A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.

The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.     

创伤后迟发性脑肿胀的临床特点与治疗

目的 探讨创伤后迟发性脑肿胀的临床特点、发病机制与治疗。方法 回顾性分析1998年1月～2005年6月年收治的17例迟发性脑肿胀患者的临床特点和救治情况。结果 所有颅脑损伤患者采用保守治疗后均有好转，但于伤后5-10d出现恶化，CT复查有脑肿胀，经加强综合脱水等治疗后16例治愈，1例死亡。结论 迟发性脑肿胀好发于对冲性额、颞叶挫裂伤伴明显蛛网膜下腔出血、硬膜下薄层血肿及早期CT有脑肿胀者。其发病机制可能与创伤后的迟发性脑血管痉挛、微循环障碍、静脉回流障碍及甘露醇作用下降等因素有关。此类患者病情隐蔽性强，应加强观察、积极行CT复查，如能早期明确诊断，保守治疗多数效果良好。     

Experimental stress fractures of the tibia. Biological and mechanical aetiology in rabbits

We have shown that stress fractures can be induced in the tibial diaphysis of an animal model by the repeated application of non-traumatic impulsive loads. The right hind limbs of 31 rabbits were loaded for three to nine weeks and changes in the bone were monitored by radiography and bone scintigraphy. The presence of stress fractures was confirmed histologically in some cases. Most animals sustained a stress fracture within six weeks and there was a positive correspondence between scintigraphic change and radiological evidence. Microscopic damage was evident at the sites of positive bone scans. The progression, location, and time of onset of stress fractures in this animal model were similar to those in clinical reports, making the model a useful one for the study of the aetiology of stress fractures.     

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p < 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (–6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p < 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p < 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.     

EEG findings in hypomelanosis of Ito.

The EEG findings in 15 children with Hypomelanosis of Ito have been reviewed and related to the clinical and CT scan data. Although no consistent electroclinical associations were found in the group as a whole, there was some association between the presence of abnormal rhythmic EEG activity and the radiological appearances of neuronal migration defects. In addition, the possibility is raised that there may be a distinctive sub-group of children with Ito's syndrome who present with an early onset of intractable seizures and who have a neuronal migration defect.     

A new fluorescent mitochondrial antibody: Disease association

The case notes of 34 patients whose sera contained an antibody giving an unusual immunofluorescent staining pattern were reviewed. This antibody designated M2(1) gave a slightly different pattern of staining on composite sections of rat liver, kidney and stomach from the primary biliary cirrhosis associated M2 antimitochondrial antibody. Anaemia was present in 10 patients, endocrine disease in 7 patients and autoimmune liver disease in 6 patients. We did not find the presence of M2(l) antibody to be of specific diagnostic significance. Although the M2(l) antibody is rare, caution is required in order to avoid confusion between this antibody and the M2 antimitochondrial antibody of primary biliary cirrhosis.     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.