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Biomedical subjects

L J Carr

Publications and source records attributed to L J Carr.

18 recordsLinked to original sources
PubMed2006

Medical, surgical, and health outcomes of gastrostomy feeding.

A prospective controlled study with repeated measures before and after surgery examined the medical, surgical, and health outcomes of gastrostomy for children with disabilities at a tertiary paediatric referral centre in the North Thames area, UK. Anthropometric measures included weight, mid-upper-arm and head circumference. Five-day prospective food diaries were completed and data on physical health and surgical outcomes recorded. Seventy-six children participated and underwent gastrostomy (44 males, 32 females; median age 3 y 4 mo, range 4 mo-17 y 5 mo), and 35/76 required an anti-reflux procedure. Categories of disability were: cerebral palsy (32/76), syndrome of chromosomal or other genetic origin (25/76), slowly progressive degenerative disease (11/76), and unconfirmed diagnosis (8/76). Most children had gross motor difficulties (99%) and were non-ambulant (83%). Oromotor problems were identified in 78% of children, 69% aspirated, and 65% were fed nasogastrically before surgery. The mean weight before surgery was -2.84 standard deviation score (SDS; SD 2.21, range -9.8 to 3.4). Two-thirds of children achieved catch-up growth postoperatively: weight-for-age (mean difference 0.51 SDS, 95% CI 0.23-0.79, p=0.001) and mid-upper arm circumference (mean difference 1.12 cm, 95% confidence interval 0.50-1.75, p=0.001). Health gains included a reduction in drooling, secretions, vomiting, and constipation. Major surgical complications were found in 13/74 children. The study provides evidence that catch-up growth and health gains are possible following gastrostomy.

Adolescent↗
PubMed2002

Management of cerebral palsy: the neurologist's view.

Cerebral palsy is a complex disorder which compromises motor abilities. Other systems are often involved and its effects on the child and their family may be profound. This article examines clinical aspects of cerebral palsy and discusses the approach to comprehensive management, with particular reference to the role of the neurologist.

Attitude of Health Personnel↗
PubMed1997

Onset of speech after left hemispherectomy in a nine-year-old boy.

Case Alex, with Sturge-Weber Syndrome affecting the left hemisphere, failed to develop speech throughout early boyhood, and his comprehension of single words and simple commands remained stagnant at an age equivalent of 3-4 years. But then, following left hemidecortication at age 8.5 years and withdrawal of anticonvulsants when he was more than 9 years old, Alex suddenly began to acquire speech and language. He also showed an unusual degree of residual motor capacity on his right side. Alex's remarkable progress in learning speech and language, and the development of his other cognitive abilities, were measured periodically from the age of 9 to 15 years. His most recent scores on tests of receptive and expressive language place him at an age equivalent of 8-10 years. Comparison with the level of function attained in these domains by nine other left hemispherectomized patients with early onset of disease and comparable IQ (range, 40-68) but with early development of speech and language, suggests that, surprisingly, Alex has suffered no permanent disadvantage from his protracted period of mutism and severely limited comprehension. Although the findings in Alex, as in other left-hemispherectomized patients, indicate define limits to the cognitive and linguistic capacity of the isolated right hemisphere, Alex's achievements appear to challenge the widely held view that early childhood is a particularly critical period for acquisition of speech and language or any of their selective aspects, including phonology, grammar, prosody and semantics. It is concluded that clearly articulated, well structured, and appropriate language can be acquired for the first time as late as age 9 years with the right hemisphere alone.

Adolescent↗
PubMed1996

Development and reorganization of descending motor pathways in children with hemiplegic cerebral palsy.

Reorganization of descending motor pathways was explored in 33 subjects with hemiplegic cerebral palsy. Subjects were assessed neurologically and surface electromyographic recordings were taken from homologous muscles of both hands. Functional corticospinal projections were assessed using focal magnetic stimulation of the motor cortex. In control subjects this evokes EMG responses in the contralateral hand at short latency. Similar results were seen in 12 of the hemiplegic subjects following stimulation of the undamaged motor cortex. In the remaining 22 subjects novel corticospinal pathways were demonstrated arising from the undamaged cortex, where stimulation evoked short latency EMG responses in both hands. Cross-correlation analysis performed from EMGs recorded between the two hands revealed short duration central peaks in 11 of these subjects, all of whom had strong mirror movements of the hands. These findings suggested that two patterns of central reorganization may follow early unilateral cortical insult. Examination further indicated that hand function in hemiplegic subjects could be related to the neurophysiological results.

Adolescent↗
PubMed1995

Requirement of glycolytic substrate for metabolic recovery during moderate low flow ischemia.

Low flow ischemia with stable hemodynamic function can result in partial metabolic recovery characterized by an increase in phosphocreatine (PCr). Prior data suggest that glycolytic production of adenosine triphosphate (ATP) may be critical for this recovery and that the ATP produced by oxidative phosphorylation alone may be insufficient. This study tested the hypotheses that, during moderate low flow ischemia, (a) metabolic recovery is dependent on glycolytic production of ATP, and, therefore, (b) a mitochondrial substrate such as pyruvate alone is inadequate to allow metabolic recovery. High energy phosphates, pH, and lactate release were measured during 2 h of moderate low flow ischemia. Hearts were perfused with either a glycolytic plus mitochondrial substrate (glucose, insulin and pyruvate) or a mitochondrial substrate alone (pyruvate). Flow reductions required to reduce PCr by approximately 8% resulted in stable and equal reductions of rate-pressure product in each group. PCr recovered fully during the ischemic period in control hearts with glycolytic substrate, associated with preservation of normal end-diastolic pressure, and increased lactate release during the first hour of ischemia. Reperfusion of these hearts restored hemodynamic function and increased PCr above baseline values. In contrast, the use of pyruvate alone as a substrate resulted in a progressive fall of PCr during ischemia, increased end-diastolic pressure, and no significant increase in lactate release. Reperfusion in these hearts restored hemodynamic function, but did not result in normalization of PCr. Both groups had significant reductions in ATP during ischemia. Recovery of PCr during ongoing moderate low flow ischemia is observed in the presence of mixed glycolytic and mitochondrial substrates (glucose, insulin and pyruvate) but is not observed with pyruvate as a sole mitochondrial substrate. These data support a critical role for glycolytic flux under these conditions, suggesting that ATP generated solely by oxidative phosphorylation is not sufficient to promote metabolic recovery or maintain diastolic function during moderate low flow ischemia.

Adenosine Diphosphate↗
PubMed1995

Effects of glycogen depletion on ischemic injury in isolated rat hearts: insights into preconditioning.

Limitation of myocardial injury and infarction has been demonstrated by interventions such as ischemic preconditioning or the use of pyruvate as a substrate, which reduces glycogen content before, and acidosis during, ischemia. An isolated perfused rat heart model of global ischemia was employed to test the hypothesis that glycogen depletion reduces ischemic injury as measured by creatine kinase release. 31P-nuclear magnetic resonance spectroscopy was used to measure high-energy phosphates (ATP and phosphocreatine), phosphomonoesters (PME), and intracellular pH. Compared with control glucose-perfused hearts with normal glycogen content (1.49 +/- 0.13 mg Glc/g wet wt), glycogen-depleted pyruvate, ischemic preconditioned, and glycogen-depleted glucose hearts all had reduced glycogen content before ischemia (0.62 +/- 0.16, 0.81 +/- 0.10, and 0.67 +/- 0.12 mg Glc/g wet wt, respectively; P = 0.003) and significantly higher pH at the end of ischemia (5.85 +/- 0.02, 6.33 +/- 0.06, 6.24 +/- 0.04, and 6.12 +/- 0.02 in control, glycogen-depleted pyruvate, preconditioned, and glycogen-depleted glucose-perfused hearts, respectively; P < 0.01), although acidification during the initial phase of ischemia was differentially affected by the three interventions. Glycogen-depleted pyruvate and preconditioned hearts had reduced PME accumulation, greater recovery of function and phosphocreatine, and lower creatine kinase release on reperfusion, whereas glycogen-depleted glucose-perfused hearts were similar to control hearts. In summary, glycogen depletion by these three methods limits the fall in pH during global ischemia, although glycogen depletion in the absence of preconditioning does not limit ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Evidence for bilateral innervation of certain homologous motoneurone pools in man.

1. Surface EMG recordings were made from left and right homologous muscle pairs in healthy adults. During each recording session subjects were requested to maintain a weak isometric contraction of both the left and right muscle. 2. Cross-correlation analysis of the two multiunit EMG recordings from each pair of muscles was performed. Central peaks of short duration (mean durations, 11.3-13.0 ms) were seen in correlograms constructed from multiunit EMG recordings obtained from left and right diaphragm, rectus abdominis and masseter muscles. No central peaks were seen in correlograms constructed from the multiunit EMG recordings from left and right upper limb muscles. 3. To investigate descending pathways to the homologous muscle pairs, the dominant motor cortex was stimulated using a focal magnetic brain stimulator whilst recording from homologous muscle pairs. 4. Following magnetic stimulation of the dominant motor cortex, a response was recorded from both right and left diaphragm, rectus abdominis and masseter muscles. In contrast, when recording from homologous upper limb muscles, a response was only seen contralateral to the side of stimulation. 5. The finding of short duration central peaks in the cross-correlograms constructed from multiunit recordings from left and right diaphragm, rectus abdominis and masseter, suggests that muscles such as these, that are normally co-activated, share a common drive. The mechanism is discussed and it is argued that the time course of the central correlogram peaks is consistent with the hypothesis that they could be produced by a common drive that arises from activity in last-order branched presynaptic fibres although presynaptic synchronization of last-order inputs is also likely to be involved. 6. The results of the magnetic stimulation experiments suggest that this common drive may involve the corticospinal tract. 7. We saw no evidence for a common drive to left and right homologous muscle pairs that may be voluntarily co-activated but often act independently.

Abdominal Muscles↗
PubMed1994

Are age-related differences in response to myocardial ischemia and cardioplegia pH dependent?

Phosphorus-31 nuclear magnetic resonance and left ventricular pressure development (dP/dt) were used to test the hypothesis that age-related differences in myocardial functional recovery after ischemia and cold crystalloid cardioplegia (CCC) are the result of an inverse relationship between recovery and the decrease in intracellular pH (pHi) during ischemia. Neonatal (3-8 days) and adult rabbit hearts were Langendorff perfused using two protocols: (1) control--30 min perfusion, 30 min global ischemia, 2 h reperfusion; (2) CCC--the same except ischemia was initiated after a 4-min infusion of cold hyperkalemic solution. Analysis of variance and the Tukey test showed the following significant differences between the protocols (p < 0.05). CCC decreased inorganic phosphate (Pi) during ischemia in both age groups, but more in adult hearts, and decreased Pi during reperfusion in adult hearts. CCC increased pHi during ischemia and ATP during ischemia and reperfusion in both age groups but more in adult hearts. CCC increased dP/dt during reperfusion only in adult hearts. The results are consistent with the hypothesis.

Adenosine Triphosphate↗
PubMed1993

Patterns of central motor reorganization in hemiplegic cerebral palsy.

Central motor reorganization was studied in 33 subjects with hemiplegic cerebral palsy. Corticospinal projections were investigated using focal magnetic stimulation of the motor cortex. Reflex pathways were examined with digital nerve stimulation. Cross-correlation analysis of multi-unit EMG was used to detect activity in branched common stem last order presynaptic inputs to motor neuron pools. The neurophysiological findings were related to the clinical outcome. In 21 of the subjects studied (64%), there was evidence for reorganization of central motor pathways. The clinical and neurophysiological findings revealed two different forms of reorganization. In both forms focal magnetic stimulation demonstrated novel ipsilateral motor pathways from the undamaged motor cortex to the hemiplegic hand. Ipsilateral projections were not demonstrated from the damaged motor cortex. Eleven subjects had intense mirror movements. In these subjects cross-correlation analysis and reflex testing suggested that corticospinal axons had branched abnormally and projected bilaterally to homologous motor neuron pools on both sides of the spinal cord. The remaining 10 subjects did not have intense mirror movements and in these subjects there was no evidence for last order branching of corticospinal axons. It was found that good function of the hemiplegic hand was associated with the presence of EMG responses in that hand following magnetic stimulation of the contralateral motor cortex. When EMG responses were absent, hand function was poor unless the subject had intense mirror movements.

Adolescent↗
PubMed1993

Myocardial adaptation during acute hibernation: mechanisms of phosphocreatine recovery.

OBJECTIVES: Acute hibernation, defined as a prolonged period of moderately reduced oxygen supply and stable haemodynamic function, results in metabolic adaptation characterised primarily by an increase in phosphocreatine. The mechanism of this increase in phosphocreatine is unknown, but has been postulated to result from either an increase in adenosine triphosphate (ATP) production or a decrease in ATP utilisation under conditions of constant myocardial oxygen consumption (MVO2). These experiments were performed to test the hypotheses that (1) acute hibernation could be modelled in an isolated perfused rat heart exhibiting metabolic adaptation; and (2) recovery of phosphocreatine could be explained by alterations in relative creatine kinase flux during hibernation. METHODS: Nuclear magnetic resonance techniques were used in an isolated, perfused rat heart model of acute hibernation to determine the changes in metabolites and creatine kinase kinetics. A flow reduction from 12.5 to 5.4 ml.min-1 was employed for two hours, followed by reperfusion. RESULTS: Reduction of flow resulted in a stable 44% reduction in rate-pressure product. Phosphocreatine had a significant decrease of 9% within the first 15 minutes of ischaemia, but recovered to control values by the end of ischaemia. ATP and [ADP], although unchanged in the early phase of ischaemia, were progressively reduced during the later phase of ischaemia. Intracellular pH fell from 6.99(0.04) to 6.92(0.03) after 15 minutes of ischaemia with little recovery. Saturation transfer measurements showed stability of the forward flux in the creatine kinase reaction during ischaemia, but a progressive reduction in the calculated reverse flux. CONCLUSIONS: These data show that acute hibernation can be modelled in an isolated perfused heart, exhibiting recovery of phosphocreatine despite progressive reductions in ATP. Metabolic changes during acute hibernation have a phasic response characterised by an early ischaemic phase and a later adaptive phase. There is a time related change in measured creatine kinase flux, consistent with a differential change in either ATP production via an increase in MB creatine kinase isoenzyme or a shift in the activity of mitochondrial v cytosolic creatine kinase, a reduction in ATP utilisation via increased efficiency of ATP utilisation at the myofibril, or a changing contribution of glycolytically produced ATP.

Adenosine Diphosphate↗
PubMed1992

Age-related response of rabbit heart to normothermic ischemia: a 31P-MRS study.

The age-related response of the myocardium to 30 min of 37 degrees C global ischemia and 120 min of 37 degrees C reperfusion, measured by phosphorus-31 magnetic resonance spectroscopy and the recovery of isovolumic function, was evaluated by using perfused neonatal (3-8 days old, n = 10), immature (24-30 days old, n = 10), and adult (2-4 mo old, n = 5) rabbit hearts. Basal intracellular pH (pHi) was highest in neonatal hearts and decreased with age. The basal phosphocreatine (PCr)-to-ATP ratio differed in each group, increasing with age. Rapid depletion of PCr occurred in all groups during ischemia; ATP retention was greater in adults than in neonates. Reperfusion resulted in no measurable recovery of ATP in any group. Postischemic pHi stabilized above preischemic values in neonatal and immature hearts and below preischemic values in adult hearts. Recovery of PCr and cytosolic Pi (Pcyi) content, heart rate, and coronary flow during reperfusion was greater in neonatal and immature than in adult hearts. During the final 20 min of ischemia, pHi was lower in immature than in neonatal or adult hearts. Postischemic recovery of left ventricular maximum rate of pressure rise (+dP/dtmax) was depressed in immature compared with neonatal and adult hearts. These results demonstrate increased tolerance of the neonatal heart and increased susceptibility of the immature heart to unprotected normothermic ischemic injury relative to the adult heart and suggest that maturational changes in myocardial pHi regulation may be responsible for the observed age-related response.

Adenosine Triphosphate↗
PubMed1991

Activity of urokinase diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored in glass or plastic syringes.

The effects of the diluent, the container, the i.v. set, and the drug concentration on the adsorption of urokinase to i.v. administration systems were studied, along with the compatibility of urokinase with plastic and glass syringes. Solutions of urokinase 1500 and 5000 IU/mL in 0.9% sodium chloride injection and 5% dextrose injection in glass and polyvinyl chloride (PVC) containers were sampled at 2 and 30 minutes. Administration sets were attached to PVC containers containing the urokinase-5% dextrose injection solutions, and samples were collected at 90 and 150 minutes. Glass and polypropylene syringes containing urokinase 5000 IU/mL in 0.9% sodium chloride injection or 5% dextrose injection were sampled at 0, 4, 8, and 24 hours. Urokinase activity was measured by an in vitro clot lysis assay. No urokinase diluted in 0.9% sodium chloride injection adsorbed to glass or PVC containers. For urokinase 1500 IU/mL in 5% dextrose injection, a loss of 15% to 20% occurred almost instantaneously in PVC containers; additional losses to the infusion sets were minimal. However, for urokinase 5000 IU/mL in 5% dextrose injection, no losses were observed in the PVC systems. No drug loss to glass bottles was seen for urokinase 1500 or 5000 IU/mL in 5% dextrose injection. Urokinase potency remained constant in polypropylene and glass syringes for 24 hours. To minimize urokinase sorption to PVC containers, higher concentrations of urokinase diluted in 5% dextrose injection should be used, provided that clinical safety and efficacy are not compromised. The use of 0.9% sodium chloride injection as a diluent also prevents sorption losses.

Adsorption↗
PubMed1987

Effect of sampling site on early kinetics of blood radioiodide and pertechnetate.

Radioiodide (I) and radiopertechnetate (TcO4) were sampled simultaneously from left ventricle, right atrium, and femoral vein early after intravenous injection to pentobarbital sodium-anesthetized cats. Concentrations of both tracers in femoral vein blood was lower than in left ventricular (arterial) blood, with rapid narrowing of the differences over 20 min and gradual approach to steady state. Right atrial blood concentrations were intermediate. When these data were fitted to three-compartment mamillary models, representing blood and tissue pools, compartment size and kinetics differed according to which sampling site was taken as representative of each cat's blood. We have developed a model incorporating subcompartmentalization of the blood with an exchange compartment connecting to the pulmonary circulation as well as compartments exchanging with peripheral sites. With the use of this model, all data sets fitted well. The pulmonary exchange compartment and a large rapid exchange compartment in the femoral vein drainage areas are essential to reconciling the differences among sampling sites.

Animals↗