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Biomedical subjects

L R Shapiro

Publications and source records attributed to L R Shapiro.

At least 37 records · Page 2Linked to original sources

The fragile X syndrome--clinical overview.

The Fra(X) syndrome is the most common inherited cause of mental retardation. It is associated with an unusual form of X-linked inheritance where both men and women can be carriers. The "X-inactivation imprinting model" proposed by Laird et al currently offers one explanation of the unusual genetics. Recognition of clinical features and accurate cytogenetic diagnosis is important because of the prevalence of this disorder and the necessity and demand for genetic counseling. A combination of fra(X) cytogenetic studies and DNA-based linkage analysis for carrier detection and prenatal diagnosis is currently in use and is undergoing development and improvement.

Chromosome Fragility↗

Three-generation dominant transmission of the Silver-Russell syndrome.

We report on 7 patients with the Silver-Russell syndrome (SRS) in two 3-generation families. Three patients in each of the families had an undergrowth of the left side of the body when compared with the normal right side. The clinical courses were mild as compared to the severity sometimes described in sporadic cases. These patients and a review of 190 SRS cases from the literature showed that there were 23 families in which 38 patients had completely expressed SRS. In 17 of the families, multiple maternal relatives had complete or partial expressions of the SRS. Most SRS patients have been reported to occur sporadically; however, of the 197 propositi analyzed, 19% had more than one affected individual in a family and several different modes of inheritance could have been responsible. Two families (8.7%) had spontaneous dominant mutations (twins) and possible autosomal recessive transmission was present in 4 families (17.4%). Because no male-to-male transmission has yet been documented in the 21 families in the literature and the two families reported here, X-linked dominant inheritance is a possibility in 17 families (74%). Thus, although sporadic occurrences and genetic heterogeneity appear to be involved in the SRS, dominant inheritance may be a major causal factor.

Adult↗

Deletion of 16q with prolonged survival and unusual radiographic manifestations.

Deletion of 16q is characterized by mental retardation, microcephaly, a characteristic combination of minor facial anomalies, and broad halluces. Various break points have been described. This patient's phenotype is typical of this syndrome, but in addition, unusual radiographic findings were present. This chromosome abnormality is compatible with survival into adulthood. Expression of this phenotype does not appear to be correlated with specific break points.

Abnormalities, Multiple↗

Establishment of new human prostatic cancer cell line (JCA-1).

The establishment of a new human prostatic cancer cell line is described. This cell line was derived from a poorly to moderately differentiated prostatic adenocarcinoma. It has been maintained in tissue culture for fourteen months and has been passed fifty-two times. This cell line has an ability to form colonies in soft agar suspension cultures, and also is transplantable to nude mice. Tumors grown in nude mice revealed a poorly differentiated adenocarcinoma with positive PSA staining. Acid phosphatase activity was detected in freeze-thawed cells by enzymatic assay. A karyotype analysis demonstrated aneuploidy with a model chromosomal number of 69 and six marker chromosomes.

Acid Phosphatase↗

Disomic balanced reciprocal translocation.

The previously unreported and unique finding of a complete disomy of an apparently balanced reciprocal translocation is described. The parents are second cousins once removed and each parent contributed the same balanced reciprocal translocation chromosome. Although the complete disomy involves balanced translocation chromosomes from unaffected parents, it is possible that a hemizygous state of some genes may be present on each translocation chromosome, which in a disomic homozygous state could result in an abnormal phenotype, as manifested by infantile seizures in this patient.

Chromosomes, Human, Pair 16↗

Short-term fluctuation as an estimate of variability in visual field data.

The short-term fluctuation index (SF) is one of several values that provide an indication of a patient's response reliability during an automated perimetry examination. The authors investigated the number of visual field locations used and the number of determinations per location as factors affecting the SF estimate. A computer simulation program for perimetry was used to measure the SF index for 350 normal visual fields with various levels of response fluctuation. As expected, the variability of the SF estimate decreased as the number of locations used to estimate SF increased. There was a more important finding that, for an equal number of threshold estimates, a larger number of determinations at a smaller number of locations produced greater consistency in the SF estimate (eg, ten determinations at two locations instead of two determinations at ten locations). However, it is also important to sample from a representative spatial distribution of visual field locations. These results suggest that five determinations at four locations in the visual field is optimal for most clinical perimetric testing situations.

Computer Simulation↗

Acrocallosal syndrome: additional manifestations.

The acrocallosal syndrome (ACS) is a probable autosomal recessive condition of macrocephaly, craniofacial and hand and foot abnormalities, absence of the corpus callosum, and mental retardation. This patient had characteristics of the ACS but also had a severe congenital heart defect and other visceral malformations. After comparing the ACS with and contrasting it to other disorders, we concluded that the internal organ abnormalities found in this patient probably represent further manifestations of the ACS.

Abnormalities, Multiple↗

The trajectory of cognitive development in males with fragile X syndrome.

The trajectory of cognitive development in males with fragile X syndrome was identified in a cross-sectional study of 56 males and in a smaller, longitudinal study of 10 fragile X males. Results from both studies indicated steady cognitive growth until late childhood and early adolescence (10 to 15 years of age), at which point mental age plateaued and IQ declined. Males with higher initial IQ scores manifested more IQ decline than those with initial lower levels of intelligence. The trajectories of IQ differ from those in other etiological groups and mixed groups of retarded individuals. Results have direct implications for intervention strategies with fragile X males. Parents and teachers should be informed about the possibility of an early plateau in mental age, the impact this may have on the child's academic performance, and that the plateau and IQ decline may not be apparent in the child's adaptive behaviors.

Adolescent↗

Trisomy 5 mosaicism in amniotic fluid with normal outcome.

A case of prenatally diagnosed true mosaicism for trisomy 5 with a clinically normal outcome is presented. Trisomy 5 was detected in 23% of cells obtained by amniocentesis, but it was not detected from cells obtained by fetal blood sampling. While in this case the finding at amniocentesis did not reflect the status of the fetus, care must be exercised in reaching this conclusion in all cases.

Adult↗

Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) is resistant to effective therapy for Ph1-negative ALL.

Amsacrine with high-dose cytarabine is effective therapy for Philadelphia chromosome (Ph1)-negative acute lymphoblastic leukemia (ALL). We examined the effectiveness of this regimen in 19 patients with Ph1-positive lymphoblastic leukemia. Four had an antecedent chronic phase of chronic myelogenous leukemia and 15 presented with ALL. There were no complete responders in either group. All 14 patients whose bone marrow could be assessed after completion of therapy showed persistent leukemia. We conclude that patients with Ph1-positive lymphoblastic leukemia have a disease that is resistant to treatment that is highly effective in patients with Ph1-negative ALL.

Adolescent↗

Pitfalls in Tay-Sachs carrier detection: physician referral patterns and patient ignorance.

Tay-Sachs carrier detection testing prior to pregnancy is more desirable than intra-pregnancy testing because it is technically easier, less expensive, and associated with less anxiety and less urgency. However, more than 80% of individuals referred for testing were pregnant women and/or their partners. The literature of the last several years has been silent on these and related issues. A questionnaire designed to determine the factors responsible for these circumstances was sent to 404 physicians (231 obstetrician/gynecologists and 173 internists and family physicians). Of the delivered questionnaires, 49.5% were completed and returned. The majority of obstetrician/gynecologists responding refer patients for Tay-Sachs carrier detection. Internists and family physicians do not, and their responses indicate a lack of pertinent knowledge. In addition, despite physician referral, patients delayed testing until pregnancy. While educational efforts have been targeted to obstetrician/gynecologists, expanded educational activities for internists, family physicians, and patients are required.

Education, Medical, Continuing↗

The use of early simultaneous percutaneous umbilical blood sampling (PUBS) and amniocentesis for prenatal fragile X chromosome diagnosis.

Early simultaneous percutaneous umbilical blood sampling (PUBS) and amniocentesis for prenatal diagnosis were undertaken for the first time in a 17-week gestation fetus at risk for the fragile X [fra (X)] syndrome. Metaphase spreads from 300 fetal lymphocytes were examined within 5 days following PUBS, while approximately 5 weeks were required for the analysis of 148 amniocytes. The chromosomes were interpreted as normal (46,XX) and the fetus as fragile X-negative at the time of prenatal diagnosis. This was cytogenetically confirmed after delivery of a healthy term female infant. Our results suggest that early PUBS may become a useful adjunct to amniocentesis because of shorter culture time and earlier diagnosis.

Amniocentesis↗

Prior hospitalization experience of DRG outliers versus inliers.

The Diagnosis-Related Group (DRG)-based Medicare Prospective Payment System has raised a number of concerns. One major concern has centered on both the definition of outlier patients and how hospitals are to be paid for their care. The epidemiology of outlier patients, however, has received relatively little attention. Using a retrospective database, we constructed a case control study in which the cases were DRG outliers and the control patients were DRG-matched inlier patients. We then examined both the prior hospitalization experience of outlier patients and inlier controls, and the prior outlier experience of the attending physicians of outlier patients and inlier control patients. We demonstrated that DRG-based outlier patients were more likely to have had prior admissions to the hospital as compared with DRG-matched inlier control patients. Moreover, DRG-matched outlier cases were more likely to have had prior outlier admissions as compared to controls--an effect that was more pronounced when only the subset of patients who actually had a prior admission was evaluated. Finally, physicians of the DRG outlier patients were more likely to have had previous outlier patients than physicians of the DRG-matched inlier control patients. In summary, we were able to demonstrate that DRG-based outlier patients have a different prior admission and outlier experience than DRG-matched inlier control patients. However, because we showed the same relationship when we evaluated the outlier experience of physicians of outlier patients as compared to physicians of DRG-matched inlier controls, we were unable to determine if the effect was patient- or physician-based.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis-Related Groups↗

Minimum points and views for the recovery of three-dimensional structure.

Mathematical analyses of motion perception have established minimum combinations of points and distinct views that are sufficient to recover three-dimensional (3D) structure from two-dimensional (2D) images, using such regularities as rigid motion, fixed axis of rotation, and constant angular velocity. To determine whether human subjects could recover 3D information at these theoretical levels, we presented subjects with pairs of displays and asked them to determine whether they represented the same or different 3D structures. Number of points was varied between two and five; number of views was varied between two and six; and the motion was fixed axis with constant angular velocity, fixed axis with variable velocity, or variable axis with variable velocity. Accuracy increased with views, decreased with points, and was greater with fixed-axis motion. Subjects performed above chance levels even when motion was eliminated, indicating that they exploited regularities in addition to those in the theoretical analyses.

Depth Perception↗

In utero thickening of the chordae tendinae. A cause of intracardiac echogenic foci.

Asymptomatic hyperechoic foci were noted within the left cardiac ventricular chamber on the prenatal sonograms of 26 patients between 16 and 20 weeks of gestation. Their range of occurrence, the prenatal follow-up in 12 patients and postnatal echocardiograms in six patients, indicate a clinically insignificant congenital anomaly associated with the chordae tendinae.

Adult↗