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Biomedical subjects

P Hammond

Publications and source records attributed to P Hammond.

At least 19 recordsLinked to original sources
PubMed1995

Accumulation of enkephalin, proenkephalin mRNA, and neuropeptide Y in immunologically denervated rat adrenal glands: evidence for divergent peptide regulation.

To investigate transsynaptic effects on peptides of adrenal chromaffin cells in the rat, presynaptic sympathetic terminals were destroyed by intravenous injection of monoclonal antibodies to acetylcholinesterase. At several times thereafter, neuropeptide Y (NPY)-like immunoreactivity (NPY-IR) and methionine-enkephalin-like immunoreactivity (Met-Enk-IR) were measured by radioimmunoassay. Within 2 days of antibody injection, adrenal Met-Enk-IR increased five- to 10-fold and NPY-IR increased 50%. These effects were accompanied by large increases in proenkephalin A mRNA assayed by polymerase chain reaction. The peptide responses could reflect either an acute activation, as presynaptic terminals degenerated, or a chronic synaptic inactivation after terminal degeneration. To test the possibilities, muscarinic and nicotinic receptors were inhibited by repeated injection of atropine (1 mg/kg) and chlorisondamine (5 mg/kg). Measurements of urinary free catecholamine excretion showed that this treatment prevented the paroxysmal release of norepinephrine and reduced the release of epinephrine that normally followed injection of acetylcholinesterase antibodies. When the drugs were given alone for 2 or 4 days, adrenal Met-Enk-IR increased modestly and NPY-IR remained steady or declined. When given together with acetylcholinesterase antibodies, the cholinergic antagonists blocked the increase of NPY-IR but not Met-Enk-IR. Adding naloxone (1 mg/kg) to the treatment regimen enhanced the blockade of epinephrine excretion and largely prevented the antibody-induced increase in Met-EnK-IR. These findings indicate that adrenal NPY and enkephalin are not regulated identically. Adrenal NPY behaves as though controlled by transsynaptic cholinergic input. On the other hand, adrenal enkephalin may be regulated by additional or different mechanisms, possibly involving peptidergic transmission or synaptic inactivation.

Acetylcholinesterase↗
PubMed1995

The effect of major operations on heart rate, respiratory rate, physical activity, temperature and respiratory gas exchange in infants.

Perioperative changes in heart rate (HR), respiratory rate (RR), physical activity, body temperature, oxygen consumption (VO2), carbon dioxide production (VCO2) and resting energy expenditure (REE) were studied in fourteen infants (weight 3.1 +/- 0.2 kg) who had a major operation. VO2 and VCO2 were measured by indirect calorimetry preoperatively, and postoperatively for the first 12 hours continuously and at 24 hours, 48 hours and 5 days. HR, RR and physical activity were recorded on a minute to minute basis, and rectal temperature was recorded hourly. REE was calculated. HR, RR, VO2, VCO2 and REE increased postoperatively, peaking at 2-4 hours, and returned to baseline levels by 12-24 hours. In all of these variables, peak levels were significantly higher than Baseline levels (p < 0.001 for all variables). Physical activity and rectal temperature did not vary significantly throughout the study. This study demonstrates that newborn infants exhibit a short-lived postoperative increase in HR, RR, VO2, VCO2 and REE, which is not related to any alteration in physical activity or body temperature.

Body Temperature↗
PubMed1995

Formalisation of safety reasoning in protocols and hazard regulations.

Written protocols are often employed to guide patient care. For treatment within a clinical trial, compliance with the trial protocol may be critical in ensuring efficacy and safety. Previous empirical work has established generic safety principles for reasoning about adverse events in clinical trials and their formalisation has been applied in a decision support system for managing treatment plans in oncology. The same generic knowledge can be reused to generate specific safety clauses when designing new treatment plans. Typically, clinicians devise trial protocols relatively infrequently and so software aids, especially those assisting with regulatory/safety conformance, will encourage more effective use of their time. A similar approach to the formalisation of safety knowledge in the control of hazardous industrial processes is discussed.

Artificial Intelligence↗
PubMed1994

Binocular attributes of length summation and end stopping in cat striate cortex.

Length selectivity for each eye was compared as response increment-decrement to optimal sine-wave grating patches, in strongly binocular, striate cortical neurons in adult cats. Neurons were characterized as simple, or as standard, intermediate or special complex, on criteria that included length summation. Length summation was characterized for stimulus length, incremented symmetrically about the receptive field, up to optimal response levels. Many neurons additionally showed end stopping: response decrement to supra-optimal lengths. Optimal length and/or end stopping for each eye differed in most neurons, although the distributions of optimal length or percentage end stopping for each eye were comparable for the overall sample and for each neuronal subclass. However, paired comparisons of length and end-stopping data for each neuron revealed a marked tendency for receptive fields to be relatively smaller on average, but more strongly end stopped, for contralateral input. On the Wilcoxon signed rank test, these differences were statistically significant for standard complex neurons. There was also a tendency for differences in end stopping to be greater and more widely scattered for neurons with near-horizontal than near-vertical orientation preferences. Although the functional value of skew in the distributions of interocular differences in optimal length and end stopping remains conjectural, the scatter and balanced distribution of these differences in length specificity across the neuronal population may provide a basis for encoding visual perspective cues.

Animals↗
PubMed1994

Regional variation in expression of acetylcholinesterase mRNA in adult rat brain analyzed by in situ hybridization.

To investigate the molecular basis of regional variation in expression of brain acetylcholinesterase (AChE; EC 3.1.1.7), steady-state levels of AChE activity and mRNA were examined. Relative AChE activity in Triton extracts from six areas of the rat brain varied as follows: cortex < cerebellum < medulla < pons-midbrain < thalamus < striatum. In contralateral samples from the same brains, AChE mRNA was assessed by Northern blotting with random-primed 32P-labeled cDNA. The regional abundance of the major 2.4-kb AChE transcript differed from that of the enzyme activity: cortex < striatum < cerebellum < medulla < thalamus < pons-midbrain. In situ hybridization with a 33P-labeled antisense AChE oligonucleotide provided evidence for high levels of AChE message in cells of the nucleus basalis, nucleus accumbens, neostriatum, substantia nigra, motor nucleus of the facial nerve, and spinal nucleus of the trigeminal nerve. In the caudate-putamen, large, heavily labeled neurons were not numerous, but they were approximately as frequent as the cholinergic interneurons revealed by choline acetyltransferase immunocytochemistry. The relatively low number of these AChE-expressing cells probably explains the relative dearth of AChE mRNA-like material in the neostriatum.

Acetylcholinesterase↗
PubMed1994

Spatial correlation of suppressive and excitatory receptive fields with direction selectivity of complex cells in cat striate cortex.

The aim of the study was to account for direction selectivity of visual cortical neurons through systematic positional mismatch between excitatory and suppressive influences on each neuron. Direction-selective complex neurons were therefore recorded from striate cortex of cats lightly anaesthetized with halothane in nitrous oxide-oxygen. All but small residual eye movements were eradicated with intravenous gallamine triethiodide. Excitatory receptive field (ERF) dimensions and centring were quantified with optimal sine-wave grating stimuli, appropriately windowed to limit them to variable locations along and across the receptive field (RF) centre. Related suppressive receptive fields (SRFS) were similarly mapped during binocular conditioning, induced by an optimal grating applied to the other eye and drifting continuously in each neuron's preferred direction. Its purpose was to elevate ongoing levels of discharge to reveal often concealed null suppression. ERF and SRF profiles were systematically offset, especially along the line of preferred direction such that, for stimuli moving in the non-preferred direction, the SRF lay ahead of the ERF. Derivations of ERFS and SRFS during conditioning, within a single batch of trials, excluded eye movements as a source of positional mismatch. It is concluded that this mismatch may provide the basis for direction selectivity and the emergence of null suppression.

Animals↗
PubMed1994

Influence of stimulus width on directional bias in striate cortex.

Width summation of complex neurones in cat striate cortex was assessed for moving sine-wave gratings. Summation was restricted in special complex neurones, approximately matched receptive field width in intermediate complex neurones and exceeded it in most standard complex neurones. Responses to preferred and opposite directions of motion were compared: 12 of 20 complex neurones showed similar directional bias for moving sinewave gratings and for single moving bars of either contrast polarity; 8 of 20 were similarly or more weakly direction-selective for bars than for grating patches, dependent on patch width. In two of these, this was despite the fact that the directional bias for gratings was invariant with patch width. In the remaining six, differences could be accounted for by progressive increase or decrease in directional bias for gratings, as grating patch width was systematically increased. In conclusion, directional bias of a substantial proportion of complex cells is determined by stimulus configuration.

Animals↗
PubMed1994

Quantification of excitatory receptive fields of complex neurones in cat striate cortex.

Excitatory receptive field (ERF) response profiles and length summation functions were derived from complex neurones in cat striate cortex. Measured length summation was compared with summation predicted from integration over ERF profiles. In a minority of neurones, measured and predicted summation were well matched. In the majority, whether end-stopped or not, responsiveness in length summation tests was appreciably greater than predicted for short stimuli, compared with ERF profiles. The mismatch was least in standard and greatest in special complex neurones; in the latter group, response levels to long stimuli fell well below predicted levels. In end-stopped neurones the decremental portion of length summation functions was not predicted by ERF profiles. These results implicate the involvement of non-linear mechanisms, whereby concomitant stimulation of central regions of the receptive field (RF) potentiate the efficacy of loci towards either end of the RF.

Animals↗
PubMed1994

A new equation to predict the resting energy expenditure of surgical infants.

It is essential that adequate calories are provided to newborns to cover their energy expenditure. This is difficult to measure and varies significantly between individuals. The aim of this study was to develop an equation to predict the basal energy requirements of stable surgical infants, using easily measurable parameters. Resting energy expenditure (REE) was measured using computerized open-circuit indirect calorimetry. One hundred twenty-two measurements were made on different days in 46 stable nonventilated infants. The measured REE was 34.41 +/- 0.46 cal/kg/min; (mean +/- SEM). Three body-size measurements correlated significantly with REE (cal/min): weight in kilograms (r = .87; P < .00001), body surface area in square meters (r = .86; P < .00001), and lean body mass in kilograms (r = .81; P < .00001). Five other independent variables correlated significantly with REE (cal/kg/min): heart rate in beats per minute (r = .60; P < .00001), postnatal age in days (r = .49; P < .00001) caloric intake in cal/kg/min (r = .44; P < .00001), gestational age in weeks (r = .43; P < .00001), and rectal temperature in degrees Celsius (r = .19; P = .04). Weight, heart rate, age, gestational age, and temperature were regarded as independent predictor variables of REE for the multiple stepwise regression analysis. Three variables entered this highly significant equation: REE (cal/min) = -74.436 + (34.661 x weight in kg) + (0.496 x heart rate in beats/min) + (0.178 x age in days) (r = .92; F = 230.07; significance, F < .00001).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Surface Area↗
PubMed1994

Catecholamine release and excretion in rats with immunologically induced preganglionic sympathectomy.

Plasma and urinary catecholamines were quantified to assess global sympathoadrenal function in rats with preganglionic lesions caused by antibodies to acetylcholinesterase (AChE). Rats were given intravenous injections of normal mouse IgG or murine monoclonal anti-acetylcholinesterase IgG (1.5 mg). Five or 16 days afterward, basal blood samples were taken through indwelling arterial cannulate. A few hours later, the rats were immobilized for 10 min in padded restrainers, and another blood sample was drawn. HPLC determinations showed low basal levels of norepinephrine and epinephrine (< 0.2 ng/ml in all rat plasma samples). In control rats, immobilization stress increased levels of plasma catecholamines up to 35-fold. In rats tested 5 days after injection of antibody, the norepinephrine response was much smaller (15% of control), and the epinephrine response was nearly abolished (5% of control). There was some recovery at 16 days after antibody treatment, but stress-induced catecholamine release was still markedly impaired. Reduced stress-induced release was not accompanied by major changes in tissue epinephrine or norepinephrine (heart, spleen, adrenal glands, and brain), although adrenal dopamine content dropped by 60%. Urinary excretion was studied in parallel experiments to gain insight into the effects of AChE antibodies on basal sympathoadrenal activity. Epinephrine, norepinephrine, dopamine, and selected metabolites were quantified in 24-h urine samples collected at frequent intervals for 30 days after antibody injection. No statistically significant changes were detected in the urinary output of dopamine, 3-methoxytyramine, normetanephrine, or 3-methoxy-4-hydroxyphenylglycol. On the other hand, epinephrine and norepinephrine output increased sharply at the time of antibody injection and then fell significantly below control levels. Norepinephrine output returned to normal after 2 weeks, but epinephrine output remained depressed. These results are consistent with previous evidence of widespread and persistent antibody-mediated damage to the preganglionic sympathetic system.

Acetylcholinesterase↗
PubMed1994

Safety and decision support in oncology.

The management of patients with cancer involves the administration of complex treatment protocols with frequent monitoring of the effects of treatment on the malignant disease as well as on the general health of the patient. The number and wide variety of protocols used in treatment trials, and the amount of clinical data generated suggest the need for computer-based support. The toxicity of many of the treatments used and the severity of the disease itself underline the safety-critical nature of all decisions made by oncologists, the physicians and surgeons who treat cancer patients. This paper presents recent work on the analysis of safety issues arising from the design and implementation of a prototype decision-support system for oncologists. It illustrates the benefits of combining both informal and formal approaches to the analysis and representation of safety, firmly based on a thorough and detailed study of the domain in cooperation with oncologists, pharmacists and medical informaticians.

Antineoplastic Agents↗
PubMed1994

Cat striate cortex: monocular and interocular comparisons of spatial-frequency selectivity.

Spatial frequency and bandwidth characteristics were determined for neurones in cat striate cortex. Responses to drifting sine-wave gratings, optimized for orientation, direction and velocity, were determined over a range of spatial frequencies. Comparative measurements of spatial frequency tuning at constant velocity and at constant temporal drift frequency revealed that, overall, tuning derived by either method was similar. Results were evaluated in relation to neuronal class (simple or complex); complex cell subclass (standard, intermediate or special), defined by length summation; directionality; and velocity selectivity. Distributions of optimal spatial frequency for simple and complex neurones were comparable. By contrast, bandwidths of simple neurones were markedly narrower than for complex neurones. Standard complex neurones, in turn, had narrower bandwidths than special or intermediate complex neurones. Optimal spatial frequency correlated inversely with optimal velocity, directly with orientation selectivity. Thus, neurones tuned to high spatial frequencies tended to respond optimally to low velocities, and were more sharply orientation selective, than neurones tuned to low spatial frequencies. In binocular neurones, spatial frequency tuning characteristics of the two monocular inputs were compared. For either eye, spatial frequency tuning curves were reproducible over time. In a minority of neurones, spatial frequency characteristics were matched for the two eyes. A majority showed mismatch in spatial frequency characteristics between the eyes. Individual neurones were tuned to different bands of spatial frequencies through either eye; more sharply spatial-frequency selective through one eye than the other; or had both dissimilar bandwidth and spatial frequency. Changing input spatial-frequency resulted in profound, systematic shifts in ocular dominance. These were progressive in the case of spatial-frequency mismatch. In cases of bandwidth, or bandwidth and spatial-frequency mismatch, the eye associated with more sharply-tuned input exerted relatively greater influence at centre frequencies, the other eye relatively greater influence at extreme frequencies. There was a marginal tendency for the dominant (or contralateral) eye to be tuned to higher spatial frequencies than the more weakly driving (or ipsilateral) eye. By contrast, interocular differences in bandwidth were pronounced: in a majority of neurones the dominant eye was more broadly tuned than the more weakly driving eye. Related to the established preponderance of contralaterally dominated cortical neurones, the input from the contralateral eye was markedly more broadly tuned than that from the ipsilateral eye, consistent with the notion that stronger drive is associated with greater pooling of inputs. These differences have important implications for binocular vision and, potentially, for coding of visual perspective.

Animals↗
PubMed1993

Glucose utilization in the surgical newborn infant receiving total parenteral nutrition.

Glucose is the main source of nonprotein calories in total parenteral nutrition (TPN). However, its use has been associated with various nutritional, metabolic, and respiratory complications. The aim of this study was to determine, in the stable surgical newborn infant, the characteristics of carbohydrate metabolism, in particular the maximum oxidative threshold for intravenous glucose and the thermogenic effect of glucose. Twenty-one studies were done on 11 infants (weight 2.82 +/- 0.19 kg) receiving TPN containing constant amounts of amino acids (2.5 g/kg/d) and fat (3.0 g/kg/d), and different amounts of glucose (range, 10 to 25 g/kg/d). Oxygen consumption (VO2), carbon-dioxide production (VCO2), and resting energy expenditure (REE) were measured by indirect calorimetry. Urinary nitrogen excretion rate was measured and substrate utilization calculated from the nonprotein respiratory quotient (NPRQ). There was a positive correlation between the predictor variable glucose intake and the dependent variables VO2 (r = .55; P < .05), VCO2 (r = .83; P < .0001), REE (r = .65; P < .005), NPRQ (r = .94; P < .0001), respiratory rate (r = .46; P = .06), and plasma triglycerides level (r = .67; P < .01). When glucose intake exceeded 18 g/kg/d the NPRQ was greater than 1.0, indicating glucose conversion to fat. Above this level of intake, the gradient of the correlation between the predictor variable glucose intake and the dependent variables VCO2 and REE increased. From this study we conclude that: (1) Glucose intake is the principal determinant of glucose utilization and exerts an influence on the metabolism of exogenous fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Indirect↗
PubMed1993

Death of intermediolateral spinal cord neurons follows selective, complement-mediated destruction of peripheral preganglionic sympathetic terminals by acetylcholinesterase antibodies.

Systemically injected anti-acetylcholinesterase antibodies in rats cause selective lesions of preganglionic sympathetic neurons. Adult rats were examined up to four months after a single i.v. injection of murine monoclonal acetylcholinesterase antibodies or normal immunoglobulin G (1.5 mg). Within 4 h, antibody-treated rats developed ptosis, a sign of sympathetic dysfunction that was never reversed. Persistent pupillary constriction reflected preserved and unopposed parasympathetic function. Weight gain was depressed, but locomotor activity, excitability, and sensorimotor responses were normal, and gross neuromuscular performance was near normal. These findings were supported by biochemical evidence for selective sympathetic damage. Acetylcholinesterase activity was reduced for the whole period of observation in sympathetic ganglia and adrenal glands but fell only transiently in muscle and serum. At all times, choline acetyltransferase activity (a marker of presynaptic terminals) was unaffected in muscle but grossly depleted in ganglia. Light and electron microscopy showed that preganglionic sympathetic terminals of superior cervical ganglia were severely damaged while parasympathetic ganglia were less affected and motor endplates of skeletal muscle were apparently spared. Immunocytochemistry revealed punctate deposits of murine immunoglobulin G and complement component C3 in ganglionic neuropil 12 h after antibody injection. This finding was consistent with complement-mediated lysis of preganglionic terminals. Morphometric analysis of preganglionic neurons in the intermediolateral nucleus of the spinal cord showed progressive loss of cholinergic perikarya over several months. We conclude that antibody-induced destruction of ganglionic terminals leads to death of preganglionic sympathetic neurons and, hence, permanent dysautonomia.

Acetylcholinesterase↗
PubMed1993

Lesion of central cholinergic systems by systemically administered acetylcholinesterase antibodies in newborn rats.

To determine if systemically administered antibodies could reach antigenic targets and cause immunologic lesions in brains of newborn rats, murine monoclonal antibodies against rat acetylcholinesterase were injected i.p. on the first postnatal day. As early as 24 h after injection, antibodies were detected immunocytochemically in brain parenchyma, along with punctate debris that showed intense cholinesterase activity. Total acetylcholinesterase activity in the brain dropped by 30%, and 10S activity was almost undetectable at day 3, implying true enzyme loss since the antibodies did not directly impair catalytic function. At day 7, 10S acetylcholinesterase began to recover but the activity remained only half that of controls. At day 12, total acetylcholinesterase activity was still reduced (30% in whole brain, 40% in cerebral cortex), consistent with lasting damage to cholinesterase-expressing cortical neurons. This conclusion was confirmed by histochemical experiments showing a nearly complete disappearance of acetylcholinesterase fiber-staining in cerebral cortex and basal ganglia at days 4 and 8, with residual deficits at day 12. Choline acetyltransferase activity decreased in the cerebral cortex, implying a loss of cholinergic terminals, but specifically immunoreactive perikarya remained abundant in the basal forebrain. Immunocytochemistry showed no obvious changes in three non-cholinergic markers: tyrosine hydroxylase, tryptophan hydroxylase, and glutamic acid decarboxylase. Overall, it appeared that acetylcholinesterase antibodies induced widespread but reversible damage of cholinergic fibers and terminals, while sparing cholinergic cell bodies and many other neural systems.

Acetylcholine↗
PubMed1993

Logic-based integrity constraints and the design of dental prostheses.

This paper describes the ongoing development of a design assistant, RaPiD, for use in prosthetic dentistry. RaPiD integrates computed-aided design, knowledge-based systems and databases, employing a logic-based representation as the unifying medium. The user's manipulation of icons representing the developing design is interpreted as a set of transactions on a logic database of design components. The rules of design expertise are represented as constraints in first order predicate logic and design alterations are subject to the checking of the constraints. When design rules are contravened as the result of some proposed alteration, a suitable critique is presented to the user. RaPiD is being developed for use in both dental education and practice.

Artificial Intelligence↗
PubMed1993

The metabolic response to operative stress in infants.

The aim of this study was to characterize energy metabolism and substrate utilization in infants following an operation. Nineteen infants (weight 3.2 +/- 0.2 kg) who had an operation were studied. Anesthesia was standardized and operative stress score (OSS) was recorded. Five infants had a minor operation (OSS < 7), and 14 infants had a major operation (OSS > or = 7). Energy and nitrogen intake were constant during the 48-hour study period. Respiratory gas exchange was measured by indirect calorimetry preoperatively, and postoperatively for the first 12 hours continuously and at 24 hours, 48 hours, and 5 days. Urinary nitrogen excretion rate was measured for the first 48 hours following the operation. Physical activity was scored. Resting energy expenditure (REE) and nonprotein respiratory quotient (NPRQ) were calculated. REE increased postoperatively, peaking at 2 to 4 hours, and returned to baseline levels by 12 to 24 hours. Peak REE was significantly higher than baseline REE (P < .001). Substrate utilization was not altered by operation. The increase in REE was significantly greater in infants having a major operation than in infants having a minor operation (P < .05). Among infants having a major operation, the increase in REE was significantly greater in those infants more than 48 hours old, than in those infants less than 48 hours old (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Indirect↗