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Biomedical subjects

K Murphy

Publications and source records attributed to K Murphy.

At least 37 records · Page 2Linked to original sources

Localization of adenosine A1-receptors to the terminals of the perforant path.

The localization of adenosine A1-receptors in the dentate gyrus was investigated using discrete lesioning techniques and autoradiographic procedures. In rats with unilateral knife-cut lesions to the perforant-path (the major input to the dentate gyrus), A1-receptor binding in the dentate gyrus was greatly reduced on the lesioned side. Unilateral infusion of 0.25 microliter colchicine into the dentate gyrus which partially destroyed granule cells did not affect A1-adenosine binding. These results suggest that adenosine A1-receptors are localized on the terminals of the perforant path.

Adenosine

Small increases in pH decrease uptake of Escherichia coli by human neutrophils in vitro.

Increases in pH from 7.4 to 7.8 decreased the ability of human neutrophils in serum to ingest and kill Escherichia coli ATCC 29552 in vitro. In contrast, similar increases in pH did not decrease the bactericidal activity of neutrophils in serum against Staphylococcus aureus 502A. Increases in pH did not alter opsonization of E. coli by serum or the growth of E. coli but rather appeared to alter neutrophil uptake of bacteria by a direct effect on the neutrophil.

Escherichia coli

Biological safety cabinets, decontamination or sterilization with paraformaldehyde.

Bacillus subtilis var. niger spores were used to determine the exposure time for formaldehyde decontamination of biological safety cabinets. Formaldehyde contact times less than 3 hr were insufficient for sterilization. A contact time of 4 hr or more resulted in a reproducible killing of the spore strips placed inside the cabinets. At 6 hr sufficient formaldehyde had diffused through the high efficiency particulate air (HEPA) filter to sterilize the strips with lower spore counts. A minimum of 5 to 6 logs of killing were observed after 4 to 6 hr of treatment.

Bacillus subtilis

The effects of exercise and subject age on pulsed Doppler measurements of left ventricular ejection in normal man.

Pulsed Doppler measurements of ascending aortic blood velocity and acceleration were made in a group of normal subjects on exercise. The aims of the study were: (1) to document the normal response to exercise and its variability at various ages as a baseline for future studies in abnormal subjects, and (2) to investigate the accuracy and reproducibility of these noninvasive measurements. Doppler measurements were related to oxygen consumption in normal subjects aged between 22 and 69 years, during a submaximal 4 min incremental cycle exercise protocol. Computer-aided ensemble averaging of digital spectral data was used to reduce the effects of noise and respiratory variations in the signals. The mean relationship between cardiac output (Q) and oxygen consumption (Vo2) was Q = 5.75 Vo2 + 4.22 1 min-1, r = 0.84 in subjects aged under 45 years, compared to Q = 6.16 Vo2 + 3.87 1 min-1, r = 0.65 in older subjects; this difference was not significant. These values are similar to those previously described in invasive studies. There was a wide range of individual responses especially in the older subjects. These inter-subject differences probably reflect true physiological differences between subjects rather than methodological errors because they were consistent on repeated testing in the same individual, similar differences occurred in heart-rate responses between individuals where Doppler errors do not apply, and inter-subject variability of similar magnitude was found in comparable studies using invasive methods. Peak velocity (PV) rose from 73 +/- 10 cm s-1 at a Vo2 of 0.4 1 min-1 to 101 +/- 11 cm s-1 at a Vo2 of 1.21 min-1 in subjects aged under 45 years; corresponding values in the older subjects were significantly lower at 48 +/- 12 and 64 +/- 10 cm s-1 respectively. Maximum acceleration was also significantly higher at rest and on exercise in subjects under 45 years compared to older subjects. Despite these differences, stroke volume and cardiac output responses showed no significant age dependence, suggesting that differences in ejection velocity are due to increasing aortic cross-sectional area with age. The wide variety of individual responses found suggests an underlying variability in the arteriovenous oxygen difference on exercise between subjects.

Adult

Ventilatory and circulatory responses at the onset of exercise in man following heart or heart-lung transplantation.

1. Ventilatory and cardiovascular responses to the onset of voluntary and electrically induced leg exercise were studied in six patients following heart transplantation and five following heart-lung transplantation; the results were compared between the patient groups and also with responses from a group of normal subjects. 2. Oxygen consumption, carbon dioxide production and ventilation and its components were measured over two 30 s periods prior to, and two 30 s periods following, the onset of exercise. Relative changes in stroke volume and cardiac output were derived from ensemble-averaged Doppler measurements of ascending aortic blood velocity over the same 30 s periods. 3. None of the groups of subjects showed any significant differences in responses to voluntary exercise compared to electrically induced exercise of similar work pattern and intensity. 4. Compared to normal controls, the transplanted subjects showed higher resting heart rates which did not increase at the onset of exercise; stroke volume increased, but less than in the normal subjects. The resulting cardiac output increases in the transplanted subjects were minimal compared to the normal subjects. 5. Ventilation and oxygen uptake increased immediately and with similar magnitude in all three groups. 6. These results show that in the same individual it is possible to have an appropriate ventilatory response to the onset of exercise in the presumed absence of a normal corticospinal input to the exercising muscles (electrically induced exercise) and afferent neural information from the lungs and heart, and in the absence of a normal circulatory response to exercise. The mechanisms underlying this ventilatory response remain undetermined.

Adult

Nitrous oxide: cardiovascular effects in infants and small children during halothane and isoflurane anesthesia.

Two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular function in 31 unmedicated infants and small children. In 15 patients, the cardiovascular effects of equipotent levels of halothane were compared with and without N2O. In 16 patients, the cardiovascular effects of isoflurane with and without N2O were compared. Prior to anesthesia induction, cardiovascular measurements of heart rate (HR), mean blood pressure (MBP), and two-dimensional and pulsed Doppler echocardiography were recorded. The echocardiographic measurements were used to determine cardiac output (CO), stroke volume (SV), ejection fraction (EF), and left ventricular end-diastolic and end-systolic volume (LVEDV and LVESV). Twenty minutes after mask inhalation induction with halothane or isoflurane with N2O and O2 (3:2 liters/min), cardiovascular measurements were repeated with end-expired halothane or isoflurane maintained at 0.9 MAC. A third set of cardiovascular data was collected 10 minutes after the discontinuation of N2O, with inspired isoflurane or halothane levels in O2 (5 liters/min) increased to maintain 1.5 MAC end-expired levels. Ventilation was controlled throughout the study period and the study was completed before intubation and the start of elective surgery. Heart rate and MBP decreased to similar degrees below awake levels in both patient groups during N2O with halothane or isoflurane. When N2O was discontinued and end-expired levels of halothane or isoflurane increased, MBP remained at levels observed during N2O-O2 with halothane or isoflurane. Heart rate increased during isoflurane in O2. Cardiac output decreased significantly and similarly below awake levels during both halothane of isoflurane with and without N2O.

Blood Pressure

Medical management of malignant pericardial effusion by tetracycline sclerosis.

Fifty-eight patients with malignant pericardial effusion were seen from 1979 to 1986. A Kifa catheter was inserted into the pericardial sac and allowed to drain for 12 to 24 hours during electrocardiographic monitoring. Lidocaine hydrochloride, 100 mg, was instilled intrapericardially, followed by tetracycline hydrochloride, 500 to 1,000 mg, in 20 ml of normal saline solution. The catheter was clamped for 1 to 2 hours and then reopened. This procedure was repeated daily until the net drainage was less than 25 ml/24 hours. There were 22 male and 36 female patients (median age 58 years). The primary malignancy included lung (27 patients), breast (16 patients), stomach (3 patients), adenocarcinoma of unknown primary (7 patients), mesothelioma (2 patients) and chronic granulocytic leukemia, ovary and lymphoma (1 patient each). Fifty-six patients received 1 to 5 tetracycline instillations. In 1 patient, the catheter could not be inserted and in another, clotting occurred within the catheter before injection of tetracycline. Complications included transient atrial arrhythmias (5 patients), pain after injection (9 patients) and temperature higher than 37.5 degrees C (5 patients). One patient had a cardiac arrest during pericardiocentesis. Forty-three patients (74%) had control of their effusions for longer than 30 days (median survival 168 days, range 30 to 1,149+), and 5 patients (9%) died before 30 days without effusion. Eight patients (14%) did not achieve control. One declined further therapy after 1 instillation, and 3 died within 6 days with progressive malignancy. One patient had persistent drainage after 3 instillations, and 3 had reaccumulation of fluid 2, 6 and 27 days after catheter removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Evidence for individuality of breathing patterns in resting healthy man.

This study attempts to answer the question of whether there is a characteristic individuality of breathing pattern in conscious man. Measurements of breathing pattern, electroencephalograms and electrooculograms were made on 41 healthy individuals under standardised conditions of relaxed wakefulness, with a minimum of visual, auditory, and tactile input. Noninvasive measurement techniques were utilised and the subjects did not know that their breathing was being monitored. Measurement periods of only 5 min were used in order to avoid sleep. To estimate reproducibility, subjects were studied four times over two days. A variety of statistical tests on respiratory and cardiovascular variables indicate that the differences between individuals are highly significantly greater than the differences within an individual on repeated measurements under these standardised conditions. There was a high degree of reproducibility of breathing pattern within a subject; respiratory frequency was the most reproducible variable.

Adult

The effect of visual and auditory stimuli upon resting ventilation in man.

We have quantified the effect of visual, and auditory stimulation upon the breathing pattern in resting healthy man. Only noninvasive instrumentation was used. For the visual experiment we studied 36 subjects in each of three conditions: relaxed wakefulness with eyes closed (EC); with eyes open and directed at a white screen (EO); and whilst reading a standardised text (R). For the auditory experiment we studied 18 subjects under three analogous situations: no auditory input (N); listening to white noise (W); and listening to a story (V). In each study, all subjects underwent four replications (over two days) of one of the six permutations of the three experimental conditions; each condition lasted 5 min. A balanced analysis of variance on 10,368 breaths showed that, from baseline EC, both EO and R significantly increased respiratory frequency and ventilation by approximately 6%. Using 5184 breaths in the auditory study the analysis showed qualitatively similar results between analogous situations. The results demonstrate the importance of defining the conditions under which resting VI is measured.

Acoustic Stimulation

Is hypercapnia necessary for the ventilatory response to exercise in man?

1. Continuous recordings of arterial pH, ventilation, airway CO2 and heart rate were made during rest and during 3-4 min periods of rhythmic leg exercise in four renal patients with arteriovenous shunts. 2. The patients were anaemic (haemoglobin 6.5-9.0 g/dl) but had a normal ventilatory response to exercise as judged by the ratio of the change in ventilation to the change in CO2 production. 3. Breath-by-breath oscillations in arterial pH disappeared for the majority of the exercise period in each patient. 4. Changes in mean arterial pH and end-tidal CO2 tension with exercise were inconsistent between subjects but consistent within a given subject. On average, mean arterial pH rose by 0.011 pH unit. Changes in end-tidal CO2 tension reflected changes in mean pHa by falling on average by 1 mmHg (0.13 kPa). 5. Hypercapnia and acidaemia were not found to be necessary for the ventilatory response to moderate exercise.

Adult

T-cell mitogenesis and natural killer cell activity in colonic tumor-bearing and nontumor-bearing rats fed diets high in lipid with and without cholesterol.

It has been shown that rats fed diets high in lipid and cholesterol develop more 1,2-dimethylhydrazine (DMH)-induced bowel tumors than those fed diets low in lipid or without cholesterol. To further explore the effects of these dietary regimens on immune function, rats were fed diets containing 20% safflower or coconut oil, with or without cholesterol (1%) and cholic acid (0.3%), for 35 weeks during which time they were given DMH. Only rats bearing one or more colon tumors and that showed no evidence of weight loss were utilized. Two parameters of cell-mediated immune function were assessed in tumor- and nontumor-bearing control rats: a) response to the T-cell mitogen, phytohemaglutinin (PHA), and b) natural killer cell activity (NKCA). Nearly total suppression of PHA response was observed in the polyunsaturated fat diet group compared with the saturated fat diet groups. Addition of cholesterol to either the polyunsaturated or saturated fat diets diminished PHA response and, to a lesser degree, of T-lymphocytes from rats fed these diets. NKCA, however, was unaffected by either the quality of dietary fat or cholesterol. There were no detectable effects of DMH per se 15 weeks after the last injection (or in the presence or absence of tumors) on T-lymphocyte response to PHA or on NKCA. The relationships among lipid nutrition, carcinogen-induced tumorigenesis, and immunologic events is obviously complex. These studies imply that nutritional interventions may have a selective rather than a generalized effect on various immunocompetent cell populations. Furthermore, the effects of lipid nutriture, rather than long-term effects of carcinogen administration, or the presence of bowel tumors appear to play the major role on perceived alterations in in vitro immune function. Thus the effects of these lipid nutritional interventions on DMH-induced tumorigenesis seem independent of their effects on immune phenomena with the immune probes utilized.

1,2-Dimethylhydrazine

Validation of beat by beat pulsed Doppler measurements of ascending aortic blood velocity in man.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.

Aorta

The early circulatory and ventilatory response to voluntary and electrically induced exercise in man.

1. The ventilatory and circulatory responses to electrically induced leg exercise (EEL) were studied in seven normal subjects and compared with the responses to performing the same exercise voluntarily (EV). 2. EEL was produced by surface electrode stimulation of the quadriceps and hamstring muscle groups. This produced a push-relax pattern of exercise against a spring load and was free of any pain or discomfort. EV, at the same level, was achieved by subjects copying a display of timing and force information on a storage oscilloscope. 3. Cardiac output was estimated using validated Doppler ultrasound measurements of the velocity in the ascending aorta, combined with an estimate of aortic cross-sectional area using M-mode echocardiography. 4. Data from EV and EEL exercise runs were matched, within subjects, for the increase in oxygen consumption during the first 30 s of exercise; there were no significant differences between the resting states prior to either form of exercise. 5. The first ten beats of exercise were used to study the circulatory on-transient. The cardiac output responses to both EV and EEL were similar; however, in EV alone there was an initial significant drop in stroke volume and a slightly greater rise in heart rate. 6. The first five breaths of the response were used to study the ventilatory on-transient, and by measuring cardiac output, stroke volume and heart rate throughout each breath, the relationship between circulatory and ventilatory variables could be assessed. Ventilation showed a significantly greater rise at the onset of exercise during EV than during EEL; PET,CO2 (end-tidal CO2 pressure) showed small but significant falls for both EV and EEL. 7. The circulatory changes on a breath-by-breath basis are similar for EV and EEL although the ventilatory changes differ. In both EV and EEL the average increase in ventilation at the onset of exercise is proportionally greater than the average increases in cardiac output. Individual exercise runs show no particular relationship between circulatory and ventilatory change. 8. The results provide no support in man during mild leg exercise for a 'cardiodynamic' drive to breathing.

Adult

Respiratory modulation of left ventricular stroke volume in man measured using pulsed Doppler ultrasound.

1. Beat-by-beat changes in left ventricular stroke volume (l.v.s.v.) with breathing were recorded in four normal subjects using pulsed Doppler ultrasound. The l.v.s.v. fell during inspiration and rose during expiration; these changes were exaggerated at high tidal volumes. 2. Respiratory changes in l.v.s.v. persisted when respiratory rate was increased to 25 breaths/min despite an associated reduction in the degree of sinus arrhythmia. 3. During relaxed breath-holding, respiratory variations in l.v.s.v. ceased immediately, and on resumption of breathing a significant fall in l.v.s.v. occurred with the first inspiratory effort. 4. Inspiratory efforts against an occluded mouthpiece were accompanied by significant variations in l.v.s.v., although the magnitude of these changes was smaller than during unoccluded breathing with similar pleural pressure changes. 5. A resistive inspiratory load increased the respiratory variations in l.v.s.v. in the three subjects studied. 6. In three patients with implanted dual-chamber pacemakers set to constant heart rates, breathing was associated with larger variations in l.v.s.v. 7. In two patients who had undergone pericardectomy, the magnitude of respiratory changes in l.v.s.v. was less than in the normal subjects. 8. We conclude that inspiration directly lowers l.v.s.v. in man by a direct mechanism which is largely independent of lung volume changes, is dependent on changes in pleural pressure, and persists in the absence of sinus arrhythmia. All these results, particularly those in pericardectomy patients, are compatible with previous animal work on the anatomical and functional interdependence of right and left ventricles during breathing.

Adult

Technetium-99m imaging of bone trauma: reduced sensitivity caused by hydrocortisone in rabbits.

This study evaluates the effect of hydrocortisone on the sensitivity of 99mTc-scintigraphy for the detection of bone trauma in three groups of rabbits: a control group that received no hydrocortisone, a low-dose group that received 0.8 mg/kg/day, and a high-dose group that received 20 mg/kg/day. Scintigrams of the tibial diaphyses were obtained at 48 hr, 1 week, 2 weeks, and 3 weeks after surgical creation of a simulated fracture (a 1.5-mm hole in the cortex). The mean sensitivity for detecting fractures in control animals was 95% at 48 hr and 100% at all other times. Mean sensitivity for rabbits given the high dose of hydrocortisone was 41% at 48 hr. Mean sensitivity for the low-dose group was 75% at 48 hr, but this was not significantly different from the control group. Sensitivity in both groups treated with hydrocortisone improved with time. At 3 weeks, the mean was 93% in the low-dose group and 83% in the high-dose group. These data suggest that 99mTc scintigraphy may be less sensitive in detecting bone trauma in patients on glucocorticoid therapy than in patients in the general population.

Animals

Single-dose chloroquine therapy for Plasmodium falciparum in children in Togo, West Africa.

Chloroquine, in a single dose of 10 mg of base/kg, was given orally to Togolese children less than 5 years of age as primary therapy for Plasmodium falciparum malaria. A simplified World Health Organization in vivo method was used, as was a sequential analysis procedure for determining if the drug trial was a success or failure. A total of 178 children in 3 regions were treated; 174 (98%) responded successfully, which required a greater than or equal to 75% reduction in parasites by day 2 and elimination of parasites by day 7. All 4 failures had low blood levels of chloroquine and desethylchloroquine at day 7. A single dose of chloroquine for treating malaria can be considered for those areas of Africa where the efficacy of such therapy is documented, and where an antimalarial drug sensitivity monitoring system is operating.

Administration, Oral