Characteristics associated with early (less than or equal to 3 months) versus late (greater than 3 months to less than or equal to 3 years) mortality after acute myocardial infarction

To define the independent variables predictive of early versus late mortality after acute myocardial infarction (AMI), 420 consecutive patients were studied and divided into 3 groups: the 45 patients who died within the initial 3 months (group 1), the 45 patients who died greater than 3 months and less than or equal to 3 years after AMI (group 2) and the 330 greater than 3-year survivors (group 3). The stepwise logistic discrimination method was applied to clinical and laboratory variables recorded during hospitalization to distinguish among the 3 groups. Six independent variables were found to be predictive of early mortality: left ventricular function score (chi-square 26.2; p less than 0.00001), ventricular fibrillation (chi-square 9.3; p = 0.002), bundle branch block (chi-square 9.0; p = 0.003), history of previous AMI (chi-square 8.7; p = 0.003), age (chi-square 5.8; p = 0.02) and atrioventricular block (chi-square 3.8; p = 0.05). Three independent variables were found predictive of late mortality: age (chi-square 13.8; p = 0.0002), anterior location of the AMI (chi-square 4.0; p = 0.04) and a low peak creatine kinase-MB level (chi-square 3.8; p = 0.05). Only 2 variables were able to distinguish between early and late nonsurvivors: peak creatine kinase-MB level (chi-square 8.7; p = 0.003) and ventricular fibrillation (chi-square 4.6; p = 0.03). Thus, the sets of independent risk factors for early and late mortality after AMI are substantially different--suggesting that differing mechanisms are responsible for outcome.     

Short-chain fatty acids do not alter jejunal motility in man

Short-chain fatty acids (SCFAs) alter ileal and colonic motility, but their effects on duodenojejunal motility are unknown. Simultaneous jejunal manometric recordings and hydrogen breath tests after lactulose were performed in eight healthy subjects during continuous duodenal infusion of either saline or SCFAs. These experiments were conducted in the fasting state and postprandially. The effects of various boluses of SCFAs on duodenojejunal motility were also determined in six subjects. During the fasting period, the number and characteristics of migrating motor complex, prolonged propagated contractions, discrete clustered contractions, motility indes, and orocecal transit time were similar during saline and SCFAs. Similarly, the motility index and the duration of the postprandial period were not different between SCFAs and saline after the meal. The motility index was significantly increased after each of the 100-ml boluses (saline or SCFAs), but was not altered after the 12.5-ml boluses, suggesting a volume-related effect. Thus, SCFAs do not seem to affect proximal small bowel motility in healthy humans.This work was supported in part by a research grant from Institut National de la Santé et de la Recherche Médicale (INSERM) (CRE 887009), and by Smith Kline and French (Paris, France).     

Short- and long-term prognostic importance of complete bundle-branch block complicating acute myocardial infarction

Among 1013 consecutive patients with acute myocardial infarction (AMI), 104 (10%) developed complete bundle-branch block (BBB). The clinical characteristics and the short- and long-term prognosis were similar in the 53 patients with right and the 51 patients with left BBB. Compared to the 909 patients without this conduction disturbance, these 104 patients were older (64 +/- 9 vs. 58 +/- 10 years, p less than 0.001), more frequently women (26 vs. 17%, p less than 0.05), had a larger infarct (peak CK 1672 +/- 1124 vs. 1356 +/- 1089 IU/l, p less than 0.001), more frequently anterior (60 vs. 37%, p less than 0.001). They had a higher incidence of Killip class greater than 1 (63 vs. 38%, p less than 0.001), pericarditis (40 vs. 23%, p less than 0.001), atrial fibrillation or flutter (22 vs. 12%, p less than 0.01), ventricular fibrillation (15 vs. 9%, p less than 0.05), and atrioventricular block (23 vs. 11%, p less than 0.001). Both hospital mortality (32 vs 10%, p less than 0.001) and 3-year posthospital mortality (37 vs. 18%, p less than 0.001) were much higher among patients with complete BBB. Transient BBB had the same deleterious prognosis as BBB persistent at discharge (mortality 33 vs. 39%, NS). The prognostic importance of BBB was more prominent during the first 6 months after infarction (mortality between 6 and 36 months: 18% with BBB vs. 11% without BBB, NS).     

Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice.

A precise targeting of the SV40 T early region expression in the liver of transgenic mice was obtained using 700 bp of the antithrombin III regulatory sequences to control oncogene expression. In the strain expressing the highest level of large T antigen (Tag), the incidence of hepatocarcinoma was 100%. The evolution was reproducible and characterized by a marked cytolysis occurring as early as 4 weeks, when no morphological and histological modifications were visible, a preneoplastic state marked by a progression from hyperplasia to proliferative nodules composed of highly differentiated cells exhibiting a high Tag expression, which elicited tumor formation in nude mice and could proliferate in vitro, and hepatocellular carcinoma associated, in 10% of the cases, with lung metastasis. These transgenic mice constituted a useful model for therapeutic assays and fundamental studies on carcinogenesis.     

Ultrastructural evidence for endogenous somatostatin-like immunoreactivity in the pituitary gland

The tetradecapeptide, somatostatin (SRIF), is a potent inhibitor on pituitary hormone release, by a direct effect. The immunocytological method was used with the aim of localizing SRIF at the cellular and subcellular levels. Rat pituitaries were fixed and frozen. Ultrathin sections obtained by cryoultramicrotomy, were incubated with anti-SRIF serum. The antigen-antibody reaction was detected by 4-chloro-1-naphthol. SRIF immunoreactivity was observed in somatotrophs, thyreotrophs and prolactin cells, but not in corticotrophs or gonadotrophs. Im immunoreactive cells, SRIF was found in the cytoplasmic matrix, in the secretory granules and in the nucleus distributed primarily in the euchromatin, in the vicinity of the heterochromatin regions. SRIF immunoreactivity was also observed at the plasma membrane. No immunoreactivity was observed when nonimmune serum or anti-SRIF serum incubated with SRIF was used. No modification was observed when anti-SRIF serum incubated with gonadoliberin, thyroliberin or vasopressin was used. These data (1) provide immunocytological evidence for the presence of somatostatin in pituitary gland, and (2) indicate the presence of SRIF peptide in the somatotrophs, thyreotrophs and prolactin cells.     

Evidence for somatostatin-like immunoreactivity in discrete cells of the anterior pituitary of camel (Camelus dromedarius)

Immunocytochemical methods were applied to camel pituitaries. ACTH, beta-lipotropin (LPH), LH beta, GH, TSH, and PRL immunoreactive cells were identified. They were located on different parts of anterior pituitary and had different organization and shape. In addition, somatostatin-like immunoreactivity was seen in cells situated at the top of pituitary cleft specially in a cone-shaped extension of the intermediate lobe. The role and the eventual origin of these cells have yet to be established and their occurrence related to age and life conditions.     

"Once apical ballooning, always apical ballooning?"

It is important that a cardiologist knows and recognizes the entity of takotsubo cardiomyopathy or apical ballooning, but remains aware that a subsequent similar episode is not necessarily a recurrence of this syndrome. Relapse may be caused by "classical" coronary atherosclerosis, as described in this case report.     

Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity

Background

A complication of diabetes is neuropathy, a condition of sensory axon degeneration that originates in the epidermis. The mechanisms remain unknown but reactive oxygen species (ROS) have been implicated in this condition. In this study, we assessed the role of ROS and a candidate downstream target, MMP-13 in glucose-induced sensory axon degeneration in zebrafish and mice.

Enhancement of neutrophil function by granulocyte-macrophage colony- stimulating factor involves recruitment of a less responsive subpopulation

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances numerous functions of mature neutrophils (PMN) including phagocytosis, superoxide responses to chemotaxins, antibody-dependent cellular cytotoxicity, and expression of complement receptors. A central question concerns whether the mechanism of enhancement involves quantitative increases in the response of all cells v subpopulation recruitment. The effects of GM-CSF on individual cell light scatter changes, membrane potential, and oxidant responses induced by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) were assessed by flow cytometry and by scoring individual cells for nitroblue tetrazolium dye (NBT) reduction. GM-CSF produced a dose- and time-dependent shift in forward light scatter that was very similar in character to that seen with FMLP or leukotriene B4 stimulation. Although not capable of depolarizing the cells directly, GM-CSF primed PMNs for enhanced membrane potential responses to FMLP by significantly increasing the proportion of depolarizing cells when compared with diluent-treated controls after a 60-minute incubation at 37 degrees C (79.4% +/- 3.4% v 29.5% +/- 4.7% GM-CSF v diluent, mean +/- SE, P less than .005, n = 11). Subpopulation recruitment by GM-CSF treatment was also demonstrated by the FMLP-elicited NBT test. Taken together, these results indicate that GM-CSF can modulate the function of mature PMN by enhancing the proportion of responsive cells.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.