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Biomedical subjects

D Hunter

Publications and source records attributed to D Hunter.

At least 55 records · Page 3Linked to original sources
PubMed2000

A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.

Aged↗
PubMed2000

Predictors of CD4+ lymphocyte count among HIV-seropositive and HIV-seronegative pregnant women in Dar es Salaam, Tanzania.

OBJECTIVE: To determine the predictors of CD4+ lymphocyte count among pregnant women in Dar es Salaam, Tanzania. METHODS: Between 04/1995 and 03/1997, HIV-seropositive (n=1,027) and HIV-seronegative (n=280) pregnant women were interviewed to obtain socio-demographic characteristics. Later, blood samples was collected for determination of T-lymphocyte subsets and other haematological indices. RESULTS: CD4+ lymphocyte count was significantly higher among HIV-seronegative women (mean=770 cells/mm3, standard deviation (SD)=232 cells/mm3) than HIV-seropositive women (mean=422 cells/mm3, SD=205 cells/mm3). Most HIV-seropositive women were asymptomatic, in WHO clinical stage 1 (84.3%). Among HIV-seropositive women, total white blood count (WBC) and erythrocyte sedimentation rate (ESR) remained significantly correlated with CD4+ after adjusting for other predictors in multivariate analyses. For women of average age 25 years, the CD4+ lymphocyte count increased by about 16 cells/mm3 for each increment of 1000 WBC cells/mm3, while each 10 mm/hr increase in ESR was associated with a reduction of CD4+ lymphocyte count of about 8 cells/mm3. CONCLUSION: These results show that simple and inexpensive haematological indices cannot be recommended for use as alternative measures of HIV-related immunosuppression in this population of mainly asymptomatic women.

Adult↗
PubMed2000

Susceptibility of elk to lungworms from cattle.

Two studies were conducted to determine the infectivity of the lungworm, (Dictyocaulus viviparus) of cattle origin, in Rocky Mountain elk (Cervus elaphus nelsoni) or wapiti. In the first study, each of three 9-mo-old elk was administered 3,000 D. viviparus larvae from cattle using a nasogastric tube. In the second study, four 16-mo-old elk were each inoculated with 2,000 D. viviparus from cattle using a nasogastric tube. Elk were observed daily for signs of respiratory disease, and fecal samples were collected during the studies and evaluated for lungworm larvae using a modified Baermann technique. One elk was euthanatized during the patent period for recovery of adult lungworms, and three elk were euthanatized after larvae were no longer detected in feces. Lungworm larvae were not detected before inoculation in any of the 16-mo-old elk, but were detected 22 days after inoculation in one elk, 23 days after inoculation in two elk and 24 days after inoculation in all four elk. The prepatent period of this cattle isolate of D. viviparus in elk is therefore 22 to 24 days. The precise prepatent period was not determined in the three 9-mo-old elk, but larvae were detected in all three elk 25 days after inoculation. Numbers of larvae ranged from 1/ to 101/g feces with peak larval detection occurring 32 to 50 days after inoculation. Elk shed larvae from 22 to 83 days after inoculation, and patent periods of the parasite ranged from 24 to 62 days. Clinical signs of respiratory disease, with the exception of mild coughing after exercise, were not observed during the infections. Results from this experiment indicated that D. viviparus larvae of cattle origin can mature in elk and larvae can be passed in large numbers in feces, but this cattle isolate of D. viviparus was not highly pathogenic in elk.

Animals↗
PubMed2000

Musculoskeletal examination teaching in rheumatoid arthritis education: trained patient educators compared to nonspecialist doctors.

OBJECTIVE: To assess whether students taught by trained patients acquire the same levels of competence in musculoskeletal examination skills as students taught by nonspecialist doctors. METHODS: Year 1 Graduate Medical Program (GMP) students (N = 25) at Hospital A were randomized to 8 tutorial groups, each comprising 3-4 students. Groups were taught hand and wrist examination skills by patient educators trained by the Searle Patient Partners in Arthritis program (patient partners). Students at Hospitals B and C (N = 12) remained in their normal tutorial groups, each comprising 3-4 students. Groups at Hospitals B and C were taught hand and wrist examination skills by doctors who had no specialized training in musculoskeletal medicine or orthopedics, with an untrained patient present. RESULTS: Students' mean self-ratings of examination skills before and students' patient partners, and consultants' mean ratings of students' examination skills after the tutorial were summed. Before the tutorial there were no significant differences in level of skill between students at Hospitals A, B, and C as measured by students' self-ratings. After the tutorial all students showed clear gains in levels of skill. Students taught by patient partners had higher levels of skill than those taught by doctors for 3 (p<0.01) and 4 (p<0.05) out of 14 examination skills and all 4 communication skills (p<0.05), as measured by both patient partners' and consultants' ratings. Students taught by doctors showed higher levels of skill for 2 observation skills, but these differences were not significant. CONCLUSION: Patient partners are either equal or superior to doctors not specifically trained in musculoskeletal medicine or orthopedics, in the teaching of musculoskeletal examination techniques and basic communication skills.

Arthritis, Rheumatoid↗
PubMed1999

Quantitative heel ultrasound as a predictor for osteoporosis.

OBJECTIVE: To determine the diagnostic value of quantitative ultrasound (QUS) to predict bone mineral density (BMD) categories as defined by dual-energy x-ray absorptiometry. DESIGN: Cross-sectional survey. SETTING: Rheumatology department of a tertiary care hospital (Royal North Shore Hospital, Sydney, NSW), 1997-1998. SUBJECTS: 326 healthy women aged 45-80 years who had volunteered for a twin study. Our study included both members of non-identical twin pairs but only one randomly selected member of identical twin pairs. MAIN OUTCOME MEASURES: BMD categories as defined by dual-energy x-ray absorptiometry of lumbar spine and left hip, and QUS of calcaneus; sensitivity, specificity and likelihood ratios (LRs) of QUS parameters to diagnose osteoporosis as defined by BMD. RESULTS: The sensitivity of QUS to diagnose BMD osteoporosis varied between 9% and 47%, depending on the QUS parameter. The specificity of QUS was high (88%-100%). If all QUS parameters were normal, osteoporosis was unlikely (LR, 0-0.2). One QUS parameter, broadband ultrasound attenuation (BUA), was highly predictive of osteoporosis by BMD when in the osteoporotic range (LR, infinity), but had low sensitivity (9%). QUS results in the osteoporotic range for other parameters and all QUS results in the osteopenic range were less predictive (LR, 1.0-5.2) of osteoporotic BMD. CONCLUSION: These results suggest that, for most of those tested for osteoporosis by QUS in the community, uncertainty remains about expected BMD.

Absorptiometry, Photon↗
PubMed1999

Emerging recombinant human immunodeficiency viruses: uneven representation of the envelope V3 region.

OBJECTIVE: To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombinant genomes. MATERIALS AND METHODS: The envelope C2-C5 and the gag p24-p7 regions from one hundred infants infected perinatally in Tanzania were compared using phylogenetic and recombination analysis. Exact binomial and Fisher's exact tests were used to assess if various genomic regions were more likely to be overrepresented in intersubtype recombinants. RESULTS: Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) showed exclusively subtype A sequence in gag and env. Subtype C accounted for twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seven infections (37%). The V3 region from subtype A was found in all fifteen A-D recombinants (P = 0.00003) and the V3 region from subtype C was found in all twelve C-D recombinants (P = 0.0002). Conversely, subtype D gag sequences were preferentially represented in the gag of A-D recombinants (P = 0.0003) as well as C-D recombinants (P = 0.002). In A-D recombinants, the V3 region of subtype A was generally surrounded by subtype A C3-C5 sequences. In contrast, the V3 region from subtype C was surrounded by subtype D C3-C5 sequences in C-D recombinants. Significant differences were not found in the number of subtype A or subtype C sequences in A-C recombinants. CONCLUSION: We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombination patterns showed that the V3 region of subtypes A or C was always selected in A-D and C-D recombinants. This selection suggests that the fitness of subtype D-V3 in perinatal transmission may be reduced with respect to V3 from subtype A and/or subtype C. The elevated number of recombinants transmitted perinatally suggests that co-infection or super-infection by two HIV-1 subtypes is not uncommon in this population.

Amino Acid Sequence↗
PubMed1999

Protective immune responses induced by vaccination with an expression genomic library of Leishmania major.

To develop an effective vaccine against the intracellular protozoan parasite Leishmania spp., we investigated the feasibility of expression library immunization (ELI) in the mouse. Genomic expression libraries of L. major were constructed and used to immunize mice. One of the three libraries (L1, with 10(5) clones) induced a significant protective immune response and delayed the onset of lesion development in highly susceptible BALB/c mice after i.m. immunization, compared with control mice immunized with the empty vector (EV). L1 was then divided into five sublibraries of approximately 2 x 10(4) clones each. Mice immunized with one of the sublibraries (SL1A) developed an even stronger protective effect than that induced by L1. SL1A was further divided into 20 sublibraries (SL2) of approximately 10(3) clones each. One of the SL2 libraries (SL2G) induced a strong protective effect against L. major infection. In direct comparative studies, the protective effect of the sublibraries was in the order of SL2G > SL1A > L1. Lymphoid cells from mice vaccinated with SL2G produced more IFN-gamma and NO, compared with cells from control mice injected with EV. Serum from the vaccinated mice also contained more parasite-specific IgG2a Ab, compared with controls. Therefore, these data demonstrate that ELI is feasible against this complex intracellular parasitic infection, by preferentially inducing the development of Th1 responses. Furthermore, by sequential division of the libraries, this approach may be used to enrich and identify protective genes for effective gene vaccination against other parasitic infections.

Animals↗
PubMed1999

Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women.

BACKGROUND: The remarkable similarity of lifestyle and environmental risk factors for type 2 (non-insulin-dependent) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer. We prospectively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976. METHODS: The women, who were enrolled in the Nurses' Health Study, were assessed for history of diabetes at baseline and during follow-up by use of biennial questionnaires. Self-reported diabetes was validated by information obtained from a supplemental questionnaire on symptoms and treatment and was confirmed by medical record review in a sample of the participants. Incident cases of colorectal cancer were ascertained through medical record review. All reported P values are two-sided. RESULTS: During 18 years of follow-up (201061 person-years), we documented 892 new cases of colorectal cancer. After adjustment for age, body mass index (weight in kg/height in m2), physical activity, and other covariates, relative risks (RRs) were 1.43 (95% confidence interval [CI] = 1.10-1.87; P = .009) for colorectal cancer, 1.49 (95% CI = 1.09-2.06; P = .01) for colon cancer, 1.11 (95% CI = 0.56-2.21; P = .76) for rectal cancer, 1.56 (95% CI = 1.07-2.28; P = .02) for advanced colorectal cancer, and 2.39 (95% CI = 1.46-3.92; P = .0005) for fatal colorectal cancer. CONCLUSION: Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women.

Adult↗
PubMed1999

Elevated maternal urine level of beta-core fragment of human chorionic gonadotropin versus serum triple test in the second-trimester detection of down syndrome.

OBJECTIVE: This study was undertaken to compare the Down syndrome screening efficiency of elevated maternal urine level of the beta-core fragment of human chorionic gonadotropin with that of the traditional serum triple test. STUDY DESIGN: Urinary beta-core fragment and serum analyte levels were measured prospectively in women with singleton pregnancies who were undergoing second-trimester genetic amniocentesis. Urinary analyte levels were measured within a week of specimen collection. In some cases only alpha-fetoprotein was measured initially and human chorionic gonadotropin and unconjugated estriol levels were subsequently determined from the stored serum specimens. The Down syndrome screening efficiency of urinary concentration of beta-core fragment plus maternal age was compared with that of the traditional triple test. Receiver operating characteristic curves were generated for each algorithm and the areas under the curves were compared to determine which algorithm was superior. RESULTS: There were a total of 926 study patients, of whom 21 (2.3%) carried fetuses with Down syndrome. The mean (+/-SD) gestations at amniocentesis were 16.6 +/- 1.5 weeks for the fetuses without Down syndrome and 17.7 +/- 2.3 for the fetuses with Down syndrome. A total of 539 women (4 of whom carried fetuses with Down syndrome) had serum alpha-fetoprotein alone measured initially. Urinary concentration of beta-core fragment had a 61.9% detection rate with a 4.9% false-positive rate for Down syndrome, whereas the values for the triple screen were 57. 1% and 11.2%, respectively. The areas under the receiver-operating characteristic curves were 0.8744 for elevated urinary beta-core fragment level and 0.7504 for the triple screen (P =.1116). When the false-positive rate was fixed at an ideal threshold value (</=5%) the urine test was superior (area under the curve, 0.0212 vs 0.0133, P <.05). Similarly, when we considered only cases in which the complete triple screen was performed prospectively (17 fetuses with Down syndrome and 431 fetuses without Down syndrome), the urine test was significantly better (area under the curve, 0.873 vs 0.624, P =.012). CONCLUSION: In this first reported direct comparison we consistently observed higher sensitivity values for screening with urinary levels of beta-core fragment than for serum triple screen, suggesting an equivalent or superior Down syndrome screening performance for the urinary analyte. It is important that freezing and prolonged urine storage before testing be avoided. The reduced cost (single- versus triple-analyte testing) and excellent screening performance support large-scale testing and evaluation of maternal urinary beta-core fragment measurement as an alternative to the traditional serum triple test.

Adult↗
PubMed1999

Health sector reform and the interpretation of policy context.

Health sector reform is on the policy agenda of national governments and international agencies. This paper focuses on the policy process of health sector reform and, more specifically, the policy context. The importance of understanding policy context is emphasised and the elements of policy context are discussed. These are: demographic and epidemiological change; processes of social and economic change; economic and financial policy; politics and the political regime; ideology, public policy and the public sector. The paper then discusses the means for, and methods of, interpretation of the policy context. Particular emphasis is placed on linking policy context with an overall understanding of the policy process, the 'messiness' of policy-making, the interrelationship between the contextual factors, the contextual factors interpreted by policy actors, the use of analytical categories in the policy analysis. The paper concludes on the importance of strengthening policy analysis for effective health sector reform.

Developing Countries↗
PubMed1999

Intraoperative scanning laser Doppler flowmetry in the assessment of gastric tube perfusion during esophageal resection.

BACKGROUND: Ischemia from tissue hypoperfusion in the gastric tube after esophagectomy is believed to contribute significantly to postoperative complications associated with anastomotic failure. This study assessed the ability of the new technique of laser Doppler flowmetry to measure differential levels of blood flow in human gastric tubes during esophagectomy. STUDY DESIGN: Gastric perfusion was measured in 16 patients undergoing esophagectomy by making laser Doppler scans of the stomach before mobilization and after formation of the gastric tube. Mean perfusion was calculated within the whole anterior surface of the stomach or tube and within 1 cm2 regions of interest, each of which contained 1,750 individual measurements of perfusion. These regions represented the cephalic end of the gastric tube, 10 adjacent 1 cm2 regions distally along the tube, and the proposed anastomosis site. Results were expressed as mean perfusion units, and tissue blood flow from each scan in each region was compared. RESULTS: There were significant decreases in gastric perfusion measured with the scanning laser Doppler in all patients after formation of the gastric tube. Mean perfusion of the stomach fell 41% (p<0.0005) after mobilization. In all patients there was a gradient of perfusion from the proximal end of the tube where flow was poor, to more distal areas where it was higher. At the proximal end of the tube perfusion fell by a mean of 72%, 5 cm distally the mean fall was 44%, and 10 cm from the proximal end of the tube the mean fall was 28%. At the anastomosis site mean perfusion fell 55%. CONCLUSIONS: This new technique can be used intraoperatively and appears to overcome the limitations of single point laser Doppler flowmetry. It has measured large differences in perfusion at different sites within the gastric tubes and could therefore have widespread clinical applications.

Adult↗
PubMed1999

Peripheral nerve revascularization: histomorphometric study of small- and large-caliber grafts.

The revascularization of nerve grafts was investigated using histologic and morphometric techniques. Small-diameter nerve grafts (sciatic in the rat and sural in adult ewes) were studied, as was a large-diameter peroneal nerve graft in the ewe. Ninety-six hours after sciatic nerve engraftment, rats were injected with an intravascular fluorescent tracer. Evans blue albumin (EBA). Specimens were observed for the number of vessels perfused. Analysis showed no difference in vascular pattern between the grafted nerves and their control nerves, suggesting that spontaneous revascularization had occurred to establish a vascular tree essentially identical to the native nerve. Sural and peroneal nerve grafts were evaluated in adult ewes at 7 or 40 days post-nerve grafting. Similar to the rat sciatic nerve, the small-diameter sural nerve grafts were completely revascularized, with an equal number of perfused vessels at both time periods, with respect to control specimens. In contrast, the larger-caliber peroneal nerve grafts were not perfused at 7 days, and very poorly perfused at 40 days. This correlated with scant neural regeneration at 40 days. The finding suggests that small-diameter nerve grafts spontaneously revascularize, and revascularization using microvascular techniques is not necessary. In contrast, the larger-diameter nerve graft did not revascularize well. Such a large-diameter nerve graft would provide a suitable model to investigate the potential merits of a vascularized nerve graft.

Animals↗