A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy.

PURPOSE: Eleven patients with progressive advanced malignancy after administration of a cancer vaccine received a fully human anti-CTLA-4 monoclonal antibody (ipilimumab). The primary end point was to determine drug toxicity. Tumor response, tumor-specific CD8+ T-cell immune responses, and modulation of CD4+ CD25+ FoxP3+ regulatory T-cell (Treg) numbers were secondary end points. EXPERIMENTAL DESIGN: Three patients with colon cancer, four with non-Hodgkin's lymphoma, and four with prostate cancer were treated. The first dose was given at 3 mg/kg and subsequent doses were administered monthly at 1.5 mg/kg for a total of four cycles. RESULTS: Tumor regression was observed in two patients with lymphoma; one of which obtained a partial response of 14-month duration. Ipilimumab was well tolerated with predominantly grade 1/2 toxicities. One drug-related grade 3 toxicity was observed. One patient died within 30 days of treatment due to progressive colon cancer. No increase in vaccine-specific T-cell responses was observed after therapy. Tregs as detected by expression of CD4+CD25+CD62L+ declined at early time points but rebounded to levels at or above baseline values at the time of the next infusion. CONCLUSIONS: Ipilimumab treatment depressed Treg numbers at early time points in the treatment cycle but was not accompanied by an increase in vaccine-specific CD8+ T-cell responses in these patients previously treated with a variety of investigational anticancer vaccines. A partial response was observed in one patient with follicular lymphoma. A phase I/II trial evaluating ipilimumab in patients with follicular lymphoma is currently ongoing.     

Campath-1H therapy in refractory ocular inflammatory disease

BACKGROUND: Standard therapy for severe, immune mediated, ocular inflammation has significant side effects, and may fail to control the disease. T cell directed monoclonal antibody (mAb) therapy can provide long term remission of inflammatory disease in experimental models. The Campath-1H mAb was administered to patients with severe, refractory, ocular inflammation. METHODS: 10 patients with severe, refractory, non-infectious ocular inflammatory disease were treated with Campath-1H mAb. This is a fully humanised mAb which recognises the pan-lymphocyte antigen CD52. RESULTS AND DISCUSSION: Following Campath-1H therapy, all 10 patients showed an initial resolution of their ocular symptoms and signs. Long lasting remissions were achieved in eight patients, in whom baseline immunosuppression could subsequently be reduced to minimal levels. The possible mechanisms of action of Campath-1H therapy are discussed.     

Ultrasonic diagnosis in children with mesenteric cysts

Two cases of Mesenteric Cysts in infancy are described. Since there is no continuity with the lumen of the bowel radiological evaluation may be very difficult. In contrast abdominal sonography can give information about size, contents and position in relation to other abdominal organs. The use of ultrasound shortens the preoperative workup and certainly reduces the number of X-ray examinations.     

Fragmentation of uric acid calculi with the holmium: YAG laser produces cyanide

BACKGROUND AND OBJECTIVES: To independently test previously reported findings of cyanide evolution under holmium:yttrium aluminum garnet (Ho:YAG) (holmium) lithotripsy of uric acid calculi, determine if this occurs with other forms of intracorporeal lithotripsy, and establish if this occurs due to a photothermal, photochemical, or photoacoustic reaction. STUDY DESIGN/MATERIALS AND METHODS: Human uric acid calculi were fragmented in vitro through exposure to holmium, ultrasound, and electrohydraulic (EHL) energy sources. The following parameters were varied: total laser energy, individual laser pulse energy, ultrasonic energies, and EHL energies. Uric acid powder was suspended in solution and exposed to holmium laser energy in vitro. Serum and irrigant samples from a human patient were collected following intrarenal holmium lithotripsy of a uric acid calculus. All samples were analyzed for hydrogen cyanide (HCN) content. RESULTS: Holmium lithotripsy of solid uric acid calculi produces cyanide. The yield is linearly dependent upon total laser energy delivered. Pulse energy does not affect cyanide yield. Photothermal mechanisms coupling laser energy to the solid crystal lattice are responsible for the production of cyanide. Ultrasound and EHL lithotripsy do not produce cyanide. A clinically insignificant level of cyanide was detected in the blood of a single patient following laser lithotripsy of a uric acid calculus. CONCLUSIONS: Our study confirms that cyanide is produced by a photothermal mechanism during holmium laser lithotripsy of uric acid calculi, and that the amount produced is clinically insignificant.     

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants

This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on post-partal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of <33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. Conclusion Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life. Received: 10 February 2000 / Accepted: 12 April 2000