PubMed Health⌕ Search

Biomedical subjects

A Mortimer

Publications and source records attributed to A Mortimer.

At least 19 recordsLinked to original sources
PubMed2005

Estrogen for schizophrenia.

BACKGROUND: In terms of clinical outcomes, women with schizophrenia seem to fare better then men, but appear more vulnerable to psychotic illness in the period after birth and menopause. As these vulnerable periods to psychosis are associated with estrogen withdrawal, this hormone has been proposed as a treatment for schizophrenia. OBJECTIVES: To evaluate the clinical effects of estrogens alone or in combination with progesterone, as a sole treatment or as an adjunctive therapy, for the treatment of schizophrenia or schizophrenia-like illnesses. SEARCH STRATEGY: Electronic searches of the Cochrane Schizophrenia Group's Register (October 2003) was supplemented with manual reference inspection of all identified studies. Authors of trials were contacted for further material and archive information. SELECTION CRITERIA: All randomised clinical trials comparing estrogens with or without progesterone, as a sole or adjunctive treatment for people with schizophrenia or other similar serious, non-affective psychotic illness. DATA COLLECTION AND ANALYSIS: We evaluated data independently and analysed on an intention to treat basis. For binary data we calculated the fixed effect relative risk (RR) and its 95% confidence interval (CI). For continuous non-skewed data, we calculated weighted mean differences. MAIN RESULTS: All available evidence relates to women. Four studies (n=108) compared estrogen only with placebo. Short-term scores for general mental state showed no significant difference between groups (n=24, 1 RCT, WMD PANSS for 100mcg comparison -2.26 CI -15.4 to 10.9). Data from all four studies showed overall loss from the studies was low ( 5%), with no significant differences between groups (n=96, 4 RCTs, RR 0.95 CI 0.2 to 6.1). Skewed continuous data from two studies showed no clear differences in ratings of movement disorders. One medium-term unpublished study (n=14) compared estrogen and progesterone with placebo. Data at six months showed no difference between groups for total scores (n=9, WMD PANSS -25.3 CI -51 to 0.1). For negative symptoms, results favoured the estrogen and progesterone group (n=9, WMD PANSS negative subscale -9.0 CI -17 to -0.9). For loss to follow up there was no difference between groups (n=10, RR 0.33 CI 0.02 to 6.7). This trial used many cognitive tests and one visual retention test showed statistically significant differences favouring the treatment group: total scores (n=8, WMD -3.5 CI -5.7 to -1.3). AUTHORS' CONCLUSIONS: Adjunctive estrogen with or without progesterone does not appear to offer convincing advantages over placebo. Before any more research is undertaken in this area, all completed and unpublished work should be made available in order to ensure that more trials are justified.

Estrogens↗
PubMed2000

beta-Scission of C-3 (beta-carbon) alkoxyl radicals on peptides and proteins: a novel pathway which results in the formation of alpha-carbon radicals and the loss of amino acid side chains.

Exposure of proteins to radicals in the presence of O(2) brings about multiple changes in the target molecules. These alterations include oxidation of side chains, fragmentation, cross-linking, changes in hydrophobicity and conformation, altered susceptibility to proteolytic enzymes, and formation of new reactive groups, including hydroperoxides. These processes can result in the loss of structural or enzymatic activity. Backbone fragmentation is known to occur via a number of mechanisms, most of which involve hydrogen abstraction from the alpha-carbon site on the backbone. In this study, we demonstrate that initial attack at a side chain site, the beta-position (C-3), can give rise to formation of alpha-carbon radicals, and hence backbone cleavage, via the formation and subsequent beta-scission of C-3 alkoxyl radicals. This beta-scission reaction is rapid (k estimated to be >10(7) s(-)(1)) even with primary alkoxyl radicals derived from Ala residues, and occurs when the alkoxyl radicals are generated from a variety of precursors, including hydroperoxides and nitrate esters. These reactions release the former side chain as a reactive aldehyde or ketone; thus, Ala peptides release high yields of methanal (formaldehyde). This product has been quantified with a number of oxidized peptides and proteins, and can account for up to 64% of the initial attacking radicals with some Ala peptides. When quantified together with the hydroperoxide precursors, these species account for up to 80% of the initial radicals, confirming that this is a major process. Methanal causes cell toxicity and DNA damage and is an animal carcinogen and a genotoxic agent in human cells. Thus, the formation and subsequent reaction of alkoxyl radicals formed at the C-3 position on aliphatic amino acid side chains on peptides and proteins can give rise to both backbone fragmentation and the release of further reactive species which can cause cell toxicity and mutagenicity.

Alcohols↗
PubMed1999

Study on genotoxic effects of the space environment: a comparison between experienced cosmonauts and unexposed Russian twins.

The molecular analysis of T-lymphocytes from experienced cosmonauts and seven pairs of unexposed twins was performed [M. Khaidakov, D. Young, H. Erfle, A. Mortimer, Y. Voronkov, B.W. Glickman, Molecular analysis of mutations in T-lymphocytes from experienced soviet cosmonauts, Environ. Mol. Mutagen, 30 (1997) 21-30; J. Curry, G. Bebb, J. Moffat, D. Young, M. Khaidakov, A. Mortimer, B.W. Glickman, Similar mutant frequencies observed between monozygotic twins, Human Mutation, 9 (1997) 445-451]. Hprt mutant frequencies (MF) in both datasets were considerably higher (38.0+/-14.6x10(-6) in cosmonauts, and 18.5+/-8.9x10(-6) in twins) than in the background Western control (8-12x10(-6)), [A.D. Tates, F.J. van Dam, H. van Mossel, H. Shoemaker, J.C.P. Thijssen, V.M. Woldring, A.H. Zwinderman, A.T. Natarajan, Use of the clonal assay for the measurement of frequencies of HPRT mutants in T-lymphocytes from five control populations, Mutation Res., 253 (1991) 199-213; R.F. Branda, L.M. Sullivan, J.P. O'Neill, M.T. Falta, J.A. Nicklas, B. Hirsch, P.M. Vacek, R.J. Albertini, Measurement of HPRT mutant frequencies in T-lymphocytes from healthy human populations, Mutation Res., 285 (1993) 267-279]. The distribution of mutations by class in the twin dataset was essentially similar to the background Western control, whereas cosmonaut samples demonstrated a significant excess of splice errors and complex mutations. The distribution of base substitutions showed similar trends in both the cosmonaut and twin samples, which are quite distinct compared to those seen in the Western control. The differences observed between cosmonaut and twin samples (a 2-fold higher MF and an excess of complex mutations in cosmonaut mutational spectra) could be an indication of possible effects of the space environment. However, these changes could also be age-related because the twin group was, on average, 17 years younger. Moreover, very similar patterns of base substitution distribution in both datasets suggest the involvement of certain region-specific factors reflected in mutational spectra. In order to discriminate between occupation and region-specific factors contributing to mutagenesis, an additional study involving trainees and cosmonauts with recent long-term flight experience is required.

Adult↗
PubMed1999

Symptom dimensions in old-age schizophrenics. Relationship to neuropsychological and motor abnormalities.

In most factor analytical studies of schizophrenic symptomatology, a three-factor solution was found. The aim of this study was to investigate symptomatological dimensions in old age and to clarify whether the dimensions correlate differently with neuropsychological and motor parameters. One hundred and thirty-one DSM-III-R chronic schizophrenics (mean age 68 years) were assessed using SANS, SAPS, a neuropsychological test battery and motor scales. Exploratory and confirmatory factor analyses yielded a model with three dimensions (negative, disorganized, paranoid), two of which (negative, disorganized) showed different correlations with neuropsychological and motor phenomena. Thus, three symptomatological dimensions could also be demonstrated in a chronic, old-age schizophrenic sample. The pathophysiological significance of the different correlations with neuropsychological and motor parameters should be clarified in neuroimaging and neuropathological studies.

Age Factors↗
PubMed1999

Active monitoring of 12,760 clozapine recipients in the UK and Ireland. Beyond pharmacovigilance.

BACKGROUND: People prescribed clozapine for treatment-resistant schizophrenia have mandatory haematological monitoring through a case register for identifying reversible neutropenia. AIMS: To quantify risk factors for agranulocytosis in subjects receiving clozapine. METHOD: Data from 12,760 subjects registered to receive clozapine from January 1990 to April 1997 were analysed. Risk factors for agranulocytosis were quantified using a Cox proportional-hazards regression analysis. RESULTS: The risk for agranulocytosis in Asian subjects was 2.4 times that in Caucasians (P = 0.03). There was an age-related increase in risk of 53% per decade (P = 0.0001). CONCLUSIONS: The case register yielded valuable information for guiding research into the causes of the haematological reactions.

Adolescent↗
PubMed1998

[Dimensions of schizophrenia in the elderly. Correlations with cognitive and motor symptoms].

In most factor analytical studies of schizophrenic symptomatology a three-factor solution was found. The aim of this study was to investigate symptomatological dimensions in old age and to clarify whether the dimensions correlate differently with neuropsychological and motor parameters. A total of 131 DSM-III-R schizophrenics (mean age 68 years) were assessed using SANS, SAPS, a neuropsychological test battery and motor scales. A factor analysis yielded three dimensions (negative, disorganized, paranoid), two of which (negative, disorganized) showed different correlations with neuropsychological and motor phenomena. Thus, three symptomatological dimensions could also be demonstrated in a chronic, old-age schizophrenic sample. The pathophysiological significance of the different correlations with neuropsychological and motor parameters should be clarified in neuroimaging and neuropathological studies.

Aged↗
PubMed1998

Prospective study into factors associated with aggressive incidents in psychiatric acute admission wards.

BACKGROUND: Factors associated with aggression among psychiatric in-patients are still poorly understood. Inconsistent published findings are partly attributable to methodological problems. Much previous research has been under taken in specialist settings, where conditions are likely to differ from those in acute admission wards. METHOD: Levels of aggression were ascertained weekly by staff report, using a reliable measure, for every patient on five acute admission wards and one locked intensive care ward at two hospitals prospectively over a five-month period. RESULTS: Levels of aggression varied considerably among the admission wards. Aggression was more common on the locked ward and among younger patients. Factors associated with aggression changed with time since admission (seldom examined in previous studies). Complex associations were found with gender, ethnic group and diagnosis. CONCLUSIONS: Some of the findings might be explicable by differences in ward environment, and staff-patient inter-actions. Further investigation into these is warranted.

Adolescent↗
PubMed1997

Similar mutant frequencies observed between pairs of monozygotic twins.

The relative contribution of both genetic and environmental factors to spontaneous mutation frequency in humans is unknown. We have investigated the contribution of genetic factors to this phenomenon by determining the in vivo mutant frequency at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in circulating T-lymphocytes obtained from pairs of monozygotic twins. hprt mutant frequencies were determined three times over fourteen days in six sets of monozygotic male twins (mean age 30) taking part in a Russian Space Program inclined bed rest experiment. Blood samples were obtained prior to, during, and immediately following the experiment. Mononuclear cells were separated, frozen, and flown to Canada for analysis using the hprt T-lymphocyte clonal assay. There is no evidence within this data set to demonstrate that the period of inclined bed rest to simulate the effects of weightlessness had any effect on the observed mutant frequency. However, the average mutant frequency for the six sets of Russian twins was found to be three times higher than that of Western counterparts. More surprisingly, the spontaneous mutant frequency of monozygotic twins was found to be much more similar within pairs than between pairs of twins. These data suggest that the contribution of genetics in the determination of mutation frequency is substantial. However, whether high concordance within twin pairs reflects shared environmental experience as well as common genetic factors is not entirely clear. More data will be required to distinguish genetic from environmental factors and to determine the degree to which mutant frequency is genetically determined.

Adult↗
PubMed1997

Molecular analysis of mutations in T-lymphocytes from experienced Soviet cosmonauts.

Somatic mutation in five cosmonauts who have completed spaceflights of 7 to 365 days was analyzed using the clonal HPRT assay. The doses received in space by the cosmonauts ranged from 4 to 127 mGy. hprt mutant frequencies were 2.4-5.0-fold higher than age-corrected values established for healthy, unexposed subjects in western countries [Tates et al. (1991): Mutat Res 253: 199-213; Branda et al. (1993): Mutat Res 285: 267-279] and 2- to 3-fold higher than those determined for unexposed individuals residing in Russia [Jones et al. (1995): Mutat Res 338: 129-139]. A total of 107 collected mutant clones were analyzed by multiplex PCR. No excess of deletions was detected and their frequency did not correlate with either accumulated dose or the age of the cosmonauts. In 62 mutants cDNA was isolated by RT-PCR and sequenced. Those with splicing errors, as well as the mutants that did not produce cDNA, were further analyzed by the sequencing of exon(s)-containing fragments amplified from genomic DNA. The mutational spectrum recovered from the cosmonauts differed substantially from that of unexposed healthy subjects (P = 0.042), and exhibited an increased incidence of splicing errors, frameshifts, and complex mutations. Higher frequencies of contribution of AT-->GC transitions and GC-->TA transversions were also observed. The increased mutant frequencies and observed shifts in mutational spectra likely indicate a combination of potential influences, including environment, lifestyle, and occupational exposures. Further elucidation of these potential influences will require a more extensive study involving the general population sharing similar environment, cosmonauts in training and cosmonauts participating in space flights.

Adult↗
PubMed1996

NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia.

We investigated the expression of the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor, in brains from a population of well characterized schizophrenic patients who prospectively consented to tissue donation. Levels of NR-1 mRNA in tissue homogenates of superior temporal cortex were reduced by 30% in cognitively impaired schizophrenic patients compared with controls (p < 0.04), while levels in patients without cognitive impairment showed no such reduction. The NR-1 mRNA deficit was significantly correlated with general cognitive function as rated with the Global Deterioration scale (p < 0.001), the Mini-Mental State examination (p < 0.01) and the premorbid IQ determined using the National Adult Reading Test (NART, p < 0.01). NR-1 mRNA concentration was not correlated with age, sex, pH or postmortem delay in the control and schizophrenia group when analysed separately or combined. There was, therefore, a significant correlation between NR-1 mRNA loss and cognitive deterioration in patients with schizophrenia.

Adult↗
PubMed1995

Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia.

No consistent markers of pathology have been established yet in schizophrenia, although abnormalities in frontal and temporal structures are indicated from positron emission tomography (PET) studies. We have used in situ hybridization to investigate functional changes focusing on the quantitation of cholecystokinin (CCK) mRNA, whose product has been shown to be depleted in schizophrenia. CCK mRNA and G(o) alpha-subunit mRNA were measured in eight schizophrenic and eight control subjects matched for age and postmortem delay. The study revealed a marked decrease in CCK mRNA of 83% in frontal cortex (BA10) and 63% in superior temporal cortex (BA22) in schizophrenia with no change in G(o) alpha-subunit mRNA in either region. This study was extended to a further series of eight patients to determine the reproducibility of this effect and to quantitate laminar changes in CCK mRNA. Quantitation of CCK mRNA in inner cortical layers (layer V/VI) was carried out in frontal and temporal cortex in comparison with G(o) alpha-subunit mRNA, which is also concentrated in this region; this study showed a similar selective decrease in CCK mRNA in frontal and temporal cortex of 47% and 51%, respectively. A confirmatory decrease in CCK mRNA was also obtained by slot blot analysis of CCK mRNA in tissue extracts of frontal cortex by reference to levels of beta-tubulin mRNA, CCK mRNA:beta-tubulin mRNA was significantly decreased (67%) in schizophrenic tissue compared to control tissue. There was no significant correlation of CCK mRNA loss with neuroleptic treatment or duration of illness.

Adult↗
PubMed1995

Elder abuse and dementia--a pilot study.

An anonymous postal questionnaire was distributed to 200 members of a voluntary organisation providing information and support for the carers of dementia sufferers. Carers were asked about the possible occurrence of verbal, physical abuse and neglect. Those carers who admitted to any form of abuse were compared with those who did not and risk factors in both carers and patients were analysed to determine risk factors for abuse. Fifty-five per cent of carers admitted to some form of abuse with verbal abuse being the most common form. Verbal abuse was associated with a poor premorbid relationship and social isolation of the carer and was found to be a risk factor for physical abuse. Those carers who had high GHQ scores and who had been caring for longer were more likely to physically abuse the person they cared for. This study supports the hypothesis that various categories of abuse have different correlates.

Adult↗
PubMed1994

Space radiation dosimetry using bubble detectors.

Bubble detectors--a new development in radiation detection--has only recently been used for radiation measurements in space. One important characteristic of the bubble detector is that it operates on a phenomenon which bears considerable resemblance to biological response. Recent experimental results from irradiating bubble detectors with high-energy heavy ions point to the need to re-examine the methodology used for assessing space radiation and the relevance of conventional quantities such as dose equivalent for space dosimetry. It may be that biological hazard associated with the intensely ionizing events--associated with nuclear fragmentation but delivering relatively small dose equivalent--may be much more important than that associated with lightly ionizing events which comprise the bulk of the conventional radiation dose equivalent.

Canada↗
PubMed1992

Propofol to provide sedation after coronary artery bypass surgery. A comparison of two fixed rate infusion regimens.

Propofol (2,6, di-isopropylphenol) was given by continuous intravenous infusion to provide sedation following coronary artery bypass surgery. The need for additional sedation, analgesia and hypotensive agents was assessed at two propofol infusion rates (10 or 25 micrograms/kg/min). Both rates provided clinically satisfactory conditions. There were no differences in the requirements for analgesia or vasodilators between the groups. The higher infusion rate of 25 micrograms/kg/min was associated with a lower requirement for additional sedation but a more frequent need to stop the infusion temporarily to prevent hypotension.

Adult↗