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。     

Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients

The purpose of this study was to evaluate the short-term efficacy of topical capsaicin treatment in patients severely affected by fibromyalgia. One hundred and thirty fibromyalgia patients were randomly divided into two groups. The control group, 56 women and 4 men who continued their medical treatment, and the capsaicin group, 70 women who apart from continuing their medical treatment, also underwent topical capsaicin 0.075 % 3 times daily for 6 weeks. At the beginning of the program, there were no significant differences between the two groups in any of the analyzed parameters. At the end of the treatment, there were significant improvements in the capsaicin group in the myalgic score (5.21 vs 3.8, p = 0.02) and global subjective improvement (22.8 vs 5 %, p = 0.001). Six weeks after the end of the treatment, the experimental group showed significant differences in Visual Analogue Scale of depression (5.63 vs 7.35, p = 0.02), Fibromyalgia Impact Questionnaire (67.89 vs 77.7, p = 0.02), role limitations due to emotional problems (36.17 vs 17.2, p = 0.05), Fatigue Severity Scale (6.2 vs 6.6, p = 0.04), myalgic score (3.94 vs 2.66, p = 0.02) and pressure pain threshold (79.25 vs 56.71, p = 0.004). In conclusion, patients severely affected by fibromyalgia can obtain short-term improvements following topical capsaicin 0.075 % treatment three times daily for 6 weeks.     

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.     

Incidence and prevalence of autoimmune hepatitis in the area of the Hospital de Sagunto (Spain)

Thirteen cases of autoimmune hepatitis (AIH) were diagnosed from 1990 to 2003 in the area of the Hospital de Sagunto (Valencia, Spain), which attends a population of 112,003 inhabitants aged more than 14 years (54,622 males and 57,381 females). The diagnostic criteria of the International Autoimmune Hepatitis Group were used and patients who, despite having a probable diagnosis of AIH, presented hepatitis C virus infection were excluded. The diagnosis was probable in one patient and definitive in 12. All patients, 11 females and two males aged 45.9 12.2 years (range: 28-66), were classified as AIH type 1. Among the population aged more than 14 years, the mean annual incidence of AIH was 0.83 cases/100,000 inhabitants (95% CI, 0.44-1.42) (range: 0-2.68), showing a significant trend to increase (b = 0.132; p = 0.019). The incidence was higher in women than in men (RR = 5.24; 95% CI, 1.16-23.62). The mean annual incidence was 1.37 (95% CI, 0.68-2.46) (range: 0-3,49) in women and was 0.26 (95% CI, 0.02-0.96) (range: 0-1.83) in men. By age, the maximum mean annual incidence was observed in the group aged 55-64 years (1.6 cases/100,000 inhabitants). The prevalence of AIH in September 2003 was 11.61 cases/100,000 inhabitants aged more than 14 years (95% CI, 6.78-19.86). The prevalence was 3.66 (95% CI, 1-13.35) in men and was 19.17 (95% CI, 10.70-34.33) in women.     

Epidemiology of biopsy proven giant cell arteritis in northwestern Spain: trend over an 18 year period

OBJECTIVE: In Europe giant cell arteritis (GCA) is more common in Scandinavian countries than in southern regions. Epidemiological studies on GCA in other more distant countries have indicated a progressive increase in incidence. A regular cyclical pattern in incidence of GCA over 20 years has been reported in Olmsted County (Minnesota, USA). In contrast, no cyclical fluctuation has been recently reported in Sweden. To investigate further the epidemiology of GCA in southern Europe the trend in incidence and fluctuations of this vasculitis over 18 years in the Lugo region of northwestern Spain were examined. METHODS: A retrospective study of biopsy proven GCA diagnosed between 1 January 1981 and 31 December 1998 at a single hospital for a well defined population of almost 250 000 people. Annual incidence was calculated for the whole group of patients and for men and women separately. Monthly variations, annual peaks of incidence, and trend in the incidence of biopsy proven GCA with and without polymyalgia rheumatica (PMR) were also examined. RESULTS: One hundred and sixty one Lugo residents were diagnosed with biopsy proven GCA between 1981 and 1998. The average annual incidence for the population aged 50 and older was 10.24/100 000 (men 11.00/100 000, women 9.57/100 000). A progressive increase in the incidence in both men and women was seen. In men there was an annual increase of 8% (95% CI 4% to 13%; p<0.0001). In women the annual increase was 11% (95% CI 5% to 17%; p<0.0001). The overall annual increase for men and women was 10% (95% CI 6% to 14%; p<0.0001). No seasonal pattern or peaks in the incidence were seen. During the period 1981-94 GCA was more common in men than in women. In contrast, during the last years of study the increase in incidence was higher in women. In women the annual ratio of incidence of GCA with PMR/incidence of GCA without PMR was generally higher than 1. However, in men the annual ratio was initially 1 but decreased gradually, indicating a progressive decrease in the proportion of men with biopsy proven GCA associated with PMR. CONCLUSION: In northwestern Spain there has been a progressive increase in GCA incidence. As seen in other countries where GCA is more common, during the past few years the increase in incidence has been mainly due to a higher number of new cases in women.     

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.