Cotrimoxazole therapy ofToxoplasma gondii encephalitis in AIDS patients

Twenty-four consecutive HIV-positive patients affected byToxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75 % response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients withToxoplasma gondii encephalitis.Deceased.     

Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen

OBJECTIVES: To evaluate the condition of oxidative stress in patients undergoing prolonged exposure to hyperbaric oxygen (HBO) and the possible modifications of the antioxidant defense systems in the absence of antioxidant supplementation. DESIGN AND METHODS: Twelve patients exposed to 15 HBO treatments for pathological conditions related to hypoxia were included in the study. Oxidative stress indices as well as plasma and erythrocyte antioxidant levels were measured in blood samples collected both at the 1st and 15th HBO session. RESULTS: The repeated exposures to HBO led to a significant accumulation of plasmatic reactive oxygen metabolites (ROM) and malondialdehyde (MDA). After 15 HBO sessions, no relevant differences were detected for reduced glutathione (GSH), alpha-tocopherol, and retinol plasma levels; however, a significant decrease in erythrocyte superoxide dismutase (SOD) and catalase (CAT) activity was observed when compared to the 1st HBO exposure; glutathione peroxidase (GPx) activity remained almost unchanged. CONCLUSIONS: In the absence of antioxidant supplementation, the prolonged HBO treatment leads to a condition of oxidative stress that seems to affect in particular the response of the enzymatic antioxidant defense system; the possible relationship between the chemical modifications of the enzymes caused by oxygen reactive species and the consequent inactivation of the proteins is under investigation.     

AIDS related neoplasms in Genoa,Italy

The study defines the epidemiological characteristics of HIV-infection in the population of Genoa and estimates the entity of AIDS-cancer association. The cohort includes 317 subjects resident in the Municipality of Genoa, aged above 14 years and notified prior to 31 December 1991 and/or dead from AIDS in the period 1988–1991. From 1984 to 1991, 44 cases of tumour were recorded. The comparison between the rate ratios found in the AIDS patients' cohort and in the general population of Genoa strengthen the significant association highlighted in literature regarding overall cancer, 26.7 (p<0.05), and in particular, Kaposi's sarcoma, 3239.4 (p<0.05); non-Hodgkin's lymphomas, 84.8 (p<0.05); Hodgkin's lymphomas, 20.6 (p<0.05). Moreover, a significant increase in the risk of testicular seminoma, 61.5 (p<0.05) and lung cancer, 18.0 (p<0.05) is confirmed.     

Thalidomide-dexamethasone versus Interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study

Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive α-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P  = 0·024) and overall survival (84% vs. 68%; P  = 0·030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm ( P  = 0·014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.     

Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma

We present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria. Seventeen (34%) patients achieved CR, 7 (14%) nCR, 5 (10%) VGPR, 15 (30%) PR, and 5 (10%) MR, resulting in an ORR of 98%. Only 1 patient (2%) presented progressive disease. Time to progression (TTP), event-free survival (EFS), and overall survival (OS) projected at 3 years were 60%, 57%, and 74%, respectively, and these parameters were significantly higher in those patients achieving a response of at least VGPR versus those who did not. Grade 3 and 4 nonhematologic adverse events were constipation (10%), fatigue (6%), tremors (4%), mucositis (4%), and palmar-plantar erythrodysesthesia (2%). Grade 3 and 4 neutropenia occurred in 12% of patients. Grade 3 and 4 infections and thromboembolic accidents were observed in 22% and 14% of patients, respectively. In the treatment of elderly patients with newly diagnosed multiple myeloma, ThaDD is a very effective regimen with manageable toxicity.     

Thalidomide-dexamethasone plus pegylated liposomal doxorubicin vs. thalidomide-dexamethasone: a case-matched study in advanced multiple myeloma

OBJECTIVES: Nearly all patients with multiple myeloma (MM) relapse or become refractory to front-line therapy. Several salvage therapies have been explored, but the optimal combination regimen has not been defined. We performed a case-matched study comparing patients with relapsed/refractory MM receiving thalidomide-dexamethasone alone or the combination thalidomide-dexamethasone-liposomal pegylated doxorubicin. METHODS: Forty-seven patients received thalidomide (100 mg/d), dexamethasone (40 mg p.o. on days 1-4 and 9-12), and pegylated liposomal doxorubicin (40 mg/m(2) on day 1 every 28 d) (ThaDD). Their clinical outcome was compared with that of 47 pair mates selected from patients treated at relapse with thalidomide (100 mg/d) and dexamethasone (40 mg p.o. on days 1-4) (Thal-Dex) and matched for age, beta2-microglobulin and previous therapy. RESULTS AND CONCLUSIONS: Overall response rate was significantly higher in ThaDD group (92% vs. 63.5%; P < 0.0001) as partial response rate (> or =PR) (75.5% vs. 59.5%; P = 0.077), very good partial response rate (> or =VGPR) (36% vs. 15%; P = 0.018) and near complete remission rate (> or =nCR) (30% vs. 10.5%; P = 0.002). Non-hematologic toxicity was similar in the two groups of patients whereas hematologic toxicity and infections were significantly higher in ThaDD patients. Median progression-free survival, event-free survival, and overall survival were significantly longer in patients receiving ThaDD than in those treated with Thal-Dex. ThaDD regimen significantly improved response rate and overall survival in comparison with Thal-Dex. Although the frequency of hematologic toxicity and infections resulted higher in ThaDD group compared with control group, they were not particularly frequent after adequate prophylaxis was added and were easily managed when occurred.