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Biomedical subjects

M J Walsh

Publications and source records attributed to M J Walsh.

At least 37 records · Page 2Linked to original sources
PubMed1998

Transventricular pressure-velocity wave propagation in diastole: adherence to the Moens-Korteweg equation.

In the latter half of the diastolic phase of the cardiac cycle, the left atrium contracts and generates a pressure-velocity wave which enters the left ventricle. The wave moves through the inflow tract of the ventricle, reflects off the apex and heads towards the aortic valve. The time taken for the pressure-velocity wave to propagate through the ventricle, referred to as the A-Ar interval, may be measured using pulsed Doppler echocardiography and occurs in the range 20-80 ms. It has been shown previously that there is a significant negative linear correlation between the A-Ar interval and the passive elastic modulus of the ventricular wall (r = -0.782, p < 0.001). This relationship may be explained by modelling the left ventricle as a folded-over elastic tube through which the pressure-velocity wave is propagated according to the principles of the Moens-Korteweg equation.

Algorithms↗
PubMed1998

Functional outcomes following treatment for advanced laryngeal cancer. Part I--Voice preservation in advanced laryngeal cancer. Part II--Laryngectomy rehabilitation: the state of the art in the VA System. Research Speech-Language Pathologists. Department of Veterans Affairs Laryngeal Cancer Study Group.

This two-part investigation assessed functional outcomes related to communication (including amount of speech therapy), swallowing and eating, and employment status for patients who received one of the two treatment modalities for advanced laryngeal cancer (stage III or IV laryngeal squamous cell carcinoma) in Veterans Administration Cooperative Study #268. One hundred sixty-six patients were randomized to primary surgery (laryngectomy) and radiotherapy (RT), and 166 to induction chemotherapy (CT) and RT. The first investigation dealt with examining and comparing functional outcomes for patients in the two treatment arms of the main study. Results showed clearly that patients with advanced laryngeal cancer are better off from the standpoint of speech communication if they can be treated for this disease without removal of the larynx. In contrast, there were few significant differences between patient groups for other non-speech-related measures. The second investigation focused on communication-related outcomes associated with the rehabilitation of total laryngectomy patients. Results revealed that only relatively small percentages of total laryngectomy patients (6%) developed usable esophageal speech or remained nonvocal (8%), and that a majority of patients ended up as users of artificial electrolarynx (55%) or tracheoesophageal (31%) speech. The results from both investigations are discussed with respect to factors that can influence the rehabilitation process and long-term outcome status of patients who are treated for advanced laryngeal cancer with these two strategies.

Adult↗
PubMed1998

Evaluation of orthopedic testing of the low back for nonspecific lower back pain.

OBJECTIVE: To assess the value of some commonly used orthopedic tests used in evaluating nonspecific lower back pain where there are no demonstrable pathological or neurological deficits. DESIGN: Retrospective analysis of patient files. SETTING: Chiropractic teaching clinic, Royal Melbourne Institute of Technology. SUBJECTS: Five hundred sixty-four files of patients presenting to the above clinic with nonspecific lower back pain were analyzed. DATA ANALYSIS: The data were entered into a spreadsheet, contingency tables were created, and the data were analyzed using chi 2 tests. Statistical significance was set at p < .05. RESULTS: Kemp's and Yeoman's tests were most commonly positive, whereas Bonnet's, supported Adams' and axial compression tests showed relatively low positive results. The factors studied that affected the rate of positive responses were age, gender, pain site, duration and cause. The number of previous episodes of lower back pain had no effect on the positive test rates. CONCLUSION: For cases of nonspecific, mechanical lower back pain, orthopedic testing has limited clinical value once nerve root problems and pathologies have been ruled out. Kemp's and Yeoman's tests were the most frequently positive, and seemed to be the most useful in diagnosing nonspecific lower back pain. When selecting the most appropriate tests to use, one needs to take into account the patient profile and history.

Adolescent↗
PubMed1997

Immunohistochemical localization of the neuron-specific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody.

Neuronal regulation of glutamate homeostasis is mediated by high-affinity sodium-dependent and highly hydrophobic plasma membrane glycoproteins which maintain low levels of glutamate at central synapses. To further elucidate the molecular mechanisms that regulate glutamate metabolism and glutamate flux at central synapses, a monoclonal antibody was produced to a synthetic peptide corresponding to amino acid residues 161-177 of the deduced sequence of the human neuron-specific glutamate transporter III (EAAC1). Immunoblot analysis of human and rat brain total homogenates and isolated synaptosomes from frontal cortex revealed that the antibody immunoreacted with a protein band of apparent Mr approximately 70 kDa. Deglycosylation of immunoprecipitates obtained using the monoclonal antibody yielded a protein with a lower apparent Mr (approximately 65 kDa). These results are consistent with the molecular size of the human EAAC1 predicted from the cloned cDNA. Analysis of the transfected COS-1 cells by immunocytochemistry confirmed that the monoclonal antibody is specific for the neuron-specific glutamate transporter. Immunocytochemical studies of rat cerebral cortex, hippocampus, cerebellum, substantia nigra and spinal cord revealed intense labeling of neuronal somata, dendrites, fine-caliber fibers and puncta. Double-label immunofluorescence using antibody to glial fibrillary acidic protein as a marker for astrocytes demonstrated that astrocytes were not co-labeled for EAAC1. The localization of EAAC1 immunoreactivity in dendrites and particularly in cell somata suggests that this transporter may function in the regulation of other aspects of glutamate metabolism in addition to terminating the action of synaptically released glutamate at central synapses.

Adult↗
PubMed1997

Correlation of end-diastolic pressure and myocardial elasticity with the transit time of the left atrial pressure wave (A-Ar interval).

Contraction of the left atrium in diastole generates a pressure wave that moves along the postero-lateral wall of the left ventricle (LV), rebounds off the LV apex, and is then directed toward the outflow tract. The movement of this atrial pressure wave may be detected with pulsed Doppler echocardiography by placing a sample volume in the LV outflow tract. The resulting spectral profile shows the initial. A velocity wave and also the Ar velocity wave, which is caused by the atrial pressure wave rebounding off the LV apex. The transit time from the inflow tract to the outflow tract of the atrial pressure wave (A-Ar interval) may be determined from the time axis of the spectral profile by measuring the peak-to-peak separation of the A and Ar, velocity waves. It occurs in the range 25 to 80 milliseconds. The primary determinant of the A-Ar interval is the elasticity of the LV myocardium. We correlated ventricular elasticity with the A-Ar interval in 47 patients and found a significant negative linear correlation (r = -0.782, p < 0.001). Because the pressure in a viscoelastic conduit such as the LV is determined by the elasticity of the ventricular wall, we correlated end-diastolic pressure with the A-Ar interval and again showed a significant negative linear correlation (r = -0.701, p < 0.001). The A-Ar interval is an easily measured noninvasive index of the diastolic function of the LV that reflects its intrinsic elasticity and end-diastolic pressure. It is therefore a quantitative measurement of LV wall stiffness and end-diastolic pressure.

Adult↗
PubMed1997

The ontogeny of canine small intestinal submucosa regenerated bladder.

PURPOSE: Small intestinal submucosa has previously been shown to promote regeneration of transitional epithelium, smooth muscle and peripheral nerves in rat and dog bladders. The origin of these regenerated components is presently unknown. This study attempts to define the origin of vascular, smooth muscle and peripheral nerve regeneration. MATERIALS AND METHODS: A total of 22 adult male dogs weighing 25 to 30 kg. underwent partial cystectomy and immediate augmentation with a small intestinal submucosa patch graft. The small intestinal submucosa graft-native bladder interface was marked with permanent marking sutures for future reference. Small intestinal submucosa regenerated bladders were harvested at 2, 3, 4, 6, 8 and 10 weeks after augmentation. The tissue was then studied with routine histology and immunohistochemistry using factor VIII, smooth muscle specific actin (1A4) and neurofilament staining. RESULTS: Results demonstrated that epithelialization of the graft surface was complete by 3 to 4 weeks with normal transitional histology. In the early periods neovascularization was prominent throughout the entire graft, as shown by factor VIII staining. Later more mature vessels were noted. Early in muscle formation sheets of elongated spindle cells extended into the graft from the incised native bladder at both surgical margins and ran parallel to the mucosal surface. At 4 weeks this spindle cell proliferation completely traversed the graft. Trichrome stained sections of the 4-week-old grafts showed no evidence of muscle differentiation and the spindle cells appeared to be fibroblasts. However, these cells stained positive for smooth muscle specific actin (1A4), indicating myogenic potential. Between weeks 4 and 6 the spindle cells became more haphazardly arranged and were separated by loose interstitium. By weeks 8 to 10 there was distinct smooth muscle bundle formation within these areas of proliferating myocytes. Neural regeneration appeared to coincide with smooth muscle development. Early neurofilament positive cells were noted predominantly at the graft-native bladder interface. At 4 weeks neurofilament positive cells were present throughout the graft and by 10 weeks nerve trunks composed of several nerve fibers were identified in association with newly formed smooth muscle bundles. CONCLUSIONS: Small intestinal submucosa serves as a platform for bladder regeneration. Neovascularization smooth muscle and neural regeneration appear to occur through pannus ingrowth from the graft-native bladder interface. Smooth muscle regeneration seems to begin with the maturation of myofibroblasts, which migrate into the graft as early as 2 weeks after augmentation, and it progresses to the formation of distinct smooth muscle bundles by 10 weeks.

Animals↗
PubMed1996

Natural history of isolated bundle branch block.

The purpose of this study was to determine the long-term outcome of patients with bundle branch block (BBB) who have no clinical evidence of cardiovascular disease. Among 110,000 participants in a screening program, 310 subjects with BBB without apparent of suspected heart disease were identified. Their outcome after a mean follow-up of 9.5 years was compared with that of 310 similarly screened age- and sex-matched controls. Among the screened population, isolated right BBB was more prevalent than isolated left BBB (0.18% vs 0.1%, respectively; p<0.001), and the prevalence of each abnormality increased with age (p<0.001). Total actuarial survival was no different for those with left BBB or right BBB and their respective controls. Cardiac mortality, however, was increased in the left BBB group when compared with their controls (p=0.01, log rank test). Left BBB, but not right BBB, was associated with an increased prevalence of cardiovascular disease at the follow-up (21% vs 11%; p=0.04). In the absence of clinically overt cardiac disease, the presence of left BBB or right BB is not associated with increased overall mortality. Isolated left BBB is associated with an increased risk of developing overt cardiovascular disease and increased cardiac mortality.

Adult↗
PubMed1996

The role of glutamine, short-chain fatty acids, and nucleotides in intestinal adaptation to gastrointestinal disease.

Important first steps have been taken towards establishing how some nutrients interact with genes and affect intestinal adaptation. These mechanisms may be typical of how other nutrients influence cell function and turnover and help to maintain intestinal integrity. The dietary effects of nucleotides on intestinal cell mucosa act at the gene transcription level. The dietary effects of nucleotides on immune suppression also may act through similar mechanisms. The effects of the other trophic agents may interact at this level or at other levels. Scientific interest in how the various tropic factors work to maintain and repair the gastrointestinal tract is manifested by a growing body of research that demonstrates potential mechanisms for nutrient-gene interaction and how much interactions affect intestinal development and turnover. It seems clear that intestinal gene transcription and the activity of transcription factors are at least sometimes directly related to nutrition. The techniques of molecular biology now permit the exploration and explanation of how dietary factors, such as glutamine, SCFAs, and nucleotides, affect normal and pathologic intestinal mucosal development, function, adaptation, and repair.

Adaptation, Physiological↗
PubMed1996

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction.

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarction is reperfusion of the infarct-related coronary artery. Duteplase is a double-chain recombinant tissue-type plasminogen activator. Its efficacy and safety were evaluated in patients with acute myocardial infarction treated within 4 h of onset of chest pain in this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase 0.6 MU.kg-1 over 4 h, with concomitant oral aspirin and intravenous heparin. Coronary arteriography was performed at 60 min, 90 min and approximately 24 h after the start of duteplase infusion to assess the perfusion grade (TIMI scoring) of the infarct-related coronary artery. Safety was assessed by monitoring patients closely for bleeding and for all other adverse experiences during the 72-h study period. Reinfarction during the study period was also recorded, and deaths at any time during the period in hospital were documented. TIMI grade 2 or 3 patency of the infarct-related coronary artery at 90 min was achieved in 70% of the patients and 7% of these "patent' infarct-related coronary arteries had reoccluded by 20 to 36 h. Clinical reinfarction during the 72-h study period was observed in 7%. Total in-hospital mortality was 8%. Serious or life-threatening bleeding occurred in 4% of the patients. There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirin and intravenous heparin, in acute myocardial infarction resulted in patency of the infarct-related coronary artery and a safety profile comparable to those reported for the other form of tissue-type plasminogen activator, alteplase. However, there remains a problem with reocclusion and reinfarction after initially successful thrombolysis.

Adult↗
PubMed1996

[Dysphonia and inhalation of corticoids: a prospective study].

Dysphonia or hoarseness is a well recognised but poorly understood complication of inhaled steroid therapy. 20 asthmatics were investigated, using a perceptual rating score of hoarseness, videolaryngoscopy and videostroboscopy, prior to and after three months of high dose inhaled steroid therapy (1 mg/day). A group of 22 healthy volunteers acted as controls. Prior to commencing inhaled steroid therapy six of the asthmatics were hoarse. Erythema and oedema was noted in 10 asthmatics and vocal fold nodules in 2 asthmatics. 4 of the control group had erythema and oedema. There was significantly more vocal fold pathology in the asthmatic group, p = 0.0135. After three months of inhaled steroid therapy, improvement in voice was noted in 2 of the 6 hoarse asthmatics. This was associated with resolution of vocal fold nodules in one case and with resolution of oedema in another. One asthmatic developed a mid glottic chink. This study demonstrates that asthmatics have significantly more vocal fold pathology than healthy controls. These findings improve with commencement of inhaled steroid therapy. The development of steroid induced myopathy of the vocal folds is a possible cause for the development of a mid glottic chink in one of our subjects. Further studies are necessary to investigate this area further.

Administration, Inhalation↗
PubMed1995

Transcription of cystic fibrosis transmembrane conductance regulator requires a CCAAT-like element for both basal and cAMP-mediated regulation.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene in man is controlled by a tightly regulated and weak promoter. The architecture of the CFTR promoter suggests regulatory characteristics that are consistent with the absence of a TATA-like sequence, including the ability to initiate RNA transcription at numerous positions. Detailed investigation of the most proximal region of the human CFTR gene promoter through deletion and mutational analysis reveals that expression is contingent on the conservation of the inverted CCAAT sequence. Basal expression of CFTR transcription and cAMP-mediated transcriptional regulation require the presence of an imperfect and inverted CCAAT element recognized as 5'-AATTGGAAGCAAAT-3', located between 132 and 119 nucleotides upstream of the translational start site. RNA isolated from a transfected pancreatic cell line carrying integrated wild-type and mutant CFTR-directed transgenes was used to map the 5' termini of the transgenic transcripts. Analysis of the transcript termini by ribonuclease protection analysis reflects the direct association of the conserved inverted CCAAT sequence in promoting transcript initiation. Because of the requirement for the inverted CCAAT sequence for promoting transcription of CFTR, the involvement of CCAAT-binding factors is suspected in the regulation of CFTR gene transcription. To test this, we used electrophoretic mobility shift assays to demonstrate that the majority of the binding to the inverted CCAAT element, between -135 and -116, was easily competed for by binding to cognate nucleotide sequences for CCAAT-enhancer binding protein (C/EBP). An antibody specific for the C/EBP-related protein, C/EBP delta, detected C/EBP delta as part of a nuclear protein complex bound to the inverted CCAAT sequence of the CFTR gene. Also, the detection of specific activating transcription factor/cyclic-AMP response element binding protein antigens by antibody supershift analysis of nuclear complexes suggest that species of this family of transcription factors could be involved in the formation of complexes with C/EBP delta within the CFTR gene inverted CCAAT-like element. These studies raise the possibility of interactions between individual members of the C/EBP and activating transcription factor/cyclic-AMP response element binding protein families potentially contribute to the tight transcriptional control rendered by the CFTR gene promoter.

Activating Transcription Factor 1↗
PubMed1995

E2F-1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription.

The cell cycle-dependent transcription factor, E2F-1, regulates the cyclin-like species of the DNA repair enzyme uracil-DNA glycosylase (UDG) gene in human osteosarcoma (Saos-2) cells. We demonstrate, through the deletion of the human UDG promoter sequences, that expression of E2F-1 activates the UDG promoter through several E2F sites. The major putative downstream site for E2F, located in the first exon, serves as a target for E2F-1/DP1 complex binding in vitro. We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F. High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F-mediated transcription. Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase. This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription, likely through E2F. This implicates E2F as a multifunctional target for proteins and enzymes, possibly, responsive to DNA damage through the negative effect of UDG on E2F-mediated transcriptional activity.

Antigens, CD↗
PubMed1995

National perspective of acute coronary care in the Republic of Ireland.

OBJECTIVE: To assess the use of acute coronary care facilities in the Republic of Ireland with regard to case mix, patient characteristics, mortality and factors associated with mortality, time intervals to admission, utilisation of thrombolysis, and risk factor profiles. DESIGN: A 1 week prospective census of all hospitals admitting acute coronary cases. These comprised 23 coronary care units (CCU) and 17 combined coronary care/intensive care units (CCU/ICU). Data were collected by standardised methods on each new patient "upon whom a cardiac monitor was placed". RESULTS: Acute coronary heart disease was confirmed in 185 (44.9%) of 412 patients. Of these 109 (26.4%) had a confirmed myocardial infarction and 76 (18.4%) unstable angina. Women were significantly older than men in all groups. Of those with proven acute coronary heart disease, 42.6% were current smokers, 23.1% were aware of having a raised cholesterol concentration, and 42.3% gave a history of prior hypertension. Only 44% were transported by ambulance. Median delay time from the onset of symptoms to admission was 6 h in Dublin and 4 h elsewhere. 34.9% of patients with a confirmed myocardial infarction received thrombolysis. Mortality of patients with myocardial infarction CCU/ICU at 7 days was 10.9 %. CONCLUSIONS: There is potential for considerable improvement in the management of coronary heart disease in the Republic of Ireland through a reduction in delay times to admission to hospital, increased use of thrombolytic treatment, and intensification of advice on primary and secondary risk factors.

Adult↗
PubMed1995

Gene expression in the intestine: the effect of dietary nucleotides.

There is scientific concern regarding the role of dietary nucleotides in the maintenance and repair of the gastrointestinal tract. This concern is based on a growing body of research that demonstrates potential mechanisms for dietary nucleotides to affect intestinal development and turnover. It seems clear that intestinal gene transcription as well as the activity of transcription factors is at least sometimes directly related to nutrition. Implications of this work include the potential role of dietary nucleotides in infant nutrition and in intestinal repair. The techniques of molecular biology will now allow us to explore and explain how dietary factors such as nucleotides affect intestinal mucosal development, function, adaptation, and repair.

Animals↗
PubMed1994

Does the amount of endurance exercise in combination with weight training and a very-low-energy diet affect resting metabolic rate and body composition?

Effects of large (LA; 400 min/wk) and moderate (MA; 200 min/wk) amounts of endurance exercise in combination with weight training (3 d/wk) were compared with the effects of no exercise (C) in 23 obese females after a 12-wk, 3360-kJ/d very-low-energy diet (VLED). The LA group lost 6.5 kg more weight, mainly as fat (6.4 kg), than the C group (P < 0.05). No measurable differences were found among groups for decreases in resting metabolic rate (-729 to -1233 kJ/d; NS) or fat-free mass (-2.9 to -3.9 kg; NS). No improvements in aerobic capacity were achieved with the addition of exercise to a VLED (-0.079 to -0.037 L/min; NS). Strength indexes were improved (+16 to +5 kg; P < 0.05) or maintained with exercise (-3 kg; NS) whereas a loss (-9.3 kg; P < 0.05) or maintenance (+4.5 kg; NS) was found for VLED alone. Large amounts of endurance exercise in combination with weight training added to a VLED appear to improve weight and fat loss compared with a VLED alone.

Adipose Tissue↗
PubMed1993

Regulation of cytokine mRNA expression in lipopolysaccharide-stimulated human macrophages.

One of the responses of the human macrophage to lipopolysaccharide (LPS) is the production of a number of cytokines. The regulation of these cytokines is still not clearly understood. To study this regulation, mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-8/neutrophil chemotactic factor were determined in 10-day-old differentiated macrophages following stimulation with a low dose of LPS (0.001 to 10 ng/mL) with use of the polymerase chain reaction. Increased levels of mRNA for IL-8 were detectable after exposure to a very low dose of LPS (0.001 ng/mL) and levels of IL-1 beta and TNF-alpha were detectable only after stimulation with doses of 0.01 ng/mL. The mRNA for IL-8 was detected 30 minutes after the addition of LPS, while those for IL-1 beta and TNF-alpha were only measurable at 1 hour. The mRNAs for IL-1 alpha, IL-6, and GM-CSF were detectable only with a higher dose of lipopolysaccharide and only after a longer exposure time. In addition, the messages for IL-6 and GM-CSF were measurable for a short time, while those of IL-8 and of IL-1 beta were detectable for a longer time. The secretion of TNF-alpha and GM-CSF tightly followed gene activation, and that of IL-6 and IL-8 steadily increased even after the mRNA level of these cytokines returned to baseline. Secretion of IL-1 alpha and IL-1 beta was hardly detected, although their gene activation was obvious. These data indicate that cytokine mRNA levels following lipopolysaccharide stimulation are highly regulated. Individual cytokines show variable patterns of response. These responses are both dose and time dependent and are not necessarily associated with the secretion of protein.

Adult↗