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Biomedical subjects

A Diamond

Publications and source records attributed to A Diamond.

At least 19 recordsLinked to original sources
PubMed2005

The effect of deep brain stimulation on quality of life in movement disorders.

Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.

Anxiety↗
PubMed2001

National level promotion of physical activity: results from England's ACTIVE for LIFE campaign.

STUDY OBJECTIVE: To assess the impact of a national campaign on awareness of the campaign, change in knowledge of physical activity recommendations and self reported physical activity. DESIGN: three year prospective longitudinal survey using a multi-stage, cluster random probability design to select participants. SETTING: England. PARTICIPANTS: A nationally representative sample of 3189 adults aged 16-74 years. MAIN OUTCOME MEASURES: Awareness of the advertising element of the campaign, changes in knowledge of physical activity recommendations for health and self reported physical activity. RESULTS: 38% of participants were aware of the main advertising images, assessed six to eight months after the main television advertisement. The proportion of participants knowledgeable about moderate physical activity recommendations increased by 3.0% (95% CI: 1.4%, 4.5%) between waves 1 and 2 and 3.7% (95% CI: 2.1%, 5.3%) between waves 1 and 3. The change in proportion of active people between baseline and waves 1 and 2 was -0.02 (95% CI: -2.0 to +1.7) and between waves 1 and 3 was -9.8 (-7.9 to -11.7). CONCLUSION: The proportion of participants who were knowledgeable about the new recommendations, increased significantly after the campaign. There was however, no significant difference in knowledge by awareness of the main campaign advertisement. There is no evidence that ACTIVE for LIFE improved physical activity, either overall or in any subgroup.

Adolescent↗
PubMed2000

Alkaline response genes of Saccharomyces cerevisiae and their relationship to the RIM101 pathway.

Environmental pH exerts broad control over growth and differentiation, but the molecular responses to external pH changes are poorly understood. Here we have used open reading frame macroarray hybridization to identify alkaline response genes in Saccharomyces cerevisiae. Northern or lacZ fusion assays confirmed the alkaline induction of two ion pump genes (ENA1 and VMA4), several ion limitation genes (CTR3, FRE1, PHO11/12, and PHO84), a siderophore-iron transporter gene (ARN4/ENB1), two transcription factor genes (NRG2 and TIS11), and two predicted membrane protein genes (YAR068W/YHR214W and YOL154W). Unlike ENA1 and SHC1, these new alkaline response genes are not induced by high salinity. The known pH-responsive genes in other fungi depend on the conserved PacC/Rim101p transcription factor, but induction of several of these new genes relied upon Rim101p-independent pH signaling mechanisms. Rim101p-dependent genes were also dependent on Rim13p, a protease required for Rim101p processing. The Rim101p-dependent gene VMA4 is required for growth in alkaline conditions, illustrating how Rim101p may control adaptation. Because Rim101p activates ion pump genes, we tested the role of RIM101 in ion homeostasis and found that RIM101 promotes resistance to elevated cation concentrations. Thus, gene expression surveys can reveal new functions for characterized transcription factors in addition to uncovering physiological responses to environmental conditions.

Base Sequence↗
PubMed2000

A single-transformation gene function test in diploid Candida albicans.

The fungal pathogen Candida albicans is naturally diploid, and current gene disruption strategies require two successive transformations. We describe here a genetic construct (UAU1) for which two copies may be selected. Insertion of UAU1 into one genomic site, after a single transformation, allows selection for segregants with two copies of the insertion. Major classes of segregants are those carrying homozygous insertion mutations and allelic triplications, which have two insertion alleles and a wild-type allele. Thus nonessential and essential genes may be distinguished rapidly through PCR tests for homozygosis and triplication. We find that homozygous mutations may be isolated at three nonessential loci (ADE2, RIM20, and YGR189), while only allelic triplications were found at two essential loci (SNF1 and CDC28). We have unexpectedly isolated homozygous mutants with mutations at CDC25; they are viable but defective in filamentation on serum-containing medium. The UAU1 cassette is thus useful to assess rapidly the essentiality of C. albicans genes.

Base Sequence↗
PubMed2000

An audit of subcutaneous syringe drivers in a non-specialist hospital.

The use of syringe drivers as a method of drug delivery to control symptoms in palliative care is a common and accepted practice, but one which has evolved rather than been subject to close multiprofessional scrutiny and guideline formation. There is evidence that adverse incidents may arise as a result of syringe driver use (Medical Devices Agency (MDA), 1998), for example, errors in drug calculations, drug stability, equipment failure (including disconnection) and the wrong rate of infusion. Inadequate user training, poor servicing of equipment and inadequate documentation and record keeping are all thought to be contributing factors (MDA, 1998). In the hospital where this audit was carried out, syringe drivers are used to administer drugs to patients with cancer during the palliative phase of illness. The purpose of this clinical audit was to establish the standard of current practice in wards where syringe drivers were being used. A retrospective study of 13 cases of syringe driver use is presented. The results highlight many areas of unregulated practice with regard to setting up, monitoring and maintenance of syringe drivers. The choice of drugs and doses prescribed, evaluation of treatment responses and review of treatment regimens were also areas of concern. Guidelines for the use of syringe drivers in non-specialist hospitals are put forward.

Adult↗
PubMed2000

The prevalence and types of coronary artery anomalies in Northern Ireland.

Coronary artery anomalies are uncommon, with a reported prevalence ranging from 0.2% to 1.6%. It is important that those who undertake coronary angiographic procedures are aware of the spectrum of these anomalies. Interventional percutaneous coronary revascularisation procedures are widely used in the management of patients with symptomatic coronary atherosclerosis. The presence of a coronary artery anomaly may make these procedures technically challenging. We have reviewed the Cardiac catheterisation database at the Royal Victoria Hospital, Belfast, and report the prevalence and types of these anomalies.

Adult↗
PubMed1999

Cognitive deficits in a genetic mouse model of the most common biochemical cause of human mental retardation.

Phenylalanine hydroxylase (Pah)-deficient "PKU mice" have a mutation in the Pah gene that causes phenylketonuria (PKU) in humans. PKU produces cognitive deficits in humans if it is untreated. We report here the first evidence that the genetic mouse model of PKU (Pah(enu2)) also produces cognitive impairments. PKU mice were impaired on both odor discrimination reversal and latent learning compared with heterozygote littermates and with wild-type mice of the same BTBR strain. A small container of cinnamon-scented sand was presented on the right or left, and nutmeg-scented sand was presented on the other side; left-right location varied over trials. Digging in sand of the correct scent was rewarded by finding phenylalanine-free chocolate. To prevent scent cuing, new containers were used on every trial, and both containers always contained chocolate. Digging in the incorrect choice was stopped before the chocolate was uncovered. Once criterion was reached, the other scent was rewarded. PKU mice were impaired on reversals 2, 3, and 4. They were also impaired in latent learning. On day 1, half the mice were allowed to explore a maze and discover the location of water. On day 2, all mice were water-deprived and were placed in the maze. Whereas pre-exposed wild-type and heterozygous mice showed evidence that they remembered the location of the water and hence could find the water faster on day 2, pre-exposed PKU mice showed no significant benefit from their pre-exposure on day 1.

Animals↗
PubMed1999

Early developments in the ability to understand the relation between stimulus and reward.

Delayed nonmatching to sample (DNMS) is used to test the recognition memory function dependent on the medial temporal lobe. Children cannot succeed on this task until about 21 months. Because robust recognition is present well before then, the late emergence of another ability must account for the late success on DNMS. Evidence is presented here that the critical late-maturing competence is the ability to grasp the relation between stimulus and reward--that is, to understand that the stimulus is a symbol or marker for the reward. Infants of 9 and 12 months were tested on 3 conditions of DNMS. A sample object was presented. After a delay, the sample and a novel object appeared; choice of the novel object was rewarded. In the standard task, the reward was in a well beneath the stimulus. In the verbal-reward condition the reward was not a separate object but was praise and applause. In the Velcro condition, the reward, although a separate and separable object, was attached to the base of the stimulus. Most infants at both ages succeeded in the verbal-reward and Velcro conditions but not in the standard condition.

Adult↗
PubMed1997

Ischemic left ventricular free wall rupture: prediction, diagnosis, and treatment.

Left ventricular free wall rupture is the third leading complication and the second most common cause of death after myocardial infarction. Its occurrence has been considered an unpredictable event usually leading to death. An increased appreciation for the clinical presentation of this syndrome and the nearly ubiquitous use of echocardiography have fostered a rise in the antemortem diagnosis of left ventricular free wall rupture, allowing the possibility of operative repair. Despite the increased reporting of left ventricular free wall rupture, the experience of any one surgeon or surgical group tends to be quite small. We review the current status of rupture prediction, clinical presentation, diagnosis, and treatment options. A recent case of left ventricular free wall rupture referred to the Baylor Cardiothoracic Surgery Group with the misdiagnosis of ruptured dissection of the ascending thoracic aorta is presented to illustrate our approach to this clinical situation.

Heart Rupture, Post-Infarction↗
PubMed1997

Prefrontal cortex cognitive deficits in children treated early and continuously for PKU.

To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed.

Age Factors↗
PubMed1996

Evidence for the importance of dopamine for prefrontal cortex functions early in life.

There is considerable evidence that dorsolateral prefrontal cortex subserves critical cognitive abilities even during early infancy and that improvement in these abilities is evident over roughly the next 10 years. We also know that (a) in adult monkeys these cognitive abilities depend critically on the dopaminergic projection to prefrontal cortex and (b) the distribution of dopamine axons within dorsolateral prefrontal cortex changes, and the level of dopamine increases, during the period that infant monkeys are improving on tasks that require the cognitive abilities dependent on prefrontal cortex. To begin to look at whether these cognitive abilities depend critically on the prefrontal dopamine projection in humans even during infancy and early childhood we have been studying children who we hypothesized might have a selective reduction in the dopaminergic innervation of prefrontal cortex and a selective impairment in the cognitive functions subserved by dorsolateral prefrontal cortex. These are children treated early and continuously for the genetic disorder, phenylketonuria (PKU). In PKU the ability to convert the amino acid, phenylalanine (Phe), into another amino acid, tyrosine (Tyr), is impaired. This causes Phe to accumulate in the bloodstream to dangerously high levels and the plasma level of Tyr to fall. Widespread brain damage and severe mental retardation result. When PKU is moderately well controlled by a diet low in Phe (thus keeping the imbalance between Phe and Tyr in plasma within moderate limits) severe mental retardation is averted, but deficits remain in higher cognitive functions. In a four-year longitudinal study we have found these deficits to be in the working memory and inhibitory control functions dependent upon dorsolateral prefrontal cortex in PKU children with plasma Phe levels 3-5 times normal. The fact that even infants showed these impairments suggests that dopaminergic innervation to prefrontal cortex is critical for the proper expression of these abilities even during the first year of life. To test the hypothesis about the underlying biological mechanism we have created the first animal model of early and continuously treated PKU. As predicted, the experimental animals had reduced levels of dopamine and the dopamine metabolite, homovanillic acid (HVA), in prefrontal cortex and showed impaired performance on delayed alternation, a task dependent on prefrontal cortex function. Noradrenaline levels were unaffected; however some reduction in serotonin levels and in dopamine levels outside the prefrontal cortex was found. If prefrontal cortex functions are vulnerable in children with a moderate plasma Phe:Tyr imbalance because of the special properties of the dopamine neurons that project to prefrontal cortex, then other dopamine neurons that share those same properties should also be vulnerable in these children. The dopamine neurons in the retina share these properties (i.e. unusually high firing and dopamine turnover rates), and we have found that PKU children with plasma Phe levels 3-5 times normal are impaired in their contrast sensitivity, a behavioural measure sensitive to retinal dopamine levels.

Animals↗
PubMed1996

Development of an aspect of executive control: development of the abilities to remember what I said and to "do as I say, not as I do".

Luria's tapping test (tap once when E taps twice, tap twice when E taps once) was administered to 160 children (80 males, 80 females) between 3 1/2 to 7 years old. Older children were faster and more accurate than younger children, with most of the improvement occurring by the age of 6. All children tested demonstrated understanding of the instructions during the pretest, and most started out performing well, but younger subjects could not sustain this. Over the 16 trials, percentage of correct responses decreased, especially among younger subjects. Performance here was compared with performance on the day-night Stroop-like task. The most common error on both tasks was to comply with only one of the two rules. Other errors included tapping many times regardless of what the experimenter did and doing the same thing as the experimenter, rather than the opposite. It is suggested that the tapping task requires both the ability to hold two rules in mind and the ability to inhibit a strong response tendency, that these abilities improve between 3-6 years of age, and that this improvement may reflect important changes within frontal cortex during this period of life.

Aptitude↗
PubMed1996

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.

Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinase receptor family expressed in endothelium. We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12. Our data suggest a critical role for ALK1 in the control of blood vessel development or repair.

Activin Receptors↗
PubMed1996

Impaired sensitivity to visual contrast in children treated early and continuously for phenylketonuria.

Contrast sensitivity was assessed in 47 children aged 5.4-9.8 years: 12 with phenylketonuria (PKU), six unaffected siblings and 29 children from the general population. Children with PKU, despite early and continuous treatment and despite phenylalanine (Phe) levels within accepted limits, were impaired across the range of spatial frequencies [1.5-18.0 cycles per degree of visual angle (c.p.d.)]. They were most impaired at the next to the highest spatial frequency, where "group' accounted for 70% of the variance in sensitivity to contrast, controlling for acuity, sex, age and test site. Never, at any spatial frequency, was the contrast sensitivity of any PKU subject better than that of his or her sibling. All subjects were tested under conditions of 20/20 vision, with correction if needed. The mean IQ of PKU subjects was 99; IQ was not significantly related to contrast sensitivity performance. We interpret these findings as support for Diamond's hypothesis that moderately elevated plasma Phe levels (3-5 x normal), combined with reduced plasma tyrosine (Tyr), moderately reduce the levels of Tyr reaching the eye and brain, which adversely affects those dopamine neurons that fire and turn over dopamine most rapidly (the dopamine neurons in the retina and those projecting to prefrontal cortex). This would lead to the deficit in contrast sensitivity found here and to the selective deficit in prefrontal cortex cognitive functions previously reported in PKU children under moderately good dietary control.

Analysis of Variance↗
PubMed1995

Evidence of robust recognition memory early in life even when assessed by reaching behavior.

Infants of only 5-6 months prefer to look at something new when given the choice of looking at a stimulus shown earlier or something new, even after a long delay (the visual paired comparison task). However, if infants must reach and displace a stimulus to retrieve a reward, even 18-month-olds respond randomly when given the choice of reaching to the stimulus shown earlier or to something new, even after a brief delay (the delayed nonmatching to sample task). To investigate this paradox we modified the delayed nonmatching to sample task to make it more similar to visual paired comparison. Each stimulus served as its own reward; no rewards were hidden under any stimuli. Infants were habituated to a sample object, a delay was imposed, and then the sample and a new object were presented. Infants could choose to look at (in visual paired comparison) or reach for (in delayed nonmatching to sample (stimulus = reward)) either object. One hundred twenty infants were tested: 60 (20 each at 4, 6, and 9 months) on visual paired comparison and 60 (20 each at 6, 9, and 12 months) on delayed nonmatching to sample (stimulus = reward). The same 10 pairs of stimuli were used on both tasks. Each subject was tested twice at all five delays (10, 15, 60, 180, and 600 s). At even the youngest age that reaching was tested (6 months), infants showed evidence of recognition memory on the reaching task at delays at least as long as those at which they demonstrated recognition memory on the looking task. Indeed, when subjects reached, not in order to obtain something else, but to obtain the stimulus itself, they succeeded on a recognition memory task even at delays 10 min long very early in life.

Age Factors↗
PubMed1995

Microdissection and microcloning of chromosomal alterations in human breast cancer.

The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1-4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5-8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band- or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10-13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.

Breast Neoplasms↗
PubMed1995

High prevalence of multidrug-resistant Streptococcus pneumoniae among children in a rural Kentucky community.

In 1992 drug-resistant Streptococcus pneumoniae was cultured with increasing frequency from aspirates of middle ear fluid from children with acute otitis media in a rural Kentucky community. To determine the prevalence of carriage of drug-resistant S. pneumoniae in the community, we obtained nasopharyngeal swabs from 158 (70%) of 227 children attending a child daycare center and from 82 children attending the county health center. S. pneumoniae was isolated from 126 children. Among 123 isolates tested 65 (53%) were penicillin-resistant, including 41 (33%) strains that were highly resistant; 61 (50%) were multidrug-resistant. Serotypes 19F, 6B, 23F and 6A comprised 89% of the penicillin-resistant isolates. Detection of a variety of serotypes and drug resistance patterns among nasopharyngeal isolates of S. pneumoniae suggests that multidrug-resistant pneumococcal strains are endemic in this community. Surveillance for drug-resistant pneumococci with the use of respiratory secretions obtained by nasopharyngeal swab may provide useful information on the prevalence of drug-resistant strains causing invasive disease and otitis media. Such information could be used to guide empiric therapy of pneumococcal infections.

Carrier State↗