Selective blood-tumor barrier disruption by leukotrienes.

The authors have previously reported that intracarotid infusion of 5 micrograms leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 microgram to 50.0 micrograms (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 micrograms compared to vehicle alone (90.00 +/- 21.14, 92.68 +/- 15.04, and 80.17 +/- 16.15 vs. 39.37 +/- 6.45 microliters/gm/min, respectively; mean +/- standard deviation; p less than 0.01). No significant change in Ki within the tumors was observed at the 0.5-microgram LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 +/- 15.04 microliters/gm/min), but declined at 30 minutes (56.58 +/- 12.50 microliters/gm/min) and 60 minutes (55.40 +/- 8.10 microliters/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 3 1/2-fold compared with vehicle alone (139.86 +/- 23.95 vs. 39.37 +/- 6.45 microliters/gm/min).     

Symptoms and health status before and six weeks after open cholecystectomy: a European cohort study.ECHSS Group. European Collaborative Health Services Study Group.

The impact of open cholecystectomy on patients' symptoms and health status and their level of satisfaction has been examined to provide a basis for comparison with newer rival treatments. A prospective cohort study using patient and surgeon completed questionnaires before and six weeks after surgery was carried out in 14 general hospitals in eight European countries. Five hundred and eighty three patients were recruited consecutively in 1990 to 1991. Information on their symptoms, general health status, activities of daily living, and satisfaction with their care were collected. After surgery 42.8% of patients reported that they were free of symptoms. Symptoms varied in their responsiveness to surgery--six weeks after surgery 89% of those who had complained of vomiting had improved, 81% of nausea, 69% of loss of appetite, 65% of abdominal pain, and 51% of flatulence. In contrast 28.1% of patients still suffered from flatulence and 23.5% continued to complain of abdominal pain. Most patients' (62.7%) general health improved, 28% were unchanged, and 9.3% were worse. After surgery most patients reported no restrictions in their normal social activities (75-90% depending on the activity) and most (89.5%) felt the results of their operation had been as expected or better than expected. Most patients undergoing open cholecystectomy reported an improvement in their symptoms, health status, and social functioning. This was reflected in their high level of satisfaction. Some patients, however, gained no benefit and a small proportion were worse than before surgery.     

Type II sodium channels in spinal cord astrocytes in situ: Immunocytochemical observations

The expression of sodium channel α-subunit isoforms in astrocytes in adult rat spinal cord and optic nerve was examined utilizing immunocytochemical methods with antibodies generated against conserved and subtype-specific sequences of the sodium channel. In adult rat spinal cord, astrocytes within the dorsal and ventral funiculi were immunolabelled with antibody SP20, which recognizes a conserved sequence within sodium channel types I, II, and III. In addition, astrocytes within these spinal cord white matter tracts were immunostained with antibody SP11-II, which recognizes sodium channel type II. Antibodies SP11-I and SP32-III, which are directed against subtype-specific sequences in sodium channel types I and III, respectively, did not label astrocytes in the dorsal and ventral funiculi of the spinal cord. In optic nerves, astrocytes were immunostained with antibody SP20. However, no detectable labelling of cells within the optic nerve was observed with antibodies SP11-I, SP11-II, and SP32-III. These observations demonstrate that sodium channel II is expressed by astrocytes in spinal cord white matter. Moreover, these data suggest that regional factors regulate the level of sodium channel isoform expression in astrocytes.     

Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the mice were treated topically with 8-MOP and then exposed to UVA (5 J/cm²). Mice receiving the omega-3 fatty-acid source exhibited a marked decrease in inflammatory response and a more rapid repair, as expressed both grossly and microscopically. In support of the latter response, i.e. repair, ornithine decarboxylase activity was about 20% greater in animals receiving the omega-3 fatty-acid source. The effects of the dietary fatty acid sources on PUVA tumorigenesis were examined in long-term studies in which animals were treated topically with 0.01% 8-MOP thrice weekly after which they were exposed to UVA (1 J/cm²). These studies indicated that a dietary lipid rich in omega-3 fatty acid and known to exhibit anti-inflammatory properties can markedly ameliorate the course of PUVA toxicity but does not impede the course of PUVA tumorigenesis     

Autoimmune progesterone dermatitis: absence of contact sensitivity to glucocorticoids, oestrogen and 17-α-OH-progesterone

Autoimmune progesterone dermatitis is a rare condition, characterized by recurrent premenstrual exacerbations of a dermatosis, in which sensitivity to progesterone can be demonstrated. The sensitizing mechanism is unknown. The aim of this study was to test the hypothesis that cross-sensitivity between steroid groups could induce allergy to endogenous progesterone in these patients. 5 patients with autoimmune progesterone dermatitis and 1 with oestrogen-sensitive dermatitis have been patch tested with a corticosteroid series, conjugated oestrogen 1% in petrolatum (pet.), and 17-α-OH-progesterone 2% pet. There were no immediate or delayed reactions at 2 and 4 days to any steroid group. We have therefore been unable to demonstrate steroid cross-sensitivity, or a use for 17-α-OH-progesterone in the investigation of oestrogen - and progesterone-sensitive dermatoses.     

Aggressive angiomyxoma with gastrointestinal communication: a case report

We report the imaging findings of an abdominal aggressive angiomyxoma, which communicated with the gastrointestinal tract. The literature on this rare tumor is reviewed.     

Transoesophageal echocardiography in heart disease—old technologies, new tricks

Cardiac ultrasound and upper gastrointestinal endoscopy are relatively old technologies. With the introduction of new ultrasound probes and by incorporating ultrasound technology into conventional endoscopes, ‘new tricks’ in cardiac imaging were discovered. Posterior structures of the heart are now able to be imaged clearly by the ultrasound probe from the oesophagus. Consequently, better resolution of cardiac anatomy allows more accurate diagnosis of cardiac pathologies which is not possible using conventional transthoracic (TT) approach. Over a period of two years, 1200 cases of transoesophageal echocardiography (TOE) were undertaken in our institution. The major indications were diseases of the aorta (10%), source of cardioembolism (28%), assessment of native and prosthetic valve function (20%), suspected endocarditis and its complication (17%), pre and post percutaneous transluminal mitral valvotomy (PTMV [13%], congenital heart disease (2%) and others (10%). The greatest impact with TOE is in the diagnosis of aortic dissection and transection, TOE is superior to conventional TT approach in detecting potential source of embolism, valvular vegetations and its complication, native and prosthetic valve dysfunction and LA thrombus prior to PTMV. Observations by TOE such as spontaneous echo contrast (SEC) in the left atrium open new challenges for further research in its role in the pathogenesis of LA thrombus and its association with cardioembolic event. Other areas of interest include; reclassification of distal aortic dissection and the use of TOE in intra-operative work.