Magnitude of stromal hemangiogenesis correlates with histologic subtype of non-Hodgkin's lymphoma.

PURPOSE: Tumor stromal microenvironment promotes neoplastic growth and angiogenesis. We have previously shown that recruitment of marrow-derived vascular endothelial growth factor receptor-1(+) (VEGFR-1(+)) proangiogenic hematopoietic progenitors contributes instructively and structurally to neoangiogenesis in mouse models. Here, we investigated whether stromal incorporation of CD68(+) hemangiogenic cells and alpha-smooth muscle actin(+) (alpha-SMA(+)) stromal cells correlates with neoangiogenesis and progression in human non-Hodgkin's lymphoma subtypes. EXPERIMENTAL DESIGN: Spatial localizations of vascular and stromal cells expressing CD34, VEGFR-1, alpha-SMA, and CD68 were examined by immunohistochemistry in 42 cases of non-Hodgkin's lymphoma, including diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and compared with benign follicular hyperplasia. RESULTS: Compared with indolent lymphomas, there was a profound increase in recruitment of CD68(+) cells and VEGFR-1(+) neovessels in aggressive subtypes (including those transformed from indolent subtypes), where CD68(+) cells were localized to the perivascular region of neovessels as well as the stromal compartment. The perivascular CD68(+) cells expressed VEGFR-1 and VEGF-A. In contrast, there was a diffuse increase in alpha-SMA incorporation throughout the stromal compartment of indolent subtype of CLL/SLL compared with the scant perivascular pattern in aggressive subtypes. Overall, there was no correlation between CD34(+) microvessel density and lymphoma histologic subtype. CONCLUSIONS: Heightened stromal hemangiogenesis as marked by infiltration of proangiogenic VEGFR-1(+)CD68(+)VEGF-A(+) cells and their paracrine cross-talk with neovasculature appears to be a distinct feature of aggressive lymphoma, providing novel targets for antiangiogenic therapy, whereas alpha-SMA(+) stromal vascular network may be differentially targeted in CLL/SLL.     

Nutritional status and food intake in nine patients with chronic low-limb ulcers and pressure ulcers: importance of oral supplements

OBJECTIVES: Chronic low-limb ulcers and pressure ulcers are a serious and costly issue. Malnutrition is a risk factor. Searching for intervention strategies in elderly patients referred for surgical closure of their ulcers, the trial aimed at investigating the micronutrient status, determining the food intake of such patients, and the role of oral liquid supplements. METHODS: Observational cohort study in 9 patients, starting 5 days prior to surgery until day 10 after surgery. Variables: body mass index (BMI), food intake assessed using standardized meals (energy target 25 kcal/kg/day). Oral liquid supplements were provided between meals. Laboratory: blood count, plasma proteins, antioxidant status, vitamins, Fe, Se, and Zn. RESULTS: The patients were aged 71+/-10 y (mean+/-SD), with a BMI of 23.3+/-3.3. Baseline blood samples showed anemia and strong inflammation in 4 patients: albumin, retinol, and selenium were low; iron and zinc were very low. Food intake was largely variable and covered only about 76% (31-95%) of energy requirements. Breakfast provided 225+/-110, lunch 570+/-215, and dinner 405+/-150 kcal. Supplements were willingly consumed covering 35+/-12% of energy target. While vitamin supply was adequate, selenium and zinc requirements were not met. CONCLUSIONS: Most patients with chronic skin ulcers suffered micronutrient status alterations, and borderline malnutrition. Meals did not cover energy requirements, while oral supplements covered basic micronutrient requirements and compensated for insufficient oral energy and protein intakes, justifying their use in hospitalized elderly patients.     

Preparing the "soil": the premetastatic niche

Current focus on cancer metastasis has centered on the intrinsic factors regulating the cell autonomous homing of the tumor cells to the metastatic site. Specific up-regulation of fibronectin and clustering of bone marrow-derived cellular infiltrates coexpressing matrix metalloproteinases in distant tissue sites before tumor cell arrival are proving to be indispensable for the initial stages of metastasis. These bone marrow-derived hematopoietic progenitors that express vascular endothelial growth factor receptor 1 mobilize in response to the unique array of growth factors produced by the primary tumor. Their arrival in distant sites represents early changes in the local microenvironment, termed the "premetastatic niche," which dictate the pattern of metastatic spread. Focus on the early cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to detect and prevent metastasis at its earliest inception.     

Circulating interleukin-6, soluble interleukin-2 receptors,tumor necrosis factor alpha,and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography

Nineteen patients with juvenile chronic arthritis (JCA), ten with systemic (s)-JCA, and nine with polyarticular-onset (p)-JCA were examined for interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-2R, and IL-10 levels. Power Doppler sonography (PDS) for the more affected knee was used in all of them to evaluate soft tissue vascularity. Serum levels of IL-6 were significantly higher in JCA patients than in controls (P<0.007). Patients with p-JCA showed higher levels of IL-6 than patients with s-JCA, and the difference was statistically nonsignificant. Serum IL-6 levels in all patients correlated significantly with the degree of vascularity detected by PDS (P<0.01). This correlation was more pronounced in p-JCA patients (P<0.01 in p-JCA vs P<0.05 in s-JCA). Serum levels of TNF-alpha were higher in patients with JCA than in controls (P<0.0001). Serum levels of TNF-alpha were significantly greater in patients with s-JCA than in p-JCA (P=0.008). Soluble IL-2R levels were higher in patients with JCA than controls (P<0.0002). Serum levels of IL-2R correlated significantly with pannus thickness in p-JCA (P<0.01) and inversely with methoxetrate (MTX) duration in s-JCA (P<0.05). Serum levels of IL-10 were significantly higher in JCA patients than in controls ( P<0.0008). Serum IL-10 levels in all patients correlated significantly inversely with hemoglobin levels (r=-0.50, P<0.05), total leukocytic count (TLC) (r=-0.58, P<0.01), and intra-articular steroid injection (r=+0.56, P<0.01). In s-JCA, IL-10 levels correlated significantly with MTX weekly dose ( P<0.05). In conclusion, a significant correlation of serum IL-6 levels with the degree of knee joint vascularity was found, and this correlation was more pronounced in p-JCA, which may stress the role of IL-6 as an inducer of neoangiogenesis in JCA.     

Comparative prediction of perinatal human immunodeficiency virus type 1 transmission,using multiple virus load markers

Maternal plasma human immunodeficiency virus (HIV) type 1 RNA load has a role in perinatal transmission, but significant overlap in the range of plasma virus loads among transmitters and nontransmitters is often observed, which makes it difficult to predict transmission outcome. We measured several virus markers in a drug-naive population of HIV-1-infected mothers in Botswana. Maternal plasma HIV-1 RNA load, peripheral blood mononuclear cell-associated blood HIV-1 DNA load, and cervicovaginal fluid (CVF) HIV-1 DNA load were determined using quantitative real-time polymerase chain reaction. The overall rate of transmission among these mother-infant pairs was 35.7%. Median infant age was 2.5 months. An association between increased plasma HIV-1 RNA load and perinatal transmission was observed (odds ratio [OR], 2.20/1-log virus load; 95% confidence interval [CI], 1.15-4.18). However, the association between increased blood HIV-1 DNA load and perinatal transmission was stronger (OR, 10.30; 95% CI, 2.11-50.38). When blood HIV-1 DNA load was combined with CVF HIV-1 DNA load, the association with transmission increased (OR, 25.0; 95% CI 2.73-228.60).     

Probucol in the treatment of non-alcoholic steatohepatitis: a double-blind randomized controlled study

BACKGROUND/AIMS: A final step in the pathology of non-alcoholic steatohepatitis (NASH) is oxidative damage to hepatocytes. Probucol is a lipid-lowering agent with strong antioxidant properties. We designed a double-blind randomized controlled study to evaluate the effects of probucol in NASH. METHODS: Thirty cases of biopsy-proven NASH were included. Subjects were randomly allocated to either the treatment group or to the control group by a 2:1 ratio. The treatment group was given 500 mg of probucol daily for 6 months, and the control group, an identically appearing placebo. RESULTS: Twenty-seven cases completed the study. The mean aspartate transaminase (AST) and alanine transaminase (ALT) levels changed from 81.9 to 36.2 and 102.2 to 44.7 in the treatment group and from 57.6 to 49.6 and 96.8 to 96.2 in the control group, respectively. The decrease in ALT level in the treatment group as compared to the control group was significant at the P<0.005 level (95% confidence interval: 20.2-93.7 IU). Both AST and ALT levels dropped to normal in nine cases of the treatment group (50%) but none of the control group (P=0.01). CONCLUSIONS: Probucol appears to be significantly effective in decreasing the ALT levels in patients with NASH.     

Probucol in the treatment of nonalcoholic steatohepatitis: an open-labeled study

GOALS: To evaluate the effects of probucol, an agent with strong antioxidant properties, in reversing biochemical changes in nonalcoholic steatohepatitis (NASH). BACKGROUND: There is currently no well-established medical treatment of NASH. It is believed that oxidative stress plays a major role in hepatic damage in these patients. STUDY: Cases of biopsy-proven NASH referring to a referral center in Tehran during a 12-month period were included in the study. Viral, autoimmune and other hepatic diseases were excluded. Alcohol ingestion was excluded by repeated questioning of the patient and at least two family members. Patients were given 500mg of probucol daily for 6 months. Serum levels of liver enzymes, the serum lipid profile, and weight was recorded monthly. RESULTS: A total of 17 patients completed the study. The mean age was 37.2 years, 13 patients were male and 4 female. The mean pretreatment value of ALT and AST was 93.5 and 80.4 U/L, and the mean posttreatment value was 41.8 and 35.9 U/L respectively ( = 0.001 and 0.006). CONCLUSION: Probucol, even in the low dose of 500 mg/d, appears to be significantly effective in decreasing the ALT and AST levels in patients with NASH.     

Successful treatment of acetaminophen overdose associated with hepatic failure

Acetaminophen is the most widely used antipyretic and analgesic drug in the world. Acetaminophen poisoning and the following hepatic failure are not rare and are the most common indications of liver transplantation in the USA and Europe. In this case report, the patient was a 25-year old woman with hepatic failure who was brought to Loghman-Hakim Poison Centre 24 hours after attempted suicide with 100 tablets of acetaminophen, 325 mg. She was treated with N-acetylcysteine (NAC) and discharged from the hospital 12 days after admission and followed up for 1 month. In conclusion, acetaminophen poisoning should be considered in the differential diagnoses of hepatic failure. In acetaminophen-induced hepatic damage the administration of NAC must always be considered even after 24 hours of overdose.