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M H Lewis

Publications and source records attributed to M H Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer.

Brain-derived neurotrophic factor (BDNF) was expressed via injection of viral vector into the substantia nigra pars compacta (SNc) to investigate its influence on nigrostriatal dopaminergic activity and locomotor behavior. The recombinant adeno-associated virus (rAAV) vector, pTR-BDNFmyc, incorporated the neuron-specific enolase (NSE) promoter and the internal ribosome entry site (IRES) element driving expression of both epitope-tagged BDNF and green fluorescent protein (GFP) bicistronically. The control vector, pTR-UF4, incorporated NSE promoter-driven GFP expression only. Transgene expression persisted in both vector groups throughout the 9 month course of the study. Partial 6-hydroxydopamine (6-OHDA) lesions were conducted in the SNc ipsilateral to, and 6 months after, transduction with either the pTR-BDNFmyc or the pTR-UF4. Transgenic BDNFmyc had no effect on the number of tyrosine hydroxylase (TH)-labeled neurons in the SNc after 6-OHDA-lesions, but did block the amphetamine-induced, ipsiversive, turning-behavior caused by the lesion in the pTR-UF4 group. The BDNFmyc-transduced group also demonstrated more locomotor activity and rotational activity contralateral to the lesioned side than did the pTR-UF4-transduced group. Long-term, stable expression of BDNF can therefore modulate locomotor activity without significantly affecting nigrostriatal dopaminergic survival.

Adrenergic Agents↗
PubMed1999

Differences in NK cell function in mice bred for high and low aggression: genetic linkage between complex behavioral and immunological traits?

In previous studies, we found differences in cellular immune responsiveness in Institute for Cancer Research (ICR) mice selectively bred for high and low levels of aggression. Compared to the high aggressive line, the low aggressive line had low levels of natural killer (NK) and T cell activity and increased susceptibility to tumor development. To dissect further this novel association, experiments were designed to test two competing hypotheses. The first hypothesis was that the phenotypic expression of the line differences in NK cell activity are dependent on and regulated by the expression of high and low levels aggressive behavior in the lines. The alternative hypothesis was that the differences in immune status are independent of the expression of aggression by the lines, suggesting linkage between a subset of genes involved in determining these complex behavioral and immunological traits or pleiotropic gene effects on both traits. In Experiment 1, three conditions of postweaning social experience (mice singly housed, group housed within line, or group housed between lines) were tested in males to determine whether experiential conditions which modify the expression of aggression would in turn modify the line differences in NK cell activity. This experiment revealed that the difference in NK cell activity between high aggressive and low aggressive male mice was attributable to line only. The different postweaning social conditions examined had no effect on modifying the differences in NK activity, and social dominance hierarchy did not correlate with levels of NK cell activity. Whereas males of the high and low lines exhibit differences in aggressive behaviors across most contexts, females do not exhibit such differences except in response to an intruder during the postpartum period. Therefore, in Experiment 2 we compared the NK cell activity of nulliparous females of the high and low aggressive lines. Under these conditions, females of the low aggressive line had low levels of NK activity compared to high aggressive females (differences comparable to those seen between males of the high and low lines). Taken together, these experiments lend support to the hypothesis that this association may be due to a genetic linkage between subsets of genes involved in determining these complex behavioral and immunological traits, or may possibly represent a fortuitous association which occurred during the selective breeding.

Aggression↗
PubMed1999

A rodent model of spontaneous stereotypy: initial characterization of developmental, environmental, and neurobiological factors.

Stereotypies are patterns of motor behavior that are repetitive, excessive, topographically invariant, and that lack any obvious function or purpose. In humans, stereotyped behaviors are associated with psychiatric, neurological, and developmental disorders. In animals, stereotypy has been frequently associated with adverse environmental circumstances and often related to alterations in striatal dopamine. To assess the development of stereotyped behaviors and to test the hypothesis that these behaviors are associated with environmental restriction, deer mice were housed in either standard laboratory cages or larger, enriched cages, and the development of stereotypy was followed from weaning over a 17-week period. Standard-caged deer mice engaged in stereotyped behaviors at a higher rate and developed these behaviors more quickly when compared to animals in enriched caging. Additionally, enriched caging was associated with higher rates of patterned running, whereas jumping and backward somersaulting were typically observed in standard cages. In addition, there was a significant effect of litter, but no effect of sex or cage, on the time to develop stereotypy. No differences were found in the density of either striatal D1 or D2 dopamine receptors or the concentration of striatal dopamine or its metabolites as a function of rearing condition or as a function of whether the animals developed stereotypy. These results characterize the development of stereotypies in this species, demonstrate the importance of environmental conditions in the genesis of stereotypy, and suggest that alterations in striatal dopamine content or dopamine receptor density do not account for the expression of stereotyped behaviors in this model.

Aging↗
PubMed1999

Variation in vascular activity in the United Kingdom: an analysis of five regions.

BACKGROUND: The aim of this study was to define variations in vascular activity that may exist between different demographic regions of the UK. METHODS: Five regions were studied. Data were obtained on OPCS codes for vascular surgery 1994-95 from the Department of Health or Welsh Office. Mortality and cause of death statistics were calculated for each region from OPCS data. RESULTS: Ranges of vascular reconstruction, iliac and superficial femoral artery angioplasty and major amputation were 26.2-44, 10.5-23.0 and 11.5-15.7 per 100,000 population, respectively. The highest rates of amputation were seen in areas of high standard mortality and highest death rate from atheroma and ischaemic heart disease. Rates of amputation also rose in proportion to the number of men in the population aged > 60 years. CONCLUSION: Variations exist in vascular activity between different regions. This may be caused by demographic differences in the population. It needs to be considered when calculating the number of vascular surgeons required in different areas of the country.

Amputation, Surgical↗
PubMed1999

Mortality from ruptured abdominal aortic aneurysm in Wales.

BACKGROUND: The aim of this study was to identify the incidence of, and mortality in, patients with a ruptured abdominal aortic aneurysm (AAA) reaching hospital alive in Wales. METHODS: Patients who presented with a ruptured AAA between September 1996 and August 1997 were analysed. Data were collected prospectively by an independent body, observing strict confidentiality. RESULTS: Some 233 patients with a confirmed ruptured AAA were identified, giving an incidence of eight per 100 000 total population. Some 133 patients (57 per cent) underwent attempted operative repair; 85 (64 per cent) of these died within 30 days. Of the 233 patients, 92 were admitted under the care of a vascular surgeon and 141 under a non-vascular surgeon. Vascular surgeons operated on 82 patients (89 per cent), of whom 50 (61 per cent) died, whereas non-vascular surgeons operated on 51 patients (36 per cent), of whom 35 (69 per cent) died. DISCUSSION: This study is unique as it is an independent prospective study of mortality in patients with a ruptured AAA who reached hospital alive. Mortality was independent of the operating surgeon, but vascular surgeons turned down significantly fewer patients than non-vascular surgeons (11 versus 64 per cent, P < 0.001).

Aged↗
PubMed1999

A prospective controlled trial of the efficacy of isopropyl alcohol wipes before venesection in surgical patients.

It has previously been suggested that skin preparation before venesection with antiseptic agents is unnecessary. However thousands of doctors and medical students continue to use isopropyl alcohol (IPA) swabs for venesection, at an estimated cost of 10,000 P per annum in a 500 bed hospital. An audit of IPA swab use among junior doctors and medical students at our institution was undertaken; 76% of doctors and 100% of medical students routinely prepared the skin with alcohol before venesection and only one used the swabs correctly. A randomised single-blind controlled trial was conducted of IPA versus no IPA skin preparation before venesection. There were 194 patients in the study, 93 in the IPA group and 101 controls. There was no statistical difference with respect to complications at the venepuncture site between the two groups.

2-Propanol↗
PubMed1999

Prevalence of abdominal aortic aneurysms in urology patients referred for ultrasound.

During a 3-year period, all urology patients over the age of 50 years referred for ultrasound investigation of the renal tract, underwent routine examination of the abdominal aorta. A total of 2281 patients were examined (1798 men and 483 women) and an abdominal aortic aneurysm was detected in 57 (2.5%). In men over the age of 65 years, 47 aneurysms were detected (4.9%). The mean time taken to scan the aorta was 43 s. We recommend the routine practice of examining the abdominal aorta in all men over the age of 60 years referred for ultrasound examination of the renal tract.

Age Distribution↗
PubMed1998

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: transgenic rescue and interactions with gene background.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an approximately 50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKCepsilon expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKCepsilon expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes.

Animals↗
PubMed1998

D1 dopamine receptors and the reversal of isolation-induced behaviors in mice.

In a previous study, it was demonstrated that the high rates of social reactivity exhibited by isolated male mice in a dyadic encounter were mediated, at least in part, by an increased sensitivity of the D1 dopamine receptors. The present research was guided by the hypothesis that the behavioral effects of isolation are reversible, and that changes in dopaminergic function support this reversibility. To this end, mice selectively bred for high and low levels of aggression were reared in isolation from weaning (21 days) to puberty (45 days), at which point they were either assigned to groups or left in isolation until day 69. By comparison to the continuous isolation condition, mice that eventually formed groups exhibited significantly less reactivity in a dyadic test conducted on day 69, showed a reduced response to dihydrexidine (DHX), and a decreased density of D1 dopamine receptors. This experiment provided evidence for the plasticity of the neurobiological system supporting reactive responses, and confirmed the view that its functional organization is open to experientially-induced changes.

Animals↗
PubMed1998

D2-like dopamine receptor mediation of social-emotional reactivity in a mouse model of anxiety: strain and experience effects.

We examined the effects of the D2-like dopamine receptor agonist quinpirole on social-emotional reactivity in two inbred mouse strains. An important objective of this study was to determine whether these effects could be modulated by differential housing conditions (i.e., isolation versus group housing). Moreover, as motor activity is an important control for the assessment of drug effects on emotional behavior, the effects of quinpirole were tested in two inbred mouse strains (A/J and C57BL/6J) low and high in motor activity, respectively. Levels of emotional reactivity were assessed in response to mild social stimulation provided by a nonaggressive conspecific. Quinpirole increased stationary forms of reactivity (i.e., startle, kicking, defensive posture, vocalization) in both isolated and group-housed A/J mice. This effect was more pronounced and observed at lower doses in isolated than in group-housed A/J mice. Quinpirole also induced jump behavior in isolated but not group-housed A/J mice. The shift to the left in the dose-response curve of quinpirole in isolated A/J mice indicated that D2-like dopamine receptor functions can be altered by social experience. Quinpirole only marginally increased stationary and locomotor reactivity (i.e., jump) in isolated C57BL/6J mice, whereas it markedly reduced motor activity in group-housed mice of this strain. The investigation of emotional reactivity within a social context and using strains that differ in motor activity permitted the effects of drugs on emotional reactivity to be dissociated from the effects on motor activity. Given that social-emotional reactivity was elicited by what typically should have been mild and nonthreatening stimuli, this model may be highly relevant to understanding the neurobiology of anxiety. Finally, these data support an important role for dopamine in the mediation of social-emotional reactivity.

Animals↗
PubMed1998

Accuracy of centrally recorded OPCS codes for vascular surgery in the United Kingdom.

AIM: Centrally recorded OPCS codes are based upon district returns. The aim of this study is to determine the accuracy of this system with regard to vascular surgery. METHODS: Prospectively recorded audit data for vascular and endovascular procedures were compared with those obtained from the Department of Health and Welsh Office. Five U.K. hospitals were involved in the study. Data were obtained for the twelve months, 1 April 1994-30 March 1995 (these being the most up to date figures available). RESULTS: The total number of arterial reconstructions based on audit data was 1082. Those recorded by the OPCS codes were 743. This represents a discrepancy of -31.3% (range for the five hospitals: -13.1% to -63.8%). When examining specific codes similar discrepancies were seen. For example, in one hospital 38 AAA repairs were carried out but only two were centrally recorded. However, examination of ICD9 codes (relating to hospital admissions) for that hospital showed that 38 patients with AAA were admitted. A similar wide variation was seen when examining iliac and superficial femoral artery endovascular procedures. Despite the discrepancies of audit and OPCS data, the codes for reconstructions did reflect relative workload of the different hospitals. CONCLUSION: This study shows that there is a marked underestimate of vascular workload when comparing central recorded data with that obtained from local audit. Marked variation is seen in the accuracy of data submitted from different hospitals.

Angioplasty, Balloon↗
PubMed1998

A survey of current attitudes of British and Irish vascular surgeons to venous sclerotherapy.

AIM: To determine current practice amongst vascular surgeons regarding venous sclerotherapy. METHOD: A postal questionnaire was sent to 350 members of the Vascular Surgical Society of Great Britain and Ireland. RESULTS: There were 218 replies (62%). Forty surgeons (18.3%) never injected varicose veins (VV) although six injected venous flares. Most surgeons (n = 168, 77.1%) reserved sclerotherapy for residual VV postoperatively. Primary varicose veins without proximal incompetence were injected by 152 (69.7%) and recurrent VV without proximal incompetence by 141 (64.7%). Sixteen surgeons only injected residual postoperative VV. Few surgeons injected VV in the presence of proximal incompetence. Where specified, 46% of respondents were injecting fewer VVs than in previous years. Only 5% were injecting more. By contrast, 44% were injecting more venous flares than previously (p < 0.001). Eight different sclerosants were used, the commonest being STD (146 surgeons) and Sclerovein (33). The median number of patients treated with sclerotherapy was 11-50 per year compared with 51-150 per year who were operated upon. The median time advised for compression was 2 weeks (range--a few minutes--2 months). Treatment was repeated at a median of 4 weeks (0-6 months). Thirty-two surgeons obtained written consent. All but eight respondents discussed potential complications, the commonest being staining and ulceration. Forty-six surgeons had patients who had experienced serious complications, the commonest being ulceration. There was one reported death from a pulmonary embolus. CONCLUSION: Sclerotherapy is being used less frequently for VV. Most surgeons use it for residual VV and for those without proximal incompetence.

Attitude of Health Personnel↗
PubMed1997

Effects of the putative dopamine D3 receptor antagonist PNU 99194A on motor behavior and emotional reactivity in C57BL/6J mice.

Due to the regional expression of D3 dopamine receptors in limbic areas of the brain, there has been considerable interest in the potential role of this receptor subtype in mediating emotional behavior. Previous studies in habituated rats have shown that the putative dopamine D3 receptor antagonist 5,6-dimethoxy-2-(di-n-propylamino)indan (PNU 99194A) increased locomotor behavior. The present study examined the effects PNU 99194A on motor and emotional behaviors in C57BL/6J mice. Motor behavior was assessed in both habituated and nonhabituated mice. Emotional behavior was assessed using the elevated plus-maze and a social context involving an isolated C57BL/6J mouse and a nonaggressive conspecific. In mice habituated to the activity chamber prior to drug administration, PNU 99194A increased locomotion and rearing at lower doses (5, 10 mg/kg) whereas higher doses (20, 30 mg/kg) reduced these behaviors early in the test session. Thigmotaxis was increased independently of the effects on motor behavior. In mice exposed to the activity chamber for the first time, PNU 99194A produced a weak motor activation at lower doses and an initial decrease in motor behavior at higher doses that was followed by an increase in locomotion later in the test session. PNU 99194A had no systematic effects on activity in the elevated plus-maze, but dose-dependently increased flight reactivity in the social reactivity paradigm. These and previous findings raise questions about the role of dopamine D3 receptors in mediating motor behavior and emotional reactivity as well as the pharmacology of this putative dopamine D3 receptor antagonist.

Animals↗