Epidemiological features of influenza in Canadian adult intensive care unit patients.

To identify predictive factors and mortality of patients with influenza admitted to intensive care units (ICU) we carried out a prospective cohort study of patients hospitalized with laboratory-confirmed influenza in adult ICUs in a network of Canadian hospitals between 2006 and 2012. There were 626 influenza-positive patients admitted to ICUs over the six influenza seasons, representing 17·9% of hospitalized influenza patients, 3·1/10,000 hospital admissions. Variability occurred in admission rate and proportion of hospital influenza patients who were admitted to ICUs (proportion range by year: 11·7-29·4%; 21·3% in the 2009-2010 pandemic). In logistic regression models ICU patients were younger during the pandemic and post-pandemic period, and more likely to be obese than hospital non-ICU patients. Influenza B accounted for 14·2% of all ICU cases and had a similar ICU admission rate as influenza A. Influenza-related mortality was 17·8% in ICU patients compared to 2·0% in non-ICU patients.

Empirical evaluation of neutral interactions in host-parasite networks.

While niche-based processes have been invoked extensively to explain the structure of interaction networks, recent studies propose that neutrality could also be of great importance. Under the neutral hypothesis, network structure would simply emerge from random encounters between individuals and thus would be directly linked to species abundance. We investigated the impact of species abundance distributions on qualitative and quantitative metrics of 113 host-parasite networks. We analyzed the concordance between neutral expectations and empirical observations at interaction, species, and network levels. We found that species abundance accurately predicts network metrics at all levels. Despite host-parasite systems being constrained by physiology and immunology, our results suggest that neutrality could also explain, at least partially, their structure. We hypothesize that trait matching would determine potential interactions between species, while abundance would determine their realization.

Complete sequences of a novel blaNDM-1-harbouring plasmid from Providencia rettgeri and an FII-type plasmid from Klebsiella pneumoniae identified in Canada.

OBJECTIVES: Emergence of plasmids harbouring bla(NDM-1) is a major public health concern due to their association with multidrug resistance and their potential mobility. METHODS: PCR was used to detect bla(NDM-1) from clinical isolates of Providencia rettgeri (PR) and Klebsiella pneumoniae (KP). Antimicrobial susceptibilities were determined using Vitek 2. The complete DNA sequence of two bla(NDM-1) plasmids (pPrY2001 and pKp11-42) was obtained using a 454-Genome Sequencer FLX. Contig assembly and gap closures were confirmed by PCR-based sequencing. Comparative analysis was done using BLASTn and BLASTp algorithms. RESULTS: Both clinical isolates were resistant to all ß-lactams, carbapenems, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole, and susceptible to tigecycline. Plasmid pPrY2001 (113 295 bp) was isolated from PR. It did not show significant homology to any known plasmid backbone and contained a truncated repA and novel repB. Two bla(NDM-1)-harbouring plasmids from Acinetobacter lwoffii (JQ001791 and JQ060896) shared 100% similarity to a 15 kb region that contained bla(NDM-1). pPrY2001 also contained a type II toxin/antitoxin system. pKp11-42 (146 695 bp) was isolated from KP. It contained multiple repA genes. The plasmid backbone had the highest homology to the IncFIIk plasmid type (51% coverage, 100% nucleotide identity). The bla(NDM-1) region was unique in that it was flanked upstream by IS3000 and downstream by a novel transposon designated Tn6229. pKp11-42 also contained a number of mutagenesis and plasmid stability proteins. CONCLUSIONS: pPrY2001 differed from all known plasmids due to its novel backbone and repB. pKp11-42 was similar to IncFIIk plasmids and contained a number of genes that aid in plasmid persistence.

Molecular epidemiology of vancomycin-resistant enterococcal bacteraemia: results from the Canadian Nosocomial Infection Surveillance Program, 1999-2009.

OBJECTIVES: Vancomycin-resistant enterococci (VRE) can be associated with serious bacteraemia. The focus of this study was to characterize the molecular epidemiology of VRE from bacteraemia cases that were isolated from 1999 to 2009 as part of Canadian Nosocomial Infection Surveillance Program (CNISP) surveillance activities. METHODS: From 1999 to 2009, enterococci were collected from across Canada in accordance with the CNISP VRE surveillance protocol. MICs were determined using broth microdilution. PCR was used to identify vanA, B, C, D, E, G and L genes. Genetic relatedness was examined using multilocus sequence typing (MLST). RESULTS: A total of 128 cases of bacteraemia were reported to CNISP from 1999 to 2009. In 2007, a significant increase in bacteraemia rates was observed in western and central Canada. Eighty-one of the 128 bacteraemia isolates were received for further characterization and were identified as Enterococcus faecium. The majority of isolates were from western Canada (60.5%), followed by central (37.0%) and eastern (2.5%) Canada. Susceptibilities were as follows: daptomycin, linezolid, tigecycline and chloramphenicol, 100%; quinupristin/dalfopristin, 96.3%; high-level gentamicin, 71.6%; tetracycline, 50.6%; high-level streptomycin, 44.4%; rifampicin, 21.0%; nitrofurantoin, 11.1%; clindamycin, 8.6%; ciprofloxacin, levofloxacin and moxifloxacin, 1.2%; and ampicillin, 0.0%. vanA contributed to vancomycin resistance in 90.1% of isolates and vanB in 9.9%. A total of 17 sequence types (STs) were observed. Beginning in 2006 there was a shift in ST from ST16, ST17, ST154 and ST80 to ST18, ST412, ST203 and ST584. CONCLUSIONS: The increase in bacteraemia observed since 2007 in western and central Canada appears to coincide with the shift of MLST STs. All VRE isolates remained susceptible to daptomycin, linezolid, chloramphenicol and tigecycline.

Carbapenem-resistant Gram-negative bacilli in Canada 2009-10: results from the Canadian Nosocomial Infection Surveillance Program (CNISP).

OBJECTIVES: To investigate the occurrence and molecular mechanisms associated with carbapenemases in carbapenem-resistant Gram-negative isolates from Canadian cases. METHODS: Twenty hospital sites across Canada submitted isolates for a 1 year period starting 1 September 2009. All Enterobacteriaceae with MICs ≥ 2 mg/L and Acinetobacter baumannii and Pseudomonas aeruginosa with MICs ≥ 16 mg/L of carbapenems were submitted to the National Microbiology Laboratory (NML) where carbapenem MICs were confirmed by Etest and isolates were characterized by PCR for carbapenemase genes, antimicrobial susceptibilities, PFGE and plasmid isolation. RESULTS: A total of 444 isolates (298 P. aeruginosa, 134 Enterobacteriaceae and 12 A. baumannii) were submitted to the NML of which 274 (61.7%; 206 P. aeruginosa, 59 Enterobacteriaceae and 9 A. baumannii) met the inclusion criteria as determined by Etest. Carbapenemase genes were identified in 30 isolates: bla(GES-5) (n = 3; P. aeruginosa), bla(KPC-3) (n = 7; Enterobacteriaceae), bla(NDM-1) (n = 2; Enterobacteriaceae), bla(VIM-2) and bla(VIM-4) (n = 8; P. aeruginosa) bla(SME-2) (n = 1; Enterobacteriaceae) and bla(OXA-23) (n = m9; A. baumannii). PFGE identified a cluster in each of Enterobacteriaceae, P. aeruginosa and A. baumannii corresponding to isolates harbouring carbapenemase genes. Three KPC plasmid patterns (IncN and FllA) were identified where indistinguishable plasmid patterns were identified in unrelated clinical isolates. CONCLUSIONS: Carbapenemases were rare at the time of this study. Dissemination of carbapenemases was due to both dominant clones and common plasmid backbones.

Soft Tissue Special Issue: Chondroid Neoplasms of the Skull.

Clinically, radiologically, and pathologically, chondroid neoplasms of the skull can be diagnostically challenging due to overlapping features in each of these domains. Compounding the problem for the pathologist, there is also significant morphologic, immunophenotypic, and molecular genetic overlap between benign and malignant cartilaginous lesions, and the majority of these lesions are encountered quite rarely in routine surgical pathology practice. Each of these factors contribute to the diagnostic difficulty posed by these lesions, highlighting the importance of radiologic-pathologic correlation in the diagnosis. This review is intended to provide an update for surgical pathologists on some of the most commonly encountered chondroid neoplasms in the skull, and includes the following lesions: chondromyxoid fibroma, synovial chondromatosis, chondrosarcoma and variants, and chordoma and variants. For each of these lesions, the differential diagnosis and useful ancillary tests will be discussed in the context of a broad range of additional primary and secondary lesions.

Destabilizing and stabilizing forces to assess equilibrium during everyday activities.

Postural stability is essential to functional activities. This paper presents a new model of dynamic stability which takes into account both the equilibrium associated with the body position over the base of support (destabilizing force) and the effort the subject needs to produce to keep his/her centre of mass inside the base of support (stabilizing force). The ratio between these two forces (destabilizing over stabilizing) is calculated to provide an overall index of stability for an individual. Preliminary results from data collected during walking at preferred and maximal safe speed in four older adults (aged from 64 to 84yr) showed that both forces are lower for subjects with reduced maximal gait speed. In addition, the stabilizing force increases by 2-3 times from preferred to maximal speed, while the destabilizing force barely changes with gait speed. Overall, the model through the index of stability attributes lower dynamic stability to subjects with lower maximal gait speed. These preliminary results call for larger-scale studies to pursue the development and validation of the model and its application to different functional tasks.

A chair with a platform setup to measure the forces under each thigh when sitting, rising from a chair and sitting down.

This paper describes the design, technical characteristics and first results of an adjustable instrumented chair with a sitting surface that records the forces under each thigh. The seat includes a force platform assembly suitable for measuring the magnitude, position and direction of the force applied to each thigh while sitting or rising from the chair. The natural frequency of the chair fixed to the floor was found to be 14.0 +/- 2 Hz with an estimated damping of xi = 0.20. Static tests showed that the maximal errors were 2% of the full-scale output (726 N vertically, 164 N horizontally) for both vertical and horizontal forces. The root mean square error of the center of pressure location was estimated as 5 mm. Preliminary data on the net joint moment at the hips of one healthy subject computed with and without consideration for the forces under the thighs revealed significant amplitude differences. In conclusion, the results indicate that the characteristics of the instrumented chair are acceptable and the chair can be used to assess the biomechanics of sitting and sit-to-stand and stand-to-sit tasks in various subject populations.

Ear and Temporal Bone Pathology: Neural, Sclerosing and Myofibroblastic Lesions.

Neural, sclerosing, and myofibroblastic lesions of the ear and temporal bone present diagnostic challenges for both clinicians and pathologists due to significant overlap in their clinical presentations, histologic appearances, and immunohistochemical profiles. While some of these lesions, such as schwannomas, are relatively common, others are rendered even more difficult because they are encountered very rarely in routine surgical pathology practice. This review is intended to provide an update on the pathology of some of the most commonly encountered primary diagnostic entities for the ear and temporal bone, and includes the following neural lesions: schwannoma, meningioma, and encephalocele/meningocele. Sclerosing lesions that will be discussed include spindle cell and sclerosing rhabdomyosarcoma, sclerosing epithelioid fibrosarcoma, and sclerosing paraganglioma. Finally, myofibroblastic lesions that will be reviewed are nodular fasciitis, IgG4-related disease, and solitary fibrous tumor. For each of these lesions, the differential diagnosis and useful ancillary tests will be discussed in the context of a broad range of additional primary and secondary lesions.

Point prevalence survey for healthcare-associated infections within Canadian adult acute-care hospitals.

A survey of adult patients 19 years of age and older was conducted in February 2002 in hospitals across Canada to estimate the prevalence of healthcare-associated infections (HAIs). A total of 5750 adults were surveyed; 601 of these had 667 HAIs, giving a prevalence of 10.5% infected patients and 11.6% HAIs. Urinary tract infections (UTI) were the most frequent HAI, shown by 194 (3.4%) of the patients surveyed. Pneumonia was found in 175 (3.0%) of the patients, surgical site infections (SSI) in 146 (2.5%), bloodstream infections (BSI) in 93 (1.6%) and Clostridium difficile-associated diarrhoea (CDAD) in 59 (1%). In this first national point prevalence study in Canada, the prevalence of HAI was found to be similar to that reported by other industrialized countries.

Antimicrobial use and antimicrobial resistance trends in Canada: 2014.

BACKGROUND: There is a global concern that the emergence of antimicrobial resistance (AMR) threatens our ability to treat infectious diseases. The Canadian Antimicrobial Resistance Surveillance System (CARSS) was created in response to the Government of Canada's commitment to addressing AMR. CARSS integrates information from nine different national surveillance systems for tracking antimicrobial use (AMU) and AMR in both humans and animals to inform AMU/AMR research and policy. OBJECTIVE: To provide highlights of CARSS data on antimicrobial use in humans and animals, AMR trends in human infections in both hospital and community settings and AMR bacteria found in food production animals. METHODS: Information on AMU in animals and humans is purchased and additional information on AMU in animals is collected through the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). AMR data in humans focuses on first priority organisms. Data on priority organisms for hospital-based AMR is collected through Canadian Nosocomial Infection Surveillance Program (CNISP), Canadian Tuberculosis Laboratory Surveillance System (CTBLSS), Canadian Tuberculosis Laboratory Surveillance System (CTBRS), Canadian Tuberculosis Reporting System (CTBRS) and CIPARS. Data on community-based AMR is collected through CTBLSS, CTBRS, CIPARS, the Antimicrobial-resistant Neisseria gonorrhoeae Surveillance System (ARNGSS) and the National Surveillance of Invasive Streptococcal Disease (NSISD). AMR data on animals is collected through CIPARS. RESULTS: In terms of antibiotic usage in 2014, approximately 82% of antimicrobials were directed to food production animals, 18% to humans and less than one percent each to companion animals (e.g., pets) and crops. Over the past five years, 73% of antimicrobials distributed to food production animals belonged to the same classes as those used in human medicine. Antibiotic usage in humans has remained relatively stable. Trends in 2014 for AMR in hospitals include declining rates of hospital-acquired Clostridium difficile to 3.4 cases per 1,000 patient admissions, methicillin-resistant Staphylococcus aureus (MRSA) infections to 2.89 cases per 10,000 patient days and vancomycin-resistant Enterococci (VRE) to 0.45 cases per 10,000 patient days. Resistance to a number of antimicrobials used to treat Streptococcus pneumoniae has decreased since the introduction of pneumococcal vaccine in 2010. In contrast, trends in 2014 for AMR in the community included increasing rates of community-acquired N. gonorrhoeae - 52.4% of isolates were resistant to at least one antibiotic. Trends for carbapenem-resistant Enterobacteriaceae (CRE) were stable at 0.22 cases per 10,000 patient days. Also, between 2004 and 2014, nine percent of tuberculosis (TB) culture positive cases were resistant to at least one first line anti-tuberculosis drug and this has remained relatively stable over that time. Trends in 2014 for AMR in food production animals showed decreasing resistance of Escherichia coli and Salmonella species to third-generation cephalosporins (ceftriaxone) in poultry associated with a decrease in cephalosporin use on chicken farms, but resistance to ciprofloxacin in Campylobacter species in chicken and cattle has been increasing. CONCLUSION: Overall, antibiotic use in humans has not declined despite concerns about overuse. Although resistance rates of C. difficile, VRE, MRSA and AMR S. pneumoniae have been gradually decreasing and drug-resistant tuberculosis and CRE have remained stable, community-associated drug-resistant N. gonorrhoeae has been increasing. Although efforts to decrease antibiotic use in animals have been met with some success, AMR continues to occur in fairly high levels in food production animals.

A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.

A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.

Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma.

Gemcitabine has modest activity in the treatment of advanced pancreatic cancer and is a potent radiosensitizer. We conducted a Phase I trial to determine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically proven, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 cGy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed in over half the patients treated. Nonhematological toxicities were significant and included fatigue, anorexia, nausea, vomiting, and dehydration. Forty-four % of the patients required admission to the hospital for management of nausea/vomiting and dehydration. The risk of hospitalization appeared to be dose-related; all of the three patients treated at 500 mg/m(2)/week required hospital admission during treatment. Seventeen patients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partial response to therapy. The median survival for the entire group was 6 months. The 1-year survival rate for patients with an objective response to therapy was 66%. The clinical responses observed in this group of patients suggest gemcitabine is a clinically relevant radiosensitizer in patients with pancreatic adenocarcinoma. However, the toxic effects are significant, suggesting that until dose and scheduling issues are explored further, concomitant administration of gemcitabine and radiation therapy should still be considered investigational.

Quantification of level of effort at the plantarflexors and hip extensors and flexor muscles in healthy subjects walking at different cadences.

The plantarflexor, hip extensor and hip flexor muscle groups contribute by their concentric action to generate most of the energy during level gait in healthy subjects. The goal of the present study was to determine, during the main energy generation phases, the relative demand of these three groups in 14 healthy subjects walking at four cadences (self-selected, 60, 80 and 120 steps/min). The muscular utilization ratio (MUR), that compares the net joint moment obtained during gait to the maximal potential moment (MPM) at each percentage of the gait cycle, was used to estimate the mechanical relative demand. The MPM values were obtained by regression equations developed from torque data measured with a Biodex dynamometric system. The results showed that the peak MURs increased with gait cadence. The peak values were not significantly different between sides for all cadences despite mean absolute lateral differences ranging from 7% to 10%. The mean peak MURs of both sides ranged from 51.3% to 62.6%, from 20.7% to 49.9% and from 14.9% to 42.5%, for the plantarflexors, hip flexors and hip extensors, respectively. Highly significant associations were found between the MURs and net moments (numerator of the MUR ratio), with Pearson coefficients (r) superior to 0.80 for all muscles groups. The association between the MURs and the maximal potential moments (denominator of MUR ratio) was lower (0.01

A mechanism for the RNA-catalyzed formation of 5'-phosphates. The origin of nucleases.

Processes involved in RNA metabolism can be distinguished by the nature of the sugar phosphate substitution (5' or 3') in intermediates or products. Although it is known that 3'-phosphates are produced via a 2',3'-cyclic phosphate intermediate, formed by nucleophilic attack on the phosphodiester bond by the adjacent 2'-OH, little is known about the production of 5'-phosphate products. We attribute 5'-phosphate intermediates and products to a preferred configuration of the pentavalent phosphorus intermediate resulting from the attack of a distant nucleophile. This intermediate is favored, since its formation is possible without major conformational changes in the molecule. Based on the two products of nucleic acid hydrolysis we define: the conjunct and disjunct nucleophile mechanisms, each of which would have independent origins. Indeed, the products of an overwhelming number of nucleases and RNases are consistent with one of these mechanistic models demonstrating that the origin of these enzymes are deeply rooted in the intrinsic chemistry of phosphate esters.

Ca(2+)-channel blockers and nucleoside triphosphate diphosphohydrolase (NTPDase) influence of diltiazem, nifedipine, and verapamil.

The nucleoside triphosphate diphosphohydrolases (NTPDase; EC 3.6.1. 5) are a family of ectonucleotidases associated with vascular endothelial and smooth muscle cells. These ectonucleotidases are involved in the control of vascular tone by regulating the level of circulating ATP. Ca(2+)-channel blocking agents are currently used for the treatment of hypertension. Considering the external localization of the NTPDase catalytic site and its Ca(2+) requirement for enzyme activity, a possible interference of calcium antagonists (nifedipine, verapamil-HCl, and diltiazem-HCl and some of its metabolites) could be anticipated. To test that hypothesis, an NTPDase-enriched particulate fraction was used. Our results show that verapamil, diltiazem, and its metabolites all produced a concentration-dependent inhibition of NTPDase, at concentrations greater or equal to 0.1 mM with verapamil and to 0.5 mM with diltiazem and its metabolites, whereas no significant effect was observed with nifedipine. Kinetic studies, carried out to define the mode of action of these drugs, showed a mixed type of inhibition. Based on their respective K(i) values (in parentheses, in mM), inhibitory potencies of these molecules were in the following order: desacetyl-N-desmethyldiltiazem (M(2)-HCl; 0.6) > verapamil (0.76) > N-desmethyldiltiazem (M(A;) 0.9) > diltiazem (2.4) > desacetyl-O-desmethyldiltiazem (M(4)-HCl; 3.5) > desacetyl N, O-desmethyldiltiazem (M(6)-HCl; 3.9). Hence, these calcium antagonists can be considered as weak NTPDase inhibitors. Moreover, based on these K(i) values and the range of concentrations found in the blood, NTPDase would not be inhibited significantly in vivo.

Phase-I and phase-ii trials of a laboratory-derived synergistic combination of Cisplatin and 2'-deoxy-5-azacytidine.

Phase I and phase II trials of a laboratory-derived synergistic combination of cisplatin (cDDP) and 2'-deoxy-5-azacytidine (5-aza-CdR) were conducted. The maximum tolerated doses (MTDs) were 50 mg/m(2) of 5-aza-CdR and 75 mg/m(2) of cDDP. A response rate of 17% (90% confidence interval (CI) = 0%-37%) was observed in patients with metastatic carcinoma of unknown primary (UPC). The 5-aza-CdR/cDDP combination was safely administered at doses mirroring concentrations that significantly lessen cDDP resistance of human ovarian cancer cells in vitro. While the observed response rate did not warrant further study in UPC, evaluation of this regimen should be considered in patients with cDDP-resistant ovarian cancer.

Metastatic carcinoma resulting in hepar lobatum.

Hepar lobatum is an acquired liver deformity mostly known as the end-stage of tertiary syphilis. The authors report two cases of hepar lobatum resulting from metastatic mammary ductal carcinoma in the liver and reassess the clinicopathologic features of seven previously reported cases (two in the German language). A liver of near-normal weight with an irregularly lobulated contour, capsular indentations/crevices from which intersecting (carcinoma-bearing) fibrous septa extended deep into the parenchyma, a predominant centrifugal distribution of lesional areas, and many septa abutting on the degenerated center of tumor nodules were the salient gross features. No significant tumor/fibrous occlusion of intrahepatic branches of portal or hepatic veins, nor cirrhotic type nodular hepatocellular regeneration was observed. Both of these patients experienced a drastic decrease in CEA serum levels during multiagent palliative chemotherapy. In one patient, abundant macrophages in conjunction with minimal residual tumor were present within intrahepatic septa. The pathogenesis of this condition appears largely related to an active phase of chemo-induced tumor regression with subsequent tissue collapse, followed by an organizing phase of healing and scar contraction.

Catecholamine sulfates: end products or metabolic intermediates?

Dopamine-beta-hydroxylase catalyzes the beta-oxidation of dopamine to noradrenaline while phenylethanolamine-N-methyltransferase converts noradrenaline to adrenaline. Since catecholamine sulfates represent the predominant form of catecholamines in human tissues, we have studied the role of dopamine sulfate and noradrenaline sulfate as alternate substrates for dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase, respectively. Dopamine 3-sulfate, dopamine 4-sulfate and noradrenaline 3-sulfate were chemically synthesized and exhaustively purified by ion-exchange chromatography. Dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase were partially purified from human adrenals. Using tyramine as substrate, dopamine-beta-hydroxylase is slightly inhibited by dopamine 3-sulfate according to some irreversible or mixed mechanisms. When dopamine-beta-hydroxylase was incubated with dopamine 3-sulfate or dopamine 4-sulfate, we were not able to find any synthesis of either noradrenaline sulfate or free noradrenaline. Using phenylethanolamine as substrate, the enzymatic activity of phenylethanolamine-N-methyltransferase remains unchanged with addition of dopamine 3-sulfate, dopamine 4-sulfate or noradrenaline 3-sulfate. It was concluded that dopamine sulfate is not an alternate substrate for either dopamine-beta-hydroxylase or phenylethanolamine-N-methyltransferase nor is noradrenaline 3-sulfate an alternate substrate for phenylethanolamine-N-methyltransferase.

Influence of contractile tension development on dynamic strength measurements of the plantarflexors in man.

The influence of the contractile tension rise time on isokinetic force-angle records has been inferred from static force-time curves but has not been experimentally determined. The purpose of this study is thus to describe the influence of the contractile rise time on the force-angle curves produced during maximal voluntary, acceleration controlled, isokinetic plantarflexions at 30 degrees/s. Since we could not measure directly the period of force development unbiased by changes in muscle length during the movements, we devised an experimental strategy which allowed the computation of the dynamic force-time curve. Thus in five normal men, we first recorded force-angle curves produced during maximal voluntary plantarflexion movements preceded by maximal static pre-loading (D:-10 degrees Max) in order to eliminate the period of tension development from the force-angle record. Next, we recorded force-angle curves produced during maximal voluntary contractions initiated from two different starting angles without pre-loading (D:-10 degrees Min and D:0 degrees Min) to include the period of tension rise. The dynamic force-time curve was computed by correcting these force-angle curves (D:-10 degrees Min and D:0 degrees Min) for the hypothetical loss in force due to muscle shortening. We compared the relative (to remove the effects of force magnitude) computed dynamic force-time curves with relative static force-time curves measured at three different angles. We found the shape and several other parameters of all three static and both computed dynamic force-time curves to be similar (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)