Isolated hyperthermic liver perfusion with cytostatic-containing perfusate activates the complement cascade.

Eight patients with advanced liver malignancy undergoing isolated hyperthermic liver perfusion with melphalan and cisplatin were studied with regard to complement activation and formation of anaphylatoxins (C3a and C5a) and terminal C5b-9 complement complexes (TCCs). Blood samples for complement variables (C1-INH, C3, C4, C5, C3a, C5a and TCCs) were taken before surgery, 1 min before the start of perfusion, 1, 2 and 3 h after the start of perfusion, and 24 h after operation. Samples were drawn from the perfusate 1 h after the start of perfusion. Activation of complement was observed during perfusion. Raised plasma concentrations of C3a and TCCs were recorded and high levels of C3a and TCCs were found in the perfusate. In vitro tests indicated that melphalan and cisplatin may activate complement. This activation occurred at 37 and 42 degrees C but was more pronounced at 42 degrees C.     

Effects of tobacco-smoke on radiation-induced pneumonitis in rats.

To investigate the effect of exposure to tobacco smoke (TS) on the development of irradiation-induced pneumonitis in rats, five groups of animals were investigated including controls (C), tobacco smoke exposed (S), irradiated (RNS) and irradiated and tobacco smoke exposed (RS). An additional group (RS/NS) was exposed to tobacco before irradiation but not afterwards. Rats were exposed to diluted mainstream cigarette smoke at a concentration of about 0.4 mg/l in a nose-only exposure system for 1/day, 5 days/week for 10 weeks. Exposure to TS started 3 weeks before irradiation in which the basal one-third of both lungs was exposed to a single dose of 28 Gy. In previous studies this dose had been shown to cause significant pneumonitis. All the animals were killed at 7 weeks after irradiation. Examination of the morphology of lung sections showed less pulmonary inflammation in the RS group than in the RNS group. This was also reflected in the results of bronchoalveolar lavage (BAL) which showed a decline in cell recovery and a marked decrease in the numbers of mast cells and neutrophils in the RS rats compared with the RNS animals. The concentration of hyaluronan in lavage fluid was increased in the RNS and RS/NS group while no increase was found in the RS group. A marked increase in BAL protein was also seen in the RNS and RS/NS groups as compared with the RS group but all were significantly higher than in unirradiated controls. This indicates that smoking suppresses the radiation-induced inflammation but to a lesser degree affects the radiation-induced increase in membrane permeability as reflected by increased protein levels in BAL. Moreover, the marked effects on the numbers of mast cells and neutrophils in the RS group may indicate that these cells play an important role in the mechanism by which tobacco smoke modulates the effects of irradiation. When exposure to tobacco smoke was terminated immediately after irradiation (RS/NS), the inflammatory response was unaffected.     

A novel anticholinesterase THB013: Biochemical and behavioural studies

Summary Clinical trials with tacrine (THA) have resulted in elevations of liver enzymes in Alzheimer patients that showed improvement. In an effort to minimize these side effects several THA analogues were synthesized. These analogues were compared to THA in biochemical as well as behavioural studies. In this study, the biochemical effects of THA and one of these analogs, THB 013, on plasma cholinesterase activity, cholinergic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. THB 013 was, at lower concentration, more efficacious in inhibiting plasma cholinesterase as well as blocking the scopolamine induced disruption of spatial learning when administered 10 min before the scopolamine injection. It is possible that THB 013 with more potent cholinergic effects than THA might be useful in the treatment of Alzheimer's disease.     

Upper gastrointestinal bleeding. With special reference to blood transfusion.

Upper gastrointestinal haemorrhage in 978 unselected patients during a 9-year period was reviewed in regard to incidence, diagnosis, treatment and mortality rate. The annual incidence was 1/1,000 of the catchment population. The source of bleeding was established in 89% of cases. Peptic ulcer accounted for 53% of total admissions. Blood transfusion was given only when the haemoglobin was less than 8.0 g/dl or if the patient was in shock. Emergency surgery was performed on only 31 patients (3%). The perioperative mortality was 13% and the overall mortality 6%. It is concluded that current treatment policy resulted in low rates of operation and mortality in these unselected cases of upper gastrointestinal haemorrhage. The results support the theory that a hypercoagulable state in gastrointestinal bleeding is counteracted by citrated stored blood.     

Effects of smoking and irradiated volume on inflammatory response in the lung of irradiated breast cancer patients evaluated with bronchoalveolar lavage

Quantitative measurements of the effects of irradiation on normal tissues in humans have been hard to obtain because most tissues are inaccessible and/or direct responses are difficult to quantify in a nondestructive manner. Pneumonitis and fibrotic lung disease are adverse effects seen in varying intensity in patients treated with radiotherapy for carcinomas of the thorax, e.g., breast cancer. In the present study the aim was to evaluate the inflammatory reaction in the underlying parenchyma following postoperative irradiation with bronchoalveolar lavage technique. Twenty-one patients (11 smokers, 10 nonsmokers) with breast cancer stage T1N0M0 received radiotherapy with photons to a target dose of 56 Gy following breast conservative surgery. Nineteen healthy controls were also included. The results showed a clear elevation of neutrophils, mast cells, eosinophils, and lymphocytes in the total irradiated groups, compared to controls. When subclassifying the material according to smoking habit, it was obvious that the smokers displayed a significantly decreased inflammatory reaction, i.e., reduced levels of mast cells and lymphocytes, compared to both nonsmoking controls and patients. Eosinophils were seen in an elevated number in all irradiated patients. Radiological signs of pneumonitis were observed in three patients, all in the nonsmoking group. No correlation was found between the volume of lung irradiated and the inflammatory response. It is concluded that bronchoalveolar lavage is a suitable and sensitive method for investigating radiotherapy-induced reactions in the human lung. Furthermore, ongoing smoking during the treatment depressed the inflammatory response in the lung parenchyma induced by irradiation. The present study as well as earlier observations justify further studies concerning the possibility of interaction of smoking with cancer treatment, both from the view of therapeutic failures and reduced adverse effects.     

Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia

Muscle energy metabolism was studied by chemical analysis of biopsy samples from: 1) trigger points in the trapezius muscle from 15 patients with primary fibromyalgia (PF), 2) nonpainful, anterior tibial muscle from 6 patients with PF, and 3) the trapezius muscle from 8 healthy controls. We found a decrease in the levels of adenosine triphosphate, adenosine diphosphate, and phosphoryl creatine, and an increase in the levels of adenosine monophosphate and creatine, in the trapezius muscles from the patients. These findings support the notion that the pain in patients with PF is of muscular origin.     

Integrating virtual patients into courses: follow-up seminars and perceived benefit

Medical Education 2012: 46 : 417–425 Context The use of virtual patients (VPs) suggests promising effects on student learning. However, currently empirical data on how best to use VPs in practice are scarce. More knowledge is needed regarding aspects of integrating VPs into a course, of which student acceptance is one key issue. Several authors call for looking beyond technology to see VPs in relation to the course context. The follow‐up seminar is proposed as an important aspect of integration that warrants investigation. Methods A cross‐sectional explanatory study was performed in a clinical clerkship introduction course at four teaching hospitals affiliated to the same medical faculty. The VP‐related activities were planned collaboratively by teachers from all four settings. However, each setting employed a different strategy to follow up the activity in the course. Sixteen questionnaire items were grouped into three scales pertaining to: perceived benefit of VPs; wish for more guidance on using VPs, and wish for assessment and feedback on VPs. Scale scores were compared across the four settings, which were ranked according to the level of intensity of students’ processing of cases during VP follow‐up activities. Results The perceived benefit of VPs and their usage were higher in the two intense‐use settings compared with the moderate‐ and low‐intensity settings. The wish for more guidance was high in the low‐ and one of the high‐intensity settings. Students in all settings displayed little interest in more assessment and feedback regarding VPs. Conclusions High case processing intensity was related to positive perceptions of the benefit of VPs. However, the low interest in more assessment and feedback on the use of VPs indicates the need to clearly communicate the added value of the follow‐up seminar. The findings suggest that a more intense follow‐up pays off in terms of the benefit perceived by students. This study illustrates the need to consider VPs from the perspective of a holistic course design and not as isolated add‐ons.