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Biomedical subjects

D Simmons

Publications and source records attributed to D Simmons.

At least 55 records · Page 3Linked to original sources

Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins.

Neuropilins are receptors for class 3 secreted semaphorins, most of which can function as potent repulsive axon guidance cues. We have generated mice with a targeted deletion in the neuropilin-2 (Npn-2) locus. Many Npn-2 mutant mice are viable into adulthood, allowing us to assess the role of Npn-2 in axon guidance events throughout neural development. Npn-2 is required for the organization and fasciculation of several cranial nerves and spinal nerves. In addition, several major fiber tracts in the brains of adult mutant mice are either severely disorganized or missing. Our results show that Npn-2 is a selective receptor for class 3 semaphorins in vivo and that Npn-1 and Npn-2 are required for development of an overlapping but distinct set of CNS and PNS projections.

Age Factors↗

Cloning, characterization and immunolocalization of human ameloblastin.

Amelogenesis imperfecta is a broad classification of hereditary enamel defects, exhibiting both genetic and clinical diversity. Most amelogenesis imperfecta cases are autosomal dominant disorders, yet only the local hypoplastic form has been mapped to human chromosome 4q between D4S242 1 and the albumin gene. An enamel protein cDNA, termed ameloblastin (also known as amelin and sheathlin), has been isolated from rat, mouse and pig. Its human homolog has been mapped to chromosome 4q21 between markers D4S409 and D4S400, flanking the local hypoplastic amelogenesis imperfecta critical region. Therefore, ameloblastin is a strong candidate gene for this form of amelogenesis imperfecta. To facilitate genetic studies related to this dental disease, we isolated and characterized a human ameloblastin cDNA. A human third molar cDNA library was screened and two ameloblastin clones identified. Nucleotide sequencing of these cDNAs indicated alternative splicing of the putative open reading frame, use of different polyadenylation signals, and a high degree of similarity to reported rat, mouse and porcine cDNAs. Immunohistochemistry studies on embryonic human teeth using an antibody to recombinant ameloblastin indicated ameloblastin expression by ameloblasts with localization in the enamel matrix associated with the sheath structures.

Alternative Splicing↗

Enamelin maps to human chromosome 4q21 within the autosomal dominant amelogenesis imperfecta locus.

Amelogenesis imperfecta is a group of hereditary enamel defects. Of the autosomal dominant forms, only the local hypoplastic type has been mapped to human chromosome 4q 13-4q21. Enamelin is a large enamel matrix protein secreted by ameloblasts. The purpose of this study was to determine the human chromosomal localization of enamelin to establish an association with various forms of amelogenesis imperfecta. Chromosomal mapping was performed by polymerase chain reaction (PCR) amplification using somatic hybrid and deletion/derivation cell line panels with an enamelin primer set based on 100% conserved regions between pig and mouse cDNAs. Sequence-tagged site content mapping using eight markers within the critical local hypoplastic amelogenesis imperfecta region was then performed using an isolated human enamelin genomic BAC clone. The human enamelin amplicon was confirmed by DNA sequence analysis, revealing 81% and 73% identity to pig and mouse cDNAs, respectively. PCR amplification using a somatic cell hybrid panel placed enamelin on chromosome 4 with analysis of a regional chromosome 4 mapping panel refining the localization to 4q 13.1-q21.23. An identified human enamelin BAC genomic clone was shown to contain markers D4S2604 and D4S2670, as well as the first exon of the human ameloblastin gene, placing enamelin in the critical amelogenesis imperfecta locus between markers HIS1 and D4S2604 at 4q21. Our results suggest that enamelin is a strong candidate gene for this disease. Furthermore, human 4q21 may contain a second cluster of enamel matrix genes located proximally to the identified cluster of dentin and bone genes.

Amelogenesis Imperfecta↗

Roles and activities of the Commonwealth Government University Departments of Rural Health.

Since 1996, University Departments of Rural Health (UDRH) have been established at Broken Hill, Mount Isa, Shepparton, Launceston, Whyalla, Alice Springs and Geraldton. Each UDRH is underpinned by Commonwealth funding for an initial period of 5 years. The role of the UDRHs is to contribute to an increase in the rural and remote health workforce through education and training programs, as well as a reduction in the health differentials between rural and urban people and between indigenous and non-indigenous peoples. A strong population health focus involving partnerships between existing health providers in a targeted region and the university sector underpins their operation. While UDRHs have been established as a means of addressing a national workforce problem, their organisational arrangements with universities and local service providers vary widely, as does the program mix of activities in education, research service development, facilitation and advocacy. This article outlines some of the activities and progress of the UDRHs to date.

Australia↗

The development of a national agreed minimum diabetes dataset for New Zealand.

The development of a minimum diabetes dataset (MDD) for monitoring diabetes in New Zealand was intended to facilitate diabetes quality initiatives. Existing published datasets were reviewed and a draft MDD for New Zealand was distributed to all 147 specialist, general practice and relevant community groups. Data definitions were either identical or compatible with other datasets and dataset items included if there were at least six supportive replies. All groups were followed up by letter and telephone. A total of 26 (18%) replies were received. Comments were reviewed and the recommended MDD finalised. There was agreement that this dataset would be embedded into the software of at least three commercially available patient management systems. In conclusion, developling an agreed national MDD was difficult, in spite of its potential utility for local, regional and national collation of diabetes data allowing those involved to generate a picture of diabetes and its outcomes.

Database Management Systems↗

Incidence and risk factors for neonatal hypoglycaemia among women with gestational diabetes mellitus in South Auckland.

AIMS: To describe the incidence and risk factors for neonatal hypoglycaemia among the offspring of women with gestational diabetes mellitus (GDM) in South Auckland, New Zealand METHODS: A retrospective audit was undertaken of singleton pregnancies delivered between 1991 and 1994. Data were obtained for 373 women and their deliveries (57 European, 76 Maori, 198 Pacific Islands, 42 other). RESULTS: Pacific Islands women were most likely to have large babies with neonatal hypoglycaemia in spite of a high use of insulin. Postnatally Maori and Pacific Islands women had a high incidence of Type 2 diabetes mellitus (21.4, 21.7 vs. 4.3% Europeans, 12.0% others, P =0.035). Babies experiencing hypoglycaemia were more likely to have a mother with past GDM (51.2 vs. 27.2%, P = 0.01) and greater hyperglycaemia (at diagnosis fasting 6.8 +/- 1.7 vs. 5.7 +/- 1.1 mmol/l, P < 0.001; finger-prick glucose 5.7 +/- 1.0 vs. 5.2 +/- 0.8 mmol/l, P < 0.001). Macrosomia, Caesarian section and special care baby unit admission were more common in pregnancies complicated by neonatal hypoglycaemia. CONCLUSIONS: Maternal hyperglycaemia was a major contributing factor to neonatal hypoglycaemia in this population. Undiagnosed Type 2 diabetes was common among Maori and Pacific Islands women, confirming the need for earlier detection and treatment.

Adult↗

Capture-recapture, epidemiology, and list mismatches: two lists.

In recent years, capture-recapture methods for closed populations have been extensively applied to epidemiology. For example, suppose we have several incomplete lists of diabetics and we wish to estimate the total number of diabetics by estimating the number missing from all the lists. A major problem is that the information about individuals on the lists may have been given incorrectly or the information may have been typed incorrectly so that some list matches are missed. Using the concept of tag loss borrowed from animal population studies, we consider methods for estimating both the probabilities of making list errors and the population size for just two independent lists. The effect of heterogeneity on the errors is examined. The methods are applied to a large data set of diabetic persons consisting of a list obtained from a survey and a list obtained from doctors' records. It was found that the error rates were high and that ignoring the errors led to a gross overestimate of the total number of diabetic persons.

Biometry↗

Frequency-dependent effect of nitric oxide donor nitroglycerin on bone.

Recently, we showed that supplementation with nitric oxide (NO) via donor nitroglycerin (NG) alleviated the ovariectomy and corticosteroid-induced bone loss in rats. In humans, high doses or frequent applications of NG (i.e., for angina) lead to rapid loss of its efficacy in relieving angina. To examine whether there is a similar effect on the loss of efficacy of NG on bone, we examined the frequency-dependent effects of NG on bone mineral density (BMD), bone mass, trabecular bone volumes (BV/TV), and blood pressure in rats. Thirty 7-month-old female Brown Norway rats underwent ovariectomy, and an additional six rats were sham-operated. The ovariectomized rats were treated either with vehicle (ovariectomized control), 17beta-estradiol (E2; positive control), or 0.2 mg NG (via dermal application) once, twice, or three times a day. Before and at the end of the 10-week treatment period, BMD of the lumbar spine was measured by dual-energy X-ray absorptiometric (DXA) scanning and expressed as a percentage change. BMD in ovariectomized rats was significantly lower (-2.5 +/- 2.0%) compared with the sham-operated rats (+6.3 +/- 5.3%; p < 0.01). Estrogen therapy completely abolished the ovariectomy-induced potential bone loss (+5.9 +/- 3.4%). Application of NG once daily also completely prevented (+6.2 +/- 2.8%; p < 0.01) the ovariectomy-induced bone loss (i.e., it was as effective as estrogen). However, the beneficial effects of NG on BMD were significantly reduced with increased frequency of application of NG (+1.9 +/- 2.1%, twice a day and -0.2 +/- 3.3% three times a day). Estrogen or once daily administration of NG preserved femur weights, BV/TV, and decreased urinary deoxypyridinoline levels as expected. However, a higher level of serum osteocalcin and bone-specific alkaline phosphatase levels were maintained only with once daily administration of NG. There were no adverse effects of these doses of NG on blood pressure, but a tendency to lower blood pressure was noticed with increased frequency of NG. These results confirmed our previous findings that NO donors counteract the bone loss associated with estrogen deficiency. However, these beneficial effects of maintaining BMD are lost with increased frequency of NG application.

Animals↗

Prevalence and characteristics of diabetic patients with no ongoing care in South Auckland.

OBJECTIVE: To describe the prevalence of default from diabetes care and to reveal associated characteristics among patients with known diabetes in urban South Auckland, New Zealand. RESEARCH DESIGN AND METHODS: We developed a cross-sectional household study of patients with known diabetes and compared those patients with and without ongoing care. Ongoing care was defined as having been clinically reviewed at least once in the previous 10 months. RESULTS: Of the 1,488 European, Maori, and Pacific Islander subjects with known diabetes, 107 (6.3%) had not seen a general practitioner or a diabetes service in the previous 10 months. Subjects not attending a diabetes service were more likely than subjects attending a diabetes service to have been diagnosed when screened asymptomatically (11.7 vs. 5.2%, P = 0.008) and after gestational diabetes (39.7 vs. 11.7%, P < 0.001). Maori were most likely to have no ongoing care (10.8 vs. 5.8% European and 6.6% of Pacific Islander subjects, P = 0.01). Nonattenders were younger, were diagnosed at a younger age, knew less about diabetes, were less satisfied with past care, and were less likely to require medication. CONCLUSIONS: The elevated number of diabetic individuals not attending ongoing care is a significant problem in this population, and it may reflect a decisional balance as seen in problem behaviors. Diagnosis when asymptomatic may contribute to default from ongoing care; in this case, caution is required if population-based screening programs are being considered.

Adult↗

Can medication packaging improve glycemic control and blood pressure in type 2 diabetes? Results from a randomized controlled trial.

OBJECTIVE: To assess the impact of calendar blister pack (CBP) use on glycemic and blood pressure control. RESEARCH DESIGN AND METHODS: We conducted an 8-month randomized controlled double-blind study among diabetic patients with poor glucose control (HbA1c >9.0%) in an urban area of South Auckland, New Zealand, with a high proportion of Maori and Pacific Islands people. Subjects included 68 consecutive patients, of whom 50% were prescribed three or more medications per day RESULTS: HbA1c was reduced by 0.95+/-0.22% in the CBP group and 0.15+/-0.25% in the control group (P = 0.026). Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group (P = 0.0041). Systolic blood pressure did not change significantly CONCLUSIONS: CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications.

Antihypertensive Agents↗

Managers' tactics of influence: perceptions of regular and temporary employees.

The paper concerns managers' perceived influence tactics with regular and temporary employees. 156 subordinates completed the Behavioral Alteration Techniques Scale. Mean ratings of managers' use of tactics of influence with regular employees were significantly higher than those with temporary employees on 9 of the 22 measured techniques.

Communication↗

When time is muscle.

Explore the source record for details and available documents.

Emergency Medical Services↗

The personal costs of diabetes: a significant barrier to care in South Auckland.

AIM: To estimate the out-of-pocket expenses associated with diabetes care and their impact on self-care activities in inner urban South Auckland. METHODS: Follow-up, cross-sectional household survey among 1629 residents with known diabetes. A brief questionnaire was completed during either two consecutive mail surveys or a subsequent household visit to diabetic patients identified in a previous household survey. RESULTS: Responses were obtained from 802 (75%) of the 1075 subjects remaining resident in the area. Median annual costs of scripts, shoes, clinic and general practice visits ranged between $191-$329 depending on ethnic group. Costs were higher among males, those requiring insulin therapy and those aged under 60 years. A significant proportion of subjects reported that these costs prevented regular self-blood-glucose monitoring (18-49%), self-medication (11-47%) and regular insulin therapy among insulin-treated patients (8-52%). CONCLUSIONS: The out-of-pocket expenses associated with diabetes remain a substantial portion of disposable income and a barrier to the prevention of diabetes-related complications. These data support the provision of preventive diabetes care at no cost to the patient at the point of care.

Adult↗

Community networking as a means for identifying people with diabetes in a rural, predominantly bicultural community in New Zealand.

AIMS: To assess the use of community networking to estimate the prevalence of diabetes in a predominantly New Zealand Maori and European community. METHODS: A cross-sectional survey of people with known diabetes identified either through general practice or community networks (others with diabetes, public notices or public meetings) was undertaken. Ascertainment was compared using capture-recapture methods for two independent samples. RESULTS: Overall ascertainment by community networking was greater for Maori than Europeans (40 +/- 3% vs 15 +/- 2%, p < 0.001). Ascertainment using general practice registers was comparable in the two ethnic groups (48 +/- 4% vs 55 +/- 5%, respectively). Women were more likely than men to be contacted through community networking (odds ratio 1.47, 1.05-2.06). CONCLUSION: In closely knit communities, community networking provides an independent source for estimating the prevalence of diabetes.

Community Health Planning↗

Prevalence of known diabetes in different ethnic groups in inner urban South Auckland.

AIM: To describe the prevalence of known diabetes in different ethnic groups in inner urban South Auckland. METHOD: Cross-sectional household survey of 27,419 residences in the multi-ethnic community of inner urban South Auckland 1992-1995. RESULTS: Responses from 91.3% of households included 90,477 residents, 1862 (2.1%) of whom had diabetes. The all-age adjusted prevalence of known diabetes was 1.9 (1.7-2.0)% in Europeans, 5.2 (4.9-5.5)% among Maori, 4.0 (3.8-4.2)% among Pacific Islands people and 4.3 (3.8-4.9) 2% among other ethnic groups. There was heterogeneity within the Pacific Islands and "other" groups with the highest prevalence present in South Asians, Niueans and those from the Middle East. A non-significantly lower prevalence of diabetes was found among Chinese respondents. These data predicted 85,581 people with known diabetes in New Zealand in 1996. The greatest growth, due to demographic changes alone (i.e. without taking account of the known increased incidence of diabetes), was predicted among non-European, non-Polynesian groups, with a 181% increase in numbers with diabetes since 1991. CONCLUSION: Demographic pressures have been sufficient to increase the number with known diabetes by 13.9% in five years. This would have underestimated the epidemic in view of the observed growth in the age-adjusted incidence of diabetes in overseas studies.

Adolescent↗