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PubMed2001

Effect of methyldopa on renal function in rats with L-NAME-induced hypertension in pregnancy.

BACKGROUND: Pregnancy-induced hypertension is characterized by an increased sympathetic activity and probably by a decreased synthesis/activity of nitric oxide. The aim of the present study is to evaluate whether the beneficial action of the sympathetic antagonist methyldopa (a first-choice hypotensive agent in the treatment of PIH) may be associated to changes in nitric-oxide synthesis. METHODS: Forty pregnant Wistar rats received L-NAME (NO synthase inhibitor, 9-10 mg/kg/day) from mid-pregnancy (day 11) through to term. Some rats were treated with daltroban (TxA receptor antagonist, 60 mg/kg/day), diltiazem (calcium channel blocker, 30 mg/kg/day), methyldopa (central adrenergic antagonist, 400 mg/kg/day) or L-arginine (260 mg/kg/day) from mid-pregnancy. The effect of the different treatments on systolic blood pressure (SBP), creatinine clearance (CCR), urine protein excretion (UP) and urinary nitrate excretion (UNO(3), representing urine NO metabolite) were evaluated and the results compared with those found in normal pregnancy. Normal pregnant rats receiving similar treatment were used as controls. RESULTS: In normal pregnant (P) rats, SBP values decreased from 94 +/- 2 to 83 +/- 3 mm Hg at the end of pregnancy (p < 0.01) and CCR augmented significantly. Drug treatment had no significant effect. In NAME-treated rats, at the same period, the SBP augmented from 92 +/- 1 to 129 +/- 1.8 mm Hg (p < 0.01). At the end of pregnancy, NAME rats had significantly lower CCR values and higher UP excretion when compared with P rats. UNO(3) increased significantly in P and in P rats treated with methyldopa. As expected, in NAME rats UNO(3) excretion was significantly reduced. Treatment with methyldopa normalized SBP, improved CCR and proteinuria and was associated with an increase in UNO(3). Similar results were obtained with L-arginine treatment. Diltiazem lowered SBP significantly but had no effect on renal function or UNO(3) and daltroban had no effect. CONCLUSION: The increased UNO(3) found in NAME rats treated with methyldopa suggests that the vasoconstriction secondary to chronic NO inhibition may be partially related to an increased sympathetic activity. The efficient action of the sympathetic antagonist methyldopa may be due not only to its antihypertensive effects but also by its stimulating effect on NO synthesis leading also to an improvement of renal function.

Animals↗
PubMed2002

Effects of L-arginine and L-NAME on the renal function in hypertensive and normotensive subjects.

BACKGROUND/AIM: Renal vasodilation in response to L-arginine has been reported to be diminished in hypertensive (HT) subjects. If this diminished renal vasodilator response indicates disturbance of the renal NO pathway, a diminished renal vasoconstrictor response to NO synthase inhibition may be present in HT subjects as well. The present study was conducted to compare the effects of L-arginine and N(G)-nitro-L-arginine methyl ester (L-NAME) on renal and systemic hemodynamics between HT and normotensive (NT) subjects. METHODS: The responses of renal and systemic vascular resistances (RVR and SVR) and plasma noradrenaline and renin (NOR and PRA) to systemic NO stimulation and inhibition were studied in patients with grade 1 essential HT and age- and sex-matched NT subjects. On separate occasions, after baseline values were obtained, 40-min randomly administered intravenous infusions of L-arginine (12.5 mg.kg(-1).min(-1)) or L-NAME (0.0125 mg.kg(-1).min(-1)) were given. RESULTS: Baseline values of RVR (129 +/- 21 and 162 +/- 10 resistance units) and SVR (15.1 +/- 4.3 and 21.6 +/- 5.1 resistance units) were higher (p < 0.01) in HT than in NT subjects, whereas the baseline values of NOR and PRA were similar. Infusion of L-arginine caused similar decrements in SVR (29 +/- 10 and 31 +/- 11%), but the decrease in RVR was smaller (22 +/- 8 and 35 +/- 12%, respectively; p < 0.05) in HT than in NT subjects. In response to L-NAME, the increments in RVR (66 +/- 10 and 61 +/- 25%) and SVR (36 +/- 21 and 34 +/- 18%) were similar in HT and NT subjects. In both groups, infusion of L-arginine was associated with similar increments, whereas infusion of L-NAME was associated with similar decrements in NOR and PRA. CONCLUSIONS: This study confirms the smaller renal vasodilator response to L-arginine in HT than in NT subjects. Whether this is caused by a disturbance of the renal NO pathway remains doubtful considering the observed similar L-NAME-induced increments in RVR and SVR in the two groups of subjects.

Adult↗
PubMed2002

Modality-specific deterioration in naming verbs in nonfluent primary progressive aphasia.

A longitudinal study of oral and written naming and comprehension of nouns and verbs in an individual (M. M. L.) with nonfluent primary progressive aphasia (PPA) is reported. M. M. L. showed progressive deterioration of oral naming of verbs well before deterioration of written naming of verbs and before deterioration of oral or written naming of nouns. Her comprehension of both nouns and verbs remained intact, at least relative to oral naming of verbs. Her performance is compared to that of two other individuals with nonfluent PPA, who were tested at two time points. These patients showed similar patterns with respect to grammatical word class (verbs more impaired than nouns) and modality (spoken production more impaired than written production), but somewhat different courses of deterioration. The modality-specific nature of the observed verb production deficits rules out a semantic locus for the grammatical class effects. The results provide a new source of evidence for the hypothesis that there are distinct neural mechanisms for accessing lexical representations of nouns and verbs in language production.

Aged↗
PubMed2005

Different effects of dexamethasone and the nitric oxide synthase inhibitor L-NAME on caerulein-induced rat acute pancreatitis, depending on the severity.

Effects of dexamethasone and N(G)-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on caerulein-induced acute pancreatitis were examined in rats. Acute pancreatitis was induced by caerulein (20 mug/kg, s.c.) given repeatedly 2 or 4 times every hour, and serum amylase levels, pancreas weight and myeloperoxidase (MPO) activity were measured 6 h after the first injection of caerulein. Dexamethasone (3 mg/kg) and L-NAME (30 mg/kg) were administered p.o. 30 min before the first injection of caerulein. Caerulein caused moderate or severe pancreatitis, depending on the times of injections, resulting in different degrees of increase in serum amylase levels and pancreas weight, and the marked elevation of MPO activity was observed only after injections of caerulein given 4 times per hour. Both dexamethasone and L-NAME suppressed the severity of pancreatits, yet the effect of L-NAME as compared with dexamethasone was more potent against mild pancreatitis but less potent against severe pancreatitis. These results suggest that caerulein-induced acute pancreatitis shows different responsiveness to L-NAME and dexamethasone, depending on the severity; the former is more effective against pancreatitis with less inflammation, while the latter is more effective against pancreatitis with severe inflammation. It is assumed that endogenous NO may be involved in oedema formation as the early event in the development of acute pancreatitis.

Acute Disease↗
PubMedDate not supplied

Naming speed, phonological awareness, and orthographic knowledge in second graders.

Concurrent relationships among measures of naming speed, phonological awareness, orthographic skill, and other reading subskills were explored in a representative sample of second graders. Hierarchical regression analyses revealed that naming speed, as measured by the the rapid automatized naming (RAN) task, accounted for a sizable amount of unique variance in reading with vocabulary and phonemic awareness partialled out. The unique contribution of naming speed to reading was relatively stronger for orthographic skills, whereas the contribution of phonemic skills was stronger for nonword decoding. In further analyses, marked difficulties on a range of reading tasks, including orthographic processing, were seen in a subgroup with a double deficit (slow naming speed and low phonemic awareness) but not in groups with only a single deficit. These findings are broadly consistent with Bowers and Wolf's (1993a, 1993b; Wolf & Bowers, 1999) double-deficit hypothesis of reading disability.

Child↗
PubMedDate not supplied

Naming-speed processes, timing, and reading: a conceptual review.

This article integrates the findings in the special issue with a comprehensive review of the evidence for seven central questions about the role of naming-speed deficits in developmental reading disabilities. Cross-sectional, longitudinal, and cross-linguistic research on naming-speed processes, timing processes, and reading is presented. An evolving model of visual naming illustrates areas of difference and areas of overlap between naming speed and phonology in their underlying requirements. Work in the cognitive neurosciences is used to explore two nonexclusive hypotheses about the putative links between naming speed and reading processes and about the sources of disruption that may cause subtypes of reading disabilities predicted by the double-deficit hypothesis. Finally, the implications of the work in this special issue for diagnosis and intervention are elaborated.

Child↗
PubMed1997

L-NAME-sensitive and -insensitive nonadrenergic noncholinergic relaxation of cat airway in vivo and in vitro.

The neurotransmitters responsible for neurogenic airway relaxation are still unknown. We investigated the effects of N omega-nitro-L-arginine methylester (L-NAME) on nonadrenergic and noncholinergic (NANC) relaxation evoked by electrical stimulation of vagus nerves in vivo and in vitro in cat. To that end, we measured pulmonary resistance during vagal nerve stimulation (VS) in vivo, and isometric tension of small bronchi (1-3 mm outer diameter) during electrical field stimulation (EFS) in vitro. During infusion of 5-hydroxytryptamine (5-HT), VS transiently decreased total pulmonary resistance in the presence of atropine and propranolol, with peak relaxation at several seconds after the VS and a gradual return to baseline within 2-3 min. L-NAME abolished the initial peak relaxation and reduced the peak amplitude, but did not affect the duration of the NANC relaxation. In small bronchi obtained from control cats, EFS evoked a biphasic NANC relaxation, comprising an initial fast component followed by a second slow component, and L-NAME (10(-5) M) selectively abolished the first component without affecting the second. Whilst in the small bronchi obtained from L-NAME pretreated cats, EFS elicited only the slow component of NANC relaxation, which was insensitive to L-NAME but sensitive to tetrodotoxin. These results indicate that nonadrenergic noncholinergic relaxation induced by vagal nerve stimulation during infusion of 5-hydroxytryptamine can be classified into two components, and that at least two neurotransmitters, including nitric oxide, are involved in the relaxation.

Airway Resistance↗
PubMed1998

Effect of nitric oxide synthesis inhibition with nebulized L-NAME on ventilation-perfusion distributions in bronchial asthma.

Patients with clinically stable asthma may show ventilation-perfusion (V'A/Q') mismatch. Nitric oxide (NO), a potent endogenous vasodilator, is increased in exhaled air of asthmatics. Such an increased NO production may be detrimental for optimal V'A/Q' balance owing to the potential inhibition of hypoxic pulmonary vasoconstriction. This study was undertaken to investigate the relationship between the concentration of NO in exhaled air and the degree of gas-exchange impairment and to assess the effect of nebulized N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthesis, on gas exchange in patients with asthma. Twelve patients (four females and eight males, aged 31+/-5 yrs) with clinically stable asthma (forced expiratory volume in one second (FEV1) 80+/-5%) not treated with glucocorticoids and increased exhaled NO (58+/-9 parts per billion (ppb)) were studied. Exhaled NO, respiratory system resistance (Rrs), arterial blood gases and V'A/Q' distributions were measured before and 30, 60, 90 and 120 min after placebo or L-NAME (10(-1) M) nebulization; in eight patients pulmonary haemodynamics were also measured. At baseline no relationships between exhaled NO and gas-exchange measurements were shown. Nebulized L-NAME induced a significant decrease in exhaled NO (p< 0.001), which was maximal at 90 min (-55+/-5%). However, after L-NAME no changes in Rrs, arterial oxygen tension, the alveolar-arterial pressure difference in oxygen or V'A/Q' distributions were shown and nebulized L-NAME did not modify pulmonary artery pressure. In conclusion, the degree of gas-exchange impairment in stable asthma is not related to nitric oxide concentration in exhaled air and nitric oxide synthesis inhibition with N(G)-nitro-L-arginine methyl ester does not alter gas exchange or pulmonary haemodynamics, such that ventilation-perfusion disturbances do not appear to be related to an increased synthesis of nitric oxide in the airways.

Administration, Inhalation↗
PubMed2004

Mistaken identifiers: gene name errors can be introduced inadvertently when using Excel in bioinformatics.

BACKGROUND: When processing microarray data sets, we recently noticed that some gene names were being changed inadvertently to non-gene names. RESULTS: A little detective work traced the problem to default date format conversions and floating-point format conversions in the very useful Excel program package. The date conversions affect at least 30 gene names; the floating-point conversions affect at least 2,000 if Riken identifiers are included. These conversions are irreversible; the original gene names cannot be recovered. CONCLUSIONS: Users of Excel for analyses involving gene names should be aware of this problem, which can cause genes, including medically important ones, to be lost from view and which has contaminated even carefully curated public databases. We provide work-arounds and scripts for circumventing the problem.

Animals↗
PubMed2006

A scalable machine-learning approach to recognize chemical names within large text databases.

MOTIVATION: The use or study of chemical compounds permeates almost every scientific field and in each of them, the amount of textual information is growing rapidly. There is a need to accurately identify chemical names within text for a number of informatics efforts such as database curation, report summarization, tagging of named entities and keywords, or the development/curation of reference databases. RESULTS: A first-order Markov Model (MM) was evaluated for its ability to distinguish chemical names from words, yielding approximately 93% recall in recognizing chemical terms and approximately 99% precision in rejecting non-chemical terms on smaller test sets. However, because total false-positive events increase with the number of words analyzed, the scalability of name recognition was measured by processing 13.1 million MEDLINE records. The method yielded precision ranges from 54.7% to 100%, depending upon the cutoff score used, averaging 82.7% for approximately 1.05 million putative chemical terms extracted. Extracted chemical terms were analyzed to estimate the number of spelling variants per term, which correlated with the total number of times the chemical name appeared in MEDLINE. This variability in term construction was found to affect both information retrieval and term mapping when using PubMed and Ovid.

Computational Biology↗
PubMed2001

Brief report on the effect of providing single versus assorted brand name condoms to hospital patients: a descriptive study.

OBJECTIVES: This study examined condom acquisition by persons in a hospital setting when single versus assorted brand name condoms were provided. METHODS: Condom receptacles were placed in exam rooms of two clinics. During Phase 1, a single brand name was provided; for Phase 2, assorted brand names were added. Number of condoms taken was recorded for each phase. RESULTS: For one clinic there was nearly a two-fold increase in number of condoms taken (Phase 1 to Phase 2); for the second clinic there was negligible difference in number of condoms taken. CONCLUSIONS: The provision of assorted brand name condoms, over a single brand name, can serve to increase condom acquisition. Locations of condoms and target population characteristics are related factors.

Adolescent↗
PubMed1999

The neuropsychological examination of naming in Lyme borreliosis.

Although subjective complaints of word finding and naming deficits are commonly reported by patients with Lyme Borreliosis (LB), the existence of these disturbances has not been thoroughly investigated. Forty-four patients with LB and 43 healthy controls were administered a symptom questionnaire, the Boston Naming Test (BNT), the Controlled Oral Word Association Test (COWAT), and a series of category naming tasks. LB patients had a higher rate of complaints of word-finding disturbance (55% vs. 14%). Lower mean scores were observed on the BNT, but not on the COWAT, nor on category naming tasks. Thirty-six percent of the LB sample exhibited BNT scores in the impaired range. BNT scores in this group were correlated with a measure of memory retrieval, but not with verbal fluency indexes. There was no relation between naming scores and depression. LB patients exhibit impairments in word finding that appear to be secondary to a generalized retrieval deficit.

Adult↗
PubMed1984

Recovery of naming in aphasia: relationship to fluency, comprehension and CT findings.

We assessed oral naming skill after left hemisphere ischemic stroke in 54 right-handed aphasics. Initially, almost all had moderate to severe disability in oral naming. After 6 months, normal scores were achieved by one-third of the patients, all with lesions less than 60 cm3 in volume. Only 2 of 18 patients who were nonfluent at 6 months had normal naming then. Among patients with lesions less than 60 cm3 and persistently poor naming, there were two discrete lesion sites: posterior superior temporal-inferior parietal (semantic paraphasic errors) and insula-putamen (phonologic paraphasic errors). Individual variability was notable, with several patients regaining normal naming ability despite posterior temporal or insula-putamen lesions.

Adult↗
PubMed1997

Inhibitory effects of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on 2-deoxy-D-glucose-induced hyperglycemia in rats.

The inhibitory effects of a potent nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on 2-deoxy-D-glucose (2-DG)-induced hyperglycemia were investigated in rats. L-NAME significantly inhibited 2-DG-induced hyperglycemia, although N(G)-nitro-D-arginine methyl ester (D-NAME) did not affect it. A similar NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), also inhibited 2-DG-induced hyperglycemia. The antagonistic effects of L-NAME are unrelated to the cholinergic system, since the muscarinic receptor antagonist scopolamine did not affect 2-DG-induced hyperglycemia. The neuronal NO synthase inhibitor 7-nitroindazole (7-NI) did not reduce 2-DG-induced hyperglycemia, but rather enhanced it. Our results suggest that NO may be involved in glucose homeostasis and that the inhibitory effects of L-NAME on 2-DG-induced hyperglycemia are not related to muscarinic receptors or neuronal NO synthase.

Animals↗
PubMed2006

[Development of the measures to evaluate the similarity of drug brand names].

Brand name confusion is one of the most common causes of drug-related errors. The aim of this study was to develop quantitative measures of similarity among brand names of drugs. We modified the fragmentary pattern-based measure, a measure of similarity for character strings based on the string resemblance system, to develop three novel measures of similarity, i.e., the head and tail-weighted fragmentary pattern-based measure (htfrag), visually weighted htfrag (vwhtfrag), and auditorily weighted htfrag (awhtfrag). The 227 pairs of brand names for which confusion errors have been reported were used as a positive control group. Ten sets of 2270 random pairs of brand names were generated as negative controls. Then we evaluated the measures developed by using the geometric mean of sensitivity and selectivity as an objective function, in comparison with two conventional measures of similarity based on the vector space model (cos1 and htco). The measures developed, htfrag, vwhtfrag, and awhtfrag, provided better discrimination with mean objective function values of 0.953, 0.962, and 0.940, respectively, which were higher than those for the conventional measures cos1 and htco (0.922 and 0.892, respectively). The rates of false-positives and false-negatives were 3.3-10.7% and 5.3-11.9% for cos1, respectively, while the rates for vwhtfrag were 4.8-5.9% and 2.2%, respectively. The measures of similarity developed may provide significant information to avoid drug-related errors associated with brand name confusion.

Medication Errors↗
PubMed2001

Converting patients from brand-name clozapine to generic clozapine.

OBJECTIVE: To evaluate safety and dosage requirements when patients taking brand-name clozapine (Clozaril, Novartis Pharmaceuticals) are converted to generic clozapine (Zenith Goldline). METHODS: In November 1999, patients at Colorado Mental Health Institute at Pueblo taking Clozaril were changed to generic clozapine. Seventeen patients had been prescribed Clozaril for three years and were included in the study. Drug dosage, white blood cell (WBC) count values, and adverse drug reaction reports were compared. Data regarding patients on the brand-name product were evaluated retrospectively for the months of November, December, January, and February during the years 1996/1997, 1997/1998, and 1998/1999. These data were compared with those from the same patients after switching to generic clozapine for the same months in 1999/2000. A one-year comparison of brand-name (1998/1999) with generic drug (1999/2000) was also performed. Statistical analysis included a standard test comparing WBC values and a Brown-Forsythe test for comparing dosages. RESULTS: There were no differences between the values obtained for the brand-name and generic products. WBC counts for the three-year data resulted in a p value of 0.9992. There was no difference when comparing the samples one year prior to switching and after the switch (p = 0.9991). There was no difference in dosages at three years or one year (p = 0.9999 and p = 0.9993, respectively). No adverse events were noted with the generic product. CONCLUSIONS: No differences were found between the brand-name and generic clozapine groups with regard to WBC count, dosage, and adverse events. The conversion to the generic product is projected to save the pharmacy $90,000 annually.

Antipsychotic Agents↗
PubMed2000

Real age of acquisition effects in word naming and lexical decision.

Age of acquisition (AoA) has been reported to be a predictor of the speed of reading words aloud (word naming) and lexical decision, with early-acquired words being responded to faster than later-acquired words in both tasks. All previous studies of AoA effects have, however, relied upon adult estimates of word learning age the validity of which it is easy to cast doubt upon. Using objective age of acquisition norms derived from children's naming data, this study shows that AoA effects do not depend upon the use of adult ratings. In addition to effects of real AoA, influences of word frequency and orthographic neighbourhood size were obtained in both word naming and lexical decision. Imageability affected lexical decision but not word naming, while the characteristics of the word's initial phoneme affected word naming but not lexical decision.

Adult↗
PubMed2003

Semantic priming in the name retrieval of objects and famous faces.

Researchers interested in face processing have recently debated whether access to the name of a known person occurs in parallel with retrieval of semantic-biographical codes, rather than in a sequential fashion. Recently, Schweinberger, Burton, and Kelly (2001) took a failure to obtain a semantic context effect in a manual syllable judgment task on names of famous faces as support for this position. In two experiments, we compared the effects of visually presented categorically related prime words with either objects (e.g. prime: animal; target: dog) or faces of celebrities (e.g. prime: actor; target: Bruce Willis) as targets. Targets were either manually categorized with regard to the number of syllables (as in Schweinberger et al.), or they were overtly named. For neither objects nor faces was semantic priming obtained in syllable decisions; crucially, however, priming was obtained when objects and faces were overtly named. These results suggest that both face and object naming are susceptible to semantic context effects.

Adult↗