Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins

A major problem that arises when radiolabeled serum proteins are used for tumor imaging is the presence of a large amount of circulating background activity that persists for several days. This delays imaging for at least 2 days following injection and necessitates computer subtraction of simulated background (second radiopharmaceutical injection) which introduces artifacts that are difficult to control. We propose here the injection of specific antibody immediately before imaging as an alternate way of reducing blood background through clearance of the immune complex by the liver. 111In-alkyl human transferrin and IgG were injected IV in BALB/c tumor mice, and followed in 18 h by anti-human transferrin and anti-human IgG antibody IV. Two hours later, the tumor and organ distribution of activity was compared with control mice not receiving antibody. 111In-transferrin blood activity was reduced to 1/48 of control with no decrease in tumor concentration: as a result, the tumor to blood ratio increased from 1.4:1 to 78:1. 111In-IgG blood activity was reduced to 1/17 of control, again with no decrease in tumor. The tumor to blood ratios increased from 0.7:1 to 17:1. The liver picked up most of the blood activity with none of the complex going to spleen, bone marrow, or kidney. Dog experiments showed clearance of blood was 90% complete in less than 15 min following antibody injection. Simultaneous scintillation images showed complete clearance of activity from the heart and great vessels in the chest and neck, and over the abdomen, with a concomitant increase in liver activity but no increase in spleen, kidney, or bone marrow activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.     

Plasma RANTES increase during the first month of life independently of the feeding mode

The chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) plays a significant role in the innate immunity, which is particularly important in the neonatal period. In this study, we aimed to investigate the ability of the neonate to increase plasma levels of RANTES in the first month of life, and the possible impact of breast feeding on this ability. The study population consisted of 125 healthy term neonates that were exclusively breast-fed (n = 62) or formula-fed (n = 63) for at least 1 month after birth. Plasma RANTES concentrations (ELISA) as well as circulating leukocytes and platelets were measured on days 1 and 30 of life. Median RANTES concentrations of the total group showed a significant increase between day 1 [1000 (448–2100) pg/mL] and day 30 [3688 (1488–5400) pg/mL, p < 0.0001], as did median total lymphocyte, T-cell, B-cell, NK-cell and eosinophil counts (all p values <0.0001). Monocyte and platelet counts did not change significantly over the neonatal period. Further analysis according to the mode of feeding showed that RANTES levels as well as leukocyte populations and platelet counts did not differ significantly between breast-fed and formula-fed neonates on either day 1 or 30. Healthy term neonates are capable of increasing plasma RANTES levels during the 1st month after birth independently of the mode of feeding.     

Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

Neurological Sciences - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal...     

Urinary neopterin,a new marker of the neuroinflammatory status in amyotrophic lateral sclerosis

Journal of Neurology - To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS. We performed an observational,...     

Risk of malignancy in patients with rheumatoid arthritis,psoriatic arthritis and ankylosing spondylitis under immunosuppressive therapy: a single-center experience

Systemic inflammatory rheumatic diseases are associated with an increased risk of malignancy, in particular of lymphoproliferative disorders. Chronic inflammation, due to the disease itself, generates a microenvironment able to promote cancer development, but it is still controversial whether immunosuppressive therapy may contribute to carcinogenesis. The aim of the study was to evaluate the risk of malignancy in 399 patients affected by rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis, all treated with either tumor necrosis factor α-inhibitors plus disease-modifying anti-rheumatic drugs (DMARDs) or DMARDs alone. The risk of malignancy in this cohort of patients, observed in the period between 2005 and 2011 at S. Andrea Hospital-Sapienza University of Rome, was compared with that of the general Italian population, matched for age, sex, and area of residence. Fourteen (3.5 %) malignancies, five of which were hematologic, have been observed. The overall cancer risk was not significantly increased in comparison to the general population, whereas the risk of hematologic malignancies appeared significantly higher in RA patients (SIR 4.94, 95 % CI 1.35–12.64), particularly in female gender (SIR 6.9, 0.95 % CI 1.88–17.66). No significant association between therapy and malignancy was demonstrated in RA patients.     

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21–29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.     

MRI and pathological examination of post-mortem brains: the problem of white matter high signal areas

We examined 21 brains from individuals more than 65 years of age by MRI and neuropathological methods to study the frequency and morphology of white matter changes. There were 16 brains from neurologically normal subjects (Group 1) while the remaining 5 (Group 2) had neurological disturbances. In Group 1 MRI showed high signal areas in the periventricular white matter in 12 brains and in the deep white matter in 9. All had focal areas, with confluent zones in 4; 3 cystic infarcts were also detected. Neuropathology in this Group showed periventricular changes of variable extent in all cases, vacuolated myelin around the perivascular spaces in 14 and degenerate myelin in 4. Macroscopic inspection showed 3 cystic lacunar infarcts, while areas of recent infarction were present on histology in 2. Four of the Group 2 brains had periventricular MRI changes; high signal areas in deep white matter were focal in 2 and confluent in 1. Cystic infarcts were detected in 3 cases. Neuropathology showed periventricular changes in all the brains; in 4 myelin around the perivascular spaces was vacuolated while degenerate myelin was demonstrated in 1. There were also old (1) and recent (2) lacunar infarcts. High signal areas in the white matter thus have different histological backgrounds but only in a minority of cases do they seem to be of pathological significance and, as a rule, they are not related to the presence of neurological disturbances. Correlative MRI-neuropathological studies are helpful for characterising abnormalities detected by techniques, like MRI, which are sensitive but not very specific.