Late results of combined mitral valve replacement and coronary bypass surgery

The incremental risk of coronary bypass surgery was analyzed in 718 patients undergoing mitral valve replacement between 1971 and 1983. Ninety-eight patients (14%) had significant coronary artery disease requiring coronary bypass surgery. In 70 of these patients, the origin of the mitral valve disease was nonischemic, whereas 28 patients had ischemic mitral regurgitation unsuitable for conservative valve surgery. There were six operative deaths (9%) and four perioperative myocardial infarctions (6%) after mitral valve replacement and coronary bypass surgery for nonischemic mitral valve disease. Operative mortality was related to low output cardiac failure before operation or perioperative myocardial infarction. Actuarial curves predict survival (+/- standard error) of 55 +/- 7% at 5 years and 43 +/- 8% at 10 years. Preoperative functional class was the only significant predictor of long-term survival in this group (p less than 0.05). The actuarial survival of the 620 patients without coronary artery disease who underwent mitral valve replacement alone was 63 +/- 3% at 10 years. This was significantly better than that of the 70 patients who underwent mitral valve replacement and coronary bypass surgery for nonischemic mitral valve disease (p less than 0.001). Conversely, 5 year survival of the 28 patients with ischemic mitral regurgitation was 43 +/- 10%. This confirms the negative detrimental effect of an ischemic origin of mitral valve disease on survival after mitral valve replacement and coronary bypass surgery (p less than 0.0001).     

Comparison of open live donor nephrectomy, laparoscopic live donor nephrectomy, and hand-assisted live donor nephrectomy: a cost-minimization analysis

BackgroundLive donor kidney transplantation is the treatment of choice for end-stage renal disease. Open donor nephrectomy (ODN) was the standard until the introduction of the laparoscopic donor nephrectomy (LDN) in 1995. Hand-assisted laparoscopic donor nephrectomy (HALDN) was added shortly thereafter. The laparoscopic techniques are associated with increased operating room times and equipment costs; however, these techniques speed patient return to normal activity. The aim of this study is to evaluate the cost of these techniques.Materials and MethodsA decision analysis model was developed to simulate outcomes for donors undergoing ODN, LDN, and HALDN. Outcomes were simulated from both the institutional perspective (IP) and the societal perspective (SP). Baseline values and ranges were determined from a systematic review of the literature. Sensitivity analyses were conducted to test model strength.ResultsFrom the IP, ODN is the least costly strategy with a cost of $11,000, while the cost is $15,200 for HALDN and $15,800 for LDN. From the SP, HALDN is the least costly strategy costing $27,800, while the cost for LDN is $29,000 and for ODN is $41,000. In sensitivity analysis, ODN only became the dominant strategy if the days till return to work exceeded 58 in the HALDN strategy. LDN and HALDN were nearly equivalent as the rate of open conversion of LDN approached zero.ConclusionsHALDN is the least costly donor nephrectomy strategy, especially from the SP. The primary determinants of cost in this model are conversion to open and days till return to work.     

Altered ATP-dependent mitochondrial Ca2+ uptake in cold ischemia is attenuated by ruthenium red

BACKGROUND: Graft dysfunction as a result of preservation injury remains a major clinical problem in liver transplantation. This is related in part to accumulation of mitochondrial calcium (Ca(2+)), which has been linked to activation of proapoptotic factors. We hypothesized that cold ischemia increases mitochondrial Ca(2+) uptake in a concentration dependent fashion and that ruthenium red (RR) will attenuate these changes by inhibiting the mitochondrial Ca(2+) uniporter. METHODS: Rat livers perfused with cold University of Wisconsin (UW) solution (4 degrees C) with or without RR (10 microM) via the portal vein (n = 3 per group) were processed immediately (no ischemia) or after 24 h cold-storage (24 h cold ischemia). Mitochondria were separated by differential centrifugation, and adenosine triphosphate (ATP)-dependent (45)Ca(2+) uptake was determined in the presence of ATP (5 mM), adenosine diphosphate (ADP), or adenosine 5'-beta,gamma-imidotriphosphate (AMP-PNP); variable concentrations of extramitochondrial (45)Ca(2+) were used. All measurements were performed in triplicate. Student's t test with P < 0.05 was taken as significant. RESULTS: Our data demonstrate the following: 1) ATP-dependent (45)Ca(2+) uptake in mitochondria separated from livers following 24 h of cold ischemia in UW alone was higher than in mitochondria isolated from non-ischemic livers; the increased uptake was dependent on the concentration of (45)Ca(2+) in the incubation buffer. 2) There was no difference in ATP-dependent (45)Ca(2+) uptake between nonischemic mitochondria and those separated from livers stored in UW-RR for 24 h. 3) (45)Ca(2+) uptake in mitochondria from livers subjected to 24 h of cold ischemia in UW-RR was significantly lower compared to those from livers stored in UW alone when (45)Ca(2+) concentrations were greater than 1 microM. CONCLUSION: 1) Cold ischemia affects mitochondrial Ca(2+) handling, especially when it is challenged by high extramitochondrial Ca(2+) concentrations. 2) The addition of RR in preservation solution attenuates the effects of cold ischemia on mitochondrial Ca(2+) handling. 3) Inhibition of mitochondrial Ca(2+) uniporter with RR protects mitochondria from Ca(2+) overload at high Ca(2+) concentrations. These findings may offer a potentially effective strategy for prevention of ischemia-reperfusion injury in liver transplantation.     

Strabismus in adults with uveal melanoma following episcleral plaque brachytherapy

PURPOSE: To ascertain the incidence of persistent strabismus in patients treated with plaque brachytherapy and its subsequent treatment. METHODS: A single center retrospective case note review of adult patients with persistent diplopia or strabismus following plaque brachytherapy for all types of intraocular tumors between 1996 and 2004. RESULTS: A total of 929 consecutive adults underwent plaque brachytherapy during the study period at a single center. Sixteen patients (1.7%) with treated uveal melanoma developed persistent diplopia or strabismus. In 11 patients (69%) the timing of onset was in the first year, in 2 (13%) in the second year, and one each (6% each) in years 5, 7, and 8. Two patients (13%) did not require any intervention. Fourteen patients (88%) required treatment: 7 (50%) were treated with prisms only, 3 (21%) underwent botulinum toxin (BTXA) injections, and 4 (29%) were treated with extraocular muscle surgery (3 required one operation and one required 2 procedures). CONCLUSIONS: The incidence of ocular motility disorders following plaque brachytherapy in our cohort was 1.7% over 8 years and we include this in the consent process for conservative treatment of intraocular tumors. Options for treatment for persistent diplopia or strabismus include prisms, botulinum toxin injection, or surgery.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.