Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest

In this report, we extend our previous findings that IgG or F(ab')2 fragments of HD37 anti-CD19 antibody (Ab) in combination with the immunotoxin (IT), RFB4-anti-CD22-deglycosylated ricin A chain (dgA) (but neither reagent alone), prolonged the survival of SCID mice with disseminated human Daudi lymphoma (SCID/Daudi mice) to 1 year at which time they still remained tumor-free. We explored the mechanisms by which the HD37 Ab exerts antitumor activity in vivo by studying its activity in vitro. We found that it has antiproliferative activity (IC50 = 5.2 - 9.8 x 10(-7) mol/L) on three CD19+ Burkitt's lymphoma cell lines (Daudi, Raji, and Namalwa) but not on a weakly CD19-positive (CD19lo) pre-B cell tumor (Nalm-6). The inhibitory effect was manifested by cell cycle arrest, but not apoptosis. Results using three additional anti-CD19 Abs, suggest that the affinity of the antibody and possibly the epitope which it recognizes may effect its capacity to transmit a signal that induces cell cycle arrest. Hence, therapeutically useful Abs may exert anti-tumor activity by a variety of mechanisms, each of which should be evaluated before undertaking clinical trials in humans.     

Height loss in older women: Risk of hip fracture and mortality independent of vertebral fractures

We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual‐energy X‐ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986–1988) and year 15 (2002–2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow‐up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self‐reported height at age 25 (?40 years) to measured height age >65 years (Year 0)] demonstrated consistent results. Height loss >5 cm (2″) in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality—independent of incident VFx and BMD. © 2012 American Society for Bone and Mineral Research     

Late Onset Coeliac Disease in the Monozygotic Twin of a Coeliac Child

ABSTRACT. A case of late onset coeliac disease (confirmed by serial intestinal biopsies) is described in the monozygotic twin of a coeliac patient. This is the second case reported in literature. The permanent discordance for coeliac disease in monozygotic twins is questioned.     

Predictors of weight loss during radiation therapy

OBJECTIVE: To define risk factors for weight loss or dehydration during radiation therapy (RT). STUDY DESIGN AND SETTING: Retrospective chart review, academic tertiary care center. RESULTS: The incidence of severe weight loss during RT was 32.7%, the incidence of dehydration was 10.9%, and the rate of prophylactic feeding gastrostomy tube placement was 32%. The patients most likely to suffer severe weight loss included patients with tumor sites of nasopharynx and base of tongue, those treated with chemoradiation, and patients with severe pretreatment weight loss. Prophylactic feeding gastrostomy tube placement before RT significantly reduced the incidence of severe weight loss and hospitalization during RT. CONCLUSION: Severe weight loss and dehydration during RT for head and neck cancer is common. Prophylactic feeding gastrostomy tubes significantly reduce the incidence of severe weight loss and hospitalization for dehydration during RT when placed before onset of RT. Patients at risk for severe weight loss include those with severe pretreatment weight loss, tumors of the nasopharynx and base of tongue, or treatment with chemoradiation.     

CRYOGLOBULINEMIA AND CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS WITH HEPATITIS C VIRUS INFECTION

Background. Mixed cryoglobulinemia (MC) is a systemic disorder, characterized by a typical clinical triad: purpura, weakness, and arthralgias, with visceral complications such as liver and renal involvement. The objective was to study the association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia (EMC). Patients and Methods. Markers of HCV infection in 11 patients with cryoglobulinemia were examined and hepatitis C virus (HCV) was detected in eight of them. These patients were included in a clinical and histologic study. Anti-HCV antibodies were determined by a second-generation enzyme-linked immunosorbent assay (ELISA-2) in sera and cryoprecipitates. Studies on HCV-RNA were performed by a two-stage polymerase chain reaction (PCR) in the serum. A control group, consisting of 28 patients with other cutaneous disorders, was studied for HCV infection using ELISA-2 and PCR. Results. All patients had liver dysfunction, arthralgias, and purpura. Three patients had involvement of the peripheral nervous system, two had renal involvement, and one patient had Sjögren's syndrome. Cryocrits ranged from 3% to 20%. Six patients had type III cryoglobulinemia and the remaining two had type II. Markers for hepatitis B virus (HBV) were negative in all serum samples. Anti-HCV antibodies and HCV-RNA were positive in the serum of all the cases with MC. Anti-HCV antibodies were positive in all cases except for one of the cryoprecipitates tested. Four patients received recombinant interferon alfa. In two of them, serum aminotransferases became normal and cryoglobulins disappeared. Conclusions. The results strongly suggest that HCV infection is responsible for the cryoglobulinemia and vasculitis in patients with MC and that treatment with interferon alfa is presently the treatment of choice for such patients.