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BACKGROUND: Prospective data on the use of prilocaine for ambulatory spinal anaesthesia remain limited. We compared the behaviour and characteristics of subarachnoid block using prilocaine and fentanyl with that of bupivacaine and fentanyl. METHODS: In a prospective, double-blind, randomized controlled trial, 50 patients undergoing elective ambulatory arthroscopic knee surgery received subarachnoid anaesthesia, with either prilocaine 20 mg and fentanyl 20 µg (Group P) or plain bupivacaine 7.5 mg and fentanyl 20 µg (Group B). Primary endpoints included times for onset of maximum sensory block level and regression of sensory block to L4, and also motor block at 1 and 2 h, and levels of haemodynamic stability. Comparisons between the groups were made by χ² test for proportions and the Mann-Whitney test for ordinal data. Time-to-event data were analysed by the Mann-Whitney test for uncensored data or the logrank test for censored data. RESULTS: At 2 h, motor block in Group P had fully resolved in 86% of patients, compared with 27% in Group B (P<0.001). Median time to regression of sensory block to L4 was significantly shorter in Group P (97 min) than in Group B (280 min) (P<0.001). A clinically significant decrease in arterial pressure was more common in Group B (73%) than in Group P (32%) (P=0.004). Two patients in Group P required conversion to general anaesthesia, but for reasons unrelated to prilocaine itself. CONCLUSIONS: The combination of prilocaine and fentanyl is a better alternative to that of low-dose bupivacaine and fentanyl, for spinal anaesthesia in ambulatory arthroscopic knee surgery.

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Along with apolipoprotein (apo) E, which promotes cholesterol efflux from foam cells, apoA1-containing high density lipoprotein (HDL) is thought to facilitate the transport of cholesterol from lesions. This role for apoA1 was tested in vivo by lethally irradiating apoE-deficient and apoE- plus apoA1-deficient mice and reconstituting them with bone marrow cells isolated from wild-type (WT) mice. ApoE, but not apoA1, was synthesized by the transplanted bone marrow-derived cells. Therefore, this transplantation procedure generated apoE-deficient animals with atherosclerotic lesions that contained both apoE and apoA1 (E/A1 mice) and apoE-deficient animals with lesions that contained apoE but no apoA1 (E/A1o mice). As shown previously, the transplanted WT macrophage-derived apoE dramatically lowered the plasma hypercholesterolemia in both groups. On feeding with an atherogenic diet after transplantation, plasma cholesterol levels were raised in both groups of mice, but the levels in the E/A1 mice at 20 weeks were 2- to 3-fold higher than in E/A1o mice. Immunohistochemical staining verified that apoE was abundant in lesions of both groups, whereas apoA1 was detected in the lesions of E/A1 mice only. Despite a 2- to 3-fold lower total plasma cholesterol in the E/A1o mice, the free cholesterol recovered from isolated aortas was approximately 60% higher and the mean lesion area in serial sections of the aortic valves 45% larger. Therefore, apoA1 reduces free cholesterol accumulation in vivo in atherosclerotic lesions.

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The inverse correlation between plasma high density lipoprotein (HDL) levels and the risk for cardiovascular disease has been attributed in part to the role of HDL in facilitating the transport of cholesterol to the liver for catabolism. One component of this reverse cholesterol transport is removal of excess cholesterol from peripheral cells. An immunochemical approach was employed to evaluate the role of human apolipoprotein (apo) A-I in cellular cholesterol efflux and to test the hypothesis that discrete structural domains of the molecule mediate this function. Two apoA-I-specific monoclonal antibodies (AI-11 and AI-14) inhibited in vitro cellular cholesterol efflux from THP-1 monocytic cells to HDL or apoA-I proteoliposomes by approximately 50%. Six other antibodies had no effect although three of these bound significant proportions of the apoA-I proteoliposomes. Antibody AI-11 binds apoA-I amino acid residues 96-111 (Banka, C. L., Bonnet, D. J., Black, A. S., Smith, R. S., and Curtiss, L. K. (1991) J. Biol. Chem. 266, 23886-23892). The AI-14 epitope was localized to residues 74-105. Therefore, the two antibodies that inhibited HDL promotion of cellular cholesterol efflux bound overlapping but distinct regions of the apoA-I molecule.

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Apolipoprotein (apo) A-I, the major apoprotein of human high density lipoprotein, is a vital cofactor for lecithin-cholesterol acyltransferase (LCAT), the plasma enzyme responsible for esterification of free cholesterol associated with high density lipoprotein. This esterification is an important component of the reverse cholesterol transport process. An immunochemical approach was used to test the hypothesis that a discrete region of apoA-I was important for LCAT activation. Three human apoA-I-specific monoclonal antibodies were found to inhibit LCAT activation in vitro in a manner directly proportional to their ability to bind to apoA-I-proteoliposomes in fluid phase immunoassays. This relationship was not observed with another four apoA-I-specific antibodies that also were able to bind to the apoA-I proteoliposomes. The use of synthetic peptides representing short amino acid sequences of the apoA-I molecule facilitated the identification of discrete but overlapping apoA-I epitopes for those antibodies that interfered with LCAT-mediated cholesterol esterification. These epitopes spanned amino acid residues 95-121 of mature apoA-I. Therefore, this region is most likely involved in the activation of LCAT by apoA-I.

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The human monocytic leukemia cell line, THP-1, shares many properties with human monocyte-derived macrophages and might be a useful model for studying foam cell formation in vitro. Therefore, we examined the ability of THP-1 cells to accumulate cholesteryl esters, the hallmark feature of foam cells, in response to culture with native low density lipoprotein (LDL), modified LDL, and platelets. THP-1 cells stored more cholesteryl esters than macrophages in response to 200 micrograms/ml of LDL. Down-regulation of LDL receptors occurred in macrophages at lower LDL concentrations than in THP-1 cells. Phorbol ester-treated THP-1 cells stored more cholesteryl esters than human macrophages in response to 25-200 micrograms/ml of acetylated LDL. Because we have previously demonstrated that activated platelets enhanced macrophage cholesteryl ester storage, we examined the ability of THP-1 cells to store cholesteryl esters in response to coculture with platelets. Compared with macrophages, dividing THP-1 cells and phorbol ester-treated THP-1 cells accumulated only 50% and 33% as much cholesteryl esters, respectively. Furthermore, although platelets induced a 90% reduction in cholesterol synthesis in macrophages by day 5, cholesterol synthesis in THP-1 cells and phorbol ester-treated THP-1 cells was inhibited less than 50% by platelets. Nevertheless, both THP-1 cells and macrophages responded to platelets by increasing their secretion of apolipoprotein E. Therefore, we conclude that dividing THP-1 cells and phorbol ester-treated THP-1 cells are capable of forming foam cells in response to physiologic doses of both LDL and acetylated LDL, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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The early fatty streak lesions of atherosclerosis are characterized by the presence of cholesteryl ester-loaded macrophages or "foam cells." Platelets are also present in the early lesions of atherosclerosis and are often found in close association with foam cells. We have investigated the hypothesis that platelets contribute to foam cell formation by inducing macrophage cholesteryl ester accumulation. Using an in vitro culture system of human monocyte-derived macrophages and autologous platelets, we have demonstrated a platelet-dependent stimulation of macrophage cholesterol esterification and cholesteryl ester accumulation. The response is specific to platelets and is dependent upon activation of the platelets. An active fraction can be isolated from the releasates of thrombin-stimulated platelets that contain large cholesterol-rich platelet membrane vesicles. The results suggest that platelet-derived free cholesterol is required for platelet-induced macrophage foam cell formation.

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This study set out to determine whether the term 'inflammatory' in a cervical smear report implies underlying infection or whether it could be masking cancerous or precancerous changes. Of 826 smears taken in one practice over one year, 42 demonstrated some degree of inflammatory change. Thirty four of these women presented for swabs and almost half (47%) had a microbiologically proven infection. This group was further subdivided, and of those whose smears were reported as simple 'inflammation', just over one third (35%) were infected but of those whose smears were reported as 'severe inflammation', over two thirds were infected (73%). The commonest organisms isolated were Gardnerella vaginalis and Candida albicans. It would therefore appear to be worthwhile to treat patients who report severe inflammation with metronidazole and with anti-fungal pessaries before the smear is repeated. Following treatment two women went on to show dyskaryosis within five months. On colposcopy one of these women was found to have invasive cervical squamous cell carcinoma. It is concluded that whether women with inflammatory smears are treated or not, it is mandatory to repeat the smear, ideally within five months.

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Because of a close association between platelets and macrophages in early fatty streak lesions, the hypothesis was tested that platelets contribute to lesion progression by directly enhancing macrophage cholesteryl ester (CE) accumulation. Both the rate of cholesterol esterification and the accumulation of CE were increased within 24 h of the co-culture of adherent macrophages with platelets. Maximum increases in esterification and CE accumulation were observed within 3 to 4 d of culture and were greater than 10-fold over controls. Optimum accumulation of CE by 5 X 10(5) was obtained with 5 X 10(8) autologous platelets. When similar amounts of free cholesterol were supplied with platelets, red blood cells (RBC), RBC ghosts, or sonicated RBC, only platelets enhanced macrophage CE accumulation, which indicates specificity for platelets. Products released from platelets 30 min after thrombin stimulation were active as well. The results suggest that platelets and/or substances shed by activated platelets are potent mediators of macrophage CE accumulation.

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The deposition of calcium and phosphorous salts in the soft tissues can be classified into three categories: metastatic calcification, dystrophic calcification, and calcinosis. Metastatic calcification occurs when the calcium-phosphorous levels are elevated. The calcifications involve normal tissues. Associated disease include hyperparathyroidism, neoplasms, milk-alkali syndrome, hypervitaminosis D, and tumoral calcinosis. Dystrophic calcification occurs in the presence of normal metabolism in damaged or devitalized tissues. Disorders included in this classification are: Ehlers-Danlos syndrome, pseudoxanthoma elasticum, arteriosclerosis obliterans, venous calcifications, crystal deposition disorders, and calcification resulting from neurologic disorders. Calcinosis is also found in persons with normal metabolism. It occurs most often in subcutaneous tissues, skin, and related connective tissues. Associated disorders include: calcinosis universalis, calcinosis circumscripta, scleroderma, dermatomyositis, and systemic lupus erythematosus.

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