY DESIGN/MATERIALS AND METHODS: The investigation was completed under double-blind conditions using a standardised form of the submaximal effort tourniquet technique. Healthy male volunteers naive to the experimental conditions (n = 45) attended on two occasions for the purposes of pain induction, the first during which baseline data were obtained and on a second occasion during which they were randomly allocated to one of two treatments or a placebo condition. For the treatment conditions, irradiation was applied to the ipsilateral Erb's point at the parameters stated; for the placebo condition, sham "irradiation" was delivered using a dummy unit. Pain was measured using computerised visual analogue scales and McGill Pain Questionnaires (MPQ) to assess "current pain intensity" and "worst pain experienced," respectively. RESULTS: Analysis of variance and appropriate post hoc tests demonstrated only a weak (but significant) hypoalgesic effect compared to placebo (P < 0.05) in the treatment group irradiated at 16Hz for the sensory component of the MPQ; other comparisons were found to be nonsignificant. CONCLUSIONS: These results do not provide convincing evidence for the hypoalgesic potential of combined monochromatic light/laser irradiation, at least at the parameters used here, and thus indicate the necessity of additional work to investigate this modality further in order to assess the potential benefit, if any, of such treatment in the clinical setting.

Analgesia↗
PubMed1995

The anxiolytic-like activity of GR159897, a non-peptide NK2 receptor antagonist, in rodent and primate models of anxiety.

The non-peptide NK2 receptor antagonist, GR159897, was evaluated in two putative models of anxiety, the mouse light-dark box and the marmoset human intruder response test. Effects were compared to the structurally dissimilar NK2 antagonist, (+/-) SR48968 and the benzodiazepines, diazepam and chlordiazepoxide. GR159897 (0.0005-50 micrograms/kg SC) caused significant and dose-dependent increases in the amount of time mice spent in the more aversive light compartment of the light-dark box, with no effect on locomotor activity. (+/-)SR48968 (0.0005-0.5 microgram/kg SC) and diazepam (1-1.75 mg/kg SC), also increased time spent in the light compartment, without effect on locomotor activity. In the marmoset human intruder response test, GR159897 (0.2-50 micrograms/kg SC) significantly increased the amount of time marmosets spent at the front of the cage during confrontation with a human observer ("threat"). Similar effects were produced by (+/-)SR48968 (10-50 micrograms/kg SC) and chlordiazepoxide (0.3-3.0 mg/kg SC). These results provide further evidence, in both rodent and primate species, for the ability of NK2 antagonists to restore behaviours which have been suppressed by novel aversive environments. Such effects indicate that NK2 antagonists may have anxiolytic activity.

Animals↗
PubMed1994

Effect of low intensity laser (830 nm) irradiation on skin temperature and antidromic conduction latencies in the human median nerve: relevance of radiant exposure.

The effects of low intensity near-infrared laser radiation (830 nm; 1.5-12 J/cm2; continuous wave) on peripheral neurophysiology and skin temperature were investigated using antidromic conduction studies in the human median nerve in vivo. Healthy human volunteers (n = 80) were recruited and randomly allocated to one of two control (n = 30) or five laser groups (1.5, 3.0, 6.0, 9.0, and 12 J/cm2; n = 10 per group). Analysis of variance (ANOVA) in negative peak latency difference scores (NPLDs) and skin temperature over a 20 min period post-irradiation demonstrated a significant decrease in skin temperature following irradiation at the lowest radiant exposure (1.5 J/cm2) coupled with a significant increase in NPLDs (P < 0.05). While no such (significant) changes were found in the other laser groups, it was found that observed changes (increases and decreases) in NPLDs were inversely related to changes in skin temperature. These findings demonstrate measurable peripheral neurophysiological effects of laser radiation concomitant with changes in skin temperature; however, further studies are indicated to establish the precise relationship between the observed effects on skin temperature and nerve conduction.

Adolescent↗
PubMed1994

Effects of dietary vitamin E and selenium on in vitro cellular immune responses in cattle.

Four groups of calves depleted of alpha-tocopherol and selenium (Se) were supplemented with alpha-tocopherol or Se or alpha-tocopherol and Se or received no supplement. In vitro lymphocyte proliferative responses were measured in fetal calf serum (FCS), in autologous serum and in pooled sera from each group. In FCS, the responses to pokeweed mitogen were significantly enhanced for calves supplemented with alpha-tocopherol. In autologous serum, the mean responses to keyhole limpet haemocyanin (KLH) were greatest for calves supplemented with Se alone. In pooled sera from each group, lymphocytes from calves supplemented with Se alone showed enhanced responses to KLH in the presence of serum from calves supplemented with alpha-tocopherol. The calves depleted of alpha-tocopherol had increased circulating percentages of BoCD2 lymphocytes, apparently due to changes in the BoCD4 subpopulation. The percentages of B cells were greatest in calves supplemented with alpha-tocopherol and Se. The results indicate that alpha-tocopherol and Se have interactive effects on lymphocyte responses to antigen and suggest that micronutrient status is important when interpreting the results of in vitro assays of lymphocyte function.

Animals↗
PubMed1994

GR138676, a novel peptidic tachykinin antagonist which is potent at NK3 receptors.

GR138676, a conformationally constrained analogue of neurokinin B, is a novel, potent NK3 receptor antagonist. GR138676 was a competitive antagonist of neurokinin B-dependent arachidonic acid mobilization from prelabelled Chinese hamster ovary cells stably transfected with a human NK3 receptor gene (pKB 8.3) and of contractions induced by senktide in rat portal vein (pKB 8.2). However, GR138676 was also a competitive antagonist of the increase in intracellular calcium evoked by the selective NK1 agonist, GR73632, in the human astrocytoma U373MG cell-line (pKB 8.3). GR138676 had little activity at NK2 receptors, inhibiting binding of the NK2 antagonist radioligand [3H]-GR100679 to Chinese hamster ovary cells transfected with the human ileum NK2 receptor with a pKi of 6.0. In summary, despite its activity at NK1 receptors, GR138676 will be a useful tool for characterizing NK3 receptors as well as defining the physiological and pathophysiological function of this receptor subtype.

Amino Acid Sequence↗