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1.
Pneumologie ; 74(8): 515-544, 2020 Aug.
Article in German | MEDLINE | ID: mdl-32823360

ABSTRACT

The present guideline aims to improve the evidence-based management of children and adolescents with pediatric community-acquired pneumonia (pCAP). Despite a prevalence of approx. 300 cases per 100 000 children per year in Central Europe, mortality is very low. Prevention includes infection control measures and comprehensive immunization. The diagnosis can and should be established clinically by history, physical examination and pulse oximetry, with fever and tachypnea as cardinal features. Additional signs or symptoms such as severely compromised general condition, poor feeding, dehydration, altered consciousness or seizures discriminate subjects with severe pCAP from those with non-severe pCAP. Within an age-dependent spectrum of infectious agents, bacterial etiology cannot be reliably differentiated from viral or mixed infections by currently available biomarkers. Most children and adolescents with non-severe pCAP and oxygen saturation > 92 % can be managed as outpatients without laboratory/microbiology workup or imaging. Anti-infective agents are not generally indicated and can be safely withheld especially in children of young age, with wheeze or other indices suggesting a viral origin. For calculated antibiotic therapy, aminopenicillins are the preferred drug class with comparable efficacy of oral (amoxicillin) and intravenous administration (ampicillin). Follow-up evaluation after 48 - 72 hours is mandatory for the assessment of clinical course, treatment success and potential complications such as parapneumonic pleural effusion or empyema, which may necessitate alternative or add-on therapy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Pneumonia/drug therapy , Practice Guidelines as Topic , Pulmonary Medicine/standards , Adolescent , Anti-Bacterial Agents/administration & dosage , Child , Community-Acquired Infections/diagnosis , Community-Acquired Infections/virology , Europe , Germany , Humans , Infant , Pneumonia/diagnosis , Pneumonia/virology , Societies, Medical
3.
Euro Surveill ; 20(28)2015 Jul 16.
Article in English | MEDLINE | ID: mdl-26212142

ABSTRACT

Sequence-based typing (SBT) for Legionella pneumophila (Lp) has dramatically improved Legionnaires' disease (LD) cluster investigation. Microbial whole genome sequencing (WGS) is a promising modality for investigation but sequence analysis methods are neither standardised, nor agreed. We sought to develop a WGS-based typing scheme for Lp using de novo assembly and a genome-wide gene-by-gene approach (core genome multilocus sequence typing, cgMLST). We analysed 17 publicly available Lp genomes covering the whole species variation to define a core genome (1,521 gene targets) which was validated using 21 additional published genomes. The genomes of 12 Lp strains implicated in three independent cases of paediatric humidifier-associated LD were subject to cgMLST together with three 'outgroup' strains. cgMLST was able to resolve clustered strains and clearly identify related and unrelated strains. Thus, a cgMLST scheme was readily achievable and provided high-resolution analysis of Lp strains. cgMLST appears to have satisfactory discriminatory power for LD cluster analysis and is advantageous over mapping followed by single nucleotide polymorphism (SNP) calling as it is portable and easier to standardise. cgMLST thus has the potential for becoming a gold standard tool for LD investigation. Humidifiers pose an ongoing risk as vehicles for LD and should be considered in cluster investigation and control efforts.


Subject(s)
Genetic Variation , Legionella pneumophila/classification , Legionella pneumophila/genetics , Molecular Typing/methods , Multilocus Sequence Typing/methods , Sequence Analysis, DNA , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Genome, Bacterial , Humans , Legionella pneumophila/isolation & purification , Molecular Epidemiology/methods , Molecular Sequence Data , Polymorphism, Single Nucleotide
4.
Caries Res ; 48(1): 24-31, 2014.
Article in English | MEDLINE | ID: mdl-24216710

ABSTRACT

Early childhood caries (ECC) is closely related to high numbers of mutans streptococci, lactobacilli and Candida albicans. Oral colonization of these microorganisms was monitored in a prospective clinical study in order to investigate the effect of comprehensive treatment under general anesthesia and the sustainability of microbial changes. Saliva samples were collected from 50 healthy infants with ECC before and in regular intervals up to 12 months after treatment. Microorganisms were detected by cultivation on selective agars (CRT® bacteria and Sabouraud/CandiSelect™) and scored. Additionally, plaque on upper front teeth and the dmft were recorded. Parents were repeatedly interviewed regarding the children's diet and oral hygiene, accompanied by corresponding advice. Plaque frequency and the numbers of mutans streptococci, lactobacilli and yeasts were significantly reduced as a result of treatment (p < 0.0001, Wilcoxon test). Nevertheless, this effect was not permanent. An ordinal regression model on the follow-up period revealed that the odds for bacteria and yeasts to reach a higher score increased linearly over time (p < 0.01) with an odds ratio of 2.244 per year. One third (34%) of the children developed new dentinal lesions within 1 year postoperatively. High scores of lactobacilli before treatment predicted caries relapse (p < 0.05). Nutritional and oral hygiene habits changed only slightly despite advising. Elimination and restoration of ECC lesions under general anesthesia proved to be an effective procedure in reducing cariogenic bacteria and yeasts. A satisfactory and sustainable success, however, could be achieved neither regarding microbiologic parameters nor with respect to the relapse rate. More suitable strategies are needed.


Subject(s)
Candida/isolation & purification , Dental Caries/therapy , Lactobacillus/isolation & purification , Streptococcus mutans/isolation & purification , Bacterial Load , Bacteriological Techniques , Candida/classification , Child, Preschool , Colony Count, Microbial , Composite Resins/chemistry , Counseling , DMF Index , Dental Caries/microbiology , Dental Materials/chemistry , Dental Plaque Index , Dental Prophylaxis , Dental Restoration, Permanent/methods , Feeding Behavior , Follow-Up Studies , Humans , Infant , Oral Hygiene , Prospective Studies , Recurrence , Saliva/microbiology , Tooth Extraction , Treatment Outcome
5.
Eur J Clin Microbiol Infect Dis ; 31(7): 1673-7, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22120420

ABSTRACT

Legionnaires' disease is diagnosed predominantly by urinary antigen detection, and patient isolates are rarely available. The lipopolysaccharide (LPS) epitope pattern of isolates detected by monoclonal antibodies is an accepted marker for the phenotyping of L. pneumophila serogroup 1 strains into monoclonal subgroups. L. pneumophila LPS is the dominant antigen in patients' urinary specimens. By using commercially available microtiter wells coated with rabbit anti-Legionella serogroup 1 IgG as the catching antibody, LPS components in urine specimens were bound and detected separately by corresponding monoclonal antibodies of the Dresden Panel. The subtyping of LPS on urinary antigen molecules by using enzyme-linked immunosorbent assay (ELISA) allows deducing of first evidences for the identity/non-identity of environmental isolates and the legionellosis pathogen. Most importantly in our study, urinary antigen typing possesses high probability to distinguish (or does not distinguish) if the pathogen belongs to the MAb 3/1-negative L. pneumophila strains, which are widespread contaminants of water systems, but represent the minority of patient isolates.


Subject(s)
Antibodies, Bacterial , Antibodies, Monoclonal , Antigens, Bacterial/classification , Bacterial Typing Techniques/methods , Legionella pneumophila/classification , Legionnaires' Disease/microbiology , Urine/microbiology , Antigens, Bacterial/analysis , Epidemiologic Methods , Humans , Legionnaires' Disease/epidemiology , Urine/chemistry
6.
Eur J Clin Microbiol Infect Dis ; 31(5): 781-9, 2012 May.
Article in English | MEDLINE | ID: mdl-21842293

ABSTRACT

Infectious agents are likely to play a role in the pathogenesis of chronic inflammatory diseases, including abdominal aortic aneurysms (AAAs). The goal of this study was to determine if Borrelia burgdorferi sensu lato (sl), a microorganism responsible for Lyme disease, is involved in the etiology of AAAs. The presence of serum antibodies against B. burgdorferi sl was measured with enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting in 96 AAA and 108 peripheral artery disease (PAD) patients. Polymerase chain reaction (PCR) was used for the detection of Borrelia-specific DNA in the aneurysm wall. Among AAA patients 34% and among PAD patients 16% were seropositive for B. burgdorferi sl antibodies (Fisher's exact test, p = 0.003; odds ratio [OR] 2.79; 95% confidence interval [CI] 1.37-5.85). In the German general population, 3-17% are seropositive for Borrelia antibodies. No Borrelia DNA was detected in the aneurysm wall. Our findings suggest a relationship between AAAs and B. burgdorferi sl. We hypothesize that the underlying mechanism for B. burgdorferi sl in AAA formation is similar to that by the spirochete Treponema pallidum; alternatively, AAAs could develop due to induced autoimmunity via molecular mimicry due to similarities between some of the B. burgdorferi sl proteins and aortic proteins.


Subject(s)
Antibodies, Bacterial/blood , Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/etiology , Borrelia burgdorferi Group/immunology , Lyme Disease/complications , Aged , Aged, 80 and over , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged
7.
J Appl Microbiol ; 112(6): 1212-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22413947

ABSTRACT

AIMS: We undertook a series of experiments to investigate the susceptibility of Legionella pneumophila grown under extracellular and intracellular conditions and other water-related bacteria to silver ions. METHODS AND RESULTS: In this study, the antimicrobial effect of silver ions to intra- and extra-cellular grown Legionella bacteria was investigated. The minimal inhibitory concentration (MIC) after 24 h exposure, leading to a 5 log reduction, was c. 64 µg l(-1) AgNO(3) for extracellular grown Legionella and other tested Gram-positive and Gram-negative bacteria. In contrast, the MIC for intracellularly grown Legionella was up to 4096 µg l(-1) AgNO(3) after 24 h. Furthermore, the heterotrophic bacteria grown within a biofilm model were killed at a concentration of 4-16 µg l(-1) AgNO(3). In contrast, biofilm-associated Legionella were less sensitive (MIC 128-512 µg l(-1) AgNO(3)). CONCLUSION: Intracellularly and biofilm-grown legionellae are less sensitive against silver compared with agar-grown bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The reduced sensitivity of Legionella grown in amoebae might explain why the effect of silver decontamination requires an extended exposure in field trials.


Subject(s)
Acanthamoeba castellanii/microbiology , Biofilms , Legionella pneumophila/drug effects , Legionella pneumophila/growth & development , Silver Nitrate/pharmacology , Agar , Bacteriological Techniques
8.
Sci Rep ; 12(1): 22453, 2022 12 27.
Article in English | MEDLINE | ID: mdl-36575230

ABSTRACT

In the COVID-19 pandemic, children were considered to play a major role in SARS-CoV-2 transmission similar to influenza. Thus, mitigation measures have been focused on children, impacting their everyday life severely. Despite this, infectivity in this age group regarding SARS-CoV-2 is not yet clarified. We performed a serology study in households with confirmed SARS-CoV-2 infection to evaluate virus transmission with focus on children and adolescents. Between January and July 2021, 341 minors and 650 adults from 300 households with a confirmed index case participated in the FamilyCoviDD19-study including serological assessment for SARS-CoV-2 antibodies and a questionnaire on demographics, recent and ongoing symptoms, hygiene measures and comorbidities. 45 (16.3%) of all index cases were < 18 years old. Thereof, 55.6% reported COVID-19 associated symptoms, while nearly all adult index cases were symptomatic (94.8%). There was significantly less virus transmission by children and adolescents compared to adult index cases with a secondary attack rate of 0.29 vs. 0.54. With the caveat that the results do not necessarily apply to the Delta and Omicron variants, we conclude that children and adolescents are less susceptible for SARS-CoV-2 infection, more frequently show an asymptomatic course of disease and are less infective than adults.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Adult , Child , Adolescent , COVID-19/epidemiology , Pandemics , Family Characteristics
9.
J Appl Microbiol ; 110(4): 1032-44, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21276147

ABSTRACT

AIMS: To perform an international trial to derive alert and action levels for the use of quantitative PCR (qPCR) in the monitoring of Legionella to determine the effectiveness of control measures against legionellae. METHODS AND RESULTS: Laboratories (7) participated from six countries. Legionellae were determined by culture and qPCR methods with comparable detection limits. Systems were monitored over ≥10 weeks. For cooling towers (232 samples), there was a significant difference between the log mean difference between qPCR (GU l(-1) ) and culture (CFU l(-1) ) for Legionella pneumophila (0·71) and for Legionella spp. (2·03). In hot and cold water (506 samples), the differences were less, 0·62 for Leg. pneumophila and 1·05 for Legionella spp. Results for individual systems depended on the nature of the system and its treatment. In cooling towers, Legionella spp. GU l(-1) always exceeded CFU l(-1) , and usually Legionella spp. were detected by qPCR when absent by culture. The pattern of results by qPCR for Leg. pneumophila followed the culture trend. In hot and cold water, culture and qPCR gave similar results, particularly for Leg. pneumophila. There were some marked exceptions with temperatures ≥50°C, or in the presence of supplementary biocides. Action and alert levels for qPCR were derived that gave results comparable to the application of the European Guidelines based on culture. Algorithms are proposed for the use of qPCR for routine monitoring. CONCLUSIONS: Action and alert levels for qPCR can be adjusted to ensure public health is protected with the benefit that remedial actions can be validated earlier with only a small increase in the frequency of action being required. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms it is possible to derive guidelines on the use of qPCR for monitoring the control of legionellae with consequent improvement to response and public health protection.


Subject(s)
Legionella/isolation & purification , Real-Time Polymerase Chain Reaction , Water Microbiology , Legionella/genetics , Legionella pneumophila/genetics , Legionella pneumophila/isolation & purification , Temperature
10.
Article in German | MEDLINE | ID: mdl-21626373

ABSTRACT

Legionellae are environmental bacteria that can be frequently isolated from technical water supply systems. The most prevalent species is Legionella pneumophila, especially serogroup 1. In the environment, legionellae multiply in amoebae. Since Legionella pneumonias cannot be distinguished from pneumonias caused by other microbial pathogens, special microbiological tests, e.g., urinary antigen assays, are essential to detect Legionella infections. All water supply systems to which the patient is exposed during the incubation time of 2 to 10 days might be the source of the infection. This can be confirmed or excluded by molecular typing of isolates from patients and the environment. The most commonly used techniques are monoclonal antibody typing and sequence-based typing (SBT). Some sequence types (ST) are frequently found among clinical strains but are seldom isolated from the environment, e.g., ST 23, 42, 47, 62, and 146. It is safe to assume that such strains are highly virulent. Conversely, it does not seem to be justified to dedicate the same awareness to all environmental Legionella strains.


Subject(s)
Environmental Pollutants/isolation & purification , Genetic Variation/genetics , Legionella pneumophila/genetics , Legionella pneumophila/isolation & purification , Legionnaires' Disease/microbiology , Humans , Legionella pneumophila/classification
11.
Article in German | MEDLINE | ID: mdl-21626372

ABSTRACT

Legionella are present in the environment as well as in biofilms of water installation systems. Most Legionella live in amoebae. More than 51 different species of Legionella have been identified; however, most pneumonias are caused by Legionella pneumophila serogroup 1. Legionnaire's disease has an incidence of about 4% in Germany. Most cases of Legionnaire's disease are sporadic. Microbiological identification of Legionella can be achieved by cultivation of Legionella spp. on specific media, performing of Legionella-specific PCR from respiratory samples, or Legionella urinary antigen testing. Patients with severe underlying diseases, patients receiving immunosuppression, and patients who are heavy smokers have a predisposition to Legionnaire's disease. Men are significantly more often affected. Whereas outpatients show a mild clinical course, mortality for hospitalized patients is 11.2%. It can be assumed that only a minority of cases of Legionnaire's disease is recognized and reported in Germany.


Subject(s)
Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Disease Outbreaks/statistics & numerical data , Legionella pneumophila/isolation & purification , Legionnaires' Disease/epidemiology , Legionnaires' Disease/microbiology , Community-Acquired Infections/diagnosis , Female , Germany/epidemiology , Humans , Legionnaires' Disease/diagnosis , Male , Prevalence , Sex Distribution , Sex Factors
12.
Article in German | MEDLINE | ID: mdl-22015788

ABSTRACT

Between December 2009 and the end of January 2010, the largest hitherto known outbreak of Legionella in Germany took place in the cities of Ulm and Neu-Ulm. Of a total of 64 patients involved, 60 patients had to be hospitalized, and 5 patients died from the infection. This event was caused by a wet cooling tower of a large air conditioning system in the city center of Ulm. The search for the source of the Legionella emission was extremely difficult, since these plants are neither notifiable nor subject to authorization in Germany. We report about the search for the source and the measures to control the outbreak. We also discuss communication and coordination during these investigations. Regulatory measures as proposed by the World Health Organization (WHO) and the European Network for Legionellosis (EWGLI) and already implemented in numerous other European countries would be desirable to prevent such outbreaks in the future.


Subject(s)
Air Conditioning , Cooperative Behavior , Disease Outbreaks/prevention & control , Interdisciplinary Communication , Legionnaires' Disease/prevention & control , Cause of Death , Cluster Analysis , Communicable Disease Control/methods , Contact Tracing , Disease Notification , Germany , Hospitals, University , Humans , Legionnaires' Disease/mortality , Legionnaires' Disease/transmission , Survival Rate , Water Microbiology
13.
Eur J Clin Microbiol Infect Dis ; 29(4): 481-7, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20119676

ABSTRACT

A total of 57 isolates of Legionella pneumophila were randomly selected from the German National Legionella strain collection and typed by monoclonal antibody subgrouping, seven-gene locus sequence-based typing (SBT) scheme and a newly developed variable element typing (VET) system based on the presence or absence of ten variable genetic elements. These elements were detected while screening a genomic library of strain Corby, as well as being taken from published data for PAI-1 (pathogenicity island) from strain Philadelphia. Specific primers were designed and used in gel-based polymerase chain reaction (PCR) assays. PCR amplification of the mip gene served as a control. The end-point was the presence/absence of a PCR product on an ethidium bromide-strained gel. In the present study, the index of discrimination was somewhat lower than that of the SBT (0.87 versus 0.97). Nevertheless, the results obtained showed as a 'proof of principle' that this simple and quick typing assay might be useful for the epidemiological characterisation of L. pneumophila strains.


Subject(s)
Bacterial Typing Techniques/methods , DNA Fingerprinting/methods , DNA, Bacterial/genetics , Legionella pneumophila/classification , Legionella pneumophila/genetics , Polymerase Chain Reaction/methods , DNA Primers/genetics , Genotype , Germany , Humans , Sensitivity and Specificity , Sequence Analysis, DNA , Serotyping
14.
Euro Surveill ; 15(4): 19472, 2010 Jan 28.
Article in English | MEDLINE | ID: mdl-20122385

ABSTRACT

Currently an investigation is ongoing to explore and control an outbreak of Legionnaires disease, affecting 65 people as of 22 January 2010, in the cities of Ulm and Neu-Ulm, south-west Germany. A hitherto unidentified wet cooling system in these twin cities is considered as the most likely source of infection.


Subject(s)
Disease Outbreaks , Legionnaires' Disease/epidemiology , Adult , Aged , Aged, 80 and over , Female , Germany/epidemiology , Humans , Legionnaires' Disease/diagnosis , Legionnaires' Disease/therapy , Male , Middle Aged
15.
Pneumologie ; 64(3): 184-93, 2010 Mar.
Article in German | MEDLINE | ID: mdl-19918719

ABSTRACT

The frequency and range of bacterial pathogens in respiratory tract infections depends on a variety of variables. The aetiology is influenced by the type of respiratory tract infection (acute bronchitis, acute exacerbation of chronic bronchitis, community-acquired pneumonia, nosocomial pneumonia), geographic and seasonal factors, and by the diagnostic methods implemented to identify the pathogens. Furthermore, there exists a considerable uncertainty concerning the clinical relevance of positive bacteriological findings in respiratory secretions because they are retrieved from non-sterile or contaminated environments. To differentiate infection from contamination, both microbiological and clinical findings have to be assessed, which might be difficult in the setting of systemic or local immunosuppression.


Subject(s)
Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Microbiological Techniques/trends , Mycoses/diagnosis , Mycoses/microbiology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/microbiology , Humans
16.
J Family Med Prim Care ; 9(9): 5004-5009, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33209836

ABSTRACT

CONTEXT: Vulnerable population groups such as migrant workers are identified as emerging high-risk groups for oral cancer owing to the high prevalence of smokeless tobacco consumption. Premature deaths due to oral cancer can be prevented by screening the population with high tobacco consumption practices and detecting early reversible stages of oral mucosal cavity lesions and facilitating linkages for further care. AIM: To assess prevalence of potentially malignant oral mucosal cavity lesions among tobacco consuming migrant construction workers in sub-urban Chennai, India. SETTINGS AND DESIGNS: A workplace based cross-sectional study design. MATERIALS AND METHODS: A cross-sectional study was conducted at workplaces i.e., construction sites for screening potentially malignant oral mucosal cavity lesions among migrant workers across 23 construction sites of Chennai during September 2019 - February 2020. An onsite, group health education session was provided about the harms of tobacco use to the migrants. STATISTICAL ANALYSIS USED: Data entered in MS Excel was analysed using SPSS and multivariate analysis was performed. RESULTS: Among 640 migrants included in the study, 411 (64.2%) were less than 30 years of age, 623 (97.4%) were from north-eastern states of India such as West Bengal, Bihar, Rajasthan, Uttar Pradesh, Jharkhand. A considerable size (272, 42.5%) could not read or write and 355 (55.4%) earn a monthly income of less than ten thousand rupees. Current tobacco users were 619 (96.7%), smokeless tobacco users (463, 72.34%), smokers (206, 32.2%) and dual users (52,8.12%). Inflammatory mucosal lesions in the oral cavity were 70.97% and more among smokeless tobacco users comparable to 22.58% among tobacco smokers and was significantly associated with up to 20 years of tobacco consumption. CONCLUSIONS: Prevalence of Potentially malignant oral lesions among smokeless tobacco using interstate migrant construction site workers is very high and need urgent interventions.

17.
J Agromedicine ; 24(4): 449-461, 2019 10.
Article in English | MEDLINE | ID: mdl-31293222

ABSTRACT

Background: The seafood processing industry is critical to Alaska's economy and hazardous to workers; however, limited research has addressed workers' safety and health. Safety and health program management is a decisive factor in preventing fatalities, injuries, and illnesses. We interviewed managers to gain their views on their safety and health programs.Methods: Semi-structured interviews were conducted with 14 upper-level managers who oversaw programs for Alaskan worksites. Interviews were audio-recorded and transcribed. Qualitative content analysis techniques, including inductive coding, were utilized to explore participants' experiences and views regarding: management and workers' roles; hazard control systems; safety and health training; regulatory and economic factors; and programs' challenges and successes.Results: The 14 participants represented 13 companies that operated 32 onshore plants and 30 vessels with processing capabilities. Participants reported managing programs for an estimated 68% of the Alaskan seafood processing industry's workforce. Based on participants' responses, we identified five factors that could be modified to improve safety and health industry-wide: manager training and knowledge sharing; worker training; organizational aspects related to safety culture; application of ergonomic principles; and work hours. Participants reported that fully engaging workers in programs was beneficial.Conclusions: Industry members should more widely share their best practices for protecting workers' safety and health. Occupational safety and health practitioners and researchers should support the development and evaluation of (a) training for non/limited-English-speaking-workers, (b) ergonomic interventions, and (c) fatigue risk management systems. Future research should engage worksite managers and workers to characterize their safety and health experiences and needs.


Subject(s)
Food Handling/standards , Occupational Health/standards , Adult , Alaska , Ergonomics , Evaluation Studies as Topic , Female , Food Handling/economics , Health Promotion , Humans , Knowledge , Male , Middle Aged , Occupational Health/economics , Qualitative Research , Workplace/standards
18.
Curr Med Res Opin ; 13(5): 264-73, 1995.
Article in English | MEDLINE | ID: mdl-7555035

ABSTRACT

In order to evaluate the pharmacokinetics and excretion of ramipril in man, 8 cholecystectomy patients aged between 53 and 68 years received 5 mg ramipril orally as a single dose. All patients had a T-drain inserted to permit bile collection; all gave their informed consent to participate in the trial. Serum samples were collected half-hourly until 2 hours, then hourly until 6 hours, then at 8, 10, 24 and 25 hours after intake. Urine was collected in 2-hour fractions until 8 hours, followed by a 4- and a 12-hour fraction. Bile was collected hourly until 6 hours, followed by a 6- and a 12-hour collecting fraction. Concentrations of ramipril and ramiprilat in serum, and determinations in urine and bile of ramipril, ramiprilat, ramipril glucuronide, ramiprilat glucuronide, diketopiperazine and diketopiperazine acid were made; total amounts excreted were calculated. Peak concentrations of ramiprilat in plasma (8.7 +/- 1.6 ng/ml) were reached after about 8 hours. AUC0-8 and AUC0-24-values were 36.5 and 111.9 ng.h/ml, respectively. Ramiprilat Cmax-concentrations were about 300-fold higher in bile than in plasma, the corresponding difference for ramipril between bile and plasma was about 4-fold. The main fractions excreted in the urine were diketopiperazine acid and ramiprilat amounting to 13.2 +/- 5.6 and 4.4 +/- 2.4%, respectively, of the dose administered. Only a very small fraction of the dose was excreted with urine as unchanged ramipril, on average 0.9 +/- 1.0%. The main fractions excreted in the bile were diketopiperazine acid, ramiprilat glucuronide and diketopiperazine, 9.0 +/- 5.3, 3.4 +/- 4.2 and 2.0 +/- 1.2% in 24 hours, respectively, of the dose administered. Only a negligible fraction of the dose (average 0.1 +/- 0.1%) was excreted with bile as unchanged ramipril. In conclusion, there is strong evidence that circulating ramipril and ramiprilat are eliminated by both the liver and the kidneys. For the patients studied it can be estimated from late collection periods that some 2/3 of circulating ramipril and ramiprilat are eliminated by the kidneys and 1/3 eliminated by the liver.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/metabolism , Bile/metabolism , Ramipril/analogs & derivatives , Ramipril/metabolism , Administration, Oral , Aged , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , Biotransformation , Cholecystectomy , Chromatography, Gas , Female , Humans , Kidney/metabolism , Least-Squares Analysis , Liver/metabolism , Male , Middle Aged , Radioimmunoassay , Ramipril/pharmacokinetics , Time Factors
19.
J Heart Valve Dis ; 4(5): 532-9; discussion 539-41, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8581198

ABSTRACT

Five laboratories carried out measurements of cavitation threshold for a common set of six mechanical prosthetic heart valves, two each from three different manufacturers. This study was intended to evaluate to what extent FDA's current guidance for cavitation testing would lead to consistent results in a variety of laboratory settings and to seek areas for improvement in the recommended test protocol. The inter-laboratory study protocol specified: (1) characterization of the test fluid by oxygen content and electrical conductivity, (2) location and frequency response of pressure sensors, (3) determination of ventricular and atrial pressures (P) and loading rates (dP/dt) averaged over the time period of valve closure and over the time periods of 1 ms, 5 ms, and 20 ms prior to video visualization. The protocol did not specify: (1) the fluid pumping equipment to be used to generate cavitation, (2) the pump or fluid parameters adjusted to raise or lower the loading rate, (3) the equipment, technique, or sensitivity used to visualize cavitation, and (4) a specific definition of the threshold for cavitation. Results from the five laboratories are reported. Significant differences in results were observed in dP/dt and in the pressure difference across the valves during closure at cavitation threshold. Specific differences in test systems included a wide range of ventricular compliance and single valved versus double valved test systems. Three single valve systems with compliant ventricles produced results in reasonable agreement with one another. Further similarity in test equipment should be specified to assure adequate interlaboratory reliability for cavitation testing. Areas needing better specification include the design of the valve mount, the design of the cavitation generators, and qualitative criteria for detection of threshold cavitation.


Subject(s)
Biocompatible Materials , Carbon , Heart Valve Prosthesis , Materials Testing/standards , Evaluation Studies as Topic , Humans , Materials Testing/instrumentation , Materials Testing/methods , Prosthesis Design , Prosthesis Failure , Stress, Mechanical , United States , United States Food and Drug Administration/standards
20.
Eur J Cardiothorac Surg ; 11(2): 287-92, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9080157

ABSTRACT

OBJECTIVE: To compare hydrodynamic characteristics of a new bileaflet heart valve, the CarboMedics kinetic cardiac valve prosthesis, with those of a St. Jude Medical (SJM) heart valve. METHODS: Hydrodynamic characteristics were determined in the mitral and aortic positions of a Vivitro Systems pulse duplicator for size 23 Kinetic aortic values, size 23 SJM aortic valves, size 29 Kinetic mitral valves and size 29 SJM mitral valves. Test conditions were 72 beats per min with cardiac outputs of 2, 5 and 7 l/min. Values of forward flow pressure drop (delta P), regurgitant and energy loss were determined for each valve. The test results for the two valve designs were compared by valve size. RESULTS: The test results show that both the size 23 and size 29 Kinetic valves have 8-14% lower delta P values and 5-10% greater effective orifice area (EOA) values. The size 29 Kinetic mitral valve has a 1-2 ml lower regurgitant volume, while the size 23 Kinetic aortic valve has a 0.5 ml greater regurgitant volume than the corresponding SJM values. These factors combine to provide a 5-10% lower energy loss for size 23 Kinetic aortic valves and a 15-25% lower energy loss for size 29 Kinetic mitral valves over the cardiac cycle than for corresponding sizes of SJM valves. CONCLUSIONS: The Kinetic valve's fluid dynamics are superior to equivalent sizes of SJM valves. This is especially impressive considering that the tissue annulus diameters for Kinetic valves are approximately 0.5 mm less than equivalent size SJM valves. The primary reasons for the superior hydrodynamic performance of Kinetic valves are (1) the larger orifices which result in lower forward flow delta P values and (2) the opening angles, which have been customized for each valve size to minimize energy loss.


Subject(s)
Heart Valve Prosthesis , Hemodynamics/physiology , Aortic Valve/physiopathology , Aortic Valve/surgery , Blood Pressure/physiology , Equipment Failure Analysis , Humans , Mitral Valve/physiopathology , Mitral Valve/surgery , Models, Cardiovascular , Prosthesis Design , Pulsatile Flow/physiology , Ventricular Function, Left/physiology
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