Carrageenan: an asset or detriment in infant formula?
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Biomedical subjects
Publications and source records attributed to J L Vilde.
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We reviewed the data on 26 patients with permanent endocardial pacemakers who had 28 episodes of bacteremia to determine whether removal of the wire is required. Patients recovered completely from the first episode in seven of 20 cases of staphylococcal bacteremia and in six of six cases of nonstaphylococcal bacteremia (P = .015). Definitive cure was not achieved during the first episode in seven cases of staphylococcal bacteremia related to the pacing system when the wire was not withdrawn; however, cure was achieved in five of six cases when the whole pacemaker was removed (P < .01). The duration of treatment was longer for the patients from whom the wire was not removed during the first episode (P < .01). Whether cases of staphylococcal bacteremia were related to the pacing system or not, the rate of recovery of the responsible microorganism from the wires was similar for both groups of patients (six [82%] of seven and three [75%] of four, respectively). Nonstaphylococcal bacteremia was unrelated to the pacing system in five of six cases; these patients were all cured without removal of the wire.
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We compared the activities of two different biological-response modifiers with that of clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. Mice were pretreated daily with clarithromycin (50 mg/kg of body weight subcutaneously [s.c.]), RU-40555 (100 mg/kg s.c.), or granulocyte colony-stimulating factor (G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment, clarithromycin significantly decreased the level of infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment, G-CSF at low dose had no activity, but G-CSF in combination with clarithromycin was more effective than clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of G-CSF was as effective as the low dose. RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that clarithromycin alone or in combination with G-CSF should be further evaluated for the prophylaxis of M. avium complex infection.
C57BL/6 mice were pretreated with rifabutin or clarithromycin alone or combined with minocycline 3 days before intravenous challenge (day 0) with Mycobacterium avium. Treatment was continued until sacrifice at days 1, 8, 15, and 21. Rifabutin or clarithromycin decreased the level of infection in both the lungs and the spleen. Rifabutin was as effective as clarithromycin in the lungs but was less [corrected] effective in the spleen. The clarithromycin-minocycline combination was as effective as clarithromycin alone.
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Two strains of Legionella pneumophila of different virulence were examined for their influence on the metabolic oxidative activity of human polymorphonuclear leukocytes. The leukocytes exhibited decreased rates of oxygen consumption and diminished chemiluminescence activity following phagocytosis of a virulent strain of L. pneumophila serogroup 1. In contrast, phagocytosis of its multipassaged derivative rendered avirulent, was accompanied by increased rates of both oxygen consumption and chemiluminescence activity. Although no differences were observed in oxygen uptake induced by the virulent legionellae compared to leukocytes at rest, statistically significant differences were observed in the chemiluminescence responses. These observations were not unexpected, since the luminol-enhanced chemiluminescence assay, is more sensitive than the oxygen uptake assay. In spite of decreased metabolic activity of PMN in the presence of virulent legionellae, electron microscope studies showed higher numbers of intracellular L. pneumophila than the avirulent subtype. Thus, virulent and avirulent L. pneumophila can be differentiated on the basis of oxygen consumption and chemiluminescence assays.
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The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.
Secretion of N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes by human blood monocyte-derived macrophages in response to zymosan and human recombinant interferon-gamma was studied. Macrophages were found to release NAG in response to zymosan, but interferon-gamma has no effect on secretion. Isoenzyme separation by isoelectric focusing demonstrates that non stimulated and zymosan or interferon-gamma treated macrophages release predominantly NAG B and, to a lesser extent, NAG A isoenzymes. In all these conditions, the intracellular intermediate form NAG I could not be detected in the media. Thus, activated macrophages may not be the source of NAG intermediate forms I and P in pathological or maternal serum. In contrast, macrophages could contribute to a significant elevation of urinary activity and NAG B excretion in response to inflammatory conditions.
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Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.
Clarithromycin, a new macrolide, is effective in treating experimental Toxoplasma gondii infection. A pyrimethamine-clarithromycin combination was evaluated for the treatment of acute Toxoplasma encephalitis in 13 AIDS patients. The scheduled regimen was 2 g of clarithromycin per day and 75 mg of pyrimethamine per day for 6 weeks. The protocol was completed in eight patients and stopped in five patients (because of voluntary withdrawal by two patients, deterioration of neurological condition and thrombocytopenia in two patients, and suspicion of liver toxicity in one patient). The clinical and computed tomography scan responses at week 6 of treatment were 80 and 50%, respectively. Two patients died, one of toxoplasmic encephalitis and the other of cerebral bleeding due to pyrimethamine-induced thrombocytopenia. Adverse events related to therapy were nausea and/or vomiting (38%), skin rash (38%), significant increase of liver tests (24%), hearing loss (15%), and severe hematological abnormalities (31%). In this pilot study, a pyrimethamine-clarithromycin combination was shown to be comparable to the conventional regimen for the treatment of acute Toxoplasma encephalitis in AIDS patients.
The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection.
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The clinical and bacteriological features of 51 infections due to Streptococcus milleri observed in 43 patients over a 2-year period were reviewed. Clinical syndromes included bacteremia in 6 cases, endocarditis in 4 cases, cellulitis and subcutaneous abscesses in 8 cases, pleural empyema in 8 cases, brain abscesses in 5 cases, abdominal infections in 5 cases, and other miscellaneous infections in 15 cases. An underlying condition was associated with infection in 33/43 patients (77%). S. milleri was the only pathogen isolated in 19 patients (44%). All strains of S. milleri were susceptible to penicillin. Surgery was combined with antimicrobial therapy in 27 (63%) patients. Nine patients died during hospitalization, and death was directly related to S. milleri infection in 4 patients (9%). These results confirm that S. milleri frequently causes serious suppurative infections and that species identification is a clinically useful procedure.
In this retrospective study, 36 cases of Listeria monocytogenes meningitis were reviewed. A bacteriological confirmation was obtained for every patient either by lombar puncture or blood culture. The clinical picture and the composition of the cerebrospinal fluid were polymorphous. Most patients were previously in good health, while 10 of them (28%) had a predisposing factor: pregnancy, gastrectomy, diabetes mellitus, alcoholism or immunosuppression. The outcome was favorable in 23 patients (64%); 8 patients were cured with sequelae (22%); 5 patients died (14%). Death occurred in patients suffering from concomitant underlying disease, such as coronary insufficiency (n = 1) or immunosuppression (n = 2), or in the case of delayed diagnosis and treatment (n = 2).
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