Pharmacokinetics of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in healthy male volunteers.
AIMS: The aim of this open, randomised, crossover, parallel-group study was to compare the pharmacokinetics and neutrophil responses of lenograstim when administered subcutaneously (s.c.) and intravenously (i.v.). METHODS: A total of 27 healthy male volunteers was recruited. Lenograstim doses (0.5, 2, 5, or 10 microg kg(-1)) were administered s.c. or i.v. once-daily for 5 days, and then, after a 10-day washout period, vice versa for a further 5 days. Lenograstim concentrations and absolute neutrophil counts (ANCs) were measured predosing and postdosing on days 1 and 5. RESULTS: Maximum serum concentrations of lenograstim were higher following i.v. dosing (mean 5.2-185.5 vs 0.7-30.0 ng ml(-1) after s.c. dosing on day 1) and attained sooner (median 0.5-0.8 vs 4.7-8.7 h on day 1). However, apparent elimination half-lives of lenograstim were longer following s.c. dosing (mean 2.3-3.3 vs 0.8-1.2 h after i.v. dosing on days 1 and 5). ANCs increased in a dose-dependent manner with both routes of lenograstim, but more prolonged rises and higher ANC peaks were attained following s.c. doses. ANCs peaked on day 6 following 5 microg kg(-1) s.c. doses (mean peak=26.3x10(9) cells l(-1)), but on day 2 after 5 microg kg(-1) i.v. doses (mean peak = 12.4 x 10(9) cells l(-1)). Irrespective of route, the most common adverse events were headaches and back/spine pain; at doses of up to 5 microg kg(-1) these were mild and generally well tolerated. CONCLUSIONS: While supporting the use of both s.c. and i.v. administered lenograstim to treat neutropenia, these results demonstrate that neutrophil responses are more sustained and prolonged with the s.c. route. (+info)
Characterization of antimicrobial resistance in Streptococcus pyogenes isolates from the San Francisco Bay area of northern California.
During 1994 and 1995, 157 isolates of Streptococcus pyogenes from patients with invasive disease were consecutively collected in the San Francisco Bay area to determine the frequency of antimicrobial resistance. Susceptibility testing was performed according to the guidelines of the National Committee for Clinical Laboratory Standards by the disk method and by broth microdilution. For comparison of susceptibility patterns, an additional 149 strains were randomly collected from patients with pharyngitis. For San Francisco County, 32% of the isolates from invasive-disease-related specimens but only 9% of the isolates from throat cultures from the same period were resistant to erythromycin (P = 0.0007). Alameda County and Contra Costa County had rates of resistance of +info)
Improving diagnostic accuracy of bacterial pharyngitis by near patient measurement of C-reactive protein (CRP)
BACKGROUND: Sore throat or pharyngitis is an extremely prevalent condition in primary care. There is a diagnostic dilemma in differentiating bacterial and non-bacterial infections for adequate use of antibiotics. Standard diagnostic procedures take too long for an immediate decision. AIM: To evaluate, if near patient C-reactive protein measurement in the general practice surgery improves diagnostic accuracy. METHOD: One hundred and seventy-nine consecutive patients with sore throat, from 15 general practitioners (GPs) in southern Germany (phase 1) and 161 consecutive patients from 14 GPs (phase 2), were examined physically and a throat-swab was taken and white blood-cell count (WBC) and CRP-measurement were performed. In phase 1, CRP was measured centrally to assess the method's diagnostic value and the adequate threshold. In the second phase, near patient CRP was measured and CRP values were used to make a diagnosis. RESULTS: Using relative operating characteristics (ROC) analysis, the diagnostic value of CRP measurement was much better than WBC count (area under curve = 0.85 versus 0.68). All diagnostic parameters improved when using the near patient CRP measurement. Sensitivity went up from 0.61 (95% confidence interval = 0.45-0.75) to 0.78 (0.61-0.90), specificity went up from 0.73 (0.65-0.81) to 0.82 (0.73-0.88). Positive and negative predictive value improved significantly as well. Diagnostic accuracy went up from 70.1% to 81.0%. Out of 1000 theoretical patients with sore throat, 109 more will be treated correctly when using CRP measurement as a diagnostic tool. CONCLUSIONS: Use of near patient CRP measurement can improve diagnostic accuracy in the differentiation of bacterial and non-bacterial pharyngitis in primary care, and potentially results in a more adequate use of antibiotics. (+info)
Lemierre's syndrome (necrobacillosis).
Lemierre's syndrome or postanginal septicaemia (necrobacillosis) is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections. Fusobacterium necrophorum is the most common pathogen isolated from the patients. The interval between the oropharyngeal infection and the onset of the septicaemia is usually short. The most common sites of septic embolisms are the lungs and joints, and other locations can be affected. A high degree of clinical suspicion is needed to diagnose the syndrome. Computed tomography of the neck with contrast is the most useful study to detect internal jugular vein thrombosis. Treatment includes intravenous antibiotic therapy and drainage of septic foci. The role of anticoagulation is controversial. Ligation or excision of the internal jugular vein may be needed in some cases. (+info)
Health effects among workers in sewage treatment plants.
OBJECTIVES: To further assess the presence of fatigue, symptoms of diarrhoea, and inflammation of airways among people working in sewage plants and the relation to airborne bacterial endotoxin at the workplace. METHODS: 34 Employees in sewage treatment plants and 35 controls were selected. They underwent a questionnaire investigation, and spirometry and airway responsiveness were measured. Measurements were made of airborne endotoxin at different workplaces. RESULTS: The amount of airborne endotoxin varied between 3.8 and 32,170 ng/m3. Workers reported significantly higher nose irritation, tiredness, and diarrhoea. Airway responsiveness was increased among sewage workers, but no differences between the groups were found for spirometry. CONCLUSIONS: The results confirm previous studies on the presence of airways and intestinal inflammation among workers in sewage treatment plants. The most likely causative agent is endotoxin, and at 14 of 23 workplaces, concentrations exceeded recommended guidelines. (+info)
Group C streptococci isolated from throat swabs: a laboratory and clinical study.
AIMS: To determine the prevalence of beta haemolytic, Lancefield group C streptococci in throat swabs taken in routine clinical practice, and correlate the species identified with presenting clinical features. METHODS: One year, laboratory based prospective study, using a questionnaire to elicit clinical information. RESULTS: 4.4% of throat swabs yielded group C streptococci, of which 38% belonged to S equisimilis and 53% to S anginosus-milleri group (SAM). Pyrexia was more common in patients with S equisimilis, but other clinical features did not differ significantly between the two groups. No S zooepidemicus was isolated. CONCLUSIONS: Species identification of group C streptococci from throat swabs does not appear to be clinically useful in this patient population. However, the prevalence and spectrum of organisms is similar to that reported in N America, where studies suggest a possible role in some cases of severe pharyngitis. Observational studies such as this lack power to resolve the issue of pathogenicity, for which a placebo controlled trial of antibiotic treatment is ideally required. (+info)
A study of small-colony, beta-haemolytic, Lancefield group C streptococci within the anginosus group: description of Streptococcus constellatus subsp. pharyngis subsp. nov., associated with the human throat and pharyngitis.
beta-Haemolytic, Lancefield group C streptococci within the anginosus-species group were shown by genetic and phenotypic criteria to be heterogeneous and to constitute two distinct taxa related at subspecies level to Streptococcus constellatus and Streptococcus anginosus, respectively. The first group, referred to here as DNA group 1, comprised six strains with 86-100% intragroup overall genomic DNA relatedness; five of the strains were originally isolated from the human throat and one was from an abdominal mass. They shared 61-77% DNA relatedness (delta Tm values = 1.2-1.5 degrees C) with reference strains of S. constellatus and were clearly differentiated from S. constellatus (now named Streptococcus constellatus subsp. constellatus) by the ability to produce beta-N-acetylgalactosaminidase, beta-N-acetylglucosaminidase, beta-D-fucosidase, beta-D-galactosidase and beta-D-glucosidase. The name S. constellatus subsp. pharyngis is proposed for these strains on the grounds that they are genetically and phenotypically distinct and exhibit a predeliction for the human throat, being isolated also from cases of pharyngitis. The DNA G + C content is 35-37 mol%. The type strain is MM9889aT (= NCTC 13122T). The second group (DNA group 2) was formed by five beta-haemolytic, Lancefield group C strains originally isolated from various human infections. DNA group 2 strains (81-100% intragroup DNA relatedness) shared 60-72% DNA relatedness (delta Tm values = 2.1-4.1 degrees C) with S. anginosus strains NCTC 10713T and MAS 283 but were not clearly differentiated phenotypically from S. anginosus, showed no clear pattern of clinical association, and therefore are not formally proposed as a new subspecies here. (+info)
Characteristics of Streptococcus pyogenes serotype M1 and M3 isolates from patients in Japan from 1981 to 1997.
Streptococcus pyogenes isolates obtained in 1981 to 1997 from patients and healthy subjects were characterized by pulsed-field gel electrophoresis (PFGE) patterns, biotyping, and the presence of spe genes encoding streptococcal pyrogenic exotoxins. Changes in the profiles were shown in the serotype M1/T1 isolates from pharyngitis over this period, but not in serotype M3/T3 isolates. The characteristics of isolates from patients with toxic shock-like syndrome (TSLS) were comparable to those of the other isolates, including those from healthy subjects. This finding suggests that further phenotypic and molecular characterization, such as investigating the genomic difference represented by the pathogenicity island, of isolates with apparently the same profiles would be necessary to determine the etiology of diseases caused by S. pyogenes, including TSLS. (+info)