A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy

Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48- hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.     

Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease

Three murine monoclonal antibodies, named 2H9, 1E9 and 1A2, were produced after immunization of BALB/c mice with cells of the SU-DHL-1 cell line from a true histiocytic lymphoma. In frozen sections from various lymphomas, 2H9 and 1A2 selectively stained the cell membranes of neoplastic cells in true histiocytic lymphoma and Hodgkin's disease. Antibody 1E9 stained the nuclear membranes of the tumor cells in true histiocytic lymphoma and malignant histiocytosis. No staining was seen in 56 cases of B and T cell lymphoma. Several tissue culture cell lines, including T cell acute lymphoblastic leukemia and pre-B cell lines, were not stained. With 2H9, however, a positive reaction was noted for two Epstein-Barr virus (EBV)-positive African Burkitt's lymphoma cell lines (Daudi and P3HRI), one human T cell lymphoma/leukemia-virus-positive cell line (HUT 102), and one EBV- transformed normal B lymphoblastoid cell line (RPMI 8057). In normal lymphoid tissues, 2H9 and 1E9 reacted with the nuclear membranes of histiocytes and interdigitating reticulum cells, whereas 1A2 stained only rare cells of an unknown type. All three antibodies failed to react with B or T cells in frozen tissue sections of normal lymphoid tissues. The use of these three antibodies should facilitate the diagnosis of histiocyte and interdigitating reticulum (IR) cell-related neoplasms, namely, true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. True histiocytic lymphoma and Hodgkin's disease exhibit similar reactivities with these three and with two other monoclonal antibodies (HeFi-1 and Tac), suggesting that these two types of lymphoma are related. In contrast, malignant histiocytosis was negative for 2H9, 1A2, Tac, and HeFi-1. The difference in the phenotypic expression of true histiocytic lymphoma and malignant histiocytosis indicates that they are two different disease entities.     

Fatal graft-versus-host disease in a patient with lymphoblastic leukemia following normal granulocyte transfusion

A woman with lymphoblastic lymphoma was treated with combination chemotherapy. She subsequently became febrile while granulocytopenic and was given unirradiated granulocyte transfusions from normal, unrelated donors. She recovered, but 12 days later noted the onset of progressive skin rash, hepatic dysfunction, diarrhea and pancytopenia and, 22 days after her last granulocyte transfusion, died of gram negative septicemia. Histologic examination of multiple tissues including the skin, liver, and intestinal tract showed changes characteristic of acute graft-versus-hose disease (GVHD). Y-chromatin analysis of the patient's peripheral blood just before death indicated the presence of male cells. HLA typing of lymphocytes and skin fibroblasts from the patient and lymphocytes from the family and granulocyte donors was also consistent with engraftment of cells from one of the male granulocyte donors. This donor most likely was homozygous for one of the patient's halotypes, perhaps facilitating engraftment of his cells and subsequent development of transfusion- induced acute GVHD. Until more precise guidelines can be established, we recommend that all cellular blood products given to patients receiving intensive chemotherapy be irradiated with 1500 rad.     

Intra‐abdominal vacuum‐assisted closure (VAC) after necrosectomy for acute necrotising pancreatitis: preliminary experience

Infection of pancreatic necrosis, although present in less than 10% of acute pancreatitis, carries a high risk of mortality; debridment and drainage of necrosis is the treatment of choice, followed by ‘open’ or ‘close’ abdomen management. We recently introduced the use of intra‐abdominal vacuum sealing after a classic necrosectomy and laparostomy. Two patients admitted to ICU for respiratory insufficiency and a diagnosis of severe acute pancreatitis developed pancreatic necrosis and were treated by necrosectomy, lesser sac marsupialisation and posterior lumbotomic opening. Both of the patients recovered from pancreatitis and a good healing of laparostomic wounds was obtained with the use of the VAC system. Most relevant advantages of this technique seem to be: the prevention of abdominal compartment syndrome, the simplified nursing of patients and the reduction of time to definitive abdominal closure.     

Children in conflict zones

The nature of war has changed dramatically. Today's conflicts happen where people live and they take a brutal toll on children. Heavy bombardment and destruction in war creates a humanitarian crisis where there is lack of adequate food, clean water and medicine. The consequences of war can have major impact on the health of children for years to come. Traumatic events can have a profound and lasting impact on the emotional, cognitive, behavioral and physiological functioning of an individual. Depending on the circumstances, the psychosocial impacts of disasters can range from mild stress reactions to problems such as anxiety, depression, substance abuse and post traumatic stress disorders (PTSD).     

Dietary compliance in screening-detected coeliac disease adolescents

In 1992–94 we screened 6315 students for coeliac disease (CD) by testing antigliadin antibodies (AGA) as the first-level investigation. We found 28 biopsy-proven coeliac patients who were invited to start the gluten-free diet (GFD). The aim of this study was a clinical and laboratory follow-up in these screening–detected coeliac adolescents. Patients were 17 females and 11 males with a mean age at diagnosis of 12.8 ± 1 years (range 11–14). Mean follow-up duration time was 23 ± 7 months (range 9–37). Twenty-three of the 28 screening-detected coeliac patients came to the control visit, 3 refused the follow-up and 2 subjects were not found. Twelve patients (52.2%) stated that they never ate any gluten-containing food, while 11 of them (47.8%) reported occasional transgressions to the diet. GFD acceptance was reported as good ( n = 6), moderate ( n = 11) or low ( n = 6). After starting the GFD, signs of improvement were seen in most patients, such as weight gain, increased height velocity and increased feeling of well-being. AGA (both IgG and IgA classes) and antiendomysium antibodies (AEA) were normal in 19 subjects, 2 cases had IgG-AG A and AEA positivity, 1 patient showed abnormal AGA and AEA levels, while isolated IgA-AGA positivity persisted in 1 case. This study shows that even silent CD cases can clinically benefit from the GFD. The consequences of occasional transgressions to the GFD remain unclear.     

Characterization of carbohydrates in commercial infant formulae

Human milk has always been the reference parameter for the preparation of commercial formulae. The advent of more advanced technologies has enabled increasingly precise information on the composition of human milk to be obtained. Our knowledge in the field of carbohydrates also has improved considerably in the last few years following the pioneering studies of Montreuil (1, 2). From a quantitative point of view it has been demonstrated that in the different phases of lactation, in addition to lactose, human milk contains a consistent amount of oligosaccharides (about 20 g/1 in colostrum and 10–13 g/l in mature milk) (3, 4), whereas monosaccharides make up only about 1% of the total carbohydrates (4). More than 100 different types of oligosaccharides have been identified so far in human milk (5–7), mostly tri-octasaccharides (8). From a biochemical point of view, oligosaccharides are constituted by glucose, galactose, N -acetyl-glucosamine, fucose and sialic acid, and present a linear or branching structure (5). Little is known yet about their physiological role or metabolic fate (9); nevertheless, it has been demonstrated that, in addition to their nutritional function, they participate also in the regulation of the intestinal ecosystem, encouraging the growth of bifid flora (10) and contributing to the defense mechanisms against pathogens in various organs (11–13).     

Peripheral blood stem cells used to augment autologous bone marrow transplantation

Peripheral blood stem cells (PBSC) were used to augment autologous bone marrow transplantation (ABMT), aiming to hasten engraftment after high dose treatment in a group of heavily pretreated patients. PBSC were obtained by leukapheresis during the rebound after standard chemotherapy. In 11 patients aged 7-17 years, high dose chemotherapy consisted of busulphan 16 mg/kg orally with melphalan 160 mg/m2 intravenously for seven patients, and melphalan 200 mg/m2 intravenously alone for four. The median number of granulocyte-macrophage colony forming units in the reinfused PBSC was 3.42 x 10(4)/kg (3.03-18.01) and bone marrow 12.4 x 10(4)/kg (4.16-28.6). Neutrophil recovery to > or = 0.5 x 10(9)/l and platelet transfusion independence occurred at a median of 14 days (11-18) and 22 days (9-84) respectively. In five patients the early engraftment was transient with neutrophils again dropping below 0.5 x 10(9)/l then slowly recovering. There was one toxic death due to sepsis. PBSC harvesting in these children was undertaken without interrupting routine chemotherapy and without the use of bone marrow growth factors. In some patients PBSC failed to influence engraftment and the use of combined chemotherapy and growth factor priming for PBSC collection may give improved results.     

Efficacy of Nebulised Epinephrine versus Salbutamol in Hospitalised Children with Bronchiolitis

Background

The use of bronchodilators in bronchiolitis lacks consensus. The efficacy of nebulised epinephrine versus salbutamol in bronchiolitis and the safety profile of the bronchodilators was studied.

Methods

Effects of nebulised epinephrine and salbutamol were compared in children with moderate to severe acute bronchiolitis. Thirty children between 2 to 24 months of age were recruited, 15 in each treatment group. Children received periodic (0,30,60 minutes followed by 4 hourly) doses of either 1:1000 laevo- epinephrine (0.5ml/kg subject to a maximum of 2.5ml with 3ml saline) or salbutamol (0.15mg/kg with 3ml saline) via nebuliser with oxygen. Changes in heart rate (HR), respiratory rate (RR), respiratory distress assessment instrument (RDAI), oxygen saturation (SpO2), oxygen requirement, duration of hospital stay and the side effects were studied.

Results

The respiratory status was better with significant improvement in RR, RDAI score and SpO2, decreased oxygen requirement and shorter hospital stay in the epinephrine group. There were no significant side effects in either group.

Conclusion

Nebulised epinephrine is a useful and safe drug for moderate/severe bronchiolitis and is superior to salbutamol.Key Words: Bronchiolitis, Nebulised bronchodilators, Epinephrine, Salbutamol     

Trends in provision of photodynamic therapy and clinician attitudes: a tracker survey of a new health technology

Background  

There has been debate about the cost-effectiveness of photodynamic therapy (PDT), a treatment for neovascular age-related macular degeneration. We have been monitoring trends for the provision of PDT in the UK National Health Service. The fourth annual 'tracker' survey took place as definitive National Institute for Clinical Excellence (NICE) guidance was issued. We assessed trends in PDT provision up to the point of release of the NICE guidance and identified likely sources of pressure on ophthalmologists to provide PDT.