Spontaneous rupture of the spleen revealing primary human immunodeficiency virus infection.
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Biomedical subjects
Publications and source records attributed to F Raffi.
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OBJECTIVE: To define the factors associated with diagnosis of toxoplasmic encephalitis (TE) in AIDS patients; and to establish a rational procedure for the clinician faced with a decision concerning empiric antitoxoplasma therapy. DESIGN: A 15-month prospective multicentre cohort study in France. METHODS: One hundred and eighty-six consecutive HIV-positive inpatients undergoing empiric antitoxoplasma therapy for a first episode of presumed TE were monitored. The clinician's initial estimation of the probability of response to antitoxoplasma therapy was recorded. In addition, a validation committee classified cases as TE or non-TE. RESULTS: Among the 186 patients, the following variables were significantly more frequent in TE (n = 113) than non-TE (n = 73) patients: fever (59% versus 40%). headache (55% versus 33%), seizures (22% versus 11%), suggestive lesions on the brain scan (98% versus 76%), positive Toxoplasma serology (97% versus 71%). Median CD4+ lymphocyte count was significantly higher in TE than in non-TE (27 x 10(6)/l versus 11 x 10(6)/l). The rate of TE in patients on systemic antiprotozoal prophylaxis at entry was 43% as compared with 75% in patients without previous prophylaxis. Pre-therapy estimation of response to empiric therapy was highly correlated with final diagnosis. Multivariate logistic regression analysis showed that the following variables contributed independently to the diagnosis of TE: clinician's estimation of response to treatment at entry > 75%; absence of systemic antiprotozoal prophylaxis; seizures; headache; suggestive lesions on CT or MRI brain scan; and positive Toxoplasma serology. CONCLUSIONS: A linear logistic model is proposed which uses significant variables, which are readily available. This model gives good accuracy to classify suspected cases of TE.
OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.
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Thrombotic microangiopathy (TMA) has been rarely described in HIV-infected patients. We report four cases of TMA during HIV infection and we analyse clinical, biological, etiologic, therapeutic and evolutive aspects of these four cases. Initial symptomatology is non specific and diagnosis is often delayed. Peripheric thrombopenia with haemolytic anemia and renal failure must be suggestive of the diagnosis. TMA can be present at any stage of HIV infection. Physiopathological mechanism of TMA during HIV infection remains unclear. These cases lead to suspect the role of opportunistic infections, neoplasia or HIV directly by endothelial injury or indirectly by cytokines secretion. Therapy of TMA is not different from non-HIV patients. Improvement with treatment must be obtained but long-term prognosis remains poor in account of HIV infection.
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We determined the safety and efficacy of deoxycholate-amphotericin B (d-AmB) mixed with Intralipid (IL) as the initial treatment of AIDS-associated cryptococcal meningitis in a phase II, multicentre, non-comparative open study, assessing two dosages of ILd-AmB: 1 mg/kg (group A, n = 9) and 1.5 mg/kg (group B, n = 6). Patients were treated daily for 2 weeks, then three times weekly for 4 weeks. The ILd-AmB dosage was decreased due to toxicity in three patients in each group. Serum creatinine increased significantly on day 14 in group A and on day 7 in group B. Nephrotoxicity, (serum creatinine level > 165 mumol/L) was noted in two and five patients in groups A and B, respectively. Nine adverse haematological events were noted (seven cases of anaemia requiring transfusion, and two cases of neutropenia < 750/mm). Two patients had an increase in serum alkaline phosphatase. In each cohort, 15% of the infusions were associated with fever and/or chills. Successful outcome was obtained in half of the patients. We conclude that, in AIDS patients with cryptococcosis, tolerance to ILd-AmB was acceptable when the daily dosage did not exceed 1 mg/kg, but the higher 1.5 mg/kg daily dosage was associated with an unacceptable rate of nephrotoxicity. Neither of these relatively high daily dosages of ILd-AmB achieved an improved rate of successful outcomes compared with lower daily dosages of conventional d-AmB in glucose.
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Inappropriate macrophage activation is responsible for clinical, biological and histological features characterized by diffuse non malignant histiocytic tissue infiltration called "reactive hemophagocytic syndrome" (RHS). We report here 23 new cases. Immunodepression (10 cases), hematologic malignancies (13 cases) and infection (10 cases) are the most favorable conditions associated with RHS. In many cases, several conditions were present at time of diagnosis of RHS and increased its severity. Mechanisms of RHS remains unclear, but cytokine may play a role. Outcome is variable, but death is the most common issue (17 deaths in our series related to RHS). Corticosteroids, etoposide can improve some situations. Further study is needed to establish the role of cyclosporine A or allogenic bone marrow transplantation.
Three men and one woman (mean age 52 years) were admitted to hospital for septicemia (2 cases), sudden partial loss of visual acuity (1 case) and suspected conjunctivitis (1 case). Three of the patients showed risk factors (diabetes, alcohol intoxication, immunosuppression). Panophthalmitis (affecting all tunics of the eye) was apparent from the initial examination in all 4 cases (2 bilateral and 2 unilateral). Ocular involvement was associated with endocarditis and meningitis (pneumococcus) in 1 case, with nocardiosis (pulmonary, cerebral and nodal) in 1 case, and with septicemia with bacterial arthritis (Escherichia coli, streptococcus A) in 2 cases. Hemocultures were positive in 3/4 cases. The micro-organism was also detected in the joint (n = 2), urine (n = 1) and cerebrospinal fluid (n = 1), during pulmonary transparietal puncture (n = 1) and in intraocular biopsy tissue (n = 1). All patients received appropriate antibiotic therapy intravenously and intraocularly. The infection was cured in all cases, but with severe functional sequelae: blindness in 2 cases, and unilateral enucleation in the other 2 cases.
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OBJECTIVES: Nocardial infection is usually localized in the immunocompetent patient and occurs as an opportunistic disseminated infection in about half of the cases in immunoincompetents patients. METHODS: We report a retrospective assessment of 9 cases of nocardial infection diagnosed between January 1991 and February 1994. RESULTS: Six of the patients were immunodepressed: 3 had a disseminated infection with pulmonary (n = 2), brain (n = 2), skin (n = 3) and/or ocular (n = 1) localizations. There were 3 immunocompetent patients with an isolated local infection: skin and bone mycetoma, knee joint and lung. Diagnosis was made on samples obtained invasively in 7 patients. Nocardia asteroides was isolated in 5 patients, N. farcinica in 3 and N. caviae in 1. These organisms showed in vitro sensitivity to amoxicillin-clavulanic acid 5/9, cefotaxime 5/9 (0/3 for N. farcinica), imipeneme 7/9, amikacin 8/8, minocyclin 5/8, pefloxacin 0/8 and trimethoprime-sulfamethoxazol (TMP-SMX) 3/9. Clinical outcome was favourable in all cases and was not always correlated with laboratory sensitivity. CONCLUSION: TMP-SMX remains the reference antibiotic. For one patient, only TMP-SMX (resistant in vitro) was effective; with all the other antibiotic tried (sensitive in vivo) treatment failed.
Cytomegalovirus (CMV) infection is the most frequent systemic viral opportunistic infection in AIDS, occurring in almost 40% of patients, at a stage of profound immunodeficiency, with a CD4 cell count lower than 50/microL. The most frequent localizations are retinal and gastrointestinal. Diagnosis of retinis, which can be totally asymptomatic, is based on fundus examination, which should be performed regularly in patients with AIDS and/or low CD4 count. Diagnosis of colitis, as of other rare manifestation (oesophagitis, hepatitis, encephalitis, myeloradiculitis, pneumopathy), relies on the association of suggestive clinical symptoms and CMV inclusions in biopsy specimens and/or CMV positive culture. The 2 drugs available for treatment of CMV disease, ganciclovir and foscarnet, are administered by intravenous route, with 2 infusions per day for induction therapy (usually 2 to 3 weeks), then once a day as lifelong maintenance therapy, to lessen or delay recurrences. Active drugs which could be given orally, combination of 2 drugs, new potent drugs and the development of prophylaxis in at-risk patients should help to improve the prognosis of CMV infection in AIDS.
The aim of this report is to draw the attention of clinicians to the possible occurrence of endometrial cancers of rare histological type among women currently undergoing or having in the past undergone tamoxifen therapy, in particular for breast cancer. We report a case of heterologous mixed malignant müller tumor occurring in an 80-year-old woman. At 69, she had been diagnosed with breast cancer and received tamoxifen for a total of 55 months over a 6-year period. In the 5th year after cessation of tamoxifen therapy, an endometrial carcinosarcoma was diagnosed. Although the association between tamoxifen use and endometrial cancer is recognized, only a few reports of occurrence long after cessation of therapy exist. We believe ours is the second for this particular histological type. Tamoxifen may have played a role in the occurrence of this tumor although it is also known that this type of tumor may arise de novo in elderly women. The etiologic hypothesis obtained from this case description will now be tested in a formal epidemiological investigation which hopefully will provide more definitive evidence.