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Biomedical subjects

M Durkin

Publications and source records attributed to M Durkin.

At least 37 records · Page 2Linked to original sources

Increased gastrointestinal symptoms in chronic alcoholics.

Although chronic alcoholics frequently present with gastrointestinal (GI) symptoms, the precise prevalence of GI symptoms in this group is unknown. Accordingly, we compared the frequency and severity of GI symptoms in 48 male alcoholics with those of 48 nonalcoholic controls. A standardized questionnaire was administered on two separate occasions to all subjects, and 14 GI symptoms were evaluated for three periods (during active drinking, early withdrawal, and sobriety). Symptom severity was assessed with a visual analog scale (1-10). Both actively drinking and withdrawing alcoholics had more frequent heartburn, nausea, vomiting, diarrhea, and flatulence, and more severe chest pain, milk intolerance, and postprandial fullness. These symptoms were transient and did not correlate with the quantity of alcohol consumed. Thus, alcoholics have more frequent and more severe GI symptoms which resolve quickly during abstinence and which predominantly occur while actively drinking rather than during withdrawal.

Adult↗

Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.

An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.

Adenylyl Cyclase Inhibitors↗

Transesophageal two-dimensional echocardiographic analysis of right ventricular systolic performance indices during coronary artery bypass grafting.

Sixteen patients (aged 59 +/- 14 years) undergoing coronary artery bypass surgery were evaluated to delineate the intraoperative course of transesophageal echocardiographic right ventricular (RV) systolic performance indices. Pre-induction data included thermodilution RV ejection fraction (RVEFTD), 0.43 +/- 0.13, RV end-diastolic volume index (EDVI), 110 +/- 33 mL/m2, cardiac index (CI), 3.4 +/- 1.0 L/min/m2, RV end-diastolic pressure (EDP), 7.1 +/- 4.2 mmHg, and mean pulmonary artery pressure (PAP), 21 +/- 6 mmHg. Eleven patients had significant right coronary artery (RCA) disease (> 70% occlusion). Five patients arrived with an ongoing nitroglycerin infusion (1 to 3 micrograms/kg/min), which was maintained intraoperatively. Echocardiographic measurements included longitudinal-axis (LA) and short-axis (SA) planimetered area excursion fractions (2DLA and 2DSA, respectively) and LA maximal major and minor axis shortening fractions (max majorLA and max minorLA, respectively). Hemodynamic measurements included RVEFTD, EDVI, CI, EDP, and PAP. Measurements were determined following induction/endotracheal intubation, following sternotomy/pericardiotomy, and after cardiopulmonary bypass (CPB) with the chest open. All patients were maintained on vasodilator therapy post-CPB (nitroglycerin, 1 to 3 micrograms/kg/min [N = 16] and nitroprusside, 0.5 to 4.5 microgram/kg/min [N = 4]) post-CPB. Two patients received inotropic support (epinephrine, 0.2 to 0.3 microgram/kg/min). CPB was associated with significant decreases in max major axisLA and 2DLA (P < 0.05) as compared to measurements determined prior to CPB. Maximum major axisLA values pre-CPB were 0.35 +/- 0.06 and 0.33 +/- 0.08 versus post-CPB values of 0.24 +/- 0.08.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

The relationship between "normal" transesophageal color-flow Doppler-defined tricuspid regurgitation and thermodilution right ventricular ejection fraction measurements.

Twenty coronary artery revascularization patients, aged 58 +/- 15 years, were studied intraoperatively to define the impact of Doppler-defined tricuspid regurgitation on measurement of thermodilution right ventricular ejection fraction (50 msec response pulmonary artery catheter). Right ventricular function was also estimated using a measurement technique independent of flow patterns across the tricuspid valve (transesophageal two-dimensional echocardiographic 5.0 MHz phased-array transducer). Measurements included transverse plane long- and short-axis planimetered area ratio, respectively, and tricuspid annular plane systolic excursion ratio (ratio = end-diastolic minus end-systolic value divided by end-diastolic value). Data were expressed as thermodilution-echocardiographic gradients, ie, thermodilution ejection fraction minus long-axis planimetered area ratio, short-axis planimetered area ratio, and tricuspid annular plane systolic excursion ratio, respectively. Tricuspid regurgitation was quantified by color-flow Doppler perimetry of maximal regurgitation jet area and analysis of transduced right atrial pressure waveform. Doppler estimates were expressed as absolute values and as a function of corresponding atrial area (tricuspid regurgitation index = planimetered jet area divided by right atrial area). Data were obtained following endotracheal intubation, sternotomy, pericardiotomy, cardiopulmonary bypass, and chest closure. Data were evaluated by regression analysis, with separate analyses performed for each time period. Profiles were unassociated with right atrial pressure waveform abnormalities. There was no significant relationship between thermodilution ejection fraction variance values and tricuspid regurgitation jet area or regurgitation index, respectively. In each measurement period, thermodilution-echocardiographic gradients were also unrelated to the tricuspid regurgitation estimates.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization, Swan-Ganz↗

Concomitant eyeblink and heart rate classical conditioning in young, middle-aged, and elderly human subjects.

Pavlovian heart rate (HR) and eyeblink (EB) conditioning were assessed in 4 groups of Ss who differed in age: young = 19-33 years, young middle-aged = 35-48 years, old middle-aged = 50-63 years, and old = 66-78 years. A 100-ms corneal airpuff was the unconditioned stimulus and a 600-ms tone was the conditioned stimulus. A nonassociative control group received explicitly unpaired tone and airpuff presentations. All Ss were studied for 2 100-trial sessions separated by approximately 7 days. An impairment in acquisition of both the EB and HR responses occurred in the old and middle-age Ss, but all age groups showed significantly greater conditioning than did the control group. Slight increases in performance resulted from a 2nd session of training. These findings suggest an age-related impairment in a general associative process.

Adult↗

Esophagitis and esophageal motor abnormalities in patients with chronic spinal cord injuries.

To investigate the frequency and severity of esophagitis and esophageal dysmotility in patients with chronic spinal cord injury (SCI), 46 males with chronic SCI completed a questionnaire regarding gastrointestinal symptomatology. Eleven of these patients subsequently underwent upper gastrointestinal (GI) endoscopy with esophageal biopsies and 10 of the 11 also had esophageal motility studies. A significantly higher percentage of SCI patients experienced heartburn (SCI 61%; controls (C) 40%), esophageal chest pain (SCI 33%; C 6.4%), and intermittent dysphagia (SCI 30%; C 8.5%). Forty-five percent of SCI patients had endoscopic evidence of mild esophagitis, and 91% of them had histologic evidence of esophagitis. SCI patients had low amplitude, slowly propagating abnormal (double-peaked) peristatic esophageal contractions. We conclude that SCI patients experience significantly more esophageal symptoms than controls. They have a higher incidence of esophagitis and esophageal motor abnormalities. The clinical relevance of these abnormalities remains to be evaluated.

Adult↗

Increased production of luminol enhanced chemiluminescence by the inflamed colonic mucosa in patients with ulcerative colitis.

Reactive oxygen species have been implicated as mediators of inflammation in ulcerative colitis. Chemiluminescence is a reliable means of estimating reactive oxygen species in biological media. Increased reactive oxygen species values in the inflamed colonic mucosa in rats were seen by chemiluminescence. The aims of the study were to find out if chemiluminescence is raised in the colonic mucosa of patients with ulcerative colitis and correlates with disease activity, and to elucidate the sources of the chemiluminescence. It was found that reactive oxygen species, as measured by the chemiluminescence technique, are raised in inflamed colonic mucosa and correlates with symptom score, sigmoidoscopic score, disease activity, and activity of the neutrophil enzyme myeloperoxidase. Chemiluminescence was inhibited by a myeloperoxidase inhibitor (azide) and an H2O2 scavenger (catalase) but not by allopurinol, an inhibitor of the enzyme xanthine oxidase. Chemiluminescence was also inhibited by indomethacin, but this did not seem to be related to inhibition of cyclo-oxygenase. These findings suggest that a likely cellular source of reactive oxygen species in the inflamed colon of patients with ulcerative colitis is the neutrophil and that myeloperoxidase conversion of H2O2 to hypochlorous acid, contributes to the chemiluminescence signal and possibly, to the tissue injury. Neither cyclo-oxygenase nor lipoxygenase seem to play a part as sources for the chemiluminescence.

Adult↗

Secondary esophageal contractions are abnormal in chronic alcoholics.

It is known that primary (swallow-induced) esophageal contractions are abnormal in alcoholics. Data concerning acid-induced esophageal contractions, which appear to be important in cleansing refluxed acid from the esophagus, are lacking. To determine whether acid-induced esophageal contractions are also affected by chronic ethanol exposure, we studied secondary (acid or saline-induced) esophageal motor events in 19 male alcoholics [6 actively drinking (ADA), 13 withdrawing (WA)]. Esophageal motility was performed in response to wet swallows (5 ml of water) and to intraesophageal injection of 5 ml of 0.1 N HCl (0.1 N) or saline. Lower esophageal sphincter pressure (LESP), amplitude (ECA), duration (ECD), and velocity (ECV) of esophageal contractions in response to swallowing and injection of acid or saline were similar in controls and alcoholics. There were more simultaneous and double-peaked contractions in response to acid and saline than to swallows in both alcoholics and controls. However, there was no difference between HCl- and NaCl-induced contractions. ECA in alcoholics was significantly higher than in controls. ECD in alcoholics was significantly more prolonged than in controls. There was no significant different between alcoholics and controls in ECV, LESP, or LES relaxation. These data indicate that similar to primary esophageal contractions, secondary esophageal contractions are also abnormal in both actively drinking and withdrawing alcoholics.

Adult↗

Thermodilution right ventricular ejection fraction measurement reproducibility--a study in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To assess the effects of heart rate, right ventricular systolic performance (ejection fraction), chamber dimensions, and flow rate (cardiac index) on the reproducibility of algorithm-derived triplicate thermodilution right ventricular ejection fraction measurements. DESIGN: Prospective study; combined hemodynamic and echocardiographic clinical evaluation. SETTING: Operating room in a university hospital. PATIENTS: Twenty-one coronary artery bypass graft patients. MEASUREMENTS AND MAIN RESULTS: The right atrial delivery site was positioned by analysis of transduced pressure waveform and echocardiographic imaging of tracer agitated saline cavitations. Measurement reproducibility was quantified by determining the variation (standard deviation) within 101 triplicate thermodilution measurement sets. There was no significant relationship between measurement reproducibility and estimates of right atrial area (21.6 +/- 6.9 cm2), diameter (5.1 +/- 0.8 cm) and supero-inferior length (5.1 +/- 0.9 cm) and right ventricular maximal minor axis diastolic diameter (4.21 +/- 1.05 cm). Reproducibility was also unrelated to right ventricular end-diastolic volume index (97.9 +/- 32.7 mL/m2) and cardiac index (2.9 +/- 0.9 L/min/m2). Measurement reproducibility was directly related to mean right ventricular ejection fraction (0.39 +/- 0.14) and inversely related to heart rate (80.8 +/- 18.6 beats/min) (p < .01 and < .001, respectively). CONCLUSIONS: Thermodilution-derived right ventricular ejection fraction measurement reproducibility was unrelated to estimates of right atrial and ventricular dimensions and cardiac index. Measurement reproducibility was a direct function of right ventricular systolic performance and an indirect function of heart rate. Measurement should be interpreted with these constraints in mind.

Adult↗

Identification of childhood disability in Jamaica: the ten question screen.

This is the first in a series of papers that report the testing of two instruments for the identification and assessment of childhood disability by community workers (CWs) in Third World countries. It is part of the International Epidemiologic Study on Childhood Disability. The Ten Question Screen (TQ) was used as the main instrument to identify disability in a two stage population-based survey of 5478 children aged 2-9 years in Clarendon, Jamaica. In the second stage, TQ positive and 8% of the screen negative controls were professionally assessed by a doctor and a psychologist using standard criteria based on the main classification system of the ICIDH. Sensitivity of the TQ as a whole varied in different strata of the group and amongst different disabilities, from perfect in girls under 6 years, fits and motor disabilities and for serious disability in all group except boys over 5 years with cognitive disability. Specificity was good but the false positive rate was unacceptably high at 74%. It was concluded, firstly, that the validation of a simple questionnaire of perceptions of behaviour against objective measurements of impairments was perhaps not fair to the TQ. In spite of this, the TQ would be a very useful instrument in collecting disability data or for identifying people in need of rehabilitation help, if a way of reducing false positives could be found.

Child↗

Concomitant heart rate and eyeblink Pavlovian conditioning in human subjects as a function of interstimulus interval.

Pavlovian heart rate and eyeblink conditioning were simultaneously assessed in human subjects. Tone durations of 0.6, 1.1, and 2.1 s were employed in separate groups of subjects as the conditioned stimulus. A 100-ms corneal airpuff, which served as the unconditioned stimulus, overlapped the last 100 ms of the tone in each group, thus producing interstimulus intervals of 0.5, 1.0, and 2.0 s. Other groups of pseudoconditioning subjects received explicitly unpaired tone and airpuff presentations of identical durations but in a pseudorandom sequence so that they never occurred together. The best eyeblink conditioning was observed in the group with the .5-s interstimulus interval, although the 1.0-s group also demonstrated some evidence of eyeblink conditioning. The group with the 2.0-s interstimulus interval showed a lower overall rate of conditioned response occurrence and the highest rate of pseudoconditioned responding. The conditioned heart rate response in all three conditioning groups consisted of cardiac decelerations, but tone-evoked cardiac accelerations were observed in the pseudoconditioning groups. The magnitude of the cardiac deceleration was comparable in all three conditioning groups.

Adult↗

Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.

Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.

Acquired Immunodeficiency Syndrome↗

Transesophageal echocardiographic evaluation of aortic valve integrity with antegrade crystalloid cardioplegic solution used as an imaging agent.

Forceful intravascular injection of crystalloid causes microbubble (cavitation) formation. The resulting ultrasound-opaque medium is widely used in echocardiography as a source of contrast. The following study was performed to determine the feasibility of using antegrade crystalloid cardioplegic solution as a transesophageal two-dimensional echocardiographic imaging agent to evaluate aortic valve integrity. In patients with preexisting aortic regurgitation (n = 12), cardioplegic solution administration (driving pressure 150 to 200 mm Hg) was associated with the appearance of intracardiac cavitations in 12 of 12 patients. Among patients without preexisting valve dysfunction (n = 22), intracardiac cavitations were manifested in 20 of 22, with extension of the cavitations to the left atrium in 17. Associated cardiac dimensions (left ventricular outflow tract area and left ventricular diameter) did not exceed preceding cardiopulmonary bypass values in these patients (2.0 +/- 1.6 cm2 versus 2.6 +/- 1.2 cm2 and 1.4 +/- 0.7 cm versus 1.5 +/- 0.8 cm, respectively). It was concluded that antegrade crystalloid cardioplegic solution can be used as an echocardiographic contrast agent in this context. The inability to establish a relationship between the extent of cardioplegic intracardiac penetration and left ventricular dimensional changes limits the technique, as presently employed, to qualitative analysis of valve dysfunction.

Adult↗

Alterations of local cerebral blood flow and glucose uptake by electroconvulsive shock in rats.

The effects of single and repeated electroconvulsive shock (ECS) treatment on regional cerebral blood flow (rCBF) and on rates of glucose flow from blood to local brain areas (rCGF), were investigated in pentobarbital-anesthetized rats, using quantitative autoradiographic techniques. Effects of single ECS on rCBF were assessed at two average time points of 15 and 55 sec after the application of the electric current, whereas the effects on rCGF were assessed at 70 and 110 sec. Effects of repeated ECS were assessed 24 hr after the last ECS in a series of eight daily treatments. Single ECS caused marked increases in rCGF in different brain structures, but no significant effects were observed after repeated ECS. Similarly, substantial increases in rCBF were seen during and immediately after the ECS-induced seizure, but not 24 hr after the last treatment of repeated ECS. Single ECS appeared to have differential effects on rCBF in hind-brain structures as compared to more anterior regions. A linear relationship between rCBF and rCGF values was established in control animals, indicating coupling of these two variables with a constant rCBF/rCGF ratio. ECS caused an apparent increase in the CBF/CGF ratio, which might be attributed to the different temporal resolution of the two methods used here to estimate rCGF and rCBF. Analysis of the increments of rCGF and rCBF extrapolated to the same point in time after a single ECS (10 sec), revealed that in many of the examined structures the CBF/CGF ratio was similar to that observed in control animals, indicating that the coupling of CBF and CGF is maintained during the seizure. But in some brain stem structures such as the dorsal raphe, inferior colliculi, superior olivary nucleus, and the vestibular nucleus there were large increases in CGF associated with a marked drop in the CBF/CGF ratio. This observation suggests that high metabolic demands can be met by increased local blood flow up to a given "ceiling" keeping the glucose clearance from blood to brain tissue constant. However, when the metabolic demands exceed this upper limit, the additional demands could be met by an increased clearance of glucose without a change in CBF.

Animals↗

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗

Autoradiographic study of iron-binding sites in the rat brain: distribution and relationship to aging.

Specific binding of 59Fe to various brain structures was investigated in rats using nanomolar concentrations of 59FeCl3 and quantitative autoradiography. Saturation studies revealed high affinity binding (kd in the nanomolar range) with binding sites density (Bmax) which varied in different brain regions from 462 fmol per mg tissue in the central thalamic nuclei to over 4 pmol per mg tissue in the cerebral peduncle. Binding was seen in both white and gray matter structures. Bmax values for frontal cortex, dentate gyrus, and substantia nigra were significantly lower in older rats. The distribution of 59Fe binding sites was not consistent with the distribution of brain iron as reported by other investigators. 59Fe binding was reduced significantly in the presence of free radicals. These observations suggest that high affinity binding sites for iron are localized differentially in various brain structures and may play an important role in the translocation and storage of potentially harmful ferric cations in brain. The finding that the capacity of the brain tissue to bind iron diminished with age in discrete brain regions suggests that in the aged animal, the removal of "free" iron from the cellular domain may be impaired in such regions, leading to increased susceptibility to iron-enhanced lipid peroxidation and cell death.

Aging↗

A comparison of efficacy of the key informant and community survey methods in the identification of childhood disability in Jamaica.

A comparison of the efficacy of the key informant and the community survey methods for identifying children with disability was carried out in the Jamaican component of an international epidemiological study of childhood disability. Approximately 130 key informants were exposed to a 2-day workshop giving information on signs of disability, aspects of the project, and available services. Questionnaires were given to enable the informants to refer children and they were reminded 6 months later. In the survey method, eight community workers completed a house-to-house survey of all families and administered the 10-question screen with probes on 5475 children, 2 to 9 years old. Seventeen referrals were made by the key informants; of these, two were found to have disabilities. Of the 821 children who tested positive on the 10-question screen in the house-to-house survey, 193 had disabilities. We concluded that the key informant method would not be a satisfactory way of identifying cases of childhood disability.

Child↗