Modulation of pulmonary inflammation after endotoxin inhalation with a platelet-activating factor antagonist (48740 RP)

An acute pulmonary response was induced in guinea pigs and hamsters by inhalation of bacterial endotoxin in the form of a purified lipopolysaccharide (LPS). Pretreatment with the platelet-activating factor (PAF) antagonist, 48740 RP, inhibited damage to endothelial cells, decreased vascular permeability and the number of neutrophils in the airways 24 h after exposure to LPS. The increase in the number of platelets in the airways caused by endotoxin was not affected. The results suggest that PAF modulates early inflammation after endotoxin inhalation.     

Demonstration of complex dysregulation of anti-cytomegalovirus T-cellular immunity in Kaposi's sarcoma following renal transplantation

An increased incidence of Kaposi's sarcoma is well known in renal transplant recipients in whom it may represent up to 3 p. 100 of all de novo tumours. This sarcoma has a close relationship with the potential oncogenicity of the cytomegalovirus (CMV) and with chronic immunological deficiency. Anti-CMV immunity is based on the integrity of cytotoxic cellular functions such as those of cytotoxic T lymphocytes (CTL), "natural killers" cells, and K cells which function in the antibody-dependent cell cytotoxicity (ADCC) system. Two cases of Kaposi's sarcoma were observed out of a total of 700 renal transplant recipients; they underwent the following investigations: lymphocyte sub-group counts by murine monoclonal antibodies, lymphocyte proliferation to lectins and allogenic cells, NK activity and generation of specific auxiliary and cytotoxic anti-CMV cells. Both cases of Kaposi's sarcoma were seropositive for CMV and seronegative for LAV. In one case, an abnormal number of peripheral OKT9 + lymphocytes (normally a thymocytic marker) was observed with small numbers of OKT4/OKT8, a reduced proliferative response to mitogens and allogenic cells. All these in vitro changes persisted despite reduction of immunosuppressive therapy and clinical improvement. A clinical and biological cure was only obtained after withdrawal of immunosuppressive therapy and return to haemodialysis. In the second case of Kaposi's sarcoma, the initial biochemical changes were minimal and a clinical cure was obtained by decreasing the immunosuppressive therapy. These two cases illustrate the complex dysregulation of the immune system in Kaposi's sarcoma.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

放疗联合西妥昔单抗治疗局部中晚期头颈部肿瘤：五年生存期及疗效分析

2006年NEngl J Med报道了一项初始放疗联合西妥昔单抗治疗头颈部局部中晚期鳞状上皮细胞癌（LASCCHN）Ⅲ期随机试验,结果显示患者3年总生存率提高。最近Lancet发表了该试验的5年生存数据,以及西妥昔单抗所致皮疹与生存期的相关性分析。     

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.