Modeling Intermittent Running from a Single-visit Field Test.

This study assessed whether the distance-time relationship could be modeled to predict time to exhaustion (TTE) during intermittent running. 13 male distance runners (age: 33±14 years) completed a field test and 3 interval tests on an outdoor 400 m athletic track. Field-tests involved trials over 3 600 m, 2 400 m and 1 200 m with a 30-min rest between each run. Interval tests consisted of: 1 000 m at 107% of CS with 200 m at 95% CS; 600 m at 110% of CS with 200 m at 90% CS; 200 m at 150% of CS with 200 m at 80% CS. Interval sessions were separated by 24 h recovery. Field-test CS and D' were applied to linear and non-linear models to estimate the point of interval session termination. Actual and predicted TTE using the linear model were not significantly different in the 1 000 m and 600 m trials. Actual TTE was significantly lower (P=0.01) than predicted TTE in the 200 m trial. Typical error was high across the trials (range 334-1 709 s). The mean balance of D' remaining at interval session termination was significantly lower when estimated from the non-linear model (-21.2 vs. 13.4 m, P<0.01), however no closer to zero than the linear model. Neither the linear or non-linear model could closely predict TTE during intermittent running.

Enhanced recovery protocols in total joint arthroplasty: a review of the literature and their implementation.

BACKGROUND: During recent years, there has been an exponential demand for joint arthroplasty, which has coincided with the global economic recession. In response, the management of patients following arthroplasty is continuously evolving, with the average inpatient length of stay decreasing from weeks to days, and more recently, we have witnessed the development of "outpatient arthroplasty" as a novel concept which aims to address the high volume of patients. The reduction in length of stay has been made possible via implementation of "enhanced recovery programmes" encompassing each stage of the patient journey. Such programmes have aimed to maximise efficiency, whilst maintaining patient satisfaction and achieving exceptional functional outcomes. OBJECTIVE: We have undertaken a thorough review the literature in relation to enhanced recovery programmes (ERPs) and the research that has underpinned individual elements of enhanced recovery. A literature search of enhanced recovery protocols was carried out using PubMed, Cochrane, Embase and OVID. No language restrictions were imposed on the search. REVIEW: ERPs represent a multifactorial framework which may be subdivided into several phases. Pre-operative education programmes, outpatient consultation, pre-anaesthetic assessment, pre-procedural physiotherapy, day-of-surgery admission, pre-operative medications, type of anaesthesia, blood loss reduction protocols, multimodal analgesia delivery, day-of-surgery mobilisation, thromboembolic prophylaxis and ongoing rehabilitation are essential in enhanced recovery. CONCLUSION: These successful strategies have streamlined the patient pathway of arthroplasty surgery in a cost-effective manner, whilst reducing length of hospital stay and maintaining patient outcomes. Further studies are required to appropriately quantify the impact of individual variables and development of an internationally agreed ERP.

Inhibition of beta-propiolactone-induced mutagenesis and neoplasia by sodium thiosulfate.

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the stomach. Sodium thiosulfate (STS) is a potent nucleophile and in initial experiments was found to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA100 to the direct-acting carcinogens beta-propiolactone and styrene oxide. In in vitro experiments STS was shown to maintain its nucleophilicity in the acid pH range. It reacted with beta-propiolactone as rapidly at pH 2 as at pH 7.4. Thus STS has the prerequisite attributes to inhibit the carcinogenic effects of electrophiles in the stomach. Experiments were performed in which STS was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of beta-propiolactone. Under these conditions, inhibition of formation of the forestomach tumors occurred. The data obtained suggest that use of nucleophiles to protect against direct-acting carcinogens is a potential strategy for chemoprevention.

Inhibition of beta-propiolactone-induced neoplasia of the forestomach and large bowel by 4-mercaptobenzene sulfonate in mice and rats.

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the lumen of the gastrointestinal tract and thus prevent these carcinogens from attacking tissues of the host. Sodium 4-mercaptobenzene sulfonate (4-MBSNa) is a potent nucleophile and was found to react rapidly in vitro with the direct-acting carcinogen beta-propiolactone (BPL). In further investigations 4-MBSNa was shown to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA-100 to BPL and a second direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine. Subsequent experiments were performed to determine if 4-MBSNa would inhibit BPL-induced carcinogenesis in vivo. In the first of these, 4-MBSNa was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of BPL. Under these conditions inhibition of carcinogenesis of the forestomach occurred. In a second experiment, 4-MBSNa was given by rectal intubation 5 min before BPL also administered intrarectally. Administration of BPL intrarectally produced adenomatous polyps of the large intestine. The occurrence of these neoplasms was inhibited by the prior administration of 4-MBSNa. The data presented show that 4-MBSNa has the capacity to trap direct-acting carcinogens and to inhibit the occurrence of BPL-induced neoplasia.

Methylation of DNAase-digestible DNA and of RNA in chromatin from rats treated with dimethylnitrosamine.

After injecting rats with di[14C]methylnitrosamine we have prepared liver chromatin and have examined firstly, the methylation level of the DNAase I-degradable fraction of the DNA and secondly, the level of methylation and the stability of methylated sites in chromatin RNA. Our results show that the level of 7-methylguanine in the degradable DNA is about 1.3 times that of whole DNA; therefore in the 20% or so of the DNA which is undegradable by DNAase I, the level must be very low or zero. Experiments using chromatin from rats injected with unlabelled dimethylnitrosamine plus [3H]thymidine show that the specific activity is similar in the DNAase I degradable and undegradable fractions, suggesting that there is no preferential repair in the latter region. In chromatin RNA, the level of 7-methylguanine is higher than that of whole DNA and decreases fairly rapidly within 30 h after dimethylnitrosamine treatment. Our results indicate that this decrease is due to some type of excision or repair process rather than to normal turnover.

Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure.

OBJECTIVES: This study evaluated the effects of oral therapy with coenzyme Q on echocardiographic and hemodynamic indexes of left ventricular function and on quality of life in patients with chronic left ventricular dysfunction. BACKGROUND: Coenzyme Q is a coenzyme for oxidative phosphorylation and an antioxidant and free radical scavenger. It has been claimed to improve symptoms, quality of life, left ventricular ejection fraction and prognosis in patients with cardiac failure. METHODS: Thirty patients with ischemic or idiopathic dilated cardiomyopathy and chronic left ventricular dysfunction (ejection fraction 26 +/- 6%) were randomized to a double-blind crossover trial of oral coenzyme Q versus placebo, each for 3 months. Right heart pressures, cardiac output and echocardiographic left ventricular volumes were measured at baseline and after each treatment phase, and quality of life was assessed using the Minnesota "Living With Heart Failure" questionnaire. It was calculated that to demonstrate an increase in left ventricular ejection fraction from 25% to 30% with a standard deviation of 5% using 95% confidence intervals with a power of 80% we would require 17 patients. RESULTS: Twenty-seven completed both treatment phases. There was no significant difference in left ventricular ejection fraction, cardiac volumes or hemodynamic and quality of life indices after treatment with coenzyme Q or placebo, although plasma coenzyme Q levels increased from 903 +/- 345 nmol/l(-1) to 2,029 +/- 856 nmol/l(-1). CONCLUSIONS: In patients with left ventricular dysfunction, treatment for three months with oral coenzyme Q failed to improve resting left ventricular systolic function or quality of life despite an increase in plasma levels of coenzyme Q to more than twice basal values.

Recombination and the progression of meiosis in Saccharomyces cerevisiae.

Recombination is an essential part of meiosis: in almost all organisms, including Saccharomyces cerevisiae, proper chromosome segregation and the viability of meiotic products is dependent upon normal levels of recombination. In this article we examine the kinetics of the meiotic divisions in four mutants defective in the initiation of recombination. We find that mutations in any of three Early Exchange genes (REC104, REC114 or REC102) confer a phenotype in which the reductional division occurs earlier than in an isogenic wild-type diploid. We also present data confirming previous reports that strains with a mutation in the Early Exchange gene. MEI4 undergo the first division at about the same time as wild-type cells. The rec104 mutation is epistatic to the mei4 mutation for the timing of the first division. These observations suggest a possible relationship between the initiation of recombination and the timing of the reductional division. These data also allow these four Early Exchange genes examined to be distinguished in terms of their role in coordinating recombination with the reductional division.

Isolation of mutants defective in early steps of meiotic recombination in the yeast Saccharomyces cerevisiae.

Using a selection based upon the ability of early Rec- mutations (e.g., rad50) to rescue the meiotic lethality of a rad52 spo13 strain, we have isolated 177 mutants. Analysis of 56 of these has generated alleles of the known Rec genes SPO11, ME14 and MER1, as well as defining five new genes: REC102, REC104, REC107, REC113 and REC114. Mutations in all of the new genes appear to specifically affect meiosis; they do not have any detectable mitotic phenotype. Mutations in REC102, REC104 and REC107 reduce meiotic recombination several hundred fold. No alleles of RED1 or HOP1 were isolated, consistent with the proposal that these genes may be primarily involved with chromosome pairing and not exchange.

Analysis of meiotic recombination pathways in the yeast Saccharomyces cerevisiae.

In the yeast, Saccharomyces cerevisiae, several genes appear to act early in meiotic recombination. HOP1 and RED1 have been classified as such early genes. The data in this paper demonstrate that neither a red nor a hop1 mutation can rescue the inviable spores produced by a rad52 spo13 strain; this phenotype helps to distinguish these two genes from other early meiotic recombination genes such as SPO11, REC104, or MEI4. In contrast, either a red1 or a hop1 mutation can rescue a rad50S spo13 strain; this phenotype is similar to that conferred by mutations in the other early recombination genes (e.g., REC104). These two different results can be explained because the data presented here indicate that a rad50S mutation does not diminish meiotic intrachromosomal recombination, similar to the mutant phenotypes conferred by red1 or hop1. Of course, RED1 and HOP1 do act in the normal meiotic interchromosomal recombination pathway; they reduce interchromosomal recombination to approximately 10% of normal levels. We demonstrate that a mutation in a gene (REC104) required for initiation of exchange is completely epistatic to a mutation in RED1. Finally, mutations in either HOP1 or RED1 reduce the number of double-strand breaks observed at the HIS2 meiotic recombination hotspot.

Inhibition of carcinogen-induced pulmonary and mammary carcinogenesis by chalcone administered subsequent to carcinogen exposure.

A study of the capacity of chalcone to inhibit benzo[alpha]pyrene(BP)-induced carcinogenesis of the lungs and forestomach in female A/J mice and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats has been carried out. Chalcone, 5 mg/g of diet, had a inhibitory effect on pulmonary adenoma formation (29%) and on mammary tumor formation (49%) when the compound was fed starting one week after final carcinogen administration. Chalcone did not inhibit forestomach tumor formation. In an additional study, chalcone started 4 weeks after MNU and fed for 3-week courses alternating with 3-week courses of control diet for the duration of the protocol also inhibited mammary tumor formation by 49%. The data showing that chalcone has inhibitory effects against both pulmonary and mammary carcinogenesis when given after carcinogen administration provides the basis for further investigations of this and possibly other chalcones as chemopreventive suppressing agents.

N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps.

This investigation is part of an effort to develop chemoprevention for carcinogenesis of the large bowel. The agent investigated is N-acetylcysteine (NAC). We used as a predictive biomarker, the proliferative index (PI), in a short-term human study. Patients with previous adenomatous colonic polyps are a cohort with increased risk for colon cancer and an increased PI of colonic crypts. They were randomly assigned to an experimental group given 800 mg/day of NAC for 12 weeks or a placebo group. Using proliferative cell nuclear antigen immunostaining, the PI of colonic crypts was measured prior to and after the treatments. The PI of the NAC group was decreased significantly (P < 0.02) while the placebo group showed no difference (P > 0.45). Since this decrease in PI may be an indicator of decreased risk of colon cancer, more extensive studies of the potential of NAC as a chemopreventive agent for colon cancer appear warranted.

Aortic wall stress profile after repair of coarctation of the aorta. It is related to subsequent true aneurysm formation?

UNLABELLED: True aneurysm formation at the site of coarctation repair has been increasingly recognized after synthetic patch aortoplasty. A mathematical model was developed to determine the aortic wall stress profile after coarctation repair with this technique. METHODS: A two-dimensional nonlinear mathematical model and a three-dimensional finite element model were developed for different physiologic, geometric, and materials properties variables, which were incorporated into an idealized coarctation repair. RESULTS: The models demonstrated that the major variable affecting stress levels in the aortic wall after coarctation repair was the patch geometry. If the patch was allowed to balloon out, the aortic wall stress increased out of proportion to the increase in aortic diameter because of nonlinear effects. The maximal aortic wall stress concentration occurred opposite the patch. Patch stiffness was also an important variable, with a lower stiffness (subclavian flap repair) leading to a higher aortic wall stress for the same patch geometry as a synthetic patch repair. Inferences: Development of true aneurysms after coarctation repair by synthetic patch aortoplasty is likely to result from excessive aortic wall stress due to patch geometry.

The prevalence of infective endocarditis after aortic valve replacement.

Replacement valve endocarditis occurred in 3.7% of 2443 patients who underwent primary or redo aortic valve replacements at The Prince Charles Hospital between December 31, 1969 and January 1, 1992, based on a cross-sectional follow-up in 1992 which was 98.8% complete. Because some patients had re-replacements during the study period, a total of 2686 operations were considered for analysis. A variety of replacement devices were used, including 571 allografts (21%), 1152 xenografts (43%), and 880 mechanical valves (36%). Insertion of an allograft valve resulted in a constant risk of endocarditis which, by multivariable hazard function analysis, negated the effect of any early-phase factors (p < 0.0001). With other replacement devices, the risk of infection peaked early after operation (9 weeks) and then gave way to a constant risk. Compared with the risk associated with allograft valves, constant risk was higher when the replacement device was a Carpentier-Edwards xenograft (n = 1021, p = 0.02) and lower when a St. Jude Medical mechanical valve was used (n = 505, p = 0.05). In nonallograft recipients, the presence of active preoperative endocarditis (p < 0.0001) or a concomitant synthetic synthetic aortic root replacement (p = 0.0006) increased the magnitude of the early peaking risk. Regardless of replacement device, constant risk was increased in patients with renal dysfunction (p = 0.01), in younger patients 0.04). When preoperative endocarditis was caused by Staphylococcus aureus, culture-positive postoperative wound infection was associated with increased risk of replacement valve infection (p < 0.001) and when it occurred, the same organism was usually responsible (86%). Identification of patients at increased risk for replacement valve infection may lead to reduced morbidity through strategies such as selective use of replacement devices and antimicrobial prophylaxis.

An analysis of valve re-replacement after aortic valve replacement with biologic devices.

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death. One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves). By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement. However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement. In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves. However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.

The effect of synthetic patch repair of coarctation on regional deformation of the aortic wall.

BACKGROUND: A long-term complication of synthetic patch repair of coarctation is true aneurysm formation. AIM: An in vitro study was undertaken to determine the effects of patch angioplasty on aortic geometry and strain adjacent to the patch. METHODS: Segments of human descending thoracic aorta were subject to 10 pressure loading cycles (10-120 mm Hg; 1.36-16.32 kPa) before and after simulated coarctation repair with a synthetic patch. Local curvature and strain were estimated by fitting a geometric model to reconstructed three-dimensional surface marker points. RESULTS: In the control aortas, when pressure increased from 11 +/- 1.0 to 124 +/- 4.0 mm Hg (1.5 +/- 0.14 to 16.86 +/- 0.54 kPa), average circumferential curvature decreased from 0.1543 +/- 0.03 to 0.1065 +/- 0.03 mm(-1). The average major extension reached a maximum of 1.43 +/- 0.08. After patch implantation, the average circumferential curvature was reduced relative to control at all pressures. Average major extensions were significantly greater than paired control values and reached a maximum of 1.55 +/- 0.08 at 122 +/- 4.0 mm Hg (16.59 +/- 0. 54 kPa). Substantial strain inhomogeneity was observed and major extensions were greatest immediately adjacent to the patch. INFERENCE: Synthetic patch repair of coarctation of the aorta increases wall strain and produces significant regional gradients in strain. With control aortic material properties there may be a substantial increase in wall stress immediately adjacent to the aorta, which could lead to true aneurysm formation.

Aortic valve infection. Risk factors for death and recurrent endocarditis after aortic valve replacement.

Patients (n = 195) undergoing aortic valve replacement (n = 209) for native or prosthetic valve endocarditis were studied to determine risk factors for death and recurrent endocarditis and also to determine the valve type least likely to be associated with recurrent endocarditis. Ten-year survival was 60%, the highest risk of dying occurring within the first 3 postoperative months. Risk factors for death in this early phase included increased urea concentration, higher New York Heart Association functional class, prosthetic valve endocarditis, infection status (lower in patients with healed endocarditis), longer duration of cardiopulmonary bypass, and nonuse of an allograft valve. In the late phase (beyond 3 months), risk factors included age at operation and Staphylococcus aureus infection (only in New York Heart Association functional class V). Ten years after aortic valve replacement, 79% of valves were free of recurrent endocarditis. The highest risk of recurrence was in the first 4 months. Longer duration of cardiopulmonary bypass was a weak risk factor for recurrent endocarditis in the early phase, and in the late phase risk factors were S. aureus infection (only in New York Heart Association functional classes III, IV, and V) and the use of now discontinued biologic valves. Allograft aortic valve replacement was shown to be associated with a low and constant risk of recurrent endocarditis, whereas other valve types were associated with a high early risk. The allograft valve should be the preferred replacement device for aortic root infection.

An analysis of risk factors for death and mode-specific death after aortic valve replacement with allograft, xenograft, and mechanical valves.

From September 1967 to January 1990, a total of 2100 patients underwent 2366 aortic valve replacements with a variety of allograft, xenograft, and mechanical valves. Concomitant procedures were performed in 764 patients. Actuarial survival at 12 years was 59.6% (70% confidence limits 57.8% to 61.4%). Hazard function for death was highest immediately after operation, falling to merge with a slowly rising phase of risk at approximately 3 months. Actuarial freedom from sudden death at 12 years was 88.0% (70% confidence limits 86.7% to 89.3%). The shape of the hazard function for sudden death was similar to that for death. Actuarial freedom from death with cardiac failure at 12 years was 87.9% (70% confidence limits 86.5% to 89.2%). The shape of the hazard function for death with cardiac failure was also similar to that for death. Risk factor analysis revealed the important deleterious impact on long-term survival resulting from impaired left ventricular structure and function because of aortic valve disease. No current-era valve used in this study (allograft, xenograft, or mechanical) was a risk factor for death. Both aortic wall disease and endocarditis necessitating aortic valve replacement substantially decreased long-term patient survival. Aortic valve replacement is advisable much earlier in the natural history of aortic valve disease before secondary left ventricular damage occurs.

A note on the failure of CGP 19835 A (MTP-PE) to influence the course of influenza A2 infection in human volunteers.

A single dose of the immunomodulator CGP A (MTP-PE) given intranasally to human volunteers 24 h prior to challenge with influenza A2 virus failed to protect against infection or ameriolate any subsequent illness.

Mycotic false aneurysm of the aortic suture line after heart transplantation.

Aortic suture line infection caused by Pseudomonas aeruginosa occurred in a 31-year-old man 2 months after orthotopic heart transplantation. Incomplete resection of the mycotic aneurysm and replacement of the ascending aorta with allograft aorta was performed. Subsequently, the infection recurred on the proximal suture line, and reoperation with complete excision of the mycotic aneurysm and allograft replacement of the ascending aorta was performed successfully, without recurrence of the infection.

In vivo endogenous spore formation by Coxiella burnetii in Q fever endocarditis.

AIMS: To determine whether Coxiella burnetii, the aetiological agent of Q fever, undergoes endogenous spore-like formation, the crucial stage of the developmental cycle, in the infected cardiac valves of patients with chronic Q fever endocarditis. METHODS: Surgically removed valves from three cases of Q fever endocarditis were processed for electron microscopy. Sections were stained with potassium permanganate and uranyl acetate before being extensively examined by transmission electron microscopy. RESULTS: In all three cases endogenous spore-like formation was seen in the infected cardiac valves. CONCLUSIONS: As the factors that govern sporogenesis in C burnetii are still largely unknown, it is uncertain how important are the implications of the discovery of endogenous spore-like formation in Q fever endocarditis. However, this finding may add new dimensions to current thinking about the treatment of chronic Q fever.