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Biomedical subjects

D Hunt

Publications and source records attributed to D Hunt.

At least 55 records · Page 3Linked to original sources
PubMed1997

Evidence-based disease management.

Disease management is an approach to patient care that emphasizes coordinated, comprehensive care along the continuum of disease and across health care delivery systems. Evidence-based medicine is an approach to practice and teaching that integrates pathophysiological rationale, caregiver experience, and patient preferences with valid and current clinical research evidence. Using diabetes mellitus as an example, we describe the importance of evidence-based medicine to the development of disease management programs. We present a method for developing and implementing evidence-based clinical guidelines, clinical pathways, and algorithms and describe the creation of systems to measure and report processes and outcomes that could drive quality improvement in diabetes care. Multidisciplinary teams are ideally suited to develop, lead, and implement evidence-based disease management programs, since they play an essential role in the preventive, diagnostic, and therapeutic decisions for patients with diabetes throughout the course of their disease.

Algorithms↗
PubMed1997

Comparison of the Chiron Quantiplex branched DNA (bDNA) assay and the Abbott Genostics solution hybridization assay for quantification of hepatitis B viral DNA.

Several assays for quantification of DNA have been developed and are currently used in research and clinical laboratories. However, comparison of assay results has been difficult owing to the use of different standards and units of measurements as well as differences between assays in dynamic range and quantification limits. Although a few studies have compared results generated by different assays, there has been no consensus on conversion factors and thorough analysis has been precluded by small sample size and limited dynamic range studied. In this study, we have compared the Chiron branched DNA (bDNA) and Abbott liquid hybridization assays for quantification of hepatitis B virus (HBV) DNA in clinical specimens and have derived conversion factors to facilitate comparison of assay results. Additivity and variance stabilizing (AVAS) regression, a form of non-linear regression analysis, was performed on assay results for specimens from HBV clinical trials. Our results show that there is a strong linear relationship (R2 = 0.96) between log Chiron and log Abbott assay results. Conversion factors derived from regression analyses were found to be non-constant and ranged from 6-40. Analysis of paired assay results below and above each assay's limit of quantification (LOQ) indicated that a significantly (P < 0.01) larger proportion of observations were below the Abbott assay LOQ but above the Chiron assay LOQ, indicating that the Chiron assay is significantly more sensitive than the Abbott assay. Testing of replicate specimens showed that the Chiron assay consistently yielded lower per cent coefficients of variance (% CVs) than the Abbott assay, indicating that the Chiron assay provides superior precision.

DNA, Viral↗
PubMed1997

Preoperative ultrasound to predict conversion in laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) is the established treatment for symptomatic cholelithiasis. With its decreased postoperative stay, it is being performed increasingly in short-stay or outpatient settings. It is particularly important to identify preoperative factors that may predict conversion to open cholecystectomy (OC) at LC, with its concomitantly prolonged hospital recovery. In this series of 738 patients, the ultrasound features of stone size, gallbladder wall thickness, diameter of the common bile duct, number of stones, and the appearance of a contracted gallbladder were assessed preoperatively in all patients. The overall conversion rate was 3.5% (26 of 738). By logistic regression analysis, factors found to increase significantly the risk of conversion were patient age > 70 years (p < 0.01), a stone at least 20 mm in diameter (p < 0.05), a gallbladder wall thicker than 4 mm (p < 0.05), a common bile duct wider than 6 mm (p < 0.05), and contracted gallbladder on ultrasound (p < 0.02). The number of stones in the gallbladder was not significant. Using these risk factors, it was possible to divide patients into high- and low-risk groups. The 118 patients in the high-risk group had 18 of the 26 conversions, for a conversion rate of 15.3%. The 620 patients in the low-risk group had eight of the 26 conversions, for a conversion rate of 1.3%. This low-risk subgroup represented 84% of the series of 738 LC procedures and may have been suitable for outpatient LC. Using preoperative ultrasound, it is possible to predict patients who are at low risk of conversion and are suitable for ambulatory surgery.

Age Factors↗
PubMed1996

The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product.

Tumors express peptide antigens capable of being recognized by tumor-specific cytotoxic T lymphocytes (CTL). Immunization of mice with a carcinogen-induced colorectal tumor, CT26, engineered to secrete granulocyte/macrophage colony-stimulating factor, routinely generated both short-term and long-term CTL lines that not only lysed the parental tumor in vitro, but also cured mice of established tumor following adoptive transfer in vivo. When either short-term or long-term CTL lines were used to screen peptides isolated from CT26, one reverse-phase high performance liquid chromatography peptide fraction consistently sensitized a surrogate target for specific lysis. The bioactivity remained localized within one fraction following multiple purification procedures, indicating that virtually all of the CT26-specific CTL recognized a single peptide. This result contrasts with other tumor systems, where multiple bioactive peptide fractions have been detected. The bioactive peptide was identified as a nonmutated nonamer derived from the envelope protein (gp70) of an endogenous ecotropic murine leukemia provirus. Adoptive transfer with CTL lines specific for this antigen demonstrated that this epitope represents a potent tumor rejection antigen. The selective expression of this antigen in multiple non-viral-induced tumors provides evidence for a unique class of shared immunodominant tumor associated antigens as targets for antitumor immunity.

Animals↗
PubMed1996

Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials.

OBJECTIVE: To review the effect of calcium supplementation during pregnancy on blood pressure, preeclampsia, and adverse outcomes of pregnancy. DATA SOURCE: We searched MEDLINE and EMBASE for 1966 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials. STUDY SELECTION: Fourteen randomized trials involving 2459 women were eligible. DATA EXTRACTION: Reviewers working independently in pairs abstracted data and assessed validity according to six quality criteria. DATA SYNTHESIS: Each trial yielded differences in blood pressure change between calcium supplementation and control groups that we weighted by the inverse of the variance. The pooled analysis showed a reduction in systolic blood pressure of -5.40 mm Hg (95% confidence interval [CI], -7.81 to -3.00 mm Hg; P<.001) and in diastolic blood pressure of -3.44 mm Hg (95% CI, -5.20 to -1.68 mm Hg; P<.001). The odds ratio for preeclampsia in women with calcium supplementation compared with placebo was 0.38 (95% CI, 0.22 to 0.65). CONCLUSIONS: Calcium supplementation during pregnancy leads to an important reduction in systolic and diastolic blood pressure and preeclampsia. While pregnant women at risk of preeclampsia should consider taking calcium, many more patient events are needed to confirm calcium's impact on maternal and fetal morbidity.

Blood Pressure↗
PubMed1996

Characterization and purification of fucosyltransferases from the cytosol of rat colon.

The occurrence and baseline characteristics of fucosyltransferases (alpha-1,2, alpha-1,3 and alpha-1,4) in the cytosol (soluble) and pellet (membrane-bound) of rat colon have been studied since the fucosylation process is known to alter in colon pathology. All enzymes studied in the colon pellet had higher activity when compared to the cytosol. The colon pellet alpha-1,3 fucosyltransferase preferred desialylated alpha 1-acid glycoprotein as acceptor substrate. Both soluble and membrane-bound enzymes, alpha-1,2 and alpha-1,3 fucosyltransferases, required Mn2+, Mg2+ and Ca2+ for maximum activity but were inactivated by Cu2+ ions. Both soluble alpha-1,2 and alpha-1,3 fucosyltransferases showed optimal activity at pH 6.0, whereas the optimum for their membrane-bound activities were at pH 5.8 and 6.2, respectively. Furthermore, a soluble alpha-1,3 fucosyltransferase from rat colon was purified and during purification the co-presence of alpha-1,3/4 fucosyltransferase was detected. The acceptor of preference for the purified soluble alpha-1,3 fucosyltransferase was desialylated glycoprotein while low molecular weight substrates were poor acceptors. Both the purified fucosyltransferases were inhibited by N-ethylmaleimide. The M(r) values determined by SDS-PAGE electrophoresis of alpha-1,3/4 fucosyltransferase and of alpha-1,3 fucosyltransferase were 68,780 and 40,680 respectively. In conclusion, based on their properties, the purified soluble colon alpha-1,3 fucosyltransferase appeared to be of plasma-type (or FT-I) while the soluble alpha-1,3/4 fucosyltransferase corresponded to Lewis-type or FT-III.

Animals↗
PubMed1996

Specific stimulation of alpha 2-6 sialyltransferase activity by a novel cytosolic factor from rat colon.

A factor present in the 100,000 g supernatant from the homogenate of rat colon stimulated the activity of purified Gal beta 1-4GLcNAc alpha 2,6 sialyltransferase [alpha 2-6ST(N)] from rat liver and alpha 2-6ST(N) from either liver microsomes or Golgi membrane. The stimulation of alpha 2-6ST(N) activity by the colon factor using protein acceptors was about four-fold and highly reproducible when the reaction product of the alpha 2-6ST(N) was assayed by either precipitation or affinity chromatography. In contrast, the colon factor did not stimulate the Gal beta 1-4GlcNAc alpha 2,3 sialyltransferase [alpha 2-3ST (N)], from rat jejunum microsomes or purified Gal beta 1-3GalNAc alpha 2,4 sialyltransferase [alpha 2-3ST (O)] from porcine liver, of purified beta 1,4 galactosyltransferase (GT) from bovine milk. In addition to rat colon, the 100,00 g supernatant from the homogenates of rat brain and kidney also stimulated the alpha 2-6ST(N) activity. The stimulation of alpha 2-6ST(N) by the colon factor resulted in a decrease in the Km (by about two-fold) and an increase in Vmax (about 2- to 3-fold) for desialylated alpha 1 acid glycoprotein and CMP-[14C]N-acetylneuraminic acid. The stimulation of alpha 2-6ST(N) activity by the colon factor was temperature dependent, protease sensitive and was inhibited by CTP, but did not need the presence of either metal ions or detergent. The cytosolic factor was partially purified by ion-exchange chromatography with the retention of the activator activity in the peaks containing low molecular weight proteins, but the activity was lost on attempts to further purification. A specific marked stimulation of the alpha 2-6ST(N) activity by cytosolic factors in certain tissues might suggest a physiological role for these factors in the regulation of alpha 2-5ST(N) activity.

Animals↗
PubMed1996

Characterization of two myotrophic neuropeptides in the FMRFamide family from the segmental ganglia of the moth Manduca sexta: candidate neurohormones and neuromodulators

We have characterized two new members of the FMRFamide family of neuropeptides from the segmental ganglia of the tobacco hornworm Manduca sexta. Levels of peptides in ganglia used for purification were enhanced by manipulating their exposure to the steroid molting hormones. Explants of ganglia were cultured in the low-level ecdysteroid environment of diapausing pupae shown previously to evoke accumulation of FMRFamide-like immunoreactivity (FLI). Sufficient material for sequencing was obtained from 180 explanted ganglia. Extracts of ganglia were fractionated using two reverse-phase liquid chromatography procedures, and the immunoreactive fractions were subjected to sequence analysis using electrospray mass spectrometry. The sequences of the two peptides were determined to be GNSFLRFamide and DPSFLRFamide. These peptides have been named MasFLRFamide II and MasFLRFamide III, respectively; the previously characterized M. sexta FLRFamide (pEDVVHSFLRFamide) has been renamed MasFLRFamide I. The three peptides show distinctive tissue and developmental distributions as determined from fractionated extracts of larval and adult central nervous system structures and neurohemal organs. In the retrocerebral corpora cardiaca/corpora allata, MasFLRFamide I was the predominant form, while in the segmental ganglia MasFLRFamides II and III predominated. Higher levels of MasFLRFamide I and II were found in the adult, whereas there was little apparent change in the level of MasFLRFamide III upon metamorphosis. Determinations of peptide levels in fractionated hemolymph of newly emerged moths revealed that levels of MasFLRFamide I and III could exceed 10 nmol l-1. The actions of the three peptides were tested on the moth ileum. MasFLRFamides II and III were found to be stimulatory. At 1 nmol l-1, these peptides induced robust increases in the rate of rhythmic longitudinal and peristaltic waves of contractions. In contrast, MasFLRFamide I was ineffective even at 20 nmol l-1. Thus, while all three peptides have the characteristics of neurohormones in M. sexta, the physiological findings show that the heptapeptide FLRFamides have properties distinct from those of the decapeptide.

Journal Article↗
PubMed1996

Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial.

Seventy-eight patients having elective total hip replacement were randomised into 3 groups A) control; B) low molecular weight heparin: (enoxaparin 40 mg once daily) and C) enoxaparin (40 mg once daily) plus graduated elastic compression (TEDR stockings) for 8-12 days. All patients had a preoperative perfusion lung scan and chest X-Ray and a postoperative perfusion/ventilation scan together with bilateral ascending venography on days 8-12. A blood sample was taken preoperatively, on the 1st, 3rd and 5th postoperative day and at the end of the study. The control group received placebo injections. The venograms and V/Q scans were reported blindly by an independent panel of three and one radiologists respectively. An independent panel of assessors stopped entry in the control group when a total of 45 patients were admitted according to Ethics Committee directives. The study continued with groups B and C. The incidence of DVT (including isolated asymptomatic calf thrombi) was as follows: Group A (n = 14) 93%; Group B (n = 32) 38%; Group C (n = 32) 25% (chi 2; p < 0.001 for group A versus B or C). The incidence of proximal DVT was: Group A 57%; group B 28%; group C 13% (chi 2; p = 0.057 for group A versus B and p < 0.005 for group A versus C). The incidence of silent pulmonary embolism (PE) (new defect on V/Q scan) was 28% (8 out of 29) in patients with and 5% (2 out of 43) in patients without DVT (chi 2; p < 0.02). The combination of high TAT and low anti-Xa activity on the 1st postoperative day identified a high risk group of patients who had a 56% incidence of proximal DVT on the 8th to 12th postoperative day. Further studies are needed to confirm the suggested increased efficacy in prophylaxis by the combination of LMWH and GEC as compared with LMWH alone.

Aged↗
PubMed1995

Isolation of Ala1-proctolin, the first natural analogue of proctolin, from the brain of the Colorado potato beetle.

Methanolic head and brain extracts of the Colorado potato beetle contain several myotropins, active in the Locusta oviduct motility assay. Reversed phase high performance liquid chromatography (RP HPLC) gave evidence for the presence of three myotropic factors, with retention times close to that of proctolin. Both strongly stimulated the frequency, amplitude and tonus of the myogenic oviduct contractions. Gas phase sequencing and FAB-MS revealed that, besides proctolin (Arg-Tyr-Leu-Pro-Thr), two natural proctolin analogues were present. The first one is Ala-Tyr-Leu-Pro-Thr and is designed as Ala1-proctolin. The threshold concentration for biological activity of Ala1-proctolin was 10(-7) M, compared to 10(-10) M for proctolin itself. Ala1-proctolin is the first identified biological analogue of proctolin. The full nature of the first amino acid of a third proctolin-analogue (x-Tyr-Leu-Pro-Thr) is probably a modified amino acid of which the identity could as yet not be revealed. Our results suggest the existence of a family of proctolin-like peptides.

Amino Acid Sequence↗
PubMed1995

Chromosomal localization of three mouse diacylglycerol kinase (DAGK) genes: genes sharing sequence homology to the Drosophila retinal degeneration A (rdgA) gene.

There is growing evidence to support some form of light-activated phosphoinositide signal transduction pathway in the mammalian retina. Although this pathway plays no obvious role in mammalian phototransduction, mutations in this pathway cause retinal degenerations in Drosophila. These include the retinal degeneration A mutant, which is caused by an alteration in an eye-specific diacylglycerol kinase (DAGK) gene. In our efforts to consider genes mutated in Drosophila as candidates for mammalian eye disease, we have initially determined the map position of three DAGK genes in the mouse.

Animals↗
PubMed1995

Structural transitions during bacteriophage HK97 head assembly.

Bacteriophage HK97 builds its head shell from a 42 kDa major head protein, but neither this 42 kDa protein nor its processed, 31 kDa form is found in the mature head. Instead, each of the major head-protein subunits is covalently cross-linked into oligomers of five, six or more by a protein cross-linking reaction that occurs both in vivo and in vitro. Mutants that block prohead maturation lead to the accumulation of one of two types of proheads, termed Prohead I and Prohead II. Prohead I is assembled from about 415 copies of the 42 kDa (384 amino acids) protein subunit and accumulates in infections by mutant amU4. Following assembly, the N-terminal 102 amino acids of each subunit are removed, leaving a prohead shell constructed of 31 kDa subunits, called Prohead II, which accumulates in infections by mutant amC2. During DNA packaging, when the prohead shell expands, all of the head protein subunits become covalently cross-linked to other subunits. Purified Prohead II (or, less completely, Prohead I) becomes cross-linked in vitro in response to any of a number of conditions that induce shell expansion, including conditions commonly used for protein analysis. In vitro cross-linking occurs efficiently in the absence of added cofactors of enzymes, and we propose that cross-linking is catalyzed by shell subunits themselves. Shell expansion is easily monitored by observing a decrease in electrophoretic mobility of Prohead II in agarose gels. Using the mobility shift in agarose gel to monitor expansion and SDS/gel electrophoresis to monitor cross-linking in vitro, we find that expansion precedes and is required for cross-linking, and we propose that expansion triggers the cross-linking reaction. Comparison of peptides isolated from Prohead II and in vitro cross-linked Prohead II shows a single altered major cross-link peptide in which a lysine, originating from lysine169 of the protein sequence, is linked to asparagine356, presumably derived from the neighboring subunit. Examination of the cross-link-containing peptide by mass spectrometry shows that the cross-link bond is an amide between the side-chains of the lysine and the asparagine residues.

Amino Acid Sequence↗
PubMed1995

A novel phosphatidylcholine hydrolysing action of C-reactive protein.

We have observed a novel time and dose dependent stimulatory effect of CRP on the hydrolysis of dipalmitoyl phosphatidylcholine (DPPC) into phosphorylcholine (P-choline) and diacylglycerol (DAG). This effect was shared by rat, rabbit, human and asialo-rat CRP but not by other serum proteins, i.e., albumin, ovalbumin and alpha 1-acid glycoprotein. DPPC was also hydrolysed by normal rat serum (contains CRP) but not when serum was depleted of CRP. There is a requirement of Ca2+ for this unsuspected effect which was observed over a wide range of pH and the effect was markedly increased in temperatures up to 48 degrees C. The hydrolysis of DPPC showed a 3-fold decrease in Km when the assays included rat CRP. Massive increase of CRP in response to inflammation and its involvement in host defense reactions have been well documented. Significance of the present study rests on the possibility that the mechanism of action of CRP in cellular metabolism might be related to the production of DAG and P-choline known to have roles respectively in signal transduction and growth factor stimulated DNA synthesis.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Humoral immune response to human aortic valve homografts.

The humoral response to homograft valves in humans is largely unknown. The anti-human lymphocyte antigen (HLA) antibody production, specificity, and immunoglobulin class were examined sequentially in 73 patients undergoing aortic valve replacement. In addition, the long-term production of antibodies was examined in a cross-sectional study of 160 patients at periods varying from 1 to 15 years postoperatively. Human lymphocyte antigen antibodies were produced in 17 of 30 antibiotic-sterilized homografts (56%) and in 15 of 15 "homovital" homograft recipients, compared with 6 of the 28 control xenograft recipients (21%) (p < 0.001). The HLA antibodies were immunoglobulin G in all 15 homovital homografts, in 11 of 17 antibiotic-sterilized homografts, and in four of the six xenograft cases. Human lymphocyte antigen specificities could be assigned to the antibodies in 21 cases. In 10 of 11 cases in which donor HLA typing data were available, the antibodies detected were directed against donor HLA class I antigens. Of six possible determinants of HLA antibody production, the type of homograft valve implanted (homovital or antibiotic sterilized) correlated with antibody formation. In the cross-sectional study, 66 of the 85 homovital homograft recipients tested for HLA antibodies after 1 year were found to have antibodies, compared with 29 of 75 antibiotic-sterilized homograft recipients (p = 0.00003). We conclude that homografts appear to stimulate a strong donor HLA-specific antibody response, particularly of the immunoglobulin G class. This is most common in homovital valve recipients. These antibodies can persist for 15 years after operation. The clinical significance of this response requires further investigation.

Antibody Specificity↗
PubMed1995

V/Q defects and deep venous thrombosis following total hip replacement.

Seventy-two patients undergoing elective total hip replacement were studied with bilateral venography, pre-operative and post-operative lung scans. Twelve belonged to a control group that received placebo injections and 60 patients to treatment groups that received low molecular weight heparin. The incidence of deep venous thrombosis was 11 (92%) of 12 patients in the control group and 18 (30%) of 60 patients in the treatment group (X2: P < 0.001). The incidence of pulmonary embolism (new unmatched perfusion defects) was five (42%) of the 12 patients in the control group and five (8.3%) of the 60 patients in the treatment groups (X2: P < 0.002). The incidence of pulmonary embolism (new unmatched perfusion defects) was eight (27.5%) of 29 patients with deep venous thrombosis and two (4.6%) of 43 without deep venous thrombosis (X2: P < 0.02). Of the ten patients who had pulmonary embolism according to this study's criteria (one or more new defect on perfusion, unmatched on the ventilation scan), eight would have been classified as high probability by the Biello criteria, and only five by the PIOPED criteria, if the pre-operative scans were not available. We conclude that having a pre-operative lung scan improves ability to interpret the postoperative lung scans in high risk patients.

Elective Surgical Procedures↗
PubMed1995

Neutralising antibodies after streptokinase treatment for myocardial infarction: a persisting puzzle.

OBJECTIVE: To determine the development of titres of streptokinase (SK) neutralising antibodies after a single dose of SK, to establish when titres decrease to levels at which a second dose might be effective. DESIGN: Analyses of blood samples taken from patients at intervals after SK administration. SETTING: Australian public hospital. PATIENTS: 104 patients with acute myocardial infarction who were treated with SK and 27 controls who were not. OUTCOME MEASURE: SK neutralising antibodies were measured once in each of the 27 controls and on 166 occasions in the 104 treated patients. RESULTS: Titres of SK neutralising antibodies rose after SK administration but returned to control levels by 2 years. CONCLUSIONS: SK might be effective again as a thrombolytic agent as early as 2 years after a single dose. These results are at variance with most previously published data and the reasons for this are not clear. Data evaluating patency rates after standard doses of streptokinase in patients with increased titres of neutralising antibodies are necessary before re-exposure to streptokinase can be recommended.

Antibodies↗
PubMed1995

Localisation of the gene encoding diacylglycerol kinase 3 (DAGK3) to human chromosome 3q27-28 and mouse chromosome 16.

The gene encoding a 90 kDa diacylglycerol kinase protein, DAGK3, that is predominately expressed in the retina, was localised by fluorescence in situ hybridisation to human chromosome 3q27-28. This was subsequently confirmed by mapping of its mouse homologue to chromosome 16, a region syntenic to this part of human chromosome 3. No retinopathies have so far been assigned to this region.

Animals↗