Epidemiological study of myasthenia gravis in Sardinia, Italy (1958–1986)

From 1.1.1958 to 31.12.1986, 110 cases of MG were observed in Sardinia, with a mean annual incidence of 2.5 x 1,000,000 inhabitants and prevalence rates of 7.5, 17.6, 31.4 and 45.0 x 1,000,000 inhabitants respectively (prevalence days: 15.10.1961, 24.10.1971, 25.10.1981 and 31.12.1986). The disease was found to be more frequent in women. There were no differences in the distribution of MG in various areas of the island. The muscle group more frequently involved at onset was the ocular. In 6.4% of patients an association with thyroid disorders was observed. The mortality of MG patients was significantly higher than expected. Removal of the thymus, carried out in 58 patients, was shown to be useful in the treatment of the disease, particularly in patients without thymomas. No familial cases were observed.     

Sclerosteosis: report of a case in a black African man

Sclerosteosis is a rare genetic disorder of bone modelling, similar to, but distinct from, van Buchem disease; it has been described almost exclusively in Afrikaners of South Africa, a white population of Dutch ancestry. Isolated cases have been reported in a girl in Japan, a boy in Spain, and in multiracial families in Brazil and USA.
Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly; nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry.     

Outcome assessment in cancer management

The goals of cancer treatment may be prevention, cure, or palliation. In each case, the length and quality of survival are the ultimate outcomes to assess when evaluating the success of treatment. Some surrogate or intermediate endpoints, however, may be considered, such as toxicity or the tumor response. The first section of this article considers traditional outcomes and endpoints and intermediate or surrogate endpoints for survival and quality of life. The second section specifically addresses the issue of the quality-of-life outcome, which has become increasingly important over the last 2 decades. The last section suggests that combining survival and quality of life may not be easy. Costs are increasingly important in management of diseases, and the outcomes of cancer treatment frequently are measured against them. Although the definitions of cost-effectiveness and cost-utility are mentioned at the end of this article, the article does not deal with the problems of decision making for health resource allocation.     

腹腔镜与开腹结肠切除术在八旬结肠直肠癌患者中的疗效：一项病例配对的对照研究

目的：比较评估腹腔镜与开腹结肠切除术对八旬老年结肠直肠癌患的早期疗效。方法：根据性别、年龄、手术时间、肿瘤位置以及入院并发症等条件，选取相匹配的分别接受腹腔镜结肠切除术（腹腔镜组）与开腹结肠切除术（开腹组）的结肠直肠癌患各61例，同时对其入院和出院时的状况进行评估。结果：腹腔镜组年龄82．3±3．5岁，开腹组年龄83．1±3．3岁，其术式转换率为6．1％。腹腔镜组的手术时间较开腹组多49min（P=0．001），两组手术总死亡率为2．4％。腹腔镜组与开腹组的术后发病率分别为21．5％和31．1％（P=0．30），其中腹腔镜组术后结肠功能恢复较快（P=0．01），平均住院时间明显缩短（9．8dvs12．9d；P=0．001），术后独立存活期较长（P=0．02）。结论：对八旬老年结肠直肠癌患施行腹腔镜结肠切除术安全有效，且患住院时间明显缩短，术后独立存活期明显延长。     

T cell vaccinology: Exploring the known unknowns

The objective of modern vaccine development is the safe generation of protective long-term immune memory, both prophylactic and therapeutic. Live attenuated vaccines generate potent cellular and humoral immunity 0005, 0010 and 0015, but numerous problems exist with these vaccines, ranging from production and storage issues to adverse reactions and reversion to virulence. Subunit vaccines are safer, more stable, and more amenable to mass production. However the protection they produce is frequently inferior to live attenuated vaccines and is typically confined to humoral, and not cellular immunity. Unfortunately, there are presently no subunit vaccines available clinically that are effective at eliciting cellular responses let alone cellular memory [4]. This article will provide and overview of areas of investigation that we see as important for the development of vaccines with the capacity to induce robust and enduring cellular immune responses.     

Antileukaemic effect of PI3K‐mTOR inhibitors in acute myeloid leukaemia‐gene expression profiles reveal CDC25B expression as determinate of pharmacological effect

Acute myeloid leukaemia (AML) is a heterogeneous malignancy. Intracellular signalling through the phosphatidylinositol 3‐kinase (PI3K)‐Akt‐mammalian target of rapamycin (mTOR) pathway is important for regulation of cellular growth and metabolism, and inhibitors of this pathway is considered for AML treatment. Primary human AML cells, derived from 96 consecutive adult patients, were examined. The effects of two mTOR inhibitors (rapamycin, temsirolimus) and two PI3K inhibitors (GDC‐0941, 3‐methyladenine) were studied, and we investigated cytokine‐dependent proliferation, regulation of apoptosis and global gene expression profiles. Only a subset of patients demonstrated strong antiproliferative effects of PI3K‐mTOR inhibitors. Unsupervised hierarchical clustering analysis identified two main clusters of patients; one subset showing weak or absent antiproliferative effects (59%) and another group showing a strong growth inhibition for all drugs and concentrations examined (41%). Global gene expression analyses showed that patients with AML cell resistance against PI3K‐mTOR inhibitors showed increased mRNA expression of the CDC25B gene that encodes the cell cycle regulator Cell Division Cycle 25B. The antileukaemic effect of PI3K‐Akt‐mTOR inhibition varies between patients, and resistance to these inhibitors is associated with the expression of the cell cycle regulator CDC25B, which is known to crosstalk with the PI3K‐Akt‐mTOR pathway and mediate rapamycin resistance in experimental models.