Human tissue-engineered blood vessels for adult arterial revascularization

There is a crucial need for alternatives to native vein or artery for vascular surgery. The clinical efficacy of synthetic, allogeneic or xenogeneic vessels has been limited by thrombosis, rejection, chronic inflammation and poor mechanical properties. Using adult human fibroblasts extracted from skin biopsies harvested from individuals with advanced cardiovascular disease, we constructed tissue-engineered blood vessels (TEBVs) that serve as arterial bypass grafts in long-term animal models. These TEBVs have mechanical properties similar to human blood vessels, without relying upon synthetic or exogenous scaffolding. The TEBVs are antithrombogenic and mechanically stable for 8 months in vivo. Histological analysis showed complete tissue integration and formation of vasa vasorum. The endothelium was confluent and positive for von Willebrand factor. A smooth muscle-specific alpha-actin-positive cell population developed within the TEBV, suggesting regeneration of a vascular media. Electron microscopy showed an endothelial basement membrane, elastogenesis and a complex collagen network. These results indicate that a completely biological and clinically relevant TEBV can be assembled exclusively from an individual's own cells.     

Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis

Background

Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy.

Methods

We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups.

Results

We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25).

Interpretation

Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer.Anemia related to cancer may be due to the cancer itself or it may be a complication of chemotherapy. Because anemia is associated with adverse clinical outcomes in people with cancer, including impaired quality of life¹ and decreased survival,² treatment with erythropoiesis-stimulating agents has been widely used. These agents are costly, and reimbursement policies for their use in patients with cancer-related anemia vary across Canadian jurisdictions. Recent studies suggest that their use in such patients may be associated with an increased risk of adverse events such as thromboembolism.³ Potential adverse effects have also been identified in patients with chronic kidney disease.^4,5Therefore, an assessment of the efficacy and harms of erythropoiesis-stimulating agents in patients with cancer-related anemia would be useful to clinicians, and to jurisdictions that seek to develop an evidence-based reimbursement policy for these drugs. We conducted a systematic review based on work done for the Canadian Agency for Drugs and Technologies in Health⁶ to summarize the clinical efficacy and harms of these agents in adults with anemia related to cancer.     

Biochemical genetics of phosphohydrolase polymorphism in Culex pipiens complex.

1. Single 4th-instar larvae were used in the investigation of alkaline phosphohydrolase (APH) variability in Culex pipiens quinequefasciatus. The genetic basis of isozyme variability was determined from genetic crosses performed with isogenic and hybrid strains of mosquitoes. 2. Isozyme electromorphs presented four enzyme activity zones, three monomorphic and one polymorphic, correspondent with four APH gene loci (aph1, aph2, aph3 and aph4). 3. All isozymes migrated anodically, with aph4 isozymes migrating most rapidly. 4. Enzyme polymorphism was evident only at aph4 locus, with three allozymes present. 5. aph4 allozymes are conditioned by multiple, co-dominant alleles transmitted in a Mendelian manner. 6. Differential frequencies and selection for aph4 alleles and genotypes are suggested by data from genetic crosses.     

Difference in the response of two hybrid stocks of mice to X-ray induction of chromosome aberrations in spermatogonial stem cells

Ionizing radiation induces balanced reciprocal translocations in spermatogonial stem cells of mice. From cells carrying these rearrangements, which can be scored cytologically in the diakinesis-metaphase I stage, balanced normal, balanced translocated and unbalanced (duplication/deficiency) sperm can be produced. The relationship between expected (calculated from cytological data) and observed frequencies of embryonic lethality (presumably as a result of unbalanced sperm fertilizing the egg) following exposure of spermatogonial stem cells to X-rays was studied in two hybrid stocks. A marked difference in the incidence of induced embryonic lethality was found between the two stocks. Similarly, a difference in the cytological frequencies of translocations was also found, although smaller than that observed for embryonic lethality. Thus, it appears that the difference between the two stocks in the frequencies of embryonic lethality may be attributable both to processes occurring prior to metaphase I and to a difference in the rate of transmission of unbalanced chromosome constitutions.     

Receptors for luteinizing hormone and follicle-stimulating hormone in largest follicles of postpartum beef cows

Follicles collected from cows destined to enter relatively normal or short luteal phases if induced to ovulate were compared for numbers of receptors for luteinizing hormone (LH) in granulosal and thecal cells and for follicle-stimulating hormone (FSH) in granulosal cells. Eleven suckled beef cows received ear implants of 6 mg norgestomet for 9 days (expected normal luteal phase) and 11 served as controls (expected short luteal phase). At 48 h after implants were removed (average 34 days postpartum), the ovary containing the largest follicle was identified by transrectal ultrasound and removed. The largest follicle was dissected free of surrounding ovarian stroma and frozen in liquid nitrogen. Thecal and granulosal cells were isolated, and numbers of receptors for LH and FSH in granulosal cells and for LH in thecal cells were quantified. Concentrations of estradiol were measured in follicular fluid. Both granulosal and thecal cells from norgestomet-treated cows had greater numbers of receptors for LH than did those from control cows (p less than 0.01). Numbers of receptors for FSH in granulosal cells did not differ between treated and control cows. Follicles from norgestomet-treated cows were heavier (p less than 0.01) than follicles from control cows, mostly due to greater amounts of follicular fluid (p less than 0.01). Concentrations of estradiol were higher in follicular fluid from the treated cows (p less than 0.05). It is suggested that increases in numbers of follicular receptors for LH and secretion of estradiol are integral components of a sequence of events by which norgestomet prepares follicles to become fully functional corpora lutea.     

An autonomic routing framework for sensor networks

Current routing services for sensor networks are often designed for specific applications and network conditions, thus have difficulty in adapting to application and network dynamics. This paper proposes an autonomic framework to promote the adaptivity of routing services in sensor networks. The key idea of this framework is to maintain some feature functions that are decoupled from originally-integrated routing services. This separation enables significant service changes to be done by only tuning these functions. Measures including parameterization are taken to save the energy for changing these functions. Further, this framework includes a monitoring module to support a policy-based collaborative adaptation. This paper shows an example autonomic routing service conforming to this framework. Some of this work was done while the author was at ISI