Showing papers by "Boston Children's Hospital published in 1985"

A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment.

Abstract: Steroids that lack glucocorticoid or mineralocorticoid activity were found to inhibit angiogenesis in the presence of heparin or specific heparin fragments. This newly discovered steroid function appears to be governed by distinct structural configurations of the pregnane nucleus. These compounds are here named angiostatic steroids.

Antiviral effect of flavonoids on human viruses.

Abstract: The effect of several naturally occurring dietary flavonoids including quercetin, naringin, hesperetin, and catechin on the infectivity and replication of herpes simplex virus type 1 (HSV-1), polio-virus type 1, parainfluenza virus type 3 (Pf-3), and respiratory syncytial virus (RSV) was studied in vitro in cell culture monolayers employing the technique of viral plaque reduction. Quercetin caused a concentration-dependent reduction in the infectivity of each virus. In addition, it reduced intracellular replication of each virus when monolayers were infected and subsequently cultured in medium containing quercetin. Preincubation of tissue culture cell monolayers with quercetin did not affect the ability of the viruses to infect or replicate in the tissue culture monolayers. Hesperetin had no effect on infectivity but it reduced intracellular replication of each of the viruses. Catechin inhibited the infectivity but not the replication of RSV and HSV-1 and had negligible effects on the other viruses. Naringin had no effect on either the infectivity or the replication of any of the viruses studied. Thus, naturally occurring flavonoids possess a variable spectrum of antiviral activity against certain RNA (RSV, Pf-3, polio) and DNA (HSV-1) viruses acting to inhibit infectivity and/or replication.

Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism.

Abstract: Children with the Beckwith-Wiedemann syndrome have a greatly increased potential for the specific development of the embryonal tumours hepatoblastoma, rhabdomyosarcoma and Wilms' tumour. Data obtained with molecular probes suggest that the association between these disparate, rare tumour types reflects a common pathogenetic mechanism that entails the somatic development of homozygosity for a mutant allele at a locus on human chromosome 11.

Further segregation analysis of the fragile X syndrome with special reference to transmitting males

Abstract: A new series of 96 pedigrees with the fra(X) syndrome was analysed using complex segregation analysis with pointers, defining affection as any degree of mental impairment. These families were found to exhibit the same segregation pattern as the first series of 110 pedigrees (Sherman et al. 1984). The best estimate for penetrance of mental impairment in males was 79% and in females was 35% for the combined data. Again, there was little evidence for sporadic cases among affected males. Many more intellectually normal transmitting males have been observed since the existence of such males and the concomitant need to investigate the paternal side of pedigrees was recognized. On further investigation of all 206 pedigrees from the old and new data sets, the sibships of nonexpressing males appeared to be different from those of expressing males. Our analysis, using mental impairment as the phenotype, suggested that obligate carrier mothers and daughters of intellectually normal transmitting males are rarely, if ever, mentally impaired and that the sibs of transmitting males are much less likely to be retarded than the sibs of mentally impaired males. Though mothers and daughters of transmitting males are similar in phenotype, the expression of the gene in their offspring appears to be different: the penetrance of mental impairment is higher in offspring of intellectually normal daughters of transmitting males than in offspring of intellectually normal mothers of transmitting males. The implications of these observations for genetic counseling and for genetic models of the fra(X) syndrome are discussed.

Inhibition of calcification of bioprosthetic heart valves by local controlled-release diphosphonate

Abstract: Bioprostheses fabricated from porcine aortic valves are widely used to replace diseased heart valves. Calcification is the principal cause of the clinical failure of these devices. In the present study, inhibition of the calcification of bioprosthetic heart valve cusps implanted subcutaneously in rats was achieved through the adjacent implantation of controlled-release matrices containing the anticalcification agent ethanehydroxydiphosphonate dispersed in a copolymer of ethylene-vinyl acetate. Prevention of calcification was virtually complete, without the adverse effects of retarded bone and somatic growth that accompany systemic administration of ethanehydroxydiphosphonate.

Adenovirus Infections in Patients Undergoing Bone-Marrow Transplantation

Abstract: Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease.

Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization

Abstract: Human factor VIII--von Willebrand factor (vWF) is a large, multimeric glycoprotein that plays a central role in the blood coagulation system, serving both as a carrier for factor VIIIC (antihemophilic factor) and as a major mediator of platelet-vessel wall interaction. Diminished or abnormal vWF activity results in von Willebrand's disease (vWD), a common and complex hereditary bleeding disorder. Overlapping vWF cDNA clones that span 8.2 kilobases of the vWF messenger RNA have been obtained. vWF accounts for approximately 0.3 percent of endothelial cell messenger RNA and was undetectable in several other tissues examined. A large single copy gene for vWF is located on the short arm of chromosome 12 (12p12----12pter). No gross gene rearrangement or deletion was detected in the DNA of two patients with severe vWD.

Noonan syndrome: a review.

Abstract: After an introduction dealing with the "historical evolution" of the Noonan syndrome (NS), we try to define the NS phenotype based on clinical descriptions published since 1883. The theories concerning the cause of the NS are discussed fully. The peculiar cardiac involvement deserves special attention and raises the question of whether the Watson and LEOPARD syndromes are indistinguishable from NS. Finally, the recent contributions to the variability of the NS phenotype (reports on lymphatic dysplasia, partial deficiency of factor XI, malignant hyperthermia, perceptual-motor disabilities, and endocrine evaluation) are also described.

Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment

Abstract: The Duchenne muscular dystrophy (DMD) locus has been localized to the short arm of the human X chromosome (Xp21) by detection of structural abnormalities and by genetic linkage studies A library highly enriched for human DNA from Xp21 was constructed using DNA isolated from a male patient who had a visible deletion and three X-linked disorders (DMD, retinitis pigmentosa and chronic granulomatous disease) Seven cloned DNA probes from this library and the probe 754 (refs 5, 8) are used in the present study to screen for deletions in the DNA isolated from 57 unrelated males with DMD Five of these DMD males are shown to exhibit deletions for one of the cloned DNA segments and at least 38 kb of surrounding DNA In addition, two subclones from the same region detect four restriction fragment length polymorphisms which exhibit no obligate recombination with DMD in 34 meiotic events These new DNA segments will complement the existing Xp21 probes for use in carrier detection and prenatal diagnosis of DMD Elucidation of the end points of the five deletions will help delineate the extent of the DMD locus and ultimately lead to an understanding of the specific sequences involved in DMD

Fragile sites on human chromosomes

Abstract: Fragile sites have been documented at 2q11, 10q23, 10q25, 11q23, 16q12, 16q22, 20p11 and Xq27. These are heritable chromosome markers which can be demonstrated in lymphocyte culture. Special culture medium is required for all except the one at 16q22: it must be free of folic acid and thymidine to demonstrate all the others with the exception of the site at 10q25 which requires the presence of BrdU. The autosomal sites are without apparent phenotypic effect in the heterozygote but homozygotes have not been documented. The BrdU requiring site is present in about 1 in 35 of the South Australian population, hence if homozygotes are viable about 4 per yr would be born in the State. The fragile site at Xq27 produces a mental retardation syndrome, which is the commonest chromosomally determined cause of mental retardation after Down’s syndrome. From the South Australian population of approximately 1.2 million, 25 such males have been identified and the fra(X)(q27) chromosome has been shown to be segregating in 9 families, most of which are of Anglo-Saxon origin. Difficulties have been encountered in demonstrating this fragile site, especially in females and skin fibroblasts.

Method and apparatus for transmyocardial revascularization using a laser

Abstract: A surgical carbon dioxide laser is disclosed which includes a handpiece for directing a laser beam to a desired location. Mounted on the forward end of the handpiece is a hollow needle precisely aligned along the laser path. This permits the laser to be used in surgical applications where the needle perforates a porton of tissue to provide the laser beam direct access to distal tissue. The needle is mounted to the handpiece in a manner which provides for forward and lateral adjustment of the needle relative to the laser beam path which insures co-axiality between the laser beam and the needle lumen. This is crucial for the safe use of the laser. The needle is adjusted such that the focal point of the laser beam is approximately at the tip of the needle. This provides maximum energy at the tip of the needle where it is required. This apparatus is particularly useful in transmyocardial devices utilized to provide ischemic endocardial tissue direct access to blood within the ventricular cavity. The device is inserted within the epicardium of the heart; the laser is then activated to vaporize a channel of tissue through the endocardium. This provides for perforation of the endocardium with minimal damage to the epicardium.

Otitis media with effusion in preschool children.

Abstract: The incidence, prevalence, and natural history of otitis media with effusion (OME) and middle ear high negative pressure (HNP) were investigated in a group of 2 to 6 year old preschool children. The children were examined monthly over a two year period from September 1981 to August 1983. The middle ear status was assessed using a decision-tree algorithm which combined the findings of pneumatic otoscopy, tympanometry, and acoustic reflex measurements. Fifty-three percent of the children in the first year and 61% in the second year developed OME; also during the two years, HNP was documented in 66% of the children. Eighty percent of OME episodes lasted only two months. The prevalence of OME and HNP showed a seasonal variation and a strong association with the presence of upper respiratory infections (URIs). The incidence of OME was independent of age. These data indicate that OME and HNP are prevalent conditions with a high spontaneous recovery in the preschool population.

Assessing children's copy productions of the Rey-Osterrieth complex figure

Abstract: This report describes developmental changes in children's memory productions of the Rey-Osterrieth Complex Figure and in the relation of memory to copy productions, and a method for evaluating these productions that is sensitive to parameters relevant to neuropsychological diagnosis. Based on protocols from a standardization sample of 454 children between the ages of 5 and 14 (Waber & Homes, 1985), a system was devised for objectively evaluating organization, production style, and accuracy. Normative findings are described and implications for the use of this instrument in the neuropsychological assessment of children discussed.

Rehabilitation of the pitching shoulder

Abstract: Shoulder pain is a common complaint among baseball pitchers. Frequently, the nature of shoulder pathology can be traced to lack of flexibility and muscular imbal ance.This paper describes: (1) the normal biomechanics of a properly functioning shoulder during a baseball pitch, (2) pathomechanics of shoulder problems, (3) flexibility requirements of the throwing shoulder, and (4) the muscular balance necessary for an effective throwing shoulder. Appropriate examination procedures are de scribed along with remedial exercises which ensure normal glenohumeral motion and integrated muscle action.

The epidemiology of diabetes in Swedish children 0-14 years--a six-year prospective study.

Abstract: Since 1 July 1977, all newly diagnosed diabetic children in Sweden aged 0–14 years have been reported to a central register. During the first 6 years, 2300 newly diagnosed diabetic children out of a population of 1.6 million children were registered. The degree of certainty was close to 100%. The mean of the yearly incidence rate for the whole 6 year period was 23.6 per 100000. The prevalence of insulin dependent diabetes mellitus on 1 July 1980 was 1.48 per 1000 and 1.52 on 1 July 1983. Comparing the first and second 3-year periods, an increase was found (22.7–25.1 per 100000). This increase was consistent when analyzing incidence rates by age, sex, and geographical distribution. Cumulative incidence rates revealed a risk of developing diabetes by the age of 15 years of 3.6 per thousand for boys and 3.2 per thousand for girls. The higher incidence for boys was consistent throughout the study period. Seasonal variations in the incidence rate were also consistent, showing yearly incidence peaks in the autumn and winter months. Incidence peaks were noted for both sexes in the pubertal ages. Age- and sex-standardized morbidity ratios varied significantly within the country. 12.8% of the probands had a first degree relative with Type 1 diabetes, and it was twice as common that this relative was a father as a mother. The high and rapidly increasing incidence of Type 1 diabetes in a genetically stable population such as Sweden calls for case-control studies directed towards the identification of environmental pathogens.

Event-related brain potential correlates of the processing of novel visual and auditory information in autism.

Abstract: Event-related brain potentials (ERPs) elicited by visual and auditory stimuli were recorded from nonretarded individuals with autism (ages 13-25 years) and age-matched normal controls. In "no-task" conditions, subjects simply looked at or listened to these stimuli; only one difference was found between subject groups. Several ERP differences between groups were found in "task" conditions; subjects pressed a button at the occurrence of target stimuli intermixed with unexpected, novel stimuli and also with expected, nonnovel stimuli. Visual ERP abnormalities in the autistic group differed from auditory abnormalities. Results suggest that (1) nonretarded autistic individuals may have a limited capacity to process novel information--they are neither hypersensitive to novel information nor misperceive it as nonnovel and insignificant; (2) classification of simple visual information may be less impaired than auditory; and (3) with one exception, visual and auditory ERP abnormalities do not seem to reflect maturational delay.

Mental health in Dutch children: II. The prevalence of psychiatric disorder and relationship between measures.

Abstract: This study concerns the second, more clinically oriented, part of our epidemiological project. The prevalence of child psychiatric disorders in random samples of 8- and 11-year-old children is assessed by using standardized parent- and child-interviews. The relationships between different measures of child psychopathology are determined. Furthermore, additional validity measures of the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) developed by Achenbach, are provided. Of the 153 8- and 11-year-old children selected through a two-stage sampling procedure, 116 (76%) children and their parents were intensively clinically assessed. The correlation between CBCL and direct child assessment is .42, whereas the correlation between the TRF and direct child assessment is .28. The correlation between TRF and CBCL is .26. The implications of the low correlation between raters who saw children is different situations are emphasized. The weight given to reports from different sources varies with the kind of problem the child exhibits. It is concluded that more research is needed to investigate the relative value of different types of data for different conditions. Seven percent of the 8- and 11-year-olds were judged severely disordered, whereas for 26% the clinicians judged the child to be moderately or severely disordered. The high prevalence rates found in our study compared with others is partly attributed to the arbitrary nature of clinical judgement. ANOVAs and discriminant function analysis were performed to obtain those CBCL items that showed the best discrimination between children who were clinically judged disordered and children from the normative comparison group. Many items found to be good discriminators of clinical status in this study were among the best discriminators of referral status in the earlier reported part of the study. A number of family and social factors were found to be associated with psychiatric disorder. These findings support those in other studies.

Regulation of drug release from polymer matrices by oscillating magnetic fields

Abstract: The reproducible regulation of release of a macromolecule (bovine serum albumin) from biocompatible polymer systems has been demonstrated. Small magnetic spheres or cylindrical magnets were embedded within the polymer matrix which was then subjected to an oscillating magnetic field. In this fashion baseline release rates could be increased 5- to 10-fold with 5-10% standard error. Parameters critical to the regulation of this release included the position, orientation, and magnetic strength of the embedded objects and the amplitude and frequency of the applied magnetic field. Scanning electronmicrographs of the polymer matrix surface reveal that a gap, approximately 100/microns wide, is formed between the embedded object and adjacent polymer material after repeated exposure to an oscillating magnetic field.

Dark rearing prolongs physiological but not anatomical plasticity of the cat visual cortex.

Abstract: Recent studies (Cynader and Mitchell, '80; Mower et al., '81) have shown that total dark rearing prolongs susceptibility to the physiological effects of monocular deprivation (MD) in visual cortex beyond the normal age limits. The present study addressed whether this delayed physiological plasticity is accompanied by delayed anatomical plasticity in the geniculocortical pathway. Ocular dominance (OD) columns as defined by transsynaptic autoradiography following injection of 3H proline into one eye were studied both qualitatively and quantitatively in 17 cats. Compared to normal rearing (N-3), both binocular eyelid suture (N-2) and total dark rearing (N-3) resulted in incomplete segregation of OD columns in area 17. This apparent immaturity after binocular deprivation, however, did not reflect a delayed capacity for development and plasticity. Visual experience after dark rearing produced no marked changes. In cats who experienced MD after dark rearing, injection of either the nondeprived (N-2) or deprived eye (N-3) resulted in a nearly uniform distribution of label throughout layer IV of area 17. The same result occurred with binocular vision after dark rearing (N-1). MD from birth, however, produced expansion of columns from the nondeprived eye (N-1) and contraction of columns from the deprived eye (N-1). MD imposed after 4 months of normal vision resulted in normal OD columns (N-1). Electrophysiological studies revealed a high proportion of binocular cells within layer IV in cats who experienced monocular or binocular vision after dark rearing. Outside of layer IV there were clear environmental effects on OD of single cells in these cats. Measurements of cell sizes in the clateral geniculate nucleus showed shrinkage of cells innervated by the deprived eye when MD was initiated at birth (N-3). MD after dark rearing (N-4) produced no differences in cell sizes. It is concluded that visual input is necessary for the formation of normal OD columns, the critical period for formation and environmental modification of OD columns is limited to early life, and the physiological effects of visual experience after dark rearing reflect changes occurring beyond the geniculocortical pathway.

Biomechanical Comparison of Rising from Two Types of Chairs

Abstract: This study compared the joint moments and ranges of motion of healthy subjects and patients during rising from a standard chair with a seat height of 0.43 m and a specially designed chair (E-Z Up Artherapedic Chair) with a seat height of 0.64 m. Ten healthy male subjects and four male patients with lower extremity disabilities rose from each chair with and without the use of their upper extremities. Hip, knee, and ankle joint moments and angles were calculated with film analysis and force plate data. An analysis of variance with repeated measures showed the following results for the healthy subjects: 1) no effect of upper extremity use on joint angles, 2) no effect of chair type on ankle joint angles or moments, 3) significantly smaller hip and knee flexion angles with use of the E-Z chair than of the standard chair (p less than .05), and 4) significantly smaller hip and knee extension moments with use of the E-Z chair than of the standard chair (p less than .05) or with use of the upper extremities. Similar results were found with the four disabled subjects. Use of the E-Z chair can significantly decrease the joint moments and ranges of motion needed at the hip and knee and thus make rising from a chair less stressful to these joints.