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Biomedical subjects

B Landa

Publications and source records attributed to B Landa.

13 recordsLinked to original sources

Analysis of variability of clinical manifestations in Waardenburg syndrome.

Expression of clinical findings of Waardenburg syndrome type 1 (WS1) and type 2 (WS2) is extremely variable. Using our collection of 26 WS1 and 8 WS2 families, we analyzed the occurrence, severity, and symmetry of clinical manifestations associated with WS. We found significant differences between WS1 and WS2 in deafness, and in pigmentary and craniofacial anomalies. Factor analysis was used to identify manifestations which covaried, resulting in 2 orthogonal factors. Since mean factor scores were found to differ when compared between WS1 and WS2, we suggest that these factors could be useful in distinguishing WS types. We found that the WS gene was transmitted from mothers more often than from fathers. We also extensively examined the W-Index, a continuous measure of dystopia canthorum. Our data suggest that use of the W-Index to discriminate between affected WS1 and WS2 individuals may be problematic since 1) ranges of W-Index scores of affected and unaffected individuals overlapped considerably within both WS1 and WS2, and 2) a considerable number of both affected and unaffected WS2 individuals exhibited W-index scores consistent with dystopia canthorum. Misclassification of families may have implications for risk assessment of deafness, since WS2 families have been reported to have greater incidence of deafness, as confirmed in our study.

Age Factors

B cells in autoimmune (NZB x NZW)F1 mice show altered IgG isotype switching upon T cell-dependent antigenic stimulation in vitro.

Humoral immune responses of (NZB x NZW)F1 (BWF1) autoimmune mice to T cell-dependent antigens often exhibit a predominance of IgG2 antibodies, while normal mice produce IgG1 antibodies. In order to determine whether this results from differences in properties of the B cells or the T cells involved, the responses of both primary and secondary BWF1 B cells to the antigen DNP-hemocyanin (Hy) were measured in limiting dilution splenic fragment cultures in the presence of normal T cell help. Furthermore, the capacity of Hy-primed lymph node T cells from BWF1 mice to provide help to BALB/c nu/nu B cells was determined in modified splenic fragment cultures. These experiments indicated that (a) stimulation of primary BWF1 B cells with DNP-Hy and normal T cell help failed to yield significant numbers of clones which produced any of the IgG isotypes; (b) antigenic stimulation of BWF1 secondary B cell clones also demonstrated a paucity of IgG1, but elevated production of IgG2 isotypes; and (c) Hy-primed BWF1 lymph node T cells were comparable to those derived from BALB/c mice in their capacity to provide both help for nu/nu B cell responses and modulation of IgG isotype switching. BWF1 B cells apparently differ from normal murine B cells in their capacity to produce IgG antibodies upon T cell-dependent antigenic stimulation.

Animals

Methylphenidate and growth in hyperactive children. A controlled withdrawal study.

The effect of stimulants on growth has been controversial. Among hyperactive children receiving long-term methylphenidate hydrochloride treatment, we examined the effects of methylphenidate withdrawal on the growth of hyperactive children randomly assigned to be taken off, or remain on, the medication regimen over two consecutive summers. After one summer, no group difference in height was found, but weight was higher in the group that had been taken off methylphenidate therapy. In contrast, two summers of being off methylphenidate treatment had a significant positive effect on height but not on weight. The results document a linkage between exposure to methylphenidate and reduction in growth velocity. However, they do not address whether the medication has long-term effects on height.

Adolescent

Depressive symptoms and life events in physically ill hospitalized adolescents.

To study life events and depressive symptoms in adolescents hospitalized for physical illness, we administered the Coddington Life Events Survey and the Beck Depression Inventory (BDI) to 43 acutely ill adolescents, 42 chronically ill adolescents, and 140 adolescents from a general population. There were no differences between the three groups in total BDI, Psychological BDI, and Coddington Life Change Categories adjusted for hospitalization. The Somatic BDI was significantly greater in the acutely ill and chronically ill than in the general population sample (p less than 0.01). In the chronically ill, the Family Life Change score correlated with the psychological BDI (r = 0.44, p less than 0.01) but the Undesirable Life Change score did not. In the acutely ill and the general population, the Undesirable Life Change Score correlated with the Psychological BDI (r = 0.44, p less than 0.01), (r = 0.43, p less than 0.01) but the Family Life Change Score did not.

Acute Disease

Relationship of psychologic factors to frequent symptomatic ventricular arrhythmia.

Since there is very little available systematic information on the psychological profile of patients with cardiac arrhythmia, a battery of 12 standardized personality inventories was administered to 102 patients ranging in age from 19 to 69 years. Thirty-eight patients with frequent ventricular premature beats (more than 30 per hour) without myocardial infarction were significantly more psychologically symptomatic than 34 age- and sex-matched general medical/surgical patients. The variables found to be significant portray the patient with frequent ventricular premature beats without myocardial infarction: high scores for hysteria, less moral orientation, more anxiety, depression and social alienation, and an inhibited and low respectful style. This combination of psychological variables produced a discriminant function (p less than 0.001) that accounted for 53 percent of the variance between the arrhythmia/no myocardial infarction group and the medical/surgical control group and could correctly predict group membership in 83.3 percent of cases. These results may have further implications in nonpharmacologic and psychotropic adjuncts to antiarrhythmic therapy.

Adult

Scoring system to aid in diagnoses of appendicitis.

Problems related to the diagnosis of appendicitis are evidenced by the significant negative laparotomy rate. The present study sought to assess the feasibility of decreasing this diagnostic error by studying two groups of patients and identifying and weighing details of history, physical examination and laboratory findings utilizing 23 predictive factors. One hundred consecutive cases of proven appendicitis (AAp) were retrospectively reviewed and compared with 100 consecutive cases that had normal appendices removed because of erroneous preoperative diagnosis of appendicitis (NAp). Rates of occurrence for each predictive factor were determined separately for both groups. These were converted into weights which were then added to yield a diagnostic score for each patient. A cutoff point established the score which designated one group for observation and the other for surgery. Scores were assessed at three different points by balancing risks of missed diagnoses against benefits of avoiding unnecessary operations. Seven predictive factors had differentiating weights and reached statistical significance (p less than or equal to 0.05):-sex, age, duration of symptoms, GU symptoms, involuntary right lower quadrant muscle spasm, right-sided rectal mass, and white blood cell count. Using these seven predictors, at a "-3" cutoff, 38% NAPs would have been spared laparotomy and about 5% of the AAps would have been indicated for observation. Analysis indicated little risk in observing the 5% AAp (5/7 history less than or equal to 1 day), and progressive improvement for NAps with increasing time. This simple scoring system could have eliminated over one third of the unnecessary laparotomies in the present sample, indicating potential value as an aid in surgical decision-making.

Acute Disease

Five methoxy-2-methyl-3-indole acetic acid. A metabolite and alkali hydrolysis product of indomethacin, markedly inhibits platelet aggregation only in the presence of aorta or a product released by aorta.

5-methoxy-2-methyl-3-indole acetic acid (5MIAA) is a metabolite and alkali hydrolysis product of indomethacin. This indole derivative was previously found to be an effective in vivo inhibitor of platelet aggregation in an experimental model of microvascular injury in the mouse. In a standard aggregometer assay, the in vitro inhibitory action of 5MIAA was weak and failed to explain its in vivo effect. The present study employed two assay systems testing the capacity of 5MIAA to increase the aggregate inhibiting activity of the aorta. In one series of experiments the aorta, the drug and platelet rich plasma were incubated together, and in another series aliquots of aortic incubation media were transferred to PRP. Both types of study showed that 5MIAA interacts with the aorta and with a substance(s) produced by aortic wall to markedly inhibit aggregation stimulated by arachidonic acid. Thus, when 100 micrograms/ml of 5MIAA, which by itself had a negligible effect on aggregation, was added to a cuvette containing both aorta and PRP, the inhibitory effect of the aorta was enhanced three fold. The substance with which 5MIAA interacts was eliminated by cyclooxygenase inhibitors, but direct tests of 5MIAA's ability to potentiate the effect of prostacyclin were unsuccessful.

Animals

Subclinical levels of lead and developmental deficit--a multivariate follow-up reassessment.

Scores on the McCarthy Scales of Children's Abilities, school reading tests, teacher ratings, and several exploratory measures were obtained for urban black school-aged children, first studied five years previously. These were related, for 63 children, to preschool blood lead, school-age blood lead, and free erythrocyte protoporphyrin levels, and, for 34 children, to dentine lead. Most outcome variables were not significantly related to the lead variables. Preliminary analyses indicated that results of several of the McCarthy Scales, including the critical General Cognitive Index and Verbal Scales, and the reading test were significantly impaired in higher lead level groupings. However, incorporating a brief measure of parent IQ into the analyses decreased variance associated with lead and led to a strong suspicion of the remaining significant results. Few investigators reporting positive effects have considered parent intelligence, which is known to be a major determinant of developmental status. For this and other admittedly difficult methodologic reasons, conclusions from prior studies are questioned.

Child Development

Analysis of locus heterogeneity in Waardenburg syndrome types 1 and 2 using highly informative microsatellite markers.

We performed linkage and locus heterogeneity analyses of Waardenburg syndrome (WS) types 1 and 2 using 9 DNA markers from 2q35-q37, including two highly polymorphic microsatellites very closely linked to the PAX3 candidate gene. None of 5 WS type 2 (WS2) families showed linkage to the PAX3 candidate region. We localized the marker D2S102 to less than 1 cM from PAX3 (lod = 33.7, theta = 0), but a complete absence of crossovers prevented determining whether it maps distal or proximal to PAX3. Study of 14 WS type 1 (WS1) families yielded a maximum lod score of 27.81 at PAX3, theta f = 0.010, theta = 0.007 assuming homogeneity. However, we found significant evidence of locus heterogeneity, with one family initially classified as WS1 unlinked to the PAX3 region. Reevaluation of the clinical features of this family revealed atypical morphology of inner canthi. This produced the appearance of dystopia canthorum and high W-index scores. While our one unlinked WS1 family exhibits atypical canthal morphology, our type 1 families with classic dystopia appear to be homogeneously linked to PAX3. These and other findings identify precautions that need to be addressed before using PAX3-linked markers for diagnostic purposes.

Chromosome Mapping