Morphine and Enkephalins Potently Inhibit [3H]Noradrenaline Release from Rat Brain Cortex Synaptosomes: Further Evidence for a Presynaptic Localization of μ-Opioid Receptors

Synaptosomes prepared from rat cerebral cortex and labeled with [3H]noradrenaline (NA) were superfused with calcium-free Krebs-Ringer-bicarbonate medium and exposed to 10 mM K+ plus 0.1 mM Ca2+ so that [3H]NA release was induced. 6,7-Dihydroxy-N,N-dimethyl-2-aminotetralin (TL-99) strongly inhibited synaptosomal K+-induced [3H]NA release (EC50 = 5-10 nM) by activating alpha 2-adrenoceptors. Release was also inhibited (maximally by 40-50%) by morphine (EC50 = 5-10 nM), [Leu5]enkephalin (EC50 = approximately 300 nM), [D-Ala2,D-Leu5]enkephalin (DADLE), and Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) (EC50 values = approximately 30 nM). In contrast to the mu-selective opioid receptor agonists morphine and DAGO, the highly delta-selective agonist [D-Pen2,D-Pen5]enkephalin (1 microM) did not affect [3H]-NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both delta- and mu-opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like alpha 2-adrenoceptors, mu-opioid receptors mediating inhibition of NA release in the rat cerebral cortex are localized on noradrenergic nerve terminals.     

Percutaneous closure of an adult patent ductus arteriosus

A 23-year-old asymptomatic male was referred to our outpatient clinic because of an incidentally discovered grade III continuous machinery murmur at the third intercostal space on the left sternal edge. The echocardiography showed the presence of a patent ductus arteriosus (PDA).     

Differential effects of chronic agonist administration on mu-opioid receptor- and muscarinic receptor-regulated adenylate cyclase in rat striatal neurons.

In cultured rat striatal neurons exposed to 10 microM morphine or oxotremorine for 24 hours, we observed an increased (about 30%) dopamine D1 receptor-stimulated cyclic AMP production, whereas no desensitization of mu-opioid receptor or muscarinic cholinergic receptor was found. However, whereas upregulation of dopamine D1 receptor-stimulated adenylate cyclase activity upon 7 days morphine exposure was at least as pronounced as observed after 24 hours of exposure to the opioid, this adaptive phenomenon was virtually absent following one week of oxotremorine treatment. This reduced adenylate cyclase sensitization upon 7 days oxotremorine exposure appeared to coincide with desensitization of muscarinic cholinergic receptors. A possible role of the resistance of mu receptors to desensitization and the (resulting) upregulation of the neuronal adenylate cyclase system upon chronic receptor activation in the development of opiate tolerance and dependence is suggested.     

Application of beta-irradiation through the struts of a previously deployed stent

The application of beta-radiation in coronary arteries is a promising new technique for the treatment of in-stent restenosis. This is the first case in which the 5 F. delivery catheter of the Beta-Cath trade mark system was advanced through the struts of a stent, previously deployed in an adjacent branch, so as to deliver radiation to the target vessel.     

Endovascular brachytherapy in coronary arteries: the Rotterdam experience

Purpose: The use of endovascular coronary brachytherapy to prevent restenosis following percutaneous transluminal coronary angioplasty (PTCA) began in April 1997 at the Department of Interventional Cardiology of the Thoraxcenter at the University Hospital of Rotterdam. This article reviews the more than 250 patients that have been treated so far.Methods and Materials: The Beta-Cath System (Novoste), a manual, hydraulic afterloader with 12 90Sr seeds, was used in the Beta Energy Restenosis Trial (BERT-1.5, n=31), for compassionate use (n=25), in the Beta-Cath System trial (n=27) and in the Beta Radiation in Europe (BRIE, n=14). Since the Beta-Cath System has been commercialized in Europe, 57 patients have been treated and registered in RENO (Registry Novoste). In the Proliferation Reduction with Vascular Energy Trial (PREVENT), 37 patients were randomized using the Guidant-Nucletron remote control afterloader with a 32P source wire and a centering catheter. Radioactive 32P coated stents have been implanted in 102 patients. In the Isostent Restenosis Intervention Study 1 (IRIS 1), 26 patients received a stent with an activity of 0.75-1.5 μCi, and in the IRIS 2 (European 32P dose response trial), 40 patients were treated with an activity of 6-12 μCi. In two consecutive pilot trials, radioactive stents with non-radioactive ends (cold-end stents) and with ends containing higher levels of activity (hot-end stents) were implanted in 21 and 17 patients, respectively.Results: In the BERT-1.5 trial, the radiation dose, prescribed at 2 mm from the source train (non-centered), was 12 Gy (10 patients), 14 Gy (10 patients) and 16 Gy (11 patients). At 6-month follow-up, 8 out of 28 (29%) patients developed restenosis. The target lesion revascularization rate (TLR) was 7 out of 30 (23%) at 6 months and 8 out of 30 (27%) at 1 year. Two patients presented with late thrombosis in the first year. For compassionate use patients, a restenosis rate (RR) of 53% was observed. In the PREVENT trial, 34 of 37 patients underwent an angiographic 6-month follow-up. The doses prescribed at 0.5 mm depth into the vessel wall were 0 Gy (8), 28 Gy (9), 35 Gy (11) and 42 Gy (8). TLR was 14% in the irradiated patients and 25% in the placebo group. One patient developed late thrombosis. In the IRIS 1 trial, 23 patients showed an RR of 17% (in-stent). In the IRIS 2 trial, in-stent restenosis was not seen in 36 patients at 6-month follow-up. However, a high RR (44%) was observed at the stent edges.Conclusions: The integration of vascular brachytherapy in the catheterization laboratory is feasible and the different treatment techniques that are used are safe. Problems, such as edge restenosis and late thrombotic occlusion, have been identified as limiting factors of this technique. Solutions have been suggested and will be tested in future trials.     

Cytologic diagnosis of hemophagocytic lymphohistiocytosis in ascitic fluid: a case report

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), also known as macrophage activation syndrome, is a rare, fatal hematopoietic disease. Its cytologic features may be subtle because the abnormal histiocytes may not be recognized if one is not aware of this entity. We report a case of HLH involving the ascitic fluid. CASE REPORT: A 73-year-old man developed weakness, lethargy, decreased appetite and progressive shortness of breath after a cholecystectomy. Physical examination revealed hypotension, tachycardia and chest dullness with decreased breath sounds bilaterally. Radiologic examination revealed bilateral pleural effusions. The patient accumulated fluid in the peritoneal cavity, lungs, retroperitoneum and mediastinum. Bone marrow biopsy showed abundant histiocytes infiltrating the marrow cavity, and many of these histiocytes contained cellular debris. A diagnosis of HLH was therefore made. The abdominal paracentesis specimen contained many similar histiocytes exhibiting erythrophagocytosis and lymphophagocytosis. These abnormal histiocytes were positive for CD68 and negative for AE1/AE3, confirming the diagnosis of HLH. The patient died soon after from disseminated aspergillosis. CONCLUSION: HLH is cytologically characterized by the presence of abnormal histiocytes with ingested cellular debris. In serous effusions they should not be confused with mesothelial cells. Immunohistochemical studies may help confirm the diagnosis.     

Acute myocardial infarction system of care in the third world

Background

We studied the characteristics of ST-elevation myocardial infarction (STEMI) patients from a local acute coronary syndrome (ACS) registry in order to find and build an appropriate acute myocardial infarction (AMI) system of care in Jakarta, Indonesia.

Methods

Data were collected from the Jakarta Acute Coronary Syndrome (JAC) registry 2008–2009, which contained 2103 ACS patients, including 654 acute STEMI patients admitted to the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia.

Results

The proportion of patients who did not receive reperfusion therapy was 59% in all STEMI patients and the majority of them (52%) came from inter-hospital referral. The time from onset of infarction to hospital admission was more than 12 h in almost 80% cases and 60% had an anterior wall MI. In-hospital mortality was significantly higher in patients who did not receive reperfusion therapy compared with patients receiving acute reperfusion therapy, either with primary percutaneous coronary intervention (PPCI) or fibrinolytic therapy (13.3% vs 5.3% vs 6.2%, p < 0.001).

Conclusion

The Jakarta Cardiovascular Care Unit Network System was built to improve the care of AMI in Jakarta. This network will harmonise the activities of all hospitals in Jakarta and will provide the best cardiovascular services to the community by giving two reperfusion therapy options (PPCI or pharmaco-invasive strategy) depending on the time needed for the patient to reach the cath-lab.