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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 271 records · Page 15Linked to original sources
PubMed1994

An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease.

Cost-effectiveness and cost-utility analyses of immunisation strategies against invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a hypothetical birth cohort of 250,000 non-Aboriginal Australian children. The model predicted that, without immunisation, 625 cases of invasive Hib disease would occur in under-five-year-olds, with direct costs of $10.2 million. Universal public sector vaccination beginning before six months of age (6MVAC) prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and at 18 months (18MVAC) 46 per cent. At a vaccine cost of $15 per dose, 18MVAC gave the lowest cost per quality-adjusted life year (QALY) over a wide range of model assumptions, with 6MVAC the 'best' alternative. The best estimate ($ per QALY) for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC $1231 (one dose). The cost per QALY of single dose catch-up immunisation of older children was estimated at $8630 at two years, $27,000 at three years and $117,000 at four years if done at a scheduled visit; these values were increased if an additional medical visit was included. The threshold cost per vaccine dose at which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC and 18MVAC as $11, $10 and $14. Even under a worst-case scenario, an immunisation program at 6, 12 or 18 months became cost-saving if indirect costs of death were included. Comparison with previous analyses revealed the importance of the incidence and age distribution of disability and assumptions about vaccine administration costs in determining model outcomes.

Child↗
PubMed1993

Alkylation and oxidative-DNA damage repair activity in blood leukocytes of smokers and non-smokers.

The levels of 3 DNA repair enzymes involved in alkylation and oxidative DNA damage repair in human peripheral blood leukocytes were measured in 20 smokers and 17 non-smokers. No differences in O6-alkylguanine-DNA-alkyltransferase (AGT) activity were found between the 2 groups and the AGT distribution within the population appeared to be unimodal. In contrast, the mean activities of both the methylpurine (MeP)- and the 2-6-diamino-4-hydroxy-5N formamidopyrimidine (FaPy)-DNA glycosylases were higher in the smokers, although only the difference between the MeP-DNA glycosylase means was statistically significant. The standard deviations of these 2 enzymes were also higher in the smokers. The MeP-DNA glycosylase activity showed a bimodal distribution when all subjects were considered. This may in part be due to the smoking habit; 83% of the subjects with enzyme activities higher than 500 fmoles/mg protein were current smokers, whilst 85% of the non-smokers had lower enzyme activities. However, if the smokers were considered separately, a bimodal distribution of this enzyme activity could still be observed. No strong correlation was observed between enzyme activity and age, although the slopes of the regression lines of enzyme activity on age were all negative. The relationship between enzyme activities was studied by bivariate distribution and a strong correlation was only found between the MeP-DNA glycosylase and the FaPy-glycosylase, with the highest values of both enzyme activities being observed in the smokers and the lowest in the non-smokers. Our results suggest that the activity of certain DNA repair enzymes can be modulated by environmental exposure.

Adult↗
PubMed1993

Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.

OBJECTIVE: To compare safety of salmeterol and salbutamol in treating asthma. DESIGN: Double blind, randomised clinical trial in parallel groups over 16 weeks. SETTING: General practices throughout the United Kingdom. SUBJECTS: 25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516). INTERVENTIONS: Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study. MAIN OUTCOME MEASURES: All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs. RESULTS: Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event. CONCLUSIONS: Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.

Administration, Inhalation↗
PubMed1993

Preliminary crystallographic analysis of coxsackievirus A9.

Coxsackievirus A9 has been crystallized as small rhombic dodecahedra of maximum dimension 0.3 mm. These crystals have been shown, using synchrotron radiation, to diffract X-rays to beyond 3 A, and to have a stability in the beam comparable to that of other related virus crystals. The unit cell is tetragonal with dimensions a = b = 495 A, c = 695 A and alpha = beta = gamma = 90 degrees, with a space group of P4n22. A substantial body of diffraction data has been collected and this crystal form appears to be suitable for structure determination. Phasing of these data will be attempted using molecular replacement.

Animals↗
PubMed1993

Secretion of a prokaryotic cellulase in bacterial and mammalian cells.

The catalytic domain of mature Clostridium thermocellum endoglucanase E (EGE') and derivatives of the enzyme fused to prokaryote and eukaryote signal peptides (SP), were produced in Chinese hamster ovary (CHO) cells and Escherichia coli. All three forms of the endoglucanase were secreted into the periplasm of Escherichia coli, but only derivatives of the enzyme containing an N-terminal SP were exported from CHO cells. Extracellular EGE', purified from E. coli and CHO cultures, displayed similar properties suggesting that glycosylation of the enzyme in the eukaryote did not significantly alter the protein's properties. Data presented in this report indicate that mature EGE' contains secretion signals which are recognised only by the E. coli protein export apparatus, suggesting that there are differences in the recognition of certain secretion signals in eukaryotes and prokaryotes. As mature EGE' does not contain secretion signals recognised by the mammalian cell, membrane translocation of the bacterial cellulase in a higher eukaryote is directed by an N-terminal prokaryotic SP.

Animals↗
PubMed1993

A cost-utility approach to the use of 5-fluorouracil and levamisole as adjuvant chemotherapy for Dukes' C colonic carcinoma.

OBJECTIVE: To perform an economic evaluation of the joint use of 5-fluorouracil and levamisole as adjuvant chemotherapy in patients with fully resected Dukes' Stage C carcinoma of the colon, compared with resection and no chemotherapy. The evaluation was prompted by a study (N Engl J Med 1990; 322: 352-358) which recommended a new treatment standard for colon cancer: a 52-week course of fluorouracil, with levamisole every second week, as adjuvant chemotherapy. This recommendation raised several concerns, particularly about the quality of life of patients undergoing such a long course of chemotherapy and the costs to the health care system. METHODS: The cost of the surgery plus chemotherapy was estimated and compared with the cost of surgery alone. Descriptions of quality of life were developed from interviews with patients and health professionals, and the time trade off technique was then used to derive utility weights from a small sample (16) which were used to adjust length of life to reflect quality, in terms of a "quality adjusted life year" (QALY). RESULTS: Chemotherapy increases the total cost of treating a patient with colon cancer by $7000, from $6000 to $13,000. Incorporating quality of life reduced the extra benefit gained from the chemotherapy from 2.4 life years to 0.4 QALYs. Thus the result is a cost of $17,500 to achieve an extra QALY from this particular treatment. CONCLUSIONS: The results of this analysis are only tentative, as the quality of life descriptions were not measured over time but from a cross-sectional survey of patients, and the valuations of health states were derived from a small sample. However, we believe them to be indicative, and conclude that it is perhaps more appropriate for the use of chemotherapy to be an option rather than standard treatment until further research on these aspects is complete.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Doxycycline protects serum alpha-1-antitrypsin from human neutrophil collagenase.

Interstitial collagenases, members of the matrix metalloproteinase family, are key initiators of collagen destruction during various disorders such as rheumatoid arthritis. Recently interstitial collagenases were found to efficiently degrade an additional non-collagenous substrate, the serum alpha-1-antitrypsin (AAT also called alpha-1-proteinase inhibitor or serpin). Serpins are major endogenous inhibitors of serine proteinases, particularly neutrophil elastase. Of relevance to neutrophil-mediated collagen degradation, the tetracycline family of antibiotics are now known to inhibit inhibit mammalian collagenases by a mechanism unrelated to their antimicrobial activity. This study identifies an additional mechanism by which tetracyclines may retard tissue breakdown during inflammatory diseases. Doxycycline, added to the reaction mixture as in concentrations as low as 10 microM, which correspond to levels of the drug readily achieved in vivo, produced detectable inhibition of serpinase activity of neutrophil collagenase, although levels of 50-100 microM or greater were required to reduce AAT degradation more than 75%. The concentration of doxycycline to inhibit 50% (IC50 of serpinase activity) of AAT degradation by neutrophil collagenase was found to approximate 20 microM, a value similar to the IC50 for doxycycline required to inhibit collagen degradation by neutrophil collagenase. Doxycycline was also found to inhibit at cell level neutrophil-mediated degradation of AAT. The protection of bodies' AAT-shield from serpinolytic activity of collagenase would result in inhibition of serine proteinases such as neutrophil elastase. Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase.

Collagenases↗
PubMed1993

Cardiac effects of trandolapril in hypertension.

Baseline echocardiography was performed on 25 patients with essential hypertension and a supine diastolic blood pressure of 95 to 114 mm Hg while receiving placebo. Once-daily trandolapril was then titrated from 1 to 4 mg. After 3 months of therapy, supine diastolic blood pressure decreased by 7.5% (p < 0.0001). Left ventricular hypertrophy regressed as evidenced by a 23.2% (p < 0.0001) decrease in left ventricular mass index at 3 months and a 12.4% (p < 0.05) reduction of relative wall thickness at 6 months. Although afterload decreased by 12.4% (p < 0.05) at 3 months, left ventricular systolic function remained unchanged, whereas left ventricular contractility, which was assessed from the load-independent relationship of end-systolic wall stress to velocity of circumferential fiber shortening, improved. Left ventricular diastolic function (E/A ratio) improved in 15 of 25 patients with low baseline values from 0.96 +/- 0.14 to 1.18 +/- 0.25 (mean +/- SD, p < 0.0002) at 3 months. We conclude that trandolapril effectively reduces left ventricular hypertrophy and improves diastolic function in patients with hypertension while systolic function is preserved.

Adult↗
PubMed1993

Antibiotic prophylaxis in cardiac operations.

This clinical trial, which was composed of 1,031 adults undergoing cardiac operations, compared the efficacy of a single dose of 1 g of ceftriaxone with a 48-our regimen consisting of flucloxacillin and gentamicin. There was no significant difference (p = 0.89) in the overall incidence of major infections: 30 of 515 patients (5.8%; 95% confidence interval, 5.4% to 6.2%) taking ceftriaxone and 29 of 516 patients (5.6%; 95% confidence interval, 5.2% to 6.0%) taking flucloxacillin and gentamicin. Subgroup analyses, with a lower statistical power, failed to show a significant difference between patients who received ceftriaxone and those who received flucloxacillin/gentamicin: major sternal wound infections arose in 2.7% of the patients taking ceftriaxone versus 1.6% in those on the 48-hour regimen (p = 0.20) and major limb wound infections arose in 4.2% and 5.4%, respectively (p = 0.44). Single-dose prophylaxis was associated with fewer intravenous administrations (864 doses versus 9,570 doses) and cost less (A$17,248 versus A$78,510). Although the regimen that included gentamicin was associated with the greatest biochemical impairment of renal function, the overall toxicity for both groups was low. We conclude that a single dose of ceftriaxone provided cost-efficient prophylaxis for adults undergoing cardiac operations when compared with a 48-hour regimen of gentamicin and flucloxacillin. The general principle revealed by our data is that the short-term administration of an appropriate antibiotic regimen represents optimal prophylaxis for patients undergoing cardiac procedures.

Adolescent↗
PubMed1993

Framing and labelling effects in health descriptions: quality adjusted life years for treatment of breast cancer.

At present there is a growing interest in the use of cost-utility analysis (CUA) to a point where it merits serious consideration by health care decision makers. However, there remain a number of theoretical and practical issues to be resolved including the way in which quality of life information is presented and described to subjects. Two potential sources of influence in the construction of the quality adjusted life year (QALY) values elicited for a recent Australian CUA of mammography screening have been investigated. 180 subjects were randomly allocated to nine different presentations of two breast cancer health descriptions to investigate the impact of some framing and labelling effects. No statistically significant differences were found in the valuations placed on these descriptions when framing and labelling effects were taken into account, either as separate framing and labelling factors or as interactions with one another. A significant difference was found in the particular values of descriptions that were written in the third person that differed in terms of whether the word "cancer" was used. The main contribution of these data is to the robustness of the health descriptions used in the cost-utility analysis of mammography screening.

Aged↗
PubMed1993

Manipulation of the repertoire of digestive enzymes secreted into the gastrointestinal tract of transgenic mice.

In non-ruminant livestock the energy which can be derived from dietary cellulose and xylan is limited by the inefficient microbial fermentation of these polymers in the hind-gut. Furthermore, in poultry, cereal-derived plant structural polysaccharides impair normal digestive function through the formation of gel-like structures, which trap nutrients rendering them unavailable to the animal. The nutrition of non-ruminant livestock could be significantly improved by the depolymerization of plant structural polysaccharides, through the introduction of cellulase activity into the small intestines of these animals. Here we describe the expression of Clostridium thermocellum endoglucanase E in the exocrine pancreas of transgenic mice. A non-glycosylated active enzyme is secreted into the small intestines, and is resistant to proteolytic inactivation, demonstrating the feasibility of generating non-ruminant animals with the endogenous capacity to depolymerize plant structural polysaccharides in the small intestines.

Animals↗
PubMed1993

Diagnostic classification of patients with low back pain: report on a survey of physical therapy experts.

BACKGROUND AND PURPOSE: A survey of expert orthopedic physical therapists was conducted to assist in the development of a classification system for patients with low back pain (LBP). The goal of the survey was to measure levels of agreement on labels and accompanying constellations of signs and symptoms for subgroups of patients with LBP. SUBJECTS: Twenty-four of the 30 expert orthopedic physical therapists who were originally contacted responded to the survey request. METHODS: A modified Delphi technique was used. The first stage involved a review of the literature and identification of 25 diagnostic classes of LBP. Experts were asked to rate the "appropriateness" of each diagnostic class for inclusion in a classification scheme. Clinical findings relevant to each diagnostic class were identified and rated on the degree of "essentialness" to that class. RESULTS: Three diagnostic classes--hypomobility dysfunction, nerve root adhesion, and sacroiliac hypermobility--were distinct in that the agreement criteria for the appropriateness of diagnostic classes as well as the surveyed essential signs and symptoms were met. Six of the 25 diagnostic classes did not meet the minimum levels required for agreement as appropriate diagnostic classes: facet syndrome, chronic pain behavior, muscle strain, iliolumbar ligament sprain, posterior ligament sprain, and myofascial dysfunction. CONCLUSION AND DISCUSSION: The importance of developing homogeneous subgroups of patients with LBP based on constellations of reliable clinical findings is emphasized.

Australia↗
PubMed1993

Doxycycline in the protection of serum alpha-1-antitrypsin from human neutrophil collagenase and gelatinase.

The concentration of doxycycline required to inhibit 50% (50% inhibitory concentration for serpinase activity) of alpha-1-antitrypsin degradation by purified neutrophil collagenase was found to be approximately 20 microM, a value similar to the 50% inhibitory concentration of doxycycline required to inhibit collagen degradation by neutrophil collagenase. Doxycycline also efficiently inhibited phorbol myristate acetate-triggered neutrophil-mediated degradation of alpha-1-antitrypsin. This suggests that doxycycline can protect alpha-1-antitrypsin from collagenase and gelatinase in the presence of other proteases and biologically active molecules that are released by triggered neutrophils. The protection of a body's alpha-1-antitrypsin shield from serpinolytic activity of collagenase and matrix metallproteinases can result in inhibition of serine proteases such as neutrophil elastase. Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase.

Collagenases↗
PubMed1993

Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses.

We constructed recombinant vaccinia virus vectors for expression of the structural region of hepatitis C virus (HCV). Infection of mammalian cells with a vector (vv/HCV1-906) encoding C-E1-E2-NS2 generated major protein species of 22 kDa (C), 33 to 35 kDa (E1), and 70 to 72 kDa (E2), as observed previously with other mammalian expression systems. The bulk of the E1 and E2 expressed by vv/HCV1-906 was found integrated into endoplasmic reticulum membranes as core-glycosylated species, suggesting that these E1 and E2 species represent intracellular forms of the HCV envelope proteins. HCV E1 and E2 formed E1-E2 complexes which were precipitated by either anti-E1 or anti-E2 serum and which sedimented at approximately 15 S on glycerol density gradients. No evidence of intermolecular disulfide bonding between E1 and E2 was detected. E1 and E2 were copurified to approximately 90% purity by mild detergent extraction followed by chromatography on Galanthus nivalus lectin-agarose and DEAE-Fractogel. Immunization of chimpanzees with purified E1-E2 generated high titers of anti-E1 and anti-E2 antibodies. Further studies, to be reported separately, demonstrated that purified E1-E2 complexes were recognized at high frequency by HCV+ human sera (D. Y. Chien, Q.-L. Choo, R. Ralston, R. Spaete, M. Tong, M. Houghton, and G. Kuo, Lancet, in press) and generated protective immunity in chimpanzees (Q.-L. Choo, G. Kuo, R. Ralston, A. Weiner, D. Chien, G. Van Nest, J. Han, K. Berger, K. Thudium, J. Kansopon, J. McFarland, A. Tabrizi, K. Ching, B. Mass, L. B. Cummins, E. Muchmore, and M. Houghton, submitted for publication), suggesting that these purified HCV envelope proteins display native HCV epitopes.

Animals↗
PubMed1993

Reinfusion of shed blood after orthopaedic procedures in children and adolescents.

A prospective study was done of the results of infusion of drained blood after major procedures on the spine and hip in twenty-six patients. The Solcotrans system was used to salvage drained blood in the first six hours after the operation. Transfusion requirements, blood loss, hematocrit, temperature, prothrombin time, partial prothrombin time, platelet count, results of blood cultures, and levels of factor VIII, factor V,D-dimer, antithrombin III, plasminogen, protein C, and complement C3a des arginine were determined for some or all of the patients. A mean of 375 milliliters of blood from the Solcotrans receptacle was reinfused. All of the cultures were negative. There were no febrile reactions. The mean values for the specimens of the salvaged blood were: hematocrit, 0.20; hemoglobin, seventy-one grams per liter; plasma hemoglobin, 2.36 grams per liter; C3a des arginine, 9.4 x 10(-3) grams per liter; fat particles of less than nine micrometers in diameter, 23,643 per milliliter; and D-dimer, 205 x 10(-3) grams per liter. Studies of blood samples that were collected from patients one to two hours and twelve to eighteen hours after the transfusion showed only slight increases in fibrin split products one hour after the transfusion; these values reverted to normal by eighteen hours. No clinical coagulopathy associated with reinfusion was observed. The reinfusion of unwashed, filtered shed blood that was as much as 15 per cent of the total blood volume proved to be a safe technique after major orthopaedic procedures.

Adolescent↗