Imipenem/cilastatin therapy of infections in cancer patients

Imipenem/cilastatin was administered during 153 febrile episodes occurring in cancer patients and the response rate was 68%. Considering only documented infections the response rate was 71%. Patients who received imipenem as initial therapy had a higher response rate than patients who received it after failing other antibiotics (77% versus 68%). The overall response rates for septicemias and pneumonias were 75% and 58%. Among the 57 gram-negative infections 77% responded, but the response rate was substantially higher if imipenem was used as initial therapy (94% versus 69%). The poorest response rate was observed when imipenem was given as secondary therapy for Pseudomonas infections (50%), but most of these patients had failed to respond to other appropriate antibiotics. The only serious side effect was seizures which occurred in ten patients, although eight of them had other predisposing factors. Imipenem appears to be a useful antibiotic for treatment of infections, even in neutropenic cancer patients.     

Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN- gamma -induced gene expression by TLR2-dependent and independent pathways.

Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN-gamma), resulting in decreased expression of IFN-gamma-induced genes. In the present study, we examined the inhibition of IFN-gamma-induced gene expression by Mycobacterium tuberculosis and four different Mycobacterium avium strains in mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA expression of a panel of six different IFN- gamma-induced genes. All four of the M. avium strains completely inhibited IFN-gamma-induced expression of MHC class II Aalpha and Ebeta mRNA. However, the Mac101 strain, which is serovar 1, inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium strains, which are serovar 2. In this study, we also show that mycobacteria inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and independent pathways. The inhibition of IFN-gamma-induced gene expression by M. avium was reduced but not completely blocked in macrophages from TLR2(/) mice. IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7 cells expressing dominantnegative TLR2 or myeloid differentiation factor 88 (MyD88), further indicating the existence of a pathway independent of TLR2 and MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene expression by multiple pathways involving both TLR2 and non-TLR receptors.     

Serum and Plasma Markers of Nutritional Status in Children Infected with the Human Immunodeficiency Virus

Objective To determine whether reduced serum or plasma protein and micronutrient levels are common in children infected with the human immunodeficiency virus (HIV) and whether these levels are different in children with growth retardation compared to those with normal growth.

Subjects Children were separated into three groups: (a) HIV-infected with growth retardation (HIV+Gr); (b) HIV-infected with normal growth (HIV+); (c) HIV-uninfected with normal growth (HIV-). All children were afebrile and free of acute infection at the time of study. During a 24-hour stay in the Pediatric Clinical Research Unit, blood was drawn for analysis of total protein, albumin, zinc, selenium, and vitamin A levels; growth measurements were obtained; and dietary intake was assessed by 24-hour weighed food intake and 24-hour dietary recall.

Statistical analysis Mean differences between groups were assessed by analysis of variance, and differences in the frequency of nutrient deficiency were determined by χ² analysis.

Results Thirty-eight children between 2 and 11 years of age were studied: 10 HIV+Gr, 18 HIV+, and 10 HIV-. No statistically significantly differences were noted in mean levels of albumin, prealbumin, zinc, and selenium. Mean serum level of vitamin A was significantly higher in the HIV+Gr group than in the other two groups. There were no significant differences between groups in the frequency of deficiency for any nutrient studied. Mean energy and nutrient intake was similar among groups.

Applications/conclusions Abnormal serum or plasma protein or micronutrient levels were uncommon in this cohort of HIV-infected children, even in children with growth retardation. Routine monitoring of the level of proteins and micronutrients studied is unnecessary in the absence of specific clinical indicators of deficiency. J Am Diet Assoc. 1997-97:1377-1381.     

Development of systemic lupus erythematosus in a patient on hemodialysis.

A case of systemic lupus erythematosus (SLE) that developed 2 years after beginning hemodialysis is reported. The patient had not been given any drug implicated in the production of SLE. She had been treated with deferoxamine, an in vitro inhibitory of DNA synthesis. The difficulty of the diagnosis is emphasized. Clinical improvement after prednisone treatment was impressive. SLE may appear even in patients receiving hemodialysis, despite immunological depression derived from chronic uremia.