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Biomedical subjects

O Lortholary

Publications and source records attributed to O Lortholary.

At least 19 recordsLinked to original sources

Aspergillus pericarditis with tamponade: report of a successfully treated case and review.

We report a case of aspergillus pericarditis with tamponade complicating invasive pulmonary aspergillosis in a patient treated for acute lymphocytic leukemia. Prolonged antifungal therapy and aggressive surgical treatment cured the pericarditis, without relapse, despite the fact that the patient underwent autologous bone marrow transplantation. In a review of 28 other cases of aspergillus pericarditis, we found that this condition usually had occurred in severely immunocompromised patients and was always the result of contiguous dissemination of Aspergillus from the lung or myocardium. Tamponade was present in eight of 29 patients. Aspergillus antigen was detected in the pericardial fluid of all three patients whose fluid specimens were tested. Aspergillus pericarditis was diagnosed before death in 10 of 29 patients, all of whom had established premortem diagnoses of invasive aspergillosis at other sites and had received antifungal therapy. Three of the four survivors received combined medical and aggressive surgical therapies. The performance of echocardiography early during the course of invasive pulmonary aspergillosis, together with intensive combined therapies, might lower the high mortality associated with aspergillus pericarditis.

Adult

Candidemia: a nosocomial complication in adults with late-stage AIDS.

We retrospectively analyzed 13 episodes of candidemia observed between July 1990 and July 1995 in human immunodeficiency virus (HIV)-infected adults. Candidemia was nosocomially acquired by 11 patients, among whom nine had a central venous catheter (CVC). Twelve cases were of stage C2/C3 according to the 1993 classification of the Centers for Disease Control and Prevention. The median CD4+ cell count was 10/mm3 (range, 3-400/mm3). Causative species were Candida albicans in nine episodes and Candida glabrata and Candida krusei in two episodes each. Eleven episodes occurred in 11 patients who had previously received fluconazole (mean total dose, 7.4 g), including the four episodes caused by non-albicans species. Outcome did not differ according to the administered antifungal therapy. CVCs were removed from seven patients (78%). The overall mortality was 38%. Candidemia is a potentially lethal nosocomial complication during late-stage AIDS and can be due to C. albicans and non-albicans strains.

AIDS-Related Opportunistic Infections

Colonization by Acinetobacter baumanii in intensive-care-unit patients.

We prospectively studied the value of systematic rectal swabs performed for the detection of colonization and the prediction of infections by Acinetobacter baumanii in 751 consecutive patients admitted to five intensive-care units (ICUs) over an 8-month period. Gastrointestinal tract colonization was found in 8.7% of ICU admissions. The positive and negative predictive values of rectal swabs for the detection of subsequent infection were 17% and 99%, respectively. Sensitivity and specificity were 55% and 93%, respectively. We also determined the comparative values of rectal or nasal swabs and skin cultures for the detection of A baumanii colonization in 25 patients already colonized or infected with A baumanii. The combination of rectal and nasal swabs was positive in 20 (80%) of 25. The results of the present study suggest that detection of gastrointestinal tract A baumanii colonization is not an accurate predictor of subsequent A baumanii infection and that combined rectal and nasal swabs might be used for the detection of A baumanii colonization in ICU patients.

Acinetobacter

Population pharmacokinetic study of amikacin administered once or twice daily to febrile, severely neutropenic adults.

Once-daily (o.d.) administration of 20 mg of amikacin per kg of body weight to neutropenic patients has been validated by clinical studies, but amikacin pharmacokinetics have been documented only for the 7.5-mg/kg twice-daily (b.i.d.) regimen in this population. In order to determine in neutropenic patients (i) the influence of the dosing regimen on the kinetics of amikacin, (ii) the linearity of kinetics of amikacin in the range of 7.5 to 20 mg/kg, and (iii) the influence of patient characteristics on the disposition of amikacin and (iv) to provide a rationale for dosing recommendations, we evaluated the population pharmacokinetics of amikacin administered to 57 febrile neutropenic adults (neutrophil count, <500/mm3) being treated for a hematological disorder and receiving amikacin at 7.5 mg/kg b.i.d. (n = 29) or 20 mg/kg o.d. (n = 28) and administered intravenously over 0.5 h. A total of 278 blood samples were obtained (1 to 14 samples per patient) during one or several administration intervals (1 to 47). Serum amikacin levels were measured by the enzyme-multiplied immunoassay technique. A mixed-effect modeling approach was used to fit a bicompartmental model to the data (NONMEM software). The influences of the dosing regimen and the demographic and biological indices on the pharmacokinetic parameters of amikacin were evaluated by the maximum-likelihood ratio test on the population model. The dosing regimen had no influence on amikacin pharmacokinetic parameters, i.e., the kinetics of amikacin were linear over the range of 7.5 to 20 mg/kg. Amikacin elimination clearance (CL) was only correlated with creatinine clearance or its covariates, namely, sex, age, body weight, and serum creatinine level. The interindividual variability of CL was 21%, while those of the central volume of distribution, the distribution clearance, and the tissue volume of distribution were 15, 30, and 25%, respectively. On the basis of the expected distribution of amikacin concentrations in this population, dosing recommendations as a function of creatinine clearance (CL[CR]) are proposed: for patients with normal renal function (CL[CR] of 80 to 130 ml/min), 20 mg/kg o.d. is recommended, whereas for patients with severe renal impairment (CL[CR], 10 to 20 ml/min), a dosage of 17 mg/kg every 48 h is recommended.

Adolescent

Temporal arteritis symptoms in a patient with hepatitis C virus associated type II cryoglobulinemia and small vessel vasculitis.

We describe temporal artery localization of hepatitic C virus related cryoglobulin induced vasculitis in a 66-year-old woman. The patient had features of both cryoglobulin induced vasculitis (palpable purpura, arthralgia, hypocomplementemia, no inflammatory syndrome) and temporal arteritis (recent onset of headaches, jaw claudication). In the temporal artery biopsy, the vasculitis was localized to a small adventitial artery and did not involve the superficial temporal artery. Thus temporal arteritis and jaw claudication can be signs of cryoglobulin induced vasculitis.

Aged

Hypercalcemia may indicate Richter's syndrome: report of four cases and review.

BACKGROUND: Hypercalcemia has rarely been reported in patients with Richter's syndrome (RS). In this article, the authors report four cases with complementary pathophysiologic examinations. METHODS: Four patients with hypercalcemia that indicated RS were admitted to the study unit between 1980 and 1994 with the following diagnoses: transformation of mixed follicular lymphoma, Waldenstrom's macroglobulinemia, and chronic lymphocytic leukemia, respectively, in 3 men ages 60 to 73 years, and chronic lymphocytic leukemia in a woman 73 years of age. Radiologic and histologic features were reported. Circulating levels of parathormone-related peptide (PTHrP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured. RESULTS: Radiologic skeletal abnormalities were found in three of three cases: osteopenia twice and multifocal osteolysis once. All four patients had large cell lymphoma (LCL). Bone resorption assessed histomorphometrically was elevated in two of two cases. Serum TNF-alpha and IL-6 levels were high in three of three and one of three cases, respectively. Elevated values were also found in four patients with LCL but without hypercalcemia. The serum PTHrP level was increased in the only hypercalcemic patient tested and values were normal in the three control patients. CONCLUSIONS: Hypercalcemia arising in a patient with a low grade lymphoproliferative disorder may indicate RS. Hypercalcemia is due to increased bone resorption, which may be caused by the secretion of osteoclast-stimulating factors by the LCL invading the bone marrow. Independently, TNF-alpha and/or IL-6 were unlikely causative factors of hypercalcemia in the patients in this study; however, synergism with PTHrP was suspected in one case.

Aged

[Distal gangrene and cryoglobulinemia related to hepatitis C virus infection with presence of anticardiolipin antibodies].

We report the case of a 63-year old women with toe gangrene, peripheral polyneuropathy, polyarthritis, histologically proven necrotizing vasculitis, in association with type III mixed cryoglobulinemia and hepatitis C virus (HCV) infection. Raised anticardiolipin antibodies (aCL) were found, without beta 2-glycoprotein I. HCV infection is associated with mixed cryoglobulinemia which can cause a vasculitis affecting various organs. The pathogenesis of production and clinical significance of aCL could be associated in this case with HCV infection.

Antibodies, Anticardiolipin

Serum cortisol and DHEA concentrations during HIV infection.

The progression of HIV infection is accompanied by severe immunodepression and cachexia, particularly during advanced stages. The immune depression is due largely to a dramatic drop in the number of CD4 cells. The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue. We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men. The results of five retrospective and prospective studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls. Serum cortisol was elevated at all stages of infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage IV C). In contrast, the serum DHEA concentrations were closely correlated with the stage of HIV-infection, being higher in the early stages (stages II and III or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p < .001). There was a negative linear correlation between the CD4 cell counts and cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r = +0.36, p < .01). There was no significant correlation between delta body weight and serum cortisol. In contrast, there was a negative correlation between serum DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection. This raises the question of whether there is a cause-and-effect relationship between clinical progression and circulating steroid concentrations. Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies.

Adult

Haemophilus endocarditis: report of 42 cases in adults and review. Haemophilus Endocarditis Study Group.

To define the clinical, microbiological, and therapeutic characteristics of haemophilus endocarditis, we reviewed the charts of 42 adults with haemophilus endocarditis (native valve disease, 37; prosthetic valve disease, five) who were followed up between 1983 and 1995 in France. The mean duration of symptoms before diagnosis was 34 days. The causative Haemophilus species were as follows: H. parainfluenzae (26 adults), H. aphrophilus (9), H. paraphrophilus (4), and H. influenzae (3). According to the Duke criteria, 38 cases of endocarditis were definitive and four were possible. Thirty-nine patients received combination antibacterial therapy and three received therapy with a beta-lactam agent alone (mean duration, 46 days). Arterial embolism occurred in 15 patients. Cardiac surgery was indicated for 18 patients; 16 of these surgeries were performed within 3 months. Two patients died of heart failure. In conclusion, haemophilus endocarditis is rare and is mainly due to H. parainfluenzae. Although surgery is often necessary, haemophilus endocarditis has a favorable prognosis.

Adolescent

Antifungal prophylaxis during neutropenia and immunodeficiency.

Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses.

Anti-Bacterial Agents

[Azole antifungal agents in the prevention of fungal infections in neutropenic patients and bone marrow graft recipients].

Fungal infections are often encountered in neutropenic patients and bone marrow graft recipients. Several studies have demonstrated the efficacy of antifungal prophylaxis. Regimens including azole compounds are increasingly used due to facilitate administration. The efficacy of fluconazole to prevent systemic candidiasis was recently documented in multicentric studies in bone marrow recipients but is more controversial in neutropenic patients. The risk of selecting strains of Candida with lower sensitivity to azole compounds must also be taken into consideration. There has not been any large study evidencing a primary prophylactic affect of itraconazole against invasive aspergillosis, but the results of multicentric studies should be available soon. Recent trials have attempted to determine how these compounds can best be used in empirical treatment of persistent fever in neutropenic patients and in secondary prophylaxis for mycoses during later intensive treatment protocols.

Antifungal Agents

Protein tyrosine kinases in activation signal of human basophils through the immunoglobulin E receptor type l.

Human basophils activated through high-affinity immunoglobulin E (IgE) receptors (Fc epsilon RI) are involved in the late phase of the allergic reaction. To investigate the possible involvement of protein-tyrosine kinases in this activation we used human acute basophilic leukemia (ABL) cells in culture as well as a pure population of normal basophils in vitro-derived from human bone marrow precursor cells (HBMB). ABL cells were 50-80% basophils at various stages of maturation as assessed by staining, morphology, ultrastructure, and flow cytometry analysis, and only basophils in ABL cells expressed Fc epsilon RI. Aggregation of Fc epsilon RI by IgE and anti-IgE, IgE and antigen, or anti-Fc epsilon RI monoclonal antibodies on ABL cells or on HBMB, led to increased tyrosine phosphorylation of 120-, 100-, 80-, 72-, 50- to 65-, and 38-kDa substrates. Tyrosine phosphorylations in ABL cells were in basophils because 1) they were detected after a 5-s stimulation, 2) they were observed under conditions where mediator release is minimal, i.e., in the absence of extracellular calcium, 3) hapten addition during antigen stimulation resulted in almost total disappearance of tyrosine phosphorylations within 30 s. There was correlation between histamine release and tyrosine phosphorylation in anti-IgE dose-responses and in dose-responses of the tyrosine kinase inhibitor genistein. The tyrosine kinase p72syk was detected in the cells. Stimulation of ABL cells for 1 min resulted in extracellular calcium-independent tyrosine phosphorylation and activation of p72syk. Therefore, tyrosine kinases are involved in the early steps of human Fc epsilon RI signaling in basophils. Tyrosine kinases and their substrates could represent new potential therapeutic targets to prevent the development of the allergic reaction.

Aged