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PURPOSE: To compare clinical outcomes of anterior cruciate ligament (ACL) reconstruction and investigate whether the clinical results of 4-strand hamstring tendon (HT) reconstruction are still inferior to that of the patellar tendon (PT). METHODS: We performed a comprehensive systematic review and meta-analysis of the English literature on PubMed, Scopus, Web of Science, and the Cochrane register for papers that compared clinical outcomes of PT versus HT for ACL reconstruction. Outcome measures analyzed included rate of rerupture, KT-1000, International Knee Documentation Committee grade, Lachman, pivot shift, Lysholm score, Tegner Activity Scale, anterior knee pain, and discomfort on kneeling. RESULTS: We included 19 studies from an initial 1,168 abstracts for the systematic review, and, eventually, 19 studies were included in the meta-analysis. The study population consisted of a total of 1784 patients. The average follow-up duration was 58.8 months. We found significant differences in favor of the HT technique in the domains of anterior knee pain, kneeling pain, and restriction in the range of active extension ("extension deficit"). We found no differences between the PT and HT technique in terms of rerupture rate. There were no clinically significant differences for the outcomes of Lysholm score and Tegner Activity Scale as well as the KT-1000 side-to-side at maximum manual force. CONCLUSIONS: Contemporary 4-strand HT ACL reconstruction is comparable with the PT technique in terms of clinical stability and postoperative functional status across most parameters studied. The HT technique carries lower risk of postoperative complications such as anterior knee pain, kneeling discomfort, and extension deficit. Primary ACL reconstruction using the 4-strand HT technique achieves clinical results that are comparable with the PT technique with significantly less postoperative complications. LEVEL OF EVIDENCE: Level I, systemic review and meta-analysis of Level I studies.

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AIMS: Women with remote histories of gestational diabetes mellitus can reduce their diabetes risk through lifestyle changes, but the effectiveness of interventions in women with more recent histories of gestational diabetes has not been reported. Therefore, we conducted a pilot study of a low-intensity web-based pedometer programme targeting glucose intolerance among women with recent gestational diabetes. METHODS: Women with a gestational diabetes delivery within the past 3 years were randomized to a 13-week intervention consisting of a structured web-based pedometer programme which gave personalized steps-per-week goals, pedometers and education regarding lifestyle modification, or to a letter about diabetes risk reduction and screening after delivery for gestational diabetes (control condition). The main outcome measures were change in fasting plasma glucose and 2-h glucose levels on a 75-g oral glucose tolerance test between baseline and 13-week follow-up. Weight was a secondary outcome and behavioural constructs (self-efficacy, social support, risk perception) were also assessed. RESULTS: Forty-nine women were enrolled. At 13-week follow-up, women randomized to the intervention did not have significant changes in behavioural constructs, physical activity or anthropometrics compared with women in the control group. Changes in fasting plasma glucose (-0.046 mmol/l vs. 0.038 mmol/l, P = 0.65), 2-h glucose values (-0.48 mmol/l vs. -0.42 mmol/l, P = 0.91) and weight (-0.14 kg vs. -1.5 kg, P = 0.13) were similar between the control and intervention groups, respectively. CONCLUSIONS: Structured web-based education utilizing pedometers is feasible although uptake may be low. Such programmes may need to be supplemented with additional measures in order to be effective for reduction of diabetes risk.

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BACKGROUND: Military service is considered to be a hidden variable underlying current knowledge about well-being in the elderly. This study aimed to examine life satisfaction and quality of life in Australia's surviving male Korean War veterans and a community comparison group, and to investigate any association with war deployment-related factors. METHODS: Participants completed a postal questionnaire which included the Life Satisfaction Scale, the brief World Health Organization Quality of Life (WHOQOL-Bref) questionnaire and the Combat Exposure Scale. RESULTS: Korean War veterans reported significantly lower Percentage Life Satisfaction (PLS) and quality of life scores on four WHOQOL-Bref domains, compared with similarly aged Australian men (each p value <0.001). These outcomes were most strongly associated with severity of combat exposure and low rank. Mean PLS was approximately 15% lower in veterans who reported heavy combat compared with those reporting no combat, and approximately 12% lower in enlisted ranked veterans compared with officers. CONCLUSIONS: Fifty years after the Korean War, life satisfaction and quality in Australian veterans is poor relative to other Australian men, and is associated with deployment-related factors including combat severity and low rank. In order to respond effectively to current and projected population health needs, nations with large veteran populations may need to consider the impact of military service on well-being in later life.

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Evaluating the environmental performance of municipal solid waste management options is a complex task. Part 1 of this study presents the municipal solid waste management program of the Pamplona Region in Spain, exploring the institutional, operational and economic factors of the program. In Part 2, alternative waste management scenarios that include the selective collection of organic material and composting are illustrated. The use of a Life Cycle Inventory model for waste management allows for the comparison of the environmental burdens of the different scenarios. This use of a Life Cycle Inventory model for solid waste management lets program managers and decision makers include energy use, final solid waste, and Greenhouse gas emissions in the decision making process. Additionally, the different management scenarios are evaluated on their ability to fulfil Pamplona regional objectives and meet European Packaging and Landfill Directive targets.

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Evaluating the environmental performance of municipal solid waste management options is a complex task. Part 1 of this study presents the municipal solid waste management program of the Pamplona Region in Spain and explores the operational, economic, and environmental factors of the program. In Part 2, alternative waste management scenarios that include the selective collection of organic material and composting are illustrated. The use of a Life Cycle Inventory model for waste management allows for the comparison of the environmental burdens of the different scenarios. This use of a Life Cycle Inventory model for solid waste management lets program managers and decision makers include energy use, final solid waste, and Greenhouse gas emissions in the decision making process. Additionally, the different management scenarios are evaluated on their ability to fulfil Pamplona regional objectives and meet European Packaging and Landfill Directive targets.

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The effects of dietary nickel (0, 25, 50, 75, 100, and 150 mg/kg) on the bone strength characteristics and performance parameters of male broilers were investigated. Broilers were housed in either cages or floor pens. At 6 wk of age, the shear fracture energy of the tibia from the caged birds increased when the basal diet was supplemented with 25 mg of dietary nickel per kilogram of feed. The shear force, stress, and fracture energy of the radius from the caged birds also increased at 25 mg/kg nickel. Dietary nickel had no effect on bird body weight, but the caged broilers (2,161 g) were heavier than the floor birds (2,005 g). Nickel had no effect on the strength characteristics of the tibia from the floor birds. Percent tibia bone ash, a measure of bone density, was not influenced by dietary nickel, but the tibia ash of the floor birds was greater than that of the caged birds. Overall, the data indicates that adding 25 mg/kg of dietary nickel to a poultry diet will have a positive influence on bone strength characteristics and performance.

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OBJECTIVE: To integrate evidence based medicine with the experience and expectations of consumers and GPs in the development of clinical practice guidelines for acute respiratory infections (ARI) in young children. METHOD: Focus groups and workshops were held with 21 GPs and 27 patients of young children involved in a 2 year randomised controlled trial. RESULTS: The acceptability of the guideline development process for participants was determined. Barriers were identified which would impede clinical change, including: inadequate time; lack of knowledge; fear of patient dissatisfaction; and fear of poor health outcome. CONCLUSION: This paper details a process of guideline development that addresses the realities of general practice in Australia and the concerns of consumers. We identified potential barriers to change and integrated intervention strategies with the evidence to produce realistic clinical practice guidelines.

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OBJECTIVE: To determine the level of antibiotic resistance in pneumoniae (S. pneumoniae) isolated from nasal swabs of healthy children. METHOD: Cross-sectional community survey. SETTING: Survey was undertaken in general practice settings in Canberra during March and April 1998. SUBJECTS: Four hundred and sixty-one children under 3 years of age enrolled in general practice trial of clinical practice guidelines for antibiotic use. OUTCOME MEASURES: Resistance to penicillin, erythromycin, co-trimoxazole, tetracycline, chloramphenicol and cefotaxime among the isolates of S. pneumoniae. RESULTS: A total of 461 nasal swabs were collected and S. pneumoniae was isolated from 171 (37.1%). Penicillin resistance was found in 12.3% of these isolates, with high level resistance in 0.6%. Resistance rates were higher for cotrimoxazole (44.4%) and erythromycin (18.1%) than for penicillin. Multidrug resistance was found in 19% of these isolates. There was a significant association between the attendance at a day care centre and carriage of pneumococcus (53% vs 32%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.7, P < 0.001). Children who attended day care centers and had received antibiotics during the 4 months prior to swab collection were three times more likely to carry an antibiotic-resistant isolate than children who had neither attended a day care centre nor received antibiotics (68% vs 40%, OR 3.1, 95% CI 1.2-8.4, P = 0.02). CONCLUSION: The level of antibiotic resistance in pneumococci from healthy children was of concern. Carriage of pneumococcus was significantly higher in children who attended a day care centre. Resistance was significantly correlated with antibiotic use in combination with day-care attendance. These findings warrant more judicious use of antibiotics in children.

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BACKGROUND & AIMS: Epidermal growth factor (EGF) inhibits secretagogue-stimulated gastric acid secretion via an EGF receptor located on parietal cells. The aim of this study was to examine whether this growth factor inhibited carbachol-stimulated acid secretion through a protein kinase C-dependent mechanism. METHODS: The effect of EGF on carbachol-stimulated aminopyrine uptake, inositol trisphosphate formation, and intracellular Ca2+ ([Ca2+]i) in purified cultured parietal cells was studied. The ability of protein kinase A and C inhibitors to alter the inhibitory action of EGF was assessed. EGF-mediated translocation and activation of protein kinase C in parietal cells were determined. RESULTS: EGF dose dependently inhibited carbachol-stimulated aminopyrine uptake in a pertussis toxin-insensitive, genistein (tyrosine kinase inhibitor)--sensitive manner, with a maximal inhibitory effect (37.5% +/- 6.8%) achieved at 10(-7) mol/L. EGF did not significantly inhibit carbachol-stimulated inositol trisphosphate formation and did not alter the initial transient increase or sustained plateau in [Ca2+]i stimulated by this secretagogue. The protein kinase C inhibitors H-7 and staurosporine dose dependently reversed the inhibitory action of EGF, whereas H-89 (protein kinase A inhibitor) failed to alter the effect of EGF. EGF pretreatment increased the translocation of alpha and beta 1 isoforms of protein kinase C and stimulated kinase activity in parietal cells. EGF did not down-regulate the parietal cell muscarinic receptor. CONCLUSIONS: The inhibitory action of EGF on carbachol-stimulated parietal cell activity seems to involve protein kinase C.

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The rate of thermal inactivation of Torpedo AChE at pH 8.5 was increased by the sulfhydryl reagent 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). At 30 degrees C or 37 degrees C, inactivation rates with 0.3 mM DTNB increased about 5-fold for the wild-type enzyme and for two site-specific mutants, D72S and V129R. The reversible active site inhibitor, ambenonium, completely stabilized the wild type enzyme and partially stabilized the D72S mutant. However, ambenonium did not protect against the destabilization introduced by DTNB, which still accelerated inactivation of D72S 5-fold. When the only free sulfhydryl group in AChE was removed by replacing cysteine 231 with serine, increased rates of thermal inactivation were observed. The inactivation rate increased by a factor of 2 to 3 for the single mutant (C231S) and by a factor of 5 for the double mutant V129R/C231S. Even in the C231S mutants, DTNB still had an additional effect. It increased the inactivation rate for C231S and V129R/C231 by a factor of about 1.5 to 3 beyond the rates seen in the absence of DTNB. Therefore, at least part of the destabilization seen with DTNB in enzymes that retain C231 does not involve reaction of DTNB with C231.

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The acetylcholinesterase active site consists of a gorge 20 A deep that is lined with aromatic residues. A serine residue near the base of the gorge defines an acylation site where an acyl enzyme intermediate is formed during the hydrolysis of ester substrates. Residues near the entrance to the gorge comprise a peripheral site where inhibitors like propidium and fasciculin 2, a snake neurotoxin, bind and interfere with catalysis. We report here the association and dissociation rate constants for fasciculin 2 interaction with the human enzyme in the presence of ligands that bind to either the peripheral site or the acylation site. These kinetic data confirmed that propidium is strictly competitive with fasciculin 2 for binding to the peripheral site. In contrast, edrophonium, N-methylacridinium, and butyrylthiocholine bound to the acylation site and formed ternary complexes with the fasciculin 2-bound enzyme in which their affinities were reduced by about an order of magnitude from their affinities in the free enzyme. Steady state analysis of the inhibition of substrate hydrolysis by fasciculin 2 revealed that the ternary complexes had residual activity. For acetylthiocholine and phenyl acetate, saturating amounts of the toxin reduced the first-order rate constant kcat to 0.5-2% and the second-order rate constant kcat/Kapp to 0.2-2% of their values with the uninhibited enzyme. To address whether fasciculin 2 inhibition primarily involved steric blockade of the active site or conformational interaction with the acylation site, deuterium oxide isotope effects on these kinetic parameters were measured. The isotope effect on kcat/Kapp increased for both substrates when fasciculin 2 was bound to the enzyme, indicating that fasciculin 2 acts predominantly by altering the conformation of the active site in the ternary complex so that steps involving proton transfer during enzyme acylation are slowed.

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Hemophilia B-Leyden is characterized by the gradual amelioration of bleeding after the onset of puberty. All Leyden phenotype mutations found to date lie within the Leyden-specific region, which spans roughly nt-40 to +20 in the 5' end of the human factor IX gene. With HepG2 cell nuclear extracts, the Leyden-specific region and its immediate neighboring region of the normal factor IX gene showed five DNase I footprints: FP-I (nt +4 to +19), FP-II (nt -16 to -3), FP-III (nt -27 to -19), FP-IV (nt -67 to -49), and FP-V (nt -99 to -77). Protein binding affinities of short oligonucleotides containing sequences of FP-I, FP-II, or FP-III were substantially reduced in the presence of Leyden phenotype mutations in these areas, correlating well with the negative effects of these mutations on factor IX gene expression. A Leyden phenotype mutation at nt -20 (T to A) caused a loss of both footprints FP-III and FP-II but generated a new footprint, FP-III' (nt -34 to -23), partially overlapping with FP-III, indicating mutation-dependent competitive protein binding at these sites. Although the FP-III' area contains an androgen responsive element-like sequence, the nuclear protein that binds at FP-III' is not androgen receptor. The protein was not recognized by anti-androgen receptor antibody and, furthermore, was present not only in liver but also in both androgen receptor-positive and androgen receptor-negative cells in electrophoretic mobility shift assays. The nuclear concentration of this protein increased significantly upon treatment of the HepG2 cells with testosterone. Its binding affinity to an oligonucleotide (-32sub) containing the FP-III' sequence was greatly reduced in the presence of exogenous androgen receptor, suggesting a possible interaction of this protein with androgen receptor. The affinities of both this protein and a protein which binds to FP-III (presumably HNF-4) to -32sub with a mutation at nt -26 were grossly lowered. These findings suggest that the amelioration of hemophilia B-Leyden with a mutation at nt -20 after puberty involves binding of a specific non-androgen receptor nuclear protein at FP-III' and it is able to substitute for the function of a protein bound at FP-III in the normal gene optimally through its elevated interaction with androgen receptor upon a surge of testosterone.(ABSTRACT TRUNCATED AT 400 WORDS)

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The effects of wet-deposited nitrogen on soil acidification and the health of Norway spruce were investigated in a pot experiment using an open-air spray/drip system. Nitrogen was applied as ammonium ((NH(4))(2)SO(4)) or nitrate (HNO(3)/NaNO(3)) in simulated rain to either the soil or the foliage for a period of two years five months. Symptoms of forest decline were not reproduced. Adverse effects relating to soil acidification and N saturation were observed and depended on the chemical form of N. The plant-soil system absorbed most of the soil-applied NH(+)(4) at doses of up to 65 kgN ha(-1) year(-1) but only 54% at a dose of 125 kgN ha(-1) year(-1). About 60% of soil-applied NO(-)(3) was absorbed in all treatments. Ammonium treatments acidified the soil, increased base cation leaching, and mobilised acidic cations. Nitrification was not the major source of acidity, however. Nitrate inputs increased soil pH. Critical loads calculated using current criteria were 60-120 and 30-60 kgN ha(-1) year(-1) for ammonium and nitrate, respectively. Ammonium is more likely to damage forest ecosystems, however, illustrating the need for care in the definition of critical loads.

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The effects of wet-deposited nitrogen on soil acidification and the health of Norway spruce were investigated in a pot experiment using an open-air spray/drip system. Nitrogen was applied as ammonium ((NH(4))(2)SO(4)) or nitrate (HNO(3)/NaNO(3)) in simulated rain to either the soil or the foliage. Symptoms of forest decline as observed in the field were not reproduced, and there was no evidence of direct toxicity. Treatments did, however, have significant effects on tree nutrition. Both NH(+)(4) and NO(-)(3) treatment applied to the foliage lowered foliar K concentrations. NH(+)(4) to a greater extent. Soil-applied NH(+)(4) reduced foliar Mg concentrations and increased foliar Al and Fe. Soil-applied NO(-)(3) significantly reduced foliar P concentrations, and at high doses prevented the alleviation of P deficiency by fertiliser. These effects could be important in some field situations. Ammonium deposition is predicted to be more damaging than nitrate deposition, although the latter may be critical for forests where P status is marginal, such as in parts of the British uplands.

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Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are naturally occurring peptides which are present throughout the gastrointestinal tract and are capable of inhibiting gastric acid secretion. Although previous studies have suggested that TGF-alpha may serve as an autocrine factor regulating parietal cell function, the cellular mechanisms by which it exerts its inhibitory action have not been fully elucidated. In addition, no systematic comparison has been undertaken of the effects of EGF and TGF-alpha on parietal cell function. The aims of the present studies were to compare the actions of EGF and TGF-alpha on basal and stimulated acid secretion by isolated rabbit parietal cells and to elucidate the intracellular mechanisms by which these growth factors inhibit acid secretion stimulated by agents that activate the adenylate cyclase and cyclic AMP second messenger system. Although EGF and TGF-alpha did not alter basal parietal cell function, they both inhibited histamine-stimulated [14C]aminopyrine accumulation in a identical time- and dose-dependent fashion. The maximal effect of approximately 40% inhibition for histamine-stimulated action was achieved with concentrations of 10(-6) M for both EGF and TGF-alpha. The inhibitory effect of EGF and TGF-alpha appeared to be at the postreceptor level as neither growth factor significantly altered binding of histamine to its receptor (H2) on parietal cells. Consistent with this postulated mechanism of action, both EGF and TGF-alpha dose-dependently inhibited forskolin-stimulated aminopyrine uptake with IC50 similar to those required for inhibiting the stimulatory effect of histamine. Of note, neither growth factor inhibited parietal cell activity stimulated by dibutyryl cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)

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The present study was undertaken to determine T cell response to primary human immunodeficiency virus (HIV) infection. No significant difference in T cell subsets was found between subjects who later seroconverted and a group of controls. Six subjects had multiple enumerations of T cell subsets done at the time of seroconversion. Initially, total lymphocyte and T cell subset counts were reduced. An inversion of the CD4+:CD8+ ratio due to a rise in the level of CD8+ cells was found later, followed by an appreciable increase in the number of CD8+ cells and further inversion of the CD4+:CD8+ ratio. Finally, the CD8+ cell count returned toward normal but remained higher than the CD4+ cell count; the inverted ratio was maintained. Lymphocyte hyporesponsiveness to mitogens and antigens was found during the seroconversion illness in one subject. In three of five subjects for whom data were available, an increase in the absolute number of CD8+ cells followed a decrease in the serum HIV antigen level.

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This paper briefly reviews some major mechanisms by which deposition of inorganic N compounds from the atmosphere could be damaging forest and natural ecosystems. Twelve issues which needed further discussion or research were identified. These were: has N deposition increased; what is a N-saturated ecosystem; can the time of onset of N saturation be predicted; can fertiliser experiments simulate the effects of atmospheric deposition; are there relationships between N input and N leaching; is N deposition leading to acidification; does high N input lead to toxicity symptoms in trees; does N input increase tree susceptibility to stress; does N input induce nutrient deficiency; does increasing N affect natural plant communities; what are the effects on aquatic ecosystems; can a 'critical load' for protection of ecosystems be defined? There is a brief critical discussion of each issue. It is concluded that there is not enough understanding of ecosystem function to define a critical load objectively, but that limits can be defined for some ecosystems.