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J Horn

Publications and source records attributed to J Horn.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review.

BACKGROUND AND PURPOSE: Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials. METHODS: - We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Embase. We assessed whether these studies showed a beneficial effect of active treatment. In-depth analyses were performed on infarct size and amount of edema, and subgroup analyses were performed on the length of the time window to the initiation of treatment and the methodological quality of the studies. RESULTS: - Of 225 identified articles, 20 studies were included. The methodological quality of the studies was poor. Of the included studies, 50% were in favor of nimodipine. In-depth analyses showed statistically significant effects in favor of treatment (10 studies). No influence of the length of time to the initiation of treatment or of the methodological quality on the results was found. CONCLUSIONS: - We conclude that the results of this review did not show convincing evidence to substantiate the decision to perform trials with nimodipine in large numbers of patients. There were no differences between the results of the animal experiments and clinical studies. Surprisingly, we found that animal experiments and clinical studies ran simultaneously.

Animals↗
PubMed2001

Expertise and age-related changes in components of intelligence.

In a sample of 263 male GO players at 48 levels of expertise and ranging from 18 to 78 years of age, it was found that factors of expertise deductive reasoning (EDR) and expertise working memory (EWM) were independent of factors of fluid reasoning (Gf) and short-term working memory (STWM) that, along with cognitive speed (Gs), have been found to characterize decline of intelligence in adulthood. The main effects of analyses of cross-sectional age differences indicated age-related decline in EDR and EWM as well as in Gf, STWM, and Gs. However, interaction and partialing analyses indicated that decline in EDR and EWM decreased to no decline with increase in level of expertise. The results thus suggest that with increase in factors known to raise the level of expertise--particularly, intensive, well-designed practice--there may be no age-related decline in the intelligence that is measured in the abilities of expertise.

Adult↗
PubMed2000

Calcium antagonists for acute ischemic stroke.

BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with increased levels of calcium ions within neurones. Inhibiting this increase could protect neurones and is thought to reduce neurological impairment, disability and handicap after stroke. OBJECTIVES: The aim of this review is to determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. The influence of different drugs, dosages, routes of administration, time intervals after stroke and trial design on the risk of poor outcome was investigated. SEARCH STRATEGY: Relevant trials were identified in the Specialised Register of Controlled Trials (last searched: March 1999). SELECTION CRITERIA: All truly randomised trials comparing a calcium antagonist with control in patients with acute ischaemic stroke were included. DATA COLLECTION AND ANALYSIS: Two authors assessed all trials and extracted the data. Poor outcome, defined as death or dependency in activities of daily living, was used as the main outcome. Analyses were, if possible, "intention-to-treat". MAIN RESULTS: 46 trials were identified of which 28 were included (7521 patients). No effect of calcium antagonists on poor outcome at the end of follow-up (OR 1.07, 95% CI 0.97/1.18), or on death at end of follow-up (OR 1.10, 95% CI 0.98/1.24) was found. Intravenous administration (i.v.) of calcium antagonists was associated with an increase in the number of patients with poor outcome compared to oral administration (indirect comparisons). Comparisons of different doses of nimodipine suggested that the highest doses were associated with poorer outcome. Administration within 12 hours of onset was associated with an increase in the proportion of patients with poor outcome, but this effect was largely due to the poor results associated with i.v. administration. A subgroup analysis on nimodipine (oral, 120 mg/day) started within 12 hours of stroke onset, did not show a beneficial effect. REVIEWER'S CONCLUSIONS: No evidence is available to justify the use of calcium antagonists in patients with acute ischaemic stroke.

Brain Ischemia↗
PubMed2000

Metabolic control and psychological sense of control in women with diabetes mellitus. Alternative considerations of the relationship.

PURPOSE: Identifying psychological strategies to buffer the adverse outcomes in people with diabetes mellitus (DM) remains a priority for many health professionals. While 'locus of control' (LOC) has been repeatedly investigated to this end, research findings are contradictory. The development of more complex appraisals of psychological control, and the utilization of control inventories deriving from such analyses, presents a way forward from such contradictions. METHODS: Employing such a measure, this study examines the relationship between metabolic control and psychological sense of control in 96 women with DM. RESULTS: Optimal metabolic control is significantly associated with overall sense of control, while poor metabolic control was significantly associated with experiences of loss of psychological control and feelings of inadequacy. Furthermore, poor metabolic control was significantly associated with reduced control in the specific domains of interpersonal relationships and bodily functions. CONCLUSIONS: Multidimensional control inventories enable a more complex appraisal of the relationship between metabolic control and psychological control, and in doing so, provide a way forward from problems arising from reliance on LOC constructs. Interventions for DM management relying on aspects of psychological control need to target domains beyond traditional issues of self and bodily functions.

Adult↗
PubMed2000

The proton-pump inhibitors: similarities and differences.

OBJECTIVE: This paper examines the clinical pharmacology of the proton-pump inhibitors (PPIs) and briefly reviews some comparative studies of these agents. BACKGROUND: PPIs have emerged as the treatment of choice for acid-related diseases, including gastroesophageal reflux disease (GERD) and peptic ulcer disease. Although these drugs-omeprazole, lansoprazole, pantoprazole, and rabeprazole-share a common structure (all are substituted benzimidazoles) and mode of action (inhibition of H+,K+-adenosine triphosphatase [ATPase]), each differs somewhat in its clinical pharmacology. RESULTS: In comparative clinical trials found in MEDLINE, PPIs administered once daily produced endoscopic evidence of healing in >90% of patients with duodenal ulcer after 4 weeks of treatment, in >90% of those with gastric ulcer after 6 weeks of treatment, and in >90% of those with ulcerative or erosive GERD after 8 weeks of treatment. Maintenance therapy with daily doses of a PPI has been shown to be an effective means of preventing GERD relapse. PPIs also inhibit the growth of Helicobacter pylori, now recognized as an important factor in peptic ulcer disease, and, when administered in combination with antibiotics, provide the best treatment for eradication of the bacterium. Rabeprazole has a more rapid onset of H+,K+-ATPase inhibition than the other PPIs and, compared with omeprazole, a greater effect on intragastric pH after the first dose. Omeprazole and lansoprazole have a greater potential for drug-drug interactions than do pantoprazole and rabeprazole. CONCLUSION: Although the individual PPIs have similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

A Dictyostelium protein binds to distinct oligo(dA) x oligo(dT) DNA sequences in the C-module of the retrotransposable element DRE.

The genome of the eukaryotic microbe Dictyostelium discoideum contains some 200 copies of the nonlong-terminal repeat retrotransposon DRE. Among several unique features of this retroelement, DRE is transcribed in both directions leading to the formation of partially overlapping plus strand and minus strand RNAs. The synthesis of minus strand RNAs is controlled by the C-module, a 134-bp DNA sequence located at the 3'-end of DRE. A nuclear protein (CMBF) binds to the C-module via interaction with two almost homopolymeric 24 bp oligo(dA) x oligo(dT) sequences. The DNA-binding drugs distamycin and netropsin, which bind to A x T-rich DNA sequences in the minor groove, competed efficiently for the binding of CMBF to the C-module. The CMBF-encoding gene, cbfA, was isolated and a DNA-binding domain was mapped to a 25-kDa C-terminal region of the protein. A peptide motif involved in the binding of A x T-rich DNA by high mobility group-I proteins ('GRP' box) was identified in the deduced CMBF protein sequence, and exchange of a consensus arginine residue for alanine within the CMBF GRP box abolished the interaction of CMBF with the C-module. The current data support the theory that CMBF binds to the C-module by detecting its long-range DNA conformation and interacting with A x T base pairs in the minor groove of oligo(dA) x oligo(dT) stretches.

Amino Acid Sequence↗
PubMed1999

Intravascular sonography in the assessment of traumatic injury of the thoracic aorta.

OBJECTIVE: The objective of this study is to describe the use of intravascular sonography in the evaluation of suspected injury of the thoracic aorta as an adjunctive tool to digital subtraction arteriography (DSA). SUBJECTS AND METHODS: Images of the thoracic aorta were obtained using DSA and intravascular sonography in 20 consecutive patients who underwent arteriography after chest trauma. A 6-French, 12.5-MHz sonography catheter was used for the intravascular sonography study. Diagnoses based on the review of both studies were compared. RESULTS: Five of 20 patients had aortic or great vessel injuries confirmed by surgery. Intravascular sonographic findings were positive (one false-positive) in seven patients, whereas DSA findings were positive in six patients (one false-positive and one false-negative). Surgery showed the lesion that was false-positive using both techniques to be a ductus diverticulum. Intravascular sonographic findings included intimal flaps, intramural lesions (hematomas), pseudoaneurysms, and perivascular hematomas. CONCLUSION: In our initial limited experience, intravascular sonography of the thoracic aorta and great vessels effectively identified traumatic injuries. Intramural injury without pseudoaneurysm formation or obvious intraluminal flap was visualized by intravascular sonography in one patient but was not detected by DSA. On the other hand, a ductus diverticulum was erroneously interpreted as trauma using both techniques. Intravascular sonography is a relatively new procedure with an obvious learning curve in the interpretation of the findings. An atypical ductus diverticulum may still be mistakenly interpreted as a sign of traumatic injury of the aorta. Familiarity with intravascular sonography in the setting of aortic trauma is necessary for correct interpretation of the images. The sonographic findings offer views of the aorta that are complementary to those of aortography.

Adult↗
PubMed1998

9-Sulfooxymethylanthracene is an ultimate electrophilic and carcinogenic form of 9-hydroxymethylanthracene.

The role of electrophilic hydroxymethyl sulfate esters in the metabolic activation, DNA-damage, mutagenicity, and complete carcinogenicity of polycyclic aromatic hydrocarbons has been elucidated considerably in recent years. The observations are in agreement with a unified hypothesis which predicts that electrophilic hydroxymethyl sulfate esters and closely related aralkylating agents are major ultimate carcinogenic forms of most, if not all, carcinogenic alkyl-substituted and even unsubstituted carcinogenic polycyclic aromatic hydrocarbons. The common final step in a chain of enzymatic substitution reactions is the formation of an aralkylating agent bearing a good leaving group. Activation of hydroxymethyl derivatives, including 9-hydroxymethylanthracene, to electrophilic mutagens has been shown to be catalyzed by 3'-phosphoadenosine-5'-phosphosulfate-dependent sulfotransferase activity. Recent studies, in a complete carcinogenic model, demonstrate that a number of sulfuric acid ester derivatives are more potent than their hydroxymethyl precursors by repeated subcutaneous injection in female Sprague-Dawley rats. In this paper, these observations have been extended to include 9-sulfooxymethylanthracene as an ultimate electrophilic and carcinogenic form of 9-hydroxymethylanthracene.

Animals↗
PubMed1998

Protein kinase Cmu downregulation of tumor-necrosis-factor-induced apoptosis correlates with enhanced expression of nuclear-factor-kappaB-dependent protective genes.

Protein kinase Cmu (PKCmu) represents a new subtype of the PKC family characterized by the presence of a pleckstrin homology (PH) domain and an amino-terminal hydrophobic region. In order to analyse the potential role of PKCmu in signal-transduction pathways, stable PKCmu transfectants were established with human and murine cell lines. All transfectants showed a reduced sensitivity to tumor-necrosis-factor (TNF)-induced apoptosis, which correlated with the amount of transgene expressed and with an enhanced basal transcription rate of NF-kappaB-driven genes including the inhibitor of apoptosis protein 2 (cIAP2) and TNF-receptor-associated protein 1 (TRAF1). Sensitivity to apoptosis induced by the lipid mediator ceramide was unchanged in PKCmu transfectants. In support of a PKCmu action on NF-kappaB, we show enhancement and downregulation of TNF-induced expression of a NF-kappaB-dependent reporter gene by transient overexpression of wild-type and kinase-negative mutants of PKCmu, respectively. Interestingly, no significant changes were found in an electrophoretic mobility shift assay, indicative of PKCmu action downstream of IkappaB degradation, probably by modulation of the transactivation capacity of NF-kappaB. The dominant negative action of the kinase-negative mutant further suggest a regulatory role of PKCmu for NF-kappaB-dependent gene expression.

Apoptosis↗
PubMed1998

Carcinogenicity of 1-hydroxy-3-methylcholanthrene and its electrophilic sulfate ester 1-sulfooxy-3-methylcholanthrene in Sprague-Dawley rats.

Previous experiments have demonstrated that the carcinogen 1-hydroxy-3-methylcholanthrene is a metabolite of 3-methylcholanthrene. 1-Sulfooxy-3-methylcholanthrene, prepared by chemical synthesis from 1-hydroxy-3-methylcholanthrene, was shown to be a direct acting electrophilic mutagen and DNA damaging agent. These results imply that 1-hydroxy-3-methylcholanthrene could be metabolically activated to an ultimate electrophilic and carcinogenic form of 1-hydroxy-3-methylcholanthrene and 3-methylcholanthrene in a reaction catalyzed by 3'-phosphoadenosine-5'-phosphosulfate-dependent sulfotransferase activity. 1-Hydroxy-3-methylcholanthrene and its aralkylating reactive ester, 1-sulfooxy-3-methylcholanthrene, were individually administered to groups of 12 female Sprague-Dawley rats at a 0.2 mumol dose, three times weekly, for 20 doses. 1-Sulfooxy-3-methylcholanthrene induced sarcomas at the site of injection in 8 of 12 rats (66%) by 52 weeks, whereas 1-hydroxy-3-methylcholanthrene induced sarcomas at the site of injection in 5 of 12 rats (42%) by 52 weeks. These results, taken together with the results of previous experiments, strongly support the hypothesis that the activated electrophilic mutagen 1-sulfooxy-3-methylcholanthrene plays a major role as an ultimate electrophilic and carcinogenic form of 1-hydroxy-3-methylcholanthrene, a major metabolite of 3-methylcholanthrene.

Animals↗
PubMed1998

Prospective study of nosocomial fungal meningitis in children--report of 10 cases.

Within an 8-year period, 10 cases of fungal nosocomial meningitis in children 0-13 y old were prospectively identified, 3 caused by yeasts other than Candida spp. (Rhodotorula rubra, Aureobasidium mansoni, Clavispora lusitaniae) and 7 by Candida albicans. Seven patients survived. whereas 3 neonates with fungal meningitis (all due to C. albicans) died. Risk factors for fungal nosocomial meningitis included cancer (2 children), previous neurosurgery (2 children), cranial trauma (1 case) and prematurity with low birthweight (5 cases). All patients except 1 had received broad-spectrum antibiotics before onset of meningitis. In addition to yeasts, bacteria were isolated from CSF of 4 children. One child had additional fungaemia. Univariate analysis was used to compare 10 cases of fungal to 91 cases of bacterial nosocomial meningitis. Except for concurrent bacteraemia, (60 vs 25.3%, P < 0.03), which was more frequently observed among fungal meningitis, there were no significant differences in risk factors, sequelae or outcome (mortality) between patients with fungal vs bacterial meningitis. A review of fungal meningitis reported within the last 20 y is included.

Adolescent↗
PubMed1998

Percutaneous Application of Fibrin Sealant to Achieve Hemostasis Following Arterial Catheterization.

OBJECTIVES: The present study sought to investigate the safety and efficacy of a new fibrin sealant using percutaneous delivery techniques. BACKGROUND: The femoral approach has become the preferred means of access for percutaneous diagnostic and interventional procedures. Control of access site bleeding following catheterization, however, remains a significant problem in interventional cardiology. METHODS: Adult mongrel dogs were used in this study. Series 1 compared the effectiveness of fibrin sealant vs. manual compression alone in the presence of anticoagulants, thrombolytic, and antiplatelet agents. Series 2 assessed fibrin sealant safety. Series 3 examined fibrin sealant performance under elevated blood pressure levels. RESULTS: Series 1: Hemostasis was achieved in all fibrin sealant sites in significantly less time (8.5 +/- 4.3 min) with no major complications compared to manual compression sites (65.2 +/- 19.3 min) accompanied by serious complications. For all adjunctive agents employed, hemostasis was achieved in fibrin sealant sites in significantly less time (warfarin 9.9 +/-.2, urokinase 11.2 +/- 5.6, ReoProª 10.5 +/- 6.3 min) than for manual compression sites (warfarin 86.5 +/- 21.4, urokinase 89.8 +/- 36.3, ReoPro 77.9 +/- 26.5 min). Series 2: I25 iodine-labeled fibrinogen sealant was applied to puncture sites with no traces of circulating radioactivity observed over a one-hour period. Series 3: hemostasis was achieved under elevated blood pressure conditions in all animals. Histologic studies showed complete re-absorption of fibrin sealant 28 days post-procedure with no evidence of foreign body reaction. CONCLUSIONS: Percutaneous application of fibrin sealant to achieve hemostasis following catheterization appears to be a simple, safe, and highly effective procedure in a canine model.

Journal Article↗
PubMed1997

6-sulfooxymethylbenzo[a]pyrene is an ultimate electrophilic and carcinogenic form of the intermediary metabolite 6-hydroxymethylbenzo[a]pyrene.

Previous experiments have demonstrated that the intermediary metabolite 6-hydroxymethylbenzo[a] pyrene (HMBP) can be activated to the electrophilic mutagen, 6-sulfooxymethylbenzo[a]pyrene (SMBP), by rat and mouse liver PAPS-dependent sulfotransferase activity or by chemical synthesis. This aralkylating metabolite and 6-hydroxymethylbenzo[a]pyrene were individually administered to groups of 12 female Sprague-Dawley rats, at a 0.2 micromol dose three times weekly for 20 doses. SMBP induced sarcomas at the site of injection in 12 of 12 rats by 33 weeks, whereas HMBP induced sarcomas at the site of injection in 12 of 12 rats by 31 weeks. These results, taken together with the results of previous studies, strongly support the hypothesis that the electrophilic mutagen SMBP accounts for most, if not all, of the complete carcinogenicity of the intermediary metabolite HMBP and probably at least some of the complete carcinogenicity of 6-methylbenzo[a]pyrene (MBP), 6-formylbenzo[a]pyrene (formylBP), and even benzo[a]pyrene (BP), all of which are metabolized to HMBP.

Animals↗
PubMed1997

Molecular cloning of a cDNA encoding the nucleosome core histone H3 from Dictyostelium discoideum by genetic screening in yeast.

The one-hybrid method for genetic screening in yeast was used to search a Dictyostelium discoideum cDNA library for DNA-binding proteins that interact with the C-module of the Dictyostelium repetitive element. The C-module was formerly shown to contain two high affinity, sequence-specific binding sites for a nuclear protein factor of unknown function (CMBF). The bait DNA sequence was bound in vivo by a cDNA-encoded protein whose derived amino acid sequence showed high homology to nucleosome core histone H3, but not to partially available CMBF sequences. The D. discoideum histone H3 homolog is encoded by a single gene and shows significant sequence variation at the amino terminus of the protein, including a triple-serine insertion not found in any other histone H3.

Amino Acid Sequence↗