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Biomedical subjects

A F Johnson

Publications and source records attributed to A F Johnson.

At least 19 recordsLinked to original sources

Optical isomers of rocastine and close analogues: synthesis and H1 antihistaminic activity of its enantiomers and their structural relationship to the classical antihistamines.

The enantiomers of 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazapine-5(2H)-thione (rocastine) and two of its more potent analogues were prepared with an enantiomeric purity of greater than 99.9%. The antihistaminic activity of these compounds was assessed by their ability to block histamine-induced lethality in guinea pigs and to inhibit [3H]mepyramine binding to guinea pig cortex. In this series, compounds having the R configuration at the 2-position are at least 300 times more potent than the S isomers. Conformational analysis and molecular modeling suggest that rocastine can adopt a conformation in which the pyridine ring, ether oxygen, and protonated amine functions are positioned similarly to the corresponding elements of the probable binding conformers of some of the more classical antihistamines. This conformation, boatlike in the oxazepine ring with the side chain quasi-equatorial and folded back toward the ring, is the likely binding conformer at the histamine H1 receptor, and the available structure-activity relationship data is consistent with this interpretation.

Animals

Management of voice disorders.

Voice disorders are commonly seen in general medical practice. In some cases voice disorders represent the presenting symptom for serious underlying disease. It is important for clinicians from internal medicine, pediatrics, and family practice to be able to identify those factors in the history or observed vocal symptoms which suggest need for referral for comprehensive voice evaluation as well as to understand the distinct but complementary roles of the specific disciplines (otolaryngology and speech-language pathology) involved in diagnosis and treatment of patients with voice disorders.

Humans

Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: synthesis and structure-activity relationships of a new series of H1 antihistamines.

A series of novel benzo- and pyrido-1,4-oxazepinones and -thiones which represents a new structural class of compounds possessing H1 antihistaminic activity was synthesized, and the SARs were evaluated. The antihistaminic activity was determined by blockade of histamine-induced lethality in guinea pigs. The sedative potential was determined by comparison of the EEG profiles of the compounds with those of known sedating and nonsedating antihistamines. Several of the compounds were shown to possess potent H1 antihistaminic activity and to be free of the cortical slowing with synchronized waves and spindling activity found in the EEG of sedative antihistamines. One compound, 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazepine-5(2H)-thione (rocastine) is currently undergoing clinical evaluation as a nonsedating H1 antihistamine.

Animals

Benzo-pyrones in the treatment of chronic schizophrenic diseases.

Sixteen chronic schizophrenic subjects were treated for 3 months each with either a benzo-pyrone (Paroven/Venoruton, Zyma) or a placebo in a randomized, double-blind crossover trial. They continued to take their previous drug therapies. Therapeutic effects were measured by the Brief Psychiatric Rating Scale (BPRS), by self-assessment, and by assessment by a relative. Eleven patients completed the trial in relation to BPRS assessment. When on the active substance, as compared with the placebo, they showed a mean improvement of 27% (significant at the 1% level). Ten patients completed the trial in relation to the self and relative's assessments. There were improvements of 16% and 13%, respectively (significant at the 5% levels). Half the patients showed improvements on all the tests. Their improvements were 49%, 31%, and 21%, respectively. There was evidence that the active substance began to have an effect within 2 weeks. No side effects were observed with the active substance.

Adult

Psycho-social achievement in the latency-aged child with spina bifida within the family structure.

This project aims: 1) to appraise the psycho-social development of a sample of latency-aged spina bifida children upon entry to school; 2) to learn about the social influences that promote or impede the child's development, and 3) to identify ways that psycho-social intervention can be useful to families in which there is a congenitally disabled child. A longitudinal, observational case study was conducted over a six month period. This approach provided information on the impact of social influences, disability, and trauma on the child's development. The results indicate that a delay in reaching the important physical milestones of independent locomotion and continence hinders the achievement of standard psycho-social developmental goals; it does not exclude their achievement. By the sixth month in first grade, all of the children had adapted satisfactorily to school. Thus, the difference between the able-bodied and the spina bifida child was not one of kind, but one of degree. Spina bifida was found to put no ceiling on the child's psycho-social development.

Achievement

Assessment of parent-administered listening training for preschool children with articulation deficits.

Two studies concerning preschool misarticulating children are reported. The first study was concerned with direct effects of two varieties of parent-administered listening training. The second study focused on the influence of that same training on children's responses to sound-production training. Subjects were assigned to one of three conditions: listening, reading-talking, and control. Children in the first group were provided training by their parents that was intended to focus the child's attention on consonants in syllables or words and to teach discrimination between correctly and incorrectly articulated consonants. Parents of children in the second group read to and talked with them about the material. Neither treatment group surpassed the control group in gains made on any auditory processing or articulatory measure employed, and some parents found the listening training frustrating. In the second study, a subset of the children in each of the three groups was given sound-production training. The data obtained did not show any effect from earlier listening experiences on sound-production performance.

Attention

Identification and description of homogeneous subgroups within a sample of misarticulating children.

A multivariate, hierarchical clustering procedure was used to identify homogeneous subgroups among 98 misarticulating children age eight years through nine years, six months. Clustering was based on 40 tests or measures of language, auditory processing, school achievement, oral structure, oral form recognition, and other phenomena. Clusters were described and then compared for performance on measures of articulation status and articulation improvement with training. Clusters were also derived from subsets of children who misarticulated only one sound, either /s/or/r/. Also, the subset of children who misarticulated /s/ was compared with children who misarticulated /r/ for performance on the measures classified above. Few of the clusters identified differed in articulation status or improvement with training.

Anthropometry

Factor analysis of measures of articulation, language, auditory processing, reading-spelling, and maxillofacial structure.

This study was concerned with the correspondence between the classification of measures by clinical judgement and by factor analysis. Forty-six measures were selected to assess language, auditory processing, reading-spelling, maxillofacial structure, articulation, and other processes. These were applied to 98 misarticulating eight- and nine-year-old children. Factors derived from the analysis corresponded well with categories the measures were selected to represent.

Cephalometry

Delayed judgment speech-sound discrimination and /r/ or /s/ articulation status and improvement.

A delayed judgment test of speech-sound discrimination was correlated with measures of articulation status and articulation improvement with training in two groups of subjects, an /r/ group and an /s/ group. While the discrimination measures were reliable and internally consistent, discrimination-articulation correlations were low. Several possible psychometric explanations for the nonsignificant results are ruled out, and subject and task variables that might interfere with children's performance on discrimination measures are discussed.

Auditory Perception

Pulmonary telangiectasia.

Pulmonary telangiectasia is an uncommon developmental anomaly characterized by minute arteriovenous fistulae disseminated throughout both lungs. It should be suspected in patients with cyanosis and digital clubbing who do not have chronic lung disease or a cyanotic cardiac anomaly. The presence of telangiectases of skin or mucous membranes in the patient or members of his family is an important diagnostic clue. The chest film usually shows a coarse spidery appearance of the peripheral vascular markings in the lungs. More specific findings are obtained in the pulmonary angiogram where the normally invisible capillary phase is replaced by irregular vascular channels bridging the peripheral branches of pulmonary arteries and veins. The intrapulmonary right-to-left shunt may be confirmed by pulmonary scintigraphy using technetium-labeled albumin. Two cases are presented with a brief review of the literature.

Adolescent