Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal cancer patients.

INTRODUCTION: Angiogenesis has been correlated with increased invasion and metastases in a variety of human neoplasms. Inadequate inhibition of the growth of tumor microvessels by anticancer agents may result in treatment failure, rated clinically as progressive or stable disease. We designed this trial to investigate the modification of the vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-gamma) in advanced colorectal cancer patients during treatment with a weekly combination of cetuximab plus irinotecan. MATERIALS AND METHODS: Forty-five metastatic colorectal cancer patients were prospectively evaluated for circulating levels of VEGF and IFN-gamma during the treatment with cetuximab (initial dose of 400 mg/m(2), followed by weekly infusions of 250 mg/m(2)) plus weekly irinotecan (90 mg/m(2)). The circulating levels of the cytokines were assessed at the following time points: just before and at 1, 21, 50 and 92 days after the start of cetuximab plus irinotecan treatment. RESULTS: Basal serum VEGF median levels were significantly decreased just at the first day (after the first treatment infusion (P = 0.016). The VEGF persisted at the following time points reaching the highest statistical significance 92 days after the first infusion (P < 0.0001). On the contrary, IFN-gamma values showed a statistical significant increase one day after the first infusion (P < 0.0001). This effect persisted 21 days after the treatment start (P = 0.001), but was no more evident at the following time points. Moreover, a linear regression model with variance analysis showed a significant negative correlation between VEGF and IFN-gamma values 1, 21 and 50 days after the treatment beginning (P = 0.002, 0.001 and 0.047, respectively). CONCLUSIONS: This study suggests that a cetuximab may induce a modulation of VEGF circulating levels. The reduction of VEGF serum levels is a sudden and long lasting phenomenon. Moreover, in our study we identified a IFN-gamma increase, even if the specific role of this behavior remains to be investigated.

[A 35-year-old woman with fever, dyspnea, and pain in the left thigh]. / Donna di 35 anni con febbre, dispnea e dolore alla coscia sinistra.

A thirty-five years old woman during her twelfth pregnancy presented fever and pain at the left thigh. After cesarean delivery dyspnea added to the first two symptoms and pulmonary embolism was suspected. A clinical history revaluation suggested a diagnosis of infectious endocarditis and femoural osteomielitis due to a septic embolus.

IgM anti-hepatitis C virus in patients with chronic non-A, non-B hepatitis and their relationship to viral replication.

Patients with hepatitis C virus (HCV) infection may have different patterns of antibody response to various structural and non-structural viral antigens. We have correlated the serological patterns to the clinical features of chronic infection and to viral replication in 68 HCV-Ab-positive patients with chronic liver disease at different stages (19 with cirrhosis-hepatocellular carcinoma, 38 with chronic active hepatitis and 11 with chronic persistent hepatitis). Serum samples from each patient were assayed for HCV-IgM by enzyme immunoassay and for HCV-RNA by the polymerase chain reaction using primer sets derived from the 5'-non-coding region. The prevalence of HCV-IgM was high (54 patients (79.4%)) and the study showed a good correlation between high values of anti-HCV-IgM and the presence of HCV-RNA in serum, since HCV-RNA was detected in 35 of the 54 IgM-positive patients (64.8%) and notably in 19 of the 20 subjects with high levels of specific IgM. Conversely, all the 35 sera containing HCV-RNA were also reactive for HCV-IgM, while none of the HCV-IgM-negative sera was HCV-RNA reactive. Positivity rates for both HCV-RNA and IgM anti-HCV were higher in the more advanced stages of disease; thus, the clinical pattern of HCV chronic hepatitis seems to be strictly related to the serological pattern and the presence of HCV-RNA.

Free and antibody-complexed antigen and antibody profile in apparently healthy HIV seropositive individuals and in AIDS patients.

The pattern of free and antibody-complexed HIV antigen and the antibody profile were investigated retrospectively in 305 serum samples taken from 22 AIDS patients before and during the development of AIDS and from 40 apparently healthy seropositive individuals. Most AIDS patients were found positive for both free and complexed antigen and had high gp41 antibody titres but low or undetectable p24 antibody. Four different patterns of HIV antigenaemia were observed: 1) positive for both free and complexed antigen; 2) negative for free HIV antigen at first, but always positive for complexed antigen; 3) positive for free antigen without complexed antigen; and 4) negative for both free and complexed antigen. The development of immune complexes preceded the appearance of free antigen and might reflect the ongoing viral replication with antigen excess and binding of anticore antibodies. No correlation was found between the development of AIDS symptoms and either the duration of free antigen positivity or the level of antigenaemia. A different pattern was observed in apparently healthy seropositive individuals: 90% of whom had high antibody titres to p24 and gp41 and were persistently negative for free and complexed HIV antigen. This study demonstrates that testing HIV markers in sequentially collected serum samples from HIV seropositive individuals is a useful and simple tool for early identification of persons at risk of developing AIDS.

Sludge and stones in gallbladder after pregnancy. Prevalence and risk factors.

The prevalence of sludge and stones in the gallbladder of 298 women in the immediate post-partum period was ultrasonographically assessed. We have investigated some risk factors for the development of sludge or stones in these patients and followed up most of these patients by ultrasonography to detect the presence of sludge and/or stones in the year following their discovery. We found sludge in 80 (26.2%) and gallstones in 16 (5.2%) of these patients. Age, obesity and months of oral contraceptive use were risk factors only for the presence of gallstones. After 1 year of follow-up only 2 out of 45 patients with sludge but 13 out of 15 patients with gallstones still had abnormal ultrasonographic findings.