Risk stratification in patients with remote prior myocardial infarction using rest-stress myocardial perfusion spect: prognostic value and impact on referral to early catheterization

BACKGROUND: Little is known about the prognostic value of myocardial perfusion single photon emission computed tomography (SPECT) in patients with remote prior myocardial infarction (MI). METHODS AND RESULTS: We identified 1413 consecutive patients with remote prior MI who underwent rest-stress myocardial perfusion SPECT. Semiquantitative visual analysis of 20 SPECT segments was used to define the summed stress, rest, and difference scores. The number of non-reversible segments was used as an index of infarct size. During follow-up (>or=1 year), 118 hard events occurred: 64 cardiac deaths (CDs) and 54 recurrent MIs. Annual CD and hard event rates increased significantly as a function of SPECT abnormality. For summed stress scores less than 4, 4 to 8, 9 to 13, and more than 13, the annual CD rates were 0.4%, 0.9%, 1.7%, and 3.5%, respectively (P =.002). Patients with small MI (<4 non-reversible segments) and no or mild ischemia (summed difference score or=4 non-reversible segments) had moderate to high annual CD rates (3.7%-6.6%) regardless of the extent of ischemia. Nuclear testing added incremental prognostic information to pre-scan information. Compared with a strategy in which all patients are referred to catheterization, a strategy that referred only those patients with a risk for CD of greater than 1% by myocardial perfusion SPECT resulted in a 41.6% cost savings. CONCLUSIONS: Myocardial perfusion SPECT adds incremental value to pre-scan information and is highly predictive and cost-efficient in the risk stratification of patients with remote prior MI. Patients with normal or mildly abnormal scan results or small MI in combination with absent or mild ischemia have a low risk for CD.     

Cellular cytotoxicity mediated by granule-depleted neutrophil cytoplasts

Summary Neutrophil-derived nucleus- and granule-free cytoplasts, consisting of cytosol enclosed by an intact plasma membrane, were able to destroy ⁵¹Cr-labelled ox red blood cells (ORBC) in the presence of phorbol myristate acetate (PMA). The slope of the target cell lysis vs the log of the cytoplast number was similar to that observed with neutrophils as effector cells. Nevertheless, a number of cytoplasts 60–80 times higher than that of neutrophils was required to obtain a common level of cytotoxicity. The ability of cytoplasts and neutrophils to lyse ORBC was completely abolished by catalase and unaffected by superoxide dismutase and mannitol, suggesting the involvement of hydrogen peroxide in the target cell damage. Addition of myeloperoxidase (MPO) to cytoplasts increased lysis. The MPO inhibitor azide significantly reduced the cytolysis by neutrophils, but not the cytolysis by cytoplasts, except when experiments were carried out in the presence of MPO. The results indicate that neutrophil cytosol and plasma membrane represent the basic requirement for the PMA-dependent cytolytic process, whereas MPO behaves as a device to amplify lysis.     

β-thromboglobulin and fibrinopeptide a in diabetes mellitus as markers of vascular damage

Summary β-thromboglobulin (BTG) and fibrinopeptide A (FpA) were studied in 68 non-insulin dependent diabetic patients (NIDD) aged 32–81 with a mean duration of diabetes of 9±0.8 SEM years and 44 healthy controls, comparable for age and sex. Diabetic patients were subdivided into subsets according to the presence of microvascular disease, macrovascular disease or the absence of these lesions. Patients with microangiopathy (micro- and/or macrovascular disease) had higher HbA (p<0.01), higher blood pressure (p<0.05) than both healthy controls and uncomplicated diabetics. Plasma BTG was higher in diabetic patients than in healthy controls (p<0.02), and was higher in complicated than in non-complicated diabetic subjects. Fpa was higher in complicated than in non-complicated diabetes (p<0.05). No differences were observed between the two subsets of complicated patients. In conclusion, we have shown that increased plasma- and platelet-BTG levels are present in non-insulin dependent diabetic subjects, with normal renal function and that plasma BTG is higher in patients with than in those without vascular disease. Fibrinopeptide A, a sensitive marker ofin vivo fibrin formation, was significantly increased in NIDD with vascular complications. This study was supported by the Juvenile Diabetes Foundation Grant N. 184066 and by the National Research Council of Italy,Progetto Finalizzato di Medicina Preventiva e Riabilitativa, Sottoprogetto 4.     

Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer

BACKGROUND: We have previously reported that the glial cell-derived neurotrophic factor (GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to determine whether GDNF regulates the expression and activation of matrix metalloproteinase-9 (MMP-9) in human pancreatic cancer cells. METHODS: We used human pancreatic cancer cell line MIA PaCa-2. The effect of GDNF on mRNA and protein expression was measured by Northern blot, Western blot and enzyme-linked immunosorbent assay. MMP proteolytic activity was detected by gelatin zymography. To determine which intracellular pathways were involved, we used the following inhibitors: tyrosine kinase inhibitor Genistein, MEK-1 inhibitor PD98059 and PI3-K inhibitor Wortmannin. RESULTS: GDNF increased MMP-9 mRNA and protein expression in MIA PaCa-2 cells in a dose-dependent manner. Treatment with GDNF enhanced gelatinolytic activity of the pro and active form of MMP-9. Inhibitor experiments showed that the expression and activity of pro MMP-9 was totally inhibited by Genistein and partially by Wortmannin, whereas PD98059 had no effect. All three compounds inhibited the activity of the active form of MMP-9. CONCLUSIONS: GDNF upregulates the expression and enzymatic activity of MMP-9 through different signaling pathways in MIA PaCa-2. These findings suggest that GDNF modulates MMP-9 expression and activation, and this may promote pancreatic cancer invasion.     

Right living donor liver transplantation: an option for adult patients: single institution experience with 74 patients

OBJECTIVE: To present an institutional experience with the use of right liver grafts in adult patients and to assess the practicability and efficacy of this procedure by analyzing the results. SUMMARY BACKGROUND DATA: Living donor liver transplantation (LDLT) for the pediatric population has gained worldwide acceptance. In the past few years, LDLT has also become feasible for adult patients due to technical evolution in hepatobiliary surgery and increased experience with reduced-size and split-liver transplants. Nevertheless, some graft losses remain unexplained and are possibly due to unrecognized venous outflow problems. METHODS: From April 1998 to September 2002, we performed 74 right LDLTs (segments 5-8). The 74 donors were selected from 474 candidates according to standard protocol. The median age of the donors was 35 years (range 18-58 years) and 51 years (range 18-64 years) in recipients. Standard and extended indications for transplantation were considered. Over the period reported, technical modifications in the bile duct anastomosis (duct-to-duct, end-to-end, or end-to-side) and a new graft implantation technique that provides maximized venous outflow, leading to outcome improvement, were developed. RESULTS: 64.9% of patients had liver cirrhosis and 35.1% had malignancy. While 44 donors (59.5%) presented an uneventful postoperative course, 27% minor (pleural effusion, pneumonia, venous thrombosis, wound infection, incisional hernia) and 13.5% major (biliary leakage, death of a donor due to unrecognized hereditary liver disease, and consecutive liver insufficiency) complications were documented. In recipients, 23% biliary complications and 6.8% hepatic artery thrombosis occurred. The overall patient and graft survival rate after 1 year was 79.4% and 75.3%, respectively. In cases with extended indication, the patient survival rate was 74% and the graft survival rate 68% at 12 months. Using technical modifications in the last 10 recipients, including 2 critically decompensated cirrhotics, the survival rate was 100% at a median follow-up of 3.5 months. CONCLUSIONS: In our transplant program, living donor liver transplantation has become a standard option in the adult patient population. The critical issue of this procedure is donor morbidity. Technical improvements in the harvesting and implantation of right grafts can also offer hope to patients with challenging forms of end-stage liver disease or malignant liver tumors.     

Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference?

BACKGROUND: Acute renal failure (ARF), requiring dialysis (ARF-d), develops in 1-5% of patients undergoing cardiac surgery and is associated with higher in-hospital mortality. Age is one of the known risk factors for the development of ARF. As the ageing population is increasing, the nephrologist will be faced with a large population of elderly patients requiring dialysis following cardiac surgery. The aim of our study was to evaluate the influence of age on and the risk factors for in-hospital mortality. METHODS: Eighty-two patients with ARF following cardiac surgery and requiring dialysis between January 1997 and October 2001 were included. Two groups of patients were studied: the younger population (<70 years, 42 patients, mean age 59+/-10) and an elderly population (>/=70 years, 40 patients, mean age 76+/-4). Severity of disease was evaluated using the SAPS (Simplified Acute Physiology Score), the Liano score and the SHARF (Stuivenberg Hospital Acute Renal Failure) score. RESULTS: Overall mortality in the population with ARF-d was 56.1%. No difference in mortality rate was found between the younger (61.9%) and elderly patient group (50.0%). The two groups were very similar in baseline and procedural characteristics with exception of body weight (P=0.02) and preoperative glomerular filtration rate (P=0.0001). No significant difference was found in the scoring systems between the old and the young (SAPS P=0.52; Liano P=0.96; SHARF T0 P=0.06; SHARF T48 P=0.15). Mortality in the elderly was significantly correlated with hypotension before starting renal replacement therapy (RRT) (P=0.002), mechanical ventilation (P=0.002), presence of multiorgan failure (MOF) (P=0.0001) and higher scores in the severity models (SAPS: P=0.01; Liano: P<0.0001 and SHARF: P<0.0001). CONCLUSION: The outcome in the elderly requiring dialysis due to ARF post-cardiac surgery is comparable with the outcome in a younger population. No significant difference was found in severity of disease between the elderly and the younger. Variables predicting mortality in the elderly are the presence of MOF, mechanical ventilation and hypotension 24 h before starting RRT. These findings indicate that at the time the nephrologist is called for an elderly patient requiring dialysis due to ARF following cardiac surgery, age per se is not a reason to withhold RRT.     

Expansion of natural killer cells in patients with head and neck cancer: detection of "noninhibitory" (activating) killer Ig-like receptors on circulating natural killer cells

BACKGROUND: In a group of patients with head and neck cancers (H&NC), the expansion of the population of CD3-,CD16+ natural killer (NK) cells in the peripheral blood was studied. METHODS: Cytofluorimetric analysis of the expression of killer Ig-like receptors (KIR, namely p58.1, p58.2, p58.3, p70, and p140) and CD94-NKG2a was performed. Cytolytic activities were studied using 51Cr release assay. T and NK cell cloning was performed using limiting dilution culture conditions. Cytokine production was analyzed using commercial enzyme immunoassays. RESULTS: Phenotypic analysis showed that the expanded populations were heterogeneous. Even in the presence of a large number of circulating NK cells, "nonspecific" cytolytic capacities were heavily reduced, whereas cytolytic capacity related to T cells was virtually normal. Unlike NK cell clones derived from healthy donors, most NK cells derived from H&NC patients expressed surface "activating" NK cell receptors (KAR) for HLA, detected by use of a redirected cytolytic assay. Analysis of the CD4+ subpopulation at the clonal level demonstrated that they had a severe proliferative defect. CONCLUSION: These experimental data indicated that H&NC patients have a polyclonal expansion of functionally deficient NK cells expressing KAR. In addition, the proliferative capacity of patients' "helper" cells was strongly inhibited, thus accounting for a severe impairment of cytolytic activity of the expanded NK cells.     

Effects of heart rate on phasic Y-graft blood flow and flow reserve in patients with complete arterial myocardial revascularizaton: an intravascular Doppler catheter study.

OBJECTIVE: It is not well established whether the blood flow of arterial composite Y-grafts can efficiently respond to the flow demand of the coronary system early postoperatively. The aim of this study was to evaluate if soon after the operation, arterial composite Y-grafts can increase blood flow in response to an increase in myocardial oxygen consumption (MVO2). METHODS: Twenty-seven patients who received complete arterial myocardial revascularization using the left internal thoracic artery (LITA) and the radial artery (RA) as composite Y-graft gave their consent to a pre-discharge coronary angiography and intravascular flow velocity measurements using a Doppler guide wire. Flow measurements were performed in the LITA main stem, the distal LITA and the RA, both at rest and during atrial pacing at the 85% of the patient age-predicted maximum. The heart rate-systolic blood pressure product was considered as an indirect index of MVO2. Hyperemic flow was determined after injection of adenosine. The flow reserve (FR) was defined as the ratio of blood flow during maximal hyperemia (Qmax) to baseline flow (Qbasal). RESULTS: Atrial pacing increased MVO2 significantly (P<0.000). None of the patients developed ischemic S-T segment modifications or complained of chest pain. Q(basal) increased significantly in the LITA main stem (P=0.001), distal LITA (P=0.041) and RA (P=0.004) while Qmax did not change significantly. As a consequence, the FR decreased in the LITA main stem (P=0.002), distal LITA (P<0.000) and RA (P<0.000) but was not completely exhausted. CONCLUSIONS: Soon after the operation, arterial composite Y-grafts can significantly increase blood flow in response to conditions of increased MVO2, keeping normal the myocardial O2 supply-to-demand ratio.     

Image quality on dual-source computed-tomographic coronary angiography

Multi-detector CT reliably permits visualization of coronary arteries, but due to the occurrence of motion artefacts at heart rates >65 bpm caused by a temporal resolution of 165 ms, its utilisation has so far been limited to patients with a preferably low heart rate. We investigated the assessment of image quality on computed tomography of coronary arteries in a large series of patients without additional heart rate control using dual-source computed tomography (DSCT). DSCT (Siemens Somatom Definition, 83-ms temporal resolution) was performed in 165 consecutive patients (mean age 64 +/- 11.4 years) after injection of 60-80 ml of contrast. Data sets were reconstructed in 5% intervals of the cardiac cycle and evaluated by two readers in consensus concerning evaluability of the coronary arteries and presence of motion and beam-hardening artefacts using the AHA 16-segment coronary model. Mean heart rate during CT was 65 +/- 10.5 bpm; visualisation without artefacts was possible in 98.7% of 2,541 coronary segments. Only two segments were considered unevaluable due to cardiac motion; 30 segments were unassessable due to poor signal-to-noise ratio or coronary calcifications (both n = 15). Data reconstruction at 65-70% of the cardiac cycle provided for the best image quality. For heart rates >85 bpm, a systolic reconstruction at 45% revealed satisfactory results. Compared with earlier CT generations, DSCT provides for non-invasive coronary angiography with diagnostic image quality even at heart rates >65 bpm and thus may broaden the spectrum of patients that can be investigated non-invasively.