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Biomedical subjects

C Leport

Publications and source records attributed to C Leport.

At least 19 recordsLinked to original sources

Ocular toxoplasmosis in human immunodeficiency virus-infected patients.

The files of 45 human immunodeficiency virus-infected patients with ocular toxoplasmosis were reviewed, with a median follow-up of eight months. The condition was unilateral in 37 of the 45 patients (82%) and was bilateral in eight (18%). Inflammation of the anterior chamber and the vitreous was present in 32 of 53 eyes (60%) and 38 of 53 eyes (72%), respectively. Cytomegalovirus retinitis developed during the follow-up period in nine patients (20%). Cerebral toxoplasmosis was concurrently diagnosed with the ocular toxoplasmosis in 13 patients (29%). The efficacy of the combination of pyrimethamine and sulfadiazine or clindamycin was assessed in 42 patients for the induction therapy and in 38 patients for the maintenance therapy. Induction therapy was always effective within a median period of six weeks. During maintenance treatment, the 24-month relapse rates were 0.20 and 0.18 for the 50-mg/day and 25-mg/day dosage of pyrimethamine, respectively. The overall 12-month survival rate was 0.72. Our results suggested that ocular toxoplasmosis has a better ocular prognosis than cytomegalovirus retinitis, but that it requires appropriate treatment because life-threatening cerebral involvement is often associated.

Adult

[Non-typhic Salmonella bacteremias in HIV infections. Clinical and therapeutic data, and course in 68 patients].

Between 1982 and 1989, a retrospective study on non typhi Salmonella bacteremias was performed among patients infected with human immunodeficiency virus hospitalized in 4 departments of Infectious and Tropical Diseases in Paris. The population included 59 men and 9 women; 26.4 percent had been contamined with HIV by heterosexual contact; 17.6 percent originated from Africa or Haiti. Clinical symptoms were fever (100 percent of the cases), present since less than 5 days (65 percent of the cases), and gastrointestinal symptoms, present in 53 percent of the patients. Blood cultures were positive in all cases; Salmonella was less frequently found in other sites: stools (n = 13, 19 percent), urine (n = 5), lymph nodes (n = 1), sputum (n = 1). Mean CD4 cell count was 118 +/- 145/mm3. The serotypes were mainly S. typhimurium (n = 26), S. enteritidis (n = 23), and S. dublin (n = 15). Under antibiotic therapy, the course of the disease was initially favorable in 98.5 percent of the cases. One patient died of septic shock. At least one relapse occurred in 17 percent of the patients, 2.1 +/- 1.6 months after the end of the initial therapy. No relapse was observed in patients taking zidovudine or antibioprophylaxis, but 53 percent of the patients without antibioprophylaxis relapsed (P less than 0.001). The overall survival of the cohort was 25 percent after 18 months. These results show the poor prognosis of a first episode of Salmonella bacteremia in HIV infected patients, making the diagnosis of AIDS highly probable if cellular immunity is markedly impaired.

4-Quinolones

Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group.

OBJECTIVE: To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen. SETTING: University hospitals. PATIENTS: Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable. INTERVENTIONS: Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks. MEASUREMENTS AND MAIN RESULTS: There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover. CONCLUSIONS: The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.

Acquired Immunodeficiency Syndrome

Should pulmonary tuberculosis be an AIDS-defining diagnosis in patients infected with HIV?

Between 1983 and 1989, we cared for 56 patients with tuberculosis and human immunodeficiency virus (HIV) infection. In 37 patients (66%), tuberculosis occurred before any other AIDS-defining disease (group 1); in 10 (18%) it occurred during the same month as another AIDS-defining disease (group 2); and in 9 (16%), after the diagnosis of AIDS (group 3). Tuberculosis was entirely pulmonary in 14 patients (25%), entirely extrapulmonary in 9 (16%), and both pulmonary and extrapulmonary in 33 (59%). The frequency of extrapulmonary involvement was similar in patients from group 1 and from groups 2 and 3 (combined): 76% versus 74%. Needle biopsy of the liver revealed hepatic involvement in 18 patients (32%). The mean CD4 lymphocyte count was 232/mm3 when tuberculosis was entirely pulmonary, and 243/mm3 when extrapulmonary disease was present (difference not significant). In group 1, the onset of both pulmonary and extrapulmonary tuberculosis occurred at the same stage of HIV infection, 12 and 10 months, respectively, before any other AIDS-defining disease. Treatment, planned to last 1 year, was highly effective, despite frequent side-effects. Among the 32 patients who completed treatment, relapse of tuberculosis occurred in 2 (6%) with a mean follow-up of 16 months (0-53 months) after completion. Our results suggest that pulmonary tuberculosis should be included in the criteria for diagnosis of AIDS.

Acquired Immunodeficiency Syndrome

Serum carcinoembryonic antigen: a prognostic marker in HIV-related Pneumocystis carinii pneumonia.

Serum concentrations of carcinoembryonic antigen (CEA) were measured in 43 consecutive patients with HIV-related Pneumocystis carinii pneumonia (PCP). The subjects were divided into 2 groups according to the severity of the PCP:PaO2 in ambient air (AA) less than or equal to 50 mmHg on admission (n = 22, group 1) and PaO2 greater than 50 mmHg (n = 21, group 2). In addition, 57 HIV patients with either non-PCP pulmonary diseases (n = 34, group 3) or extrapulmonary disease (n = 23, group 4) were studied. Mean CEA levels (ng/ml) were 13 +/- 10 in group 1 and 4.9 +/- 5.5 in group 2 (p less than 0.001). The corresponding values in groups 3 and 4 were much lower (2.7 +/- 1.8 and 2.4 +/- 1.8, respectively). In group 1, mean initial CEA levels were higher (p less than 0.001) in the patients who died (n = 6; 23.5 +/- 11) than in the survivors (n = 16; 8.9 +/- 7), although the initial mean PaO2 were identical (39 +/- 7 and 39 +/- 8 mmHg, respectively) and the initial mean LDH levels were not significantly different (1544 +/- 530 and 1200 +/- 457 IU/l). CEA levels fell during specific anti-PCP therapy associated with corticosteroids but returned to normal only in the survivors. We conclude that CEA levels are increased in patients with PCP and acute respiratory distress. Among the patients with PaO2 levels of less than or equal to 50 mmHg before treatment, only high levels of CEA (greater than 20 ng/ml) were associated with a fatal outcome, regardless of anti-PCP therapy associated with corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Unexplained fever and chronic fatigue: abnormal circadian temperature pattern.

OBJECTIVES: Standard clinical and biological investigations can be used to determine the origin of persistent and moderate fever in a large number of otherwise asymptomatic patients. However, in a small proportion of cases, isolated fever and fatigue persist despite the absence of detectable organic malfunction. This study was conducted to investigate the circadian thermic pattern in patients with apparently unexplainable fever and chronic fatigue and in those with fever of recognized origin. METHODS: We recorded central temperature continuously for 24 hours in patients with moderate fever of both unexplained and recognized origin, and in a control group of healthy volunteers. A Fourier series was used for harmonic analysis. RESULTS: Thermic patterns specific to the three groups were identified by statistical and factorial analysis. The patients with fever of unknown origin and chronic fatigue were clearly characterized in terms of the phase, amplitude of the first (fundamental) harmonic and minimum circadian temperature. CONCLUSION: The abnormal central temperature pattern in these patients may prove to be an important step in the management of febrile patients.

Adolescent

[Usefulness of folinic acid in cytopenia induced by antiparasitic drugs in AIDS patients].

The scientific basis for using folinic acid in combination with the antiparasitic drugs prescribed to AIDS patients has been reviewed. In vitro and experimental data are unclear. On the basis of folinic acid metabolism and pharmacology and of clinical experience, we suggest that folinic acid should not be systematically added to the curative treatment of pneumocystosis with cotrimoxazole. Folinic acid may be added to prophylactic regimens using high-dose cotrimoxazole (i.e. 800 mg sulfamethoxazole twice a day) and in malnourished patients. It should be administered as soon as cytopenia occurs in the course of treatment. Concerning toxoplasmosis, the addition of folinic acid is recommended in doses of 10 to 20 mg/day in acute therapy and 5 to 10 mg/day in maintenance therapy. Dosage must be adjusted to the results of blood counts.

Acquired Immunodeficiency Syndrome

Long-term follow-up of patients with AIDS on maintenance therapy for toxoplasmosis.

To assess potential interactions of multiple drug regimens administered to patients with AIDS for toxicity and efficacy, we reviewed the charts of 35 patients on maintenance therapy for toxoplasmosis. Seven relapses of toxoplasmosis occurred in 6 of 35 (17%) patients, and seven episodes of pneumocystosis occurred in 6 of 35 (17%) patients. Four relapses of toxoplasmosis and 5 relapses of pneumocystosis were seen in 20 patients treated with pyrimethamine/clindamycin; 2 relapses of toxoplasmosis and 2 relapses of pneumocystosis were seen in 11 patients treated with pyrimethamine alone, and 1 relapse of toxoplasmosis was seen in 13 patients treated with pyrimethamine/sulfadiazine. Adverse effects were related to pyrimethamine in 10 patients, to clindamycin in 7 patients, and to sulfadiazine in 8 patients. These results must be compared with those of prospective trials to determine the efficacy and safety of various maintenance regimens.

Acquired Immunodeficiency Syndrome

Treatment of acute toxoplasmosis with intravenous clindamycin. The California Collaborative Treatment Group.

The interim results are presented of an ongoing large-scale, prospective, randomized study to determine the potential role of clindamycin in the treatment of toxoplasmic encephalitis. Patients were seropositive for Toxoplasma gondii antibodies and had clinical signs compatible with toxoplasmic encephalitis. Data was available on 33 patients, 15 of whom received pyrimethamine p.o./clindamycin i.v. and then p.o., and 18 of whom received pyrimethamine p.o./sulfadiazine p.o. The interim evaluation did not reveal a remarkable difference between the two regimens in the clinical or radiologic response. Adverse reactions to both regimens were common and frequently multiple, there being more adverse gastrointestinal reactions in patients on pyrimethamine/clindamycin and more adverse hematological reactions in those on pyrimethamine/sulfadiazine.

Acquired Immunodeficiency Syndrome

Mechanisms of ceftriaxone prophylaxis against late bacteremic vascular graft infection caused by Staphylococcus aureus in a dog model.

Possible mechanisms of the prophylactic effect of ceftriaxone against late bacteremic vascular graft infection in dogs were investigated. Dogs bearing an expanded polytetrafluoroethylene graft implanted as thoracoabdominal aortic bypass for one month were exposed to transient bacteremia produced by intravenous injection of 2.6 +/- 1.8 x 10(8) colony forming units Staphylococcus aureus 209P-R. To assess the effect of the antibiotic on bacteria already adherent onto the grafts, we compared the results from six untreated dogs used as controls and six dogs receiving ceftriaxone (0.5 g, intramuscularly) 90 minutes after the bacteremic challenge. The grafts were removed one week after the bacteremic challenge and cut into 10 to 15 fragments, each submitted to viable bacterial counts. The number of grafts and the number of fragments yielding bacterial growth were the same in the two groups. However, the median density of bacteria was lower (p less than 0.01) in the dogs given ceftriaxone, 64 colony forming units/cm (range: 3-8,700), than in the control dogs, 585 colony forming units/cm (range: 12-64,000), suggesting that ceftriaxone had an effect on the postadherence phase of the development of infection. To assess the effect of ceftriaxone on the adherence phase we compared the results from seven untreated dogs and seven dogs receiving ceftriaxone (0.5 g intramuscularly) 90 minutes before the bacteremic challenge. The grafts were removed two hours after the bacteremic challenge. Though all the seven grafts were colonized in each group, the number of fragments yielding bacterial growth was lower (p less than 0.05) in the dogs given ceftriaxone (59/70) than in the control dogs (90/91).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Prevention of vascular graft infection by rifampin bonding to a gelatin-sealed Dacron graft.

This study examines the efficacy of rifampin bonding to a gelatin-sealed knitted Dacron graft to prevent perioperative bacteremic vascular graft infection. Antibiotic bonding was obtained by soaking grafts for 15 minutes in a 1 mg/ml saline solution of rifampin at 37 degrees C. Nineteen dogs had thoracoabdominal aortic bypass: seven (group I) received a rifampin treated graft; six (group II) received an untreated gelatin-coated graft; and six (group III) received an uncoated Dacron graft. Two days later bacteremic challenge was produced by rapid intravenous injection of 5 x 10(5) colony forming units of methicillin resistant Staphylococcus aureus. Grafts were harvested five days after this challenge and cut into 10 fragments, each submitted to bacterial counts. Results were expressed as CFU/cm2 of graft material. In group I, no graft was infected, whereas all grafts in groups II and III were infected (p less than 0.05). Median bacterial counts from the infected fragments (median +/- SD) were similar in groups II (2.5 x 10(5) CFU/cm2) and III (4 x 10(4) CFU/cm2). Blood cultures at time of sacrifice were negative in all dogs in group I and positive in five of six dogs in groups II and III. Cultures of liver, spleen, kidney, and lung specimens were always negative in group I and positive in 22 of 24 specimens in group II and 23 of 24 specimens in group III. Soaking a gelatin-sealed Dacron graft in rifampin solution evidently prevents early bacteremic graft infection and secondary foci of infection in this model.

Animals

Resting energy expenditure is increased in stable, malnourished HIV-infected patients.

Resting energy expenditure (REE) was measured by reference to body composition in 50 malnourished patients with human immunodeficiency virus (HIV) infection and compared with that of 14 healthy subjects. Among HIV patients, 40 had acquired immune deficiency syndrome (AIDS) and 10 had AIDS-related complex (ARC). All were in stable condition and had a previous history of progressive wasting, ie, a mean body weight loss of 14.2 +/- 8.1 kg over 16.6 mo (range 2-49 ms). The mean REE was 14% higher than estimated basal energy expenditure (EBEE), according to the Harris and Benedict formula. Thirty-four patients (68%) were classified as hypermetabolic (REE greater than 110% EBEE). The best predictable variable for REE was fat-free mass (FFM), as determined by an anthropometric method (r = 0.72; P less than 0.001). The mean REE was 12% higher in HIV patients than in the control group FFM (156 +/- 19 vs 124 +/- 17 kJ.kg FFM-1.d-1). We concluded that in stable and malnourished HIV patients, the progressive wasting may be partly related to an increase in REE. The mechanism of this hypermetabolic state remains to be established.

Body Composition

Pyrimethamine-clarithromycin combination for therapy of acute Toxoplasma encephalitis in patients with AIDS.

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.

Acquired Immunodeficiency Syndrome