Search PubMed⌕ Search

Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 289 records · Page 16Linked to original sources
PubMed1997

The use of monoclonal antibodies with colloidal gold-labeled probes in postembedding immunoelectron microscopy.

This article focuses on procedures for the use of monoclonal antibodies (MAb) in immunoelectron microscopy (IEM) for the subcellular localization of antigens or to relate function with structure in prokaryotic and eukaryotic cells using postembedding immunoelectron microscopy techniques. The use of MAbs greatly increases the specificity and quality of information when used in combination with gold-labeled probes. Because of its specificity, the reactivity of MAb may be very sensitive to antigenic changes resulting from the process of sample preparation when performing IEM studies. Specific protocols for each particular combination of epitope/MAb must be usually specifically devised, since it is impossible to predict an experimental system that will successfully preserve structures and antigenic determinants for every combination. In this article, we discuss critical technical aspects that usually result in improved resolution when the procedure is used to identify structure in diverse prokaryotic and eukaryotic cells.

Animals↗
PubMed1997

Early prenatal diagnosis of triploidy.

OBJECTIVE: Our purpose was to investigate the role of ultrasonography and maternal serum human chorionic gonadotropin in the early prenatal diagnosis of triploid pregnancies. STUDY DESIGN: A retrospective study on 61,314 consecutive singleton pregnancies examined by ultrasonography at 10 to 14 weeks' gestation was performed to identify the prenatal features of those complicated by triploidy. When available, the serum human chorionic gonadotropin level was measured and ascertained retrospectively. Cases lost to follow-up or for which no karyotype was available were excluded from the final analysis. RESULTS: Overall there were 18 cases of triploidy identified in a population of 58,862 singleton pregnancies, giving a prevalence of 1 in 3270. Fetal defects were observed in 8 (44.4%) of these cases; these included holoprosencephaly (n = 4), exomphalos (n = 3), and posterior fossa cyst (n = 1). In 6 (33.3%) cases the placenta showed molar changes. The fetal crown-rump length was below the 5th percentile in 10 of the 16 (62.5%) cases for which the menstrual age was also available. Fetal nuchal translucency thickness was above the 95th percentile in 12 (66.7%) cases, and the fetal heart rate was below the 5th percentile in 4 of the 13 (30.8%) cases evaluated. The maternal human chorionic gonadotropin level was high in 11 of the 13 (84.6%) cases tested, with similar distribution of the high values in molar and nonmolar triploidies. CONCLUSION: The combination of ultrasonographic examination of the fetoplacental features and measurement of the maternal serum level of human chorionic gonadotropin enables the diagnosis of most cases of triploidy at 10 to 14 weeks' gestation.

Chorionic Gonadotropin↗
PubMed1997

Inter-relationships between angiogenesis and nerve regeneration: a histochemical study.

Whilst increases in capillary number and permeability occurring during nerve regeneration suggest an interaction between regenerating axons and blood vessels, clinical attempts to improve nerve regeneration by augmenting nerve graft vascularisation have produced conflicting results and the nature of their relationship remains obscure. A better understanding of the process might be exploited in the development of a synthetic alternative to the autologous nerve graft and bring an improvement in the clinical results of nerve repair. To clarify this relationship the growth of axons and blood vessels through mats of orientated fibronectin grafted in rat sciatic nerves was assessed morphologically. Fibronectin, which supports axonal regeneration, is initially acellular, ensuring all vascular and neural elements within the graft are newly formed. To follow the progression of the elements, grafts were harvested between 3 and 30 days and stained with antibodies against endothelial cells (RECA-1), Schwann cells (S-100) and axons (a polyclonal or monoclonal panaxonal marker). Dual fluorescence staining combined with double exposure photography allowed the simultaneous visualisation of these elements and the demonstration of their true relative positions. Graft vascularisation came initially from the adjacent muscle bed. A neovascularisation front preceded axonal regeneration, although vessel and axonal orientation appeared similar. Schwann cells and axons extended together, never exceeding the area of vascularisation and appeared most numerous in well vascularised areas containing longitudinally orientated vessels. These results suggest that provision of a well vascularised, longitudinally orientated conduit may enhance nerve regeneration.

Animals↗
PubMed1997

Perception of inflation of a single lung lobe in humans.

We tested whether subjects could detect and localize inflation confined to a single lung lobe. A balloon-sealed catheter was placed into a lobar bronchus of unsedated subjects via fiberoptic bronchoscopy. Topical anesthesia (lidocaine) was used to suppress cough and irritation associated with inflation of the sealing balloon. Small (45-60 ml) or large (100-240 ml) stimulus volumes were insufflated via the catheter. In a forced-choice protocol, subjects were readily able to detect large inflations and correctly identify the side on which the stimulus was given, but small inflations were at the threshold of detection and were not correctly localized. Additional lidocaine applied to the bronchus in two subjects did not degrade detection. Circumstantial evidence suggests that the sensation arose in the lung. We conclude that this technique is feasible for the study of pulmonary perception.

Adult↗
PubMed1997

Bestatin-mediated inhibition of leucine aminopeptidase may hinder HIV infection.

Bestatin, an inhibitor of leucine aminopeptidase (LAPase), significantly decreased HIV infection as reflected by a reduced number of positive immunofluorescent cells, p24 levels, reverse transcriptase activity and the number of proviral copies found in Bestatin-treated cells. Cellular and extracellular LAPase activity in infected cells was higher than the LAPase activity found in uninfected cells. However, cellular and extracellular LAPase activity as well as total protein kinase C activity was lower in Bestatin-treated cells. Conversely, the incubation of human lymphocytic HUT78 cells with LAPase promotes HIV infectivity. The possible role of LAPase in the pathophysiology of HIV was assessed by determining LAPase serum levels in HIV infected patients. LAPase activity levels were three orders of magnitude greater in sera obtained from HIV patients than those detected in sera of uninfected individuals. Although Bestatin reduced HIV infection, a moderate decrease in the reverse transcriptase activity of chronically-infected H9 human T-lymphocytic cells was observed. Based on the higher levels of LAPase present in the serum of HIV patients and on the combined inhibitory effect of Bestatin on LAPase and on protein kinase C activities, we suggest that LAPase may play an important role in the early events of HIV infection such as viral entry.

Anti-HIV Agents↗
PubMed1997

Patient-controlled analgesia compared with nurse-controlled infusion analgesia after heart surgery.

A randomized, controlled clinical trial was conducted on 66 patients undergoing elective cardiac surgery to compare patient-controlled analgesia (PCA) to nurse-controlled analgesia (NCA) with continuous morphine infusion. Hourly assessment of pain (at rest and on movement) using a visual analogue scale (VAS), of respiratory rate, and level of sedation took place for the 24 h following extubation. The incidence of nausea was also recorded. Mean pain scores were calculated, and peak pain and sedation scores, together with lowest respiratory rates, were identified. Morphine consumption was measured at 24 h. No significant differences were found between the groups' scores for pain or sedation. The PCA group had significantly lower respiratory rates (P = 0.02) and a lower incidence of nausea (P = 0.008). The PCA group also consumed significantly more morphine (P = 0.0001). The study suggests a beneficial effect from PCA after cardiac surgery in reducing nausea, compared to NCA. It confirms nurse-controlled infusion analgesia as an effective form of pain relief in an intensive care and high-dependency setting.

Aged↗
PubMed1997

Modelling and simulation of the hand grasping using neural networks.

In this paper we present preliminary results of a study on the use of artificial neural networks to model and simulate the hand grasping. Results of this study will provide a basic understanding of the co-ordination and control of multiple degrees of freedom upper limb prosthetic devices and robotic end effectors when interacting with the environment. We assumed the hand to be a black box with the inputs being the object and simulation time sequence, whilst the output is the grasping postures over time. We trained the network with samples of key postures of the hand grasping several object shapes and sizes. The back-propagation technique was used to update the weights of the network. We found that the neural network is able to reproduce the postures of the hand grasping objects of different shapes and sizes from a single set of neural network weights.

Computer Simulation↗
PubMed1997

Meeting patient expectations in the cancer consultation.

BACKGROUND: Low scores on satisfaction measures may be anticipated when patients' expectations of the doctor are unmet during the cancer consultation. We correlated discrepancies between patient expectations of their ideal doctor and their perceptions of their actual doctor with scores on a validated satisfaction scale to determine whether patients whose expectations were unmet were less satisfied. PATIENTS AND METHODS: The expectations questionnaire used a forced choice method designed to elicit patient preferences for either emotional or informational support from the physician. One hundred and five new patients with heterogeneous cancers, of five medical oncologists at a major teaching hospital were sampled. The patients were mostly female (55%) middle aged (mean age 54.3) and newly diagnosed with cancer (56% within two months prior to consultation). RESULTS: Patients did not demonstrate a clear preference for an emotionally or informationally supportive approach. Seventy percent of patients did not want emotionally negative physicians but most (88.4%) would tolerate negative information. The mean number of exact matches between patients expectations of the ideal and their perceptions of their actual doctor was 3.7 (from a total of six). 5.9% of patients received exactly the doctor they wanted. No significant differences in satisfaction were found between patients whose expectations were met and those whose expectations were not met. CONCLUSIONS: Patient satisfaction with the consultation was independent of patient expectation for informational or emotional support.

Adult↗
PubMed1997

Resolution of invasive central nervous system aspergillosis in a transplant recipient.

Central nervous system (CNS) aspergillosis carries a uniformly poor prognosis in bone marrow transplant recipients. Amphotericin B can be bound to lipid carriers leading to improvement of its therapeutic index. We describe the successful medical management of CNS aspergillosis in an allogeneic bone marrow transplant patient with administration of Amphotericin B Lipid Complex.

Adolescent↗
PubMed1997

Plasma cells in peripheral blood stem cell harvests from patients with multiple myeloma are predominantly polyclonal.

A flow cytometric technique has been developed to detect individual plasma cells in PBSC harvests and to establish light chain restriction as a surrogate marker of their clonality. Plasma cells were identified by high intensity CD38 (CD38++) and cytoplasmic immunoglobulin (cIg) expression. The ratio of cytoplasmic kappa to lambda expression was used to detect light chain restriction. All 25 PBSC harvests studied contained CD38++/cIg plasma cells (mean 0.7%, range 0.03-2%). Harvests from non-myeloma patients also contained plasma cells (mean 0.4%, range 0.01-1.5%). Most of the plasma cells detected in the harvests from myeloma patients were immature (CD45+/CD45++) rather than mature (CD45-). When the total plasma cell population was studied, definite isotype restriction could be detected in only 16% of harvests. Light chain restriction was found in 53% of harvests when the mature plasma cells (CD45-) were analysed but only in 9% of harvests when immature (CD45+/CD45++) plasma cells were analysed. Five percent of patients with myeloma had detectable light chain restriction in peripheral blood CD19+ cells. There was concordance between the ratio of malignant (CD19-/CD56+) to normal (CD19+/CD56-) plasma cells and light chain expression in 86% of patients studied. This study has demonstrated that the majority of plasma cells in PBSC harvests from patients with myeloma are not only immature but are also predominantly polyclonal and that monoclonality is best detected in mature plasma cells.

ADP-ribosyl Cyclase↗
PubMed1997

Expression of bak in S. pombe results in a lethality mediated through interaction with the calnexin homologue Cnx1.

Expression studies in the yeast S. pombe have been utilised to establish the basis for a genetic analysis designed to identify the lethal partners of the pro-apoptotic proteins bak and bax. Bak expression in S. pombe is lethal and this lethality is rescued by co-expression of bcl-2 or bcl-x(L). S. pombe cells expressing bak have a terminal phenotype in which the majority of cells are blocked in the G1 phase of the cell cycle while the remainder of cells, unable to complete M-phase, mis-coordinate the timing of subsequent events in the cell cycle. Although bax expression in S. pombe gives rise to a slow growth phenotype, not a lethality, bax expressing cells display the same cell cycle phenotypes described for bak. Electron microscopy of cells expressing bak reveals a dramatic accumulation of large vesicular structures. A two-hybrid screen designed to identify S. pombe proteins which interact with bak, isolated the S. pombe calnexin homologue cnx1. Genetic analysis demonstrates that the Cnx1 domain which binds to bak in two-hybrid experiments, is necessary for bak lethality in S. pombe. This report identifies a lethal interacting partner for bak and the observations suggest a model for bak mediated lethality which can be tested in higher cells.

Journal Article↗
PubMed1997

Assessment of stature in spinal cord injury.

Assessment of stature has been a neglected part of the medical assessment of individuals with spinal cord injury (SCI). In past studies of pulmonary function in SCI, it has not been stated how stature was assessed in order to calculate predicted pulmonary function. As part of a study of respiratory function in SCI, we examined the accuracy of self-report of stature and whether upper extremity measurements could be used to predict stature in 88 individuals with SCI. Although armspan and four other upper extremity measurements were significant predictors of length, recalled height was the best predictor. On average, for any value of armspan, an individual with complete SCI was 2.3 cm shorter than an individual with incomplete SCI. Individuals with complete SCI also had greater differences between recalled height and measured length compared with individuals with incomplete SCI, and this difference was not due to age or years since injury. It is likely that differences in bone demineralization account for the differences in length comparing individuals with complete and incomplete SCI. The 95 percent confidence intervals for predicted values of length based on armspan or recalled height were too wide for accurate calculation of predicted pulmonary function. In order to classify accurately the extent of pulmonary function abnormality, we suggest that measurements of supine length be made part of the medical assessment of individuals with SCI.

Adult↗
PubMed1997

Chorea-acanthocytosis: genetic linkage to chromosome 9q21.

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration and unusual red-cell morphology (acanthocytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (theta = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.

Acanthocytes↗
PubMed1997

The bcl-2 family of proteins.

The bcl-2 family of proteins play an important role in the control of apoptosis. Family members exist which are either pro- or anti-apoptotic and their activity appears to control a checkpoint between signals from the cell surface and activation of the ICE-family of proteases. Despite having a key role to play in apoptosis, the mechanism of action of these proteins can only, at present, be inferred due to the lack of understanding about their biological activity. However, some general principles can be gleaned from the large body of published work to suggest what are likely to be the best directions for future endeavour.

Amino Acid Sequence↗
PubMed1997

Measuring quality of life: a new and practical survey instrument.

Despite increasing recognition of the importance of measuring the quality of life (QOL) of people with severe mental illness, such assessments are seldom carried out because of the lack of an efficient, easy-to-use, and valid measurement instrument. To facilitate the gathering of QOL information from clients in evaluation, program improvement, or other efforts, the authors present a new short (24-item) self-administered questionnaire called the Quality of Life Questionnaire (QLQ). The questionnaire assesses subjective QOL in seven areas. Evidence for the reliability and validity of the QLQ is based on data gathered from 971 clients with serious mental illness who were receiving publicly funded mental health services at the time of the study. The results of a confirmatory factor analysis using a random split-half procedure indicated that a seven-factor solution fit the data well. Scores on the QLQ also correlated significantly with the client's functioning and satisfaction with services, providing support for the validity of the QLQ. The advantages of the QLQ over existing measures include low-cost administration and some superior psychometric properties.

Adult↗
PubMed1997

Improving the design of muscle relaxant studies. Stabilization period and tetanic recruitment.

BACKGROUND: The results from studies of muscle relaxants show wide variations among institutions. The authors hypothesized that some of this variability could be explained by differences in duration of nerve stimulation before drug administration (stabilization period). METHODS: Train-of-four stimulation was applied every 12 s to both ulnar nerves and adductor pollicis twitch tension was measured in anesthetized participants given 30 micrograms/kg vecuronium. In phase 1, the stabilization period was > 30 min for both extremities. In phase 2-4, stabilization period was 20 min for one extremity and 2 min for the other. In addition, in phase 3, a 2-s 50-Hz tetanus initiated the 2-min stimulation period; in phase 4, duration of tetanus was 5 s. Twitch recovery was recorded until stable for more than 15 min. Time to 25% recovery (clinical duration) was calculated based on two indices: predrug and final (recovery) twitch tension. Values for onset and clinical duration were compared by paired parametric and nonparametric tests. RESULTS: In phase 1, predrug and recovery twitch tension were similar in each extremity, and onset and clinical duration did not differ between extremities, permitting paired comparisons in remaining studies. In phase 2, onset was more rapid with 20-min of prestimulation. With 20-min prestimulation, predrug and recovery twitch tension were similar; with 2-min prestimulation, recovery twitch tension exceeded predrug values. When referenced to predrug twitch tension, clinical duration was shorter with 2-min, that with 20-min prestimulation. Initiating stimulation with 2-s or 5-s 50-Hz tetani (phases 3, 4) abolished differences between extremities in onset and recovery. CONCLUSIONS: With only train-of-four stimulation (no tetani), onset and clinical duration vary with duration of prestimulation, suggesting that a brief period of predrug stimulation is inadequate. However, lengthy prestimulation may be impractical in clinical studies. Tetanic stimulation for 2 or 5 s obviates the need for prolonged stabilization during studies of muscle relaxants.

Adult↗
PubMed1997

Pharmacodynamic modeling of vecuronium-induced twitch depression. Rapid plasma-effect site equilibration explains faster onset at resistant laryngeal muscles than at the adductor pollicis.

BACKGROUND: After bolus doses of nondepolarizing muscle relaxants, the adductor pollicis recovers from paralysis more slowly than the diaphragm and the laryngeal adductors, suggesting that the adductor pollicis is more sensitive than the respiratory muscles to effects of those drugs. In contrast, during onset, the respiratory muscles are paralyzed more rapidly than the adductor pollicis, suggesting that the respiratory muscles are more sensitive than the adductor pollicis. To reconcile these apparently conflicting findings, we determined vecuronium's pharmacokinetics and its pharmacodynamics at both the adductor pollicis and the laryngeal adductors. METHODS: Six volunteers were studied on two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Vecuronium (15-60 micrograms/kg) was given and arterial plasma samples were obtained from 0.5-60 min. Vecuronium doses differed by twofold on the two occasions. A pharmacokinetic model accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine relative sensitivities and rates of equilibration between plasma and effect site concentrations. RESULTS: The steady-state plasma concentration depressing laryngeal adductor twitch tension by 50% was approximately 1.5 times larger than that for the adductor pollicis. The equilibration rate constant between plasma and laryngeal adductor concentrations was about 1.5 faster than that between plasma and adductor pollicis concentrations. The Hill factor (gamma) that describes the steepness of the laryngeal adductor concentration-effect relation was approximately 0.6 times that of the adductor pollicis. CONCLUSIONS: More rapid equilibration between plasma and laryngeal adductor vecuronium concentrations explains why onset is more rapid at the laryngeal adductors than at the adductor pollicis. During recovery, both rapid equilibration and lesser sensitivity of the laryngeal adductors contribute to earlier recovery.

Adult↗