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Biomedical subjects

F J Thompson

Publications and source records attributed to F J Thompson.

At least 37 records · Page 2Linked to original sources

High dependency units in the UK: variable size, variable character, few in number.

An exploratory descriptive survey was conducted to determine the size and character of high dependency units (HDUs) in the UK. A telephone survey and subsequent postal questionnaire was sent to the 39 general HDUs in the UK determined by a recent survey from the Royal College of Anaesthetists; replies were received from 28. Most HDUs (82%, n = 23) were geographically distinct from the intensive care unit and varied in size from three to 13 beds, although only 64% (n = 18) reported that all beds were currently open. Nurse: patient ratios were at least 1:3. Fifty per cent of units had one or more designated consultants in charge, although only 11% (n = 3) had specifically designated consultant sessions. Junior medical cover was provided mainly by the on-call speciality term. Twenty units acted as a step-down facility for discharged intensive care unit patients and 21 offered a step-up facility for patients from general wards. Provision of facilities and levels of monitoring varied between these units. Few HDUs exist in the UK and they are variable in size and in the facilities and monitoring procedures which they provide. Future studies are urgently required to determine cost-effectiveness and outcome benefit of this intermediate care facility.

Health Facility Size↗

Purification of a lysophosphatidic acid-hydrolysing lysophospholipase from rat brain.

A lysophosphatidic acid (LPA)-hydrolysing lysophospholipase was purified from rat brain and characterized. This membrane-bound lysophospholipase was solubilized by using n-octyl glucoside and purified by sequential cation, hydrophobic and gel-filtration chromatography. The purified protein has a mass of 80 kDa as assayed by SDS/PAGE. This lysophospholipase catalysed the hydrolysis of a variety of lysophosphatidic acids, but with different rates, depending on the length and degree of saturation of the sn-1 acyl group (1-oleoyl-LPA approximately 1-stearoyl-LPA > 1-palmitoyl-LPA > 1-myristoyl-LPA). This enzyme had no-measurable catalytic activity when other lysophospholipids, monoacylglycerol or phosphatidic acid were used as substrates. On the basis of its chromatographic properties, substrate specificity and cellular localization, we conclude that this lysophospholipase differs from those previously purified and speculate that it has an important function in terminating biological responses to LPA.

Animals↗

Cis- and trans-regulation of feline immunodeficiency virus: identification of functional binding sites in the long terminal repeat.

Nuclear protein binding sites in the long terminal repeat (LTR) of feline immunodeficiency virus (FIV) were identified by the method of DNase I footprinting. Using nuclear protein extracts from a feline T lymphoma cell line, several discrete footprints were generated upstream of the transcriptional initiation site (-50 to -150). The specificity of protein binding was examined by competition with oligonucleotides representing consensus DNA binding sites for known transcription factors. Binding to AP-1 (-124) and ATF (-58) motifs was observed, with cross-competition between these sites. A strong footprint signal was also detected over a tandemly repeated C/EBP motif (-94, -86) and an adjacent weaker footprint was found to be specific for an NF1 motif (-72/-63). The effect on FIV LTR promoter activity of progressively deleting these nuclear factor binding sites was examined by linking LTR deletion mutants to the chloramphenicol acetyltransferase (CAT) gene. Deletion of the AP-1 site caused a 10- to 25-fold loss of CAT activity whereas deletion past the ATF site reduced activity virtually to background levels. The effects of deleting the C/EBP and NF1 sites were less marked and varied according to cell type. Transactivation of the LTR was assayed using constructs linked to a CAT reporter gene. The full-length FIV LTR was not significantly trans-activated. However, the expression of a deleted LTR construct lacking the AP-4/AP-1 site but retaining C/EBP and ATF sites was partially restored by co-infection with FIV or by co-transfection with an infectious molecular clone of FIV (FIV-PPR). These results show that host transcription factors responsive to cellular activation have a major role in regulating FIV expression, and suggest that virus-coded trans-activators acting through U3 may play a role in some cellular environments.

Animals↗

Fetal cell grafts into resection and contusion/compression injuries of the rat and cat spinal cord.

This article reviews recent findings concerning the feasibility, basic neurobiology, and potential functional benefits of fetal CNS tissue grafts into acute and chronic lesions of the adult spinal cord. In the rat, neuro-anatomical observations suggest that transplants into resection cavities establish neuritic projections that could functionally reunite separated rostral and caudal segments of the host spinal cord. Furthermore, some complementary electrophysiological evidence has been obtained for synaptic connectivity between host and graft neurons. In these studies, extracellular single-unit activity was evoked in fetal spinal cord (FSC) transplants by stimulating host dorsal roots that had been juxtaposed to donor tissue at the time of transplantation. In other investigations, we examined whether grafts could also establish axonal projections to appropriate areas of gray matter in the chronically injured spinal cord. For this purpose, fetal serotoninergic (5-HT) neurons were injected caudal to complete spinal cord transections that had been made 1-3 months earlier. Immunocytochemistry revealed that these cells projected their axons into gray matter regions normally innervated by bulbospinal 5-HT neurons. To investigate transplantation in a more clinically relevant lesion model, a third group of experiments involved injection of dissociated cell suspensions into acute [less than 24 h postinjury (p.i.)]), subchronic (7-10 days p.i), and chronic (greater than or equal to one month, p.i.) contusion lesions. Such grafts routinely filled areas that otherwise would have been regions of cavitation extending rostral-caudal distances of approximately 7 mm. FSC transplants in such injuries also appeared to influence some aspects of motoneuron excitability and hindlimb locomotion. More recent studies of the cat spinal cord have extended these findings in the rat by showing long-term survival (greater than 2 years) of fetal CNS allografts in recipients with either subtotal transection or compression lesions. Preliminary studies of connectivity have also shown host-graft projection patterns similar to those seen in the rat. Behavioral analyses are currently underway to examine the effects of fetal grafts in cats with chronic postcompression lesions. These observations in the rat and cat are discussed in the general context of basic biological and clinical issues relevant to the long-term objective of promoting functional improvement in the damaged spinal cord.

Animals↗

Altered patterns of reflex excitability subsequent to contusion injury of the rat spinal cord.

1. The present study investigated regulation of reflex excitability after experimental contusion injury of the spinal cord. 2. Four measures of H-reflex excitability were evaluated in normal rats and at 6, 28, and 60 days after contusion injury at the T8 level: 1) reflex thresholds, 2) slope of the reflex recruitment curves, 3) maximal plantar H-reflex/maximal plantar M-response (Hmax/Mmax) ratios, and 4) rate-sensitive depression (i.e., the decrease in reflex magnitude relative to repetition rate). 3. Tested as a function of the afferent volley magnitude, the thresholds for reflex initiation fell progressively subsequent to contusion injury. No change was observed at 6 days postinjury, and the decrease at 28 days was not significant. However, by 60 days postinjury, the threshold had decreased by 23% of the maximal afferent volley, and this decrease was significant, [analysis of variance (ANOVA, P < or = 0.01)]. 4. Hmax/Mmax ratios elicited in postcontusion animals at 0.3 Hz were not significantly different from those recorded in normal animals. 5. The slopes of the recruitment curves were markedly reduced subsequent to contusion injury. The decrease was greatest at 6 days postinjury. Although some recovery toward normal occurred at 28 and 60 days postinjury, the slopes of recruitment curves in postcontusion animals remained significantly decreased. 6. H-reflexes elicited at 1-5 Hz were less sensitive to rate depression in postcontusion animals than in normal animals at the same respective frequencies. The decrease was progressive in onset, becoming significant by 28 days postinjury, and of an enduring nature, i.e., still significantly different from normal in the reflexes tested 60 days postinjury. 7. Rate sensitivity of the tibial nerve monosynaptic reflex (MSR) was also compared in normal and postcontusion animals. Rate sensitivity of the tibial MSRs was significantly reduced at 28 and 60 days post-contusion, compared with normal animals. 8. These data indicate that significant changes in lumbar reflex excitability result from midthoracic contusion injury of the spinal cord. These changes include reflex threshold, slope of recruitment, and rate-sensitive depression. Although recruitment slope was most altered in the shortest postinjury interval tested, followed by some recovery, the other changes were progressive in onset and enduring in duration.

Animals↗

Neural tissue transplantation and CNS trauma: anatomical and functional repair of the injured spinal cord.

Neural tissue transplantation has become recognized widely as a powerful experimental tool for studying structure-function relationships, development, plasticity, and capacities for regeneration in the adult CNS. In addition, this area of investigation has generated considerable interest in approaches that might be applicable to a variety of catastrophic neurological disorders. In this regard, attention has been given to neural tissue grafting as a potential therapeutic strategy in various forms of neurodegenerative disease. More recently, however, other investigations have begun to focus on the possible application of peripheral and central neural tissue transplants for promoting repair in forms of CNS trauma. This review highlights various neural transplantation approaches that have been explored primarily in the context of injury to the adult CNS, with emphasis on spinal cord injury. An overview is presented of the evolution of this area of research in terms of emerging biological perspectives, technological advances, and experimental modelling. Discussion centers on progress that has been made and a variety of theoretical and practical issues that remain to be resolved.

Animals↗

Responses of spinal cord neurons following stimulation of A beta femoral-saphenous venous afferent fibers.

A population of large (A beta) afferents is known to have endings in the wall of the femoral-saphenous vein. These afferents project to the lower lumbar spinal cord. The purpose of the present study was to identify, localize, and characterize spinal neurons that receive inputs from such afferents. Responses of 50 neurons in the L6 spinal cord segment of decerebrate-spinal cats or intact cats anesthetized using alpha-chloralose were recorded following electrical stimulation of these afferents. Observations were also made on the convergence of muscle and cutaneous afferent inputs onto neurons driven by stimulation of afferents terminating in the femoral-saphenous vein. All recording sites were marked either by intracellularly staining the element characterized with HRP or by extracellularly iontophoresing a small quantity of this tracer. The cells were driven for long durations (mean of 51.5 ms, S.E.M. of 10.0) by single-shock stimulation of femoral-saphenous venous afferents. The recording sites were located in Rexed's laminae IV-VIII and X. Eight of the 50 neurons were activated by venous afferent stimulation at latencies equal to or shorter than that of the first negative wave of the cord dorsum potential; these units were driven at a mean latency of 1.4 ms (S.E.M. of 0.25) following the arrival of the afferent volley at the cord and were assumed to receive monosynaptic, or at least relatively direct, inputs from the primary afferents. Most of these cells (6 of 8) were located in lamina V. The majority of the neurons studied (37 of 50) were activated at latencies longer than 3 ms following the arrival of the afferent volley at the cord; about half (19 of 37) of those activated at longer latencies were located in lamina VII, and the rest were scattered among the other laminae. Twenty-eight of 40 venous afferent-driven cells tested could also be activated by electrical stimulation of either the posterior tibial or sural nerve. In general, the stimulation intensities necessary to activate the neurons were only sufficient to excite large (A alpha or A beta) muscle and cutaneous afferents. Neurons receiving the shortest latency inputs from the femoral-saphenous vein were less likely to receive convergent inputs from muscle or skin than were neurons activated by venous afferents at longer latency.

Action Potentials↗

Tracing of afferent pathways from the femoral-saphenous vein to the dorsal root ganglia using transport of horseradish peroxidase.

The retrograde transport of horseradish peroxidase (HRP) was used to trace afferents from the femoral-saphenous vein to the dorsal root ganglia in the cat. Afferents arising along the entire length of the vein projected to very localized spinal levels; 63% of the labeled cells counted were located in the L6 dorsal root ganglion, 37% were located in the L5 ganglion and less than 1% were located at other levels. Most of the cell bodies labeled by the application of HRP to the femoral-saphenous vein were small in size (diameter less than 35 microns). However, some large cell bodies (diameter greater than 50 microns) were also noted. It was estimated that over two-thirds of the femoral-saphenous venous afferents were C fibers; at least 15% were estimated to be A fibers. The largest venous afferents were predicted to conduct action potentials at approximately 60 m/s.

Afferent Pathways↗

Mechanosensitive afferents of femoral-saphenous vein.

Reflex contraction of cat hindlimb skeletal muscles can be induced by mechanical stimulation of afferents in the femoral-saphenous vein. Afferent fibers innervating this vein have been previously reported. Hence, it is evident that mechanoreceptors must be present in the femoral-saphenous vein, yet there have never been direct recordings of sensory nerves that respond to mechanical stimulation of the vein. This study recorded the activity of these venous mechanoreceptors and tested their response to increased intravenous pressure. The activity of single venous afferents was recorded from thin filaments of the saphenous nerve. The afferent response was recorded during external mechanical probing of the vein wall and increases in intravenous pressure. Their venous pressure threshold and adaptation to static pressures were determined. All the afferents responded to both types of mechanical stimuli. Static increases in venous pressure resulted in two types of afferent discharge behavior: slowly adapting and rapidly adapting. Venous pressure thresholds varied considerably with a range of 22.2-174.7 mmHg. The estimated conduction velocities are 2.8-7.8 m/s, suggesting type III, A-delta-myelinated mechanoreceptors. These results demonstrate the presence and mechanical sensitivity of venous afferents that transduce intravenous pressure. Their role in the reflex responses to vein distension is unclear and awaits further investigation.

Animals↗

Properties of femoral venous afferent inputs and lumbosacral distribution of spinal evoked activity.

The present studies were done to determine details of the anatomical and physiological characteristics of femoral-saphenous venous afferent input to the lumbar spinal cord. Gross anatomical examination revealed that afferent bundles could be seen coursing from the saphenous nerve to the femoral-saphenous vein. Compound action potentials elicited by femoral-saphenous venous afferent stimulation were recorded from the femoral nerve and in dorsal rootlets of the 6th lumbar cord segment. The compound action potentials included activity correlated with that of fibers conducting impulses at the rate of 31 to 61 m/s. Lumbar cord dorsum potentials elicited by femoral-saphenous venous afferent stimulation were abolished by rhizotomy of the most caudal rootlets of the 6th lumbar cord segment. L6 was also the cord segment from which the largest amplitude cord dorsum negative potentials were recorded, while action potentials with large late positive waves were recorded from more caudal cord segments. These observations suggested that the L6 segment contained the largest number of spinal neurons responding to primary femoral-saphenous venous afferent input, and that input reached the more caudal segments via intersegmental connections. A proposed physiological role of these afferents is briefly described.

Afferent Pathways↗

Respiratory-related cortical potentials evoked by inspiratory occlusion in humans.

It has long been recognized that humans can perceive respiratory loads. There have been several studies on the detection and psychophysical quantification of mechanical load perception. This investigation was designed to record cortical sensory neurogenic activity related to inspiratory mechanical loading in humans. Inspiration was periodically occluded in human subjects while the electroencephalographic (EEG) activity in the somatosensory region of the cerebral cortex was recorded. The onset of inspiratory mouth pressure (Pm) was used to initiate signal averaging of the EEG signals. Cortical evoked potentials elicited by inspiratory occlusions were observed when C3 and C alpha were referenced to CZ. This evoked potential was not observed with the control (unoccluded) breaths. There was considerable subject variability in the peak latencies that was related to the differences in the inspiratory drive, as measured by occlusion pressure (P0.1). The results of this study demonstrate that neurogenic activity can be recorded in the somatosensory region of the cortex that is related to inspiratory occlusions. The peak latencies are longer than analogous somatosensory evoked potentials elicited by stimulation of the hand and foot. It is hypothesized that a portion of this latency difference is related to the time required for the subject to generate sufficient inspiratory force to activate the afferents mediating the cortical response.

Adult↗

New federalism and health care policy: states and the old questions.

The New Federalism that evolved under the Reagan administration tends to grant states more discretion in the implementation of health care programs. It thereby rekindles old concerns about the commitment, capacity, and progressivity of the states. This paper reviews recent policy developments and reconsiders state performance from the vantage point of the mid-1980s. While hard evidence remains elusive, a plausible case exists that any gap between the states and Washington on commitment, capacity, and progressivity has diminished. State administrative capacity in particular has probably increased. The continued presence of substantial variation among the states needs to be underscored, however. Moreover, the relentless imperative of economic development, or migration, theory sets severe limits on how far states can go in adopting redistributive measures to assure adequate medical care for the poor. Given current federal laws, the most optimistic, plausible scenario envisions the rise of a technical politics of efficiency in the states. In spite of state limitations, health policy reformers need to pay increased attention to their potential role.

Costs and Cost Analysis↗

Activation of spinal cord interneurons which process inputs from the femoral-saphenous vein.

Recordings were made from single spinal cord interneurons which could be activated by electrical stimulation of afferents terminating in the wall of the femoral-saphenous vein. Interneurons were either excited or both excited and inhibited by venous afferent stimulation. Most of the venous afferent-driven interneurons could also be driven by electrical activation of A-alpha beta muscle and cutaneous afferents. Stimulation of several different muscle nerves drove single interneurons.

Animals↗

Projection of phrenic nerve afferents to the cat sensorimotor cortex.

The projection of phrenic nerve afferents to the sensorimotor cortex was studied in cats. The results of these experiments demonstrate that stimulation of phrenic nerve afferents elicits cortical evoked potentials (CEPs) in the sensorimotor cortex of cats. Cortical foci for CEPs classified as primary were found in areas 3b, 3a and 4 gamma. These foci were located medial to forelimb and lateral to hindlimb afferent representations in the sensorimotor cortex.

Afferent Pathways↗