Membrane phenotype and response to deoxycoformycin in mature T cell malignancies

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.     

Patterns of mortality in sickle cell disease in the United Kingdom.

Eighteen of 384 patients entered on the Brent sickle cell disease register died between 1974 and 1989, a mortality of one per 128 years of follow up. Two children died from acute splenic sequestration and a third died from fulminant pneumococcal septicaemia: none was taking prophylactic penicillin. Acute chest syndrome was the cause of death in eight young adults and one child. Three deaths occurred after surgery. Cerebrovascular accidents contributed to the cause of death in three cases and there were two sudden unexplained deaths. Ten of the deaths occurred at home or within 24 hours of admission to hospital. Post mortem examinations were made in 14 cases, but the histological appearances of acute chest syndrome were often not recognised. In most cases for whom information was available, the cause of death (chest syndrome, pneumococcal sepsis, postoperative complications) could have been prevented.     

Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers

Ovarian cancer is associated with a leukocyte infiltrate and high levels of chemokines such as CCL2. We tested the hypothesis that CCL2 inhibition can enhance chemotherapy with carboplatin and paclitaxel. Elevated CCL2 expression was found in three non‐MDR paclitaxel resistant ovarian cancer lines ES‐2/TP, MES‐OV/TP and OVCAR‐3/TP, compared to parental cells. Mice xenografted with these cells were treated with the anti‐human CCL2 antibody CNTO 888 and the anti‐mouse MCP‐1 antibody C1142, with and without paclitaxel or carboplatin. Our results show an additive effect of CCL2 blockade on the efficacy of paclitaxel and carboplatin. This therapeutic effect was largely due to inhibition of mouse stromal CCL2. We show that inhibition of CCL2 can enhance paclitaxel and carboplatin therapy of ovarian cancer.     

Intra-abdominal hypertension: pulmonary and cerebral complications

Intra-abdominal hypertension causes many physiologic changes, primarily by reducing thoracic compliance and secondarily causing organ failure, which is the body's normal response to trauma or acute inflammatory response. Compartment syndrome as a cause of abdominal hypertension has adverse effects on the circulation, threatening the function and viability of tissues. Intra-abdominal hypertension with the clinical picture of compartment syndrome is a reperfusion injury that is a cyclic event. Elevated intra-abdominal pressure due to whatever mechanism affects all intra-abdominal viscera, including the abdominal wall. Due to edema reducing thoracic compliance, producing severe encephalopathy and leading to severe ischemia with generation of significant quantities of reactive oxygen free radicals as well peroxidation products released from the intestine, liver and spleen. Elevated intracranial pressure causes encephalopathy and the risk of neuronal damage due to the sharp decrease in cerebral perfusion pressure. Elevated intracranial pressure is due to restriction of outflow from the lumbar venous plexus. The etiology of the sudden increase in capillary permeability remains unclear. Decompressive laparotomy leads to a rapid improvement in pulmonary parameters and oxygen delivery. The clinical state after decompression is an example of ischemia-reperfusion injury requiring therapy with inotropes and other agents to improve cardiac, respiratory, renal and cerebral hemodynamics with life saving effects.     

Possible induction of systemic lupus erythematosus by human parvovirus.

A 59 year old woman presented with an influenza-like illness preceding signs and symptoms strongly suggestive of systemic lupus erythematosus (SLE), which progressed over several months. Owing to these influenza-like symptoms, a viral cause of her illness was sought. Human parvovirus B19 serology was positive and antibodies to DNA were detected by two different methods. This patient is believed to be the first report of human parvovirus B19 infection coinciding with the onset of SLE. The evidence for B19 virus and the part it plays in autoimmunity and arthritis is discussed.     

Red cell alloimmunization in sickle cell disease

Alloimmunization to red cell antigens contributes to morbidity in transfused patients. It has been recommended that blood for sickle cell patients need not be matched for antigens other than ABO and Rh(D), as there is no greater incidence of antibody production than in other multitransfused patient populations. Post transfusion alloimmunization was studied in a group of 34 sickle cell disease patients attending a U.K. haemoglobinopathy clinic. Red cell antibodies were formed in 17.6% of the transfused patients and Rhesus and Kell antibodies accounted for 66% of this total. In order to reduce alloimmunization, a policy of performing extended red cell phenotyping on the patients, and providing blood matched for Kell, and in certain circumstances the Rhesus antigens other than Rh(D), is recommended.     

Haemostatic changes following surgery

Changes in factors V, VII and VIII and in fibrinogen were studied in 32 patients undergoing major abdominal surgery. Mean levels of factors V and VII were similar to population-based values preoperatively. Factor V fell following elective surgery and then rose above the mean pre-operative level before returning to it by the tenth post-operative day. Factor VII fell following both elective and emergency surgery and tended to remain depressed throughout the post-operative period. Pre-operative values of factor VIII and fibrinogen were higher than population-based values and higher in the emergency than in waiting-list patients. Both factor VIII and fibrinogen rose following elective surgery but no statistically significant change was seen following emergency surgery. The uncomplicated conditions leading to elective surgery, the acute complications leading to emergency surgery, and surgery itself may each have contributed to increases in factor VIII and fibrinogen levels, whereas the fall in factors V and VII was largely related to surgery itself. The findings may help in the interpretation of associations between clotting factors and thrombotic disease, particularly in the case of factor VII.     

Leukocyte-depleted blood. A comparison of filtration techniques

Febrile transfusion reactions due to leukoagglutinins are commonly seen in multitransfused patients. It has been suggested that reduction of the number of leukocytes per transfusion to 0.5 × 10(9) or less would prevent nonhemolytic febrile transfusion reactions in the majority of patients. Therefore, we have compared the ability of several filters to reduce the leukocyte content of stored whole blood drawn into citrate- phosphate-dextrose. The leukocyte absorption filters, Imugard IG500 and Erypur, produced 98.3 ± 2.4 and 98.3 ± 1.7 percent leukocyte depletion, respectively. The leukocyte adherence filter, Leuko-Pak, produced a depletion of 54.6 ± 14.7 percent. The microaggregate filters, Biotest MF10B Microfiltration set, Ultipor Blood Transfusion Filter SQ40S, and Travenol 20 micron High Capacity Transfusion Filter, produced 37.5 ± 10.8, 13.3 ± 11.2, and 44.5 ± 11.3 percent leukocyte depletion, respectively. It would appear that of the filters tested, the Imugard IG500 and the Erypur are the only filters which can invariably reduce the absolute number of leukocytes in a unit of stored whole blood to below 0.5 × 10(9).     

Screening cord blood for sickle haemoglobinopathies in Brent

Between 1981 and 1983, 3165 consecutive specimens of cord blood were tested at the Central Middlesex Hospital for the presence of an abnormal haemoglobin: the incidence of sickle cell trait was 2.8%, of HbC trait 0.9%, and the overall incidence of an abnormal haemoglobin at birth was 6.9%. Five babies with homozygous sickle cell disease, three with HbSC, and three with either HbCC or HbC beta thalassaemia were detected. Twenty two per cent of the mothers were of Afro-Caribbean origin. The cost of the test was 30p. An H6000 blood count was carried out on 1000 consecutive cord blood samples. The mean red cell volume was 97.95 (SD 3.67) fl. Thirteen cord blood samples had a mean cell volume below 85 fl, and all contained Hb Barts. In addition, six samples with a mean cell volume between 86 and 92 fl also showed Hb Barts on electrophoresis. The overall incidence of Hb Barts was 2.1%. These results indicate that the incidence of HbSS and HbSC on neonatal screening in Brent is similar to that found in the urban areas of North America and that the number may be predicted from the number of births to mothers of Afro-Caribbean origin.