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Biomedical subjects

A C Roberts

Publications and source records attributed to A C Roberts.

At least 55 records · Page 3Linked to original sources

Poor relationship between arterial [lactate] and leg net release during exercise at 4,300 m altitude.

We evaluated the hypotheses that on acute exposure to hypobaric hypoxia, sympathetic stimulation leads to augmented muscle lactate production and circulating [lactate] through a beta-adrenergic mechanism and that beta-adrenergic adaptation to chronic hypoxia is responsible for the blunted exercise lactate response after acclimatization to altitude. Five control and 6 beta-blocked men were studied during rest and exercise at sea level (SL), on acute exposure to 4,300 m (A1), and after a 3-wk sojourn at altitude (A2). Exercise was by leg cycling at 49% of SL peak O2 consumption (VO2 peak) (65% of altitude VO2 peak or 87 +/- 2.6 W); beta-blockade was by propranolol (80 mg 3x daily), femoral arterial and venous blood was sampled; leg blood flow (Q) was measured by thermodilution, leg lactate net release [ = (2) (1-leg Q) venous-arterial concentrationL] was calculated, and vastus lateralis needle biopsies were obtained. Muscle [lactate] increased with exercise and acute altitude exposure but regressed to SL values with acclimatization; beta-blockade had no effect on muscle [lactate]. Arterial [lactate] rose during exercise at SL (0.9 +/- 0.1 to 1.5 +/- 0.3 mM); exercise at A1 produced the greatest arterial [lactate] (4.4 +/- 0.8 mM), and exercise at A2 an intermediate response (2.1 +/- 0.6 mM). beta-Blockade reduced circulating [lactate] approximately 45% during exercise under all altitude conditions. increased transiently at exercise onset but then declined over time under all conditions. Blood and muscle "lactate paradoxes" occurred independent of beta-adrenergic influences, and the hypotheses relating the blood lactate response at altitude to beta-adrenergic mechanisms are rejected. During exercise at altitude, arterial [lactate] is determined by factors in addition to hypoxemia, circulating epinephrine, and net lactate release from active muscle beds.

Acclimatization↗

Perseveration and strategy in a novel spatial self-ordered sequencing task for nonhuman primates: effects of excitotoxic lesions and dopamine depletions of the prefrontal cortex.

Damage to the prefrontal cortex disrupts the performance of self-ordered sequencing tasks, although the precise mechanisms by which this effect occurs is unclear. Active working memory, inhibitory control, and the ability to generate and perform a sequence of responses are all putative cognitive abilities that may be responsible for the impaired performance that results from disruption of prefrontal processing. In addition, the neurochemical substrates underlying prefrontal cognitive function are not well understood, although active working memory appears to depend upon an intact mesocortical dopamine system. The present experiments were therefore designed to evaluate explicitly the contribution of each of these abilities to successful performance of a novel spatial self-ordered sequencing task and to examine the contribution of the prefrontal cortex and its dopamine innervation to each ability in turn. Excitotoxic lesions of the prefrontal cortex of the common marmoset profoundly impaired the performance of the self-ordered sequencing task and induced robust perseverative responding. Task manipulations that precluded perseveration ameliorated the effect of this lesion and revealed that the ability to generate and perform sequences of responses was unaffected by excitotoxic damage to prefrontal cortex. In contrast, large dopamine and noradrenaline depletions within the same areas of prefrontal cortex had no effect on any aspect of the self-ordered task but did impair the acquisition of an active working memory task, spatial delayed response, to the same degree as the excitotoxic lesion. These results demonstrate that a lesion of the ascending monoamine projections to the prefrontal cortex is not always synonymous with a lesion of the prefrontal cortex itself and thereby challenge existing concepts concerning the neuromodulation of prefrontal cognitive function.

Animals↗

The tissue adhesive indermil and its use in surgery.

Indermil, in relation to the tissue adhesives described remains the state of the art with regard to function and clinical outcome. The advantage of an inventory sterile tissue adhesive that is to say one that is in the clinic or operating theatre ready for immediate use on demand is the requirement of modern surgical practice. Cost factors are also an important consideration in today's environment. A research study by the Department of Health Economics at the University of York found the cost of the Indermil tissue adhesive system equivalent to absorbable sutures and produced projected savings per patient in relation to conventional sutures with respect to theatre time and return patients' visits (6). In parallel a survey of patients showed 90% would prefer wound closure by an adhesive in relation to traditional sutures. There are few areas of surgical practice which cannot find some application for tissue adhesives. The growing international interest in adhesives and their application would confirm their importance and potential in surgery.

Enbucrilate↗

Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: restriction to novel situations and independence from "on-line" processing.

Attentional set-shifting and discrimination reversal are sensitive to prefrontal damage in the marmoset in a manner qualitatively similar to that seen in man and Old World monkeys, respectively (Dias et al., 1996b). Preliminary findings have demonstrated that although lateral but not orbital prefrontal cortex is the critical locus in shifting an attentional set between perceptual dimensions, orbital but not lateral prefrontal cortex is the critical locus in reversing a stimulus-reward association within a particular perceptual dimension (Dias et al., 1996a). The present study presents this analysis in full and extends the results in three main ways by demonstrating that (1) mechanisms of inhibitory control and "on-line" processing are independent within the prefrontal cortex, (2) impairments in inhibitory control induced by prefrontal damage are restricted to novel situations, and (3) those prefrontal areas involved in the suppression of previously established response sets are not involved in the acquisition of such response sets. These findings suggest that inhibitory control is a general process that operates across functionally distinct regions within the prefrontal cortex. Although damage to lateral prefrontal cortex causes a loss of inhibitory control in attentional selection, damage to orbitofrontal cortex causes a loss of inhibitory control in affective processing. These findings provide an explanation for the apparent discrepancy between human and nonhuman primate studies in which disinhibition as measured on the Wisconsin Card Sort Test is associated with dorsolateral prefrontal damage, whereas disinhibition as measured on discrimination reversal is associated with orbitofrontal damage.

Animals↗

Contrasting effects of excitotoxic lesions of the prefrontal cortex on the behavioural response to D-amphetamine and presynaptic and postsynaptic measures of striatal dopamine function in monkeys.

The effects of excitotoxic lesions of the prefrontal cortex on behavioural, neurochemical and molecular indices of dopamine function in the caudate nucleus were studied in the marmoset. The lesion, which encompassed both the lateral and orbital regions of prefrontal cortex, made the animals more sensitive to the performance disrupting effects of the dopamine releasing drug, D-amphetamine, in a variation of the object retrieval task. Specifically, following drug administration, the lesioned marmosets were less able to gain access to food reward in the minimum number of responses. Analysis of the nature of the errors suggested that the deficit was not due to inhibition of a prepotent response as the lesioned monkeys were just as likely to make a detour reach to the unopened side of the box as a direct "line-of-sight" reach into the unopened front of the box. Rather, the data indicated a general disorganization of behaviour. The enhanced behavioural responsiveness to manipulations increasing presynaptic dopamine function was accompanied by neurochemical changes indicating a reduced responsiveness, as revealed by in vivo microdialysis. Thus, in lesioned animals, whilst there were no effects on baseline levels of extracellular dopamine in dorsolateral caudate, evoked release, both to systemic D-amphetamine and to a local depolarizing pulse of potassium ions, was attenuated. These opposite effects of the prefrontal cortex lesion on behavioural and neurochemical indices of striatal dopamine function occurred in the absence of any changes in striatal dopamine receptors of the D1 and D2 subtype, as determined both by radioligand binding assays and measurements of messenger RNA using in situ hydridization techniques. These data provide further insight into the interactions between prefrontal cortex and striatal dopamine function in the non-human primate. In particular, when taken in the light of our previous studies they indicate that following prefrontal manipulations, concurrence between behavioural and neurochemical indices of striatal dopamine function depends, critically, on the behavioural task. These findings are discussed with respect to the growing body of evidence implicating abnormalities in frontostriatal neurotransmission in complex disorders such as schizophrenia.

Analysis of Variance↗

The use of Indermil (n-butyl cyanoacrylate) in otorhinolaryngology and head and neck surgery. A preliminary report on the first 33 patients.

The authors present their initial experience of a new sterile medical grade cyanoacrylate adhesive (Indermil) in otolaryngeal and head and neck surgery. Thirty-three patients who underwent a variety of head and neck operations consented to have their skin incisions closed using the adhesive and 10 of those also underwent repair of the tympanic membrane, either as part of tympanoplasty or mastoid surgery. The history of the use of this class of adhesive is presented with an explanation of the chemical properties of these compounds. Advantages of using cyanoacrylate adhesives and future possible applications in otolaryngology and head and neck surgery are discussed.

Drug Delivery Systems↗

n-Butyl cyanoacrylate adhesive for skin closure of abdominal wounds: preliminary results.

Tissue adhesives offer significant potential advantages over traditional methods of wound closure. A new n-butyl 2-cyanoacrylate adhesive formulation was utilised for the closure of abdominal wounds after general and laparoscopic gastrointestinal surgery. One hundred and two patients with 240 wounds were recruited. Wounds were classified as > 10 cm, n = 39; 5-9 cm, n = 27; and < 5 cm, n = 176. Complications included one small seroma and two partial superficial dehiscences. There were no incidences of wound infection. This preliminary study indicates that this tissue adhesive can safely and effectively be utilised for general abdominal wound closure. It should now be subjected to the rigorous of a randomised controlled trial to compare its performance against the more traditional methods of wound closure.

Dermatologic Surgical Procedures↗

Dissociation in prefrontal cortex of affective and attentional shifts.

The prefrontal cortex is implicated in such human characteristics as volition, planning, abstract reasoning and affect. Frontal-lobe damage can cause disinhibition such that the behaviour of a subject is guided by previously acquired responses that are inappropriate to the current situation. Here we demonstrate that disinhibition, or a loss of inhibitory control, can be selective for particular cognitive functions and that different regions of the prefrontal cortex provide inhibitory control in different aspects of cognitive processing. Thus, whereas damage to the lateral prefrontal cortex (Brodmann's area 9) in monkeys causes a loss of inhibitory control in attentional selection, damage to the orbito-frontal cortex in monkeys causes a loss of inhibitory control in 'affective' processing, thereby impairing the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli. These findings not only support the view that the prefrontal cortex has multiple functions, but also provide evidence for the distribution of different cognitive functions within specific regions of prefrontal cortex.

Affect↗

Comparison of cognitive function in human and non-human primates.

Fundamental to any comparative study of cognitive function in monkey and man is the demonstration of behavioral homology, viz. that the same cognitive function is being studied in both species. This paper considers a variety of psychological issues that need to be taken into account when attempting to demonstrate behavioural homology. Examples are taken from studies of attentional set-shifting, discrimination reversal learning, spatial working memory and episodic memory. Whilst highlighting the pitfalls to be avoided in the future, these examples also demonstrate the enormous contribution that such studies have had to our understanding of the functions of the temporal lobes and frontal lobes. Moreover, they also illustrate the enormous potential in defining the cognitive functions and dysfunctions of the prefronto-striatal circuitry which underlie so many neurodegenerative and neuropsychiatric disorders.

Animals↗

Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset.

Using a primate analogue of the Wisconsin Card Sort Test, this study demonstrated, for the first time, that lesions of the prefrontal cortex in monkeys produce a qualitatively similar impairment in attentional set-shifting to that seen following prefrontal cortical damage in humans. Although damage to the prefrontal cortex did not disrupt the ability of marmosets, a New World monkey, to maintain an attentional set, it did disrupt their ability to shift an attentional set. It also impaired their performance on discrimination reversal, object retrieval, and spatial delayed response, consistent with the effects of prefrontal damage in Old World monkeys. Comparison of the cognitive processes underlying discrimination reversal, object retrieval, and attentional set-shifting reveals the various types of inhibitory control provided by the prefrontal cortex.

Animals↗

Detection and treatment of dysfunctional hemodialysis access grafts: effect of a surveillance program on graft patency and the incidence of thrombosis.

PURPOSE: To determine the value of a hemodialysis graft surveillance program in reducing the incidence of graft thrombosis and prolonging graft patency by means of early detection and percutaneous transluminal angioplasty (PTA) of graft-related stenoses. MATERIALS AND METHODS: For 4-1/2 years, routine graft examination and measurement of several dialysis parameters were used to identify 106 cases of suspected graft dysfunction in 57 patients (56 men, one woman; aged 27-76 years). Graft-related stenoses detected with angiography were treated with PTA. RESULTS: Abnormal physical examination findings were the most common sole indication of graft dysfunction. Of the 106 cases referred for angiographic evaluation, 97 (92%) had at least one lesion. PTA was successful in 88 of 90 treated cases. The primary patency rates at 1 year were 16% for arteriovenous fistulas (AVFs) and 23% for polytetrafluoroethylene (PTFE) grafts. Early detection of stenoses by means of surveillance and repeated PTA enabled 1-year primary assisted patency rates of 67% for AVFs and 68% for PTFE grafts. The incidence of graft thrombosis fell from 48% in 1988 to 17% in 1994 (P < .001). CONCLUSION: The hemodialysis graft surveillance program resulted in a statistically significant reduction in the incidence of graft thrombosis. Although primary patency rates after PTA were low, repeated PTA of detected stenoses allowed good primary assisted patency rates.

Adult↗

Altitude and beta-blockade augment glucose utilization during submaximal exercise.

To test the hypothesis that altitude exposure increases glucose utilization and that this increment is mediated by a beta-adrenergic mechanism, the effects of hypobaric hypoxia and beta-blockade on glucose rates of appearance (Ra), disappearance (Rd), oxidation (Rox), and leg uptake [G = 2(arteriovenous glucose difference)(1 - leg blood flow)] were measured during rest and a given submaximal exercise task. We studied six healthy beta-blocked (beta) men [26.7 +/- 1.2 (SE) yr, 74.0 +/- 6.6 kg] and five matched controls (C; 26 +/- 1.2 yr, 69.3 +/- 2.6 kg) in energy and nitrogen balance during rest and leg cycle-ergometer exercise at sea level, on acute altitude exposure to 4,300 m (barometric pressure = 463 Torr), and after 3 wk of habituation. Subjects received a primed continuous infusion of [6,6-2H]- and [1-13C]glucose, rested for > or = 90 min, and then immediately exercised for 45 min at 89 W, which elicited 49% of sea-level peak O2 consumption (VO2peak; 65% of altitude VO2peak). At sea level, resting Ra was 1.47 +/- 0.19 and 1.66 +/- 0.16 mg x kg-1 x min-1 for C and beta, respectively, and increased to 3.04 +/- 0.25 and 3.56 +/- 0.27 mg x kg-1 x min-1, respectively, during exercise. Thus glucose Ra was significantly increased by beta-blockade during rest and exercise at sea level. At sea level, beta-blockade increased leg G, which accounted for 49 and 69% of glucose disposal during exercise in C and beta, respectively. On acute altitude exposure, glucose Ra rose significantly during rest and exercise relative to sea level, whereas blockade continued to augment this increment. During exercise on acute exposure, G increased more than at sea level and accounted for a greater percentage (80 and 97%, respectively) of Rd in C and beta during exercise. Similarly, Rox values, particularly during exercise, were increased significantly at altitude relative to sea level, and beta-blockade potentiated this effect. During a given submaximal exercise task after acclimatization, glucose Ra, Rox, and G were increased relative to sea level, but these increments were less than those in response to exercise measured on acute exposure. We conclude that altitude exposure increases glucose use during rest and a given submaximal exercise bout and beta-blockade exaggerates the response.

Adrenergic beta-Antagonists↗

Acclimatization to 4,300-m altitude decreases reliance on fat as a substrate.

We tested the hypothesis that exposure to altitude decreases reliance on free fatty acids (FFA) as substrates and increases dependency on blood glucose. Therefore, the effects of exercise, hypobaric hypoxia, and altitude acclimatization on FFA, glycerol and net glucose uptake and release [= 2(leg blood flow)(arteriovenous concentration)] and on fatty acid (FA) consumption by the legs (= 3 x glycerol release + FFA uptake) were measured. Because sympathetic responses have been implicated, we utilized nonspecific beta-blockade and observed responses to exercise, altitude, and altitude acclimatization. We studied six healthy beta-blocked men (beta) and five matched controls (C) during rest and cycle ergometry exercise (88 W) at 49% of sea-level (SL) peak O2 uptake at the same absolute power output on acute altitude exposure (A1; barometric pressure = 430 Torr) and after 3 wk of chronic altitude exposure to 4,300 m (A2). During exercise at SL, FA consumption rates increased (P < 0.05). On arrival at 4,300 m, resting leg FFA uptake and FA consumption rates were not significantly different from those at SL. However, after acclimatization to altitude, at rest leg FA consumption decreased to essentially zero in both C and beta groups. During exercise to altitude after acclimatization, leg FA consumption increased significantly, but values were less than at SL or A1 (P < 0.05), whereas glucose uptake increased relative to SL values. Furthermore, beta-blockade significantly increased glucose uptake relative to control. We conclude that 1) chronic altitude exposure decreases leg FA consumption during rest and exercise; 2) relative to SL FFA uptake decreases while glucose uptake increases during exercise at altitude; and 3) beta-blockade potentiates these effects.

Acclimatization↗

Predicting treatment retention of women dependent on cocaine.

The purpose of this research was (a) to assess differences in retention patterns and discharge status across three program settings; and (b) to examine selected pretreatment characteristics that might help predict treatment retention, which was operationalized as length of time in treatment. Three groups of pretreatment characteristics were examined. They included demographic factors, drug use and treatment history, and psychological status and symptomology. Clients in the intensive day treatment program tended to stay longer and were more likely to successfully complete the program than either clients in the outpatient or the traditional residential programs. In general, pretreatment client characteristics were not helpful in predicting length of time in treatment regardless of program type. Few pretreatment characteristics were related to retention within programs and significant predictors differed across treatment settings.

Adolescent↗

Decreased bladder compliance in patients with myelomeningocele treated with radiological observation.

PURPOSE: Recently others advocated frequent radiological surveillance to detect upper urinary tract deterioration in children with neurogenic bladder secondary to spina bifida. We reviewed the consequences of such expectant management on bladder compliance and urinary continence. MATERIALS AND METHODS: We retrospectively reviewed the records of 214 children presenting to our spina bifida clinic in a 13-year period. Follow-up is available for 95 girls and 86 boys. Imaging studies of the kidneys were repeated at 6 to 12-month intervals. Urodynamics were performed when upper urinary tracts deteriorated or in incontinent school age children. RESULTS: On radiographic study there was evidence of upper urinary tract deterioration in 79 children, including hydronephrosis in 34, hydronephrosis and vesicoureteral reflux in 19, and reflux only in 26. Follow up studies performed after clean intermittent catheterization and pharmacological therapy were instituted revealed resolution or improvement of upper tract deterioration in 52 patients (69%), while bladder compliance improved in only 42%. Surgical intervention was required in 34 children, despite improvement of upper tract changes in many of these patients on follow up radiographic studies. CONCLUSIONS: Although radiological surveillance of patients with myelomeningocele allows recognition of upper tract changes, the effects of elevated outlet resistance on bladder compliance are not as readily reversible as the initial radiographic findings. The incidence of enterocystoplasty exceeds that reported for patients treated prospectively based on urodynamic findings, which should be considered in the treatment of these children.

Female↗

Prolonging the life of difficult hemodialysis access using thrombolysis, angiography, and angioplasty.

Prolonging the life of vascular access sites is one of the most pressing problems facing the nephrology team in the ongoing care of chronic hemodialysis patients. Thus, the ability to salvage a failing vascular access is important in any circumstance, but salvage is particularly critical in medically complicated situations. The following case presents just such a situation, one in which available access sites were limited and in which salvaging the function of a local access site obviated the need for major surgical intervention for more than 4 years. This example shows the efficacy of nonsurgical thrombolysis and the place of vascular radiology in the long-term preservation of access patency and follow-up care.

Aged↗