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Biomedical subjects

F Schlaeffer

Publications and source records attributed to F Schlaeffer.

At least 55 records · Page 3Linked to original sources

Neutrophil superoxide release and interleukin 8 in acute myocardial infarction: distinction between complicated and uncomplicated states.

Superoxide release in neutrophils and sera levels of interleukin 8 (IL-8) were determined in 15 patients with complicated acute myocardial infarction (MI) and 15 patients with uncomplicated MI. All patients showed increased superoxide release in unstimulated and stimulated neutrophils compared with healthy control subjects, indicating priming of these cells. Superoxide release of unstimulated or stimulated neutrophils was found to be significantly higher in patients with complicated MI than in patients with uncomplicated MI. Thrombolytic therapy did not affect the rates of superoxide release. The neutrophil chemoattractant/activator IL-8 was detected in the sera of all patients, with significantly higher levels in those with complicated MI. The highest levels of IL-8 were detected at admission to the Coronary Care Unit and significantly decreased thereafter, suggesting its contribution to neutrophil-mediated tissue injury. The high levels of IL-8 may be one of the major contributors to the priming of neutrophils in these patients.

Aged↗

Community-acquired pneumonia in old age: a prospective study of 91 patients admitted from home.

OBJECTIVE: to characterize the background, aetiology, clinical course and outcome of community-acquired pneumonia (CAP) in elderly compared with younger patients. DESIGN: a 1 year prospective study. SETTING: a university hospital in southern Israel. PARTICIPANTS: ninety-one patients over 65 years who were hospitalized from their homes with CAP. These patients were compared with a reference group of 54 CAP patients, aged 55-64 years. MEASUREMENTS: an intensive work-up (primarily serological) to identify the aetiological causes of CAP. The age groups were compared in terms of variables related to CAP. RESULTS: the proportion with pneumococcal infection, the most common aetiology for CAP, increased from 29.6% in the 55-64-year group through 45.6% in the 65-74-year group; up to 57.8% in the 75+ group (P = 0.019). Chlamydia pneumoniae was identified as the aetiological agent in 26.4% of elderly patients. Mortality in patients > or = 75 years was 20% and was significantly higher than in the two younger age groups (P = 0.019). The leucocyte count was significantly higher among the elderly group (P = 0.013) and the serum urea concentration was higher in patients 75 years and older (P = 0.025). The proportion of patients treated with antibiotics before admission decreased with increasing age (P = 0.026). CONCLUSIONS: CAP has more serious clinical and abnormal laboratory features in the elderly than younger patients, particularly in those over 75. In independent elderly people, the pneumococcus is the most common causative agent for CAP but other agents, particularly C. pneumoniae, are common. Initial antibiotic treatment for these patients should therefore include a macrolide.

Aged↗

Sequential therapy with cefuroxime followed by cefuroxime axetil in community-acquired pneumonia.

STUDY OBJECTIVES: To compare the efficacy of two sequential therapy regimens of IV cefuroxime followed by oral cefuroxime axetil for the treatment of community-acquired pneumonia (CAP). DESIGN: Prospective, multicenter, randomized, open-label, parallel-group study. SETTING: Sixty-six centers in 11 countries (Belgium, Canada, Czech Republic, Germany, Hungary, Ireland, Israel, Poland, Portugal, South Africa, and the United Kingdom). PATIENTS: Six hundred thirty-six adults with CAP requiring hospitalization and initial IV antibiotic treatment. INTERVENTIONS: Cefuroxime, 1.5 g IV tid or bid for 48 to 72 h followed by oral cefuroxime axetil, 500 mg bid for 7 days. MEASUREMENTS AND RESULTS: For clinically evaluable patients, the clinical response rates were equivalent for cefuroxime tid and bid groups posttreatment (cure/improvement, 79% and 84%, respectively) and at follow-up (maintained cure, 87% and 82%, respectively). All signs and symptoms of pneumonia showed improvement at the time of switch from IV to oral therapy. A total of 111 pathogens were isolated, the most common being Streptococcus pneumoniae (23%), Haemophilus influenzae (18%), and Enterobacteriaceae (15%). Bacteriologic clearance was obtained posttreatment in 47 of 49 and 36 of 42 of bacteriologically evaluable patients in the cefuroxime tid and bid groups, respectively. Both regimens were well tolerated with a low incidence of drug-related adverse events, the most common being GI. CONCLUSIONS: Twice daily IV cefuroxime followed by oral cefuroxime axetil is a simple and effective sequential therapy regimen for the treatment of CAP. It offers potential cost savings and can replace the current tid regimen in this indication.

Administration, Oral↗

Serious bacterial infections after endoscopic procedures.

Transient bacteremia during and after endoscopic procedures is a well- documented phenomenon, but complicated bacteremia such as endocarditis in patients at risk is considered to be extremely rare. The recommendations for prophylaxis before endoscopy in patients with valvular heart disease were recently released. We discuss 16 cases of complicated bacteremia that developed after endoscopy (eight cases previously published in the literature and eight cases we encountered). The endoscopic procedures were gastroscopy (five cases), sclerotherapy (six cases), sigmoidoscopy (three cases), and esophageal dilation (two cases). Fourteen patients had underlying disease: valvular heart disease (six patients), cirrhosis of the liver (five patients, one of whom also had a prosthetic knee), valvular heart disease and cirrhosis of the liver (two patients), and gastric carcinoma (one patient). The organisms involved were Streptococcus viridans (six cases), streptococcus group D (three cases), Streptococcus pneumoniae (two cases), Streptococcus microaerophilicus (two cases), Staphylococcus aureus (two cases), and Cardiobacterium hominis (one case). The patients presented with the following infections: endocarditis (12 patients), spontaneous bacterial peritonitis (two patients), septic arthritis (one patient), and brain abscess (one patient). The outcome was good in 15 patients; one patient died. Patients with valvular heart disease, cirrhosis of the liver, ascites, malignancies, or prosthetic joints who undergo endoscopic procedures should be considered for antibiotic prophylaxis.

Adult↗

Appropriateness of hospitalization of patients with community-acquired pneumonia.

STUDY OBJECTIVE: To investigate the association between the appropriateness of hospitalization and the course of hospitalization in patients with community-acquired pneumonia (CAP). METHODS: We carried out a prospective study of 346 adult patients hospitalized with community-acquired pneumonia (CAP). Appropriateness of hospitalization was assessed with a modified appropriateness evaluation protocol (AEP) based on vital signs and laboratory tests. Hospitalizations that ended in death, lasted more than 4 days, or involved resuscitation, incubation, monitoring, or supplemental oxygen therapy were considered complicated. RESULTS: According the AEP protocol, hospitalization was not appropriate for 210 of the 346 patients (61%). However, AEP proved to be an insensitive tool for the identification of patients with complicated hospital courses. Half of the 346 patients had complicated courses, including 82 of the 210 patients with inappropriate hospitalization (39%), according to the AEP. Four independent factors, age greater than 50 years, female sex, no antibiotic treatment before hospitalization, and more than 4 days of illness before admission predicted a complicated course in patients with inappropriate hospitalization as determined with the AEP criteria. CONCLUSION: It is important to avoid the unnecessary hospitalization of patients with CAP. However, this should not be achieved at the expense of unjustified discharge from the emergency department. In the decision to hospitalize, additional prognostic factors, such as those presented here, should be taken into consideration to improve the admission process. This is particularly relevant for cases in which the AEP is invalid and indications for hospitalization are not clear cut. In these patients, a simpler and more precise scoring system should be developed.

APACHE↗

Inhibited neutrophil functions in patients treated with nifedipine but not with verapamil or diltiazem.

Neutrophil functions were studied in patients receiving calcium channel blockers: nifedipine, diltiazem or verapamil. Neutrophils from patients treated with nifedipine showed a significantly lower superoxide generation stimulated by phorbol myristate acetate (PMA) (50 ng mL-1), opsonized zymosan (1 mg mL-1) or formyl-methionyl-leucylphenylalanine (FMLP) (10(-7) M), whereas superoxide generation by neutrophils of patients receiving diltiazem or verapamil showed only a slight and insignificant reduction compared with controls. Similarly, chemotaxis towards 10(-7) M FMLP and phagocytosis were significantly lower in patients receiving nifedipine compared with controls and were only slightly reduced in patients receiving diltiazem or verapamil. Nifedipine was the most efficient drug in inhibiting the rise in intracellular calcium ion concentration ([Ca2+]i) when added in vitro and in neutrophils of patients receiving this drug, whereas verapamil had no significant effect. The correlation between the inhibitory effect of nifedipine on neutrophil function and the elevation of [Ca2+]i suggests that nifedipine inhibits neutrophil functions through its effect on [Ca2+]i. However, it is not the sole mechanism as superoxide generation induced by PMA, an agent that does not induce a rise in [Ca2+]i, is also inhibited. The unique effect of nifedipine in reducing neutrophil functions in vivo suggests its clinical implications concerning response to acute ischaemic myocardial events.

Adult↗

Vitamin C for the treatment of recurrent furunculosis in patients with imparied neutrophil functions.

The effect of vitamin C treatment on 23 patients with a history of recurrent furunculosis with negative nasal cultures was studied. Neutrophil functions (chemotaxis, phagocytosis, or superoxide generation) of 12 patients were significantly lower than those of the matched controls. In this group, treatment with vitamin C (1 g/day) caused a dramatic clinical response as well as a significant improvement of neutrophil functions, reaching values similar to those of the controls. Two patients remained vitamin C-dependent. In the patients with normal neutrophil functions, vitamin C treatment neither affected neutrophil activity nor caused a clinical response. Therefore, patients suffering from recurrent furunculosis with defective neutrophil functions may be treated successfully with vitamin C, contributing to both neutrophil function recovery and a dramatic clinical response.

Adolescent↗

Multiple pathogens in adult patients admitted with community-acquired pneumonia: a one year prospective study of 346 consecutive patients.

BACKGROUND: The purpose of this study was to assess the causes of community-acquired pneumonia in adult patients admitted to hospital. METHODS: A prospective study was performed on 346 consecutive adult patients (54% men) of mean (SD) 49.3 (19.5) years (range 17-94) admitted to a university affiliated regional hospital in southern Israel with community-acquired pneumonia over a period of one year. Convalescent serum samples were obtained from 308 patients (89%). The aetiological diagnosis for community-acquired pneumonia was based on positive blood cultures and/or significant changes in antibody titres to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory viruses, Coxiella burnetii, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella sp. RESULTS: The aetiology of community-acquired pneumonia was identified in 279 patients (80.6%). The distribution of causal agents was as follows: S pneumoniae, 148 patients (42.8%); M pneumoniae, 101 (29.2%); C pneumoniae, 62 (17.9%); Legionella sp, 56 (16.2%); respiratory viruses, 35 (10.1%); C burnetii, 20 (5.8%); H influenzae 19 (5.5%); and other causes, 21 patients (6.0%). In patients above the age of 55 years C pneumoniae was the second most frequent aetiological agent (25.5%). In 133 patients (38.4%) more than one causal agent was found. CONCLUSIONS: The causal agents for community-acquired pneumonia in Israel are different from those described in other parts of the world. In many of the patients more than one causal agent was found. In all these patients treatment should include a macrolide antibiotic, at least in the first stage of their illness.

Adolescent↗

Mycoplasma pneumoniae community-acquired pneumonia: a review of 101 hospitalized adult patients.

The features of community-acquired Mycoplasma pneumoniae pneumonia (MP-CAP) were assessed in a prospective study of 101 adults who were hospitalized over the course of 1 year, and were compared with 245 patients who were hospitalized during the same period of time with community-acquired pneumonia (CAP) not caused by M. pneumoniae (non-MP-CAP). MP was the second most common etiology (29.2%) in all CAP patients, and the most common etiological agent (43.2%) in the 17- to 44-year age group. In 65 patients (64.3%) at least one other pathogen was identified for CAP in addition to MP. Although the disease was most prevalent among younger patients, it also involved older and even elderly patients. Compared to non-MP-CAP patients, the severity of disease was significantly lower on average in the MP-CAP group and the length of hospitalization was significantly shorter. Radiologic findings were the same in the two groups. Twenty-two MP-CAP patients recovered without receiving the treatment which is recognized as effective in this disease. We concluded that (1) in most patients with MP-CAP a second CAP pathogen can be identified serologically, (2) MP-CAP cannot be differentiated from non-MP-CAP on the basis of clinical, radiologic, or routine laboratory tests, and (3) in some MP-CAP patients the disease is self-limited, and in these patients the usefulness of standard antibiotic therapy is doubtful.

Adolescent↗

Legionella species community-acquired pneumonia. A review of 56 hospitalized adult patients.

BACKGROUND: In a prospective study, Legionella species (Lsp) was identified as the causative agent in 56 (16.2%) of 346 adult patients hospitalized over the course of 1 year with community-acquired pneumonia (CAP), in the Soroka Medical Center, Beer-Sheva, Israel. OBJECTIVE: To characterize patients with Lsp CAP in our study. METHODS: The diagnosis of infection with Lsp was based on serologic testing of antibodies using the indirect immunofluorescent method. RESULTS: In 35 (62.5%) of the patients, at least one other etiologic agent for CAP was identified in addition to Lsp. The patient population was relatively young, with relatively low rates of chronic comorbidity, and a broad spectrum of disease severity compared with previously published studies. No single epidemiologic, clinical, laboratory, or radiographic characteristic differentiated between Lsp CAP and other CAP patients in our study. Three patients (5.4%) who were not treated with erythromycin died. However, in contrast, nine patients who were treated with beta-lactam antibiotics recovered completely. CONCLUSIONS: Lsp is a common cause of CAP in our region, usually as a coinfection with another causative agent. Lsp CAP, which cannot be characterized on the basis of clinical, routine laboratory, or radiographic data, requires specific microbiologic or serologic diagnosis. Treatment with erythromycin appears to be important to reduce mortality from this disease, but in a significant number of patients, the disease may be self-limited.

Adolescent↗

Microparticle agglutination versus antibody-capture enzyme immunoassay for diagnosis of community-acquired Mycoplasma pneumoniae pneumonia.

Community-acquired Mycoplasma pneumoniae pneumonia is a common disease which is usually diagnosed by serological methods. The objective of the present study was to understand the diagnostic significance and test characteristics of two different serological tests used to identify current Mycoplasma pneumoniae infection. Three hundred sixty-six patients who suffered from community-acquired pneumonia served as the study population. Six hundred ninety-four (328 paired and 38 unpaired) sera were examined for the presence of antibodies to Mycoplasma pneumoniae with commercial kits based on two serological methods, microparticle agglutination and antibody-capture EIA. Agreement between the two kits was 85.2% when individual sera were compared (kappa = 0.62) and 88.5% when patients were compared (Kappa = 0.69). The positive predictive value and the specificity for the identification of current Mycoplasma pneumoniae infection using a single acute-phase serum were 49.3% and 86.9%, respectively, for the microparticle agglutination method, compared to 91.3% and 97.7% for the antibody-capture EIA method (p < 0.001). The negative predictive value and the sensitivity were 86.3% and 48.1% for the microparticle agglutination, not significantly different from the corresponding values of 86.5% and 61.2% for the antibody-capture EIA. It is concluded that the overall agreement between the two methods tested is good, but not perfect. The methods complement each other in the identification of Mycoplasma pneumoniae as the causative agent in patients with community-acquired pneumonia.

Adolescent↗

Q-fever pneumonia in the Negev region of Israel: a review of 20 patients hospitalised over a period of one year.

BACKGROUND: Three-hundred and forty-six patients with community acquired pneumonia were included in a prospective study of patients hospitalised over a 12-month period in the Soroka Medical Center in Beer-Sheva, Israel. Q-fever pneumonia (QFP) was diagnosed in 20 patients (5.8%). A detailed epidemiological and clinical description of this disease, is presented. METHODS: QFP was diagnosed by conventional criteria using a commercial immunofluorescent assay. RESULTS: The age of patients was 41 +/- 14 years (mean +/- S.D., range 20-69). Twelve of the patients were males. No concomitant or chronic disease was present in 16 patients. Chest radiograms revealed alveolar or air space pneumonia in 10 patients, bronchopneumonia in nine and interstitial pneumonia in one patient. The mean febrile period was 10.5 +/- 5.3 days. There was serological evidence of co-infection with Mycoplasma pneumonia in six patients, and with Legionella pneumophila in one patient. Patients treated with beta-lactam antibiotics recovered as quickly as those treated with tetracyclines or erythromycin. CONCLUSIONS: The Negev region of Israel is an endemic area for Q-fever. The diagnosis of QFP can be made only on the basis of a specific serological test. Clinical, radiologic or laboratory findings are not diagnostically definitive. The importance of specific therapy is unclear.

Adult↗

Inhibition of superoxide production in human neutrophils by combinations of heparin and thrombolytic agents.

OBJECTIVE: To investigate the effect of heparin and thrombolytic agents on superoxide generation by human neutrophils, as inhibition of superoxide production may have a role in reducing ischaemia and reperfusion injury. METHODS: Neutrophil superoxide production stimulated by phorbol myristate acetate (PMA), opsonised zymosan, or formyl methionyl leucyl phenylalanine (FMLP) was measured as the superoxide dismutase inhibitable reduction of acetyl ferricytochrome c by a microtitre plate technique. RESULTS: Heparin, at concentrations of 0.5-500 U/ml, caused a gradual inhibition of superoxide production stimulated by PMA, opsonised zymosan, or FMLP. Tissue plasminogen activator was more potent than heparin in inhibiting superoxide production induced by opsonised zymosan or FMLP, but it did not affect the activity stimulated by PMA. Streptokinase or urokinase had no effect on superoxide production. When heparin was used in combination with tissue plasminogen activator, streptokinase, or urokinase at their therapeutic concentrations there was a significant inhibition of superoxide generation (70%, 30%, and 25%, respectively). The therapeutic concentrations of tissue plasminogen activator alone caused a reduction of 40% of neutrophil superoxide production. When tissue plasminogen activator and streptokinase were both added to neutrophils, however, a synergistic inhibition of 80% was achieved. CONCLUSIONS: The inhibition of super oxide generation by these drug combinations may explain the limited inflammatory response and reduction of reperfusion injury observed in patients receiving thrombolytic treatment.

Depression, Chemical↗

Elevated NADPH-oxidase activity in neutrophils from bile-duct-ligated rats: changes in the kinetic parameters and in the oxidase cytosolic factor p47.

Stimulated superoxide generation was 2-fold higher in neutrophils from 20 rats with common bile-duct ligation (CBDL) compared to that of 20 sham-operated control rats. In order to study the mechanism of the higher NADPH oxidase activity in CBDL rats, the kinetic parameters of NADPH oxidase were analyzed. The Vmax of the NADPH oxidase in CBDL rat neutrophils was significantly higher than that of control rat neutrophils (10.2 and 5.3 nmol/min, respectively). The membrane and cytosol fractions of the oxidase were studied in a cell-free system. Neutrophil cytosol from CBDL rats added to neutrophil membranes from either CBDL or control rats produced 22.4 +/- 1.6 and 21.0 +/- 1.4 nmol/10(6) cells per 10 min, respectively. When neutrophil cytosol from control rats was mixed with neutrophil membranes from control or CBDL rats the generation of superoxide was 10.6 +/- 1.4 and 10.0 +/- 1.5 nmol/10(6) cells per 10 min, respectively. These results suggest that the cytosol components of the oxidase regulate its activity. By immunoblot analysis it was shown that the amount of the cytosolic factor p47 in neutrophils of CBDL rats is higher than that present in an equal number of neutrophils from control rats.

Animals↗