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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
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↗
PubMed1999

A novel, biodegradable polymer conduit delivers neurotrophins and promotes nerve regeneration.

OBJECTIVE/HYPOTHESIS: A wide variety of substances have been shown to promote neuritic extension after nerve injury. An obstacle to achieving the maximal benefit from these substances has been the difficulty in effectively delivering the substances over a protracted time course that promotes maximal, directed growth. In this study the delivery of a growth-promoting substance through a biodegradable conduit, using materials originally designed for drug delivery applications, was hypothesized to promote more robust neural regeneration than through conduits lacking the substance. The objectives of this study were to create a growth factor-loaded biodegradable nerve guidance conduit, and to assess in vivo nerve regeneration through the conduit compared with that through conduits lacking the substance. MATERIALS/METHODS: Inosine, a purine analogue thought to promote axonal extension following neural injury, was loaded into cylindrical polymer foams composed of a polylactide-co-glycolide copolymer. First, in vitro extravasation of inosine was measured over a several week period using spectrophotometry. Second, the foams were fashioned into single-channel cylindrical nerve guidance conduits via a novel, low-pressure injection molding technique. The conduits were then used to bridge 7-mm defects in the rat sciatic nerve (n = 8). Control conduits lacking inosine were implanted into another set of animals as controls (n = 12). RESULTS: In vitro spectrophotometric measurements indicated appreciable leaching of inosine from the loaded foams over a period of at least 9 weeks. In the in vivo model, after 10 weeks, a higher percentage cross sectional area composed of neural tissue existed through the inosine-loaded conduits compared with controls (mean 44%, SD 7.5% vs. 36%, SD 8.6%, respectively). A difference was also found in mean fiber diameter between the two groups, with the inosine-loaded tubes showing a statistically significantly larger diameter than controls (P < .05). CONCLUSIONS: A nerve regeneration conduit was successfully created that delivers growth promoting substances over a protracted time course. In an in vivo model, the presence of inosine, a purine analogue, yielded neural regeneration whose histological features suggest possible superior long-term motor function.

Absorbable Implants↗
PubMed1998

Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells.

Interleukin (IL)-18 induces interferon (IFN)-gamma synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rbeta2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R-derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin-T cell antigen receptor-alphabeta transgenic mice (D011.10). Anti-IL-18R antibody inhibited IL-18- induced IFN-gamma production by Th1 clones in vitro. In vivo, anti-IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-gamma and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.

Animals↗
PubMed1998

Klippel-Trenaunay syndrome.

Patients with Klippel-Trenaunay (KT) syndrome have a complex constellation of anomalies that includes cutaneous capillary malformation (usually on an affected limb), abnormal development of the deep and superficial veins, and limb asymmetry, usually enlargement. Mixed vascular malformations may be present and include capillary, venous, arterial, and lymphatic systems. The records of 79 patients referred for vascular anomalies were reviewed and 49 were found to have the three "cardinal" anomalies of KT syndrome. Twenty-six females and 23 males had 46 affected legs (27 right legs), 23 affected arms (15 right), 21 affected trunks, and 10 affected heads. Thirty-six had only one affected quadrant, 8 had two, and 5 had three or more. Although 40 patients had increased limb girth, measurable length discrepancy was noted in only 17 individuals. Patients were evaluated using a noninvasive imaging strategy including color duplex ultrasonography, MRI, lymphoscintigraphy, and plain radiographs. Treatment included compression, pulsed-dye laser treatment, reduction of arteriovenous malformations, and orthopedic procedures for overgrowth. All KT cases in this series occurred sporadically. We speculate that KT syndromes may be due to a somatic mutation for a factor critical to vasculogenesis and angiogenesis in embryonic development.

Adolescent↗
PubMed1998

A calcium-dependent tyrosine kinase splice variant in human monocytes. Activation by a two-stage process involving adherence and a subsequent intracellular signal.

Freshly isolated human monocytes do not express p125(FAK) but upon adherence to substrata activate the highly related calcium-dependent tyrosine kinase (CADTK), also known as Pyk2, CAKbeta, RAFTK, and FAK2. The monocyte CADTK was 5 kDa smaller than protein from epithelial cells; isolation and sequencing of the monocyte CADTK cDNA revealed a predicted 42-amino acid deletion between the two proline-rich domains of the enzyme. The nucleic acid sequence suggests that the deletion is caused by alternative RNA splicing. This species was also found in T and B lymphocytes and appears to be the predominant form of cytoskeletal associated tyrosine kinase in non-neoplastic, circulating, hematopoietic cells. CADTK was not activated when monocytes maintained in suspension were treated with agents that produce an intracellular calcium (thapsigargin) or protein kinase C (phorbol 12-myristate 13-acetate) signal including a chemokine, RANTES, that binds to the HIV co-receptor, CCK5. In contrast, monocyte adherence to tissue culture plastic-stimulated CADTK tyrosine phosphorylation, a process that was enhanced by thapsigargin, phorbol 12-myristate 13-acetate, and RANTES but that was completely blocked by preincubation with cytochalasin D. When compared with plastic, adherence to fibronectin- or collagen-coated surfaces produced only minimal CADTK activation but permitted significant stimulation by added thapsigargin. These data suggest that in a cell type that lacks p125(FAK), CADTK plays an early role in post-adherence signaling. Its activation involves two stages, cytoskeletal engagement, which is permissive, and co-stimulatory signals (calcium or protein kinase C) generated by extensive cell surface engagement, agonists, or inflammatory chemokines.

Alternative Splicing↗