Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

Background  

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers.     

经鼻内镜筛窦纸板进路眶内手术

目的探讨经鼻内镜筛窦纸板进路手术治疗眶内各种疾病的可行性并确立临床处理的基本原则.方法经鼻内镜进路眶内手术10例眶内异物取出术4例、球后海绵状血管瘤切除术1例、眶内侵犯或转移的恶性肿瘤切除术5例.结果眶内异物取出术3例成功,1例失败;球后海绵状血管瘤1例完整切除;鼻咽癌眶内转移1例手术切除+放射治疗后随访4年无复发,视力恢复至0.6;其他眶内恶性肿瘤4例,手术后随访1～4年均健在.10例手术后1例视力损伤,9例均保留原有视力,其中3例失明病例中2例视力有一定程度的恢复.结论位于视神经内侧的某些占位性病变可以经鼻内镜筛窦纸板进路完成.当代先进的放射治疗技术为眶内恶性肿瘤的保守性手术创造了条件.     

A research algorithm to improve detection of delirium in the intensive care unit

Introduction  

Delirium is a serious and prevalent problem in intensive care units (ICUs). The purpose of this study was to develop a research algorithm to enhance detection of delirium in critically ill ICU patients using chart review to complement a validated clinical delirium instrument.     

The inflammatory response in drug-induced acute urticaria: ultrastructural study of the dermal microvascular unit

BACKGROUND: Drug exposure is one of the main aetiologies of urticaria and represents the second most common cause in acute urticarias. Studies involving the ultrastructural aspects of urticaria are relatively rare in the literature. Most of the articles published report on skin biopsies of experimentally induced urticaria, and acute urticaria has been studied even less from a morphological point of view. OBJECTIVES: The aims of this study were to observe ultrastructural cell characteristics in five patients with drug-induced acute urticaria and possible aspects of the inflammatory skin response. METHODS: Clinical manifestations, light microscopy and transmission electron microscopy were evaluated. RESULTS: With light microscopy, a mild perivascular lymphocyte-monocyte infiltrate was observed with few neutrophils and dermal oedema in skin biopsies of five patients. With electron microscopy, a mild vascular dilatation was observed, with platelets in the lumen and several lymphocytes and dendritic cells close to the superficial dermal vessels. Some mast cells appeared normal, whereas others were granule-depleted. In some areas, mast cells, lymphocytes and satellite dendritic cells were closely associated, as well as some macrophages. A significant number of plasma cells, eosinophils and polymorphonuclear neutrophils were not observed; however, the presence of lymphocytes and macrophages was significant. The epidermis and the dermal-epidermal junction were preserved, except for a discrete oedema in keratinocytes. CONCLUSIONS: The ultrastructural aspect of drug-induced acute urticaria is similar to that observed in urticaria caused by Urtica dioica, intradermal histamine and cold urticaria. The presence of the cellular triad with mast cells, dendritic (or satellite) cells and lymphocytes suggests a functional interaction of these cells. These findings support the possible existence of mechanisms in the dermis that may participate in protective and/or injurious vasocentric immune reactions.     

Very low birthweight infants: outcome in a sub-Arctic population

Objective : To evaluate the outcome for very low birthweight (VLBW) infants in northern Norway. Subjects and methods: All live born infants ( n = 536) with birthweight ≤1500g born during 1978–89 to women residing in the northern health region of Norway were studied retrospectively. Data were from the Medical Birth Registry (MBR), hospital records and from follow-up recordings to 4 y of age at maternal and child health centres. Stillborn infants ( n = 269) with birthweight ≤1500g during the same period were also registered. Results : The annual incidence of live born VLBW infants (7.1/1000 live births) did not change, but the proportion of infants born alive before 26 weeks'gestation increased and the stillborn part decreased significantly. The Caesarean section (CS) rate, antenatal transfer and the use of a neonatal transport team increased significantly. Four hundred and seventy-five infants (89%) were considered viable at birth, 347 (65%) survived to 1 y and 343 (64%) to 4y. The likelihood of survival was independently related to female gender. The trend for survival to 4y of age did not increase significantly. Thirty children suffered from cerebral palsy (8.7% of survivors, 5.6% of live births) and the cerebral palsy rate for infants with birthweight 751-1000 g decreased. The proportion of survivors considered to be normal or mild disabled increased and the part suffering from moderate or severe disability decreased significantly. Conclusions : In spite of long distances and unfavourable climatic conditions VLBW infants can be adequately cared for in this sparsely populated region of Norway.     

Increased bile acid pool inhibits cholesterol 7 alpha-hydroxylase in cholesterol-fed rabbits

BACKGROUND & AIMS: Cholesterol feeding unexpectedly inhibits cholesterol 7 alpha-hydroxylase in rabbits. The aim of this study was to explore the mechanism. METHODS: Twenty male New Zealand white rabbits were fed regular chow with and without 2% cholesterol for 10 days followed by 7 days of bile drainage. The activities of hepatic cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase that control bile acid synthesis in classic and alternative pathways were related to the size and composition of bile acid pool. RESULTS: After feeding cholesterol, plasma and hepatic cholesterol concentrations increased, the bile acid pool doubled (from 254 +/- 44 to 533 +/- 51 mg; P < 0.001), cholesterol 7 alpha-hydroxylase activity decreased 68% (P < 0.01), but sterol 27-hydroxylase activity increased 66% (P < 0.05) with increased cholic acid synthesis (P < 0.01). Bile drainage in the cholesterol-fed rabbits depleted the bile acid pool and stimulated down- regulated cholesterol 7 alpha-hydroxylase activity 11.4-fold (P < 0.001), although hepatic cholesterol remained elevated. Hepatic sterol 27-hydroxylase activity was unaffected. CONCLUSIONS: Feeding cholesterol increased hepatic cholesterol and stimulated sterol 27- hydroxylase and alternative bile acid synthesis, which expanded the bile acid pool and inhibited cholesterol 7 alpha-hydroxylase in rabbits. In distinction, hepatic sterol 27-hydroxylase was insensitive to changes in the bile acid pool. (Gastroenterology 1997 Dec;113(6):1958-65)     

Reduced thrombus formation in native blood of homozygous factor VII- deficient patients at high arterial wall shear rate

Inhibition of thrombin formation in flowing native blood reduces thrombus formation on subendothelium, dacron, or collagen fibrils at arterial wall shear rates of 450 to 650 s-1. In the present study, we have investigated the role of low levels of factor VII (FVII) in thrombus formation on collagen fibrils at arterial wall shear rates of 650 s-1 (coronary arteries), 2,600 s-1 (mildly stenosed arteries), and 10,510 s-1 (severely stenosed arteries) in parallel-plate perfusion chambers. In the perfusion chamber with the highest wall shear rate, thrombus formation took place at the apex of an eccentric stenosis, which reduced the cross-sectional area of the blood flow channel by 80%, thus simulating thrombus formation at an atherosclerotic plaque rupture. Native blood from 21 healthy volunteers and 12 homozygous FVII- deficient patients was drawn by a pump directly from an antecubital vein over a surface of fibrillar collagen positioned in the respective perfusion chambers. The patients had FVII coagulant activities ranging from 1.3% to 4.5% and FVII antigen levels of 16% to 23% of normal. Immunoaffinity purification of the patients' FVII followed by electrophoresis (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) and immunoblotting showed a protein with similar molecular mass as normal FVII. In the perfusion studies, a reduction in thrombus volume of 54% of normal (P < .007) at 10,510 s-1 was observed. The deposition of fibrin on the thrombogenic surface and the plasma level of fibrinopeptide A (FPA) in blood samples collected distal to the perfusion chamber were concomitantly reduced (P < .002 and P < .04, respectively). The plasma FPA level was also reduced at 2,600 s-1 (P < .04), but not at 650 s-1. However, at the lower shear conditions, the thrombus volume and the fibrin deposition were within the ranges observed in normal blood. The platelet-collagen adhesion was not affected at any of the three shear conditions. Thus, low plasma levels of FVII result in significantly less formation of thrombin and fibrin in and around growing platelet masses at high shear condition. This may weaken the thrombus stability and reduce platelet recruitment, thereby lowering thrombus volume. In support of this theory, one patient with afibrinogenemia had an 83% reduction in thrombus volume at this high shear condition.