Early effects of total hepatectomy on haemodynamic state and organ uptake of catecholamines in the pig

In a previous study, we showed that plasma concentrations of catecholamines were increased during the anhepatic phase in pigs. In this study, we investigated if a constant depth of anaesthesia would prevent these changes and, if not, if the changes were caused by impaired extraction of catecholamines. We measured arterial and venous pressures, heart rate and cardiac output in 10 anaesthetized pigs. Hepatic arterial and portal venous flows were measured. Blood for measurement of catecholamines was sampled from carotid and pulmonary arteries and portal, hepatic and renal veins. After a 2-h observation period, the liver was removed and the circulation reconstituted. Measurements were made and samples obtained for another 2 h. Catecholamine concentrations increased 2-10-fold after hepatectomy. Before hepatectomy, noradrenaline was extracted by the lung (mean extraction ratio 23 (SEM 8)%) and the liver (30 (11)%); after hepatectomy, there was extraction by the kidney (24 (12)%) but extraction by the lung (29 (8)%) was unchanged. Before hepatectomy, adrenaline was extracted predominantly by the kidney (73 (5)%) and the liver (70 (6)%), with minimal extraction by the lung; after hepatectomy, extraction by the lung increased (25 (4)%) and decreased slightly in the kidney (56 (6)%). While mean arterial pressure did not change, heart rate increased by approximately 50% and cardiac index declined (ns) within 2 h after hepatectomy. There was a sharp increase in pulmonary vascular resistance after removal of the liver and changes correlated with increases in arterial plasma concentrations of catecholamines.      

NGF and TGF‐β mRNA expression during pregnancy in a rat corneal wound healing model

Background: Growth factors seem to play a major role in corneal wound healing and TGF‐β seems to be associated with abnormal healing after corneal surgical procedures. Few studies have analysed the role of NGF and TGF‐β on corneal wound healing during pregnancy. The aim of the present study was to create an animal model to evaluate the expression of NGF and TGF‐βs during corneal wound healing in two groups: control and pregnant rats. Methods: Corneal mRNA for NGF and the three isoforms of TGF‐β were analysed by RT‐PCR, in a time‐course experiment on different days after epithelial wounding (2, 7, 14 days) in pregnant and control groups Results: The results show high corneal mRNA expression for NGF and TGF‐β1 without any variation throughout the healing process or pregnancy evolution. However, we detected a different expression of corneal mRNAs for TGF‐β2 and TGF‐β3 in the control group. This data was not detected in the pregnant group. Discussion: Our results suggested that pregnancy could have a relevant role on TGF‐β2 and TGF‐β3 mRNA expression during the corneal wound healing process. Additional research should be performed to corroborate these findings.     

Drug-related mortality and fatal overdose risk: Pilot cohort study of heroin users recruited from specialist drug treatment sites in London

Fatal overdose and drug-related mortality are key harms associated with heroin use, especially injecting drug use (IDU), and are a significant contribution to premature mortality among young adults. Routine mortality statistics tend to underreport the number of overdose deaths and do not reflect the wider causes of death associated with heroin use. Cohort studies could provide evidence for interpreting trends in routine mortality statistics and monitoring the effectiveness of strategies that aim to reduce drug-related deaths. We aimed to conduct a retrospective mortality cohort study of heroin users recruited from an anonymous reporting system from specialist drug clinics. Our focus was to test whether (1) specialist agencies would agree to participate with a mortality cohort study, (2) a sample could be recruited to achieve credible estimates of the mortality rate, and (3) ethical considerations could be met. In total, 881 heroin users were recruited from 15 specialist drug agencies. The overall mortality rate of the cohort of heroin users was 1.6 (95% confidence interval [CI], 1.1 to 2.2.) per 100 person-years. Mortality was higher among males, heroin users older than 30 years, and injectors, but not significantly higher after adjustment in a Cox proportional hazard model. Among the 33 deaths, 17 (52%) were certified from a heroin/methadone or opiate overdose, 4 (12%) from drug misuse, 4 (12%) unascertained, and 8 (24%) unrelated to acute toxic effects of drug use. Overall, the overdose mortality rate was estimated to be at least 1.0 per 100 person-years. The standardized mortality ratio (SMR) was 17 times higher for female and male heroin users in the cohort compared to mortality in the non-heroin-using London population aged 15–59 years. The pilot study showed that these studies are feasible and ethical, and that specialist drug agencies could have a vital role to play in the monitoring of drug-related mortality.     

Use of the activated coagulation time as a measure of anticoagulation during interventional procedures

The activated coagulation time (ACT) is a reliable method of determining the degree of anticoagulation caused by the administration of heparinized saline solutions during long interventional procedures. An automated system that simplifies the determination of the ACT is available and has proved useful in preventing hemostatic complications.     

A prospective study of complications in Hickman right-atrial catheters in marrow transplant patients

One hundred forty-three large bore right-atrial catheters (RACs) in 111 bone marrow transplant recipients were prospectively analyzed for the incidence of complications interfering with catheter function. Of the 143 RACs, 108 (76%) were patent on departure from Seattle or death. Infectious complications occurred in 63 (44%) of the catheters, resulting in 18 (13%) removals. Noninfectious complications occurred with 54 (38%) of the catheters, resulting in 17 (12%) removals. Successful interventions included catheter repair, dissolving precipitates with ammonium chloride solution, and declotting catheter lumens with heparin and/or urokinase. We conclude that RACs continue to be reliable and safe devices to use in marrow transplant patients. Complications interfering with catheter function are frequent; however, most can be resolved without the need to remove the catheter.     

Monocytes enhance the bidirectional release of type I plasminogen activator inhibitor by endothelial cells

Human umbilical vein endothelial cells cultured on a collagen lattice were used to study the effects of the interaction between human monocytes and endothelial cells on the production of type 1 plasminogen activator inhibitor (PAI-1) by endothelial cells. The effects of adherence and transendothelial migration of monocytes on endothelial PAI-1 release were compared with those of other leukocytes, conditioned media from monocytes, and interleukin-1 beta (IL-1 beta). Because the cell culture system used allows simultaneous analysis of the lumenal and the subendothelial compartment of endothelial cell monolayers, we also studied into which direction PAI-1 is released by endothelial cells. Under quiescent conditions, the net amount of PAI-1 accumulated at the lumenal side was twofold higher than that accumulated at the subendothelial side (about 2.0 micrograms PAI-1/10(6) cells and 1.1 microgram PAI-1/10(6) cells, respectively, in 24 hours), as analyzed by a quantitative immunoradiometric assay (IRMA). Direct cell-cell contact between highly purified monocytes and endothelial cells strongly enhanced the PAI-1 release by endothelial cells in a dose-dependent way, whereas lymphocytes and neutrophils did not affect endothelial PAI- 1 production. The monocyte-mediated increase was first detected after 12 hours of incubation and lasted for at least 48 hours. In the presence of two monocytes per endothelial cell, the increases of PAI-1 at the lumenal side and at the subendothelial side were 87% and 32% in 24 hours, respectively. The effect of IL-1 beta on PAI-1 release by endothelial cells closely resembled that observed for monocytes. Monocyte-conditioned medium contained heat-labile product(s) which also, although to a much lesser extent than intact monocytes, enhanced endothelial PAI-1 release. Similarly, monocytes cultured on top endothelial cell separated by a microporous filter enhanced the release of PAI-1 to a lesser extent. Thus, these findings indicate that monocytes enhance endothelial PAI-1 release by mechanisms that are, at least in part, dependent on cell-cell contact.     

Responsiveness of non-IHS migraine and tension-type headache to sumatriptan

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT₁ receptors that spans a range of clinical presentations.