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Biomedical subjects

J L Vilde

Publications and source records attributed to J L Vilde.

At least 55 records · Page 3Linked to original sources

Predictive value of cytomegalovirus viraemia for the occurrence of CMV organ involvement in AIDS.

In HIV-infected patients, the presence of cytomegalovirus (CMV) viraemia is predictive of the development of acquired immunodeficiency syndrome (AIDS), but it is not known whether it predicts further occurrence of CMV organ involvement. To assess the predictive value of CMV viraemia in the occurrence of CMV organ involvement, CMV blood cultures were performed at the onset of AIDS in 71 patients. They were prospectively followed up for at least 6 months, with a mean of 16.6 +/- 7 months (6-36 months). CMV viraemia was present in 28/71 patients (39.5%) at the onset of AIDS. CMV organ involvement occurred in 18/71 patients (25.4%) after 8.7 +/- 3.3 months. Fourteen of the 28 patients (50%) with early CMV viraemia developed CMV organ involvement after 7.7 +/- 6.3 months as compared with 4/43 patients (9.3%) who were not viraemic at the onset of AIDS with a mean follow-up of 11.8 +/- 3.8 months (P less than 0.001). At the time of CMV organ involvement, CMV viraemia, however, was present in 94.4% of the cases. No differences in survival was observed between initially viraemic and non-viraemic patients. No difference has found in mean CD4 cell count between viraemic and non-viraemic patients. This high predictive value of early CMV viraemia in AIDS for the occurrence of CMV organ involvement underlines the need for repeated search for CMV organ involvement when CMV viraemia is detected, and for less toxic antiviral drugs that might be used earlier.

Acquired Immunodeficiency Syndrome↗

Absence of effect of chloroquine in vivo on neutrophil oxidative metabolism in human subjects.

High levels of antimalarial drugs have been shown to be inhibitory to the oxidative metabolism of human neutrophils in vitro. In this study, chemiluminescence of, and chloroquine concentrations in, neutrophils from volunteers treated with prophylactic or therapeutic malaria regimens were assessed. Although detectable chloroquine levels were found in neutrophils, their chemiluminescence was not reduced at prophylactic or at therapeutic drug levels, in comparison with controls without chloroquine treatment. At these clinically achievable concentrations, chloroquine was not found to interfere with the oxidative metabolism of neutrophils.

Administration, Oral↗

Hypoglycaemia and diabetes mellitus following parenteral pentamidine mesylate treatment in AIDS patients.

Of 18 AIDS patients with Pneumocystis carinii pneumonia treated with pentamidine mesylate parenterally, four developed serious to severe hypoglycaemia, three hypoglycaemia followed by insulin-requiring diabetes, and two others diabetes alone. Hypoglycaemia (blood glucose 2.1 +/- 0.2 (+/- SE) mmol l-1) occurred 9 (2-22) days after starting treatment, and diabetes (initial blood glucose 30 +/- 6 mmol l-1) after 60 (20-90) days. The other patients remained euglycaemic. The dysglycaemic patients (hypo- and hyper-glycaemic) had a higher pentamidine dosage (p less than 0.01), and higher serum creatinine levels at end of treatment (p less than 0.001), consistent with drug accumulation and dose-dependent toxicity. Plasma C-peptide levels were low in the diabetic patients, in the basal state (0.25-0.28 nmol l-1) and following stimulation by IV glucagon (0.35-0.40 nmol l-1), vs 0.80 +/- 0.06 nmol l-1 (basal) and 1.83 +/- 0.16 nmol l-1 (stimulated) in 23 healthy control subjects (mean +/- SE). Islet cell or insulin antibodies were not detected. Serum amylase levels rose abnormally in the dysglycaemic group, and pancreatitis was proved in one, and suspected in another patient. None of 28 similar AIDS patients whose P. carinii pneumonia was treated with cotrimoxazole showed blood glucose disturbance.

Acquired Immunodeficiency Syndrome↗

Potentiation of chloroquine activity against Plasmodium falciparum by the peroxidase-hydrogen peroxide system.

In this study, we examined the potential interactions between antimalarial (chloroquine, quinine, and mefloquine) and oxidant reagents. The data indicate that their effects enhance those of one another in vitro. The viability of Plasmodium falciparum in culture was assessed by [3H]hypoxanthine incorporation during 24 h of incubation in the presence of lactoperoxidase, glucose-glucose oxidase, hydrogen peroxide, chloroquine, quinine, and mefloquine, either alone or in combination. At subinhibitory concentrations, a significant inhibition was produced by the following combinations: lactoperoxidase plus hydrogen peroxide, lactoperoxidase plus glucose-glucose oxidase, lactoperoxidase plus hydrogen peroxide or glucose-glucose oxidase plus chloroquine or quinine but not with mefloquine. Deletion of any component from the system markedly decreased the toxic effect on P. falciparum. This toxic effect was not inhibited by catalase. These results indicate that the peroxidase-hydrogen peroxide system and antimalarial drugs can potentiate each other to inhibit the growth of P. falciparum.

Animals↗

Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages.

The activities of clarithromycin, sulfisoxazole, and rifabutin against three virulent strains of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome were evaluated in a model of intracellular infection. Human monocyte-derived macrophages were infected at day 6 of culture with M. avium complex. Intracellular bacteria were counted 60 min after inoculation. Extra- and intracellular bacteria were counted at days 4 and 7 after inoculation. The concentrations used were 4 micrograms of clarithromycin per ml (MICs for the three strains, 4, 4, and 4 micrograms/ml), 50 micrograms of sulfisoxazole per ml (MICs, 50, 25, and 25 micrograms/ml), and 0.5 micrograms of rifabutin per ml (MICs, 2, 0.5, and 0.5 micrograms/ml). Compared with controls, clarithromycin and rifabutin slowed the intracellular replication of the three strains (at day 7 after inoculation, P was less than 0.01 for the first strain and less than 0.001 for the two others). Sulfisoxazole was ineffective against the three strains. Clarithromycin was as effective as rifabutin. Clarithromycin plus rifabutin was as effective as each single agent. Clarithromycin plus sulfisoxazole was as effective as clarithromycin alone.

Acquired Immunodeficiency Syndrome↗

Comparative postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against intracellular multiplication of Legionella pneumophila serogroup 1.

The inhibitory and postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against virulent Legionella pneumophila serogroup 1 were evaluated in cell-free and cellular models. In the absence of macrophages (with the tissue culture medium alone), bacterial numbers remained unchanged at 24 h in the presence of 0.1 microgram of pefloxacin, ciprofloxacin, or ofloxacin per ml and 1.0 microgram of pefloxacin per ml, whereas they were reduced in the presence of 1.0 microgram of ciprofloxacin or ofloxacin per ml. Experiments to evaluate the postantibacterial effects of these drugs were therefore performed with concentrations of 0.1 microgram/ml. In the cell-free model, brief exposure (1 h) of bacteria to each antimicrobial agent resulted in a transient decrease in numbers followed by logarithmic growth. In the cellular model, all three drugs (at 0.1 and 1.0 microgram/ml) inhibited the intracellular multiplication of L. pneumophila. The intracellular postantibacterial effects of 0.1 microgram of pefloxacin, ciprofloxacin, and ofloxacin per ml, which were left in contact with L. pneumophila-infected human macrophages for 24 h, were evaluated at various times after removal of the drugs. Pefloxacin was found to exhibit a significant inhibitory effect at 72 h, whereas following the removal of ciprofloxacin and ofloxacin, rapid bacterial multiplication occurred, leading to the destruction of the macrophage monolayer within 48 h. Thus, while pefloxacin, ciprofloxacin, and ofloxacin all inhibited the multiplication of L. pneumophila in human monocyte-derived macrophages, only pefloxacin exhibited a prolonged postantibacterial effect.

Cell Division↗

[Antibiotherapy in chronic familial granulomatosis].

Antibacterial therapy in chronic granulomatous disease requires antimicrobials active on Staphylococcus aureus and enterobacteria, which also have a good intracellular penetration and activity as rifampicin, fluoroquinolone, fosfomycin, cotrimoxazole. Several trials showed that cotrimoxazole was effective for the prevention of bacterial infection: thus, this antimicrobial can be used as long-term and continuous prophylaxia. Fungal infections require the use of amphotericin B. The place of new imidazole compounds as itraconazole should be assessed.

Amphotericin B↗

Intestinal infections in patients with acquired immunodeficiency syndrome. A prospective study in 132 patients.

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P = 0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P less than 0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.

Acquired Immunodeficiency Syndrome↗

Bacterial prostatitis in patients infected with the human immunodeficiency virus.

Bacterial prostatitis was diagnosed in 17 of 209 human immunodeficiency virus-infected men hospitalized from October 1985 to October 1987. A history of urogenital disease was found in 13 of 17 patients. Clinical signs of prostatitis were present in 16 of 17 patients, including fever in 13, urinary symptoms in 11 and tender prostate on rectal palpation in 7. Bacteriuria was found in 14 of the 17 patients. Prostatic ultrasound examination showed an abscess in 11 of 16 patients studied. Prostatitis was diagnosed at autopsy in 1 patient. Within 6 weeks after onset of antimicrobial therapy 9 of 13 patients were cured and 4 of 13 did not respond to therapy. Among the 7 patients followed for more than 2 months after the end of antimicrobial therapy 5 had relapse. The prevalence of bacterial prostatitis among human immunodeficiency virus-infected patients increased from 3 per cent in asymptomatic human immunodeficiency virus-infected patients to 14 per cent in patients with the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Evaluation of teicoplanin for treatment of endocarditis caused by gram-positive cocci in 20 patients.

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated for the treatment of bacterial endocarditis in an open multicenter study from May 1985 to August 1987. A total of 20 patients with positive blood culture endocarditis received teicoplanin once daily as a mean intravenous injection of 7.3 mg/kg of body weight (range, 4.8 to 10.6 mg/kg); in 17 patients, teicoplanin was combined with another antibiotic, usually an aminoglycoside. The mean duration of therapy was 28 days (range, 7 to 66 days). The diagnosis of endocarditis was confirmed by echocardiography or anatomical findings in 15 patients and established on the basis of clinical manifestations plus positive blood cultures in 5 patients. The tricuspid valve was involved in 11 of the 20 patients. Isolates from blood were 12 Staphylococcus aureus, 1 Staphylococcus hominis, 1 Micrococcus sedentarius, 1 Enterococcus faecalis, 3 Streptococcus bovis, and 2 nongroupable Streptococcus sp. At the end of therapy, bacterial eradication was achieved in 17 of 20 patients (85%), and a favorable clinical outcome had occurred in 14 of 17 evaluable patients (82%). Of these 14 patients, one relapsed 4 months after the end of treatment. Thus, teicoplanin was effective in 13 of 17 patients (76%). Mean peak levels of teicoplanin in serum were lower, 23.1 +/- 2.9 micrograms/ml, in patients who failed than in those who were cured (45.8 +/- 8.4 micrograms/ml). Side effects occurred in 7 of 20 patients (35%), and required premature discontinuation of teicoplanin in 3 patients. These side effects were fever in three patients, rash in three patients, hearing loss in two patients, and increased serum transaminase levels in two patients. This study demonstrates the efficacy of teicoplanin in the treatment of endocarditis and the need for achieving peak levels in serum close to 40 micrograms/ml. Teicoplanin should now be further evaluated in endocarditis caused by gram-positive cocci means of controlled comparative study with standard therapy.

Adolescent↗

Role of IgG and complement component C5 in the initial course of experimental cryptococcosis.

Although cellular immunity has a crucial role during cryptococcosis, several in vitro studies have pointed out the importance of IgG anti-Cryptococcus neoformans antibodies and complement components during phagocytosis of the yeast by polymorphonuclear leucocytes and monocytes. We investigated the role of complement and specific antibodies in host defences against experimental cryptococcosis, using a monoclonal IgG1 antibody (E1) specific for cryptococcal capsular polysaccharide, and mice congenitally sufficient or deficient in the fifth component of complement (C5). During in vitro experiments, E1 and the normal mouse serum from C5-sufficient and -deficient mice were unable to inhibit the growth of C.neoformans. However, E1 was an efficient opsonin for the ingestion of C. neoformans by mouse peritoneal macrophages, acting in synergy with normal mouse serum. In vivo, E1 was protective in heavily infected C5-deficient mice (DBA/2) dying from an early acute pneumonia, but not in C5-sufficient mice (BALB/c) and in DBA/2 mice infected with a smaller inoculum dying from a late progressive meningo-encephalitis. Although protection against pneumonia is attributed to a local recruitment of phagocytes in C5-sufficient mice, this was not observed in C5-deficient mice protected with E1. In this case, IgG anti-C. neoformans antibodies seem to be an alternative for an efficient opsonization of the yeasts. Altogether, these data suggest that two main mechanisms may protect infected mice from an early fatal pneumonia: the efficient opsonization of the yeast by complement and the recruitment of phagocytes in infected tissues.

Animals↗

Pseudomonas aeruginosa sepsis presenting as peripheral subcutaneous nodules. Report of 2 cases.

Two patients developed disseminated subcutaneous nodules with febrile illness. In both cases, Pseudomonas aeruginosa was isolated from the lesions; blood cultures yielded the same organism in one case, and were negative in the other. The portal of entry was thought to be a jugular hemodalysis catheter in the first case and a necrotic zoster complicating lymphoma in the second case. Both patients' condition improved with antibiotic therapy and the Pseudomonas nodules resolved without surgical drainage.

Aged↗