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Biomedical subjects

R J Brown

Publications and source records attributed to R J Brown.

At least 37 records · Page 2Linked to original sources
PubMed2000

Psychiatric outcome after temporal lobectomy: a predictive study.

PURPOSE: The occurrence of psychiatric symptoms after temporal lobectomy is well documented. The aim of the present study was to identify preoperative factors that predict postoperative psychiatric outcome. METHODS: We studied the case notes of 121 patients (from an initial sample of 167) who underwent temporal lobectomy at the National Hospital of Neurology and Neurosurgery, Queen Square, London, between 1988 and 1997. Data concerning gender, laterality of lesion, pathology, seizure outcome, psychiatric history, psychiatric outcome, resection volume, telemetry, and MRI scans were systematically collected. Factors that predict the occurrence of postoperative psychiatric symptomatology were investigated using correlational, chi(2), and logistic regression techniques. RESULTS: Poor postoperative psychiatric outcome in general was positively associated with preoperative bilateral independent spike discharges at telemetry. The size of surgical resection was positively correlated with the occurrence of postoperative emotional lability. The laterality of the epileptogenic lesion was not associated with a poor psychiatric outcome. Developmental lesions were associated with a good psychiatric outcome at a marginally significant level. Patients with a preoperative psychiatric history and de novo psychiatric symptomatology had a poorer surgical outcome in terms of seizure frequency, also at a marginally significant level. A significant correlation was found between a past psychiatric history and seizure outcome. CONCLUSIONS: We identified a high frequency of psychiatric symptoms both before and after temporal lobectomy, demonstrating that it is not a benign procedure from the point of view of psychopathology. Our results show that there are certain predictive factors that may help identify patients most at risk for postoperative psychiatric disorders.

Adult↗
PubMed2000

The intracellular target for the antiresorptive aminobisphosphonate drugs in Dictyostelium discoideum is the enzyme farnesyl diphosphate synthase.

Aminobisphosphonate (aBP) drugs inhibit osteoclast-mediated bone resorption and also growth of amoebas of Dictyostelium discoideum apparently by interaction with the same intracellular target. Identification of the target in Dictyostelium therefore could also identify the target in osteoclasts. The aBPs (100 microM alendronate and 30 microM YM-175) inhibited conversion of [14C]mevalonate into sterols by cultures of Dictyostelium amoebas. One of three enzymes (isopentenyl diphosphate [IDP] isomerase, farnesyl diphosphate [FDP] synthase, and squalene synthase) appeared to be the target for this inhibition because conversion of [14C]IDP into squalene, the immediate precursor for sterol biosynthesis, was inhibited in extracts of wild-type amoebas by alendronate (IC50 = 75 nM) or risedronate (IC50 = 30 nM) whereas, when the extract had been prepared from amoebas of strains selected for having partial resistance to the growth-inhibitory effects of alendronate (strain MR102) or risedronate (strain RB101), the values of IC50 were increased to 700 nM for alendronate (MR102 extract) or 130 nM for risedronate (RB101 extract). Neither IDP isomerase nor squalene synthase was inhibited significantly by alendronate or risedronate but both of these aBP drugs, and all others tested, inhibited FDP synthase. Determination of the nucleotide sequences of complementary DNAs (cDNAs) encoding FDP synthase in the wild-type and aBP-resistant strains of Dictyostelium indicated that there had been no changes in the amino acid sequence of the enzyme in the mutant strains. However, both mutant strains overproduce FDP synthase. It is concluded that FDP synthase is the intracellular target for the aBP drugs.

Alendronate↗
PubMed1999

Identification of a mammalian brain sulfate transporter.

Sulfate is an essential anion involved in many biosynthetic and pharmacological reactions. Sulfate is an important constituent of myelin membranes in the brain; however, very little is known as to how sulfate enters brain cells. In this study, our aim was to determine whether the mammalian brain possesses a sulfate transporter. Injection of rat brain poly A(+) RNA into Xenopus oocytes led to an induction of Na(+)-independent sulfate transport, which was inhibited by oxalate, probenecid, phenol red, thiosulfate and DIDS. Hybrid depletion using sat-1 antisense oligodeoxyribonucleotides led to a complete inhibition of brain mRNA-induced sulfate transport in Xenopus oocytes, suggesting the presence of a functional sat-1 transcript in the brain. By RT-PCR, sat-1 mRNA was detected throughout the rat brain and in situ hybridisation showed highest sat-1 expression in the hippocampus and cerebellum. This is the first study to identify and characterise a functional mammalian brain sulfate transporter.

Animals↗
PubMed1999

Development of rivalry and dichoptic masking in human infants.

PURPOSE: To examine the development of rivalry, dichoptic masking, and binocular interactions in infants more than 5 months of age using the visual evoked potential (VEP). METHODS: VEPs were recorded in 35 infants between 5 and 15 months of age and 23 adults between 13 and 59 years of age. Counterphasing, sinusoidal, 1 cycle/deg gratings were presented dichoptically. Responses from each eye were isolated by "tagging" each half-image with a different temporal frequency (5 or 7.5 Hz). Observers were presented with fixed 80% contrast gratings in each eye in experiment 1. Rivalry was detected on the basis of a negative correlation between the simultaneously measured response amplitudes at the second harmonics of the two eye-tagging frequencies. In a second analysis of the same data, response amplitudes recorded under dichoptic viewing conditions were compared to those obtained in a monocular control condition (dichoptic masking). In experiment 2, a 40% fixed-contrast grating was presented to one eye, whereas the other eye viewed a grating that was swept in contrast from 1% to 67%. Dichoptic masking was measured as the reduction in the fixed-grating response caused by the variable contrast grating. RESULTS: Experiment 1: although adults showed evidence of VEP amplitude alternations between the eyes for cross-oriented half-images (physiological rivalry), infants did not. This immature response to rivalrous stimuli occurred despite the presence of responses at nonlinear combination frequencies recorded with gratings of the same orientation in each eye, a definitive indication of binocular interaction. In addition, both iso- and cross-oriented half-images produced less dichoptic masking in infants than in adults in this experiment. Experiment 2: dichoptic masking in the infants was equivalent to that seen in adults with parallel gratings in the two eyes; however, masking with cross-oriented configurations was approximately five times weaker in the infants relative to the adults. CONCLUSIONS: The authors have identified a set of stimulus conditions under which infants between 5 and 15 months of age fail to demonstrate physiological rivalry despite the presence of binocular interactions. The observed lack of binocular rivalry may be the result of a specific immaturity in dichoptic, cross-orientation suppression.

Adolescent↗
PubMed1998

Uniform-penalty inversion of multiexponential decay data.

NMR relaxation data and those from many other physical measurements are sums of exponentially decaying components, combined with some unavoidable measurement noise. When decay data are inverted in order to give quasi-continuous distributions of relaxation times, some smoothing of the distributions is normally implemented to avoid excess variation. When the same distribution has a sharp peak and a much broader peak or a "tail," as for many porous media saturated with liquids, an inversion program using a fixed smoothing coefficient may broaden the sharp peak and/or break the wide peak or tail into several separate peaks, even if the coefficient is adaptively chosen in accord with the noise level of the data. We deal with this problem by using variable smoothing, determined by iterative feedback in such a way that the smoothing penalty is roughly constant. This uniform-penalty (UP) smoothing can give sharp lines, not broadened more than is consistent with the noise, and in the same distribution it can show a tail decades long without breaking it up into several peaks. The noise level must be known approximately, but it can be determined more than adequately by a preliminary inversion. The same iterative procedure is used to implement constraints such as non-negative (NN) or monotonic-from-peak (MT). The significance of an additional resolved peak may be tested by finding the cost of using MT to force a unimodal solution. A bimodal constraint can be applied. Decay data representing sharp lines in contact with broad features can require substantial computing time and some controls to stabilize the iterative sequence. However, UP can be made to function smoothly for a very wide variety of decay curves, which can be processed without adjustment of parameters, including the dimensionless smoothing parameters. Extensive testing has been done with artificial data. Examples are shown for artificial data, biological tissues, ceramic technology, and sandstones. Expressions are given relating noise level to line width and for significance of increase or decrease in error of fit.

Algorithms↗
PubMed1998

Development of directional motion symmetry in the monocular visually evoked potential of infant monkeys.

Motion processing in humans and monkeys exhibit a directional asymmetry during infancy which is not present in adults except following abnormal visual rearing conditions. To characterize the time course for maturation of a symmetric response, we measured the monocular visually evoked potential (MVEP) response to 0.26 c/deg gratings oscillating horizontally at 6 Hz in 13 infant rhesus monkeys between 1 and 52 weeks of age. An asymmetric (F1) and a symmetric (F2) frequency component were extracted from the MVEP using Fourier analysis. At early ages the asymmetric F1 component measured from the two eyes exhibited a 180 deg interocular phase shift, demonstrating that there was a directional bias in opposite directions between the left and right eyes. Although our methods could not determine whether the bias was in the nasal or temporal direction, our results would be consistent with a nasal bias, as has been observed in previous motion studies. Magnitude of the asymmetry was quantified in the form of an asymmetry index, F1/(F1 + F2). Based on developmental changes in the asymmetry index, and phase and amplitudes of F1 and F2, we conclude that the MVEP loses its directional asymmetry at 6 weeks of age. The development of directional motion symmetry observed in monkeys over the first 6 weeks is similar to that observed in humans over the first 5 months.

Aging↗
PubMed1998

Differential effects of aminosubstituted analogs of hydroxy bisphosphonates on the growth of Dictyostelium discoideum.

Replacing the hydroxyl group in the bone-binding site of three clinically useful bisphosphonates (etidronate, pamidronate, and olpadronate) by an amino group resulted in great differences in their antiresorptive potencies in vitro. In the present study, this is also shown in vivo in mice treated with the six bisphosphonates at doses of up to 16 microM/kg/day for 12 days. Because binding to bone mineral is nearly the same for all tested bisphosphonates, these findings suggest that the aminosubstitution affects the cellular action of the bisphosphonates. This was tested in the cellular slime mould Dictyostelium discoideum in which cellular effects of bisphosphonates can be examined independently of binding to bone mineral. Etidronate and its aminosubstituted analog were equipotent in inhibiting amebal growth, while pamidronate was somewhat more potent than its analog. Whereas olpadronate was a potent inhibitor of axenic growth of Dictyostelium amebae, the aminosubstitution reduced its potency drastically (IC50 12 microM and 700 microM, respectively). The similarities between the inhibitory effects of the bisphosphonates tested on bone resorption in vitro and in vivo and on the growth of Dictyostelium amebae confirm that the differences in antiresorptive potencies found reflect differences in cellular effects and suggest that bisphosphonates may bind to more than one intracellular target.

Amines↗
PubMed1998

Echinococcal disease and the provision of humanitarian surgical aid in Bosnia.

The Canadian Armed Forced have been deployed to the republics of the former Yugoslavia since 1992 as part of the United Nations Protection Force and the NATO-led Implementation Force. Most of the combat arms units have been supported by small, self-contained surgical teams for essential surgery. Considerable benefit is gained by cooperating with civilian surgeons. The experience of treating five patients with complicated hydatid disease endemic to the area is examined. Treatment of these patients requires performing major surgical procedures under austere conditions and must be undertaken with care. Careful selection and communication with the surgical nursing team and civilian surgeons is essential. Well selected cases can also pay tremendous dividends in terms of maintaining the skills of personnel who must be prepared for any emergency in addition to providing vital surgical assistance to these patients.

Adolescent↗
PubMed1998

Abdominal aortic aneurysm repair via percutaneous endovascular stenting in the swine model.

Abdominal aortic aneurysms (AAAs) are the 13th leading cause of death in the United States. Endovascular stent grafts are currently being investigated in clinical trials as an alternative method for treatment of AAA. Twelve pigs underwent creation of AAA using the abdominus rectus fascia. Postoperatively, all 12 animals underwent angiography, which demonstrated turbulent flow within the created aneurysms. Four of the animals were not stented and served as controls. Eight animals underwent subsequent percutaneous placement of a covered endovascular stent via a right femoral sheath, and the stents were deployed between the renal arteries and the aortic bifurcation. The animals were maintained for 120 days before sacrifice and necropsy. Unstented animals (4) died within 6 days, 3 from rupture. Eight animals underwent endovascular stenting: 5 survived without complications, 3 deaths within 2 days were related to technical complications. The 5 surviving animals were sacrificed at 120 days, and necropsy was conducted with in situ dissections of the aorta and intact stent: 3 experimental animals had correct anatomic positioning of the stent, and 2 had inexact stent placement but survived 120 days with AAA thrombosis. Treatment of AAA in this swine model has been demonstrated via placement of a percutaneous covered stent.

Animals↗
PubMed1997

A method for investigating binocular rivalry in real-time with the steady-state VEP.

Under conditions in which the visual system cannot reconcile dissimilar images from the two eyes, perception typically alternates between the two half-images-a process known as binocular rivalry. We report a real-time, steady-state VEP method that is a sensitive detector of the continuous alternations in perceptual dominance across the eyes. This method works by labelling each half-image with a slightly different temporal frequency so that the record generated by each can be recovered from the EEG by spectrum analysis. In this way, one can track the "waxing" and "waning" of the VEP amplitudes for each eye simultaneously during spontaneous rivalry, permitting an analysis of the relative physiological dominance of each eye in real-time. Such alternations were clearly observed in the VEP amplitudes generated by each half-image during rivalry (the amplitudes for the two eyes correlated negatively). In contrast, VEP amplitudes for the two eyes varied either synchronously or randomly when the half-images were allowed to fuse. The instances of physiological dominance of each eye as evidenced by the VEP correlated well with the subjects' report of perceptual dominance. This purely electrophysiological method appears to be suitable for measuring rivalry in non-verbal human or animal subjects, as it does not require active participation from them.

Adolescent↗
PubMed1997

nNOS and Ca2+ influx in rat pancreatic acinar and submandibular salivary gland cells.

Regulation of agonist-activated Ca2+ influx by the NOS pathway through generation of cGMP is being found in an increasing number of cell types. In the present work, we examined the role of the NOS pathway in agonist-evoked [Ca2+]i oscillations and attempted to identify the NOS isoform most likely to regulate Ca2+ influx. For this, we first show that two Ca(2+)-mobilizing agonists acting on pancreatic acinar cells, bombesin (BS) and the cholecystokinin analog CCK-JMV-180 (CCKJ), evokes different type of [Ca2+]i oscillations. The BS-evoked [Ca2+]i oscillations rapidly became acutely dependent on the presence of extracellular Ca2+, whereas the CCKJ-evoked oscillations continue for long periods of time in the absence of Ca2+ influx. This differential behavior allowed us to isolate Ca2+ influx and study its regulation while controlling for non specific effects on all other Ca2+ transporting events involved in generating [Ca2+]i oscillations. Inhibitors of selective steps in the NOS pathway inhibited agonist-induced cGMP production. The inhibitors were then used to show that scavenging NO with reduced hemoglobin, inhibition of guanylyl cyclase with 1H-[1,2,4] oxadiazolo[4,3-a] quinoxaline-1-one (ODQ) and inhibition of protein kinase G with Rp-8-pCPT-cGMPS inhibited [Ca2+]i oscillations evoked by BS but not those evoked by CCKJ. These findings were extended to duct and acinar cells of the SMG. In these cells, Ca(2+)-mobilizing agonists stimulate large Ca2+ influx, which was inhibited by all inhibitors of the NOS pathway. Western blot analysis and immunolocalization revealed that the cells did not express iNOS, eNOS was expressed only in blood vessels and capillaries whereas nNOS was expressed at high levels next to the plasma membrane of all cells. Accordingly, the nNOS inhibitor 7-nitroindazole (7-NI) inhibited BS- but not CCKJ-evoked [Ca2+]i oscillations and Ca2+ influx into SMG acinar and duct cells. Thus, together, our findings favor nNOS as the isoform activated by the Ca2+ released from internal stores to generate cGMP and regulate Ca2+ influx.

Animals↗
PubMed1997

Genetic differentiation between and within strains of the saw-toothed grain beetle, Oryzaephilus surinamensis (Coleoptera: Silvanidae) at RAPD loci.

Nine strains of Oryzaephilus surinamensis have been kept in laboratory culture for periods ranging from 5 to 30 years (30-180 generations). Two RAPD primers provided sufficient information to separate the strains reliably and unambiguously. The strains are maintained at a population size of 200 breeding adults. The marked divergence between strains is consistent with the small population size, which for the older strains, according to population genetics theory, implies that roughly half the original genetic variation should now be lost from within strains. However, there is no indication that the older strains have less inter-strain variation. The results demonstrate RAPD loci can reliably detect population subdivision, which in field populations of pest species is of fundamental importance in understanding the population genetics of insecticide resistance.

Animals↗
PubMed1996

Bisphosphonates are incorporated into adenine nucleotides by human aminoacyl-tRNA synthetase enzymes.

Bisphosphonates are synthetic pyrophosphate analogues and are therapeutic inhibitors of bone resorption, although their exact mechanisms of action are unclear. Some bisphosphonates can be metabolised into non-hydrolysable ATP analogues by Dictyostelium discoideum amoebae, in a back-reaction catalysed by several Class II aminoacyl-tRNA synthetases. We have found that the same enzymes in cell-free extracts of several human cell lines are also capable of metabolising in vitro the same bisphosphonates that are metabolised by Dictyostelium. These results indicate that human cells, following drug internalisation, should be capable of metabolising certain bisphosphonates. The toxic effects of these bisphosphonates towards bone-resorbing osteoclasts may therefore be due to accumulation of non-hydrolysable ATP analogues or inhibition of aminoacyl-tRNA synthetase enzymes.

Adenine Nucleotides↗
PubMed1996

The effect of diffusion and susceptibility differences on T2 measurements for fluids in porous media and biological tissues.

A number of features of T2 measurements for fluids in porous media have shown behavior contrary to that suggested by intuition developed in other areas. For porous media with relatively uniform pore spaces the following have been observed, in each case for certain ranges only of Xv (susceptibility difference times frequency), D (diffusion coefficient), a (a pore dimension), porespace shape and distribution, echo-time t for single echoes and half-echo-spacing tau for CPMG): (1) In S(t) for FID (free induction decay, S for signal) with constant slope after an initial period of increasing slope; (2) In Ss(t) for single (subscript s) echoes linear (instead of cubic) in t after an initial period; (3) for CPMG R(tau) = 1/T2(tau) - 1/T2(tau-->0) linear in tau over a substantial range; (4) slope of R(tau) independent of D and alpha for this range; (5) slope R(s) of In Ss(t) independent of D and a, and (6) R(s)(t) and R(tau) at long times linear (instead of quadratic) in Xv. These features appear to be compatible with the assumption of a truncated Cauchy-Lorentz distribution of the local magnetic fields due to susceptibility differences. The statistics of repeated sampling of local fields in different parts of the porespace during diffusion lead to a suppression, after a short time, of the effects of diffusion on the FID decay rate and the single-echo decay rate over significant ranges of the parameters. Data are presented to extend the range of parameters studied previously.

Dental Porcelain↗
PubMed1996

Developments in core analysis by NMR measurements.

For a large suite of consolidated sandstone samples low in shale content we have measured the permeability k, irreducible water saturation Swi, porosity phi, electrical-resistivity formation factor F, porosity by NMR, geometric-mean relaxation times T1g, and stretched-exponential relaxation times T1s. We find that T1g (or T1s) is the decisive parameter for the estimation of k or Swi of porous sandstones by other than direct measurements of these quantities. The additional use of phi or F brings appreciable, but not decisive, improvement. We show isovalue maps of the error factor delta, which show substantial regions of near-minimum values of delta and show basic compatibility of our estimators for permeability with different published estimators. The exponents of T1g (or T1s) in our power-law estimators and those of various published estimators for k are not very far from 2.0 if either or both of phi and F are also used in the estimators.

Magnetic Resonance Spectroscopy↗