Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.     

Primary Hemiarthroplasty for Proximal Humeral Fractures in the Elderly: Long-Term Functional Outcome and Social Implications

Abstract Background: Primary shoulder hemiarthroplasty is an established treatment modality for complex fractures of the proximal humerus. Long-term functional outcome is often disappointing. However, little is known about social implications particularly in the elderly. Methods: A single-institution case series of consecutive geriatric patients (age > 70 years) treated with shoulder hemiarthroplasty for complex fractures of the proximal humerus between 1994 and 1997 was analysed. Postoperative morbidity, long-term function, radiological outcome and social implications were evaluated. Results: Seventy-seven patients fulfilled the study criteria. Median age at the time of operation was 80 years (range 70–93 years). Systemic and local postoperative complications were observed in 8% including 2 patients (3%) with revision surgery. Postoperative mortality was 1%. Forty-eight patients (62%) were available for follow-up (median 49 months, range 25–80 months), 22 (29%) died from causes unrelated to hemiarthroplasty before follow-up and 7 patients (9%) did not attend follow-up examination. Median Constant-Murley score was 41 points (range 17–77 points). Long-term results concerning pain were satisfying. The Oxford shoulder score ranged from 14 to 40 (median 30). Forty-one patients (85%) still lived in their original environment and managed their daily life independently despite poor shoulder function. Four patients (8%) lived in a retirement home and 3 (6%) in a nursery home. Eighty percent of our patients were still able to use public transportation, do the daily shopping and wash their whole body by themselves. Conclusion: Most patients managed their daily life independently despite poor shoulder function.     

Intraoperative somatosensory evoked potential monitoring during anterior cervical discectomy and fusion in nonmyelopathic patients--a review of 1,039 cases.

BACKGROUND CONTEXT: Intraoperative somatosensory evoked potential (SSEP) monitoring has been shown to reduce the incidence of new postoperative neurological deficits in scoliosis surgery. However, its usefulness during cervical spine surgery remains a subject of debate. PURPOSE: To determine the utility of intraoperative SSEP monitoring in a specific patient population (those with cervical radiculopathy in the absence of myelopathy) who underwent anterior cervical discectomy and fusion (ACDF) surgery. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: A total of 1,039 nonmyelopathic patients who underwent single or multilevel ACDF surgery. The control group (462 patients) did not have intraoperative SSEP monitoring, whereas the monitored group (577 patients) had continuous intraoperative SSEP monitoring performed. OUTCOME MEASURE: A new postoperative neurological deficit. METHODS: SSEP tracings were reviewed for all 577 patients in the monitored group and all significant signal changes were noted. Medical records were reviewed for all 1,039 patients to determine if any new neurological deficits developed in the immediate postoperative period. RESULTS: None of the patients in the control group had any new postoperative neurological deficits. In the monitored group there were six instances of transient SSEP changes (1 due to suspected carotid artery compression; 5 thought to be due to transient hypotension) which resolved with the appropriate intraoperative intervention (repositioning of retractors; raising the arterial blood pressure). Upon waking up from anesthesia, one patient in the monitored group had a new neurological deficit (partial central cord syndrome) despite normal intraoperative SSEP signals. CONCLUSIONS: ACDF appears to be a safe surgical procedure with a low incidence of iatrogenic neurological injury. Transient SSEP signal changes, which improved with intraoperative interventions, were not associated with new postoperative neurological deficits. An intraoperative neurological deficit is possible despite normal SSEP signals.     

31P MRS of heart grafts provides metabolic markers of early dysfunction.

OBJECTIVE: Early graft failure (EGF) is a life-threatening event still accounting for a significant percentage of early deaths after heart transplantation. We tested whether selected metabolic markers, including high-energy phosphate concentrations measured ex vivo in pre-transplant heart grafts by (31)P magnetic resonance spectroscopy (MRS) are related with early post-transplant outcome. METHODS: During a 3-year period, 26 heart grafts harvested in the vicinity of the transplantation centre were studied. Evaluation of transplantability was done conventionally. (31)P MRS was performed ex vivo approximately 60min after aortic cross-clamp to quantify ATP, P(i) and PCr concentration ratios. A MRS-score was defined as a combination of intracellular pH (pHi) and the PCr/P(i) ratio. EGF was defined as the need to abnormally extend circulatory support or to use more than two inotropes before weaning the patient from CPB after transplantation. The grafts were attributed to three groups as follows: A1, transplanted with uneventful outcome (n=14); A2, transplanted with subsequent EGF (n=3) and B, not suitable for transplantation (n=9). RESULTS: Significant differences between groups existed for the following metabolic markers: PCr/ATP (P=0.013), PCr/P(i) (P=0.0004), pHi (P=0.0016) and MRS-score (P=0.0001). The sensitivity, specificity and positive likelihood ratio for EGF with a MRS-score相似文献   

High-resolution immunophenotyping of subcellular compartments in tissue microarrays by enzyme metallography.

Ultrasensitive bright field in situ hybridization assays using enzyme metallography (EnzMet) have been developed and validated, but little is known regarding the applicability of EnzMet for immunophenotypic detection of protein via IHC. Superior resolution via discrete metallographic deposits offers the potential for enhancing high-resolution immunophenotyping. Using high-complexity tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of EnzMet to specifically localize encoded antigens in the nucleus (estrogen receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs. Results were compared with conventional IHC diaminobenzidine (DAB) immunostaining. There was full concordance between the EnzMet and conventional IHC results. Furthermore, the EnzMet reaction products did not appreciably diffuse, were dense and sharply defined, and provided excellent high-resolution differentiation of cellular compartments in paraffin sections for the nuclear, cytoplasmic, and cell membrane-localized antigens evaluated. The higher density of elemental silver deposited during enzyme metallography permitted evaluation of core immunophenotypes at a relatively low magnification, allowing more tissue to be screened in an efficient manner. This preliminary study shows the utility of using enzyme metallography for high-resolution immunophenotyping in TMAs.     

Orthotopic placement of the dunning R3327 AT-3 prostate tumor in the copenhagen X fischer rat

Orthotopic placement of in vitro propagated Dunning R3327 AT-3 tumor cells resulted in a greater percentage of tumor takes and a two-fold shift in the exponential growth curve compared to flank implantation. The orthotopic tumor appeared to disseminate preferentially to regional lymph nodes, rather than to the lungs which is characteristic of flank tumors. The results suggest an important role of stromal-epithelial interactions in the growth of this tumor. © 1995 Wiley-Liss, Inc.     

Hypolipidemic activity in rodents of phenobarbital and related derivatives

A series of 5-alkyl-5-phenylbarbituric acid analogues were shown to be potent hypolipidemic agents in rats and mice at 20 mg/kg/day. This dose is lower than that required for hypolipidemic activity for clofibrate and nicotinic acid derivatives in rodents and man. These new derivatives reduced both serum cholesterol and triglyceride levels in rodents by either the oral or intraperitoneal route of administration. Previous studies have demonstrated that similar heterocyclic compounds, i.e. cyclic imides, glutarimides and hydantoins are potent hypolipidemic agents in rodents. The barbituric acid derivatives probably interfered with de novo synthesis of cholesterol and fatty acids in the early steps since the agents inhibit the activities of ATP-dependent citrate lyase and acetyl-CoA synthetase. Triglyceride synthesis may be blocked since the agents inhibited the rate limiting enzyme, sn-glycerol-3-phosphate-acyl-transferase. Rat tissue lipids especially cholesterol and triglycerides were reduced after 14 days treatment. Fecal lipids were increased in cholesterol and phospholipid content by selected compounds. The rat serum lipoprotein after 14 days drug administration showed reduced VLDL-cholesterol and HDL-triglyceride contents. The modulation of the lipid content of the serum lipoproteins by the barbituric acids suggest that these agents may be helpful in treating clinical hyperlipidemic disease states.