Search PubMed⌕ Search

Biomedical subjects

Robert M Mentzer

Publications and source records attributed to Robert M Mentzer.

32 records · Page 2Linked to original sources
PubMed2003

The intermediary metabolite pyruvate attenuates stunning and reduces infarct size in in vivo porcine myocardium.

The intermediary metabolite pyruvate has been shown to exert significant beneficial effects in in vitro models of myocardial oxidative stress and ischemia-reperfusion injury. However, there have been few reports of the ability of pyruvate to attenuate myocardial stunning or reduce infarct size in vivo. This study tested whether supraphysiological levels of pyruvate protect against reversible and irreversible in vivo myocardial ischemia-reperfusion injury. Anesthetized, open-chest pigs (n = 7/group) underwent 15 min of left anterior descending coronary artery (LAD) occlusion and 3 h of reperfusion to induce stunning. Load-insensitive contractility measurements of regional preload recruitable stroke work (PRSW) and PRSW area (PRSWA) were generated. Vehicle or pyruvate (100 mg/kg i.v. bolus + 10 mg x kg(-1) x min(-1) intra-atrial infusion) was administered during ischemia and for the first hour of reperfusion. In infarct studies, pigs (n = 6/group) underwent 1 h of LAD ischemia and 3 h of reperfusion. Group I pigs received vehicle or pyruvate for 30 min before and throughout ischemia. In group II, the infusion was extended through 1 h of reperfusion. In the stunning protocol, pyruvate significantly improved the recovery of PRSWA at 1 h (50 +/- 4% vs. 23 +/- 3% in controls) and 3 h (69 +/- 5% vs. 39 +/- 3% in controls) reperfusion. Control pigs exhibited infarct sizes of 66 +/- 1% of the area at risk. The pyruvate I protocol was associated with an infarct size of 49 +/- 3% (P < 0.05), whereas the pyruvate II protocol was associated with an infarct size of 30 +/- 2% (P < 0.05 vs. control and pyruvate I). These findings suggest that pyruvate attenuates stunning and decreases myocardial infarction in vivo in part by reduction of reperfusion injury. Metabolic interventions such as pyruvate should be considered when designing the optimal therapeutic strategies for limiting myocardial ischemia-reperfusion injury.

Animals↗
PubMed2003

Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection.

Although the mechanisms underlying ischemia/reperfusion injury remain elusive, evidence supports the etiologic role of intracellular calcium overload and oxidative stress induced by reactive oxygen species. Activation of the sodium hydrogen exchanger (NHE) is associated with intracellular calcium accumulation. Inhibition of the NHE-1 isoform may attenuate the consequences of this injury. Although there is strong preclinical and early clinical evidence that NHE inhibitors may be cardioprotective, definitive proof of this concept in humans awaits the results of ongoing clinical trials.

Amiloride↗
PubMed2003

Molecular genetics and management strategies in hereditary cancer syndromes.

The origin, characteristics, and lifetime risk for the following five types of hereditary cancer (HCS) syndromes are briefly described in this review: hereditary breast and ovarian cancer (HBOC) syndrome, familial adenomatous polyposis (FAP), and hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, hereditary diffuse gastric cancer (HDGC) syndrome, and medullary thyroid carcinoma (MTC). Most are caused by mutations in tumor suppressor genes. In HCS, a single copy of the mutated tumor suppressor gene is inherited, and mutation of the second wild type allele of the gene is required for tumorigenesis. Patients with HCS have a higher than normal risk of a second malignancy. Management strategies to address increased cancer risk in HCS include genetic counseling and testing, targeted surveillance, chemoprevention, and prophylactic surgery. Genetic testing for high-risk family members is strongly recommended. Available data indicate surgical prophylaxis is more successful than surveillance in reducing cancer risk in carriers of BRCA, CDH1, APC, and RET mutation.

Genetic Counseling↗
PubMed2003

Nasal reconstruction.

Nasal defects commonly seen by plastic surgeons result from trauma, burn injury, or tumor resection. While nasal reconstruction is one of the oldest plastic surgery endeavors, techniques continue to evolve and be modified. Grafts and local flaps are used in smaller defects. Larger and complex defects are best reconstructed following the aesthetic unit principle. These defects also require replacement of all lost tissues to provide nasal lining, skeletal support, and skin coverage. Careful analysis of the defect and reliance on these general guidelines will allow for less obvious nasal reconstruction and a more natural appearance and function.

Esthetics↗
PubMed2002

Effects of in vivo myocardial ischemia and reperfusion on interstitial nitric oxide metabolites.

BACKGROUND: There have been numerous studies examining the role of nitric oxide (NO) in myocardial ischemia-reperfusion injury; however, few studies have included measurements of NO or related reactive nitrogen species. The purpose of this study was to determine the effects of in vivo regional myocardial ischemia on interstitial fluid (ISF) reactive nitrogen species. METHODS: Open chest pigs were submitted to one of three protocols: (1) 15 minutes coronary occlusion and 2 hours reperfusion, (2) 60 minutes coronary occlusion and 2 hours reperfusion, or (3) two-cycle ischemic preconditioning (IPC) followed by prolonged ischemia and 2 hours reperfusion. The stable NO metabolites, nitrite plus nitrate (NOx), in cardiac microdialysis samples were measured by ozone chemiluminescence. RESULTS: NOx concentration decreased 40% +/- 6% (p < 0.05) during brief ischemia but returned to baseline during reperfusion. Dialysate NOx levels decreased further after 60 minutes ischemia (60% +/- 3% of baseline, p < 0.01) but reperfusion dialysate NOx concentration increased 34% +/- 9% above baseline (p < 0.05). Preconditioning did not increase dialysate NOx but did accelerate the ischemia-induced decrease in NOx levels (p < 0.05). Reperfusion NOx levels in preconditioned pigs were significantly lower than in nonpreconditioned pigs (p < 0.05). CONCLUSIONS: These results suggest that ischemia is associated with decreased ISF NOx concentration. Reperfusion NOx levels are increased after prolonged ischemia, an effect that is significantly blunted by ischemic preconditioning.

Animals↗
PubMed2002

Aspirin and postoperative bleeding after coronary artery bypass grafting.

OBJECTIVE: To evaluate the relationship between aspirin ingestion and postoperative bleeding complications, and to test the hypothesis that there is a subset of patients who are aspirin hyperresponders with a proclivity toward platelet dysfunction. SUMMARY BACKGROUND DATA: Despite numerous retrospective and prospective analyses, it is still controversial as to whether aspirin ingestion before coronary artery bypass grafting (CABG) is associated with significant postoperative bleeding. METHODS: Between January 1995 and December 1999, the records of 2,606 consecutive patients undergoing CABG were reviewed to identify patients with a history of aspirin ingestion up until the time of surgery. Aspirin ingestion was correlated with postoperative blood transfusion using multivariate analysis. In a subset of preoperative aspirin users (n = 40), bleeding times were measured before and after aspirin use. Flow cytometry was performed in another cohort of patients with known heart disease (n = 30) to determine the effect of aspirin on platelet surface receptors. RESULTS: During the 5-year study period, 63% of the CABG patients were identified as aspirin users. Among these, 23.1% required blood transfusions compared with 19% for the nonusers. Non-red blood cell transfusions were more common in aspirin users, as was reexploration for bleeding. Stratification of these results according to the frequency of aspirin use showed that aspirin is an independent multivariate predictor of postoperative blood transfusion only in high-risk patients. In the prospective studies, aspirin treatment resulted in a significant increase in the template bleeding time, an increase in platelet PAR-1 thrombin receptor activity, and a decrease in the binding of platelets to monocytes. CONCLUSIONS: The findings support the hypothesis that aspirin is associated with a greater likelihood of postoperative bleeding. A platelet function testing algorithm that combines preoperative risk factor assessment, template bleeding times, and flow cytometry may allow the identification of aspirin hyperresponders who are at increased risk for bleeding.

Aspirin↗
PubMed2002

The National Surgical Quality Improvement Program in non-veterans administration hospitals: initial demonstration of feasibility.

OBJECTIVE: To assess the feasibility of implementing the National Surgical Quality Improvement Program (NSQIP) methodology in non-VA hospitals. SUMMARY BACKGROUND DATA: Using data adjusted for patient preoperative risk, the NSQIP compares the performance of all VA hospitals performing major surgery and anonymously compares these hospitals using the ratio of observed to expected adverse events. These results are provided to each hospital and used to identify areas for improvement. Since the NSQIP's inception in 1994, the VA has reported consistent improvements in all surgery performance measures. Given the success of the NSQIP within the VA, as well as the lack of a comparable system in non-VA hospitals, this pilot study was undertaken to test the applicability of the NSQIP models and methodology in the nonfederal sector. METHODS: Beginning in 1999, three academic medical centers (Emory University, Atlanta, GA; University of Michigan, Ann Arbor, MI; University of Kentucky, Lexington, KY) volunteered the time of a dedicated surgical nurse reviewer who was trained in NSQIP methodology. At each academic center, these nurse reviewers used NSQIP protocols to abstract clinical data from general surgery and vascular surgery patients. Data were manually collected and then transmitted via the Internet to a secure web site developed by the NSQIP. These data were compared to the data for general and vascular surgery patients collected during a concurrent time period (10/99 to 9/00) within the VA by the NSQIP. Logistic regression models were developed for both non-VA and VA hospital data. To assess the models' predictive values, C-indices (0.5 = no prediction; 1.0 = perfect prediction) were calculated after applying the models to the non-VA as well as the VA databases. RESULTS: Data from 2,747 (general surgery 2,251; vascular surgery 496) non-VA hospital cases were compared to data from 41,360 (general surgery 31,393; vascular surgery 9,967) VA cases. The bivariate relationships between individual risk factors and 30-day mortality or morbidity were similar in the non-VA and VA patient populations for over 66% of the risk variables. C-indices of 0.942 (general surgery), 0.915 (vascular surgery), and 0.934 (general plus vascular surgery) were obtained following application of the VA NSQIP mortality model to the non-VA patient data. Lower C-indices (0.778, general surgery; 0.638, vascular surgery; 0.760, general plus vascular surgery) were obtained following application of the VA NSQIP morbidity model to the non-VA patient data. Although the non-VA sample size was smaller than the VA, preliminary analysis suggested no differences in risk-adjusted mortality between the non-VA and VA cohorts. CONCLUSIONS With some adjustments, the NSQIP methodology can be implemented and generates reasonable predictive models within non-VA hospitals.

Feasibility Studies↗
PubMed2002

Cardiac myocyte adenosine A2a receptor activation fails to alter cAMP or contractility: role of receptor localization.

Adenosine A2a receptors are found in coronary vascular tissue although, their presence in myocardium is subject to investigation. Although there have been numerous studies on adenosine A2a receptor agonist effects on contractility and cAMP levels in ventricular myocytes, these have yielded conflicting results. Negative pharmacological studies have even led to the conclusion that A2a receptors are not present in cardiac myocytes. The purpose of this study was to determine whether A2a receptors are expressed in rat ventricular myocytes and what physiological effects are mediated via activation of these receptors. Western blot analysis with a polyclonal antibody raised against a peptide sequence specific to the carboxy terminus of the A2a receptor revealed the presence of a band at approximately 45 kDa. However, the immunoreactivity was located in the nonmembrane fraction of the cell lysate. The membrane fraction only exhibited an immunoreactive band > or = 50 kDa. Treatment of isolated myocytes with the adenosine A2a agonist 2-[4-[(2-carboxyethyl)-phenyl]ethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680) exerted no effects on cAMP levels or myocyte twitch amplitude. These results indicate that although rat ventricular myocytes appear to express adenosine A2a receptors, stimulation with an A2a agonist exerts no functional effects, possibly because of the subcellular localization of the A2a receptor.

Adenosine↗
PubMed2002

Heart transplants: need versus availability.

Every year in the US heart failure accounts for roughly 60,000 deaths and is the contributing cause in another 300,000 deaths. The two-year survival rate for patients with advanced heart failure is less than 50%, with the incidence of death at 106 in 100,000, more than that for AIDS and breast cancer combined. As these figures attest, the economic burden is quite extensive. The Centers for Medicaid and Medicare estimate a cost of $10 billion a year for this diagnosis alone. Both the human and financial cost have impelled doctors and researchers to improve their capacity to treat heart failure both through conventional methods and, in the most serious cases, through transplantation. Many pioneers have either directly or indirectly contributed to our ability to treat heart failure. Among these early researchers were: Dr Alexis Carrel, who was awarded the Nobel Prize for his pioneering work in vascular anastomosis; Dr John Gibbon, who did important work in the development of the cardiopulmonary bypass machine; Drs Normal Shumway, Richard Lower, and Demikhov, who developed heart transplant procedures in the canine model; Dr Christian Barnaard, who performed the first technically successful human-to-human heart transplant (1967); and Dr Thomas Hardy, who attempted the first xenotransplant (1963). While these achievements were phenomenal advances, long-term survival for transplant recipients was minimal until progress was made in immunosuppressive techniques.

Cost-Benefit Analysis↗
PubMed2002

Oral/pharyngeal squamous carcinoma: treatment strategies.

Oral/pharyngeal squamous carcinoma is a largely preventable problem. Most patients have significant tobacco and alcohol histories. Treatment reflects the locally and regionally aggressive nature of these tumors. In advanced disease neither surgery nor radiation therapy can be used as a primary modality, and often combined treatment is necessary. Chemotherapy has a less well-defined role, but is increasing control rates in advanced tumors.

Biopsy, Needle↗