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Biomedical subjects

C A Stone

Publications and source records attributed to C A Stone.

At least 37 records · Page 2Linked to original sources
PubMed1994

The conceptual basis for morpheme learning problems in children with specific language impairment.

Two groups of children were exposed to instances of a nonlinguistic conceptual rule under controlled instructional conditions to determine whether the problems children with specific language impairment (SLI) have learning and accessing language rules extend beyond the language domain into the general cognitive domain. The performance of 20 children with SLI, aged 5:0 to 6:11 (years:months), was compared to that of 20 normally developing children matched for age and nonverbal ability. These children were taught under two instructional conditions that differed only in whether the child was asked to imitate the solution to a conceptual problem after each demonstration (imitation) or merely to observe it (modeling). Contrary to previous findings regarding linguistic rule-learning using auditory or visual symbol systems and similar instructional conditions, no difference was found between the extent of overall learning displayed by the normally developing children and those with SLI. Also, the performance of the children with SLI was not uniquely better under the imitation condition than under modeling, as had been the case with the learning of a novel morpheme in an auditory linguistic task. These results are interpreted as confirming the earlier assumption that the generally lower overall learning rate of the children with SLI on both the auditory and visual tasks reflects a specific linguistic rule-learning difficulty, rather than a general deficiency in rule induction.

Child↗
PubMed1994

Indoor radon maps of the United States.

A recently published compilation of average radon levels in 1,729 U.S. counties with standard errors of approximately 20% is used to generate maps exhibiting these results and showing correlations over multicounty areas. Several large areas and numerous smaller areas with high radon levels are identified.

Air Pollution, Indoor↗
PubMed1993

Induction of a visual symbolic rule in children with specific language impairment.

In a design modeled after that of Connell and Stone (1992), two alternative instructional conditions (Modeling and Imitation) were used to teach a novel morpheme to a group of 21 children with Specific Language Impairment (SLI) (ages 5:0 to 6:11) and to 25 age- and ability-matched peers and 21 language-matched younger peers. In contrast to the use of the auditory modality in the Connell and Stone study, in the present study, the morphemes were embodied in a visual symbol system. The objects and meanings conveyed by the symbols were identical to those used in the earlier study. The present results indicated that both the children with SLI and their age-matched peers showed a benefit to their morpheme production from the requirement to imitate the use of the morpheme during learning trials. These results were interpreted as indicating that the group-specific benefit from imitation instruction on the part of the children with SLI found by Connell and Stone with their auditory task is unique to morpheme learning in the auditory modality. As in the earlier study, the children with SLI also tended to learn less than their age-matched peers in all conditions, indicating a possible general deficiency with symbolic rule induction.

Child↗
PubMed1992

Morpheme learning of children with specific language impairment under controlled instructional conditions.

Three groups of children were exposed to instances of a novel morpheme under controlled experimental conditions. The performance of 32 children with specific language impairment (SLI), aged 5:0 to 7:0 years (years:months), was compared to that of 24 normally developing children matched for age and nonverbal ability and 20 younger normally developing children matched for language development and nonverbal ability. The children were taught under two instructional conditions that differed only in whether the child was asked to imitate the new language form after each instance (imitation) or just to observe its use (modeling). Consistent with past research (Connell, 1987b), the children with SLI performed significantly better under the imitation condition than under modeling, but the age-matched controls showed no difference in response to instruction. The performance of the language-matched controls was similar to that of the age-matched controls, suggesting that the instruction-specific effect for the children with SLI is not merely a function of general language immaturity. Although the superiority of the imitation condition for the children with SLI was evident for test trials requiring production of the new morpheme (as in past research), no such effect was evident for comprehension trials. This differing effect of output demands suggests that the SLI-specific response to instruction is not a matter of different mastery of the new rule but rather is specific to the need to access the newly induced rule on production trials. The accessing of phonological representations as a possible explanation for the effect is discussed.

Audiovisual Aids↗
PubMed1991

Individual differences in the self-image of adolescents with learning disabilities: the roles of severity, time of diagnosis, and parental perceptions.

The self-images of 49 adolescents with learning disabilities (Grades 9 through 12, mean age = 15.9) and 49 normally achieving peers (Grades 9 through 12, mean age = 16.0) were compared using the Offer Self-Image Questionnaire (OSIQ). The group with LD scored significantly lower than the comparison group on 4 of the 10 OSIQ scales. Later-diagnosed adolescents with LD scored significantly higher than early-diagnosed adolescents on two of the scales. Severity of the learning disability was not found to be related to self-image scores. In a second study, parental perceptions of the self-images of 28 of the 49 students with LD were studied by administering the Offer Parent-Adolescent Questionnaire (OPAQ) and an informal questionnaire to their parents. On 6 of the 10 OPAQ scales, parents perceived their children as having a lower self-image than the adolescents themselves reported. Significant but moderate relationships were found between parents' perceptions and adolescent self-image scores. Results of the two studies are interpreted in terms of a multidimensional conception of self-image that considers factors inherent to the individual as well as interpersonal and institutional factors.

Adult↗
PubMed1989

Leucogyrophana pinastri, a wood decay fungus as a probable cause of an extrinsic allergic alveolitis syndrome.

Two patients were suspected of having extrinsic allergic alveolitis due to exposure to an agent in their home environment. On inspection of their houses, fungal decay was evident in the floorboards, and fungal spores were found deposited on many surfaces. The decay fungus was later identified as Leucogyrophana pinastri. Using an extract of the fruiting bodies and mycelium of this fungus, precipitating antibodies were identified in the sera of both patients. Based on the known exposure by the two patients to these small spores, the absence of a likely alternative allergen, the similarity between these two cases, and the positive precipitin test results, L. pinastri was considered to be the most likely cause of extrinsic allergic alveolitis in our cases.

Adolescent↗
PubMed1987

The role of bronchoalveolar lavage in the diagnosis of suspected opportunistic pneumonia.

We report 50 immunocompromised patients with pulmonary infiltrates who underwent fibreoptic bronchoscopy, including bronchoalveolar lavage, on 56 occasions. The underlying diseases were mostly lymphoma, leukemia, other malignancies and renal failure. The commonest immunodeficiency factors were chemotherapy, steroids and neutropenia. A positive diagnosis could be made from analysis of the bronchoalveolar lavage on 59% (33/56) occasions. This was a comparable yield to transbronchial lung biopsy 57% (16/27), and superior to proximal airways wash 24% (13/55), or bronchial brushings 29% (10/34). Open lung biopsy added additional diagnostic information in three of the four cases in which it was performed. The most common final diagnoses were bacterial, viral or Pneumocystis carinii pneumonia and recurrent malignancy. We conclude that bronchoalveolar lavage is a safe procedure with a high diagnostic yield in the immunocompromised host with suspected opportunistic pneumonia.

Bacterial Infections↗
PubMed1985

On the pharmacology of L-645,151: a topically effective ocular hypotensive carbonic anhydrase inhibitor.

L-645,151 [(2-sulfamoyl-6-benzothiazolyl)-2,2-dimethylpropionate] is the O-pivaloyl ester of L-643,799 (6-hydroxybenzothiazole-2-sulfonamide), topically administered L-645,151 being a substrate for ocular esterases with the resultant liberation of the active moiety, L-643,799, during penetration of the ocular surface. The minimum concentrations of topically administered suspensions (1 drop of 50 microliters into both eyes) of L-645,151, L-643,799, dichlorphenamide and methazolamide significantly lowering the elevated intraocular pressure (IOP) of the alpha-chymotrypsinized rabbit eye were 0.25, 2, 10 and 5%, respectively. IOP was not significantly decreased by 10% suspensions of acetazolamide or ethoxzolamide. The IOP lowering action of L-645,151 was local as the unilateral instillation of L-645,151 (0.25%) into the contralateral eye was devoid of effect in alpha-chymotrypsinized rabbits. L-645,151 (2%) decreased aqueous humor inflow in both the conscious rabbit and the anesthetized dog. Outflow facility in the conscious rabbit was unaltered by a 10% suspension of L-645,151. Low peak levels (0.52 microgram/g) of L-643,799 were present in rabbit renal cortex after the instillation of L-645,151 (2%) into both eyes; this treatment did not induce diuresis in the conscious rabbit. The corresponding maximum concentration in the iris + ciliary body was 4.01 micrograms/g. These preclinical studies reveal that L-645,151 is the most potent, topically effective ocular hypotensive carbonic anhydrase inhibitor described to date.

Administration, Topical↗
PubMed1984

R-enantiomer of timolol: a potential selective ocular antihypertensive agent.

Various studies were conducted to evaluate the effects of timolol, an S-enantiomer, relative to its R-enantiomer upon intraocular pressure and related ocular systems in the rabbit. The R-enantiomer was about one-third as potent as timolol in displacing 3H-dihydroalprenolol binding to iris-ciliary body tissue, reducing aqueous humor formation, and lowering intraocular pressure of alpha-chymotrypsin hypertensive eyes. In contrast, the R-enantiomer was 50 to 90 times less potent than timolol in antagonizing the effects of isoproterenol on pulmonary and atrial beta-adrenergic receptors. The data indicate that the R-enantiomer may lower intraocular pressure in man at concentrations less likely than timolol to block extraocular beta-adrenergic receptors. Finally, to account for the differential effect of the R-enantiomer upon ocular as opposed to extraocular beta-adrenergic receptors, it is tentatively suggested that this agent may also act upon a population of ocular beta-adrenergic receptors showing relatively poor stereoselectively.

Animals↗
PubMed1984

Studies on L-640,035: a novel antagonist of contractile prostanoids in the lung.

The effects of L-640,035 (3-hydroxymethyl-dibenzo [b,f] thiepin-5,5-dioxide) have been studied on pulmonary smooth muscle contraction in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-640,035 produced significant shifts in the dose-response curves to a prostaglandin (PG) endoperoxide analogue (U-44069) (pA2 7.0), PGF2 alpha (pA2 5.9) and PGD2 (pA2 6.5). L-640,035 produced no significant shift in the dose-response curves to leukotriene D4 or histamine and produced a small but statistically significant shift in the dose-response curve to 5-hydroxytryptamine (5-HT) (pA2 5.2). With the exception of PGF2 alpha, Schild analysis did not in general indicate competitive inhibition. The main metabolite of L-640,035, L-636,499, also produced significant parallel shifts in the dose-response curves to U-44069 (pA2 6.0) and PGF2 alpha (pA2 6.0), but with some reduction in the maximal contraction. When L-640,035 was administered intravenously to guinea-pigs, significant inhibition of increases in pulmonary resistance or insufflation pressure induced by U-44069 (ED50 0.16 mg kg-1), leukotriene D4 (ED50 0.25 mg kg-1) and 5-HT (ED50 3.4 mg kg-1) but not histamine (ED50 greater than 10 mg kg-1) was observed. When L-640,035 was administered intravenously to dogs a significant inhibition of increases in pulmonary resistance induced by U-44069 (ED50 0.85 mg kg-1) but not histamine (ED50 greater than 30 mg kg-1) was observed. 5 When L-640,035 was administered by the intraduodenal route to dogs at doses of 3 and 10 mg kg- significant inhibition of increases in pulmonary resistance induced by sodium arachidonate (3 mgkg1 i.v.) was observed with a duration of action of > 255 min. 6 It is concluded that L-640,035 is a novel, relatively selective, and orally active antagonist of the actions of contractile prostanoids on pulmonary smooth muscle.

Airway Resistance↗
PubMed1981

Piperazinylquinoxalines with central serotoninmimetic activity.

Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxaline enhanced serotonin reuptake blocking activity and diminished serotoninmimetic activity. Unsubstituted and 3-hydroxypiperazinylquinoxalines had primarily serotoninmimetic activity.

Animals↗
PubMed1981

Effect of N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro and its ethyl ester (MK-421) on angiotensin converting enzyme in vitro and angiotensin I pressor responses in vivo.

The parent diacid (N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro of MK-421 inhibited hog plasma angiotensin converting enzyme (ACE) by 50% (I50) at a concentration of 1.2 nM and was 17 times more potent than captopril. In vitro the I50 for MK-421, an ethyl ester, was 1200 nM because de-esterification did not occur. Similarly in the guinea-pig ileum, the diacid inhibitor and MK-421 potentiated the contractile effects of bradykinin at an AC50 of 77 pM and 18 nM, respectively. Inhibition of the pressor effects of angiotensin I by the diacid ACE inhibitor occurred at an ID50 of 8.2 micrograms/kg i.v. in rats and 6.4 micrograms/kg i.v. in dogs. Thus, the diacid was approximately 12 times more potent than captopril. The ID50 for MK-421 was 14 and 278 micrograms/kg i.v. in rats and dogs, respectively, because of differences in the rates of de-esterification. Oral ACE inhibitory activity was determined by blockade of the pressor effects of angiotensin I in conscious rats and dogs. In rats, but not in dogs, the diacid inhibitor was poorly absorbed, whereas MK-421 was well absorbed in both species. MK-421 inhibited the pressor effects of angiotensin I at 0.1 to 3.0 mg/kg p.o. for at least 6 hr in rats and dogs, and compared to captopril was 8.6 times more potent in rats and 4.6 times more potent in dogs. These data demonstrate that MK-421 and its parent diacid are potent, long-lasting orally active inhibitors of ACE. In addition, the low activity of MK-421 in vitro contrasts with its substantial in vivo activity, and supports the hypothesis that MK-421 is a prodrug that first must be de-esterified to permit full expression of its significant in vivo pharmacological activity.

Administration, Oral↗
PubMed1980

A new class of angiotensin-converting enzyme inhibitors.

Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1979

2-Mercaptoacetamidines as gastric antisecretory agents.

A series of N-substituted 2-mercaptoacetamidines was synthesized and evaluated for gastric antisecretory activity in dogs stimulated with gastrin tetrapeptide. The most potent analogues showed 80--95% inhibition of acid secretion after an oral dose of 8 mg/kg. Thus, these compounds represent a new structural type having significant antisecretory activity. Disulfides had essentially the same antisecretory potency as the corresponding mercaptoacetamidines, indicating a metabolic interconversion. Alkylation of the mercapto group decreased potency. Higher carboxamidine homologues such as 2- and 3-mercaptopropionamidines had very low activity. Hydroxyacetamidines and mercaptoacetamides also had low potency. Side effects observed with this series of compounds included emesis, tachycardia, and gastric bleeding.

Amidines↗