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PubMed1999

Analysis of highly polar DNA adducts formed in SENCAR mouse epidermis following topical application of dibenz[a,j]anthracene.

The formation of DNA adducts in mouse epidermis has been examined following topical application of dibenz[a,j]anthracene (DB[a,j]A) and its metabolites, i.e., DB[a,j]A-3,4-diol, DB[a,j]A-3,4-10, 11-bis-diol, DB[a,j]A-3,4-8,9-bis-diol, 10-OH-DB[a,j]A-3,4-diol, or 11-OH-DB[a,j]A-3,4-diol, using a 32P-postlabeling assay. At initiating doses (400-1600 nmol), DB[a,j]A produced at least 23 DNA adduct spots, including four less polar (derived from the bay-region syn- and anti-diol-epoxides) and 19 highly polar DNA adducts. DB[a, j]A-3,4-diol produced 13 DNA adduct spots, four less polar and nine highly polar DNA adducts, and DB[a,j]A-3,4-10,11-bis-diol produced nine highly polar DNA adducts. Eight and seven of the highly polar DNA adducts generated by DB[a,j]A-3,4-diol and DB[a,j]A-3,4-10, 11-bis-diol, respectively, migrated in the chromatography system like the highly polar DNA adducts produced by the parent compound. Sufficient amounts of radioactivity were associated with highly polar adduct spots 11, 13, and 22 to confirm their chromatogaphic identity in DNA samples from DB[a,j]A-, DB[a,j]A-3,4-diol-, and DB[a, j]A-3,4-10,11-bis-diol-treated mice. 10-OH-DB[a,j]A-3,4-diol and 11-OH-DB[a,j]A-3,4-diol did not produce any highly polar DNA adducts that could be detected under our experimental conditions. At an initiating dose of 400 nmol, DB[a,j]A, DB[a,j]A-3,4-diol, and DB[a, j]A-3,4-10,11-bis-diol produced 22.4 +/- 13.0, 15.6 +/- 10.1, and 5. 5 +/- 0.3 (mean +/- SD) adducts/10(9) nucleotides, of which 77, 65, and 100%, respectively, represented highly polar DNA adducts. At the same dose of 400 nmol per mouse, DB[a,j]A and its 3,4-diol were able to initiate papillomas in SENCAR mouse skin (3.08 +/- 1.89 and 3.48 +/- 2.72 papillomas per mouse, respectively, after 16 weeks of promotion with 12-O-tetradecanoyl phorbol 13-acetate), while the 3, 4-10,11-bis-diol of DB[a,j]A was inactive as a tumor initiator. A quantitative correlation (r = 0.935; p = 0.0196) between levels of less polar DNA adducts and tumor-initiating activity of DB[a,j]A, DB[a,j]A-3,4-diol, and anti-DB[a,j]ADE was observed. This study demonstrates that the highly polar DNA adducts formed from DB[a,j]A in mouse epidermis arise primarily from the DB[a,j]A-3,4-10, 11-bis-diol. However, the contribution of this metabolite to the tumor-initiating activity of DB[a,j]A appears to be small.

Administration, Topical↗

PubMed1999

Detection and quantification of 1,N(6)-ethenoadenine in human placental DNA by mass spectrometry.

Exocyclic DNA adducts have been reported to derive from various exogenous as well as endogenous sources, such as lipid peroxidation. Among them, 1,N(6)-ethenoadenine (epsilonAde) has previously been detected in tissue DNA of untreated rodents and humans by an immunoaffinity/(32)P-postlabeling method. This study reports detection and quantification of the endogenous epsilonAde adduct in the same human placental DNA by three independent assays, namely, GC/MS, LC/MS, and HPLC/fluorescence. Using a recently reported gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method [Chen, H.-J. C., et al. (1998) Chem. Res. Toxicol. 11, 1474], the level of epsilonAde in human placental DNA from a commercial source was found to be 2.3 adducts per 10(6) Ade bases. To confirm these findings, a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method was developed for epsilondAdo. With this LC/MS assay, epsilondAdo was detected at the level of 2.5 adducts per 10(6) dAdo nucleosides in the same human placental DNA. The stable isotopes of epsilonAde and epsilondAdo were added as internal standards in both GC/MS and LC/ESI/MS/MS assays, respectively, and thus provided high specificity, reproducibility, and accurate quantification. The relatively high levels of epsilonAde in this human placental DNA detected by mass spectrometry were further verified by HPLC/fluorescence analysis. The GC/MS method was validated by the HPLC/fluorescence assay using calf thymus DNA treated with chloroacetaldehyde or by the LC/MS method with 2, 3-epoxy-4-hydroxynonanal-modified calf thymus DNA. The epsilonAde level in human placental DNA freshly isolated in the presence of an antioxidant was similar to that in DNA from the commercial source. Since epsilonAde is a potential mutagenic lesion, analysis of epsilonAde by the specific and sensitive GC/NICI/MS method may provide a useful biomarker in cancer risk assessment.

Adenine↗

PubMed1999

Estrogen-nucleic acid adducts: dissection of the reaction of 3, 4-estrone quinone and its radical anion and radical cation with deoxynucleosides and DNA.

Previous studies from our laboratory have shown that 3,4-estrone quinone (3,4-EQ) can redox-cycle and is capable of inducing single-strand DNA breaks in MCF-7 breast cancer cells, as well as reacting with various deoxynucleosides to give several estrogen-nucleic acid adducts. While reactions of 3,4-EQ with all the deoxynucleosides under acidic conditions gave only the N7-Gua adduct, which could proceed by Michael addition, reactions of 3,4-EQ under reductive conditions gave several adducts, including the N7-Gua, C8-Ade, C8-Gua, N3-Thy, and N4-Cyt adducts, suggesting the involvement of a 3,4-EQ radical species. The question as to which of the reactive species, the estrogen quinone or the estrogen semiquinone, that is responsible for estrogen's genotoxic activity has been the subject of recent investigations in several laboratories. To explore this in more detail, we carried out studies on the reactivity of 3,4-EQ, the 3,4-EQ radical anion, and the 3, 4-EQ radical cation with both deoxynucleosides and calf thymus DNA under different pH conditions. Both stable and unstable adducts with guanine and thymine were observed from reactions with DNA. Although adduct levels were somewhat different, the adduct profiles obtained from reactions of 3,4-EQ and its radical anion with both DNA and deoxynucleosides were quite similar and were found to be significantly different from product profiles obtained from reactions with the 3,4-EQ radical cation. Studies conducted with the human breast tumor cell line MCF-7 demonstrated the formation of the N7- and C8-Gua adducts in which the profiles were similar to those obtained from reactions of 3,4-EQ with DNA. These results suggest that the reactive species that is responsible for adduct formation under physiological conditions is most likely to be the 3,4-EQ radical anion.

Anions↗

PubMed1998

Complementation analysis with new genetic markers in Phaffia rhodozyma.

Isolation and characterization of auxotrophic mutants from wild-type and astaxanthin mutant strains of Phaffia rhodozyma is described. Differences in survival were observed when u.v. irradiation of P. rhodozyma wild-type and astaxanthin mutant strains were incubated in the dark or exposed to photoreactivating light. Ultra-violet mutagenesis was not effective to produce auxotrophic mutants in this yeast. Auxotrophic mutants were obtained with high efficiency through a nystatin enrichment procedure after a N-methyl-N'-nitro-N-nitrosoguanidine (NGT) mutagenic treatment with a 0.12% survivor level. Stringent mutagenetic conditions were needed to obtain P. rhodozyma auxotrophs. The most frequent mutants were ade- and met- in a rather narrow auxotroph spectrum. These results may be associated with a possible diploid condition of this yeast. The high number of adenine auxotrophs obtained in relation to other auxotrophic mutants suggests the possibility of some degree of heterozygosity in the wild-type strain UCD 67-385.

Anti-Bacterial Agents↗

PubMed1998

Genetic and shared environmental influences on adolescent BMI: interactions with race and sex.

The present study uses a behavioral genetic design to investigate the genetic and environmental influences on variation in adolescent body mass index (BMI) and to determine whether the relative influences of genetic and environmental factors on variation in BMI are similar across racial groups and sexes. Data for the present study come from the National Longitudinal Study on Adolescent Health (Add Health), a large, nationally representative study of adolescent health and health-related behaviors. The Add Health sample contains a subset of sibling pairs that differs in levels of genetic relatedness, making it well suited for behavioral genetics analyses. The present study examines whether genetic and environmental influences on adolescent BMI are the same for males and females and for Black and White adolescents. Results indicate that genetic factors contribute substantially to individual differences in adolescent BMI, explaining between 45 and 85% of the variance in BMI. Furthermore, based on an analysis of opposite-sex sibling pairs, the genes that influence variation in adolescent BMI are similar for males and females. However, the relative importance of genetic and environmental influences on variation in BMI differs for males and females and for Blacks and Whites. Although parameter estimates could be constrained to be equal for Black and White males, they could not be constrained to be equal for Black and White females. Moreover, the best-fitting model for Black females was an ADE model, for White females it was an ACE model, and for males it was an AE model. Thus, shared environmental influences are significant for White female adolescents, but not for Black females or males. Likewise, nonadditive genetic influences are indicated for Black females, but not for White females or males. Implications of these results are discussed.

Adolescent↗

PubMed1994

A genetic analysis of relative weight among 4,020 twin pairs, with an emphasis on sex effects.

This study replicated previous findings showing a high heritability of obesity, as measured by body mass index (kg/m2), using a measure of relative weight that does not assume a constant regression of height on weight across different populations, and evaluated whether there are sex-limited genetic effects. Subjects were 4,020 adult twin pairs. Alternative causal structural equation models were fitted to variance-covariance matrices. The ADE model (additive genetic effects, dominant/nonadditive genetic effects, and unique environment) fit best. Allowing for sex-specific effects (common sex-limitation model) significantly improved the fit, X2(6) = 230.5, p < .001. The heritability of that portion of weight unrelated to height was large: .61 for men and .73 for women.

Adolescent↗

PubMed1997

Species differences in brain adenosine A1 receptor pharmacology revealed by use of xanthine and pyrazolopyridine based antagonists.

1. The pharmacological profile of adenosine A1 receptors in human, guinea-pig, rat and mouse brain membranes was characterized in a radioligand binding assay by use of the receptor selective antagonist, [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]-DPCPX). 2. The affinity of [3H]-DPCPX binding sites in rat cortical and hippocampal membranes was similar. Binding site affinity was higher in rat cortical membranes than in membranes prepared from guinea-pig cortex and hippocampus, mouse cortex and human cortex. pKD values (M) were 9.55, 9.44, 8.85, 8.94, 8.67, 9.39 and 8.67, respectively. The binding site density (Bmax) was lower in rat cortical membranes than in guinea-pig or human cortical membranes. 3. The rank order of potency of seven adenosine receptor agonists was identical in each species. With the exception of 5'-N-ethylcarboxamidoadenosine (NECA), agonist affinity was 3.5-26.2 fold higher in rat cortical membranes than in human and guinea-pig brain membranes; affinity in rat and mouse brain membranes was similar. While NECA exhibited 9.3 fold higher affinity in rat compared to human cortical membranes, affinity in other species was comparable. The stable GTP analogue, Gpp(NH)p (100 microM) reduced 2-chloro-N6-cyclopentyladenosine (CCPA) affinity 7-13.9 fold, whereas the affinity of DPCPX was unaffected. 4. The affinity of six xanthine-based adenosine receptor antagonists was 2.2-15.9 fold higher in rat cortical membranes compared with human or guinea-pig membranes. The rank order of potency was species-independent. In contrast, three pyrazolopyridine derivatives, (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-2-piperidine ethanol (FK453), (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinebutyric acid (FK838) exhibited similar affinity in human, guinea-pig, rat and mouse brain membranes. pKi values (M) for [3H]-DPCPX binding sites in human cortical membranes were 9.31, 7.52 and 7.92, respectively. 5. Drug affinity for adenosine A2A receptors was determined in a [3H]-2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido ade nosine ([3H]-CGS 21680) binding assay in rat striatal membranes. The pyrazolopyridine derivatives, FK453, FK838 and FK352 exhibited pKi values (M) of 5.90, 5.92 and 4.31, respectively, compared with pKi values of 9.31, 8.18 and 7.57 determined in the [3H]-DPCPX binding assay in rat cortical membranes. These novel pyrazolopyridine derivatives therefore represent high affinity, adenosine A1 receptor selective drugs that, in contrast to xanthine based antagonists, exhibit similar affinity for [3H]-DPCPX binding sites in human, rat, mouse and guinea-pig brain membranes.

Adenosine↗

PubMed2000

Effects of adenine nucleosides and nucleotides on neuromuscular transmission to the prostatic stroma of the rat.

1. The aim of this study was to investigate the effects of adenine nucleosides and nucleotides on contractility of the smooth muscle of rat prostate gland. 2. Nerve terminals within rat isolated prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 60 s). Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and adenosine had no effect on baseline smooth muscle tone but concentration-dependently inhibited electrically-evoked contractile responses. The relative order of potency was ATP congruent with AMP congruent with adenosine>ADP. 3. The inhibition by ATP and adenosine of field stimulation-induced contractions in the rat prostate was antagonized by 8-phenyltheophylline (10 microM), but not by suramin (100 microM) and only slightly by reactive blue 2 (5 microM). 4. The adenosine metabolizing enzyme adenosine deaminase (0.1 unit ml(-1)) inhibited the inhibitory effects of ATP and adenosine. The P2 purinoceptor agonist 2-methylthio ATP (10 nM - 0.1 mM), had no effect on field stimulation-induced contractions of the rat prostate. 5. ATP and adenosine did not modify the contractile responses of the rat prostate to exogenously added noradrenaline (10 microM). 6. Inhibitory concentration-response curves to a number of adenosine analogues with differing stabilities and selectivities for the different adenosine receptors yielded a relative rank order of agonist potency of: N(6)-cyclopentyladenosine (CPA)>N(6)-cyclohexyladenosine (CHA) congruent with (-)-N(6)-(2-phenylisopropyl)-adenosine (R-PIA) congruent with 5'-(N-ethylcarboxamido)-adenosine (NECA)>(+)-N(6)-(2-phenylisopropyl)-adenosine (S-PIA)>2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-ade nosine (CGS 21680). 7. These results indicate that adenine nucleoside and nucleotide induced inhibition of electrically-evoked contractions in the rat prostate occurs through activation of adenosine but not ATP receptors. The relative order of potency of adenosine analogues is consistent with activation of receptors of the A(1)-adenosine receptor subtype. These receptors appear to be prejunctional.

Adenosine Diphosphate↗

PubMed2006

A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer.

Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1-3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1-3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.19+/-1.19, 0.87+/-1.5, 0.43+/-0.56 vs controls 4.04+/-5.12 mm3). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1-3-HSA (P=0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis.

Activating Transcription Factors↗

PubMed1999

Retrospective review of flow patterns following retropubic prostatectomy.

AIM OF THIS STUDY: We retrospectively evaluated penile inflows in 103 previously potent individuals who underwent standard nerve sparing radical retropubic prostatectomy (RRP) for the treatment of prostate cancer. No effort to identify or spare the accessory pudendal artery (APA) was made in any case. Our goal was to investigate the role of the accessory internal pudendal artery (APA) in the maintenance of erections in this population. We hypothesize that if the APA is present in a significant number of men, and its ligation significantly contributes to post-RRP impotence, then there should be an increased incidence of asymmetry between R/L cavernous arterial flows among post RRP patients with vascular impotence. MATERIALS AND METHODS: One hundred and three previously potent individuals complaining of persistent erectile dysfunction for at least six months after RRP were studied with color duplex Doppler, following age specific dosing of PGE1. Vascular assessment was performed before and after self-stimulation, measuring peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI). Erections were visually rated as inadequate (INA), adequate (ADE) for penetration, or excellent (EXC) with sustained rigidity for at least 20 min. Cavernous artery asymmetry (CAA) was defined as a >10 cm/s difference between right and left sided arterial flows. RESULTS: Mean duration between surgery and Doppler study was 14.7 months. 27 out of 103 (26%) of patients developed excellent rigidity consistent with isolated neurogenic impotence (PSV=32.0 cm/s, mean RI=0.95); 24 out of 103 (23%) had adequate vascular responses making it impossible to infer presence or absences of neurogenic impotence; 52 out of 103 (51%) had inadequate rigidity consistent with vascular insufficiency (PSV=23.7 cm/s, mean RI=0.66). We noted that of patients with EXC response, 48% (13 out of 27) had CAA. Among patients with severe inflow disease (INA responders), CAA was seen in only 21% of cases (11 out of 52). CONCLUSIONS: The incidence of APA has been reported as being from 4-70%, and its significance in the maintenance of erections has been questioned. Assuming that the APA provides significant inflow in some patients, we expected an increase in CAA in individuals in whom it was sacrificed. We found a higher incidence of CAA among post-RRP patients with normal vascular erectile responses to PGE1 (48%) compared to men with true vasculogenic impotence post-RRP (21%). These data do not support the importance of the APA in the maintenance of erections in the post-RRP patient.

Aged↗

PubMed1997

Determining mutational fingerprints at the human p53 locus with a yeast functional assay: a new tool for molecular epidemiology.

In order to isolate experimentally induced p53 mutations, a yeast expression vector harbouring a human wild-type p53 cDNA was treated in vitro with the antineoplastic drug chloroethyl-cyclohexyl-nitroso-urea (CCNU) and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. p53 mutations were identified in 32 out of 39 plasmids rescued from independent ade- transformants. Ninety-two percent of CCNU induced mutations were GC-targeted single base pair substitutions, and GC > AT transitions represented 73% of all single base pair substitutions. In 70% of the cases the mutated G was preceded 5' by a purine. The distribution of the mutations along the p53 cDNA was not random: positions 734 and 785 appeared as CCNU mutational hotspots (n=3, P<0.0003) and CCNU induced only GC > AT transitions at those positions. The features of these CCNU-induced mutations are consistent with the hypothesis that O6-alkylguanine is the major causative lesion. One third of the CCNU-induced mutants were absent from a huge collection of 4496 p53 mutations in human tumours and cell lines, thus demonstrating that CCNU has a mutational spectrum which is uniquely different from that of naturally selected mutations. This strategy allows direct comparison of observed natural mutation spectra with experimentally induced mutation spectra and opens the way to a more rigorous approach in the field of molecular epidemiology.

Antineoplastic Agents, Alkylating↗

PubMed2004

Adverse drug reactions in elderly patients.

Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacology of the drug and therefore potentially avoidable. Frail elderly patients appear to be particularly at risk of ADRs and this group is also likely to be receiving several medicines. The toxicity of some drug combinations may sometimes be synergistic and be greater than the sum of the risks of toxicity of either agent used alone. In order to recognize and to prevent ADRs (including drug interactions), good communication is crucial, and prescribers should develop an effective therapeutic partnership with the patient and with fellow health professionals. Undergraduate and postgraduate education in evidence-based therapeutics is also vitally important. The use of computer-based decision support systems (CDSS) and electronic prescribing should be encouraged, and when problems do occur, health professionals need to be aware of their professional responsibility to report suspected adverse drug events (ADEs) and ADRs. "Rational" or "obligatory" polypharmacy is becoming a legitimate practice as increasing numbers of individuals live longer and the range of available therapeutic options for many medical conditions increases. The clear risk of ADRs in this situation should be considered in the context that dose-related failure of existing therapy to manage the condition adequately may be one of the most important reasons for admission of the elderly to hospital. Thus, age itself should not be used as a reason for withholding adequate doses of effective therapies.

Adverse Drug Reaction Reporting Systems↗

PubMed2001

Fatal adverse drug events: the paradox of drug treatment.

OBJECTIVE: Study patient characteristics, morbidity patterns and drug regimens associated with fatal adverse drug events (FADEs) amongst medical department inpatients. DESIGN: An observational, descriptive study using aggregated medical records, autopsies and pre and postmortem drug analyses. SETTING: A department of internal medicine at a Norwegian county hospital. SUBJECTS: All patients dying in the department over a 2-year period. RESULTS: The incidence of FADEs were 18.2% (133/732). Compared with non-FADE cases, FADE cases were older, used more drugs both on admission and at death, and had higher comorbidity (P < 0.001). Drugs suspected to cause or contribute to fatal outcome were mainly those used for treating chronic pulmonary diseases (terbutaline, theophylline), antithrombotic drugs (aspirin, warfarin, heparines) and drugs for treating coronary heart disease and heart failure (e.g. diuretics, nitrates, angiotensin converting enzymes (ACE) inhibitors, calcium channel blockers). Bronchodilatory drugs, antithrombotic drugs and cardiovascular drugs account for 26, 31 and 30 FADE cases, respectively. Patients dying from gastrointestinal diseases had the highest relative FADE occurrence (42%), cancer patients the lowest occurrence (4%). Serious drug-drug and drug-disease interactions were frequently suspected. Various degrees of inappropriateness in choice of drug, dosage or administration route were seen in 50% of FADE cases. CONCLUSIONS: This study shows a high incidence of FADEs associated with high age, high comorbidity and polypharmacy, and partly to inappropriate drug prescribing or use. Treatments frequently associated with FADEs were bronchodilatory treatment of patients with both chronic obstructive lung disease and coronary heart disease, vasodilatory treatment in patient with endstage heart failure and the combination of several antithrombotic drugs. A systematic strategy is needed to avoid unnecessary adverse drug events (ADEs).

Adult↗

PubMed1999

Frequency, consequences and prevention of adverse drug events.

Iatrogenic injuries are important because they are frequent and many may be preventable; those caused by therapeutic drugs are among the most frequent. While medication errors are common, most have little potential for harm. However, some errors, such as giving a patient a drug to which they have a known allergy, are more likely to cause injury. Error theory provides insights into the changes required to reduce medication error injury rates. Data from the Adverse Drug Event (ADE) Prevention study suggest that most serious errors occur at the ordering and dispensing stages, while another, smaller, proportion occur at the administration stage. These data suggest that physician computer-order entry, where physicians write orders on-line with decision support, including patient-specific information and alerts about potential problems, has the potential to significantly reduce the number of serious medication errors.

Australia↗

PubMed1999

Towards safer drug use in general practice.

A voluntary, anonymous incident-monitoring study was set up to identify and characterize events or circumstances which could have or did harm a patient in general practice. The study included 673 practitioners who made 2582 reports, of which half (n = 1294) involved medication problems. Amongst these reports, 1556 adverse drug events (ADE) were identified. More common in general practice than in hospitals were problems with therapeutic use (26% vs. 8%), and prescribing of contraindicated medications (15% vs. 5%). In the latter group, 64 reports (4%) involved the prescription of a medication to which the patient was known to be allergic, 66 (4%) involved medication for which there was a recognized potential for a drug interaction, and 68 (4%) involved contraindicated medications due to pathophysiological factors. It was estimated that computer-based prescribing with decision support could eliminate at least a third of these problems in general practice. Further studies are needed to develop this and other preventive strategies.

Australia↗

PubMed1996

[Estimation of radiation exposure in interventional neuroradiology of the head in children compared to exposure of adult patients].

PURPOSE: We reviewed different dosimetric results in three children investigated for haemangioma, arteriovenous malformation, and angioma of the head in comparison to global results in 11 adults. METHOD: The detailed patient dosimetry was performed using thermoluminescence dosimetry (TLD), area-dose exposure meter (ADE), and Alderson phantom. RESULTS: The patient doses of relevant organs ranged in the milli-Grays (mGy) level. The irradiation-induced risk is on a per mil level in respect of ICRP-60. The risk of cerebral angiographic procedures, radiotherapy, or surgical interventions is on a per cent level. The organ doses for staff are on a micro-Gray (microGy) scale and are higher in examination of children than of adults. A statistical limit of examinations depends on yearly or life-time dose limits with regard to the "Röntgenverordnung" (Germany).

Adult↗

PubMed1992

The natural history of acute disseminated leukoencephalitis. A serial magnetic resonance imaging study.

The natural history of acute disseminated (leuko)encephalitis (ADE) in a 3-year-old girl who did not receive steroid therapy is reported. Serial MR studies disclosed: 1) white matter lesions resolved spontaneously, though very slowly, 2) active disease persisted for around three months and coincided with the onset of new subcortical lesions. These subcortical lesions were associated with hyperactivity, suggesting a possible etiologic correlation.

Acute Disease↗

PubMed1970

Specific binding of leucyl transfer RNA to an immature form of L-threonine deaminase: its implications in repression.

The in vitro assembly of L-threonine deaminase from its constituent parts results in the formation of an inactive species of this enzyme which specifically and reversibly binds leucyl-tRNA. The native, catalytically active enzyme, which is derived from this species in the presence of maturation-inducing ligands, does not bind tRNA. The possible involvement of this protein-tRNA complex in the repression of the ilv (ADE) operon is discussed.

Carbon Isotopes↗