Human Islet Transplantation: Update

New hope for the treatment of type 1 diabetes has recently emerged from the encouraging results of islet cell transplantation in humans during the last few years. Although still facing considerable problems, the challenge to achieving insulin independence has been overcome in some patients who received an islet graft. However, the success of clinical trials is still limited by the inability to transplant enough viable human islets to compensate for the insulin-deficient state, the number of islets that engraft following transplantation, the rejection process, and the recurrence of autoimmunity. The important advances in immunosuppressive regimens, organ procurement techniques, isolation techniques, and availability of defined collagenase blends have contributed to the continuing promise of making islet cell transplantation the treatment of choice for type 1 diabetes mellitus.     

Skin wrinkling: can food make a difference?

OBJECTIVES: This study addressed whether food and nutrient intakes were correlated with skin wrinkling in a sun-exposed site. METHODS: 177 Greek-born subjects living in Melbourne (GRM), 69 Greek subjects living in rural Greece (GRG), 48 Anglo-Celtic Australian (ACA) elderly living in Melbourne and 159 Swedish subjects living in Sweden (SWE) participating in the International Union of Nutritional Sciences IUNS "Food Habits in Later Life" study had their dietary intakes measured and their skin assessed. Food and nutrient intakes were assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Skin wrinkling was measured using a cutaneous microtopographic method. RESULTS: SWE elderly had the least skin wrinkling in a sun-exposed site, followed by GRM, GRG and ACA. Correlation analyses on the pooled data and using the major food groups suggested that there may be less actinic skin damage with a higher intake of vegetables (r(s)=-0.31, p<0.0001), olive oil (r(s)=-0.29, p<0.0001), fish (r(s)=-0.24, p<0.0001) and legumes (r(s)=-0.16, p<0.0001), and lower intakes of butter (r(s)=0.46, p<0.0001) and margarine (r(s)=0.24, p<0.001), milk products (r(s)=0.16, p<0.01) and sugar products (r(s)=0.12, p<0.01). Similar findings were obtained using regression analyses, except fish was no longer significant; 32% of the variance for actinic skin damage was predicted by six out of the ten major food groups. In particular, a high intake of vegetables, legumes and olive oil appeared to be protective against cutaneous actinic damage (collectively explaining 20% of the variance); a high intake of meat, dairy and butter appeared to be adverse (explaining <5% of the variance). Prunes, apples and tea explained 34% of variance amongst ACA. CONCLUSION: This study illustrates that skin wrinkling in a sun-exposed site in older people of various ethnic backgrounds may be influenced by the types of foods consumed.     

An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma

BACKGROUND: An Investigational New Drug (IND) treatment program allows patients access to a drug that has shown activity against a serious or life-threatening disease prior to full Food and Drug Administration (FDA) review and approval. This treatment IND program, in which patients with locally advanced or metastatic pancreatic carcinoma were treated with gemcitabine, began in 1995. METHODS: Eligibility criteria were < or =1 prior chemotherapy regimen; a Karnofsky performance status (KPS) of > or =50; and adequate bone marrow, liver, and renal function. Gemcitabine was given at a dose of 1000 mg/m2 weekly x 7 followed by a week of rest, then weekly x 3 every 4 weeks thereafter. In this program, disease-related symptom improvement (DRSI) was defined retrospectively as 1) improvement in pain (on a 7-point scale) and/or analgesic class (e.g., morphine improving to codeine) and/or KPS (> or =20 points), or 2) stability of these three parameters with a 7% increase in weight from baseline. RESULTS: A total of 3023 patients enrolled. At baseline, 80% of them had Stage IV disease, and 84% had a baseline KPS > or = 70. The median age was 65 years, and 56% of the patients were male. The cumulative DRSI response rate after the fourth cycle was 18.4%. Of 982 patients with tumor response data, there were 14 with complete response and 104 with partial response, for an overall response rate of 12.0% (95% confidence interval [CI], 10.0-14.0%). For 2380 patients with survival data, the median survival was 4.8 months (95% CI, 4.5-5.1 months) and the 12-month survival was 15%. Gemcitabine was well tolerated; only 4.6% of discontinuations were due to adverse events. CONCLUSIONS: Notable disease-related symptom improvement and survival were seen with gemcitabine in this large, compassionate-use setting, and these findings were in agreement with those of earlier registration trials.     

Topoisomerase I inhibitors in the treatment of colorectal cancer

Over the past 10 years, a number of topoisomerase I inhibitors have entered into clinical trials and several of these have been evaluated in phase II and III studies to determine their activity in patients with advanced colorectal cancer. The most extensively studied of these has been irinotecan (CPT-II). In phase II trials in patients with colorectal cancer that was recurrent or refractory to 5-Ruorouracil (5-FU)based front-line therapy, response rates of 14% to 22% and median survival times of 8 to 10 months have been consistently reported by groups from Japan, Europe, and the United States using avariety of drug administration schedules Two recently reported phase III trials comparing CPT-II against infusional 5-FU or best supportive care demonstrated that CPT-II confers a survival advantage over either of the two other approaches. In front-line treatment of colorectal cancer, CPT-II produces response rates of 19% to 32% and median survival times of 11 to 12 months, figures quite similar to those achievable with bolus 5-FU and leucovorin. Further evaluation in the front-line setting has concentrated on the integration of CPT-II with 5-FU-based regimens. The role of other topoisomerase I inhibitors in colorectal cancer has been more difficult to characterize. Using a standard daily x 5 schedule, topotecan has little objective activity against relapsed or refractory colorectal cancer. Infusional topotecan appears more promising in the treatment of patients with advanced colorectal cancer. The development of an oral formulation of topotecan may make this approach more feasible and is likely to undergo dinical evaluation in the near future. Phase II evaluation of 9-aminocamptothecin (9-AC) has focused on infusional schedules of varying lengths Despite this, little antitumor activity has been observed against colorectal cancer. Other topoisomerase I inhibitors, such as DX-8951f and 9-nitrocamptothecin (9-NC, RFS2000), have not been formally tested in phase II trials against colorectal cancer. In summary, extensive evaluation of topoisomerase I inhibitors has identified a significant degree of variability in clinical activity in patients with advanced colorectal cancer. To date, only one topoisomerase I inhibitor, CPT-II, has demonstrated a level of activity sufficient for it to become an integral component of treatment for patients with 5-FU-refractory colorectal cancer. Current and future studies will focus on the development of front-line regimens combining CPT-II and 5-FU for treatment of patients with advanced-stage disease, moving topoisomerase I inhibitors into the adjuvant therapy setting, and developing combined modality regimens of surgery, radiation, and topoisomerase I inhibitors for patients with locally advanced colorectal cancer.     

Chlamydial infection of mothers and their infants.

In 340 women, cultured prospectively during their pregnancies, the rate of infection with Chlamydia trachomatis was 8.8%. The women with positive cultures tended to be younger and more often single and black than their counterparts with negative cultures. There were no statistically significant clinical differences between the two groups. Eighteen children born to Chlamydia culture-positive women and 16 born to negative women were followed for nine months to examine the potential effects of maternal infection on infant growth, development, and illness. Eleven of 18 study patients had culture or tear antibody evidence of Chlamydia infection, as opposed to one of the control subjects (P = 0.00093). Eight of these 11 had clinical conjunctivitis, and two of the eight developed pneumonia. Growth retardation and developmental abnormalities were not detected in either group. It is concluded that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in the offspring.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Obstetric and nonmalignant gynecologic bleeding: treatment with angiographic embolization

Eight patients (seven post partum, one post abortion) with massive pelvic hemorrhage related to pregnancy and one patient with uncontrollable bleeding following a cervical biopsy underwent angiography to facilitate the identification and treatment of bleeding sites. In all nine patients pelvic hemorrhage was successfully controlled with embolization under angiographic guidance. Angiographic embolization allowed preservation of the uterus in six patients referred prior to hysterectomy, and one patient subsequently became pregnant. When conservative measures and minor surgical repairs have failed, embolization should be the next step in the treatment of postpartum hemorrhage to avoid major surgery in an unstable patient and to maintain reproductive function.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

失眠的评价

失眠的定义失眠分为急性和慢性失眠.急性失眠通常持续时间不超过2 w,与应激状态有关,例如上班、搬家、婚姻或亲人朋友的去世等.而慢性失眠则是失眠持续超过3 w以上,或者不充足睡眠伴随着日间睡意和抑郁,且持续时间不少于1个月.