PubMed Health⌕ Search

Biomedical subjects

H J Dean

Publications and source records attributed to H J Dean.

At least 19 recordsLinked to original sources
PubMed2004

Short-term insulin therapy in adolescents with type 2 diabetes mellitus.

The optimum pharmacological treatment of type 2 diabetes mellitus (DM2) in youth for those who fail to achieve adequate glycemic control (HbA1c <7%) with lifestyle intervention is unknown. The aim of this pilot study was to observe the effect of short-term insulin therapy (<16 weeks duration) on glycemic control in youth with DM2. A pre-mix 30/70 insulin was given twice daily to 18 youth aged 10-18 years with DM2 for 8.7+/-4.3 weeks with a starting dose of 0.5 U/kg/day. HbA1c, body mass index (BMI) and episodes of hypoglycemia were monitored during the treatment period and for a 12-month period after insulin was stopped. Mean HbA1c decreased from 12.81% to 7.59% (95% CI 6.54, 8.64). This improvement persisted for 12 months without any further drug therapy. There was no significant change in mean BMI and there were no episodes of moderate or severe hypoglycemia. Decreasing beta-cell glucose toxicity with rapid improvement of blood glucose may play an important role in treatment of DM2 in adolescents. Early success in achieving target blood glucose levels is an important aspect of adolescent DM2 care.

Adolescent↗
PubMed2000

Diabetes-associated autoantibodies in aboriginal children.

Type-2 diabetes is increasing in aboriginal children and adolescents and must be distinguished from type-1 diabetes in this population. The absence of diabetes-associated autoantibodies supports the clinical impression of type-2 diabetes in the affected members of this population.

Adolescent↗
PubMed2000

Childhood obesity in a population at high risk for type 2 diabetes.

OBJECTIVES: To determine the prevalence of obesity and investigate its association with fasting glucose and insulin among children and adolescents in a population at high risk for type 2 diabetes. DESIGN: A cross-sectional screening survey involving anthropometry and fasting serum levels of glucose and insulin. SETTING: A remote aboriginal (Ojibwa-Cree) community in northern Manitoba, Canada. PARTICIPANTS: All children aged 4 to 19 years in the community were invited to participate, with a response rate of 82% (n = 719). MAIN OUTCOME MEASURES: Obesity is defined as body mass index exceeding the 85th percentile of the National Center for Health Statistics reference data. The diagnosis of diabetes and impaired fasting glucose is based on the new criteria of the American Diabetes Association. RESULTS: There is a high prevalence of obesity, with 64% (female) and 60% (male) exceeding the 85th percentile and 40% (female) and 34% (male) exceeding the 95th percentile. Body mass index is a significant predictor of both glucose and insulin in both sexes, independent of age. Obese children are at increased risk of being classified as having diabetes or impaired fasting glucose (odds ratio 5.1, 95% CI 1.51, 17.0). CONCLUSIONS: The early onset of type 2 diabetes in childhood is increasingly observed in many populations. Childhood obesity is a strong risk factor. Early detection and intervention directed at obesity are potential strategies to avert the long-term consequences of type 2 diabetes.

Adolescent↗
PubMed1999

Cross-protective efficacy of a bovine viral diarrhea virus (BVDV) type 1 vaccine against BVDV type 2 challenge.

A new genotype of bovine viral diarrhea virus (BVDV), designated BVDV type 2 (BVDV 2), has become prevalent in the field. BVDV 2 strains are antigenically distinct from currently available vaccine strains of the BVDV 1 genotype, raising concerns about cross-protection of these vaccines against BVDV 2 challenge. To determine cross-protective efficacy of a modified-live virus (MLV) vaccine containing BVDV 1 strain WRL (BVDV 1(WRL)), two studies were conducted in which the relative magnitude and duration of BVDV 1- and BVDV 2-specific serologic responses and protection against BVDV 2 challenge were determined. For the first study, 27 heifers were vaccinated (13 i.m. and 14 s.c.), while 13 heifers received negative control vaccine. Serum from the vaccinated heifers neutralized both BVDV 1 and BVDV 2 strains. The evolution and duration of BVDV 1 and BVDV 2 serologic responses were comparable, and antibody titers to BVDV 2 persisted through at least 105 days post-single vaccination. In a second, separate study, 17 calves were vaccinated (9 i.m. and 8 s.c.), and 11 calves were held as unvaccinated controls. Approximately seven months following vaccination, the calves were challenged intranasally with the 890 isolate of BVDV 2. Clinical signs of disease and fever were significantly reduced in vaccinates in comparison with controls. Vaccination eliminated nasal virus shedding in 87% of cattle and completely prevented viremia and leukopenia. These data indicate utility of BVDV 1(WRL) MLV vaccine in stimulation of long-term BVDV 2-specific serologic responses, protection against BVDV 2 challenge and reduction or elimination of virus shedding which can contribute to spread of BVDV 2 in herds.

Animals↗
PubMed1999

A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.

We previously reported nine children with an autosomally recessive form of congenital hypothyroidism due to an iodide transport defect in a large Hutterite family with extensive consanguinity living in central Canada. Since the original report, we have diagnosed congenital hypothyroidism by newborn TSH screening in 9 additional children from the family. We performed direct sequencing of the PCR products of each NIS (sodium/iodide symporter) gene exon with flanking introns amplified from genomic DNA extracted from peripheral blood cells of the patients. We identified a novel NIS gene mutation, G395R (Gly395-->Arg; GGA-->AGA), in 10 patients examined in the present study. All of the parents tested were heterozygous for the mutation, suggesting that the patients were homozygous. The mutation was located in the 10th transmembrane helix. Expression experiments by transfection of the mutant NIS complimentary DNA into COS-7 cells showed no perchlorate-sensitive iodide uptake, confirming that the mutation is the direct cause of the iodide transport defect in these patients. A patient who showed an intermediate saliva/serum technetium ratio (14.0; normal, > or = 20) and was considered to have a partial or less severe defect in the previous report (IX-24) did not have a NIS gene mutation. It is now possible to use gene diagnostics of this unique NIS mutation to identify patients with congenital hypothyroidism due to an iodide transport defect in this family and to determine the carrier state of potential parents for genetic counseling and arranging rapid and early diagnosis of their infants.

Animals↗
PubMed1996

Replication and pathogenicity after intranasal and intracranial inoculation of swine with a recombinant pseudorabies virus containing a deletion at the UL/IR junction.

Pseudorabies virus (PRV) is a neurotropic herpesvirus of swine. Previously, we described construction of a recombinant strain of PRV (LLT beta delta 2) which contains a 3.0-kb deletion spanning the junction of the unique long and internal repeat sequences. Compared to the parental strain, Indiana-Funkhauser, and a virus rescued for the deleted sequences (LLT beta res), LLT beta delta 2 replicated efficiently at the site of inoculation, yet exhibited significantly reduced virulence when inoculated intranasally in pigs. In this report, we investigated the effect of the deletion on PRV replication and virulence after intracranial inoculation of swine, in comparison to replication and virulence after intranasal inoculation, in order to more precisely locate the defect in LLT beta delta 2. Four-day-old pigs were infected intranasally with LLT beta delta 2 or LLT beta res and necropsied at various times postinfection. Compared to LLT beta res-infected pigs, tissue distribution of virus, PRV antigen, and lesions of LLT beta delta 2-infected pigs were comparable in all peripheral tissues examined, including trigeminal ganglia, but were reduced in tissues from the central nervous system (CNS). LLT beta delta 2 was able to replicate in the CNS after intracranial inoculation into the cerebral cortex of 2-day-old piglets and to spread from CNS to peripheral tissues. Neurovirulence of LLT beta delta 2 was somewhat reduced, as demonstrated by delayed onset of neurological signs and death in intracranially inoculated pigs. These results indicate that decreased neurovirulence after intranasal inoculation is not due to inability of LLT beta delta 2 to replicate in CNS tissues. The difference in the amount of antigen detected in CNS tissues after intracranial inoculation compared to intranasal inoculation suggests that one defect in LLT beta delta 2 is reduced ability to spread from peripheral neurons to the CNS after intranasal inoculation.

Animals↗
PubMed1996

Does growth-hormone supplementation affect adult height in Turner's syndrome?

BACKGROUND: By comparison with historical controls, the effect of treatment with growth hormone on adult height in Turner's syndrome was initially reported as uniformly and strongly positive. Because randomised controlled trials are not near completion, we report our experiences in an open study. METHODS: We examined adult height, projected and attained, in 31 patients (17 treated with subcutaneous recombinant human growth hormone, up to 15 mg a week, outside of a controlled trial and 14 untreated contemporaries). FINDINGS: Contingency table analysis of attained versus projected height showed significantly higher values in treated patients although only 4 of 17 had final heights of 5 cm or more over projection. Patients' and treatment variables (height, bone-age delay, oestrogen replacement) that interfere with adult height projection confounded the analysis of adult height data. INTERPRETATION: Girls with Turner's syndrome should be counselled cautiously about the expectation of a strongly positive effect of treatment on adult height. Completion of the randomised controlled trials to adult height is needed to establish the effect of growth-hormone supplementation on adult height in Turner's syndrome and the psychological effect of treatment.

Adult↗
PubMed1996

Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster.

The triple A or Allgrove's syndrome (MIM*231550) is an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. Since its first description by Allgrove et al. (1978) more than 70 cases from all over the world have been reported. The syndrome manifests itself during the first decade of life with severe hypoglycaemic episodes which can cause sudden death. The frequent association with neurological disorders presenting as a mixed pattern of upper and lower motor neuropathy, sensory impairment, autonomic neuropathy and mental retardation may result in a severely disabling disease. As an additional feature some patients have hyperkeratosis of their palms and soles. We have performed a systematic genome linkage scan in eight triple A families of which three were consanguineous [including the large highly inbred kindred described by Moore et al. (1991)]. We obtained conclusive evidence for linkage of the triple A syndrome locus to markers on chromosome 12q13 (D12S368, theta max = 0, Zmax = 10.81) with no indication of genetic heterogeneity. Haplotype and multipoint analyses suggest that the gene is located on a chromosomal segment flanked by the markers D12S1629 and D12S312 which are 6 cM apart. This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes.

Adrenal Insufficiency↗
PubMed1996

Mortality in Canadian children with growth hormone (GH) deficiency receiving GH therapy 1967-1992. The Canadian Growth Hormone Advisory Committee.

The objective of this study was to determine the risk of death and potential for prevention of mortality in a large population of children with growth hormone deficiency (GHD). The Canadian GH Advisory Committee registry was initiated in 1967 to include all persons in Canada treated with pituitary-derived GH (1967-1985). Since 1985, the registry has been maintained for continuous surveillance of those treated with biosynthetic GH. Thirty-seven children have died out of a total of 1366 children treated for GHD in the 25 years up to December 31, 1992. Individual cases were reviewed for circumstances before death and autopsy information. The likelihood of individual deaths being caused by potentially preventable endocrine causes was graded on a scale of 1-5. Survival curves were analyzed for the children with idiopathic GHD and craniopharyngioma. Age- and sex-specific mortality rates for children with idiopathic GHD were compared with those of the general population. The overall crude mortality rate was 2.7%. The most frequent cause of mortality was tumor recurrence (11/37). A surprisingly high proportion of deaths (9/37) were caused by the preventable endocrine complications of adrenal crisis and hypoglycemia. Children with idiopathic GHD receiving GH therapy had similar age- and sex-specific mortality rates compared with general population rates, except in a high-risk subgroup of males diagnosed with GHD before 2 yr of age. The highest mortality occurred in children with GHD secondary to craniopharyngioma. We concluded that preventable sudden deaths caused by adrenal crisis continue to occur in children with hypopituitarism. A high level of vigilance must be maintained in this population.

Adolescent↗
PubMed1995

A deletion at the UL/IR junction reduces pseudorabies virus neurovirulence.

A recombinant pseudorabies virus (PRV), designated LLT beta delta 2, which contains a 3-kbp deletion spanning the junction of the unique long and internal repeat sequences was constructed. Compared with the parental strain and a virus rescued for the deleted sequences, LLT beta delta 2 exhibited similar replication characteristics in tissue culture. When inoculated intranasally in swine, LLT beta delta 2 was significantly reduced in virulence and did not produce neurological signs characteristic of PRV infection. LLT beta delta 2 replicated efficiently at the site of inoculation and in peripheral nervous tissues, but replication was restricted in the central nervous system. These results indicate the presence of a PRV neurovirulence determinant in the vicinity of the junction.

Animals↗
PubMed1995

Viral determinants of the variable sensitivity of herpes simplex virus strains to gD-mediated interference.

Cells that express glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) resist infection by HSV-1 and HSV-2 because of interference with viral penetration. The results presented here show that both HSV-1 and HSV-2 gD can mediate interference and that various HSV-1 and HSV-2 strains differ in sensitivity to this interference. The relative degree of sensitivity was not necessarily dependent on whether the cell expressed the heterologous or homologous form of gD but rather on the properties of the virus. Marker transfer experiments revealed that the allele of gD expressed by the virus was a major determinant of sensitivity to interference. Amino acid substitutions in the most distal part of the gD ectodomain had a major effect, but substitutions solely in the cytoplasmic domain also influenced sensitivity to interference. In addition, evidence was obtained that another viral gene(s) in addition to the one encoding gD can influence sensitivity to interference. The results indicate that HSV-1 and HSV-2 gD share determinants required to mediate interference with infection by HSV of either serotype and that the pathway of HSV entry that is blocked by expression of cell-associated gD can be cleared or bypassed through subtle alterations in virion-associated proteins, particularly gD.

Amino Acid Sequence↗
PubMed1994

Identification of the pseudorabies virus UL4 and UL5 (helicase) genes.

The DNA sequence of the left end of the pseudorabies virus (PRV) BamHI-G fragment and a short adjacent sequence from the BamHI-C fragment (0.641-0.664 map units) were determined. Two open reading frames were identified and designated PRV UL4 and UL5 because they exhibit amino acid sequence homology to the herpes simplex virus type 1 UL4 and UL5 open reading frames. The PRV UL4 open reading frame codes for a 145-amino acid polypeptide of unknown function. The deduced PRV UL5 gene product is 833 amino acid residues and exhibits sequence characteristics of a helicase, including six sequence motifs which are conserved for a superfamily of helicases. PRV UL5 also contains a putative leucine zipper motif which is not present in other herpesvirus helicase sequences. PRV UL4 and UL5 are transcribed in the opposite orientation with respect to the UL1, UL2, UL3, and UL3.5 gene cluster located at the right end of BamHI-G.

Amino Acid Sequence↗
PubMed1994

Single amino acid substitutions in gD of herpes simplex virus 1 confer resistance to gD-mediated interference and cause cell-type-dependent alterations in infectivity.

Previous studies have shown that cell-associated herpes simplex virus (HSV) glycoprotein gD can interfere with infection of the cells by HSV and other alphaherpesviruses and that HSV mutants resistant to this gD-mediated interference can be isolated. Here we report that HSV mutants selected for resistance to gD-mediated interference are altered in specific infectivity for cells that do not express gD. Two independently derived mutants were shown to be impaired in ability to infect HEp-2 cells and enhanced in ability to infect Chinese hamster ovary cells, compared with the wild-type parental strain. The mutants were not significantly different from the parental strain in ability to bind to cells but differed in a postbinding step required for infectivity, probably penetration. The two mutants were shown to have different amino acid substitutions (Q27P and Q27R) in gD. Marker transfer experiments demonstrated that the resistance to gD-mediated interference as well as the altered infectivities resulted from these amino acid substitutions. Thus, small changes in gD structure can not only confer resistance to gD-mediated interference but also alter the relative efficiencies with which HSV penetrates into different cell types.

Amino Acid Sequence↗
PubMed1994

Primary hypothyroidism with intracranial hypertension and pituitary hyperplasia.

A 12-year-old girl presented with primary hypothyroidism, secondary pituitary hyperplasia, and intracranial hypertension. Cranial computed tomography revealed a sellar mass with suprasellar extension. She responded to medical treatment. Intracranial hypertension may be associated with primary hypothyroidism prior to thyroxine treatment. Because significant pituitary hyperplasia can be associated with primary hypothyroidism, it is vital to have endocrine investigation prior to consideration of surgical removal of an apparent pituitary tumor.

Cerebrospinal Fluid Pressure↗
PubMed1993

Prevention of insulin-dependent diabetes mellitus by 2'-deoxycoformycin in the BB Wistar rat.

The effect of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) on the development of insulin-dependent diabetes mellitus (IDDM) was assessed in the BB Wistar rat. Sixty-one male rats were treated from days 30 to 120 with 0, 0.5, 1.0 or 1.5 mg dCF/kg/week. The incidence of IDDM was 78% in the controls and was significantly (P < 0.01) decreased in rats receiving 1.5 mg dCF/kg/week (32%), but not in rats receiving lower doses of the drug. However, for those rats that became diabetic the mean time to the development of IDDM was unchanged in animals receiving dCF compared with control. dCF treatment did not produce significant weight loss in the animals or gross changes in the thymus, spleen or kidneys. Although the protective effect of dCF against IDDM was likely produced by immunosuppression, the different dCF dosages had similar effects on ADA suppression in spleen or thymus and on dATP accumulation in these organs.

Adenosine Deaminase Inhibitors↗