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Biomedical subjects

M Fitzpatrick

Publications and source records attributed to M Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed2006

Local and regional air pollution in Ireland during an intensive aerosol measurement campaign.

An intensive two month measurement campaign has been performed during a two year study of major component composition of urban PM10 and PM2.5 in Ireland (J. Yin, A. G. Allen, R. M. Harrison, S. G. Jennings, E. Wright, M. Fitzpatrick, T. Healy, E. Barry, D. Ceburnis and D. McCusker, Atmos. Res., 2005, 78(3-4), 149-165). Measurements included size-segregated mass, soluble ions, elemental carbon (EC) distributions, fine and coarse fraction organic carbon (OC) and major gases along with standard meteorological measurements. The study revealed that urban emissions in Ireland had mainly a local character and therefore were confined within a limited area of 20-30 km radius, without significantly affecting regional air quality. Gaseous measurements have shown that urban emissions in Ireland had clear, but fairly limited influence on the regional air quality due to favorable mixing conditions at higher wind speeds, in particular from the western sector. Size-segregated mass and chemical measurements revealed a clear demarcation size between accumulation and coarse modes at about 0.8 microm which was constant at all sites. Carbonaceous compounds at the urban site accounted for up to 90% of the particle mass in a size range of 0.066-0.61 microm. Nss SO4(2-) concentrations in PM2.5 were only slightly higher at the urban site compared to the rural or coastal sites, while NO3- and NH4+ concentrations were similar at the urban and coastal sites, but were a factor of 2 to 3 higher than at the rural site. OC was highly variable between the sites and revealed clear seasonal differences. Natural or biogenic OC component accounted for <10% in winter and up to 30% in summer of the PM2.5 OC at urban sites. A contribution of biogenic OC component to PM2.5 OC mass at rural site was dominant.

Aerosols↗
PubMed2006

A prospective, randomized, multicenter trial of tacrolimus-based therapy with or without basiliximab in pediatric renal transplantation.

In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients < 18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients < 40 kg) or 20 mg (patients > or = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.

Adolescent↗
PubMed2004

Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease.

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator. In a randomised double-blind crossover study, 23 patients with COPD (mean +/- SEM forced expiratory volume in one second 42 +/- 3% of the predicted value) inhaled salmeterol 50 microg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate. After salmeterol versus placebo at rest, volume-corrected maximal expiratory flow rates increased by 175 +/- 52%, inspiratory capacity (IC) increased by 11 +/- 2% pred and functional residual capacity decreased by 11 +/- 3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (VO2) and carbon dioxide output. Salmeterol increased peak exercise endurance, VO2 and ventilation by 58 +/- 19, 8 +/- 3 and 12 +/- 3%, respectively. Improvements in peak VO2 correlated best with increases in peak VT; increases in peak VT and resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increased VT. Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance.

Administration, Inhalation↗
PubMed2002

The effect of tezosentan, a non-selective endothelin receptor antagonist, on shear stress-induced changes in arterial diameter of the anaesthetized dog.

The effects of changes in the mean (S(m)) and pulsatile (S(p)) components of arterial wall shear stress on arterial dilatation of the iliac artery of the anaesthetized dog were examined in the absence and presence of the endothelin receptor antagonist tezosentan (10 mg kg(-1) I.V.; Ro 61-0612; [5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide]). Changes in shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and stimulation of the left ansa subclavia. An increase in S(m) from 1.81 +/- 0.3 to 7.29 +/- 0.7 N m(-2) (means +/- S.E.M.) before tezosentan caused an endothelium-dependent arterial dilatation which was unaffected by administration of tezosentan for a similar increase in S(m) from 1.34 +/- 0.6 to 5.76 +/- 1.4 N m(-2) (means +/- S.E.M.). In contrast, increasing the S(p) from 7.1 +/- 0.8 to a maximum of 11.5 +/- 1.1 N m(-2) (means +/- S.E.M.) before tezosentan reduced arterial diameter significantly. Importantly, after administration of tezosentan subsequent increases in S(p) caused arterial dilatation for the same increase in S(p) achieved prior to tezosentan, increasing from a baseline of 4.23 +/- 0.4 to a maximum of 9.03 +/- 0.9 N m(-2) (means +/- S.E.M.; P < 0.001). In conclusion, the results of this study provide the first in vivo evidence that pulsatile shear stress is a stimulus for the release of endothelin from the vascular endothelium.

Animals↗
PubMed2002

Reverse arterial wall shear stress causes nitric oxide-dependent vasodilatation in the anaesthetised dog.

The effects of a maintained increase in mean arterial wall shear stress (SS(m)) caused by blood flow in the normal and reverse direction on dilatation of the iliac artery were examined in the anaesthetised dog. Blood flow in the left iliac artery was varied in both the forwards and reverse directions by a perfusion pump connecting the right and left femoral arteries. An increase in blood flow, and therefore SS(m) in either direction, caused an increase in arterial diameter. However, an increase in forwards SS(m) (control 4.1+/-0.11 mm) caused a significantly greater change in arterial diameter than an equivalent increase in the reverse direction (control 4.3+/-0.08), 0.198+/-0.02 mm vs. 0.132+/-0.02 mm (mean+/-SEM) respectively, for the same increase in SS(m) (3.23 N/m(2)). The increase in arterial diameter in response to an increase in forwards or reverse SS(m) was attenuated by L-NAME (80 mg/kg i.v.), indicating that the arterial dilatation was mediated by nitric oxide (NO). These findings confirm that endothelial NO release is dependent on the steady-state SS(m) and that the response occurs irrespective of the direction in which this force is applied, but is attenuated in the reverse direction.

Animals↗
PubMed2002

An evaluation of the efficacy of vasoactive intestinal polypeptide antagonists in vivo in the anaesthetized dog.

The effectiveness of competitive peptide vasoactive intestinal polypeptide (VIP) receptor antagonists was evaluated on heart rate in the anaesthetized dog. Two specific antagonists, VIP (6-28) and [D-p-Cl-Phe(6), Leu(17)]-VIP, and a nonspecific antagonist, pituitary adenylate cyclase activating peptide fragment (6-27) (PACAP), were studied. VIP (6-28) and [D-p-Cl-Phe(6), Leu(17)]-VIP (100 microg i.c.) increased the heart rate, whereas PACAP (100 microg i.c.) reduced the baseline heart rate. All three shifted the VIP dose-response curve to the right by two- to threefold for 30 min. In conclusion, PACAP, VIP (6-28), and [D-p-Cl-Phe(6), Leu(17)]-VIP have a direct effect on the heart rate, are equally effective, and the effects last approximately 30 min in vivo.

Animals↗
PubMed2001

Sturgeon orphanin, a molecular "fossil" that bridges the gap between the opioids and orphanin FQ/nociceptin.

The elucidation of the cDNA sequence for sturgeon proorphanin provides a unique window for interpreting the evolutionary history of the opioid/orphanin gene family. The molecular "fossil" status of this precursor can be seen in several ancestral sequence characteristics that point to its origin as a duplication of either a prodynorphin- or proenkephalin-like gene. The sturgeon proorphanin cDNA encodes a precursor protein of 194 residues, and the orphanin heptadecapeptide itself binds not only the opioid receptor-like 1 (ORL1) receptor but also the classical (mu, kappa, and delta) opioid receptors with near equal affinity. Allowing for this broad receptor specificity are several amino acid substitutions at key positions in the heptadecapeptide sequence, relative to its mammalian orthologs, that have been linked by amino acid scans and site-directed mutagenic studies to the exclusion of mammalian orphanin FQ/nociceptin from classic opioid ligands (i.e. F1Y and L14W). The unique receptor binding profile of sturgeon orphanin not only provides insight into the evolutionary history of the opioid and opioid-related peptides but also provides an ideal context in which to investigate the underlying mechanisms by which novel and often divergent physiological functions arise in receptor-ligand systems.

Amino Acid Sequence↗
PubMed2001

Final results of a randomized trial comparing the NIR stent to the Palmaz-Schatz stent for narrowings in native coronary arteries.

The NIR stent is a novel second generation tubular stent that was designed to overcome some of the limitations of the earlier Palmaz-Schatz (PS) stent design. The NIR Vascular Advanced North American (NIRVANA) trial randomized 849 patients with single coronary lesions to treatment with the NIR stent or the PS stent. The study was an "equivalency" trial, designed to demonstrate that the NIR stent was not inferior to (i.e., equivalent or better than) the PS stent, for the primary end point of target vessel failure (defined as death, myocardial infarction, or target vessel revascularization) by 9 months. Successful stent delivery was achieved in 100% versus 98.8%, respectively, with a slightly lower postprocedural diameter stenosis (7% vs. 9%, p = 0.04) after NIR and PS stent placement, respectively. Major adverse cardiac events (death, myocardial infarction, repeat target lesion revascularization) were not different at 30 days (4.3% vs. 4.4%). The primary end point of target vessel failure at 9 months was seen in 16.0% of NIR versus 17.2% of PS patients, with the NIR proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). Angiographic restudy in 71% of a prespecified cohort showed no significant difference in restenosis (19.3% vs 22.4%). Thus, the NIR stent showed excellent deliverability with slightly better acute angiographic results and equivalent or better 9-month target vessel failure rate when compared with the PS stent.

Aged↗
PubMed2001

Influence of persistent occiput posterior position on delivery outcome.

OBJECTIVE: To evaluate the influence of intrapartum persistent occiput posterior position of the fetal head on delivery outcome and anal sphincter injury, with reference to the association with epidural analgesia. METHODS: We conducted a prospective observational study of 246 women with persistent occiput posterior position in labor during a 2-year period, compared with 13,543 contemporaneous vaginal deliveries with occiput anterior position. RESULTS: The incidence of persistent occiput posterior position was significantly greater among primiparas (2.4%) than multiparas (1.3%; P <.001; 95% confidence interval 1.4, 2.4) and was associated with significantly higher incidences of prolonged pregnancy, induction of labor, oxytocin augmentation of labor, epidural use, and prolonged labor. Only 29% of primiparas and 55% of multiparas with persistent occiput posterior position achieved spontaneous vaginal delivery, and the malposition was associated with 12% of all cesarean deliveries performed because of dystocia. Persistent occiput posterior position was also associated with a sevenfold higher incidence of anal sphincter disruption. Despite a high overall incidence of use of epidural analgesia (47% versus 3%), the institutional incidence of persistent occiput posterior position was lower than that reported 25 years ago. CONCLUSION: Persistent occiput posterior position contributed disproportionately to cesarean and instrumental delivery, with fewer than half of the occiput posterior labors ending in spontaneous delivery and the position accounting for 12% of all cesarean deliveries for dystocia. Persistent occiput posterior position leads to a sevenfold increase in the incidence of anal sphincter injury. Use of epidural analgesia was not related to the malposition.

Anal Canal↗
PubMed2001

The effects of labour and delivery on the pelvic floor.

Increasing public and professional attention has recently been focused on the issue of both faecal and urinary incontinence following childbirth and these symptoms are sometimes being cited as indications for elective caesarean section. Faecal incontinence has a female-to-male preponderance of 8:1, consistent with childbirth as the principal causative factor, although most symptomatic women do not seek medical advice until after the menopause. Similarly, urinary stress incontinence is almost an exclusively female phenomenon. Obstetric injury may take the form of direct muscular damage to the anal sphincter, as occurs during a third-degree tear, and/or may be the result of cumulative damage to the pudendal nerves. Mechanical, neural and endocrine factors may all play a causative role in faecal incontinence. Symptoms are rarely volunteered by the patient, and may be present for many years after the index pregnancy, and clinical examination alone may fail to detect specific abnormalities. The performance of anal manometry, endoanal ultrasound, urodynamics and neurophysiology studies of the pelvic floor may help to increase the diagnostic yield. Treatment for both urinary and faecal incontinence is available in the form of physiotherapy, fluid and dietary manipulation and in more severe cases, surgery. Adequate primary management of third-degree tears requires careful appraisal as this injury, in particular, is the most important risk factor for subsequent faecal incontinence symptoms. In this chapter we aim to outline the mechanism of damage to the pelvic floor during childbirth, concentrating primarily on anal sphincter damage. We describe the necessary investigations, follow-up and treatment which women with significant pelvic floor damage should receive following delivery, and we finally discuss the issue of further deliveries and, specifically, the current place of caesarean section.

Anal Canal↗
PubMed2000

Suture-mediated closure of the femoral access site after cardiac catheterization: results of the suture to ambulate aNd discharge (STAND I and STAND II) trials.

Despite advances in other aspects of cardiac catheterization, manual or mechanical compression followed by 4 to 8 hours of bed rest remains the mainstay of postprocedural femoral access site management. Suture-mediated closure may prove to be an effective alternative, offering earlier sheath removal and ambulation, and potentially a reduction in hemorrhagic complications. The Suture To Ambulate aNd Discharge trial (STAND I) evaluated the 6Fr Techstar device in 200 patients undergoing diagnostic procedures, with successful hemostasis achieved in 99% of patients (94% with suture closure only) in a median of 13 minutes, and 1% major complications. STAND II randomized 515 patients undergoing diagnostic or interventional procedures to use of the 8Fr or 10Fr Prostar-Plus device versus traditional compression. Successful suture-mediated hemostasis was achieved in 97.6% of patients (91.2% by the device alone) compared with 98.9% of patients with compression (p = NS). Major complication rates were 2.4% and 1.1%, and met the Blackwelder's test for equivalency (p <0.05). Median time to hemostasis (19 vs 243 minutes, p <0.01) and time to ambulation (3.9 vs 14.8 hours, p <0.01) were significantly shorter for suture-mediated closure. Suture-mediated closure of the arterial puncture site thus affords reliable immediate hemostasis and shortens the time to ambulation without significantly increasing the risk of local complications.

Cardiac Catheterization↗