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Biomedical subjects

D Simmons

Publications and source records attributed to D Simmons.

At least 109 records · Page 6Linked to original sources

Massive osteolysis of the skull and upper cervical spine. Case report and review of the literature.

Massive osteolysis is a type of idiopathic osteolysis in which there is spontaneous onset of bone resorption. Almost any bone in the body can be affected. The authors present the case of a 62-year-old man diagnosed with massive osteolysis of the occipital bone and the upper two cervical vertebrae. Despite extensive pneumocephalus, no neurological sign or spinal instability was evident. In this case 4000 cGy of radiation in 200-cGy fractions was administered to the diseased area while the patient was kept in a Miami-J collar. At the 2-year follow-up examination, arrest of the disease process and new bone formation was evident on radiographic studies.

Cervical Vertebrae↗

A pilot diabetes awareness and exercise programme in a multiethnic workforce.

AIMS: To evaluate the acceptability and impact of a pilot diabetes awareness and exercise programme in a mainly Polynesian workforce. METHOD: Comparison of change in questionnaire and anthropometric measurements in two hospital ancillary workforces. One group (n = 108) received one community diabetes educator presentation, one video presentation and a 4 month exercise programme. The other group (n = 99) served as controls. RESULTS: Baseline diabetes knowledge was poor (total score 26 (SD 13%)) and subjects were largely unfit with a high body mass index (31.5 (7.1) kg/m2). The exercise sessions were well attended, although attendance declined over the 4 months. Increased diabetes knowledge was retained in the intervention group after 6 months when compared with controls (total score 35(14)% vs 26(12)% respectively, p < 0.001). One month after the termination of the programme, the proportion reporting regular exercise activity (at least 30 minutes for 3 days per week) had increased by 2% in the intervention group but declined by 9% in the control group (p < 0.05). CONCLUSIONS: Diabetes knowledge and exercise can be increased in unfit subjects by the combination of culturally tailored exercise techniques and community diabetes educator/video presentations.

Adult↗

Diabetes and hyperglycaemia among patients with congestive cardiac failure in a multiethnic population.

AIM: To determine the proportion of patients with congestive cardiac failure (CCF) who also have known diabetes. METHOD: A retrospective review was undertaken of the charts of a randomly selected 30% of patients with congestive cardiac failure without myocardial infarction, and all patients with congestive cardiac failure with myocardial infarction, who attended Middlemore Hospital between 1 October 1992-30 September 1993. RESULTS: Congestive cardiac failure was coded as present in 1130 (15%) of admissions for 887 (16%) patients. Myocardial infarction had occurred in 106 (12%) of these cases. European patients were older, were more likely to have a past history of angina or acute myocardial infarction (38.6% vs 13.1% Maori, 4% Pacific Is, p < 0.001) and less likely to have known diabetes (Europeans 17% vs 34% Maori, Pacific Is 36%, p < 0.05). Among those aged 40-59 years, the proportion of Maori and Pacific Islands patients with known diabetes was around 50%. CONCLUSION: Diabetes is a major risk factor for congestive cardiac failure among Maori and Pacific Islands patients. In contrast with Europeans, ischaemic heart disease is an infrequent risk factor in these patients.

Adult↗

The epidemiology of diabetes and its complications in New Zealand.

New Zealand is a country in the South Pacific with a high proportion of Polynesians. While the prevalence of diabetes appears the same in New Zealand Europeans as Europeans elsewhere, Maori and Pacific Islands people have a 2 to 4-fold excess prevalence of diabetes. Although Europeans make up the majority of diabetic New Zealanders, the greatest concern lies with the Maori and Pacific Islands patients who experience an earlier age at diagnosis, greater obesity, higher rates of smoking (in Maori), poorer diabetes knowledge, poorer glucose control, and more end stage renal failure and blindness. Efforts are now being made to control the current epidemic.

Cardiovascular Diseases↗

A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid.

Lometrexol is an antifolate which inhibits glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for de novo purine synthesis. Extensive experimental and limited clinical data have shown that lometrexol has activity against tumours which are refractory to other drugs, notably methotrexate. However, the initial clinical development of lometrexol was curtailed because of severe and cumulative antiproliferative toxicities. Preclinical murine studies demonstrated that the toxicity of lometrexol can be prevented by low dose folic acid administration, i.e. for 7 days prior to and 7 days following a single bolus dose. This observation prompted a Phase I clinical study of lometrexol given with folic acid supplementation which has confirmed that the toxicity of lometrexol can be markedly reduced by folic acid supplementation. Thrombocytopenia and mucositis were the major toxicities. There was no clear relationship between clinical toxicity and the extent of plasma folate elevation. Associated studies demonstrated that lometrexol plasma pharmacokinetics were not altered by folic acid administration indicating that supplementation is unlikely to reduce toxicity by enhancing lometrexol plasma clearance. The work described in this report has identified for the first time a clinically acceptable schedule for the administration of a GARFT inhibitor. This information will facilitate the future evaluation of this class of compounds in cancer therapy.

Acyltransferases↗

Prostaglandin H synthase-2 in human gestational tissues: regulation in amnion.

Using reverse transcriptase-polymerase chain reaction we have established that mRNAs for prostaglandin H synthases 1 and 2 (PGHS-1 and PGHS-2) are present in amnion, chorion and decidua from women both at term before and after the onset of labour and from women at 28-35 weeks of gestation before the onset of labour. By Western blot analyses we have demonstrated that epidermal growth factor, interleukin 1 beta and phorbol 12-myristate 13-acetate all increase PGHS-2 amounts in amnion cells. The degree of stimulation caused by these substances (218-311 per cent) is less than the increase in prostaglandin production usually generated (five- to 10-fold). Hence we believe that these substances may have multiple sites of action in the pathways of arachidonic acid metabolism.

Amnion↗

Ethnic differences in diabetes care in a multiethnic community in New Zealand.

Residents of two districts of South Auckland, New Zealand with a high proportion of Maori and Pacific Islands people were visited door to door to ascertain the prevalence of known diabetes and its tissue damage. The household survey canvassed 55,518 residents in 12,770 (91%) of 14,002 residences. Diabetes interviews were available for 176,214 (82%) Europeans, 286,336 (85%) Maori and 495,585 (85%) Pacific Islands diabetic patients. Europeans were older than Maori and Pacific Islands patients currently and at diagnosis. When compared with Europeans, Maori and Pacific Islands patients had a higher chance of having had their diabetes diagnosed in pregnancy, were least likely to be receiving antihypertensive or insulin therapy, were more likely to be blind, and were more likely to have received retinal photocoagulation. There were no ethnic differences in either the proportion of those receiving no ongoing care or in the proportion seen at least once by the diabetes services. Maori people were most likely to be current smokers, were most likely to have defaulted from the diabetic diet and to be dissatisfied with the diabetes service. Pacific Islands people were least likely to have neuropathic symptoms in their feet or to report a known myocardial infarction. Significant ethnic differences in diabetes and its care exist in South Auckland.

Adult↗

What happens to women with preeclampsia? Microalbuminuria and hypertension following preeclampsia.

There is little published data on the incidence of remote hypertension, microalbuminuria (a possible marker of remote cardiovascular events) and diabetes following preeclampsia. This is of particular importance in Pacific Island populations as they have a high rate of preeclampsia, non-insulin dependent diabetes and cardiovascular related deaths. The aim of this study was to compare the rate of microalbuminuria and hypertension in 50 Samoan women with past preeclampsia (cases) with 50 Samoan women who did not have past preeclampsia (controls). Forty per cent of cases were hypertensive at follow-up compared to 2% in the control group (p < 0.0001). Microalbuminuria or proteinuria occurred in 40% of women with past preeclampsia and 18% of controls (p < 0.02). Half of the cases with microalbuminuria were hypertensive. No case or control had an elevated fructosamine, suggesting that current diabetes was an unlikely explanation for the microalbuminuria. We conclude that Samoan women with past preeclampsia are at increased risk of developing chronic hypertension and microalbuminuria. The significance of the microalbuminuria after preeclampsia is not known, but it may be a marker of either remote cardiovascular morbidity or non-insulin dependent diabetes. This study raises longterm health implications for women with preeclampsia.

Adult↗

The effects of computer-assisted versus teacher-directed instruction on the multiplication performance of elementary students with learning disabilities.

The acquisition of multiplication facts by 4 elementary students with learning disabilities was compared under two instructional delivery formats-teacher directed and computer assisted. The two interventions were compared in terms of opportunities to respond and success rate. All students mastered more facts in the teacher-directed condition. In addition, teachers provided many more opportunities to respond and showed a higher success rate than did the software program. Implications of teacher-directed and computer-assisted instruction are discussed in terms of efficacy and feasibility.

Achievement↗

Phase I study of pharmacologically based dosing of carboplatin with filgrastim support in women with epithelial ovarian cancer.

PURPOSE: The aim of this study was to increase the dose intensity of carboplatin in women with International Federation of Gynecology and Obstetrics (FIGO) Stage Ic-IV epithelial ovarian cancer with the use of granulocyte colony-stimulating factor (G-CSF; filgrastim; Amgen, Thousand Oaks, CA). PATIENTS AND METHODS: A phase I study of escalating target area under the curves (AUCs) of carboplatin with G-CSF (filgrastim) ws undertaken. The target AUCs were 5 mg/mL.min every 21 days for four cycles, 5 mg/mL.min every 14 days for four cycles, 7 mg/mL.min every 14 days for four cycles, 9 mg/mL.min every 14 days for four cycles, and 11 mg/mL.min every 14 days for four cycles. G-CSF was given at a dose of 5 microg/kg/d starting 24 hours after carboplatin administration and lasting until 24 hours before the next cycle and until day 14 after the last cycle. RESULTS: We were able to escalate to an AUC level of 9 mg/mL.min every 14 days for four cycles. At this dose, severe thrombocytopenia, that necessitated dosage delays, and failure to give subsequent cycles of carboplatin were observed. We then reduced the AUC level to 8 mg/mL.min every 14 days for four cycles. However, severe thrombocytopenia was also observed at this level. CONCLUSION: An AUC of 7 mg/mL.min every 14 days for four cycles is the maximum tolerated AUC level that can be achieved with G-CSF. Further escalations may be possible using either combinations of cytokines or peripheral stem-cell collections.

Adult↗

Dentin matrix protein-1, a candidate gene for dentinogenesis imperfecta.

Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have determined linkage between DGI type II and group-specific component (Gc, vitamin D binding protein), interferon (gamma)-induced cytokine protein 10 (INP10) and secreted phosphoprotein 1 (SSP1, osteopontin, bone sialoprotein 1, early T-lymphocyte activation 1). Therefore, the gene locus has been localized to the long arm of human chromosome 4 in the region 4q13-q21. Dentin matrix protein-1 (DMP-1, AG-1) is a new acidic, phosphorylated dentin extracellular matrix protein which has recently been identified by cDNA cloning. The purpose of this study was to establish the possible association of DMP-1 with DGI type II by determining the human chromosomal localization of this protein. A DMP-1 DNA probe was generated1using PCR amplification of the mouse full-length DMP-1 and labeled with [32P] d-CTP. A panel of rodent somatic cell hybrid clones, previously cytogenetically characterized, was used for the assignment. High stringently DNA hybridization studies and analysis of the chromosomal cell panel indicated that the DMP-1 gene locus is located on human chromosome 4. This data supports the hypothesis that DMP-1 is a candidate gene for the genetic disease DGI type II. This is based on chromosomal localization to human chromosome 4, the expression of DMP-1 mostly by odontoblasts, and its purported physical-chemical properties.

Animals↗

The distribution of the deleted in colon cancer (DCC) protein in human tissues.

A gene called deleted in colon cancer (DCC) has been identified on a region of chromosome 18, which is deleted in 70% of colorectal cancers. The DCC gene encodes a protein belonging to the immunoglobulin superfamily with similarity to the N-CAM transmembrane proteins and is a putative tumor-suppressor gene. Alternative splicing of transcripts of transmembrane proteins, including N-CAM, is known to occur, resulting in different isoforms of the protein. Using five antibodies against the DCC gene product (three monoclonal antibodies raised in our laboratory, one commercially available antibody, and a rabbit polyclonal antibody), we have demonstrated by immunostaining a DCC protein isoform in reticuloendothelial cells in human thymus, tonsil, and lymph node. This can be distinguished from another isoform described in normal colonic epithelium, because this latter is not demonstrable with the antibodies we have used. It could not be detected in normal colonic epithelium, polyps or colorectal carcinomas. This restrictive distribution suggests that not all DCC gene products are important in colonic cancer.

3T3 Cells↗

Foot care among diabetic patients in south Auckland.

AIM: To describe footcare among diabetic patients in south Auckland. METHOD: Direct interview of 331 European, 86 Maori and 123 Pacific Islands patients attending local diabetes services and a stratified subsample of general practitioners. Interviews included closed and open questions of diabetes knowledge, demographic and medical history and were followed by a thorough inspection of the feet. RESULTS: Major lesions (amputation, foot ulcer) and predisposing lesions (callus or fungal infection/maceration) were present in 48.5% of patients. Major lesions were particularly common among Pacific Islands patients (9.4%) vs European (3.9%), Maori (5.5%), (p < 0.05). Fungal infection/maceration was less common among Pacific Islands patients (23.0%) vs 42.3%, 42.2% respectively, (p < 0.001). Fungal infection/maceration was more common and callus formation less common among men when compared with women. Forty percent (n = 214) of patients, including eight with either an ulcer or a blister, had not had their feet examined over the preceding 12 months. Good foot care was present in 52.7% Europeans, 31.0% Maori and 26.8% Pacific Islands patients (p < 0.001). Diabetes knowledge was poorest in those with poor foot care among Europeans and Maori. CONCLUSION: While the provision of footcare advice, adherence to such advice and monitoring of footcare remain uneven, the hospital and community costs of the diabetic foot will continue to be high.

Adolescent↗

Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon.

Adhesion molecules are involved in facilitating cell-mediated immune events. Because lymphocyte-epithelial cell interaction has been implicated in the pathogenesis of colonic inflammation, we analysed expression of a range of adhesion molecules on colonic epithelium in vitro and in vivo using flow cytometry, immunohistochemistry and in situ hybridization. Expression of ICAM-1 by cell lines HT29 and int407 was increased by proinflammatory cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1 but not by IL-6. Vascular cell adhesion molecule (VCAM) and E-selectin were not expressed. Immunohistochemistry using sections of inflamed colon from 16 patients with ulcerative colitis (UC), five patients with Crohn's disease (CD) and seven patients with normal colonoscopic biopsies, showed no expression of ICAM-1 on colonic epithelium. VCAM was seen in isolated lymphoid aggregates and E-selectin was expressed on endothelium. In situ hybridization showed no ICAM-1 or ICAM-3 mRNA in colonic epithelium. B7, the ligand for CD28, was not found on normal or inflamed colonic epithelium. The adhesion molecules ICAM-1, ICAM-3 and B7 are not involved in lymphocyte-epithelial cell interaction in the normal or inflamed colon. This may have implications for the development of T cell tolerance to intestinal luminal antigens.

Antigen-Presenting Cells↗