FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

肌病肾病代谢综合征治疗进展

肌病肾病代谢综合征是急性动脉阻塞致骨骼肌溶解的严重并发症。积极治疗原发病，及早补液扩容、碱化尿液、早期血液净化治疗是降低截肢率、病死率的关键。本文就肌病肾病代谢综合征治疗进展作一综述。     

单独肝尾状叶血管瘤切除术

肝尾状叶由于解剖位置特殊,位置深,难以显露,手术难度大,是肝脏外科领域手术操作的难点与研究热点.随着肝血流控制技术的发展、肝实质离断技术的提高,肝尾状叶肿瘤切除率明显提高[1].2006年4月至2008年10月,我科完成单独肝尾状叶血管瘤切除术9例,现将手术技巧与疗效报道如下.     

Nicotine applied by transdermal patch induced HSV-1 reactivation and ocular shedding in latently infected rabbits.

The identification of factors involved in herpes virus latency and reactivation is critical to a better understanding of the mechanisms essential to viral neuroinvasiveness and neurovirulence. Recurrent episodes of ocular herpes infections cause irreversible corneal scarring and are the primary cause of loss of vision due to an infectious agent in industrialized countries. In this study, we examined the ability of nicotine, a compound known to be involved in stress-associated immunomodulation and recognized as one of the most frequently used addictive agents, to induce ocular shedding in rabbits latently infected with herpes simplex virus type 1 (HSV-1) strain McKrae. New Zealand white rabbits latently infected with HSV-1 at 3-4 weeks post-inoculation were randomly divided into two groups. The corneas of all rabbits were free of lesions as verified by slit lamp biomicroscopy. One group received nicotine by transdermal patch (21 mg/day) for 20 days and the other group served as the control. Reactivation data were obtained by detection of virus in tear film collected by ocular swabbing performed concurrently with the administration of nicotine. Compilation of data from three separate experiments demonstrated that 16.5% (258/1560) of the swabs taken from rabbits treated with nicotine were positive for virus, compared with 8.3% (53/639) of swabs taken from controls. Rabbits receiving nicotine exhibited a significantly (P < 0.0001) higher rate of ocular shedding than controls. The concentration of nicotine in the serum was determined at various times (0-24 hrs) after new patch replacement. Peak (average) serum level of nicotine was obtained 8 hours after patch replacement and exhibited a broad range of values (0.233 microg/mL-6.21 microg/mL). These results suggest that an initial systemic exposure to nicotine significantly increases HSV-1 reactivation. Further studies are needed to reveal any effects of nicotine dependency and nicotine withdrawal on herpesvirus reactivation.     

Spontaneous cyclic contractions of the capillary wall in vivo, impeding red cell flow: a quantitative analysis. Evidence for endothelial contractility

We have videorecorded spontaneous cyclic contractions of capillary walls which often stopped the flow of blood cells, in spleens of rat and mouse. An inverted microscope and oblique lighting were key elements in obtaining images in which the boundaries of cells composing vessel walls were clearly distinguishable. Using slow motion replay, we measured the widths of endothelial cells (C), pericytes (P, when present) and capillary lumens (L; at the site of constriction; U; 15-20 micron upstream), throughout 11-12 min sequences containing many contraction/relaxation cycles. In roughly 50% of contractions L decreased to 0-1 micron, such luminal "closures" occurring within 2-12 sec and lasting for less than 1 sec to greater than 1 min. Intervals between contractions ranged from 12 sec to 3 min (average 1 min). Documentation of one such cycle by sequential photographs from the video monitor is presented, showing dramatic bulging of an endothelial cell into the lumen. Comparison of records of L and C versus time showed that almost invariably when L decreased C increased, and vice versa; highly significant correlations existed between C and L in every case (P less than 0.0005). Multiple linear regression analysis showed that changes in C were responsible for 18-77% of the total variance in L, whereas P contributed only 0-4%; changes in U, covariance between C, P, and U, and unexplained variance were responsible for 0-20, 11-30, and 11-53%, respectively, of the total variance in L. We conclude that these spontaneous capillary contractions were primarily due to endothelial contractility.     

Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype

Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits.     

Characterization of a galactose-1-phosphate uridylyltransferase gene from the marine red alga Gracilaria gracilis

The metabolism of D-galactose is a major feature of red-algal physiology. We have cloned and sequenced a gene from the red alga Gracilaria gracilis that encodes a key enzyme of D-galactose metabolism, galactose-1-phosphate uridylyltransferase (GALT). This gene, designated GgGALT1, is apparently devoid of introns. A potential TATA box, four potential CAAT boxes, and a repeated sequence occur in the 5′-flanking region. The predicted 369-aa peptide shares significant sequence similarity with GALTs from other organisms (human, 47%; Saccharomyces cerevisiae, 49%; Solanum tuberosum, 49%). Southern-hybridization analysis reveals two related, but apparently not identical, GALT genes in the nuclear genome of G. gracilis. Sequence analysis indicates that the GgGALT1 enzyme lacks a rubredoxin “knuckle” motif, which in bacterial and fungal GALTs is involved in binding zinc. An open reading frame encoding a potential peptidyl tRNA hydrolase occurs 179 bp downstream from the GgGALT1 gene. Received: 6 April / 2 June 1998     

Vascular networks of the nucleus lentiformis

Summary The nucleus lentiformis vascular networks were studied in 30 brains by injecting the vascular system with gelatinous Indian ink. The nucleus lentiformis is divided into a medial part, the globus pallidus, and a lateral part, the putamen. These two parts differ completely from one another in their embryology, structure and functions. For these reasons, each part presents a specific vascular network. The putaminal network is dense and shows many similarities with the cerebral cortex vascular network; the pallidal one is simpler and less dense. These two vascular networks are located close to each other without overlapping. Their specificity may be in relation with the histological structure, with the morphogenetic evolution or with the functional activity of both nuclei to which they provide the vascularization.

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Les réseaux vascularies du noyau lenticulaire

Résumé L'étude des réseaux vasculaires du noyau lenticulaire (NL) est réalisée sur 30 cerveaux dont le système vasculaire a été injecté à l'encre de Chine gélosée. Le NL est constitué par deux parties, le putamen (néostriatum) et le globus pallidus (paléo-striatum), totalement différentes sur les plans morphologique, embryologique et fonctionnel. Chacune de ces parties possède un réseau vasculaire spécifique et caractéristique. Les deux réseaux se côtoient sans se chevaucher. Le réseau vasculaire putaminal est dense et présente de nombreuses similitudes avec le réseau vasculaire du cortex cérébral. Le réseau vasculaire pallidal se caractérise par sa simplicité et sa moindre densité. Leur spécificité peut être en rapport avec la structure histologique, l'évolution morphogénétique et avec l'activité fonctionnelle des noyaux dont ils assurent l'irrigation.

     

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.