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Biomedical subjects

L Noble

Publications and source records attributed to L Noble.

At least 19 recordsLinked to original sources
PubMed2004

Communication skills training in postgraduate medicine: the development of a new course.

It has long been accepted that communication is of central importance in healthcare, and a core aspect of clinical competence. Many educational institutions and Royal Colleges now reflect this and consider communication skills a priority in postgraduate examination. The new examination "Practical Assessment of Clinical and Examination Skills" has replaced the Royal College of Physicians MRCP part 2 clinical and oral examination. This examination now consists of five clinical stations, two of which focus on communication skills. A short course for postgraduate trainees has been designed to address the communication skills requirements of the part 2 clinical examination. The aims, development, and content of the course are described. Emphasis is placed on candidates practising skills with patients and receiving feedback during the course. Evidence suggests that practice with feedback is an essential ingredient of communication skills courses, and is more effective than other methods such as observing experts or video examples, or simply discussing issues in communication. Results of a preliminary evaluation indicate that the course was perceived as valuable by candidates and that the aims, format, and content were appropriate. Although the preliminary evaluation was largely positive, it could be argued that the acid test of the effectiveness of a course is an objective evaluation of skills, observed before and after the course, a development that is being considered for future evaluation of the course. Recommendations for applying this type of training to postgraduate trainees in any branch of medicine are given.

Clinical Competence↗
PubMed2001

The effects of intrauterine cocaine exposure on the respiratory status of the very low birth weight infant.

OBJECTIVES: This study examined the effects of intrauterine cocaine exposure on very low birth weight infants with respect to their surfactant requirement and need for ventilatory support. STUDY DESIGN: A retrospective cohort study was conducted on infants with birth weight between 750 and 1500 g admitted to the neonatal intensive care unit between January 1992 and January 1995. RESULTS: Of the 149 infants studied, 48 infants were exposed only to cocaine and 101 infants had no drug exposure. There were no significant differences between the two groups for gestational age, sex, abruptio placenta, prolonged rupture of membranes, and antenatal steroid usage. The cocaine-exposed group had a significantly greater birth weight (1190 vs. 1109, p<0.02), less prenatal care (48% vs. 14%, p<0.00007), older maternal age (30 vs. 24, p<0.00002), more black race (79% vs. 57%, p<0.01), and more rapid plasma reagin (RPR) positivity (25% vs. 2%, p<0.00006). There were no significant differences in median APGAR scores, or incidence of necrotizing enterocolitis, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and bronchopulmonary dysplasia (BPD) between the two groups. Cocaine-exposed infants received surfactant treatment less often (73% vs. 48%, p<0.0035), received fewer mean doses of surfactant (0.4 vs. 10.0, p<0.0014), and were intubated less frequently (44% vs. 65%, p<0.012). There was no significant difference between groups for intubation at 24 and 48 hours and for the development of bronchopulmonary dysplasia. CONCLUSION: Perinatal cocaine exposure appears to have some significant short-term effects on the need for surfactant replacement therapy and need for initial intubation in respiratory distress syndrome (RDS) but no overall effect on the development of BPD.

Bronchopulmonary Dysplasia↗
PubMed1999

A non-covalently cross-linked chitosan based hydrogel.

Hydrogels are normally formed by the covalent cross-linking of linear polymers. In the case of chitosan based hydrogels this cross-linking is often achieved with glutaraldehyde, glyoxal or other reactive cross-linking agents. Such hydrogel materials have limited biocompatibility and biodegradability. However by the attachment of hydrophobic palmitoyl groups to glycol chitosan, a water soluble chitosan derivative, we have produced a version of the amphiphilic vesicle forming polymer-palmitoyl glycol chitosan (Uchegbu et al., 1998, J Pharm Pharmacol 58, 453-458). The level of palmitoylation in this variant of the polymer (GCP11), as determined by proton neutron magnetic resonance spectroscopy, is 19.62+/-2.42% (n=4). GCP11 has been used to prepare soft, slowly eroding hydrogels suitable for drug delivery by simply freeze-drying an aqueous dispersion of the polymer. Non-covalent cross-linking to form the gel matrix is achieved by the hydrophobic interactions of the palmitoyl groups. The resulting material, as examined by scanning electron microscopy, is porous and may be hydrated to up to 20x its weight in aqueous media without any appreciable change in volume-transforming from an opaque to a translucent solid. The slow erosion of this material in aqueous environments gives a biodegradable and ultimately more biocompatible material than covalently cross-linked hydrogels. Unlike most chitosan-based gels, the gel is hydrated to 20x its weight at alkaline pH but only 10x its weight at neutral and acid pH. This is as a result of the gradual erosion of the gel at lower pH values. Hydration is also reduced from 20x the dry gel weight in water to 10x the dry gel weight in the presence of dissolved salts such as sodium chloride. GCP11 hydrogels have been loaded to 0.1% w/w with a model fluorophore, rhodamine B, by simply freeze-drying an aqueous dispersion of GCP11 in the presence of a solution of rhodamine B dissolved in either water or phosphate buffered saline (PBS, pH=7.4). The release of this model fluorophore was retarded by between 8 and 12% when PBS was contained in the gel in accordance with the hydration profiles. Rhodamine B release was also reduced by between 13 and 25% in the presence of acid as a result of the reduced solubility of rhodamine B at acid pH.

Buffers↗
PubMed1999

The effect of tennis racket string vibration dampers on racket handle vibrations and discomfort following impacts.

In this study, we evaluated the effect of the use of tennis racket string vibration dampers on racket handle vibrations, and perceptions of hand and arm discomfort experienced by tennis players owing to stationary racket impacts. Twenty tennis players (10 males, 10 females) aged 18-29 years volunteered for the study. Two different racket models were impacted at the geometric centre of the racket face and 100 mm distal to the centre both with and without string vibration dampers in place. The participants could neither see nor hear the impacts, and they indicated their discomfort immediately after each impact using a visual analogue scale. An analysis of variance (2 x 2 x 2 factorial) was performed on the scaled discomfort ratings with the factors damping condition, racket type and impact location. No significant differences in discomfort ratings between damped and undamped impacts or between the two racket types were found. Also, central impacts were found to be more comfortable than impacts 100 mm distal to the centre (P< 0.05). There were no significant interaction effects. Vibration traces from an accelerometer mounted on the racket handle revealed that string vibration dampers quickly absorbed high-frequency string vibration without attenuating the lower-frequency frame vibration. In conclusion, we found no evidence to support the contention that string vibration dampers reduce hand and arm impact discomfort.

Adolescent↗
PubMed1999

Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis.

Estrogen is the most important known factor that stimulates the growth of endometriosis. Estrogen delivery to endometriotic implants was classically viewed to be only via the circulating blood in an endocrine fashion. We recently uncovered an autocrine positive feedback mechanism, which favored the continuous production of estrogen and prostaglandin (PG)E2 in the endometriotic stromal cells. The enzyme, aromatase, is aberrantly expressed in endometriotic stromal cells and catalyzes the conversion of C19 steroids to estrogens, which then stimulate cyclooxygenase-2 to increase the levels of PGE2. PGE2, in turn, is a potent inducer of aromatase activity in endometriotic stromal cells. Aromatase is not expressed in the eutopic endometrium. Aromatase expression in endometriosis and its inhibition in eutopic endometrium are controlled by the competitive binding of a stimulatory transcription factor, steroidogenic factor-1, and an inhibitory factor, chicken ovalbumin upstream promoter-transcription factor to a regulatory element in the aromatase P450 gene promoter. In addition, we find that endometriotic tissue is deficient in 17beta-hydroxysteroid dehydrogenase type 2, which is normally expressed in eutopic endometrial glandular cells and inactivates estradiol-17beta to estrone. This deficiency is another aberration that favors higher levels of estradiol-17beta in endometriotic tissues in comparison with the eutopic endometrium. The clinical relevance of local aromatase expression in endometriosis was exemplified by the successful treatment of an unusually aggressive form of recurrent endometriosis in a postmenopausal woman using an aromatase inhibitor.

Aromatase↗
PubMed1995

Dysregulation of HOX11 by chromosome translocations in T-cell acute lymphoblastic leukemia: a paradigm for homeobox gene involvement in human cancer.

The translocation t(10;14)(q24;q11) is observed in the course of routine cancer cytogenetic studies in 5-10% of patients with T-cell acute lymphoblastic leukemia (ALL). Recent molecular dissections of t(10;14) translocations support the hypothesis that these relatively gross chromosomal mutations represent key genetic steps in neoplastic transformation. The genes consistently involved are the T-cell receptor (TCR) delta-chain gene in 14q11 and a human homeobox-containing gene in 10q24, HOX11, initially identified through cloning of t(10;14) translocations. Like other homeoproteins, HOX11 binds DNA with sequence specificity and is likely to be a transcription factor, controlling the expression of developmentally important genes. The t(10;14) translocations arise as a result of aberrant physiological recombinational events that occur at early stages of T-cell development, probably during failed attempts at TCR gene rearrangement. The net result of the aberrant genetic recombinations is inappropriate expression of HOX11 in individual T-cells that acquire the mutation. Tlx-1, the murine homolog of HOX11, is expressed embryologically in the developing spleen and in structures derived from cranial neural crest cells and migratory paraxial mesoderm. Mice homozygously deleted for Tlx-1 are asplenic. Thus, HOX11 may be one of the first examples in mammals of a "master gene" acting as a regulatory switch controlling a downstream program of organ-specific cell growth and proliferation. Preliminary tumorigenicity assays suggest that HOX11 expression in hematopoietic cells most likely plays an immortalization role in neoplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Genes, Homeobox↗
PubMed1994

A comparison of meconium, maternal urine and neonatal urine for detection of maternal drug use during pregnancy.

A large scale drug screening study was done to determine the prevalence of drug use in a large metropolitan, obstetric population. Meconium and first voided urine, as well as maternal urine were collected from 423 consecutive deliveries. Urine samples and methanolic extracts of meconium were initially screened by Enzyme Multiplied Immunoassay Technique (EMIT) and then confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Analysis of cocaine metabolite as benzoylecogonine, cannabinoid as carboxy-THC, codeine, morphine and methadone were included in the study. The positive rate for benzoylecgonine was virtually identical for meconium, maternal urine and neonatal urine (12%). Analysis of meconium was found to be more reliable than analysis of maternal or neonatal urine for the detection of benzoylecgonine. Meconium did not appear to offer an advantage over maternal or neonatal urine for detection of cannabinoid, codeine, morphine, or methadone.

Adult↗
PubMed1992

Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine.

The non-competitive NMDA receptor antagonists, PCP (phencyclidine), MK801, and ketamine produce psychosis in humans and abnormal vacuoles in posterior cingulate and retrosplenial rat cortical neurons. We show that PCP (> or = 5 mg/kg), MK801 (> or = 0.1 mg/kg), and ketamine (> 20 mg/kg) induce hsp70 mRNA and HSP70 heat shock protein in these vacuolated, injured neurons, and PCP also induces hsp70 in injured neocortical, piriform, and amygdala neurons. The PCP, MK801, and ketamine drug induced injury occurs in 30 day and older rats, but not in 0-20 day old rats, and is prevented by prior administration of the antipsychotic drugs haloperidol and rimcazole. Since haloperidol and rimcazole block dopamine and sigma receptors, and since M1 muscarinic cholinergic receptor antagonists also prevent the injury produced by PCP, MK801, and ketamine, future studies will be needed to determine whether dopamine, sigma, M1, or other receptors mediate the injury.

Amygdala↗
PubMed1992

Blood spot screening and confirmatory tests for syphilis antibody.

We developed a blood spot test for syphilis antibody using enzyme-linked immunosorbent assay (ELISA) technology. Dried blood was eluted by buffered saline or, for a supplementary confirmatory test, by treponemal-antibody test diluent. Eluates were diluted in an absorption buffer (Calypte Biomedical, Berkeley, Calif.) and added to plate wells coated with cardiolipin antigen (ADI Diagnostics, Toronto, Ontario, Canada). The wells were washed and treated sequentially with an immunoglobulin G conjugate, buffer washes, and enzyme substrate. Substrate conversion was measured photometrically, and specimen reactivity was determined by reference to nonreactive controls. The optimum test protocol was established by tests of serum and plasma. The serum ELISA specificity with normal specimens was 98.9%. The sensitivity with sera from patients with undefined syphilis was 97.4%, that with sera from patients with documented primary and secondary disease was 100%, and that with sera from patients with early and late latent disease was 95.7%. The specificity of the spot test with donor blood was 94.2%, and its specificity with newborn blood was 94.9%. The sensitivity with 25 spots spiked with reactive sera was 96%. The seroprevalence rates for parturient women in one hospital were 6.01% according to spot tests of sera from 599 newborns and 6.81% according to Rapid Plasma Reagin tests of 499 maternal serum specimens. Seventy percent of infants born to 50 seropositive women were reactive by either the newborn spot or the Rapid Plasma Reagin serum test. The results show that blood spots may be used in seroprevalence or serodiagnostic studies, especially to identify women who are infected or to identify possible cases of congenital infection. The test provides for studies of children and adults when routine venipuncture and serum handling and storage are problematic.

Antibodies, Bacterial↗
PubMed1991

MK-801 and ketamine induce heat shock protein HSP72 in injured neurons in posterior cingulate and retrosplenial cortex.

MK-801 and ketamine are noncompetitive N-methyl-D-aspartate (NMDA) receptor blockers that decrease brain injury in animal models of focal and global ischemia. Recent reports, however, suggested that MK-801 itself can damage neurons. Here we show that MK-801 (0.1 to 5.0 mg/kg) and ketamine (40 to 100 mg/kg) typically induce heat shock protein HSP72 mainly in layer 3 neurons of the posterior cingulate and retrosplenial cortex of the rat. These HSP72-immunoreactive neurons contain abnormal cytoplasmic vacuoles visualized by electron microscopy. The HSP72 immunoreactivity is maximal at 24 hours with 1.0-mg/kg doses of MK-801 and disappears by 2 weeks. Based on these data, we propose: (1) MK-801 and ketamine injure selected neurons, which express HSP72 in response to that injury. (2) Since HSP72 is induced for 1 to 2 weeks, the prolonged psychological side effects of MK-801, ketamine, phencyclidine, and related drugs could be related to this injury. (3) The neuroprotective effect of MK-801 is probably not related to HSP72 induction. (4) HSP72 immunocytochemistry is useful for studying nonlethal neuronal injury from a wide variety of brain insults.

Animals↗
PubMed1991

Glutamine stimulates growth in rat cerebral endothelial cell culture.

Endothelial cells were isolated from rat cerebral cortices using combined enzymatic digestions and Percoll gradient centrifugation. Primary cultures were subsequently grown on collagen-covered dishes in a medium containing 20% fetal calf serum and 0.6 mmol glutamine. The majority of cultures became confluent by day 7 or 8, but some could not reach confluence. The cells were fusiform in shape and exhibited immunoreactivity to factor VIII-related antigen and binding to the lectin Griffonia simplicifolia. Exposure of cultures to media containing 2.6 mmol glutamine resulted in accelerated growth (in cultures were confluent at days 3-4) and change in culture morphology, namely the formation of circular, cell-free areas. However, this treatment did not restore gamma-glutamyl transpeptidase activity that was lost during cultivation. As for other amino acids, asparagine was less potent, glycine and phenylalanine failed to mimic the glutamine effect. In summary, glutamine stimulates growth of cerebral endothelial cells in vitro and so it may supplement for other growth factors in the culture media.

Amino Acids↗
PubMed1990

Patterns of guanine nucleotide exchange reflecting disparate neutrophil activation pathways by opsonized and unopsonized Candida albicans hyphae.

Through guanosine triphosphate (GTP) regulatory proteins are crucial components in signal transduction by most soluble and opsonized particulate stimuli, previous data suggest that neutrophil (PMNL) activation by unopsonized hyphae differs. Most of the PMNL superoxide response evoked by unopsonized hyphae was independent of both Ca++ ions and pertussis toxin-sensitive guanine nucleotide regulatory proteins. To determine whether related regulatory proteins were involved in PMNL activation by unopsonized hyphae, separated PMNL plasma membranes were incubated with GTP and a poorly hydrolyzed, radiolabeled GTP analogue, 5'-guanylylimido-diphosphate, then stimulated. Particulate Candida albicans hyphae and soluble chemotactic peptide induced comparable guanine nucleotide release. In contrast, while unopsonized hyphae caused release, it was considerably delayed, though opsonization discernibly affected neither PMNL attachment nor spreading over hyphal surfaces. This paralleled earlier observations of other delayed responses by intact PMNL to unopsonized hyphae: phospholipase C activation, the rise in cytosolic free Ca++ ions, and actin polymerization.

Candida albicans↗
PubMed1990

Treatment of murine pulmonary blastomycosis with SCH 39304, a new triazole antifungal agent.

SCH 39304, a broad-spectrum azole derivative, was evaluated in an experimental mouse model of blastomycosis pneumonia. Five days after being inoculated with Blastomyces dermatitidis, infected mice were treated with either oral SCH 39304, fluconazole, or intraperitoneal amphotericin B. A dose response protective effect was observed with SCH 39304 at 5 to 100 mg/kg of body weight per day, with 5 mg of SCH 39304 per kg per day providing activity similar to that of 100 mg of fluconazole per kg per day. Colony counts of yeasts in the lungs of mice sacrificed while on therapy with SCH 39304 were consistently below those of controls, and several lungs were sterile. We conclude that SCH 39304 is effective in murine blastomycosis treatment and deserves to be evaluated in the treatment of human blastomycosis.

Amphotericin B↗
PubMed1989

Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.

Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium. In the present study we characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral fluid-percussion injury of graded severity. Physiological experiments (n = 105) demonstrated that all levels of injury produced an acute and transient systemic hypertension and bradycardia. Acute hypertension followed by significant hypotension occurred at higher magnitudes of injury. Post-injury suppression of electroencephalographic amplitude was related to the severity of injury. An increase in slow wave (delta/theta) electroencephalographic activity with a concomitant decrease in alpha/beta electroencephalographic activity were observed only at moderate and high magnitude of injury and were correlated with a worsened neurological outcome (r = 0.84; P less than 0.05) and increased mortality (r = 0.66; P less than 0.05). Alterations in brainstem auditory-evoked potentials were also observed only at the higher levels of injury. Histopathological analysis revealed that the extent of post-injury hemorrhage, cavitation and vascular disruption (as measured by extravasation of Evans Blue dye) was greater at the higher magnitudes of injury. Neurological scoring performed over a 4-week post-injury period demonstrated that lateral fluid-percussion brain injury produces a chronic neurological deficit that is directly related to the severity of injury. Survival was also significantly reduced at the higher magnitudes of injury. These data demonstrate that the lateral model of fluid-percussion injury in the rat reproduces many of the features of head injury observed in other models and species and may therefore be a useful experimental model for the study of the pathophysiology of traumatic brain injury.

Animals↗
PubMed1987

Traumatic brain injury in the rat: characterization of a midline fluid-percussion model.

Fluid-percussion models of traumatic brain injury produce injury by rapidly injecting fluid volumes into the epidural space. In the present study, we characterized the physiological, histopathological, and neurological responses in a new model of midline (vertex) fluid-percussion injury of graded severity in the rat. All levels of injury produced transient (acute) hypertension, which was followed by a significant and prolonged hypotension at the higher levels of injury. There was also postinjury suppression if EEG amplitudes, which was related to the severity of injury. However, there were no significant changes in brainstem auditory evoked potentials (BAERs) at any level of injury. Neurological scores over a 4-week postinjury period were directly correlated with the severity of injury. Survival rates were significantly decreased at the higher magnitudes of injury. The extent of postinjury hemorrhage and blood-brain barrier disruption (as evidenced by extravasation of Evans Blue Albumin complex) was related to the magnitude of injury. These data demonstrate that the midline (vertex) model of fluid-percussion injury in the rat reproduces many of the features of head injury observed in other models and species and may serve as a useful cost-effective model for the study of the pathophysiology and treatment of traumatic brain injury.

Animals↗
PubMed1987

Postmortem changes in rat brain: studies on membrane-bound enzymes and receptors.

The relationship between the stability of potential neurochemical markers and autolysis time was studied at 4 degrees C and 25 degrees C using postmortem brain samples from two rat strains. In general, qualitatively similar results were obtained with either N/Nih or Sprague-Dawley rats; however, quantitative differences were often observed, particularly in regard to benzodiazepine receptor changes. For every enzyme activity or binding property examined, no significant change was found when brains were kept at 4 degrees C for up to 72 h prior to freezing at -70 degrees C. Na,K-ATPase and low-affinity Ca-ATPase activities were also stable in brains kept at 25 degrees C for up to 72 h. Mg-ATPase activity was reduced in brains kept at 25 degrees C for 24 and 48 h. [3H]Guanidinoethylmercaptosuccinic acid [( 3H]GEMSA) binding to enkephalin convertase in the cytosol was not significantly changed in brains kept at 25 degrees C; however, a small increase was seen for [3H]GEMSA binding to the membrane fraction at 24, but not 48 and 72 h postmortem. [3H]Quinuclidinyl benzilate [( 3H]QNB) binding to muscarinic cholinergic receptors decreased in brains kept at 25 degrees C for 72 h. Opioid receptor binding also decreased in brains kept at 25 degrees C. Using [3H]2-D-alanine-5-D-leucine enkephalin to label delta opioid receptors, a statistically significant decrease in binding was observed as early as 6 h postmortem, and was completely abolished after 72 h at 25 degrees C. In contrast, [3H]naloxone binding was unchanged after 24 h at 25 degrees C, but was decreased after 48 and 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of selected softball bat loading strategies on impact reaction impulse.

Interior loading strategies to modify the location and size of the effective hitting area of aluminum softball bats were identified. The effects of these strategies on theoretically derived and empirically determined relevant mechanical parameters were compared. Loading strategies consisted of adding 315 g to the interior of three similar (790 g) aluminum softball bats: at the center of mass of the original bat (bat C); at the ends of the bat and distributed so that the center of mass was unchanged, (bat A); and at the ends of the bat and distributed so that the moment of inertia about the swing axis (I1) was the same as that of bat C (bat B). The following parameters were derived theoretically by considering the bat as a physical pendulum and empirically by observing the impact reaction impulse on the axis of suspension: moment of inertia about the suspension axis (I0); moment of inertia about the swing axis; distance from the suspension axis to the center of percussion; and the slope of the impact reaction impulse (P1) relative to the impact impulse (P) as a function of impact location. These values for each bat were compared. Both empirical and theoretically derived data indicated that: the center of percussion of bat B was farther away from the axis than bats A and C; the moment of inertia about the swing axis of bat A was much greater than that of bats B and C; and the slope of the impact reaction regression line as a function of impact location for bat B was significantly less than that of the other bats. Thus, the effective hitting area of bat B was moved toward the barrel end of the bat and enlarged without a substantial increase in the moment of inertia about the swing axis.

Baseball↗