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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 253 records · Page 14Linked to original sources
PubMed1998

Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats.

The discriminative stimulus properties of the prototypical atypical neuroleptic clozapine (5 mg/kg, IP) were characterised in rats using a fixed ratio assay. Clozapine induced full dose-related generalization in the absence of response suppression. Amphetamine and pentylenetetrazol failed to generalise at doses known to be discriminable, showing a degree of specificity for the clozapine cue. The typical neuroleptics haloperidol and loxapine induced minimal (20%) generalization at doses with marked behavioural effects; thus clozapine discrimination dissociates clozapine from typical neuroleptics. Atypical neuroleptics which are not clozapine congeners produced weak partial generalization when tested up to the highest doses that could be studied. The maximal levels of generalization induced by these agents were: amisulpiride 28%, risperidone 40% and sertindole 50%. Clozapine congeners typically caused more generalization, the novel pyridobenzoxapine JL13 inducing 70% maximal generalization. Most generalization (83%) was seen with the clozapine congener seroquel, although in contrast to clozapine, it only generalised at doses with marked effects on responding, so that no drug mimicked clozapine fully. Surprisingly, the clozapine congener olanzapine only induced a maximal level of 38% generalization. This apparently anomalous finding is attributed to an inability to test high doses of the drug due to its rate-suppressant actions. The clozapine cue can be used to rank atypical neuroleptics in terms of their similarity to clozapine in vivo. The clozapine cue is probably a compound cue, since only agents showing "polyvalent" receptor pharmacology induced substantial generalization.

Animals↗
PubMed1998

Lateral femoral scan: an alternative method for assessing bone mineral density in children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP), often nonambulatory and/or on anticonvulsants, are at increased risk for fractures. Bone mineral density (BMD) measured by the conventional techniques of dual-energy X-ray absorptiometry (DXA) often cannot be reliably or easily measured in these patients. OBJECTIVE: To find an alternative site to whole body, spine and hip that can be conveniently used to measure BMD in CP patients. MATERIALS AND METHODS: Having observed that CP patients prefer to lie on their sides, we explored measuring BMD at the distal femur in the lateral projection. A total of 92 scans were performed without sedation in 34 children and adolescents with CP, aged 4-19 years. Four femoral shaft subregions were created: two trabecular and two cortical. RESULTS: The coefficients of variation (CV %) were generally higher for opposite-side comparisons (n = 12 patients) than for same-side comparisons (n = 16 patients). For intra- and interobserver analyses, CV % were higher for cortical regions than for trabecular regions. Overall, the CV % were similar to those for hip and spine. CONCLUSION: This peripheral site in the femur should be considered as an alternative for patients with CP when whole-body, hip and spine DXA are not practical.

Absorptiometry, Photon↗
PubMed1998

Tetanus--the silent killer: how safe are you?

Despite the fact that tetanus is entirely preventable, mortality and morbidity as a result of this disease remain significant. The tetanus toxoid is one of the most potent poisons known. While immunisation programs focus on children, the elderly remain at risk of contracting immunisable diseases. Tetanus often leads to prolonged hospital stays and requires emergency and intensive care intervention and management. This case study illustrates a number of important points concerning the recognition, treatment, management and prevention of tetanus poisoning, and highlights the importance of considering the immunisation status of our elderly patients.

Aged↗
PubMed1998

DNA sequence and muscle-specific expression of human sarcosin transcripts.

We have characterized two abundant human cDNAs which, through Northern hybridization analysis, are selectively expressed in human sarcomeric muscle. DNA sequencing was performed and the two cDNAs were found to share sequence identity, with the exception of a 3' UTR extension present on the longer transcript. Our data suggest that the two transcripts are generated through alternative use of two poly(A) addition signals. The cDNAs encode a large open reading frame encompassing at least 435 codons. Through sequence comparisons, both at the DNA and predicted amino acid sequence level, we have been unable to find significant sequence similarity to any other characterized sequence. Consequently, we have termed this novel human sequence sarcosin. Although novel, Southern hybridization analysis demonstrated that the sarcosin sequence has been conserved in several mammalian species.

Amino Acid Sequence↗
PubMed1998

Influence of barrier occlusiveness on guided bone augmentation. An experimental study in the rat.

The present study was designed to test perforated and non-perforated barriers for their ability to promote augmentation of bone tissue. More specifically, 1 totally occlusive barrier and 6 barriers with perforation sizes of about 10, 25, 50, 75, 100, and 300 microns and 1 group with no barriers placed (open test chambers) were used to test the effect of a barrier's occlusiveness on the amount and composition of augmented tissue over time. The skull of the rat was used as the experimental area. Prefabricated, flexible silicone frames with an inferior flange for peripheral sealing to the bone surface and a central vertical through hole with a diameter of 3.6 mm and a height of 2 mm were used as test chambers. The barriers were inserted to cover the superior opening of the through hole. The healing periods were 4, 8, and 12 weeks. All test chambers exhibited newly formed skull bone which was augmented over time. The placement of totally occlusive barriers resulted in the slowest rate of bone tissue augmentation but in a highly predictable manner, i.e., there were only small individual variations. Placement of barriers with perforations exceeding 10 microns, on the other hand, resulted in a faster rate of bone augmentation with larger individual variations and a totally different augmentation pattern. A pronounced augmentation of calvarial soft tissue from the sagittal suture of the skull as well as ingrowth of suprabony connective tissue through the barriers were also observed. After 12 weeks of healing, no differences in the amount of augmented mineralized bone related to perforation sizes > 10 microns were found. The open test chambers also showed bone augmentation, although most of their volume was occupied by suprabony connective tissue.

Analysis of Variance↗
PubMed1998

Patient perceptions of hospital care: building confidence, faith and trust.

AIM: The aim of this study was to understand how people evaluate and make sense of their experience of hospital care. METHOD: Narrative interviews were conducted with 18 patients between 4-6 weeks after an episode of inpatient care or day surgery. Participants were deliberately sampled from a population who participated in a hospital-wide audit which took place during 1 week in June 1995. Sampling criteria ensured a mix of age, gender, type of, and reason for, admission. The interviews were audiotaped, transcribed and analysed using grounded theory. FINDINGS: Three categories: 'feeling informed', 'valued as an individual', and 'at home' contributed to a core category: 'building confidence, faith and trust'. Notably, confidence and trust were determined as much by observations of the care given to other people, as the care the participants themselves had received. CONCLUSIONS: More attention needs to be given to understanding the complex social and reflective process which underpin patient judgements about quality of care.

Adult↗
PubMed1998

Traumatic brain injury and posttraumatic stress disorder: a preliminary investigation of neuropsychological test results in PTSD secondary to motor vehicle accidents.

This study investigated the effect of traumatic brain injury on the development of posttraumatic stress disorder (PTSD). Subjects were 107 motor vehicle accident survivors including 38 individuals who were diagnosed with posttraumatic stress disorder (PTSD). Neuropsychological testing was administered to all subjects during an initial diagnostic evaluation. Results showed that subjects who had lost consciousness during their MVA had greater impairment on speed dependent tests and delayed recall of verbal material. Subjects who suffered traumatic brain injury (TBI) were also found to have developed PTSD as often as those who had not reported TBI. Implications for future research and clinical utility are discussed.

Accidents, Traffic↗
PubMed1998

An open trial of naltrexone for opiate dependence.

The objective of this study was to conduct a pilot study of naltrexone in opiate-dependent patients in order to determine the sample size for a double-blind controlled trial, to identify possible confounders and to obtain experience with the drug's side effects and acceptability to patients. Opiate-dependent patients presenting to a public hospital for treatment for their dependence were invited to participate. Patients with major organic illness, another Axis I diagnosis, or who were pregnant were excluded. Naltrexone was prescribed at a dose of 50 mg daily for 6 months. Data were collected on drug use, social stability, physical and mental health before during and after the treatment programme. Patients were seen weekly for 6 months then monthly for a further 6 months. Forty-four patients were enrolled, but three stopped naltrexone early because of possible side effects. Of the remainder, 32 were followed for at least 12 months. Eight (25%) ceased opiate use from the start, and another two were no longer using at the end of 12 months giving an abstinence rate of 31% at 12 months. Retention in treatment was 34%. Of the abstinent patients however, only two took naltrexone for the whole 6 months. Naltrexone was well tolerated and associated with a significant abstinence rate, but most patients do not feel they need to take the drug for 6 months. A double-blind controlled trial would be justified.

Journal Article↗
PubMed1998

Diabetes complications and risk factors in an Australian population. How well are they managed?

BACKGROUND: This study aimed to explore the relationship between complications and risk factors in the type 2 diabetes population, and to assess the level of assistance people with diabetes receive in controlling their risk factors. METHODS: Participants were recruited from representative population surveys of South Australians aged over 18 years. Participants were asked a series of questions about their risk factors and the advice and assistance they received from their general practitioner (GP) in modifying their risk factors. Additionally, participants were clinically tested for a number of macro and microvascular complications. RESULTS: South Australians with type 2 diabetes have a high prevalence of risk factors, with the majority being overweight or obese, doing no vigorous exercise and having high blood pressure. They also have a high prevalence of complications, with 53% having at least one macrovascular complication and 66% having at least one microvascular complication. Additionally, participants reported high levels of GP advice and assistance on the risk factors where pharmacological controls were available, but low levels of assistance where non-pharmacological interventions were needed to control the risk factor. CONCLUSIONS: The prevalence of diabetes risk factors and complications among South Australians with type 2 diabetes is a cause for concern, as is the lack of assistance offered by GPs to modify risk factors. Multi-disciplinary approaches to the control of risk factors and patient self-management and education are critical to the progression and success of diabetes care.

Adult↗
PubMed1998

Redox regulation of ubiquitin-conjugating enzymes: mechanistic insights using the thiol-specific oxidant diamide.

The ubiquitin-proteasome pathway (UPP) regulates critical cell processes, including the cell cycle, cytokine-induced gene expression, differentiation, and cell death. Recently we demonstrated that this pathway responds to oxidative stress in mammalian cells and proposed that activities of ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes (E2s) are regulated by cellular redox status (i.e., GSSG:GSH ratio). To test this hypothesis, we altered the GSSG:GSH ratio in retinal pigment epithelial cells with the thiol-specific oxidant, diamide, and assessed activities of the UPP. Treatment of cells with diamide resulted in a dose-dependent increase in the GSSG:GSH ratio resulting from loss of GSH and a coincident increase in GSSG. Increases in the GSSG:GSH ratio from 0.02 in untreated cells to > or = 0.5 in diamide-treated cells were accompanied by dose-dependent reductions in the levels of endogenous Ub-protein conjugates, endogenous E1-ubiquitin thiol esters, and de novo ubiquitin-conjugating activity. As determined by the ability to form E1-ubiquitin and E2s-ubiquitin thiol esters, E1 and E2s were both inhibited by elevated GSSG:GSH ratios. Inhibition of E1 was associated with the formation of E1-protein mixed disulfides. Activities of E1 and E2s gradually recovered to preoxidation levels, coincident with gradual recovery of the GSSG:GSH ratio. These data support S-thiolation/dethiolation as a mechanism regulating E1 and E2 activities in response to oxidant insult. Ubiquitin-dependent proteolytic capacity was regulated by the GSSG:GSH ratio in a manner consistent with altered ubiquitin-conjugating activity. However, ubiquitin-independent proteolysis was unaffected by changes in the GSSG:GSH ratio. Potential adaptive and pathological consequences of redox regulation of UPP activities are discussed.

Cell Line, Transformed↗
PubMed1998

Diagnostic continuity between child and adolescent ADHD: findings from a longitudinal clinical sample.

OBJECTIVE: To determine whether there are differences in the clinical expression and correlates of attention-deficit hyperactivity disorder (ADHD) between children and adolescents. METHOD: Subjects were 6- to 17-year old Caucasian, non-Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews, psychometric measures, and blind raters assessed psychiatric diagnoses, intellectual performance, social disability, school failure, and family functioning. RESULTS: Children and adolescents with ADHD had an almost identical pattern of correlates in multiple domains of assessment including psychosocial adversity and comorbidity with conduct, mood, and anxiety disorders. Although the rate of substance abuse differed in comparison between child and adolescent subjects, this was independent of ADHD status. CONCLUSIONS: These findings document the diagnostic continuity of ADHD between childhood and adolescence and support the inclusion of adolescent samples in ADHD research protocols.

Adolescent↗
PubMed1998

Is spectral analysis of the surface electromyographic signal a clinically useful tool for evaluation of skeletal muscle fatigue?

Normal values for initial median frequency (IMF) of the electromyographic (EMG) power-density spectrum must be determined before EMG spectral analysis can be used to evaluate clinically muscle fatigue. This study attempts to establish normal values in four muscles. Thirty-one healthy subjects performed isometric contractions of the biceps brachii, triceps, deltoid, and tibialis anterior muscles at 50% maximum voluntary contraction. Linear regression analysis was used to compute the IMF and the slope of the median frequency as it decayed with fatigue over 45 seconds. The IMF of the tibialis anterior (mean +/- standard deviation, 116 +/- 20 Hz) was significantly higher (p < 0.001) than that of the biceps (90 +/- 18 Hz), triceps (85 +/- 18 Hz), and deltoid (87 +/- 15 Hz). The deltoid and tibialis anterior had the steepest slopes. The IMF of all muscles was greater in men than in women, but gender did not affect the slope. This study attempted to establish normal values for IMF and slope in specific muscles. However, the range of normal values is so broad that it may preclude the clinical use of spectral analysis to evaluate muscle fatigue.

Adult↗
PubMed1998

Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands.

The interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using a wide range of receptor subtype-selective agonists and antagonists. Only the muscarinic receptor antagonist scopolamine generalized fully to clozapine (>80%). Partial generalization (defined here as 40% maximal generalization) was seen with the D1 receptor antagonist SCH 23390 (43% maximal generalization), the alpha1-adrenoceptor antagonist prazosin (67%) and the alpha2-adrenoceptor antagonist methoxyidazoxan (42%). All other specific agents tested induced <25% maximal generalization, including the alpha2-adrenoceptor antagonist yohimbine (24%), the histamine H1 receptor antagonist mepyramine (21%), the D2 antagonist typical neuroleptic haloperidol (23%), the D4 receptor antagonist L-745,870 (14%), the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist S-14506 (8%), the 5-HT2A receptor antagonists ketanserin (0%) and M100907 (12%), the 5-HT2B/2C receptor antagonists SB 200646A (8%) and SDZ SER 082 (6%), and the 5-HT3 receptor antagonist ondansetron (0%). The clozapine discriminative stimulus was not blocked by the dopamine D1 receptor antagonist SCH 23390, or by the 5-HT1A receptor antagonist WAY 100635, when given concomitantly with clozapine. Although the results suggest that muscarinic antagonism plays a major role in the clozapine cue, the results have to be considered in the light of the full generalization to clozapine seen with various antipsychotic agents which have very low affinity for muscarinic receptors, including zotepine, quetiapine, JL13 and PNU 96415 (a finding replicated in rats from the same breeding colony as those which generalized to scopolamine). Thus, generalization to clozapine for antipsychotics with multiple affinities but with low muscarinic affinity is probably mediated by additive or perhaps supra-additive actions at other receptors, although extensive studies with various combinations of drug mixtures are required to validate this hypothesis.

Adrenergic alpha-Antagonists↗
PubMed1998

Copper-binding compounds from Methylosinus trichosporium OB3b.

Two copper-binding compounds/cofactors (CBCs) were isolated from the spent media of both the wild type and a constitutive soluble methane monooxygenase (sMMOC) mutant, PP319 (P. A. Phelps et al., Appl. Environ. Microbiol. 58:3701-3708, 1992), of Methylosinus trichosporium OB3b. Both CBCs are small polypeptides with molecular masses of 1,218 and 779 Da for CBC-L1 and CBC-L2, respectively. The amino acid sequence of CBC-L1 is S?MYPGS?M, and that of CBC-L2 is SPMP?S. Copper-free CBCs showed absorption maxima at 204, 275, 333, and 356 with shoulders at 222 and 400 nm. Copper-containing CBCs showed a broad absorption maximum at 245 nm. The low-temperature electron paramagnetic resonance (EPR) spectra of copper-containing CBC-L1 showed the presence of a copper center with an EPR splitting constant between those of type 1 and type 2 copper centers (g = 2.087, g = 2.42 G, A = 128 G). The EPR spectrum of CBC-L2 was more complex and showed two spectrally distinct copper centers. One signal can be attributed to a type 2 Cu2+ center (g = 2.073, g = 2.324 G, A = 144 G) which could be saturated at higher powers, while the second shows a broad, nearly isotropic signal near g = 2.063. In wild-type strains, the concentrations of CBCs in the spent media were highest in cells expressing the pMMO and stressed for copper. In contrast to wild-type strains, high concentrations of CBCs were observed in the extracellular fraction of the sMMOC mutants PP319 and PP359 regardless of the copper concentration in the culture medium.

Bacterial Proteins↗
PubMed1998

Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct.

We investigated whether the motor protein cytoplasmic dynein and dynactin, a protein complex thought to link dynein with vesicles, are present in rat renal collecting ducts and associated with aquaporin-2 (AQP2)-bearing vesicles. Immunoblotting demonstrated cytoplasmic dynein heavy and intermediate chains in kidney, with relative expression levels of inner medulla > outer medulla > cortex. In addition to being present in cytoplasmic fractions, dynein was abundant in membrane fractions enriched for intracellular vesicles. Dynactin was also abundant in membrane fractions enriched for intracellular vesicles. Furthermore, both dynactin and dynein were present in vesicles specifically immunoisolated using anti-AQP2 antibodies. Immunocytochemistry revealed labeling for dynein in the collecting duct principal cells with a pattern consistent with labeling of intracellular vesicles. Moreover, quantitative double immunogold labeling confirmed colocalization of AQP2 and dynein in the same vesicles at the electron microscopic level. Thus the microtubule-associated motor protein dynein and the associated dynactin complex are present in rat renal collecting duct principal cells and are associated with intracellular vesicles, including those bearing AQP2, consistent with the view that dynein and dynactin are involved in vasopressin-regulated trafficking of AQP2-bearing vesicles.

Animals↗
PubMed1998

Physiological signs of the activation of bag2 and chain intrafusal muscle fibers of gastrocnemius muscle spindles in the cat.

A method is described for identifying the effect of single gamma static (gamma(s)) axons on bag2 or chain intrafusal fibers using random (Poisson-distributed) stimuli. The cross-correlogram of the stimuli with the firing of spindle primary afferents took one of three forms. A large, simple, brief response was taken to indicate pure chain fiber activation and a small, prolonged response to indicate pure bag2 activation. A compound response with brief and prolonged components was taken to be a sign of mixed innervation. The correlogram components could be well fitted with lognormal curves. They could also be transformed into curves of gain as a function of frequency, which were convenient for estimating the strength of the effects. In 68 effects of gammas axons on Ia afferents, 16 were pure chain, 17 pure bag2, and 35 mixed. This distribution was significantly different (P < 0. 05) from that expected from chance nonspecific innervation of chain and bag2 fibers. Making use of the estimates of the strength of chain and bag2 effects derived from the gain curves, the classification was modified by treating mixed responses that had one effect more than five times stronger than the other as belonging to the dominant type. The distribution was then as follows: chain 16, bag2 28, and mixed 24. This differed very significantly from the prediction of chance distribution (P < 0.001). This evidence for some degree of specific innervation of chain and bag2 fibers is discussed in relation to previous work and with regard to the ways in which the two fiber types might be used in natural movements.

Action Potentials↗
PubMed1998

Clinical characteristics of attention deficit hyperactivity disorder in African American children.

OBJECTIVE: The authors' goal was to explore the nature of attention deficit hyperactivity disorder (ADHD) in African American children, which has received scant attention by psychiatric researchers. METHOD: Subjects were 19 African American children with DSM-III-R ADHD and 24 African American children without ADHD. Ethnically sensitive methods were used to evaluate the children comprehensively. The findings were compared with those from an earlier study of Caucasian children with ADHD. RESULTS: African American children with ADHD had higher levels of psychiatric disorders other than ADHD than did African American children who did not have ADHD. CONCLUSIONS: Among African American children, ADHD may be characterized by a narrower pattern of psychiatric comorbidity and dysfunction than has been observed in Caucasians. Given the small number of subjects studied, these findings are preliminary and must be replicated to confirm their validity.

Adolescent↗