Modified Smoothing Algorithm for Tracking Multiple Maneuvering Targets in Clutter.

This research work extends the fixed interval smoothing based on the joint integrated track splitting (FIsJITS) filter in the multi-maneuvering-targets (MMT) tracking environment. We contribute to tackling unknown dynamics of the multi-maneuvering-targets (MMT) using the standard kinematic model. This work is referred to as smoothing MMT using the JITS (MMT-sJITS). The existing FIsJITS algorithm is computationally more complex to solve for the MMT situation because it enumerates a substantial number of measurement-to-track assignments and calculates their posteriori probabilities globally. The MMT-sJITS updates a current target track by assuming the joint (common) measurements detected by neighbor tracks are modified clutters (or pretended spurious measurements). Thus, target measurement concealed by a joint measurement is optimally estimated based on measurement density of the modified clutter. This reduces computational complexity and provides improved tracking performance. The MMT-sJITS generates forward tracks and backward tracks using the measurements collected by a sensor such as a radar. The forward and backward multi-tracks state predictions are fused to obtain priori smoothing multi-track state prediction, as well as their component existence probabilities. This calculates the smoothing estimate required to compute the forward JITS state estimate, which reinforces the MMT tracking efficiently. Monte Carlo simulation is used to verify best false-track discrimination (FTD) analysis in comparison with existing multi-targets tracking algorithms.

Multi-Sonar Distributed Fusion for Target Detection and Tracking in Marine Environment.

The multi-sonar distributed fusion system has been pervasively deployed to jointly detect and track marine targets. In the realistic scenario, the origin of locally transmitted tracks is uncertain due to clutter disturbance and the presence of multi-target. Moreover, attributed to the different sonar internal processing times and diverse communication delays between sonar and the fusion center, tracks unavoidably arrive in the fusion center with temporal out-of-sequence (OOS), both problems pose significant challenges to the fusion system. Under the distributed fusion framework with memory, this paper proposes a novel multiple forward prediction-integrated equivalent measurement fusion (MFP-IEMF) method, it fuses the multi-lag OOST with track origin uncertainty in an optimal manner and is capable to be implemented in both the synchronous and asynchronous multi-sonar tracks fusion system. Furthermore, a random central track initialization technique is also proposed to detect the randomly born marine target in time via quickly initiating and confirming true tracks. The numerical results show that the proposed algorithm achieves the same optimality as the existing OOS reprocessing method, and delivers substantially improved detection and tracking performance in terms of both ANCTT and estimation accuracy compared to the existing OOST discarding fusion method and the ANF-IFPFD method.

Long-term outcome of Non-Transecting Anastomotic Bulbar Urethroplasty for Urethral Strictures: An 8-year experience from Liaquat National Hospital Karachi.

OBJECTIVES: To determine the long-term outcome and complications of non-transecting anastomotic bulbar urethroplasty for the treatment of small bulbar urethral strictures presenting at Liaquat National Hospital, Karachi. METHODS: This interventional study was conducted from January 2012 to December 2019 with the study duration of eight year at Liaquat National Hospital, Karachi. All patients presenting in the outpatient department with urethral strictures were included in the study. Patients were evaluated postoperatively for complications and outcomes were determined. The data was analyzed using SPSS v.25. RESULTS: A total of 358 patients were treated with non-transecting anastomotic bulbar urethroplasty during this 8-years period. The most common site of stricture formation was bulbar urethra 186 (50%), followed by bulbo-membranous urethra; 103 (31%), and bulbo-penile urethra; 69 (19%). The mean stricture was 1.2 cm (0.5-2.5 cm) in length. The main postoperative complications were scrotal swelling in 7 (1.9%), wound infection in 6 (1.6%), wound dehiscence in 3 (0.8%), and transient sexual dysfunction in 31 (8.6%) patients with an overall initial success rate of 97.8%. No permanent deficit in sexual function was reported. CONCLUSIONS: Non-transecting anastomotic bulbar urethroplasty has a good outcome with insignificant postoperative complications in patients with small bulbar urethral stricture disease.

Non-Transecting Anastomotic Bulbar Urethroplasty For Urethral Stricture Disease-Experience From A Highvolume Specialist Centre.

BACKGROUND: Urethral stricture disease has significant economic impact throughout world. The bulbar urethra is the commonest site for urethral strictures (Approx 50%) followed by penile urethra in most of the published literature. In developing countries trauma (road traffic accident and iatrogenic) is the leading cause of urethral stricture disease. Younger patients have usually idiopathic type as compare to old age group, which present more frequently with iatrogenic and trauma related urethral strictures. METHODS: This Qausi Experimental study was conducted from May2012-June2016 of duration at Liaquat National Hospital Karachi. All the patients diagnosed with short urethral strictures related to bulbar urethra were included in this study. All the patients underwent non transecting bulbar urethroplasty. All patients were assessed preoperatively, peri-operatively and postoperatively and on follow-up visits as; on 2nd, 8th and 24th week. All the data regarding outcome was recorded on the Performa and analyzed on SPSS V20. RESULTS: Total of 179patients were included, mean age was 38±SD15.3years (range 20- 65years). Anatomically bulbar urethra was affected in 52% of the cases followed by bulbopenile, bulbomembranous region. Etiologically idiopathic type was found in 40% cases, while trauma 21%, iatrogenic injury 26% and UTI 13% were also reasons. Stricture length was mean1.1±SD 1.4 cm (range 0.5-2.5cm). Preoperative Uroflowmetry revealed mean Qmax of 10.5±SD 5.3 ml/sec. Mean operative time was 35±SD 4.6 minutes, 7 patients had conversion to other procedures (3.91%), Postoperative complications were minimal. Mean follow up was 12±SD 21 months (range 6 months to 3 years). On initial follow up at 8th week and 24th week, Qmax was significantly improved. Only 3 patients required DVIU after the 24th week. Initial success rate after 24th week was 98.3% and eventually 100% at the long-term follow-up. CONCLUSIONS: non-transecting anastomotic bulbar urethroplasty (NTABU) is a new standard of care for the short bulbar urethral stricture up to 2.5cm. Idiopathic aetiology, iatrogenic and posttraumatic urethral strictures in selective patients can safely be operated with this technique.

Surgical Management Of Male Incontinence, With Prolene Mesh Fixing With Prolene Sutures; A Prospective Novel Study For The Treatment Of Male Incontinence At Tertiary Care Hospital.

BACKGROUND: Urinary incontinence is an uncommon problem in males but has major impact on daily living. This study aimed to highlight the outcome of surgical treatment in terms of safety, efficacy and cost-effectiveness in the management of urinary incontinence.. METHODS: A Total of 48 patients, prospective experimental study, in the duration of 4 years conducted at Department of Urology, Liaquat National Hospital & Medical College. Patients having moderate to severe urinary incontinence for 1 year after transurethral resection of prostate, radical prostatectomy, road traffic accident with pelvic fracture causing neurologic damage were included in this study. Patients having mild incontinence, having multiple co-morbid conditions were excluded from this study. Outcome of surgery was noted during follow up visit after 13 month (median). The data was obtained and analysed by using SPSS version 20. Mean and standard deviation for quantitative data, frequency and percentage for categorical variables were presented. RESULTS: Out of 48 patients having urinary incontinence, 28 (58.3%) had severe urinary incontinence while 20 (41.7%) had moderate incontinence. After surgery, 28 (58.3%) patient had no leakage all day, 12 (25%) had some leakage while bending and 8 (16.7%) had no improvement in symptoms. On ultrasound recorded after voiding in post-surgery patients, 40 (83.3%) had no residual found in bladder while 8(16.7%) could not be assessed due to persistence of urinary incontinence. CONCLUSIONS: Our study predicted that in patients having moderate to severe urinary incontinence, Prolene Mesh repair anchoring with Prolene suture can be an efficient and costeffective treatment for the urinary incontinence with least complications.

Biopsy Induced Arteriovenous Fistula and Venous Stenosis in a Renal Transplant.

Renal transplant vein stenosis is a rare cause of allograft dysfunction. Percutaneous stenting appears to be safe and effective treatment for this condition. A 56-year-old Caucasian female with end stage renal disease received a deceased donor renal transplant. After transplant, her serum creatinine improved to a nadir of 1.2 mg/dL. During the third posttransplant month, her serum creatinine increased to 2.2 mg/dL. Renal transplant biopsy showed BK nephropathy. Mycophenolate was discontinued. Over the next 2 months, her serum creatinine crept up to 6.2 mg/dL. BK viremia improved from 36464 copies/mL to 15398 copies/mL. A renal transplant ultrasound showed lower pole arteriovenous fistula and abnormal waveforms in the renal vein. Carbon dioxide (CO2) angiography demonstrated severe stenosis of the transplant renal vein. Successful coil occlusion of fistula was performed along with angioplasty and deployment of stent in the renal transplant vein. Serum creatinine improved to 1.5 mg/dL after.

The Association between Parathyroid Hormone Levels and Hemoglobin in Diabetic and Nondiabetic Participants in the National Kidney Foundation's Kidney Early Evaluation Program.

BACKGROUND: Both anemia and secondary hyperparathyroidism are reflections of hormonal failure in chronic kidney disease (CKD). While the association of elevated levels of parathyroid hormone (PTH) and anemia has been studied among those with advanced CKD, less is known about this association in mild-to-moderate CKD. METHODS: In a cross-sectional analysis, the relationship between PTH and hemoglobin levels was investigated in 10,750 participants in the National Kidney Foundation's Kidney Early Evaluation Program with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. RESULTS: In the unadjusted analysis, higher PTH levels were associated with lower hemoglobin levels. However, after multivariable adjustment for age, race, gender, smoking status, education, cardiovascular disease, diabetes, hypertension, cancer, albuminuria, BMI, baseline eGFR, calcium, and phosphorus, the direction of association changed. As compared to the first PTH quintile, hemoglobin levels were 0.09 g/dl (95% CI: 0.01-0.18), 0.15 g/dl (95% CI: 0.07-0.24), 0.18 g/dl (95% CI: 0.09-0.26), and 0.13 g/dl (95% CI: 0.07-0.25) higher for the second, third, fourth, and fifth quintiles, respectively. Similarly, each standard deviation increase in natural log transformed PTH was associated with a 0.06 g/dl (95% CI: 0.03-0.09, p = 0.0003) increase in hemoglobin. However, a significant effect modification was seen for diabetes (p = 0.0003). Each standard deviation increase in natural log transformed PTH was associated with a 0.10 g/dl (95% CI: 0.054-0.138, p < 0.0001) increase in hemoglobin, while no association was seen among those without diabetes mellitus. CONCLUSION: After multivariable adjustment, there was a small positive association between PTH and hemoglobin among diabetics but not among nondiabetics.

Progression from Sustained BK Viruria to Sustained BK Viremia with Immunosuppression Reduction Is Not Associated with Changes in the Noncoding Control Region of the BK Virus Genome.

Changes in the BK virus archetypal noncoding control region (NCCR) have been associated with BK-virus-associated nephropathy (BKVAN). Whether sustained viremia, a surrogate for BKVAN, is associated with significant changes in the BK-NCCR is unknown. We performed PCR amplification and sequencing of (1) stored urine and (2) plasma samples from the time of peak viremia from 11 patients with sustained viremia who participated in a 200-patient clinical trial. The antimetabolite was withdrawn for BK viremia and reduction of the calcineurin inhibitor for sustained BK viremia. DNA sequencing from the 11 patients with sustained viremia revealed 8 insertions, 16 transversions, 3 deletions, and 17 transitions. None were deemed significant. No patient developed clinically evident BKVAN. Our data support, at a genomic level, the effectiveness of reduction of immunosuppression for prevention of progression from viremia to BKVAN.

Impact of hepatorenal syndrome and liver transplantation.

PURPOSE OF REVIEW: Hepatorenal syndrome (HRS) is an extremely detrimental complication of cirrhosis, with dismal survival in untreated patients. Continued advances in understanding the pathophysiology of HRS have improved HRS recognition and facilitated development of effective treatment strategies. In this article, we review current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver versus liver-kidney transplant in transplant candidates. RECENT FINDINGS: Published diagnostic criteria for HRS have improved early recognition and intervention in HRS. Increasing data support vasoconstrictor therapy for HRS reversal. Several randomized controlled trials clearly demonstrate efficacy of terlipressin therapy in HRS reversal; although comparable studies are lacking with norepinephrine, preliminary findings suggest that this regime may be the preferred alternative when terlipressin is unavailable for use. In transplant candidates without response to vasoconstrictor therapies, mounting evidence supports simultaneous liver-kidney transplantation if prolonged pretransplant dialysis is required. SUMMARY: Prompt identification and therapy initiation in transplant candidates with HRS may improve transplantation rates and posttransplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of simultaneous liver-kidney transplants in patients with HRS remains controversial and requires further analysis by the transplant community.

Role of alpha-1 blocker in expulsion of stone fragments after extracorporeal shock wave lithotripsy for renal stones.

BACKGROUND: Renal stone disease is a significant and worldwide health problem. Recent advances in stone management have allowed kidney stones to be treated using extracorporeal shock wave lithotripsy (ESWL), uretero-renoscopy (URS), and percutaneous nephrostolithotomy (PCNL). Recently, medical expulsion therapy (MET) has been investigated as a supplement to observation in an effort to improve spontaneous stone passage rates. PATIENTS AND METHODS: This study was a randomized, controlled, prospective study to determine whether the administration of Alpha-1-adrenergic receptor antagonists as an adjunctive medical therapy, increases the efficacy of ESWL to treat renal stones. Sixty patients with renal stones of 0.5-1.5 Cm in size (average size 1.2 Cm) were included in this study underwent ESWL followed by administration of Alpha-1-adrenergic receptor antagonists at department of Urology Liaquat National Hospital Karachi from Feb 2008 to Sept 2008. This was a comparative study and patients were divided into two groups. In group A patients received conventional treatment Diclofenac sodium, Anti Spasmodic (Drotverine HCl) as required and Proton Pump inhibitor (Omeprazole 20 mg) once daily after shock wave lithotripsy. In group B patients received alpha-1 blocker, Alfuzosin HCI 5 mg twice daily in addition to conventional treatment. All patients were instructed to drink a minimum of 2 litres water daily. Ultrasound guided Dornier Alpha Impact Lithotripter was utilised for shock wave lithotripsy. RESULTS: Of the 60 patients, 76.7% of those receiving Alfuzosin and 46.7% of controls had achieved clinical success at 1 month (p = 0.01). The mean cumulative diclofenac dose was 485 mg per patient in the Alfuzosin group and 768 mg per patient in the control group (p = 0.002). This difference was statistically significant. CONCLUSION: Alfuzosin therapy as an adjunctive medical therapy after ESWL is more effective than lithotripsy alone for the treatment of patients with large renal stones and is equally safe. It increases the expulsion rates of stones, decreases time to expulsion, and decreases need for analgesia during stone passage.

Cardiovascular risk in chronic kidney disease (CKD): the CKD-mineral bone disorder (CKD-MBD).

Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications, obtained through observational studies, demonstrate that vascular calcification and hyperphosphatemia are major cardiovascular risk factors. Mechanistic studies demonstrate that these two risk factors are related and that hyperphosphatemia directly stimulates vascular calcification. The role of hyperphosphatemia in stimulating vascular calcification in CKD is associated with a block to the skeletal reservoir function in phosphate balance due to excess bone resorption. This has led to the realization that renal osteodystrophy is linked to vascular calcification by disordered mineral homeostasis (phosphate) and that a multiorgan system fails in CKD, leading to cardiovascular mortality. In children with renal disease, the multiorgan system fails, just as in adults, but the outcomes have been less well studied, and perceptions of differences from adults are possibly incorrect. Vascular calcification and cardiovascular mortality are less prevalent among pediatric patients, but they are present. However, CKD-induced vascular disease causes stiffness of the arterial tree causing, in turn, systolic hypertension and left ventricular hypertrophy as early manifestations of the same pathology in the adult. Because of the role of the skeleton in these outcomes, renal osteodystrophy has been renamed as the CKD mineral bone disorder (CKD-MBD). This review, which focuses on the pediatric patient population, describes our current state of knowledge with regards to the pathophysiology of the CKD-MBD, including the new discoveries related to early stages of CKD. As a new necessity, cardiovascular function issues are incorporated into the CKD-MBD, and new advances in our knowledge of this critical component of the disorder will lead to improved outcomes in CKD.

The pathogenesis of vascular calcification in the chronic kidney disease mineral bone disorder: the links between bone and the vasculature.

Considerable scientific progress in the pathogenesis of vascular calcification that has accrued in recent years is reviewed in this article. Factors regulating mesenchymal cell differentiation and their role in the neointimal calcification of atherosclerosis and the vascular media calcification observed in chronic kidney disease and diabetes are discussed, as is the role of bone regulatory proteins in bone mineralization and vascular calcification. This includes recent studies related to fetuin-A, and the discovery of a new circulating hormone involved in regulating phosphate homeostasis and sensing skeletal hydroxyapatite precipitation. Finally, the relationship between skeletal mineralization and vascular mineralization is discussed in terms of their links, especially through serum phosphate concentrations.

Angiogenic gene cell therapy using suicide gene system regulates the effect of angiogenesis in infarcted rat heart.

BACKGROUND: Although angiogenic gene therapy has been reported to be effective in restoring ischemic heart function, there are several obstacles to its clinical application, such as unreliable efficiency of transfection and uncontrollable expression. We developed human HGF (hHGF)-producing cells that regulated hHGF production using the thymidine kinase gene of Herpes Simplex Virus (TK) and the Ganciclovir (GCV) system. We tested whether these cells induced and regulated angiogenic effects in infarcted myocardium. METHODS: NIH3T3 cells were stably transfected with an hHGF cDNA expression plasmid (NIH/HGF). Next, the NIH/HGF cells were stably transfected with TK (NIH/HGF/TK). The left anterior descending artery was ligated in the heart of severe combined immunodeficiency rats, and four materials were transplanted: 1) NIH/HGF (n=10), 2) NIH/HGF/TK, with orally administered GCV (n=10), 3) NIH3T3 (n=10), and 4) culture medium (n=10). RESULTS: In vitro, the proliferation of NIH/HGF/TK cells was suppressed by GCV. In vivo, significant increases in cardiac performance and angiogenesis were observed in the NIH/HGF and NIH/HGF/TK groups 4 weeks after transplantation. Although tumorous lesions were detected in the NIH/HGF group, their growth was completely controlled in the NIH/HGF/TK group. CONCLUSIONS: Angiogenic gene cell therapy using the TK-GCV suicide gene system induces and regulates angiogenesis under the control of cell growth, suggesting it as a promising system for therapeutic angiogenesis.

Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters.

OBJECTIVES: Cell therapy is a promising strategy for ischemic cardiomyopathy. However, the direct injection method has limitations for generalized cell delivery, especially in dilated cardiomyopathy (DCM). We hypothesized that a sheet-shaped myoblast graft would be superior to direct injection for improving cardiac performance in DCM. METHODS: Male 27-week-old BIO TO-2 (DCM) hamsters that showed moderate cardiac remodeling were used as recipients. Myoblasts isolated from BIO F1B hamsters were cultured on dishes coated with poly(N-isopropylacrylamide), a temperature-responsive polymer, and spontaneously detached as a sheet-shaped graft at 20 degrees C without enzymatic treatment. Three different therapies were conducted: (1) sheet-shaped myoblast graft implantation (S group, n=29); (2) myoblast injection (M group, n=28); and (3) sham operation (C group, n=28). In the S group, two sheet-shaped myoblast grafts were implanted on the left ventricle (LV) wall, and in the M group, myoblasts were injected into the right ventricle (RV) and LV walls. RESULTS: After the sheet-shaped myoblast grafts were implanted, echocardiography demonstrated that the dilated LV dimension was significantly reduced, whereas the hearts in other groups showed a progression of LV dilation. The fractional shortening in the M and C groups decreased significantly while that in the S group was maintained at the preoperative level for 3 months after the operation. Histological examination demonstrated that in the S group, the LV wall thickness was increased, with viable myoblasts, and myocardial fibrosis was decreased compared with the other groups. Immunohistochemical staining demonstrated alpha-sarcoglycan and beta-sarcoglycan expression on the basement membrane of the cardiomyocytes in the S group but not in the other groups. The life expectancy was significantly prolonged in the S group. CONCLUSION: Sheet-shaped myoblast graft implantation improved cardiac performance and prolonged life expectancy, associated with a reduction in myocardial fibrosis and re-organization of the cytoskeletal proteins in DCM hamsters. Thus, sheet-shaped autologous myoblast graft implantation may induce restoration of the heart in DCM.

Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium.

BACKGROUND: We hypothesized that tissue-engineered contractile cardiomyocyte sheets without a scaffold would show histological and electrical integration with impaired myocardium, leading to the regeneration of infarcted myocardium. METHODS: Neonatal rat cardiomyocytes were cultured on Poly(N-isopropylacrylamide)-grafted polystyrene dishes and detached as a square cell sheet at 20 degrees C. Two sheets were stacked to make thicker contractile cardiac sheets. In cross-section, the stacked sheets looked like homogeneous heart-like tissue. Two weeks after rats were subjected to left anterior descending (LAD) ligation, two treatments were conducted: 1) cardiomyocyte sheet implantation (T group, n=10), and 2) fibroblast sheet implantation (F group, n=10). The control group underwent no additional treatment (C group, n=10). RESULTS: Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T group 2, 4, and 8 weeks after implantation. The cardiomyocyte sheets became attached to the infarcted myocardium, showed angiogenesis, expressed connexin-43, and appeared as homogeneous tissue in the myocardium Electrophysiological experiments showed a QRS complex with one peak in the treated scar area in the T group, but two peaks, indicative of branch block, in that of the other groups. Furthermore, the threshold for pacing of the recipient heart was lower in the T group than in the other groups. CONCLUSIONS: Cardiomyocyte sheets integrated with the impaired myocardium and improved cardiac performance in a model of ischemic myocardium. Techniques using such tissue-engineered cell sheets are introducing the promising concept of tissue cardiomyoplasty to the field of regenerative medicine.

Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets.

OBJECTIVES: Autologous skeletal myoblast cell transplantation by means of the injection method is subject to the loss of intercellular communication, extracellular matrix, and cell numbers. We hypothesize that the implantation of skeletal myoblast cell sheets might be more advantageous in repairing the impaired heart by providing uniform and stable cell delivery with less cell loss and without disrupting the cell-cell microenvironment. METHODS: Left anterior descending coronary artery-ligated Lewis rat hearts (2 weeks, total n = 173) received 1 x 10(7) autologous skeletal myoblasts by means of cell transplantation either through myoblast injection or implantation of 2 monolayer-constructed myoblast sheets (5 x 10(6) cells per sheet) or through medium injection. Myoblast sheets were constructed with temperature-responsive, polymer-grafted cell-culture dishes, which release the confluent cells from the dish surface at less than 20 degrees C. RESULTS: Echocardiographic results indicated higher improvement of cardiac performance in the myoblast sheet group than among the other groups until 8 weeks after cell transplantation. Histologic comparison revealed greater cellularity and abundant widespread neocapillaries within the noticeable uniform thickened wall in myoblast sheet group hearts only. Fibrosis was substantially reduced with skeletal myoblast sheet implantation compared with skeletal myoblast cell injection. Obviously higher numbers of hematopoietic stem cells (c-kit, stem cell antigen 1, and CD34) were observed in the myoblast sheet group infarct heart region. Reverse transcription-polymerase chain reaction results showed expression of stromal-derived factor 1, hepatocyte growth factor, and vascular endothelial growth factor as follows: myoblast sheets > myoblast injection > control. CONCLUSIONS: Myoblast sheets repaired the impaired myocardium, reduced fibrosis, and prevented remodeling in association with recruitment of hematopoietic stem cells through the release of stromal-derived factor 1 and other growth factors. Our experiment indicates a therapy for patients with severe heart failure.

Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy.

OBJECTIVES: Cellular cardiomyoplasty with isolated skeletal myoblasts and bone marrow mononuclear cells is an encouraging therapeutic strategy for heart failure. We investigated the achievements accomplished with combined cell therapy of skeletal myoblast and bone marrow mononuclear cell transplantation to the ischemic canine myocardium. METHODS: Autologous skeletal myoblasts (1 x 10(8)) and autologous bone marrow mononuclear cells (3 x 10(6)) were injected directly into the damaged myocardium of canine hearts that had undergone 2 weeks of left anterior descending coronary artery ligation. Treatment groups were as follows: skeletal myoblasts plus bone marrow mononuclear cells (combined cell therapy, n = 4), myoblasts (n = 4), bone marrow mononuclear cells (n = 4), and medium only (n = 4). In similarly designed supporting experiments, angiogenic factor expression was evaluated by enzyme-linked immunosorbent assay after cell transplantation in rat hearts that had undergone left anterior descending coronary artery ligation. RESULTS: Four weeks after cell implantation, echocardiography demonstrated better cardiac performance with reduced left ventricular dilation and significantly improved ejection fraction in the combined cell therapy group compared with that seen in the other groups (pretreatment, 37.7% +/- 1.1%, vs combined cell therapy, 55.4% +/- 8.6%; myoblasts, 47.4% +/- 7.4%; bone marrow mononuclear cells, 44.4% +/- 6.7%; medium only [control], 34.4% +/- 5.4%; P < .05). A significantly high number of neovessels were observed in the group receiving combined cell therapy only (combined cell therapy, 45.5 +/- 12 x 10(2)/mm2; myoblasts, 26.5 +/- 8 x 10(2)/mm2; bone marrow mononuclear cells, 30.7 +/- 15 x 10(2)/mm2; medium only [control], 7.1 +/- 1 x 10(2)/mm2; P < .05). Immunostained sections expressed the skeletal specific marker myosin heavy chain, although they did not express the cardiac specific marker troponin T. Results of enzyme-linked immunosorbent assay showed the highest expression of vascular endothelial growth factor (combined cell therapy, 2.9 +/- 0.7 ng/g tissue; myoblasts, 0.24 +/- 0.7 ng/g tissue; bone marrow mononuclear cells, 1.9 +/- 0.2 ng/g tissue; medium only [control], 0.19 +/- 0.004 ng/g tissue; P < .05) and hepatocyte growth factor in the combined cell therapy hearts. CONCLUSIONS: Combined autologous cellular therapy induced both myogenesis and angiogenesis with enhancement of cardiac performance and reduction of cardiac remodeling, suggesting a capable strategy for treating severe ischemic cardiomyopathy clinically.