Augmentation index predicts mortality in patients with aortic stenosis: an echo-tracking study

The International Journal of Cardiovascular Imaging - Aortic valve stenosis (AS) shares similarities with the atherosclerotic process but little is known about the effect of the mechanical...     

Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a large clonal population of blood cells deriving from hematopoietic stem cells (HSCs) deficient in glycosylphosphatidylinositol (GPI)-anchored surface molecules. A current model postulates that PNH arises through negative selection against normal HSCs exerted by autoreactive T cells, whereas PNH HSCs escape damage. We have investigated the inhibitory receptor superfamily (IRS) system in 13 patients with PNH. We found a slight increase in the proportion of T cells expressing IRS. In contrast to what applies to healthy donors, the engagement of IRS molecules on T cells from patients with PNH elicited a powerful cytolytic activity in a redirected killing assay, indicating that these IRSs belong to the activating type. This was confirmed by clonal analysis: 50% of IRS+ T-cell clones in patients with PNH were of the activating type, while only 5% were of the activating type in healthy donors. Moreover, the ligation of IRS induces (1) production of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) and (2) brisk cytolytic activity against cells bearing appropriate IRS counter-ligands. In addition, these IRS+ T cells show natural killer (NK)-like cytolytic activity to which GPI- cells were less sensitive than GPI+ cells. Thus, T cells with NK-like features, expressing the activating isoforms of IRS, may include effector cells involved in the pathogenesis of PNH.     

Clinical characteristics and outcome of diabetic patients with acute myocardial infarction. Data from the BLITZ-1 study.

BACKGROUND: The determinants of a worse outcome in diabetic patients after an acute myocardial infarction (AMI) are controversial. They include delayed hospital admission, worse clinical presentation and lesser efficacy of accepted therapeutic interventions. Therefore, to improve our knowledge, we aimed to describe the clinical characteristics, treatment options and short-term outcomes of diabetic patients in a survey of consecutive AMI subjects admitted to the Italian coronary care unit (CCU) network in the current era of reperfusion. METHODS: The BLITZ study prospectively enrolled patients with AMI, within 48 hours of symptom onset, admitted to 296 out of the 341 existing Italian CCUs from October 15 to 29, 2001. Diabetic status was recorded by collecting clinical history. In-hospital and post-discharge management and outcomes were collected up to 30 days from admission. RESULTS: Overall, 434 of 1959 enrolled patients (22%) had a clinical diagnosis of diabetes. Diabetic patients were older, more frequently women, had a worse coronary risk profile, and an unfavorable clinical presentation compared to non-diabetics. Among 1275 patients with ST-elevation AMI, diabetics (20%) received a similar proportion of any reperfusion therapy (61 vs 66%, p = 0.10), but significantly less primary percutaneous coronary angioplasty (9 vs 16%, p = 0.003). Diabetic patients were treated less often with oral beta-blockers than non-diabetics both during hospitalization (56 vs 64%, p = 0.003) and at discharge (54 vs 61%, p = 0.01). In contrast, in-hospital use of angiotensin-converting enzyme inhibitors (76 vs 67%, p = 0.0003), digitalis (10 vs 5%, p = 0.0005), and diuretics (54 vs 36%, p < 0.0001) was more frequent among diabetics. During their index admission, subjects with diabetes had higher in-hospital mortality (11 vs 6%, p = 0.0004), as well as higher rates of reinfarction (6 vs 2%, p = 0.0003), new congestive heart failure (28 vs 14%, p < 0.0001), cardiogenic shock (10 vs 5%, p = 0.0005) or recurrent angina (22 vs 16%, p = 0.0034). A similar pattern was observed at 30-day follow-up. At multivariate analysis, diabetic status was not confirmed to be an independent predictor of 30-day mortality. CONCLUSIONS: Although diabetic patients with AMI admitted to the Italian CCU network have a higher in-hospital and 30-day morbidity and mortality rates compared to non-diabetics, a clinical diagnosis of diabetes has no independent predictive value on short-term outcome.     

Serum amylase and lipase concentrations and lipase/amylase ratio in assessment of etiology and severity of acute pancreatitis

We studied the behavior of serum amylase and lipase in 66 consecutive patients with acute pancreatitis in order to assess the ability of these tests and of the serum lipase-amylase ratio to establish the etiology and predict the severity of acute pancreatitis. Forty-two patients had biliary acute pancreatitis, 14 had alcoholic acute pancreatitis, and the remaining 10 nonbiliary, nonalcoholic (NBNA) acute pancreatitis. Serum amylase and lipase were abnormally high in all patients. The elevations of both serum amylase and lipase were significantly lower in patients with alcoholic pancreatitis than in those with biliary pancreatitis, although a considerable overlap was observed between the two groups. No statistically significant differences were found between NBNA patients and those with either biliary or alcoholic forms of the disease. The serum lipase-amylase ratios in patients with alcoholic pancreatitis ranged from 0.2 to 5.6, in those with biliary pancreatitis from 0.1 to 7.9, and in those with NBNA pancreatitis from 0.1 to 4.4. These differences were not statistically significant. No differences in serum enzyme levels were observed among patients without apparent imaging signs of acute pancreatitis (N=20), those with signs of Pancreatic edema (N=36), and those with necrotizing pancreatitis (N=10). The results indicate that serum amylase and lipase concentrations are not able to establish either the etiology or to predict the severity of acute pancreatitis as assessed by imaging techniques. Furthermore, the serum lipase-amylase ratio is not useful in distinguishing acute episodes of alcoholic from nonalcoholic acute pancreatitis.     

Clinical and haematological consequences of recurrent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia

We have determined the causative mutation in 12 cases of glucose-6-phosphate dehydrogenase deficiency associated with chronic non-spherocytic haemolytic anaemia. In 11 of them the mutation we found had been previously reported in unrelated individuals. These mutations comprise seven different missense mutations and a 24 base pair deletion, G6PD Nara, previously found in a Japanese boy. Repeated findings of the same mutations suggests that a limited number of amino acid changes can produce the CNSHA phenotype and be compatible with normal development. The one new mutation we have found, G6PD Serres, is 1082 C → T causing a 361 Ala → Val substitution in the dimer interface where most other severe G6PD mutations are found. Now that several patients with the same mutation have been reported we can compare the resulting clinical phenotypes. For each mutation we find a reasonably consistent clinical picture, ranging from mild (G6PD Clinic) through moderate (G6PD Nashville) to severe (G6PD Beverly Hills and G6PD Nara).     

Tumor M2-Pyruvate Kinase, a New Metabolic Marker for Pancreatic Cancer

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.