Inhospital outcome of acute myocardial infarction in patients with prior coronary artery bypass surgery

Objectives Our goals were to compare the characteristics of patients with and without prior coronary artery bypass graft (CABG) presenting with acute myocardial infarction (MI) with or without ST elevation/left bundle branch block (LBBB), and to evaluate the effect of ST shift on inhospital mortality. Methods and Results Using the National Registry of Myocardial Infarction-3 Registry, we identified 112,697 patients with acute MI without exclusion criteria. Of these, 15,936 (14.1%) had prior CABG. Patients with prior CABG had more adverse characteristics and were less likely to have ST elevation/LBBB than patients without prior CABG. The unadjusted mortality for ST elevation/LBBB patients was higher in patients with prior CABG versus without (16.2% vs 14.1%, P = .0001), whereas in patients without ST elevation/LBBB, prior CABG conferred a lower unadjusted mortality versus without (10.1% vs 12.4%, P = .0001). Adjusting for baseline differences, prior CABG was weakly associated with inhospital mortality in ST elevation/LBBB patients (odds ratio [OR], 1.11, 95% CI 1.00-1.23), but not in patients without ST elevation/LBBB (OR 0.99, 95% CI 0.92-1.07). Conclusion Acute MI patients with prior CABG are more likely to present without ST elevation/LBBB than patients without prior CABG. Prior CABG was weakly associated with inhospital mortality in patients with ST elevation/LBBB, but not in patients without these electrocardiographic findings. This suggests the differences in absolute mortality rates between patients presenting with MI with and without a history of prior CABG are largely caused by differences in baseline characteristics and presentation. (Am Heart J 2002;144:463-9.)     

Short-term effect of the lesion of the organum vasculosum of the lamina terminalis on hypothalamic LH-RH and serum LH, FSH and prolactin in adult female rats.

The short-term effect of the mechanical lesion of the organum vasculosum of the lamina terminalis (OVLT) was investigated in 4-day cycling female rats. The lesions were performed on the 2nd day of diestrus, and the animals were killed by decapitation 30 h after the lesion. Serum LH, FSH and prolactin and hypothalamic LH-RH content of 3 different parts of the hypothalamus were determined with radioimmunoassay. OVLT lesion caused a significant increase in the LH-RH content of the mid-basal hypothalamus and in serum prolactin levels and a decrease in LH and FSH serum levels. The results support the view that the OVLT may play a role in the control of pituitary gonadotrophic hormone secretion.     

Employment loss during economic crisis and suicidal thoughts in Belgium: a survey in general practice

Background

The economic crisis of 2009 led to a wave of corporate reorganisations and bankruptcies, with many dismissals of employees. GPs were confronted with subsequent health consequences.

Aim

To assess the possible relationship between losing one’s job and having suicidal thoughts.

Design and setting

A survey of patients aged 18–49 years recruited from GP practices in Belgium in Deurne (Flemish region) and La Louvière (Walloon region) from September to December 2010.

Method

Anonymous self-administered questionnaire.

Results

Of all eligible patients (n = 1818), 831 were offered the questionnaire and 377 completed it (45.4%). More than one in five had been confronted with employment loss in the past year (the responder or someone close losing their job). Almost one in ten had lost their job themselves in the past year. More than one in four had experienced suicidal thoughts and 11.7% had seriously considered ending their life in the past year. In the logistic regression analysis, the following characteristics showed a statistically significant relationship with having suicidal thoughts: being single (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.7 to 13.8), not having satisfying social contacts (OR = 5.1, 95% CI = 1.6 to 16.2), having depressive complaints (OR = 18.4, 95% CI = 5.8 to 58.4), and having lost one’s employment in the past year (OR = 8.8, 95% CI = 2.0 to 39.3).

Conclusion

This study points to a statistically significant relationship between losing one’s employment in the past year and having suicidal thoughts. It emphasises the important role of the GP in the continuous and reinforced assessment of suicidal risk in times of recession.     

Identification of a human B-cell/myeloid common progenitor by the absence of CXCR4

CXCR4 is a chemokine receptor required for hematopoietic stem cell engraftment and B-cell development. This study found that a small fraction of primitive CD34(+)/CD19(+) B-cell progenitors do not express CXCR4. These CD34(+)/CD19(+)/CXCR4(-) cells were also remarkable for the relative lack of primitive myeloid or lymphoid surface markers. When placed in B-lymphocyte culture conditions these cells matured to express CXCR4 and other surface antigens characteristic of B cells. Surprisingly, when placed in a myeloid culture environment, the CXCR4(-) B-cell progenitors could differentiate into granulocyte, macrophage, and erythroid cells at a high frequency. These data define a novel B-cell/myeloid common progenitor (termed the BMP) and imply a less restrictive pathway of myeloid versus lymphoid development than previously postulated.     

The hemochromatosis protein HFE inhibits iron export from macrophages

Hereditary hemochromatosis (HH) is a disorder of iron metabolism caused by common mutations in the gene HFE. The HFE protein binds to transferrin receptor-1 (TfR1) in competition with transferrin, and in vitro, reduces cellular iron by reducing iron uptake. However, in vivo, HFE is strongly expressed by liver macrophages and intestinal crypt cells, which behave as though they are relatively iron-deficient in HH. These latter observations suggest, paradoxically, that expression of wild-type HFE may lead to iron accumulation in these specialized cell types. Here we show that wild-type HFE protein raises cellular iron by inhibiting iron efflux from the monocytemacrophage cell line THP-1, and extend these results to macrophages derived from healthy individuals and HH patients. In addition, we find that the HH-associated mutant H41D has lost the ability to inhibit iron release despite binding to TfR1 as well as wild-type HFE. Finally, we show that the ability of HFE to block iron release is not competitively inhibited by transferrin. We conclude that HFE has two mutually exclusive functions, binding to TfR1 in competition with Tf, or inhibition of iron release.     

Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells

CXC ligand 12 (CXCL12; also known as stromal cell-derived factor 1alpha/SDF-1alpha) chemoattracts hematopoietic stem and progenitor cells (HSCs/HPCs) and is thought to play a crucial role in the mobilization of HSCs/HPCs from the bone marrow. CD26 (dipeptidylpeptidase IV [DPPIV]) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N-terminus of polypeptide chains. CD26 has the ability to cleave CXCL12 at its position-2 proline. We found by flow cytometry that CD26 is expressed on a subpopulation of normal Sca-1+c-kit+lin- hematopoietic cells isolated from mouse bone marrow, as well as Sca-1+c-kit-lin- cells, and that these cells possess CD26 peptidase activity. To test the functional role of CD26 in CXCL12-mediated normal HSC/HPC migration, chemotaxis assays were performed. The CD26 truncated CXCL12(3-68) showed an inability to induce the migration of sorted Sca-1+c-kit+lin- or Sca-1+c-kit-lin- mouse marrow cells compared with the normal CXCL12. In addition, CXCL12(3-68) acts as an antagonist, resulting in the reduction of migratory response to normal CXCL12. Treatment of Sca-1+c-kit+lin- mouse marrow cells, and myeloid progenitors within this population, or Sca-1+c-kit-lin- cells with a specific CD26 inhibitor, enhanced the migratory response of these cells to CXCL12. Finally, to test for potential in vivo relevance of these in vitro observations, mice were treated with CD26 inhibitors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization. This treatment resulted in a reduction in the number of progenitor cells in the periphery as compared with the G-CSF regimen alone. This suggests that a mechanism of action of G-CSF mobilization involves CD26.     

The role of transthoracic echocardiography in excluding left sided infective endocarditis in Staphylococcus aureus bacteraemia

In all patients with Staphylococcus aureus bacteraemia a transoesophageal echocardiogram is recommended to exclude infective endocarditis. We determined that a finding of normal to trivial valvular regurgitation on transthoracic echocardiogram in these patients significantly reduced the probability of infective endocarditis. Furthermore, in the absence of embolic phenomena the likelihood of infective endocarditis was less than 2%. This probability could be further reduced if the echocardiogram was performed greater than 5 days after the bacteraemia. Therefore, in the assessment of patients with S. aureus bacteraemia a transoesophageal echocardiogram is not always required to exclude infective endocarditis.     

Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12^–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes.     

Dehydration attenuates plasma prolactin response to suckling through a dopaminergic mechanism.

The tuberoinfundibular dopaminergic neurons projecting to the median eminence are well accepted as a major physiological regulator of adenohypophyseal PRL secretion. However, recent evidence has shown that dopamine (DA) in the neurointermediate lobe also has an inhibitory effect on PRL secretion by anterior pituitary. Since the neurointermediate is innervated by the tuberohypophyseal dopaminergic (THDA) neurons, which is known to be selectively activated by dehydration of the animal, the aim of this study was to investigate the physiological role of the THDA system in PRL release during lactation. On the day of the experiments, the litters were separated from the mothers for 4 h before initiation of the suckling stimulus. The suckling-induced PRL surge was detected on three consecutive days. On the first day the normal response was tested; then immediately after taking the last blood samples, drinking solutions were changed to the high salt (2.5% saline) containing bottles or were taken away. Suckling-induced PRL response was significantly decreased after 24 h and almost completely blocked 48 h later in dehydrated mothers. This effect could be prevented by haloperidol (a DA receptor antagonist) pretreatment (0.1 mg/kg BW sc), and it was only transient because rehydration of the mothers reestablished basal as well as suckling-induced PRL response. In addition, the effect of an acute osmotic stimulus on the plasma PRL levels (injecting 0.5 ml 10% saline solution iv) was also tested. There was a marked and immediate decrease in PRL concentration within 15 min of injection. Domperidone, another DA receptor blocker (20 micrograms/rat iv) completely abolished the depletion of plasma PRL in response to 10% saline injection. These results support our assumption that the dopaminergic regulation of PRL secretion during lactation involves the THDA system. Furthermore, these data underline the importance of an interaction between regulation of PRL secretion and water and sodium homeostasis.