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Biomedical subjects

M Sanford

Publications and source records attributed to M Sanford.

At least 19 recordsLinked to original sources

Peroxisome proliferator activated receptor gamma in colonic epithelial cells protects against experimental inflammatory bowel disease.

INTRODUCTION: Peroxisome proliferator activated receptor gamma (PPARgamma) is expressed in epithelial cells, macrophage, and T and B lymphocytes. Ligand induced activation of PPARgamma was reported to attenuate colitis activity but it is not clear whether this protection is mediated by epithelial or leucocyte PPARgamma. METHODS: Mice with targeted disruption of the PPARgamma gene in intestinal epithelial cells, generated using a villin-Cre transgene and floxed PPARgamma allele and designated PPARgamma(DeltaIEpC), were compared with littermate mice having only the PPARgamma floxed allele with no Cre transgene that expressed PPARgamma in the gut, designated PPARgamma(F/F). Colitis was induced by administering dextran sodium sulphate (DSS) and the two mouse lines compared for typical symptoms of disease and expression of inflammatory cytokines. RESULTS: PPARgamma(DeltaIEpC) mice displayed reduced expression of the PPARgamma target genes ADRP and FABP in the gut but were otherwise normal. Increased susceptibility to DSS induced colitis, as defined by body weight loss, colon length, diarrhoea, bleeding score, and altered histology, was found in PPARgamma(DeltaIEpC) mice in comparison with PPARgamma(F/F) mice. Interleukin (IL)-6, IL-1beta, and tumour necrosis factor alpha mRNA levels in colons of PPARgamma(DeltaIEpC) mice treated with DSS were higher than in similarly treated PPARgamma(F/F) mice. The PPARgamma ligand rosiglitazone decreased the severity of DSS induced colitis and suppressed cytokine production in both PPARgamma(F/F) and PPARgamma(DeltaIEpC) mice. CONCLUSIONS: These studies reveal that PPARgamma expressed in the colonic epithelium has an endogenous role in protection against DSS induced colitis and that rosiglitazone may act through a PPARgamma independent pathway to suppress inflammation.

Animals↗

The human MIP-1beta chemokine is encoded by two paralogous genes, ACT-2 and LAG-1.

Human macrophage inflammatory protein-1 beta (MIP-1beta) is an Mr 8,000 acidic protein that is upregulated upon stimulation in monocytes, T cells, and other lymphocytes. This protein belongs to the CC chemokine subfamily and directs the migration of specific subsets of leukocytes. The first molecular clone was isolated in 1988, and ever since there has been confusion regarding the exact number of genes encoding this and closely related proteins. PCR primers were designed from two genomic GenBank entries to conduct single-strand conformational polymorphism analysis, sequence analysis, and PCR-RFLP, and we conclude that previously isolated clones referred to as MIP-1beta are derived from two genes, originally called ACT-2 and LAG-1. The two proteins share a common length and are identical at 89 of 92 amino acids. The first two amino acid differences, V12M and L20P, occur in the signal peptide, while the third, G70S, is in the mature protein. Within the transcribed region, the genes differ at 25 of 662 nucleotides. A survey of the NCBI expressed sequence tag database reveals that both genes are expressed in a variety of tissues, and five clones representing LAG-1 transcripts are alternatively spliced, with the 115-bp exon 2 omitted. Database searches for putative orthologues in other species revealed that the rabbit protein is about 80% similar to the two human proteins, while those of rat and mouse are 70-75% similar. Comparative sequence analysis of the human and animal proteins indicates substantially higher rates of protein evolution in the two rodents compared to human and rabbit.

Alternative Splicing↗

Age-of-onset classification of conduct disorder: reliability and validity in a prospective cohort study.

OBJECTIVE: To test in a prospective clinical cohort study the reliability and validity of the age-of-onset subtyping of conduct disorder. METHOD: Participants were adolescents referred to psychiatric clinics who met DSM-III-R criteria for conduct disorder by structured diagnostic interview. Age of onset was the reported age of the first conduct disorder symptom. The reliability of age-of-onset report was tested by assessing agreement within informant on interviews 2 to 4 weeks apart. Age-of-onset groups were compared within informant on rates of correlates and symptom and social functioning outcomes over a period of 3 years. RESULTS: The reliability of age-of-onset report was low (kappa of 0.1 and 0.4 by adolescent and parent informant, respectively). Although the early-onset group had elevated rates of attention-deficit/hyperactivity disorder, family disadvantage, and aggressive and nonaggressive antisocial behaviors at inclusion, growth curve analysis showed that age-of-onset subtyping had no predictive validity. CONCLUSIONS: The reliability of ascertainment of age of onset of antisocial behavior requires further study. While age-of-onset subtyping has heuristic value with respect to the study of the causal pathways to conduct disorder, it is premature to use this system in clinic settings.

Adolescent↗

Patient education for discharge after coronary bypass surgery in the 1990s: are patients adequately prepared?

Short hospitalizations for patients undergoing coronary artery bypass grafting (CABG) require continuous nursing evaluation of patients' discharge education. Six institutions collaborated in surveying 300 postoperative patients with CABG to identify learning priorities and patients' perceptions of the effectiveness of discharge education. Data analysis from the self-administered questionnaire demonstrated consistent patient priorities across institutions. Differences in teaching methods and content did not affect perceived preparedness or importance scores. Regional experience demonstrates that variable teaching efforts meet patients' priorities and provide high overall patient preparedness for discharge. Patients with the shortest hospitalizations had higher preparedness scores.

Adult↗

Adequacy of interviews vs checklists for classifying childhood psychiatric disorder based on parent reports.

BACKGROUND: The advantages and disadvantages of lay-administered structured interviews and self-administered problem checklists for estimating prevalence and associated features of childhood psychiatric disorder have attracted little comment. This article compares the scientific adequacy of these 2 instruments for classifying DSM-III-R categories of childhood psychiatric disorder in general population samples. METHODS: Study data are from parental assessments of 251 children aged 6 to 16 years participating in a 2-stage measurement evaluation study. Reliability and validity were compared between the Diagnostic Interview for Children and Adolescents (the structured interview in the study) and the revised Ontario Child Health Study scales (the self-administered problem checklist used in the study). RESULTS: Reliability estimates based on the kappa statistic were comparable for the 2 instruments and ranged from 0.21 (conduct disorder) to 0.70 (depression) on the lay interview and from 0.17 (depression) to 0.61 (oppositional defiant disorder) on the self-administered checklist. Validity coefficients tended to favor the checklist categories, but only marginally. CONCLUSIONS: On balance, differences in reliability and validity were small between the 2 instruments. These differences would appear to have no discernible impact on the knowledge about prevalence and associated features of disorder generated by use of such instruments in general population surveys.

Adolescent↗

Integrating assessment data from multiple informants.

OBJECTIVE: To examine the consequences for measurement of child psychiatric disorder (conduct and oppositional disorders) of not integrating the data on the same individual from different informants compared with integrating the information from parents and teachers, using three different strategies. METHOD: Data for the study came from problem checklist assessments done by parents and teachers of children aged 6 to 16 years (N = 1,134) selected with known probability from a general population sample and from structured interviews obtained in a stratified random subsample (n = 251). RESULTS: As expected, parent-teacher agreement was low. The pattern of associated features of disorder was found to vary markedly in parent-identified compared with teacher-identified disorder. Furthermore, combining informants had the disadvantage of masking the distinctive patterns of associated features noted in informant-specific disorders. Finally, by treating disorder as informant-specific, the internal properties of the measure are not generally inferior to those obtained by combining informants in various ways. CONCLUSION: Child psychiatric disorders should be conceptualized as informant-specific phenomena.

Adolescent↗

Identifying thresholds for classifying childhood psychiatric disorder: issues and prospects.

OBJECTIVE: To evaluate empirically the implications of choosing different thresholds to classify conduct disorder and attention-deficit hyperactivity disorder for estimating prevalence, test-retest reliability of measurement, and informant (parent/teacher) agreement and for evaluating comorbidity and associated features of disorder. METHOD: Data for the study came from problem checklist assessments done by parents and teachers of children aged 6 to 16 years (N = 1,229) selected with known probability from a general population sample and from structured interviews obtained in a stratified, random subsample (n = 251). RESULTS: Estimates varied widely depending on the rationale used to set thresholds. Percent prevalence went from 0.1 to 39.2; kappa estimates of test-retest reliability went from .19 to .82. Parent-teacher agreement based on kappa went from .0 to .38. Relative odds between disorder and associated features varied twofold. CONCLUSION: Use of different rationales to set thresholds for classifying childhood psychiatric disorder in the general population has profound implications for what we learn about the epidemiology of childhood disorder.

Adolescent↗

Predicting the one-year course of adolescent major depression.

OBJECTIVE: To identify specific clinical and social functioning variables that predict persistence of major depression over a 1-year period of follow-up. METHOD: The sample consisted of 67 adolescents with major depression, drawn from consecutive referrals to psychiatric clinics in a defined, geographic catchment area. Clinical interviews and questionnaires measuring behaviors, symptoms, and social functioning were administered to both the adolescent and a parent at inception and at follow-up. Discriminant function analyses were used to identify inception variables that predicted clinical course independent of severity of depressive symptoms and global functioning. RESULTS: At 1-year follow-up, major depression remitted in 66% of subjects. Persisters were characterized at inception as older, more likely to have substance use or anxiety disorders, less involved with fathers, and less responsive to mother's discipline compared with remitters. The effect of these prognostic factors was independent of symptom severity and global functioning. CONCLUSION: These variables appear to reflect perpetuating and ameliorating factors influencing the short-term course of major depression. The findings suggest that treatments for adolescent depression that aim to enhance parent-adolescent relationships, and that specifically target coexisting disorders, should be evaluated for effectiveness.

Adolescent↗

Pathways into the work force: antecedents of school and work force status.

OBJECTIVE: The study aim was to identify risk factors for specific pathways into the work force using data from the Ontario Child Health Study Follow-up. METHOD: Potential predictor variables were derived from data collected in 1983 on adolescents aged 13 to 16 years. The subjects were followed up 4 years later and the school/work force outcome was determined. Bivariate and multivariate statistical analyses were used to identify variables with a strong independent association with this outcome. RESULTS: Subjects in the work force were four times more likely than those attending school to have come from a low-income family and at least two times more likely to have a family background of low maternal education, to have failed a grade, or to have used substances heavily during early adolescence. Subjects with two or more of these risk factors were likely to be in part-time work or unemployed. CONCLUSIONS: Preventive interventions should be targeted at children from poor families, or who fail at school, or show early onset of substance abuse and other deviant behaviors. Studies are needed to further elucidate the relationship between these risk factors and pathways into the work force and beyond.

Adolescent↗

Evaluation of the Diagnostic Interview for Children and Adolescents for use in general population samples.

This article presents evaluative data on the use of the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) to classify DSM-III-R disorders in the general population. Data for the analyses came from a probability sample (N = 251) of parent-child/adolescent dyads aged 6 to 16 separately administered the DICA-R on two occasions, 10- to 20 days apart, by trained lay interviewers and child psychiatrists. Data are presented on prevalence, test-retest reliability, parent-child/adolescent agreement, and trained lay interviewer-child psychiatrist agreement. High prevalences of oppositional defiant disorder derived from parent assessments and overanxious disorder and dysthymia derived from adolescent assessments suggest that these disorders may be overidentified. Interview data provided by 6- to 11-year olds to classify the internalizing disorders were too unreliable to be useful. Agreement between parent-child/adolescent dyads was generally low while agreement between trained lay interviewers-child psychiatrists was generally high.

Adolescent↗

Application of a biotyping system and DNA restriction fragment analysis to the study of Serratia marcescens from hospitalized patients.

We applied a nine-test biotyping system to the study of 138 Serratia marcescens isolates from 93 patients hospitalized in 33 different hospital bed units. Test reproducibility for a panel of 10 isolates tested in triplicate on 3 separate days was 100%. Overall, the biotyping system delineated 25 strains. In examining strain variation among isolates obtained from multiple anatomic sites over time we found that the same biotype was recovered from tracheal aspirates, urine, wounds, and blood in a given patient and that these strains were carried over time. In general, patients were infected or colonized with their own distinct biotype of S. marcescens. Temporally related isolates from seven surgical intensive care unit (SICU) patients and six unrelated control isolates were typed by biotyping and DNA restriction fragment analysis (RFA). The distribution of biotypes was similar among SICU outbreak and control isolates, with five distinct biotypes among the seven SICU isolates. Each isolate had a different DNA subtype by RFA, confirming the lack of nosocomial transmission of a single strain. These results will be useful in studying the epidemiology of S. marcescens.

Bacterial Typing Techniques↗

Evaluation of the revised Ontario Child Health Study scales.

This article describes the development and evaluation of the revised Ontario Child Health Study (OCHS) scales to measure conduct disorder, oppositional disorder, attention-deficit hyperactivity disorder, overanxious disorder, separation anxiety and depression based on DSM-III-R symptom criteria. Problem checklist assessments were obtained from parents and teachers of children aged 6-16 and youths aged 12-16 drawn from: (1) a general population sample (N = 1751); and (2) a mental health clinic sample (N = 1027) in the same industrialized, urban setting. Evaluation of the revised OCHS scales indicates that they possess adequate psychometric properties and provide an efficient means to obtain measurements of childhood psychiatric disorder, in general population studies, that correspond to DSM-III-R classification of disorder.

Adolescent↗

Evaluation of the original Ontario Child Health Study scales.

This article presents evaluative information on the use of the original Ontario Child Health Study scales to serve as original-level measures of conduct disorder, hyperactivity and emotional disorder among children in the general (non clinic) population. Problem checklist assessments were obtained from parents and teachers of children aged six to 16 and youth aged 12 to 16 drawn from a general population (n = 1,751); and a mental health clinic sample (n = 1,027) in the same industrialized, urban setting. The results showed that the original OCHS scales possess adequate psychometric properties to be used as original-level measures of disorder. Correlations between individual items and their hypothesized scales were very strong, indicating convergent validity, while correlations between the same items and other (non hypothesized) scales were lower, indicating discriminant validity. Item analyses indicated that individual scale items possess both convergent and discriminant validity. Although the scales were skewed to the positive end of the continuum, they demonstrated good internal consistency (all estimates > or = 0.74) and test-retest (all estimates > or = 0.65) reliability. Finally, three different validity analyses confirmed hypotheses about how the original OCHS scales should perform if they provide useful measures of disorder.

Adolescent↗

Clinical significance of type 5 patterns in platform posturography.

Several abnormal patterns have been identified on the sensory portion of the computerized dynamic posturography test. The vestibular deficit pattern, also known as the "5-6" pattern, is frequently seen in patients with either uncompensated unilateral vestibular lesions, severe bilateral peripheral vestibular loss, or dysfunction involving the vestibular pathways in the brain stem and/or cerebellum. In both sensory conditions 5 and 6, the patient's balance/equilibrium is determined primarily by the vestibular system. A subgroup of the vestibular deficit pattern has been identified, in which only sensory condition 5 is abnormal. This article presents findings in several cases identified with the 5 pattern. Implications for diagnosis and for monitoring the recovery phase after treatment are discussed.

Adolescent↗

The impact of a physically ill parent on adolescents: cross-sectional findings from a clinic population.

The degree to which the physical illness of a parent affects adolescents is unknown. This study examines this issue through a cross-sectional survey of patients referred consecutively to an adolescent outpatient psychiatry clinic. Demographic and clinical data concerning symptoms, diagnosis of major depression, peer isolation, and family functioning were collected on all subjects from both the adolescent and a parent (usually the mother). No significant differences were found between the groups on measures of family functioning, peer isolation and major depression. According to both youth and parent report, adolescents with physically ill parents had more somatic symptoms than controls. These findings are discussed in the light of the existing literature and the methodological shortcomings of the study.

Adolescent↗

A study to determine the difference in clinical judgment abilities between BSN and non-BSN graduates.

The purpose of this retrospective study is to determine the difference in clinical judgment abilities of recent baccalaureate nurses (BSN) seeking employment in a large metropolitan hospital and of nurses without a baccalaureate degree. Using an ex post facto design, the orientation records of 116 newly hired nurses were analyzed to determine the clinical judgment abilities using video vignettes produced by Medcom, Inc. Findings indicated that there was no difference in clinical judgment in newly hired BSN and non-BSN graduates. These findings indicate a need for more research studies to determine how clinical judgment is developed and to evaluate teaching strategies that facilitate clinical judgment.

Clinical Competence↗

Hemispheric asymmetry in the matching of melodies to rhythm sequences tapped in the right and left palms.

Two experiments were conducted to investigate the ability of the cerebral hemispheres to match rhythm sequences tapped in the palms of the hands to tape-recorded melodies. Reaction time (RT) for same/different judgments and accuracy of responses served as the (LP/RH) advantage was found in the ability to match tapped rhythms to tape-recorded melodies, but only on Different trials. On Same trials (which were found to be somewhat easier), both hemispheres were equally efficient at making such comparisons. In Experiment 2, there was no reliable difference between the LP/RH and the RP/LH in the ability to match tapped rhythms to tape-recorded rhythm sequences which were devoid of melodic intonation (i.e., the sound of two blocks of wood struck together in a specified rhythm). The results of these experiments taken in composite lend support to the contention that the right hemisphere advantage typically reported for the processing of musical stimuli is primarily related to pitch and/or intonation rather than rhythm.

Adult↗

Transesophageal atrial pacing threshold: role of interelectrode spacing, pulse width and catheter insertion depth.

This study evaluated the role of interelectrode spacing, pulse widths greater than 10 ms, and depth of esophageal insertion on minimizing transesophageal atrial pacing threshold in 30 patients aged 1 day to 77 years. Interelectrode spacings of 15, 22 and 28 mm were evaluated by establishing strength-duration curves in 2 or more serial studies in 12 patients; electrode spacing had no effect on pacing threshold. In 23 patients studied with 22-mm electrode spacing, pulse widths of 15 and 20 ms had no significant effect on current threshold requirements compared with 10-ms pulse widths. In 20 patients, pacing threshold and esophageal electrograms were obtained at 1.0- to 2.5-cm intervals with a 22-mm lead using a pulse width of 10 ms. Average minimal pacing threshold was 10.2 mA (range 4.5 to 20). The site of minimal pacing threshold was highly correlated with patient height (r = 0.987), and occurred within 1.1 cm (0 to 2.5 cm) of the site of the maximal bipolar atrial electrogram amplitude and 0.95 cm (0 to 3 cm) of the site of the maximal unipolar atrial electrogram. Bipolar electrode spacing of 15, 22 or 28 mm has little effect on transesophageal pacing threshold. In most patients, pulse widths greater than 10 ms do not significantly decrease pacing threshold. Correct catheter insertion depth is critical to minimize pacing threshold and may be predicted by either the site of the maximal atrial electrogram amplitude or patient height.

Adolescent↗