A combined cell therapy and in-situ tissue-engineering approach for myocardial repair

Myocardial cell-replacement strategies are hampered by limited sources for human cardiomyocytes and by significant cell loss following transplantation. We tested the hypothesis that a combined delivery of cardiomyocytes with an in-situ polymerizable hydrogel into a post-MI rat heart will result in better functional outcomes than each intervention alone. A photopolymerizable, biodegradable, PEGylated-fibrinogen (PF) hydrogel matrix was used as the carrier for the cardiomyocytes [neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)]. Infarcted rat hearts (LAD ligation) were randomized to injection of saline, NRVCMs, biopolymer, or combined biopolymer-cell delivery. Echocardiography revealed typical post-infarction remodeling after 30 days in the saline-injected control group [deterioration of fractional shortening (FS) by 31.0?±?3.6%]. Injection of NRVCMs or PF alone significantly (p?相似文献   

Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts.

OBJECTIVES: We evaluated the ability of human embryonic stem cells (hESCs) and their cardiomyocyte derivatives (hESC-CMs) to engraft and improve myocardial performance in the rat chronic infarction model. BACKGROUND: Cell therapy is emerging as a novel therapy for myocardial repair but is hampered by the lack of sources for human cardiomyocytes. METHODS: Immunosuppressed healthy and infarcted (7 to 10 days after coronary ligation) rat hearts were randomized to injection of undifferentiated hESCs, hESC-CMs, noncardiomyocyte hESC derivatives, or saline. Detailed histological analysis and sequential echocardiography were used to determine the structural and functional consequences of cell grafting. RESULTS: Transplantation of undifferentiated hESCs resulted in the formation of teratoma-like structures. This phenomenon was prevented by grafting of ex vivo pre-differentiated hESC-CMs. The grafted cardiomyocytes survived, proliferated, matured, aligned, and formed gap junctions with host cardiac tissue. Functionally, animals injected with saline or nonmyocyte hESC derivatives demonstrated significant left ventricular (LV) dilatation and functional deterioration, whereas grafting of hESC-CMs attenuated this remodeling process. Hence, post-injury baseline fractional shortening deteriorated by 50% (from 20 +/- 2% to 10 +/- 2%) and by 30% (20 +/- 2% to 14 +/- 2%) in the saline and nonmyocyte groups while improving by 22% (21 +/- 2% to 25 +/- 3%) in the hESC-CM group. Similarly, wall motion score index and LV diastolic dimensions were significantly lower in the hESC-CM animals. CONCLUSIONS: Transplantation of hESC-CMs after extensive myocardial infarction in rats results in the formation of stable cardiomyocyte grafts, attenuation of the remodeling process, and functional benefit. These findings highlight the potential of hESCs for myocardial cell therapy strategies.     

Three-dimensional positional assessment of glenoid fossae and mandibular condyles in patients with Class II subdivision malocclusion

Objectives:To test the null hypotheses that the positions of the glenoid fossae and mandibular condyles are identical on the Class I and Class II sides of patients with Class II subdivision malocclusion.Materials and Methods:Retrospective three-dimensional (3D) assessments of the positions of the glenoid fossae and mandibular condyles were made in patients with Class II malocclusion. Relative to a fiducial reference at the anterior cranial base, distances from the glenoid fossae and condyles were calculated in pretreatment cone beam computed tomographic scans of 82 patients: 41 with Class II and 41 with Class II subdivision malocclusions. The 3D distances from glenoid fossae to sella turcica in the X (right-left), Y (anterior-posterior), Z (inferior-superior) projections were calculated.Results:Patients with Class II malocclusion displayed a symmetric position of the glenoid fossae and condyles with no statistically significant differences between sides (P > .05), whereas patients with Class II subdivision showed asymmetry in the distance between the glenoid fossae and anterior cranial base or sella turcica (P < .05), with distally and laterally positioned glenoid fossae on the Class II side. (P < .05). Male patients had greater distances between glenoid fossae and anterior cranial fossae (P < .05). The condylar position relative to the glenoid fossae did not differ between the two malocclusion groups nor between males and females (P > .05).Conclusions:The null hypotheses were rejected. Patients with Class II subdivision malocclusion displayed asymmetrically positioned right- and left-side glenoid fossae, with a distally and laterally positioned Class II side, although the condyles were symmetrically positioned within the glenoid fossae.     

Ethnic differences in population approach and experience regarding complementary-alternative medicine (CAM)

PURPOSE: The aim of this survey was to characterize one urban Arab population who turns to complementary-alternative medicine (CAM). METHODS: Outpatient participants were selected randomly by their ethnical affiliation. The questionnaire was filled during patient visit to their assigned urban outpatient clinic. The answers to the first two questions determined whether the questionnaire was to be completed or not (if at least one answer was Yes, the questionnaire was completed). RESULTS: More males (19%) seek for CAM in the Arab group in comparison to more females in the Jewish population (27%). Fifteen per cent and 7% of the individuals in the Jewish and Arab groups who used CAM have academic education. Fifty-two per cent and 27% of the Jewish and Arab populations declared themselves seculars, 72% of the Arab individuals declared to be traditionalists-religious-orthodox in their believes in comparison to 47% in the Jewish population. Twenty-eight per cent and 0% in the Jewish and Arab populations, respectively, preferred a conventional doctor (MD) in CAM practice. More than 30% in both populations preferred CAM to be delivered in medical and nursing schools. CONCLUSIONS: Forty per cent and 31% in the Jewish and Arab groups experienced complementary medicine intervention at least once. When comparing people who used complementary medicine to those who did not, it is observed that the percentage of individuals holding academic degrees in the Jewish group is higher than in the Arab interviewed in the group utilizing complementary medicine. Traditionalist-religious-orthodox individuals seek more complementary medicine in the Arab population (72%) in comparison to 47% in the Jewish individuals. Only 17% of the Arab individuals and 19% in the Jewish group knew about the adverse reactions caused by CAM therapies. More than 30% in both ethnic groups were in favor of 'legalizing' complementary medicine.     

Hospital heterogeneity: what drives the quality of health care

A major feature of health care systems is substantial variation in health care quality across hospitals. The quality of stroke care widely varies across NHS hospitals. We investigate factors that may explain variations in health care quality using measures of quality of stroke care. We combine NHS trust data from the National Sentinel Stroke Audit with other data sets from the Office for National Statistics, NHS and census data to capture hospitals’ human and physical assets and organisational characteristics. We employ a class of non-parametric methods to explore the complex structure of the data and a set of correlated random effects models to identify key determinants of the quality of stroke care. The organisational quality of the process of stroke care appears as a fundamental driver of clinical quality of stroke care. There are rich complementarities amongst drivers of quality of stroke care. The findings strengthen previous research on managerial and organisational determinants of health care quality.     

Antimicrobial effect of 4 disinfectants on alginate, polyether, and polyvinyl siloxane impression materials

PURPOSE: Dental impressions often carry microorganisms that may cause cross infection from patients to dental staff. The aim of the current study was to determine the effectiveness of 4 different disinfectant solutions on 3 commonly used impression materials--alginate, polyether, and polyvinyl siloxane--to establish a protocol for disinfection of these impression materials after clinical exposure and prior to handling in the dental laboratory. MATERIALS AND METHODS: A total of 45 impressions were taken from the maxillary dentate arches of 15 dental staff participants at the Department of Dentistry, Prince Rashid Hospital, Irbid, Jordan. For each participant, 3 successive impressions were recorded in the different impression materials. For each impression, 6 specimens were dissected from 6 different locations and exposed to 6 different regimens: 1 was left untreated, 1 was immersed in sterile water for 10 minutes to serve as a control, and the remaining 4 specimens were exposed to 4 different disinfection treatments (Dimenol, Perform-ID, MD 520, and Haz-tabs). Serial dilutions of the suspension were carried out and counted by the Miles-Misra technique (inoculation on Columbia blood agar for quantification). The dilutions were aerobically incubated at 37 degrees C for 48 hours. RESULTS: The disinfectants were able to completely eliminate microorganisms carried by the impressions. For those undisinfected specimens, the results showed that untreated alginate impressions appear to carry more microorganisms (P < .05) than the other 2 rubber impression materials used in the study. For those specimens immersed in sterile water for 10 minutes (control group), the number of microorganisms eliminated was increased from 62% to 90% compared to those left untreated. CONCLUSION: Impression materials may act as a vehicle for the transfer of microorganisms from the patient's mouth to dental personnel. Impressions should be disinfected to eliminate the risk of cross contamination.     

Tissue engineering of vascularized cardiac muscle from human embryonic stem cells

Transplantation of a tissue-engineered heart muscle represents a novel experimental therapeutic paradigm for myocardial diseases. However, this strategy has been hampered by the lack of sources for human cardiomyocytes and by the scarce vasculature in the ischemic area limiting the engraftment and survival of the transplanted muscle. Beyond the necessity of endothelial capillaries for the delivery of oxygen and nutrients to the grafted muscle tissue, interactions between endothelial and cardiomyocyte cells may also play a key role in promoting cell survival and proliferation. In the present study, we describe the formation of synchronously contracting engineered human cardiac tissue derived from human embryonic stem cells containing endothelial vessel networks. The 3D muscle consisted of cardiomyocytes, endothelial cells (ECs), and embryonic fibroblasts (EmFs). The formed vessels were further stabilized by the presence of mural cells originating from the EmFs. The presence of EmFs decreased EC death and increased EC proliferation. Moreover, the presence of endothelial capillaries augmented cardiomyocyte proliferation and did not hamper cardiomyocyte orientation and alignment. Immunostaining, ultrastructural analysis (using transmission electron microscopy), RT-PCR, pharmacological, and confocal laser calcium imaging studies demonstrated the presence of cardiac-specific molecular, ultrastructural, and functional properties of the generated tissue constructs with synchronous activity mediated by action potential propagation through gap junctions. In summary, this is the first report of the construction of 3D vascularized human cardiac tissue that may have unique applications for studies of cardiac development, function, and tissue replacement therapy.     

VENOUS THROMBOEMBOLISM, FACTOR V LEIDEN, AND METHYLENETETRAHYDROFOLATE REDUCTASE IN A SICKLE CELL ANEMIA PATIENT

Vaso-occlusive crisis is the most common cause of morbidity in patients with sickle cell anemia (SCA). Central nervous system involvement that leads to hemiplegia is the most frequent neurological complication in those patients. Peripheral deep venous thromboembolism was not reported in SCA patients. Activated protein C resistance is associated with an increased risk of thrombophilia. The authors report an SCA patient with recurrent cerebrovascular accident and deep venous thrombosis. Activated protein C resistance due to factor V Leiden heterozygous and heterozygocity for the methylenetetrahydrofolate reductase were diagnosed and suspected to be the risk factors that contribute to the development of the deep vein thrombosis in this SCA patient.