Search PubMed⌕ Search

Biomedical subjects

S Rees

Publications and source records attributed to S Rees.

At least 73 records · Page 4Linked to original sources
PubMed1997

The Bentham Unit: a pilot remand and assessment service for male mentally disordered remand prisoners. II: Report of an independent evaluation.

BACKGROUND: Findings are presented from an evaluation of a pilot remand and assessment service--the Bentham Unit. The aims of the Bentham Unit are to provide rapid assessment, identify mentally disordered remand prisoners, and speed their transfer from prison to NHS care, where a need is indicated. METHOD: The number, rate and speed of referral, assessment and transfer to NHS care of offenders remanded to Wormwood Scrubs prison during periods before and after the Bentham Unit opened were compared. RESULTS: The service attracted a large volume of referrals. Between the two periods, significant increases in the numbers of referrals and hospital disposals, and major reductions in the interval between reception on remand into the prison, NHS assessment and transfer to NHS care, were observed. CONCLUSIONS: The aims of the unit were met. Implications for service configurations are discussed.

England↗
PubMed1996

Experimental hydranencephaly in the ovine fetus.

Hydranencephaly is defined as the replacement of a previously normal brain, in whole or in part, by membranous fluid-filled sacs. The etiology is not well understood, and the time course of development is unknown. Fifteen ovine fetuses were chronically cannulated and had both carotid arteries ligated at 100 days of gestation (term is 145-150 days). They were killed at 1 (n = 4), 2 (n = 6) and 4 (n = 5) weeks post-surgery, and the findings compared with those of 25 age-matched controls. By 2 weeks post-surgery the entire cerebral hemispheres and diencephalon had been replaced by fluid closely resembling cerebrospinal fluid. The choroid plexus, pituitary and brain stem remained outwardly normal, but the cerebellum showed signs of damage. Fetuses maintained normal values for blood gases and hematocrit up to 4 weeks post-surgery, and grew normally. Light microscopy of the brain stem showed significant losses of cell populations in the medulla by 4 weeks. Vascular casting and acute blood flow studies in an additional group of fetuses showed that the entire brain was perfused via the vertebral-occipital anastomosis immediately after acute bilateral carotid clamping, but that the blood flow rate was insufficient to maintain adequate oxygen delivery.

Animals↗
PubMed1996

Which cardiac potassium channel subtype is the preferable target for suppression of ventricular arrhythmias?

Prolongation of the cardiac action potential duration is the hallmark of Class III antiarrhythmic activity. Action potential duration prolongation may be achieved by several means: enhancement of inward current and, more commonly, blockade of one or more of the many outward currents that are carried by K+. However, it is far from clear whether blockade of one particular K+ channel is more efficacious than blockade of another. The objective of this review is to consider this question with particular reference to ischaemic heart disease, a condition for which effective prevention of ventricular arrhythmias continues to be sought.

Animals↗
PubMed1996

The development of diurnal rhythmicity in fetal suprachiasmatic neurons as demonstrated by fos immunohistochemistry.

Using Fos immunohistochemistry as a marker of cellular activity, we have shown that neurons in the suprachiasmatic nucleus of fetal sheep are active by 75 days gestation. From at least 90 days gestation (term is 146 days), these neurons are more active during the day (12.00) than at night (03.00) when pregnant ewes are exposed to a 12-h light-dark cycle with lights on at 07.00. The day-night difference in Fos immunoreactivity persisted when the lighting schedule was extended by 8 h to 03.00, although neurons were now more active at 03.00 than they were in fetuses maintained on the normal light-dark cycle. When ewes were maintained in constant light from 133 to 138 days, the day-night difference in Fos immunoreactivity in the fetal suprachiasmatic nucleus was abolished, suggesting that diurnal activity of the fetal suprachiasmatic nucleus is maintained by a signal related to the external lighting regime. In a twin pregnancy where one fetus was optically enucleated at 100 days gestation, the density of Fos-immunoreactive neurons in the suprachiasmatic nucleus during the day at 138 days was similar to the unoperated twin. This suggests that the effects of dim light in the uterus on the fetal retina do not account for the high level of Fos immunoreactivity in the suprachiasmatic nucleus in the daytime. We propose that a chemical messenger of maternal origin, possibly melatonin, suppresses the activity of fetal suprachiasmatic neurons during the night, and that fetal suprachiasmatic neurons have endogenous activity which is expressed fully during the daytime.

Animals↗
PubMed1996

Bicistronic vector for the creation of stable mammalian cell lines that predisposes all antibiotic-resistant cells to express recombinant protein.

We have developed an improved vector for the stable expression of recombinant protein in mammalian cells. In this vector, designated pCIN, both the recombinant cDNA and the neomycin phosphotransferase selection marker are transcribed from a single promoter element. To facilitate translation of the second open reading frame, the encephalomyocarditis virus internal ribosome entry site has been inserted into the expression cassette immediately before the start codon of this sequence. We report the use of this vector to generate stable cell lines expressing the human 5-HT1Da serotonin receptor and show that following transfection and clonal selection, all ten cell lines characterized express similar and high levels of receptor (1.5-11.9 pmol receptor/mg protein). Use of pCIN should permit the rapid and efficient production of stable mammalian cell lines for the characterization of recombinant protein, as this vector appears to predispose all transfected cells to express such protein.

Animals↗
PubMed1996

Pharmacokinetics of extended relief vs regular release Tylenol in simulated human overdose.

BACKGROUND: The purpose of this trial was to compare the pharmacokinetics of the two available acetaminophen dosage forms in simulated human overdose. METHODS: Ten healthy volunteers received acetaminophen, 75 mg/kg orally, either as the regular release or extended relief formulation in a random, crossover fashion. Blood samples were analyzed using a TDx assay and a best fit correlation of data points was determined by PCNONLIN. RESULTS: The area under the curves for extended relief acetaminophen and regular release acetaminophen were 426 mg h/L and 432 mg h/L, respectively (p = 0.768). The mean half times for extended relief acetaminophen and regular release acetaminophen were 4.02 h and 2.56 h, respectively (p < 0.001). The mean maximum serum acetaminophen concentrations were 62.6 mg/L (414.4 mmol/L:) and 94.3 mg/L (624.3 mmol/L) for extended relief acetaminophen and regular release acetaminophen, respectively (p < 0.001) and the mean time to maximum serum acetaminophen concentrations were 0.87 h and 0.75 h for extended relief acetaminophen and regular release acetaminophen, respectively (p = 0.508). CONCLUSIONS: Although the formulations appear to have equal bioavailability, their half-lives and peak concentrations were significantly different. Further study is required to determine whether these differences affect the assessment and management of poisoned patients.

Acetaminophen↗
PubMed1995

Nitric oxide synthase immunoreactivity and NADPH diaphorase staining are co-localised in neurons closely associated with the vasculature in rat and human retina.

Nitric oxide synthase (NOS) is widely distributed throughout the nervous system and is found in neurons which produce nitric oxide (NO). In attempting to elucidate the biological roles of NO in neurotransmission, vasodilation, and in neurodegeneration, nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry has been widely used. NADPHd histochemistry and NOS immunoreactivity (NOS-IR) have been assumed to stain the same population of neurons. However, there have been numerous reports which suggest that this may not always be the case, and in all neuronal populations investigated, the coincidence of NOS and NADPHd must be unequivocally demonstrated. We have examined NADPHd histochemistry and NOS immunoreactivity in the human and rat retina and shown that these are 100% co-localised. Further, we have described the morphology of NADPHd and NOS-IR neurons in the human and rat retina and shown a close association of these neurons and their processes to the retinal vasculature. We have taken the NOS-IR to the ultrastructural level and have identified NOS-IR cells in close association with the basal lamina covering endothelial cells and pericytes of the retinal capillaries. We suggest that NO released from these neurons may be involved in the regulation of retinal microcirculation.

Aged↗
PubMed1995

Prenatal development of somatosensory primary afferent connections in the sheep.

A summary is presented of recently published studies on the structural and functional development of cutaneous and muscle receptors and the connections of their afferent fibres in fetal sheep (n = 26) aged between 67 and 143 days gestation (term, 146 days). In these studies it was shown that primary afferent fibres projected to, and made synaptic connections with, dorsal horn neurons in lumbosacral spinal cord by 56-61 days gestation. Sensory innervation of the skin occurred later by about 75 days gestation and, at this age, stimulation of the skin first activated cutaneous afferent fibres and evoked a discharge in dorsal root ganglion and dorsal horn neurons. Muscle stretch first activated muscle spindles and evoked a discharge in dorsal root ganglion cells by about 75 days. Prior to this (by about 67 days) primary afferent fibres had begun to innervate motoneuron pools in the spinal cord, and motor nerves had begun to innervate muscle fibres. Both muscle spindle and cutaneous innervation were relatively simple at mid gestation indicating that the structure of sensory receptors need not be complex in order to generate a response. Neural pathways necessary for reflex activity involving muscle spindles are therefore present and functional by mid gestation as are cutaneous pathways projecting from the skin to the spinal cord.

Afferent Pathways↗
PubMed1994

Cloning and characterisation of the human 5-HT5A serotonin receptor.

The human 5-HT5A serotonin receptor has been cloned. As with the mouse and rat 5-HT5A receptors, the gene consists of two coding exons separated by a large intron. The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor. We have determined the tissue distribution of the receptor by reverse transcriptase-PCR and found expression in all regions of the brain examined with little or no expression in peripheral tissues. The receptor has been transiently expressed in Cos M6 cells and exhibits a pharmacological profile closely resembling the mouse and rat 5-HT5A receptors with high, specific binding for ergotamine and methiothepin.

Amino Acid Sequence↗
PubMed1994

The development of cutaneous afferent pathways in fetal sheep: a structural and functional study.

In this study we have examined the functional and structural development of cutaneous afferent pathways in the fetal sheep hindlimb from 67 to 143 days of gestation. The earliest age at which extracellular discharges could be evoked in dorsal root ganglia and in dorsal horn cells by natural cutaneous stimulation was 75 days. The majority of cells responded to light stroking or indentation of the skin (low threshold) although some cells responded to intense squeezing (high threshold). With increasing gestational age, the majority of cells continued to respond to low threshold stimuli with cells responding to intense mechanical stimuli being recorded less frequently. Dorsal root ganglion cells responding to the cutaneous application of noxious heat (> 45 degrees C) were first observed at 107 days. We have also shown that fibres projecting from dorsal horn cells and presumably entering the spinothalamic tract carry signals at least as far as the mid thoracic spinal cord by 104 days. Ultrastructural studies of the skin revealed bundles of unmyelinated axons located to blood vessels throughout the dermis at 68 days. Innervation of the skin was first observed by silver staining at 75 days when fibres could be seen running along blood vessels in the dermis. With increasing gestational age fibres were seen traversing the dermis to innervate the epidermis as free nerve endings. Wool/hair follicle innervation was first evident at about 100-106 days with only a few follicles being innervated at this age. By 115 days, nerve endings had begun to form circumferential wrappings around follicles and by 134 days lanceolate terminals were observed around the base of the follicles. Biocytin-labelled afferent fibres entered the dorsal horn at 56 days. This initial innervation was sparse but by 76 days there was a marked increase in both the number of afferent fibres entering the dorsal horn and in the extent of their arborisation. Ultrastructural studies revealed that terminals immunoreactive for calcitonin gene-related peptide were present in lamina I as early as 61 days. The period of maximal synaptogenesis and synaptic maturation of this group of terminals appeared to occur between 87-128 days. Therefore the commencement of activation of dorsal horn cells by natural cutaneous stimulation occurs by mid gestation (75 days) in the fetal sheep. This is at the same time or just after peripheral nerves first innervate the skin and about 2 weeks after primary afferent terminals can be identified in the dorsal horn.

Afferent Pathways↗
PubMed1994

The structural and functional development of muscle spindles and their connections in fetal sheep.

In this paper we have studied the structural and functional development of hindlimb muscle receptors and the connections of their afferent fibres in fetal sheep (n = 26) from 67-143 days of gestation (term = 146 days). By recording extracellular discharges in dorsal root ganglia (L7, S1) we have shown that muscle spindle afferents first respond to a ramp-and-hold stretch at mid-gestation (approximately 75 days). Silver-stained preparations of muscle spindles revealed that afferent fibres are just beginning to form annulospiral windings at this age. It therefore appears that the annulospiral formation is not a necessary requirement for the generation of the response. By 87-92 days some receptors had developed a discharge at resting muscle length. Discharges were generally more robust and easier to elicit and static and dynamic components could be identified in the response to stretch. Although static sensitivity was generally low it was more evident than dynamic sensitivity. By 107-115 days it was possible to clearly distinguish between muscle and tendon afferents and to tentatively classify muscle responses as originating from primary or secondary afferent spindle endings. With increasing gestational age there was a progressive increase in the length and complexity of the spindle innervation in parallel with the maturation of functional activity. Biocytin injections into the dorsal root ganglia revealed afferent projections to the motoneuron pools by 67 days. Silver-staining of muscles showed that innervation of extrafusal fibres was also present by this age. We therefore conclude that the neural pathways necessary for reflex activity involving muscle spindles are present and functional from early in gestation and could contribute to early fetal movements.

Afferent Pathways↗
PubMed1994

Morphology of parallel fibres in the cerebellar cortex of the rat: an experimental light and electron microscopic study with biocytin.

Microinjections of biocytin have been made in the granular layer of the rat cerebellar cortex in order to label the axonal projections of a localised population of granule cells. Light microscopic techniques were used to determine the lengths of the parallel fibres and to measure the spacing and size of the fibre varicosities. Fibres were longest in the superficial one-third of the molecular layer, where mean overall length was 4.7 mm, and mean length decreased to 4.2 mm in the lower one-third of the molecular layer. We found no very short fibres but a small population deep in the molecular layer had a branch length of about one-half the average. Mean intervaricosity interval and varicosity size varied with distance from proximal to distal along the fibres. Mean intervaricosity interval was 3.7 microns within 250 microns of the fibre bifurcation points and progressively increased towards the distal ends, where the mean interval was 7.4 microns. Mean varicosity size was 0.82 microns 2 in this proximal region and decreased to 0.47 microns 2 about 1.2 mm distally. Mean intervaricosity interval on the ascending axons of the granule cells was 4.0 microns. Electron microscopy revealed that a high proportion (89%) of the parallel fibre varicosities formed synaptic junctions. The majority of the synapses (91%) were formed on Purkinje cell dendritic spines. Some varicosities also formed simultaneous synaptic contacts or double synapses with two spines. These double synapses occurred more frequently in the proximal region of the fibres (11%) than on the distal ends (2%). The length of the postsynaptic density also differed according to the location of the varicosities and the mean length at the proximal parallel fibre synapses was 0.59 microns compared with 0.38 microns at the distal synapses. It is concluded that a beam or bundle of parallel fibres originating from cells in a focal region of the granular layer will exert a graded synaptic influence on its target Purkinje cells, with the most powerful influence occurring on cells located around the proximal region of the fibres where they bifurcate and the weakest action being exerted on cells located at the distal end of the fibres.

Animals↗
PubMed1994

The ontogeny of [125I]rat-alpha-CGRP binding sites in the spinal cord of sheep: a prenatal and postnatal study.

In this study we describe the ontogeny of [125I]rat-alpha-calcitonin gene-related peptide binding sites in the spinal cord of fetal and postnatal sheep. The density and distribution of binding sites has been compared with the localization of calcitonin gene-related peptide like-immunoreactivity at corresponding stages of development [Nitsos I. and Rees S. (1993) Neuroscience 54, 239-252]. At 68 days of gestation (term = 146 days), the earliest fetal tissue examined, there was no evidence of binding sites in lamina I or the outer regions of lamina II (lamina IIo), although there was a sparse distribution of binding sites in the inner region of lamina II (lamina IIi). By comparison, binding appeared to be more marked in laminae III-V and more concentrated again in laminae VI-X. This distribution essentially remained constant until 124 days, when there appeared to be a marked increase in the density of binding sites throughout the gray matter, particularly in the dorsal horn in the lateral extent of both lamina IIo and IIi as well as in laminae III, V and VI. This increase was also observed in the intermediate zone (lamina VII) and in lamina X. Binding in the ventral horn, which was diffuse until this stage, now became particularly dense in the medial and lateral regions of the horn. From 124 days to one month postnatal, there was no marked change in the density or distribution of binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Magnetic resonance volume flow and jet velocity mapping in aortic coarctation.

OBJECTIVES: Nuclear magnetic resonance (MRI) velocity mapping was used to characterize flow waveforms and to measure volume flow in the ascending and descending thoracic aorta in patients with aortic coarctation and in healthy volunteers. We present the method and discuss the relation between these measurements and aortic narrowing assessed by MRI. Finally, we compare coarctation jet velocity measured by MRI velocity mapping with that obtained from continuous wave Doppler echocardiography. BACKGROUND: The development of a noninvasive imaging method for morphologic visualization of aortic coarctation and for measurement of its impact on blood flow is highly desirable in the preoperative and postoperative management of patients. METHODS: Magnetic resonance imaging phase-shift velocity mapping was used to measure ascending and descending aortic volume flow in 39 patients with aortic coarctation and in 12 healthy volunteers. Magnetic resonance imaging was also used for anatomic and peak jet velocity measurements. The latter were compared with those available from continuous wave Doppler study in 40% of the patients. RESULTS: Whereas ascending aortic volume flow measurement did not show significant differences between the patient and healthy control groups, volume flow curves in the descending aorta did show significant differences between the two groups. Peak volume flow (mean +/- SD) was 10.6 +/- 5.3 liters/min in patients and 19.6 +/- 4.7 liters/min in control subjects (p < 0.001). Time-averaged flow was 2.5 +/- 0.9 liters/min in patients and 3.9 +/- 1.1 liters/min in control subjects (p < 0.05). The descending/ascending aorta flow ratio was 0.47 +/- 0.19 in patients and 0.64 +/- 0.08 in control subjects (p < 0.05). These variables correlate well with the degree of aortic narrowing. Peak coarctation jet velocity measured by MRI velocity mapping is comparable to that obtained from continuous wave Doppler study (r = 0.95). CONCLUSIONS: We established normal ranges for volume flow in the descending aorta and demonstrated abnormalities in patients with aortic coarctation. These abnormalities are likely to be related to resistance to flow imposed by the coarctation and could represent an additional index for monitoring patients before and after intervention.

Adolescent↗
PubMed1993

Development of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the spinal cord of fetal sheep.

In this study we have described the ontogeny of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the sacral spin cord, of fetal sheep (n = 37) from 56 to 140 days of gestation (term = 146 days). A few fine, varicose fibres immunoreactive for calcitonin gene-related peptide were present in Lissauer's tract, the dorsolateral funiculus and in laminae I and V in the dorsal horn of the spinal cord at 56-61 days of gestation. At this age, two groups of intensely staining immunoreactive cells were present in the motoneuron pool in laminae VIII and IX in the ventral horn of the spinal cord. By 77 days, immunoreactive fibres were also present in laminae II and X. With advancing gestational age, an increase in the intensity of staining was observed throughout the cord to term, with the exception of laminae VIII and IX, where a decrease was seen. Intense staining of cells in the motoneuron pool was evident until c. 128 days, after which time staining became very faint. Fine fibers immunoreactive for substance P were present in Lissauer's tract and lamina I of the spinal cord at 56-61 days of gestation. They were also present throughout laminae IV-VI and X as well as throughout the entire ventral horn. Immunoreactive fibres in lamina II were evident by 77 days. The staining increased in density but remained similar in distribution with increasing gestational age to term in the dorsal horn, but decreased markedly in the ventral horn. Cells immunoreactive for substance P were evident from 56 days, particularly on the border of laminae II and III, until late in gestation. Ultrastructural studies showed that axon terminals immunoreactive for calcitonin gene-related peptide and for substance P were present in lamina I by 61 days. Immunoreactivity for glutamate was evident at 83 days in dorsal root fibers and also in lamina I and II, where it was more prominent in cells than in fibres. At all ages examined, the dorsal horn stained more intensely than the ventral horn. Immunoreactivity for glutamate and neuropeptides appeared in the cells and fibres of dorsal root ganglia at 97-100 days. In the skin, immunoreactivity for calcitonin gene-related peptide and substance P was present at 85 days, some time after its appearance in the cord. Fibres immunoreactive for serotonin appeared in lamina I, at the neck of the dorsal horn and in the ventral horn at 83 days of gestation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗