Search PubMed⌕ Search

Biomedical subjects

J Andrews

Publications and source records attributed to J Andrews.

At least 55 records · Page 3Linked to original sources
PubMed2001

Metastatic neuroendocrine tumor presenting as spinal cord compression--a case report and brief comment.

Gastrointestinal neuroendocrine tumors are derived from the diffuse neuroendocrine system of the gastrointestinal tract which is composed of amine and acid producing cells with different hormonal profiles, depending on the site of origin. The tumors they produce can be divided into carcinoid tumors and pancreatic endocrine tumors. We believe this to be only the fourth case in the literature of a patient presenting with cord compression as a result of a metastatic neuroendocrine tumor (MEDLINE 1966-2000).

Aged↗
PubMed2001

Multisite kinetic models for CYP3A4: simultaneous activation and inhibition of diazepam and testosterone metabolism.

Some substrates of cytochrome P450 (CYP) 3A4, the most abundant CYP in the human liver responsible for the metabolism of many structurally diverse therapeutic agents, do not obey classical Michaelis-Menten kinetics and demonstrate homotropic and/or heterotropic cooperativity. The unusual kinetics and differential effects observed between substrates of this enzyme confound the prediction of drug clearance and drug-drug interactions from in vitro data. We have investigated the hypothesis that CYP3A4 may bind multiple molecules simultaneously using diazepam (DZ) and testosterone (TS). Both substrates showed sigmoidal kinetics in B-lymphoblastoid microsomes containing a recombinant human CYP3A4 and reductase. When analyzed in combination, TS activated the formation of 3-hydroxydiazepam (3HDZ) and N-desmethyldiazepam (NDZ) (maximal activation 374 and 205%, respectively). For 3HDZ, V(max) values remained constant with increasing TS, whereas the S(50) and Hill values decreased, tending to make the data less sigmoidal. Similar trends were observed for the NDZ pathway. DZ inhibited the formation 6beta-hydroxytestosterone (maximal inhibition, 45% of control), causing a decrease in V(max) but no significant change to the S(50) and Hill values, suggesting that DZ may inhibit via a separate effector site. Multisite rate equation models have been derived to explore the analysis of such complex kinetic data and to allow accurate determination of the kinetic parameters for activation and inhibition. The data and models presented are consistent with proposals that CYP3A4 can bind and metabolize multiple substrate molecules simultaneously; they also provide a generic solution for the interpretation of the complex kinetic data derived from CYP3A4 substrates.

Algorithms↗
PubMed2000

ST-Segment recovery adds to the assessment of TIMI 2 and 3 flow in predicting infarct wall motion after thrombolytic therapy.

BACKGROUND: Early resolution of ST-segment elevation (ST-segment recovery) is associated with an improved outcome after infarction. Whether this relation is present in patients with Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 flow (ie, patent) infarct-related arteries is not known. METHODS AND RESULTS: To examine the associations between time to achieve stable 50% ST-segment recovery assessed by continuous ECG monitoring, infarct artery flow, and infarct zone wall motion (at 48 hours), we studied 134 patients who underwent angiography at 99 (interquartile range 92 to 110) minutes after commencing streptokinase, initiated within 12 hours of onset of symptoms of myocardial infarction. Patients with TIMI 2 or 3 flow who failed to achieve early stable ST-segment recovery (50% ST-segment recovery sustained for > or 4 hours with <100 microV change in the peak lead) by 60 or 90 minutes had a higher fraction of chords in the infarct zone >2 SD below normal wall motion (TIMI 2: 55.5% vs 15.3%, P=0.006; and 56.5% vs 26.8%, P=0.01, respectively; and TIMI 3: 48.8% vs 28.3%, P=0.07; and 51.8% vs 29.9%, P=0.03, respectively). Time to stable ST-segment recovery was a multivariate predictor of infarct zone wall motion (P=0.04) independent of TIMI flow grade and the time from symptom onset to streptokinase therapy. CONCLUSIONS: In patients with TIMI 2 or 3 flow in infarct-related artery, early stable ST-segment recovery is associated with improved infarct zone wall motion at 48 hours. ST-segment recovery may provide additional information about the degree of myocyte reperfusion achieved in patients with a patent epicardial infarct-related artery after thrombolytic therapy.

Aged↗
PubMed2000

The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney.

Synthesis of Tyr in the human body occurs by hydroxylation of the indispensable amino acid Phe. Until now, it was believed that in humans, this process was restricted to the liver, but we provide compelling evidence of production of Tyr from Phe in the kidney. To determine whether the human kidney produces Tyr, we measured Tyr balance, the Tyr appearance rate, and the Phe-to-Tyr conversion in 12 healthy human subjects by using [(15)N]Phe and [(2)H(4)]Tyr as tracers. Renal plasma flow was measured by using paraaminohippurate, and sampling from the femoral artery and renal veins was performed. The results were compared with those obtained in 12 control subjects undergoing hepatic vein catheterization and infusion of identical tracers. In all 12 subjects, there was a net uptake of Phe by the kidney (2.2 +/- 1.2 micromol/min), whereas Tyr was released (5.3 +/- 1.5 micromol/min). In contrast, there was a net uptake of both Phe (9.5 +/- 1.2 micromol/min) and Tyr (14.3 +/- 1.3 micromol/min) by the splanchnic bed. Phe conversion to Tyr occurred at a rate of 5.2 +/- 1.2 micromol/min in kidney and 3.0 +/- 0.7 micromol/min in the splanchnic bed. The kidney contributed a substantial amount of Tyr to the systemic circulation where the splanchnic bed was a net remover of Tyr. Our results demonstrate that the kidney is the major donor of Tyr to the systemic circulation by its conversion of Phe to Tyr. This observation may have important clinical implications for patients with both renal and hepatic disease, who may be at risk of Phe overloading and Tyr deficiency, and it should be considered when parenteral or enteral nutrients are administered rich in Phe and low in Tyr.

Adult↗
PubMed2000

Effect of physiological mechanical perturbations on intact human myocardial repolarization.

OBJECTIVE: The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone. METHODS: Patients implanted with a stimulus to T wave (Stim-T) sensing pacemaker specially adapted to output a validate measure of beat to beat local repolarization (n = 9) performed Valsalva manoeuvers (40 mmHg for 15 s) while paced at a cycle length of 500 ms. Stim-T intervals were measured before and after autonomic blockade (Block: 0.03 mg/kg i.v. atropine +/- 0.15 mg/kg propranolol). Right ventricular end diastolic volume was estimated by simultaneous 2D-echocardiography. RESULTS: Without autonomic blockade, compared to baseline, repolarization significantly prolonged during Valsalva strain (1.1 +/- 0.7%) and shortened during release (-1.4 +/- 1.0%). After block, strain related repolarization prolongation was also observed (1.0 +/- 0.6%), with significantly less release related repolarization shortening (-0.8 +/- 0.8%) compared to pre-block (P < 0.05). Right ventricular end diastolic volume decreased during strain by 11 +/- 10 and 9 +/- 16% from baseline, pre- and post-block respectively (P < 0.05). CONCLUSION: In a chronically instrumented human model, an acute physiologic volume reduction modestly prolongs right ventricular repolarization independent of changes in rate or autonomic tone.

Action Potentials↗
PubMed2000

Urinary excretion of valproate metabolites in children and adolescents.

The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross-sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA-glucuronide, 3-oxo-VPA and 4-OH-VPA were calculated by relating 24-h recovery of these metabolites from urine to daily VPA dose. VPA, 3-oxo-VPA and 2-en-valproic acid (2-en-VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA-glucuronide in children 10 years and younger was smaller than in older children (p<0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p<0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA-glucuronide on multivariate analysis than did the age group (p=0.001 versus p<0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide.

Adolescent↗
PubMed2000

ASW: a gene with conserved avian W-linkage and female specific expression in chick embryonic gonad.

Vertebrates exhibit a variety of sex determining mechanisms which fall broadly into two classes: environmental or genetic. In birds and mammals sex is determined by a genetic mechanism. In mammals males are the heterogametic sex (XY) with the Y chromosome acting as a dominant determiner of sex due to the action of the testis-determining factor, SRY. In birds females are the heterogametic sex (ZW); however, it is not known whether the W chromosome carries a dominant ovary-determining gene, or whether Z chromosome dosage determines sex. Using an experimental approach, which assumes only that the sex-determining event in birds is accompanied by sex-specific changes in gene expression, we have identified a novel gene, ASW (Avian Sex-specific W-linked). The putative protein for ASW is related to the HIT (histidine triad) family of proteins. ASW shows female-specific expression in genital ridges and maps to the chicken W chromosome. In addition, we show that, with the exception of ratites, ASW is linked to the W chromosome in each of 17 bird species from nine different families of the class Aves.

Amino Acid Sequence↗
PubMed2000

Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction.

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.

Adult↗
PubMed2000

Haemophilia care in central Scotland 1980-94. I. Demographic characteristics, hospital admissions and causes of death.

To estimate the resources required to manage patients with haemophilia in Scotland, we studied the demographic features, hospital admissions and causes of deaths for individuals with haemophilia A and B and von Willebrand disease, treated with blood products, during the period 1980-94 living in central Scotland. Data were obtained from 413 adults and children (93% ascertainment). The age distribution in 1980 revealed a paucity of individuals over 60 years but the number in this age group increased over the study period. Of those with haemophilia A and B, 63 and two respectively, became HIV positive. Hospital admissions rose from 103 to 168 per annum; the number of annual bed days utilized also increased, but there was marked annual fluctuation (790-1832). The rate of admission was greater for those with severe haemophilia A and this increased during the 15-year period mainly due to the clinical consequences of human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The admission rate for haemophilia B was significantly lower than that for haemophilia A, and was similar for all degrees of severity of the disorder. Throughout the 15-year period the incidence of admissions for acute bleeds was constant, as was the average duration in hospital. For those with a factor VIII inhibitor, the rate of admission was about double the rate of those without an inhibitor, although the duration of hospital stay was similar for both groups. There were 61 deaths; the death rate increased during the study period principally due to HIV and HCV, and 12 patients died from haemorrhage. We conclude that: (i) the life expectancy for haemophiliacs in Scotland was generally increasing, although HIV and HCV caused increasing mortality and morbidity (as shown by the increase in hospital admissions); (ii) hospital bed usage for the treatment of acute bleeds continued to be required, but fluctuated greatly; and (iii) the clinical impression that haemophilia B is less clinically severe than haemophilia A is confirmed by objective data. The planning implications for haemophilia care in Scotland and similar countries are discussed.

Adolescent↗