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Biomedical subjects

A G Hunter

Publications and source records attributed to A G Hunter.

At least 37 records · Page 2Linked to original sources
PubMed1997

Clinical application of the molecular diagnosis of spinal muscular atrophy: deletions of neuronal apoptosis inhibitor protein and survival motor neuron genes.

The molecular genetic diagnosis of spinal muscular atrophy (SMA) has recently been complicated by the identification of two candidate genes, which are often deleted in affected individuals but are also occasionally deleted in apparently unaffected carriers. We present a compilation of genotypes, from our laboratory and recent reports, for the survival motor neuron (SMN) and neuronal apoptosis inhibitor protein (NAIP) genes. Bayesian analyses were used to generate probabilities for SMA when deletions are present or absent in SMN. We found that when the SMN(T) exon 7 is deleted, the probability of SMA can reach greater than 98% in some populations, and when SMN(T) is present, the probability of SMA is approximately 17 times less than the prior population risk. Deletion of NAIP exon 5, as well as SMN(T) exon 7, is associated with a 5-fold increased risk of type I SMA. Case studies are used to illustrate differing disease risks for pre- and postnatal testing, depending on the presence of information about clinical status or molecular results. These analyses demonstrate that deletion screening of candidate genes can be a powerful tool in the diagnosis of SMA.

Cyclic AMP Response Element-Binding Protein↗
PubMed1997

A prospective study to assess the frequency of familial clustering of congenital bicuspid aortic valve.

OBJECTIVES: This study sought to determine the rate of familial occurrence of congenital bicuspid aortic valve (BAV) by using echocardiography to screen family members. BACKGROUND: Congenital BAV is a common anomaly that carries with it a significant risk of potential long-term cardiac complications. Despite several reports of the familial occurrence of BAV, the condition is not generally considered to be inherited. METHODS: Thirty consecutive patients with echocardiographically documented congenital BAV were interviewed to construct three-generation family pedigrees. All first-degree relatives were contacted to undergo echocardiography to specifically determine aortic valve morphology. RESULTS: Of the 210 first-degree relatives, 190 (90.5%) agreed to undergo echocardiography. Four members had technically difficult studies. Of the remaining 186 subjects, 17 (9.1%) were identified as having BAV; 11 (36.7%) of the 30 families had at least one additional member with the condition. The male/female ratio of affected members in the 11 families was 1. In one family, two instances of male-to-male transmission were observed. The distribution of BAV in the majority of multiplex families is compatible with autosomal dominant inheritance with reduced penetrance. CONCLUSIONS: We demonstrated a high incidence of familial clustering in congenital BAV. We believe that the high rate of occurrence of the condition in immediate relatives justifies echocardiographic screening of first-degree relatives to anticipate and prevent future complications associated with this common cardiac malformation.

Aortic Valve↗
PubMed1997

Grandmother involvement in child caregiving in an urban community.

In a community-defined, epidemiologic sample in East Baltimore, we examined grandmothers' rates of co-residence and their involvement in four parenting activities. Co-residence rates exceeded the national average. Six types of family households with grandmothers were identified, and their frequency varied by race. Neither grandmother age nor employment was associated with grandmothers' parenting involvement, although family structure was. Grandmothers who were the sole parent (21%) or co-parent with a grandfather (6.5%) were most involved in child care and had the fewest number of helpers. Grandmothers living with single mothers (41%) were the next most involved, while grandmothers in mother/father households (9%) were least involved.

Adult↗
PubMed1996

Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disorder recently shown to be caused by mutations in the heparan sulfate proteoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have used Southern blot analysis and polymerase chain reaction amplification of intra-exonic sequences to identify four new GPC3 mutations and further characterize three previously reported SGBS mutations. De novo GPC3 mutations were identified in 2 families. In general, the mutations were unique deletions ranging from less than 0.1 kb to more than 300 kb in length with no evidence of a mutational hot spot discerned. The lack of correlation between the phenotype of 18 affected males from these 7 families and the location and size of the GPC3 gene mutations suggest that SGBS is caused by a nonfunctional GPC3 protein.

Abnormalities, Multiple↗
PubMed1996

Craniofacial anthropometric analysis in several types of chondrodysplasia.

Craniofacial anthropometric analysis is a generally accessible technique that potentially offers an objective tool to reduce the subjectivity of syndrome diagnosis and to aid in differential diagnosis. The chondrodysplasias might seem an unlikely target for this technique in that they mainly cause disproportionate growth and are subject to radiographic diagnoses. However, the diagnosis of skeletal dysplasias remains challenged by subjectivity of radiologic assessment, and specific radiologic signs may appear only with age or may no longer be present at the time of examination. Thus patients continue to defy diagnosis, have their diagnosis changed, and/or be misdiagnosed, even in specialized centers. Certain chondrodysplasias have obvious craniofacial involvement while others appear to share a specific gestalt. This paper reports craniofacial anthropometric analysis for several of the more common chondrodysplasias and confirms that some do display a characteristic pattern that is in keeping with what might be expected. Furthermore, the concurrent assessment of several different conditions by a single observer has emphasized the importance of considering the possibility of systematic measurement error in any such studies.

Adolescent↗
PubMed1996

Standard weight for height curves in achondroplasia.

Standard curves developed for the general population cannot be used to assess the growth of an individual who has a condition that results in disproportionate short stature. For this reason, efforts have been made to develop growth curves specific for several of the chondrodysplasias. However, data concerning weight for height have been largely lacking, although they may be of particular importance for conditions such as achondroplasia, where there is some consensus that an increased prevalence of obesity is a particular problem. In this paper we provide standard weight for height curves for males and females with achondroplasia, and discuss the use of several indices which have been applied to the assessment of body fat in the general population.

Achondroplasia↗
PubMed1996

Standard curves of chest circumference in achondroplasia and the relationship of chest circumference to respiratory problems.

Several pathogenetic factors, alone or in combination, may contribute to the increased frequency of respiratory complications in achondroplasia. It has been suggested that relatively small chest circumference sometimes may contribute. However, there are no published curves of chest circumference for age in achondroplasia with which to compare patients. Nor are there data relating chest circumference to overall size in achondroplasia. We present curves of chest circumference for males and females with achondroplasia from birth through age 7 years. Additional curves for chest circumference against height are also provided. Finally, we report some preliminary data regarding the possible association of chest size with respiratory signs and symptoms.

Achondroplasia↗
PubMed1996

A study of level of lesion, associated malformations and sib occurrence risks in spina bifida.

Neural tube defects remain the most serious common birth defect and, despite considerable progress in understanding these malformations, the etiology of most cases remains unknown. It has been proposed that the cause may vary with the type and location of the malformation but, if these variables are to be studied, a rigorous classification of cases is required. This has become more important as birth prevalence has fallen, mainly due to prenatal diagnosis and elective termination of pregnancy, and future studies will increasingly require collaboration between centres. In this study we have combined data from Ottawa, Ontario, and Boston, Massachusetts, in an attempt to examine the effect of level of spina bifida on sib occurrence rates and the rates of associated malformations, and to compare the level of lesion when determined radiographically with that recorded on the clinical chart. Malformations appeared to be more frequent with thoracic spina bifida and were more often associated with additional vertebral anomalies. Significant differences were found between the upper level of lesion recorded in the clinical file and that visible radiographically. Sib recurrences were too few for statistical comparison, but the data suggest a higher rate among sibs and more distant relatives of propositi with upper level lesions. There was not evidence to support a greater than expected concordance for level of lesion between sibs.

Boston↗
PubMed1996

Trypanosomosis research at the Centre for Tropical Veterinary Medicine (CTVM) 1970 to 1995.

This review covers aspects of research work carried out on animal trypanosomes at the Centre for Tropical Veterinary Medicine (CTVM) during the last 25 years. The review covers work on antigenic variation, tissue culture, drug resistance, immunology, biochemistry and pathology of Trypanosoma brucei, T. congolense, T. gambiense and T. evansi. It is not intended as an exhaustive review of the subject but focuses on certain aspects of these areas which are presented in relation to work carried out within the broader scientific community.

Animals↗
PubMed1996

Sweeteners, dyes, and other excipients in vitamin and mineral preparations.

Multivitamins and mineral preparations are widely used for infants and children. All of these preparations contain a variety of excipients ("inert ingredients"). Excipients are generally safe; however, adverse effects have been attributed to them. Complete information about the excipients in various preparations is not readily available. The information about sweeteners, dyes, and other excipients (flavorings, preservatives, stabilizers, and fillers) for 41 chewable/liquid multivitamin and mineral preparations was obtained and tabulated. Sucrose was present in 63% (26/41) of preparations followed by lactose in 29% (12/41) of preparations. On average, a preparation contained two sweeteners. The FD&C yellow #6 (sunset yellow) was the most common dye, present in 46% (19/41) of the preparations followed by FD&C Red #40 in 29% (12/41). For 34% (14/41) of the preparations, no color or dye was identified by the manufacturers. The tables listing excipients and their adverse effects are presented and should be helpful to health care providers in selecting preparations containing individual excipients when an adverse reaction occurs or there exists a contraindication for using the excipient. The mandatory listing of all excipients is the only way to assure that physicians and consumers will be fully informed about the hidden ingredients.

Child, Preschool↗
PubMed1996

Spondylometaphyseal dysplasia with characteristic facial appearance.

Despite expanding knowledge and technological advances there are patients whose diagnosis remains unknown, either due to failure to recognize previously reported cases, or because the patient represents an undescribed condition. The woman described in this paper has distinctive clinical signs and it is hoped this will lead to the rediscovery or recognition of similar cases.

Adolescent↗
PubMed1995

Comparison of bovine sperm capacitation systems for ability of sperm to penetrate zona-free hamster oocytes and bovine oocytes matured in vitro.

Sperm from the same ejaculate were capacitated in calcium-free Tyrode's, modified Tyrode's with bovine follicular fluid or heparin, and TEST-yolk. Capacitated sperm were coincubated with zona-free hamster oocytes at 37 degrees C for 3 h or with bovine cumulus-enclosed oocytes matured in vitro for 8 h at 37 or 39 degrees C. Bovine oocytes were transferred to fertilization medium and incubated for 72 h at 37 or 39 degrees C. Penetration of zona-free hamster oocytes was highest in calcium-free Tyrode's (53.7%), followed by Tyrode's with follicular fluid (50.6%), TEST-yolk (48.6%), and Tyrode's with heparin (34.2%). Penetration of bovine cumulus-enclosed oocytes matured in vitro at 37 degrees C was highest with heparin (48.1%), followed by TEST-yolk (35.0%), calcium-free Tyrode's (32.5%), and follicular fluid (26.4%). Sperm capacitation with heparin, assayed by penetration of bovine oocytes at 39 degrees C, was better at 39 degrees C (77.1%) than at 37 degrees C (46.1%). However, penetration rates in calcium-free Tyrode's and TEST-yolk were higher at 37 degrees C. The capacitation system with heparin at 39 degrees C and bovine oocytes was best followed by the systems using TEST-yolk and calcium-free Tyrode's at 37 degrees C.

Animals↗
PubMed1995

Comparison of various bovine sperm capacitation systems for their ability to alter the net negative surface charge of spermatozoa.

Semen was divided into five aliquots and capacitated for 4 or 6 h in calcium-free Tyrode's (37 degrees C), modified Tyrode's bovine follicular fluid (39 degrees C), modified Tyrode's heparin (39 degrees C), and TEST-yolk buffer (4 degrees C) or incubated in BSA-saline (39 degrees C). Sperm before and after capacitation were electrophoresed at 100 V of constant current for 3 and 6 min. Samples were collected, sperm were counted, and percentages of sperm migrating toward the anode at 0 h and 4 or 6 h were calculated. At 0 h, 61 to 80% of the sperm migrated with a net negative charge. After 4 or 6 h, the percentage of sperm migrating toward the anode significantly decreased in all capacitation media but not in the control. The percentage of sperm migrating toward anode was lowest in calcium-free Tyrode's (22.1%) followed by TEST (28.4%), Tyrode's follicular fluid (29.5%), and Tyrode's heparin (42.5%); these values were less than those for the control (56.0%). The movement of live sperm without the influence of current or freeze-killed sperm under the influence of electrical current (control trials) was negligible. Capacitation reduced the net negative surface charge of sperm, the magnitude of which depended on capacitation system. Net negative charge of sperm was inversely associated with efficiency in penetration of zona-free hamster oocytes.

Animals↗
PubMed1995

Effect of various capacitation systems on bovine sperm motion characteristics, acrosome integrity, and induction of hyperactivation.

Sperm from the same ejaculate were capacitated in TEST-yolk, calcium-free Tyrode's, modified Tyrode's containing follicular fluid or heparin, and analyzed at 0, 4, 8, and 12 h for motility characteristics and acrosomal integrity. Percentage of motility, progressive motility, progressive velocity, path velocity, curvilinear velocity, linearity, and amplitude of lateral head displacement differed with media and decreased with time. Calcium-free Tyrode's ranked first in maintaining most motility parameters. However, TEST-yolk sperm ranked first for lateral head displacement but last for linearity at each time. Acrosome-reacted sperm increased over time but were not different between TEST-yolk, calcium-free Tyrode's, and heparin at 4 h. The TEST-yolk sperm at 4 h had about twice the hyperactivation (62.3%) of the other sperm capacitation media. Capacitation of bovine sperm was not associated with a specific change in any measured motility parameter. Differences among the efficacies of capacitation systems were unrelated to parameters of sperm motion, hyperactivation, or acrosomal integrity.

Acrosome↗
PubMed1995

Metachondromatosis.

OBJECTIVES: To draw attention to metachondromatosis, which may be misdiagnosed as multiple osteochondromatosis, and to point out several findings that have not been emphasized in previous reports. PATIENTS AND METHOD: The authors reviewed the relevant clinical and detailed radiographic findings for five patients from different countries, who underwent imaging at various ages during childhood. RESULTS: Deformities resembling exostoses and punctate calcification were distinctive and represent previously unemphasized features of vertebral involvement in metachondromatosis. Widespread metaphyseal changes were best seen in the femoral necks, which were broad and showed prominent cartilage columns in all of the patients. Flattening of the femoral heads was observed in three patients; in one of these the flattening progressed to epiphyseal necrosis and coxa magna. In one patient the hands and feet showed no enchondromatous involvement. CONCLUSION: Metachondromatosis is a generalized bone dysplasia predominantly affecting the tubular bones and, to a lesser degree, flat bones and the vertebral column. Significant complications may include avascular necrosis of the femoral head and progressive deformity of the small joints due to expanding local exostoses. The typical involvement of the hands and the feet may not always be seen.

Adolescent↗
PubMed1995

Delivery of molecular genetic services within a health care system: time analysis of the clinical workload. The Molecular Genetic Study Group.

The most recent discoveries in molecular genetics today are rapidly incorporated into clinical practice and have resulted in an unprecedented expansion of medical options. Despite this, the impact of molecular genetics on health care services has yet to be evaluated. In order to begin this assessment, clinical genetic workload was prospectively collected from cases where molecular genetic testing was considered. Participation involved all 16 urban and outreach genetic centers regionalized to service the entire population of 10 million within the Canadian province of Ontario. Molecular genetic testing has been clinically available for > 5 years, as part of a publicly supported genetic network in which there are no direct costs to residents. Cross-sectional data were collected on 1,101 clients from 544 families involving 1,742 clinical actions relating to diseases in which molecular (DNA) tests were considered. Median times per clinical genetic action were as follows: formal counseling (60 min), case review (15 min), phone call (10 min), letter (15 min), specimen arrangement (15 min), and interpretation of molecular test results (10 min). Times varied significantly with the inheritance pattern of the disease, topics involved, and location. For any given genetic case, multiple clinical actions resulted in substantial time spent by the genetic professional. Clerical and administrative times were not captured. Workload unit measurements similar to those currently employed in hospital laboratories may be helpful for predicting the clinical resources and personnel that will be required as the use of molecular genetics by other medical specialties increases.

Analysis of Variance↗
PubMed1994

Follow-up study of patients with Wiedemann-Beckwith syndrome with emphasis on the change in facial appearance over time.

We have carried out a follow-up study of 13 children with Wiedemann-Beckwith syndrome (WBS) using a standard protocol which included facial anthropometric measurements. We confirm that most patients with WBS do well and that their clinical abnormalities become less apparent with age. We suggest that there is a characteristic neonatal appearance in WBS and that the expected pattern of facial growth generally results in a normal appearance by mid- to late childhood. We tentatively propose that there is a distinct facial anthropometric pattern profile in WBS.

Anthropometry↗