Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers

The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.     

Integrated communications perspectives and the practice of total quality management

Communication is becoming increasingly identified as a significant factor influencing the ability of the NHS to achieve high-quality outcomes. Typically, organizations have tended to conceptualize communication as a process dealing with external relationships. Emphasizes the importance of both internal and external communications, and argues that the NHS now needs to integrate both these dimensions of the communication function. Proposes a strategic framework which suggests how this can be accomplished. Proposes and discusses a communications-centred model of the management process in the light of this approach. This model integrates perspectives which have hitherto dichotomized management as either a science or an art. It also locates communication at the heart of effective management. Finally, suggests the NHS is uniquely well placed to provide data on the impact and costs of total communication programmes.     

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.     

The Organization of Projections from Subdivisions of the Auditory Cortex and Thalamus to the Auditory Sector of the Thalamic Reticular Nucleus in Galago

Anterograde and retrograde transport techniques were used to study the connexions between different subdivisions of the auditory cortex and thalamus with the thalamic reticular nucleus in the prosimian, Galago. In particular, the goal was to determine whether the primary auditory nucleus, GMv, and its cortical target, area I of the auditory cortex (A I), project to a different region of the auditory sector of the reticular nucleus from the secondary auditory nuclei, GMmc and Po and their cortical targets outside A I. The results show that the projections to and from the auditory sector are indeed segregated: injections of wheatgerm agglutinin-conjugated horseradish peroxidase into either GMmc or Po labelled cells and terminals along the medial, lateral and ventral borders of the auditory sector, forming a U-shaped pattern. Projections from area II of the auditory cortex produced almost an identical pattern of the terminal labelling in the auditory sector. In contrast, injections into GMv-labelled cells and terminals in the centre region of the auditory sector, in the 'interior' of the U-shaped region. Projections from A I were distributed to both the U-shaped border region and the central core of the auditory sector probably because A I received projections from GMmc, Po and GMv. The significance of these results depends on a comparison between the auditory and visual sectors of the reticular nucleus. Both sectors are divided into tiers or subsectors-one related to the primary relay nucleus, i.e. GLd or GMv, and the other related to the secondary relay nuclei, i.e. pulvinar nucleus, GMmc, Po, etc.     

The work of play for parents of schizophrenic children

During treatment the schizophrenic child begins to emerge from his constricted, self-centered world and to enjoy interaction, play and playfulness. Many of the parents are as constricted and unable to play as their children. The use of a play corner, dress-up clothes and a staff member who can model roles to play helps reduce the work of play for parents and child. Their resulting mutual pleasure and increased spontaneity enhances treatment.professor of psychiatry and Director of the Division of Child and Adolescent Psychiatry and Children's Psychiatric Center     

益母草的化学、药理和临床研究进展

查阅近20年有关文献，对益母草的化学成分、药理作用、临床应用研究进展进行综述。益母草主要含有生物碱类、黄酮类、二萜类、脂肪酸类、挥发油类等化合物；药理作用研究证明其具有调经止血、保护心肌缺血再灌注损伤、抗血小板聚集、降低血液黏度等作用；在临床上常用来治疗流产后出血、冠心病、心肌缺血、高黏血症、痛经等疾病。益母草具有广泛的药理活性，对其药效学物质基础进行深入研究和开发，将具有重要意义。     

Time course and predictors of symptoms after primary prostate cancer therapy.

PURPOSE: Understanding the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer (PC) may improve patients' choice of treatment and later help them adjust to its consequences. We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies. PATIENTS AND METHODS: In a prospective cohort study of 417 men we assessed urinary, bowel, and sexual function from before primary treatment to 24 months after. To control for potential confounding, we measured sociodemographic and PC prognostic factors, medical comorbidity, and pretreatment function commonly affected by PC and its treatment. RESULTS: Patients who underwent external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT) differed significantly in sociodemographic factors, cancer prognostic factors, and pretreatment symptom status, especially sexual function. Urinary incontinence increased sharply after RP, while bowel problems and urinary irritation/obstruction rose after EBRT and BT. Sexual dysfunction increased in all patients, particularly after radical prostatectomy, and nerve-sparing surgical technique had little apparent benefit. There was no change in urinary function and little change in overall bowel function after 12 months, but the time course of sexual dysfunction varied by treatment and, for bowel function, by symptom. Multiple regression modeling confirmed that treatment influences all 24-month outcomes, but residual confounding persisted. CONCLUSION: Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction. With this information, patients and their physicians may refine their choice of treatment and better anticipate its consequences.     

An immunofluorescent method using crithidia luciliae to detect antibodies to double-stranded DNA

The immunochemical specificity of the immunofluorescent Crithidia luciliae method for detection of antibodies to double-stranded DNA (dsDNA) was confirmed by demonstrating abolition of staining by DNase digestion and by absorption with dsDNA. This method was less sensitive than a Millipore filter method for detecting antibodies to DNA. It was positive only in subjects with systemic lupus erythematosus or drug-induced antinuclear factors. This technique appears suitable for study of the immunochemical characteristics of antibodies to dsDNA.