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Biomedical subjects

S Butler

Publications and source records attributed to S Butler.

At least 19 recordsLinked to original sources

Effects of lesioning noradrenergic neurones in the locus coeruleus on conditioned and unconditioned aversive behaviour in the rat.

1. The brain noradrenergic system may have a role in anxiety disorder. This study has examined the effect of bilateral 6-hydroxydopamine lesions of the noradrenergic neurones in the locus coeruleus (LC) of male Lister hooded rats on behaviour produced by unconditioned and conditioned aversive stimuli. 2. The 6-hydroxydopamine (4 microg) lesions markedly reduced the noradrenaline content of the locus coeruleus hypothalamus, frontal cortex and the periaqueductal grey area without altering the levels of either dopamine or 5-hydroxytryptamine measured 14 days after administration. 3. Exposure to ultrasound (20 kHz at 98 dB for 60 sec), an unconditioned aversive stimulus, induced a defence response in the rats characterised by an increase in activity (running and jumping) followed by a period of inactivity (freezing). 4. Lesioning of the LC significantly attenuated the duration of freezing but was without effect on the active phase of the response. A similar reduction in freezing behaviour was seen with LC lesions when rats were exposed (3 hours after the acquisition) to the contextual cue of the conditioned emotion response paradigm. 5. These findings confirm that the locus coeruleus is involved in the regulation of fear-related behaviour in the rat both in an unconditioned and a conditioned model. Furthermore the results indicate that noradrenaline modifies defence behaviour rather than being the principle activating mechanism.

Adrenergic Agents↗

Long-Term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial.

Patients with dementia with Lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline.

Aged↗

Antibody response to Burkholderia cepacia in patients with cystic fibrosis colonized with Burkholderia cepacia and Pseudomonas aeruginosa.

INTRODUCTION: This study was designed to determine the relationship between formation of serum antibodies to lipopolysaccharide (LPS) core antigen of Burkholderia cepacia and pulmonary colonization with B. cepacia and Pseudomonas aeruginosa in patients with cystic fibrosis (CF), and to define if an enhanced host humoral immune response to B. cepacia was related to a poor clinical outcome. METHODS: Serum IgG to B. cepacia LPS core antigen was measured in adult cystic fibrosis patients colonized with B. cepacia and P. aeruginosa, and serial titres were measured in 13 B. cepacia and 41 P. aeruginosa colonized patients followed prospectively over 18 months. RESULTS: The median B. cepacia antibody titre was significantly greater in the patients colonized with B. cepacia compared to those colonized with P. aeruginosa, a group which grew B. cepacia intermittently from their sputum. and nine healthy controls. The median antibody titre at recruitment into the study was significantly greater in patients who later went into exacerbations compared with those who remained clinically stable. but there was no difference between B. cepacia antibody titres in patients who died and those who survived the study duration. DISCUSSION: The degree of overlap of serum IgG levels to B. cepacia LPS core antigen in cystic fibrosis patients colonized with B. cepacia and P. aeruginosa does not allow this antibody to be used in a clinical context to define infection status. The magnitude of the humoral response to B. cepacia may influence occurrence of pulmonary exacerbations, but a more exuberant humoral immune response to B. cepacia core LPS is not the mechanism by which pulmonary deterioration occurs.

Adolescent↗

Mismatch negativity in the visual modality.

In the auditory system, the automatic detection of stimulus change provides a mechanism for switching attention to biologically significant events. It gives rise to the mismatch negativity (MMN) event related potential. It is unclear whether a similar mechanism exists in vision. To investigate this issue, evoked potentials were recorded to target stimuli in the centre of the visual field, and to frequent standard and infrequent deviant stimuli presented outside the focus of attention, in the peripheral field. Deviants evoked a more negative potential than standards 250-400 ms after the stimulus. The negativity, distributed over supplementary visual areas of occipital and posterior temporal cortex, was associated with the rarity of the deviants and not the physical features which distinguished them from standards. This negativity shares a number of characteristics with auditory MMN.

Adult↗

BMPs as mediators of roof plate repulsion of commissural neurons.

During spinal cord development, commissural (C) neurons, located near the dorsal midline, send axons ventrally and across the floor plate (FP). The trajectory of these axons toward the FP is guided in part by netrins. The mechanisms that guide the early phase of C axon extension, however, have not been resolved. We show that the roof plate (RP) expresses a diffusible activity that repels C axons and orients their growth within the dorsal spinal cord. Bone morphogenetic proteins (BMPs) appear to act as RP-derived chemorepellents that guide the early trajectory of the axons of C neurons in the developing spinal cord: BMP7 mimics the RP repellent activity for C axons in vitro, can act directly to collapse C growth cones, and appears to serve an essential function in RP repulsion of C axons.

Animals↗

Effect of a 915-MHz simulated mobile phone signal on cognitive function in man.

PURPOSE: To examine whether a simulated mobile telephone transmission at 915 MHz has an effect on cognitive function in man. MATERIALS AND METHODS: Thirty-six subjects in two groups were each given two training sessions and then three test sessions in a randomized three-way cross-over design. About 1 W mean power at 915 MHz from a quarter-wave antenna mounted on a physical copy of an analogue phone, as a sine wave, or modulated at 217 Hz with 12.5% duty cycle, or no power, was applied to the left squamous temple region of the subjects while they undertook a series of cognitive function tests lasting approximately 25-30 min. The second group was investigated for sleep, consumption of alcohol and beverages, and any other substances that might affect performance. RESULTS: In both groups, the only test affected was the choice reaction time and this showed as an increase in speed (a decrease in reaction time). There were no changes in word, number or picture recall, or in spatial memory. While an effect of visit-order was evident suggesting a learning effect of repeat tests, the design of the study allowed for this. Additionally, there was no systematic error introduced as a result of consumption of substances or sleep time. CONCLUSIONS: There was evidence of an increase in responsiveness, strongly in the analogue and less in the digital simulation, in choice reaction time. This could be associated with an effect on the angular gyrus that acts as an interface between the visual and speech centres and which lies directly under and on the same side as the antenna. Such an effect could be consistent with mild localized heating, or possibly a non-thermal response, which is nevertheless power-dependent.

Absorption↗

Impact of microbiology practice on cumulative prevalence of respiratory tract bacteria in patients with cystic fibrosis.

Investigators participating in the Epidemiologic Study of Cystic Fibrosis project began to collect microbiological, pulmonary, and nutritional data on cystic fibrosis (CF) patients at 180 North American sites in 1994. Part of this study was a survey undertaken in August 1995 to determine microbiology laboratory practices with regard to pulmonary specimens from CF patients. The survey included a section on test ordering, completed by a site clinician, and a section on test performance and reporting, completed by each site's clinical microbiology laboratory staff. Seventy-nine percent of the surveys were returned. There was intersite consistency of microbiology laboratory practices in most cases. The majority of sites follow most of the CF Foundation consensus conference recommendations. There were differences in the frequency at which specimens for culture were obtained, in the use of selective media for Staphylococcus aureus and Haemophilus influenzae, and in the use of a prolonged incubation for Burkholderia cepacia. These variations in practice contribute to prevalence differences among sites and may result in differences in clinical care.

Adolescent↗

Body perceptions of bulimic and nonbulimic groups.

A brief survey measuring satisfaction with the body, concern for physical appearance, and motivations for selection of clothing was administered to 30 women in a university-sponsored support group for bulimic students and 30 women randomly selected from a college campus. No mean differences were found between the groups on concern for physical appearance when in a social setting, but mean differences were significant on satisfaction with weight, satisfaction with body image, and concern for physical appearance when alone.

Body Image↗

Angiotensin II increases macrophage-mediated modification of low density lipoprotein via a lipoxygenase-dependent pathway.

The molecular and cellular mechanisms by which hypertension enhances atherosclerosis are poorly understood. Angiotensin II (Ang II) has been implicated in the regulation of cellular lipoxygenases (LO), which are thought to play a role in atherogenesis by inducing oxidative modification of low density lipoprotein (LDL). We sought to test the hypothesis that Ang II would stimulate murine macrophage LO activity (which has both 12- and 15-LO activity). Competitive binding studies revealed the presence of Ang II AT1 receptors on mouse peritoneal macrophages (MPM) and J-774 cells, but not on the RAW cell line. Valsartan, a specific AT1 receptor antagonist inhibited Ang II binding, whereas PD 123319, an AT2 receptor antagonist did not. Incubation of MPM or J-774 cells with Ang II (10 pM to 1 microM) for 24 h led to a 2.5-3.5-fold increase in LO activity, measured as generated 13-HODE or 12(S)-HETE. This stimulation was inhibited by valsartan, but not by PD 123319. In contrast, Ang II did not stimulate LO activity in RAW macrophages. Semiquantitative reverse transcriptase-polymerase chain reaction showed a 2-3-fold increase in LO mRNA in MPM, but not in RAW cells after treatment with Ang II. Ang II also induced an increase in 12-LO protein. In addition, pretreatment of J-774 cells with Ang II increased in a dose-dependent manner the ability of the cells to modify LDL, resulting in greater chemotactic activity for monocytes, typical of minimally modified LDL. This stimulation was inhibited by AT1 receptor blockade. In summary, these data suggest that Ang II increases macrophage LO activity via AT1 receptor-mediated mechanisms and this further increases the ability of the cells to generate minimally oxidized LDL. These studies provide a link between hypertension and the associated increased atherosclerosis observed in hypertensive patients.

Angiotensin II↗

2-Cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: structure-activity in vitro and efficacy in vivo.

A series of 2-cycloalkyl- and 2-alkyl-3-(hydroxymethyl)-1-methylindoloquinones and corresponding carbamates have been synthesized and substituted in the 5-position with a variety of substituted and unsubstituted aziridines. Cytotoxicity against hypoxic cells in vitro was dependent upon the presence of a 5-aziridinyl or a substituted aziridinyl substituent for 3-hydroxymethyl analogues. The activity of 5-methoxy derivatives was dependent upon the presence of a 3-(carbamoyloxy)methyl substituent. Increasing the steric bulk at the 2-position reduced the compounds' effectiveness against hypoxic cells. A 2-cyclopropyl substituent was up to 2 orders of magnitude more effective than a 2-isopropyl substituent, suggesting possible radical ring-opening reactions contributing to toxicity. Nonfused 2-cyclopropylmitosenes were more effective than related fused cyclopropamitosenes reported previously. The reduction potentials of the quinone/semiquinone one-electron couples were in the range -286 to -380 mV. The semiquinone radicals reacted with oxygen with rate constants 2-8 x 10(8) dm3 mol-1 s-1. The involvement of the two-electron reduced hydroquinone in the mediation of cytotoxicity is implicated. The most effective compounds in vitro were the 2-cyclopropyl and 5-(2-methylaziridinyl) derivatives, and of these, 5-(aziridin-1-yl)-2-cyclopropyl-3-(hydroxymethyl)-1-methylindole-4 ,7-dione (21) and 3-(hydroxymethyl)-5-(2-methylaziridin-1-yl)-1,2-dimethylindole+ ++-4,7-dione (54) were evaluated in vivo. Both compounds showed antitumor activity both as single agents and in combination with radiation, with some substantial improvements over EO9 (3) at maximum tolerated doses and as single agents against the RIF-1 tumor model and comparable efficacy in the KHT tumor model.

Animals↗

Child protection or professional self-preservation by the baby nurses? Public health nurses and child protection in Ireland.

An exploratory, focus group methodology was used to elicit the views of public health nurses (PHNs) on the topic of child welfare and protection in the context of new legislation and evolving child care policy in Ireland. The nurses' views were considerably at variance with the officially stated commitment to inter-disciplinary collaboration and coordination within the Community Care Programmes of Ireland's regional health boards. The PHNs feared that involvement in child care proceedings of a social control or adversarial nature would compromise them in terms of their traditional curative and preventive health roles, and, on this basis, argued that social workers should retain the bulk, if not all, of the responsibility for such child care activity. The nurses also defined their work roles in terms of their own traditional, professional commitment to individuals, families and communities, and felt less bound by or even aware of the corporate responsibility of their employing health board. It is concluded that the enactment of new legislation and allocation of additional resources do not resolve the issues of inter-disciplinary collaboration in this area.

Adolescent↗

Court-ordered assessment: impact of maternal noncompliance in child maltreatment cases.

Parental noncompliance to court orders is associated with several factors that jeopardize safe and stable child care. We advanced three hypotheses: (1) maternal noncompliance to court-ordered assessment is associated with loss of child custody; (2) noncompliance is related to court clinic custody recommendations; and (3) noncompliance is stable across child protection and court clinic settings. Based on a sample of 56 court-referred child maltreatment cases, all hypotheses were confirmed. Results are discussed in terms of: (a) maternal noncompliance as a marker for high-risk child care; (b) our limited understanding of the phenomenal meaning of noncompliance; and (c) the dearth of empirically derived intervention methods.

Analysis of Variance↗

Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization.

The study described in this report demonstrates that peripheral lymph nodes draining nonmucosal tissues can effectively serve as induction sites for the establishment of common mucosal immunity if the microenvironmental conditions are altered to mimic those normally present within mucosa-associated lymphoid tissues (e.g., Peyer's patches). Lymph node lymphocytes exposed in situ to the immunomodulatory influences of the hormone 1 alpha, 25-dihydroxy vitamin D 3 were found to produce less gamma interferon and interleukin-2 (IL-2) and far more IL-4, IL-5 and IL-10 than lymphocytes from control animals. When couples with vaccination with hepatitis B surface antigen (HBsAg), the hormone, immunomodulated switch from a peripheral lymph node phenotype to a Peyer's patch-like pattern promoted the induction of both a systemic and a common mucosal immune response. This was determined by the observed increased concentrations of serum anti-HBsAg antibody and by finding that anti-HBsAg secretory antibodies were detectable in urogenital, lachrymal, fecal and oral secretions only in the hormone-treated animals. In addition, specific antibody-secreting cells were detectable in the lamina propria of the lungs and small intestines of the hormone-treated animals subsequent to vaccination, indicating that the homing properties of antigen-specific B cells were being affected by the treatment procedure. The humoral and mucosal immune responses were further augmented if both 1 alpha, 25-dihydroxy vitamin D 3 and dehydroepiandrosterone were used together as hormonal immunomodulators. This novel immunization technique may afford new opportunities to effectively intervene in sexually transmitted diseases and other diseases caused by mucosal pathogens.

Adjuvants, Immunologic↗

High frequency chest compression therapy: a case study.

A new device, the ThAIRapy Bronchial Drainage System, enables patients with cystic fibrosis to self-administer the technique of high frequency chest compression (HFCC) to assist with mucociliary clearance. We review the literature on HFCC and outline a case study of a patient currently using the ThAIRapy Bronchial Drainage System. While mucociliary clearance and lung function may be enhanced by HFCC therapy, more research is needed to determine its efficacy, cost benefits, and optimum treatment guidelines. Although our initial experience with the patient using this device has been positive, we were unable to accurately evaluate the ThAIRapy Bronchial Drainage System.

Adult↗