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Biomedical subjects

A Baker

Publications and source records attributed to A Baker.

At least 73 records · Page 4Linked to original sources

New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury.

Early growth response factor-1 (Egr-1) binds to the promoters of many genes whose products influence cell movement and replication in the artery wall. Here we targeted Egr-1 using a new class of DNA-based enzyme that specifically cleaved Egr-1 mRNA, blocked induction of Egr-1 protein, and inhibited cell proliferation and wound repair in culture. The DNA enzyme also inhibited Egr-1 induction and neointima formation after balloon injury to the rat carotid artery wall. These findings demonstrate the utility of DNA enzymes as biological tools to delineate the specific functions of a given gene, and implicate catalytic nucleic acid molecules composed entirely of DNA as potential therapeutic agents.

Animals↗

Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males.

OBJECTIVE: To investigate the effects of changing from a medium (1.6 mg Cu/d) to a low (0.7 mg Cu/d) or a high (6.0 mg/d) Cu intake on biochemical indices of bone turnover in healthy adult males. DESIGN: A longitudinal intervention trial. SETTING: The study was conducted at the Institute of Food Research, Norwich, UK. SUBJECTS: Eleven healthy adult males aged 20-59 y were recruited from Norwich Research Park. INTERVENTION: Subjects were given medium (1.6 mg/d), low (0.7 mg/d) and high (6.0 mg/d) intakes of Cu, in that order, over consecutive 8 week periods with a minimum of 4 week washout periods. On the last d of each dietary period fasting first void urine and blood were collected. RESULTS: Serum caeruloplasmin or Cu (indices of Cu status), serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) were unaffected by dietary Cu intake. Urinary Pyr/Cr and Dpyr/Cr (biomarkers of bone resorption) were significantly increased (P < 0.05) (by 30% and 25%, respectively), when subjects were switched from the medium to the low Cu diet and were significantly decreased (P < 0.05) (by 30%) and 22% respectively), when subjects were switched from the low to the high Cu diet. CONCLUSION: The findings of the present study could have implications for bone health in individuals with marginal Cu intakes. Thus, further studies are warranted to better define the relationship of marginal Cu intakes to bone health.

Adult↗

Assessment of potential donors for living related liver transplantation.

BACKGROUND: Living related liver transplantation has been developed as an important potential source of organs for treatment of children with acute and chronic liver disease. A single UK centre performing living related liver transplantation was established in 1993. METHODS: Parents who were potential donors for their children for living related liver transplantation were assessed for suitability according to a protocol based on one developed and published by the University of Chicago Transplant Group. Records kept by the transplant coordinators were retrieved and data were extracted. RESULTS: Of 64 potential donors for 32 potential recipients ten were excluded at a preliminary stage. Fourteen ultimately became donors. Of 54 parents who began evaluation 23 were finally considered to be suitable. There were 19 non-disease-related reasons for unsuitability: blood group mismatch (eight cases), size discrepancy (six), pregnancy (two), oral contraceptive medication (one), vascular anatomy variant (one) and age (one). Sixteen were unsuitable because disease was found, namely fatty liver (four), thyroid disease (two), hepatitis B positivity (two), cardiac murmur (one), anaemia (one), glucose-6-phosphate dehydrogenase deficiency (one), diabetes mellitus (one) and psychological problems (one), and three parents were affected by the same disorder as the child (Alagille syndrome, one; mitochondrial disorder, one; recurrent cholestasis, one). Three parents were rejected for more than one reason. Both parents were unsuitable for donation in 21 per cent of cases. CONCLUSION: Parents approach living related liver transplantation with enthusiasm. They should be advised of the high chance of unsuitability, including the finding of significant pathology. The limitation of living related liver transplantation as the major source of organs for children is recognized.

Adolescent↗

Ovine bronchoalveolar lavage cellularity: reproducibility and the effect of multiple repeated lavage.

We sought to determine the normal within-sheep variability of bronchoalveolar cellular parameters and to infer the numbers of sheep required to detect a defined significant change within the same. We further sought to examine the effect of repeated bronchoalveolar lavage (BAL) on those parameters. Neither the total cell number nor the absolute numbers of any given cell type changed significantly following repeated BAL. Additionally, there was no significant change in percentage differential cell populations over time in randomly sampled lobes. However for lobes sampled repeatedly, a significant change in the percentage of lymphocytes was detected. Although the percentages of neutrophils in repeatedly and randomly sampled lobes were significantly correlated, the percentage found in the former tended to be greater and more variable than in the latter. As a consequence, larger group sizes are required to detect given changes in neutrophil percentages in repeatedly sampled lobes over time when compared with detecting equivalent changes in randomly selected lobes.

Animals↗

Treatment of photosensitive epilepsy using coloured glasses.

A recently introduced optometric technique, colorimetry, enables the perceptual effects of ophthalmic tints to be evaluated subjectively, optimized, and then prescribed in tinted spectacles. The new technique is beneficial in reducing visual stress in patients with dyslexia and migraine. We describe an open trial designed to ascertain: (1) whether the colorimetry assessment, as it is now given, is safe for the investigation of photosensitive patients in optometry clinics where colorimetry equipment is most readily available, but where EEG control is not practical; (2) what proportion of patients with photosensitive epilepsy is likely to benefit to the extent already described in individual cases; (3) whether a tint selected by colorimetry could be shown to reduce the incidence of paroxysmal epileptiform EEG activity in response to flicker and patterns, thereby validating the subjective methods and corroborating the reported seizure reduction. Twenty-four females and nine males (aged 12-43 years) took part. All the patients had suffered visually-provoked seizures, had exhibited a photoparoxysmal response on at least one previous EEG recording, and had received a diagnosis of photosensitive epilepsy. Twenty-two were currently experiencing seizures. A further EEG was recorded in all except seven cases: a routine resting record, followed by hyperventilation. Colorimetry was performed after hyperventilation and before photic stimulation. Twenty-three (70%) reported beneficial effects during colorimetry and were prescribed glasses. There was a preponderance of lenses with a rose or purple colour, in contrast to patients with dyslexia. Seventeen of the 23 patients were available at follow-up, an average of 2.4 years later. Thirteen (57%) reported benefits, and said they were still using the lenses. In six of the 13 the benefits were pronounced, including a reduction of dizziness from fluorescent lighting, elimination of aura when using computer screens etc. Only in three cases was there a reduction in seizures that could reasonably be attributed to the use of lenses; in two of these cases no medications were prescribed, and in the third the medications remained unchanged for four years, two before and two after the introduction of the glasses. In an additional four cases a reduction in seizures was observed but medication had been changed. There was a modest reduction in EEG photosensitivity with the coloured lenses but also to an equivalent or lesser extent with grey in all of the eight patients examined in this way. One patient had seizures during colorimetry, but the seizures were not accompanied by scalp EEG changes.

Adolescent↗

A 5-year follow up of mildly dyskaryotic smears, comparing colposcopy with expectant management.

The purpose of this study was to see if the National Health Service Cervical Screening Programme's guidelines were appropriate when they recommended that mildly dyskaryotic smears were repeated before referral for colposcopy. We identified all those with a mildly dyskaryotic smear, and followed them over 5 years, to compare those that had colposcopy and those that did not. In total, 269 women were followed and 35% of these only had the one mild smear. Of those whose smear returned to normal after the initial mild smear, 84% remained normal over the 5-year period. Of those whose smear did not return to normal, i.e. those that required a colposcopy, 74% returned to normal after the colposcopy.

Journal Article↗

Prediction of prolonged ventilator dependence in children by respiratory function measurements.

Complications of ventilatory support are more common if this assistance is prolonged. Our aim was to determine if results of respiratory function measurement on the first day of ventilation identified children who would develop prolonged ventilatory dependence (> or = 4 days) and whether such results were a more accurate predictor than readily available clinical data. Thirty three children, median age 2 years (range 0.1-13.6), who were supported by a constant flow ventilator and hence had measurements of compliance of the respiratory system (CRS) and resistance of the respiratory system (RRS) on the first day of ventilatory support, were retrospectively identified. Those who needed prolonged ventilatory support had a lower CRS on day one (p < 0.01) and required at any time during their ventilatory career both a higher maximum inspired oxygen concentration (p < 0.01) and peak inspiratory pressure (PIP) (p < 0.01). Logistic regression analysis demonstrated that only a low CRS and high maximum PIP were significantly correlated with prolonged ventilator dependence. A low CRS (<0.4 (ml/cmH2O) kg(-1)) and a high maximum PIP (>27 cmH2O) had similar sensitivities (83%) and specificities (71% and 67% respectively) in predicting prolonged ventilatory dependence. The CRS results, unlike the maximum PIP results, however, were always available on the first day of ventilatory support. We therefore conclude that respiratory function measurements have a role in identifying children who would benefit from strategies to prevent prolonged ventilator dependence.

Adolescent↗

Auxiliary partial orthotopic liver transplantation for Crigler-Najjar syndrome type I.

OBJECTIVE: To determine if auxiliary partial orthotopic liver transplantation (APOLT) has the long-term potential to correct the underlying abnormality in Crigler-Najjar syndrome type 1 (CNS1) without the need for total liver replacement. BACKGROUND: Orthotopic liver transplantation has been used successfully to replace the defective enzyme in CNS1. Experimental studies have shown that only 1% to 2% of the normal hepatocyte mass is needed for bilirubin conjugation. If APOLT corrects the underlying metabolic abnormality, it has the advantage of preserving the native liver, which would serve as a "safety net" should the graft fail, and there is the potential for gene therapy in the future with possible withdrawal of immunosuppression. METHODS: Seven APOLT procedures were performed in six recipients with CNS1. Median age at transplantation was 10.5 years. Six transplants were performed as a left auxiliary liver transplant, and one was performed as a right auxiliary liver transplant. Median serum bilirubin level at transplantation was 320 micromol/L. All patients required 12 to 16 hours of phototherapy daily before the transplant to maintain serum bilirubin levels between 250 and 350 micromol/L. RESULTS: Median serum bilirubin level was 50 micromol/L at day 5 after the transplant and 23 micromol/L at a median follow-up of 32 months. In four children, early severe acute rejection developed, requiring conversion to tacrolimus; one underwent a second transplant for chronic rejection and graft atrophy but died from lymphoproliferative disease 6 months after the second transplant. CONCLUSIONS: This report shows that APOLT is technically feasible and provides adequate hepatocyte mass to correct the underlying metabolic abnormality in CNS1.

Adolescent↗

Arabidopsis 22-kilodalton peroxisomal membrane protein. Nucleotide sequence analysis and biochemical characterization.

We sequenced and characterized PMP22 (22-kD peroxisomal membrane protein) from Arabidopsis, which shares 28% to 30% amino acid identity and 55% to 57% similarity to two related mammalian peroxisomal membrane proteins, PMP22 and Mpv17. Subcellular fractionation studies confirmed that the Arabidopsis PMP22 is a genuine peroxisomal membrane protein. Biochemical analyses established that the Arabidopsis PMP22 is an integral membrane protein that is completely embedded in the lipid bilayer. In vitro import assays demonstrated that the protein is inserted into the membrane posttranslationally in the absence of ATP, but that ATP stimulates the assembly into the native state. Arabidopsis PMP22 is expressed in all organs of the mature plant and in tissue-cultured cells. Expression of PMP22 is not associated with a specific peroxisome type, as it is detected in seeds and throughout postgerminative growth as cotyledon peroxisomes undergo conversion from glyoxysomes to leaf-type peroxisomes. Although PMP22 shows increased accumulation during the growth of young seedlings, its expression is not stimulated by light.

Amino Acid Sequence↗

The General Medical Health Rating: a bedside global rating of medical comorbidity in patients with dementia.

OBJECTIVE: Dementia is a serious public health problem. General medical comorbidity is common in dementia patients and critical to their care. However, little is known about medical comorbidity in these patients, and there are no straightforward bedside global rating scales for the seriousness of comorbid medical illness. This paper describes the development and measurement properties of the General Medical Health Rating (GHMR), a rapid global rating scale of medical comorbidity in dementia patients. DESIGN: Interrater reliability, concurrent validity, and predictive validity of the GMHR are reported. SETTING: An outpatient dementia clinic, assisted living, and nursing home. PARTICIPANTS: A total of 819 consecutive dementia clinic outpatients and 180 consecutive admissions to Copper Ridge, a long-term care residence for people with dementia, were included in the study. RESULTS: GMHR was found to be highly reliable (weighted kappa = .91). Across all stages and types of dementia, GMHR ratings were correlated with number of comorbid medical conditions, number of medications being taken for comorbid conditions, and with activity of daily living impairment, even after adjustment for severity of dementia. GMHR ratings were also a strong predictor of falls and of mortality in long-term care residents after adjustment for age and severity of dementia. CONCLUSION: GMHR is a reliable, valid, global bedside measure of severity of general medical comorbidity for patients with dementia that can be used for clinical and research purposes.

Accidental Falls↗

Antithrombotic efficacy of a novel murine antihuman factor IX antibody in rats.

A murine antihuman factor IX monoclonal antibody (BC2) has been generated and evaluated for its capacity to prolong the activated partial thromboplastin time (aPTT) in vitro and ex vivo and to prevent arterial thrombosis in a rat model in vivo. BC2 extended aPTT to a maximum of 60 to 80 seconds at 100 to 1000 nmol/L in vitro (rat and human plasma, respectively) and ex vivo (rat) after dosing of rats up to 6 mg/kg in vivo. BC2, administered as bolus (1 to 6 mg/kg) followed by infusion (0.3 to 2 mg x kg(-1) x h(-1)), dose-dependently prevented thrombosis of an injured rat carotid artery (FeCl(3)-patch model), increased time to artery occlusion, and reduced incidence of vessel occlusion. BC2 efficacy in preventing arterial thrombosis exceeded that of heparin (bolus 15 to 120 U/kg followed by infusion 0.5 to 4.0 U x kg(-1) x min(-1)), whereas the latter rendered the blood incoagulable (aPTT>1000 seconds). BC2 demonstrated complete antithrombotic efficacy also as a single bolus given either as prevessel or postvessel injury as evidenced by reduction of thrombus mass (from 4.18+/-0.49 to 1.80 +/-0.3 mg, P<0.001), increasing vessel patency time (from 14.9+/-0.9 minutes to 58.3+/-1.7 minutes, P<0.001) and decreasing incidence of vessel occlusion from 100% to 0% in vehicle- versus BC2-treated rats, respectively. BC2 (3 mg/kg, IV) administered in a single bolus resulted in 50% reduction in thrombus mass (P<0.01), extended vessel patency time (P<0.001), extended aPTT only 4-fold, and had no effect on blood loss via a tail surgical wound; heparin, at doses that reduced thrombus mass to a similar extent, extended aPTT beyond 1000 seconds (over 500-fold) and increased blood loss from 1.8+/-0.7 to 3.3 +/-0.6 mL (P<0.001). These data suggest that BC2 may provide enhanced therapeutic efficacy in humans at lesser interference with blood hemostasis than heparin.

Anesthesia↗

Identification of attentional and hyperactivity problems in primary care: a report from pediatric research in office settings and the ambulatory sentinel practice network.

OBJECTIVES: To 1) determine the frequency of identification of attentional and hyperactivity problems (AHPs) by clinicians, and 2) examine whether minority children or children from less well-educated, lower-income, or lower-functioning families would be more likely to be identified as having AHPs. DESIGN: Prospective cohort study of 22 059 consecutive children 4 to 15 years of age being seen for acute, chronic, and health supervision visits. SETTING: Practices of 401 pediatric and family practice clinicians in 44 states, Puerto Rico, and 4 Canadian provinces. METHODS: Parent questionnaires included demographic information and the Pediatric Symptom Checklist. Clinician questionnaires categorized psychosocial problems and addressed how assessment of problems was made. Analyses compared children with newly identified AHPs with those with other newly identified psychosocial problems. RESULTS: Clinicians identified behavior problems in 18.7% of children, with 9.2% of the entire sample identified as having AHPs. Among those with newly assessed AHPs, clinicians identified minority children and those from low-income or poorly functioning families as having AHPs at the same rate as other children. However, even after controlling for symptoms, males were more likely than females (odds ratio, 2.81) to be identified as having AHPs. Older clinicians were significantly more likely to identify children as having AHPs (odds ratio, 2.09). In assessing AHPs, clinicians used standardized tools such as behavioral questionnaires for only 36.9% of children, and Diagnostic and Statistical Manual criteria for 38.3% of children. CONCLUSIONS: AHPs are highly prevalent in primary care practice. Clinicians do not appear predisposed to label children from disadvantaged backgrounds as having AHPs. Primary care assessment of AHPs lacks standardization.

Adolescent↗

Post-traumatic stress responses following liver transplantation in older children.

Eighteen children aged between 7 and 16 years who had undergone a liver transplantation were interviewed using the Child Post-Traumatic Stress Reaction Index (CPTS-RI) to discover if they had post-traumatic stress symptoms. A case control design was used to define which factors were important for the development of post-traumatic stress. Results of a one-way analysis of variance (ANOVA), with post-traumatic stress symptom intensity as measured on the CPTS-RI as the dependent variable, revealed a significant difference between the liver transplantation group compared with children who had a chronic life-threatening illness or had undergone a routine surgical operation. A post hoc (Tukey's HSD test) statistical analysis was performed and significance at the .05 level was found between the liver transplantation group and both the chronic illness group and the routine surgical operation group. Our results indicate that the acute life-threat involved in the liver transplantation contributed to the development of post-traumatic stress. It was thought that dissociation may be important in preventing the resolution of the trauma. Additional investigations are needed with larger numbers in a longitudinal study beginning before the transplant to determine the course of the PTSD symptoms and the appropriate timing of interventions to reduce the harmful effects of these symptoms.

Adolescent↗

A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care.

BACKGROUND: Agitated behaviors are common in dementia patients residing in chronic care settings. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances. OBJECTIVE: Prior research has suggested that bright light therapy (BLT) may reduce agitated behaviors in dementia patients. The aim of this study was to test the efficacy of BLT in a randomized, controlled, crossover clinical trial. METHOD: Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were randomized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure. Patients were treated in either condition for 4 weeks, followed by 1 week on no treatment, prior to being crossed over to the other condition. RESULTS: Eight out of 15 patients completed the entire study. The rest completed at least 2 weeks of study. Patients randomized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later (p<0.05). The sleep of patients in the control condition did not improve significantly. There were no other significant differences between baseline and follow-up, nor between BLT and control treated patients on the other outcome measures, which included the Behavioral Pathology in Alzheimer Disease scale (Behave-AD) and the Cornell Scale for Depression in Dementia. CONCLUSION: Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT. However, BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles.

Aged↗

Pharmacological uses and perspectives of heavy water and deuterated compounds.

Since the discovery of D20 (heavy water) and its use as a moderator in nuclear reactors, its biological effects have been extensively, although seldom deeply, studied. This article reviews these effects on whole animals, animal cells, and microorganisms. Both "solvent isotope effects," those due to the special properties of D20 as a solvent, and "deuterium isotope effects" (DIE), which result when D replaces H in many biological molecules, are considered. The low toxicity of D20 toward mammals is reflected in its widespread use for measuring water spaces in humans and other animals. Higher concentrations (usually >20% of body weight) can be toxic to animals and animal cells. Effects on the nervous system and the liver and on formation of different blood cells have been noted. At the cellular level, D20 may affect mitosis and membrane function. Protozoa are able to withstand up to 70% D20. Algae and bacteria can adapt to grow in 100% D2O and can serve as sources of a large number of deuterated molecules. D2O increases heat stability of macromolecules but may decrease cellular heat stability, possibly as a result of inhibition of chaperonin formation. High D2O concentrations can reduce salt- and ethanol-induced hypertension in rats and protect mice from gamma irradation. Such concentrations are also used in boron neutron capture therapy to increase neutron penetration to boron compounds bound to malignant cells. D2O is more toxic to malignant than normal animal cells, but at concentrations too high for regular therapeutic use. D2O and deuterated drugs are widely used in studies of metabolism of drugs and toxic substances in humans and other animals. The deuterated forms of drugs often have different actions than the protonated forms. Some deuterated drugs show different transport processes. Most are more resistant to metabolic changes, especially those changes mediated by cytochrome P450 systems. Deuteration may also change the pathway of drug metabolism (metabolic switching). Changed metabolism may lead to increased duration of action and lower toxicity. It may also lead to lower activity, if the drug is normally changed to the active form in vivo. Deuteration can also lower the genotoxicity of the anticancer drug tamoxifen and other compounds. Deuteration increases effectiveness of long-chain fatty acids and fluoro-D-phenylalanine by preventing their breakdown by target microorganisms. A few deuterated antibiotics have been prepared, and their antimicrobial activity was found to be little changed. Their action on resistant bacteria has not been studied, but there is no reason to believe that they would be more effective against such bacteria. Insect resistance to insecticides is very often due to insecticide destruction through the cytochrome P450 system. Deuterated insecticides might well be more effective against resistant insects, but this potentially valuable possibility has not yet been studied.

Animals↗

No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults.

The influence of Cu supplementation of the usual diet for 6 weeks on biochemical markers of bone turnover and on putative indices of Cu status was investigated in healthy adults (twelve male and twelve female) aged 22-46 years, who participated in a double-blind placebo-controlled repeated crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu-glycine chelate (CuGC), and 6 mg CuGC, each separated by placebo periods of equal length. During baseline and on the last day of each dietary period, fasting morning first-void urine and fasting blood serum, plasma and erythrocytes were collected. The habitual dietary Cu intakes in males and females were approximately 1.4 and 1.1 mg/d respectively. Females had significantly higher (50%) plasma caeruloplasmin (Cp) protein concentrations than males at baseline. Cu supplementation had no effect on erythrocyte superoxide dismutase (SOD, EC 1.15.1.1) activity or plasma Cp protein (putative indices of Cu status) in the total group. Similarly, serum osteocalcin (a marker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline: Cr or deoxypyridinoline: Cr excretion (markers of bone resorption) were unaffected in either the total group or in males and females separately, by any Cu supplementation regimen. It is concluded that Cu supplementation of the usual diet in healthy adult males and females had no effect on biochemical markers of bone formation or bone resorption over 6-week periods.

Adult↗