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P McHugh

Publications and source records attributed to P McHugh.

At least 19 recordsLinked to original sources
PubMed2006

Molecular analysis of polymerase gamma gene and mitochondrial polymorphism in fertile and subfertile men.

CAG trinucleotide repeat length in the nuclear polymerase gamma gene (POLgamma) has been shown to be associated with men with reduced fertility. The present study investigated the frequency of CAG repeat length genotypes and three exonuclease motifs of the POLgamma in relation to the frequency of mitochondrial nucleotide substitutions. DNA from semen samples of 93 normozoospermic men and 192 non-normozoospermic men was isolated and the specific regions of the genes were amplified by polymerase chain reactions (PCR) and sequenced to identify mutations. The genotypic frequencies of pooled POLgamma CAG repeat lengths, =10/ not equal 10 heterozygotes and not equal 10/ not equal 10 homozygotes, were significantly different between normozoospermic and non-normozoospermic men (p < 0.05), with non-normozoospermic men having a slightly higher frequency of the =10/=10 genotypes. The allelic frequency for =10 is 0.79 and not equal10 is 0.21 for normozoospermic men and 0.85 and 0.15, respectively, for non-normozoospermic men (p < 0.025). There was no mutation detected in the exonuclease motifs in all the samples tested. Eighty normozoospermic and 124 non-normozoospermic semen samples were analysed for nucleotide substitutions in mitochondrial genes by PCR and sequencing. Heteroplasmic mutations were found in one azoospermic man, four asthenozoospermic men and two normozoospermic men. Only one asthenozoospermic man was heterozygous for the POLgamma genotype. Of the 17 men with non-synonymous nucleotide substitutions, 14 were homozygous for the POLgamma genotype. Non-normozoospermic men had twice as many nucleotide substitutions than normozoospermic men. However, there were no significant differences in the frequencies of nucleotide substitution and POLgamma genotypes in the two groups of men.

DNA Mutational Analysis↗
PubMed2003

Strain on the human sciatic nerve in vivo during movement of the hip and knee.

Injuries to the sciatic nerve are an occasional complication of surgery to the hip and acetabulum, and traction is frequently the causative mechanism. In vitro and animal experiments have shown that increased tensile strain on peripheral nerves, when applied for prolonged periods, impairs nerve function. We have used video-extensometry to measure strain on the human sciatic nerve during total hip replacement (THR). Ten consecutive patients with a mean age of 72 years undergoing primary THR by the posterior approach were recruited, and strains in the sciatic nerve were measured in different combinations of flexion and extension of the hip and knee, before dislocation of the hip. Significant increases (p = 0.02) in strain in the sciatic nerve were observed in flexion of the hip and extension of the knee. The mean increase was 26% (19% to 30%). In animal studies increases of this magnitude have been shown to impair electrophysiological function in peripheral nerves. Our results suggest that excessive flexion of the hip and extension of the knee should be avoided during THR.

Aged↗
PubMed2001

High incidence of single nucleotide substitutions in the mitochondrial genome is associated with poor semen parameters in men.

Single nucleotide polymorphisms (SNPs) in 7000 bp of the mitochondrial genome, encompassing 15 coding regions from COI to ND5, were characterized by single strand polymorphism analysis and confirmed by DNA sequencing. About 2.4% of normozoospermic men and 8.4% of men with poor semen quality had at least one nucleotide substitution. Most of the substitutions occurred in the third codon and did not change the amino acid. Hydrophobicity plots of the proteins with changes in an amino acid as a result of a nucleotide substitution suggested that they did not affect the function of the protein. The two most common substitutions at nucleotide (nt) 9055 and 11719 had significantly higher frequencies in men with reduced sperm motility. Eleven percent of the men with poor semen parameters and 1.3% of normozoospermic men had a 9055 substitution, 12% of the men with poor semen parameters had a substitution at nt 11719, but none of the normozoospermic men had this substitution. All the patients with these substitutions had reduced sperm motility and/or low sperm count. These SNPs in the mitochondrial genome were in a homoplasmic state. Thus, we propose that possessing these mitochondrial mutations compromises the semen quality of these men.

DNA, Mitochondrial↗
PubMed2000

Effect of stride length on symptoms of exercise-induced muscle damage during a repeated bout of downhill running.

The purpose of this study was to assess the effects of changes in stride length on the symptoms of exercise-induced muscle damage (EIMD) during a repeated bout of downhill running in a group of 18 men and women. Muscle tenderness, plasma creatine kinase activity (CK) and maximal voluntary isometric force were measured before and after two downhill runs, with each run separated by 5 weeks. The first downhill run was at the preferred stride frequency (PSF). Participants were then randomly allocated to one of three sex-balanced groups with equal numbers of men and women: overstride (-8% PSF), understride (+8% PSF) and normal stride frequency for the second downhill run. Stride length had no effect (P>0.05) on muscle tenderness, CK or isometric peak force. Increases in muscle tenderness (P<0.001) and CK were lower (P<0.05) following the second downhill run, although there was no difference in the pattern and extent of the strength decrement between the two runs. There were also no differences (P>0.05) in muscle tenderness, CK or the relative strength loss between the men and the women. Results suggest that the symptoms of EIMD are unaffected by gender and small alterations to the normal stride pattern during constant velocity downhill running. The observation that muscle tenderness and CK were reduced following a repeated bout of similar eccentric exercise is consistent with the phenomenon known as the 'repeated bout effect' of muscle damage.

Adult↗
PubMed1999

MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation.

Studies of MRI-derived volume of the amygdala have been mostly performed on coronal sections where its boundaries with the hippocampus and the entorhinal cortex are indistinct. To date, all reports of in vivo amygdala volume have consistently overestimated the size of the structure. We have developed a method for the MRI-based in vivo measurement of the amygdala volume which allows a better separation of the amygdala from the adjoining hippocampal formation. In nine normal volunteers we obtained three-dimensional spoiled gradient recalled acquisition, 1.3-mm thick, T1 weighted sagittal MR images and created electronically linked reformatted images in the coronal and axial planes. On the original sagittal and the reformatted axial planes, where it is more readily apparent, we delineated the boundaries between the amygdala and the hippocampus and the amygdala and the hippocampo-amygdala transition area, respectively. We then projected those markings onto the coronal plane, where the other boundaries of the amygdala are more easily seen. Using these markings as a guide and utilizing extra-amygdalar coronal landmarks for the anterior end, we outlined the whole amygdala on the coronal plane and determined its volume. We observed that 45% of the coronal slices that contained amygdala also contained some hippocampus. The amygdala measurement had high test-retest reliability, with an intra-class correlation coefficient (rICC) of 0.99 for the total volume and an rICC of 0.93 for the measurement at the level of the individual slice. The average amygdala volume was 1.05 +/- 0.17 cm3 on the right and 1.14 +/- 0.15 cm3 on the left. Our amygdala volumes are in agreement with those reported in postmortem studies, which provides the reported method with face validity.

Adult↗
PubMed1999

Comparison of the effects of topical lignocaine spray applied before or after induction of anaesthesia on the pressor response to direct laryngoscopy and intubation.

In an attempt to attenuate the cardiovascular pressor response to laryngoscopy and intubation, 30 patients presenting for routine ophthalmic surgery were studied and were randomly allocated into two groups: group A (n = 15) received direct laryngeal/tracheal lignocaine spray immediately before intubation; and group B (n = 15) received orolaryngeal lignocaine spray before the induction of anaesthesia. In both groups, general anaesthesia was induced with thiopentone 3-5 mg kg-1, followed by atracurium 0.6 mg kg-1 to facilitate tracheal intubation. Laryngoscopy and endotracheal intubation caused a significant increase in heart rate, by 28% in group A and 23% in group B (P < 0.05 in both), and in diastolic blood pressure, by 28% in group A and 24% in group B (P < 0.05 in both). In group A, the systolic blood pressure also increased significantly (by 18%) after intubation, but there was no significant change in group B. In addition, the plasma lignocaine concentrations remained well below the toxic range in both groups. It was concluded that topical lignocaine administration as an orolaryngeal spray before the induction of anaesthesia is effective in reducing but not abolishing the pressor response to laryngoscopy and endotracheal intubation.

Administration, Topical↗
PubMed1998

Caffeine and schizophrenia.

Although the database is small and not completely consistent, it appears that patients with schizophrenia have high caffeine intakes. The reasons are unclear. In nonhumans, caffeine enhances the effects of dopamine, which might be expected to worsen positive symptoms and improve negative symptoms of schizophrenia and worsen tardive dyskinesia. Eliminating caffeine among patients with schizophrenia does not appear to make them better or worse. Acute intake of large amounts of caffeine may increase psychoses and hostility. However, those who chronically use large amounts of caffeine may develop enough tolerance that these adverse effects do not occur, but whether this conjecture is true has not been tested. Interestingly, persons with schizophrenia do not develop anxiety at high doses of caffeine. Although there was initial concern that caffeine might inactivate liquid doses of neuroleptics, the clinical significance of this concern is unclear. On the other hand, caffeine might increase the level of clozapine, and more research in this area is needed.

Animals↗
PubMed1997

Mechanical characteristics of dilated polytetraflouroethylene used for transluminally placed endovascular grafts.

This study was conducted to assess the mechanical characteristics of dilated polytetraflouroethylene (PTFE) for use in transluminally placed endovascular grafts (TPEGs). Ten-centimeter lengths of 3- and 4-mm thinwalled PTFE were dilated to 8, 10, 12, and 15 mm diameters (3 mm) and 10-, 14-, 16-, and 20-mm diameters (4 mm), respectively (n = 6 for each size). The dilated PTFE segments were evaluated for leakage, further dilation, structural changes (with electron microscopy), and changes in wall thickness occurring after 24 hours of perfusion at pressures of 300-350 mmHg. Both 3- and 4-mm thinwalled PTFE could be dilated to five times their initial diameter before rupture occurred. Three-millimeter grafts dilated to 12- and 4-mm grafts dilated to 14 mm remained resistant to leakage at perfusion pressures up to 350 mmHg. When 3-mm grafts were dilated to 15 mm, the PTFE leaked saline at a rate of 20.3 +/- 9.3 cc per hour at 300 mmHg. pressure. Four-millimeter grafts dilated to 16- and 20-mm diameters leaked saline at 8.4 +/- 7.8 and 52.8 +/- 22 cc per minute, respectively, at the same pressure. No grafts were found to increase in diameter after 24 hours of pressure perfusion. Electron microscopy revealed that PTFE node size was significantly smaller in dilated grafts than in undilated grafts, but there was no significant change in internodal distance. This data suggests that thinwalled PTFE can be dilated to large diameters and retain sufficient strength to resist supraphysiologic pressures. Long-term studies are needed to determine the late structural integrity of dilated PTFE.

Blood Vessel Prosthesis↗
PubMed1997

Evaluation of a protocol to select patients of all ages for cardioversion from atrial fibrillation.

OBJECTIVE: to audit the success of a decision protocol to select patients for cardioversion from atrial fibrillation or flutter by recording the success of cardioversion and the maintenance of sinus rhythm over a 2-year period. DESIGN: retrospective case notes review. SETTING: a teaching hospital coronary care unit and cardiology department. PATIENTS: 227 consecutive patients were considered for cardioversion from atrial fibrillation or flutter from 1989 to 1992; 128 fulfilled the selection criteria. MAIN OUTCOME MEASURES: successful cardioversion and maintenance of sinus rhythm after cardioversion. RESULTS: 116 (91%) patients selected by application of the guidelines were successfully cardioverted. The probabilities of maintaining sinus rhythm at 6, 12 and 24 months were 0.92, 0.88 and 0.73 respectively. CONCLUSION: careful selection of patients in atrial fibrillation identifies a group in whom cardioversion is likely to be safe and successful regardless of age.

Adult↗
PubMed1997

Addison's disease and selective IgA deficiency in two coeliac patients.

Coeliac disease is associated with selective IgA deficiency and various autoimmune disorders. An association between Addison's disease and coeliac disease has been documented previously in the literature but never heretofore in coeliac patients with selective IgA deficiency. From a coeliac registry of over 700 biopsy-proven coeliac patients, studied closely over a 25-year period at University College Hospital, Galway, we now report the finding of Addison's disease and selective IgA deficiency in two patients with established coeliac disease. Previous reports of Addison's disease in coeliac patients were sporadic, and it was felt that the association between the two conditions was fortuitous. We now believe that coeliac patients, especially those who are selectively deficient in serum IgA, should be followed up with increased vigilance, as the association between IgA-deficient coeliac patients and Addison's disease is greater than can be explained by chance. Furthermore, we suggest that patients with established Addison's disease may have subclinical coeliac disease and should be screened with anti-reticulin or anti-endomyseal antibodies.

Addison Disease↗
PubMed1995

The efficacy of audiotapes in promoting psychological well-being in cancer patients: a randomised, controlled trial.

Open or uncontrolled studies have suggested that providing cancer patients with audiotapes of their clinical interviews can improve information recall and reduce psychological distress. We tested these hypotheses in a 'clinician-blind', prospective, randomised controlled trial. A total of 117 patients newly referred to a medical oncology clinic who were to be given 'bad news' had their consultations audiotaped. Blind to the clinician, patients were randomly allocated to receive a copy of the tape to play at home or not (control group). At 6 months follow-up, tape group patients reported positive attitudes to the audiotape and were shown to recall significantly more information about their illness than did controls. Overall improvement in psychological distress at 1 and 6 months follow-up, as measured with the 30-item General Health Questionnaire and the Hospital Anxiety and Depression Scale was no different in the two groups. However, a second-order interaction suggested that poor-prognosis patients were disadvantaged specifically by access to the audiotape, with less improvement in psychological distress at 6 months follow-up than non-tape controls. Patient access to audiotapes of clinical interviews promotes factual retention but does not reliably reduce psychological distress and may be actively unhelpful in some subgroups of patients.

Adult↗
PubMed1994

Effects of electrical stimulation on lymphatic flow and limb volume in the rat.

BACKGROUND AND PURPOSE: The mechanism by which electrical stimulation affects edema has not been elucidated. The purpose of this study was to determine whether subcontraction high-voltage stimulation (SC-HVS) (ie, electrical stimulation that did not elicit a visible contraction) applied to the right hind limbs of rats would (1) alter the rate of lymphatic uptake of injected albumin labeled with Evans blue dye (AL-EBD) and (2) affect experimentally induced edema. SUBJECTS AND METHODS: The paws of 28 anesthetized Sprague-Dawley rats (mean weight = 263 g, SD = 48 g) were injected with AL-EBD. The experimental group (n = 13) received 1 hour of SC-HVS, and the control group (n = 15) received sham treatment consisting of the same treatment administered to the experimental group but without the SC-HVS. Blood samples and volume measurements were obtained at intervals over a 7-hour period. RESULTS: Analysis of variance and post hoc testing indicated that higher amounts of AL-EBD were taken up by the lymph of the experimental group animals as compared with the control group animals at each time period following the treatment. The experimental group's AL-EBD reached significance immediately after treatment, whereas the control group required an additional 4 hours. There was no significant reduction in limb volume in either group. CONCLUSION AND DISCUSSION: The SC-HVS significantly increased the uptake of AL-EBD by lymphatic vessels, but it did not cause a significant decrease in the induced edema. The results of this study indicate that SC-HVS has the potential to reduce edema by increasing lymphatic uptake of proteins.

Albumins↗
PubMed1991

Characterization of a protein that regulates the DNA-binding activity of NF-AT, the nuclear factor of activated T cells.

NF-AT is a T-cell-restricted activity that regulates interleukin 2 expression by binding to positions -285 to -254 of the interleukin 2 gene. Prior studies have shown that NF-AT is found only in T cells that are appropriately stimulated with "two signals" and is sensitive to the immunosuppressive drugs cyclosporin A and FK506. However, NF-AT has yet to be characterized biochemically. Here we show that the activity of NF-AT in electrophoretic gel mobility-shift assays is greatly enhanced by a distinct protein with an apparent molecular mass of 28 kDa. This modulator has been enriched from the flow-through of NF-AT affinity columns and enhances by severalfold the activity of the factor that elutes from these columns. The modulator has a predominantly nuclear location, but unlike NF-AT, the modulator is found in nuclear extracts of many cell types, even unstimulated T cells and T cells immunosuppressed with cyclosporin A or FK506. This modulator protein may regulate NF-AT binding activity posttranscriptionally, and it should prove useful in the isolation and biochemical characterization of NF-AT.

Base Sequence↗
PubMed1991

Continuous ambulatory ECG monitoring in the perioperative period: relationship of preoperative status and outcome.

We have used continuous ambulatory electrocardiography in the perioperative period to monitor 108 patients with known cardiovascular disease undergoing non-cardiac surgery. There was a high incidence of ischaemic ST segment changes and ventricular arrhythmias. For the group as a whole, anaesthesia and surgery were followed by increased ventricular ectopic activity, but did not worsen myocardial ischaemia. However, the mean duration of ischaemic ST segment changes was increased significantly in those patients with treated hypertension. Of the risk factors considered, preoperative ischaemia and peroperative systolic arterial pressure were significant correlates with postoperative myocardial ischaemia.

Aged↗
PubMed1991

Effect of single doses of cisapride and ranitidine administered simultaneously on plasma concentrations of cisapride and ranitidine.

We have studied in 12 volunteers the effect of single doses of cisapride and ranitidine, administered simultaneously, on plasma concentrations of cisapride and ranitidine. Median maximum plasma concentration of ranitidine was achieved 1 h earlier when ranitidine was taken with cisapride compared with ranitidine alone (P = 0.012). There was a 24% decrease in plasma ranitidine AUC8h when ranitidine was taken with cisapride compared with ranitidine alone (P less than 0.005). Ranitidine had no effect on absorption of cisapride.

Adult↗