论高等医学院校普及医院信息系统课程

在我国,医院信息系统已是现代化医院工作的支撑环境。高等医学院校的医院信息系统课程留白,可能削弱医学生临床工作能力和职业适应力。文章阐明了高等医学院校开设医院信息系统专业课的重要性,讨论了教学目标、教学内容;详细介绍了高校与医院合作建立HIS实验室、实地教学和针对专业掌握实际操作技能的教学方法。     

Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients

Aspartyglucosaminuria (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases. An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation. These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine. Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation. Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates. However, in the Morris water maze test, a slow worsening of performance could be seen with age. The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities.      

Glycoprotein IIb and IIIa retention on fibrinogen-coated surfaces after lysis of adherent platelets

The platelet-membrane glycoprotein IIb-IIIa (GPIIb-IIIa) complex is essential for platelet aggregation and is involved in the attachment of platelets to thrombogenic surfaces. This study shows the retention of GPIIb and GPIIIa on immobilized fibrinogen after Triton X-100 (Sigma Chemical Co, St Louis, MO) lysis of adherent platelets. Glycoproteins were detected using subunit specific monoclonal antibodies in a modified enzyme-linked immunosorbent assay procedure. GPIIb-IIIa retention was judged to be specific relative to GPIb recovery, and was modulated by platelet activation. Platelet exposure to adenosine diphosphate or thrombin, but not A23187 or chymotrypsin, markedly enhanced GPIIb and GPIIIa recovery relative to that observed with unstimulated platelets, or prostaglandin E1-treated platelets. Moreover, lysis of adherent platelets in the presence of 10 mmol/L EDTA, under conditions promoting GPIIb-IIIa complex dissociation (pH 8.1, 60 minutes, 37 degrees C), had no effect on GPIIb or GPIIIa subunit recovery. Platelet activation with Zn+2 also enhanced GPIIb and GPIIIa recovery on fibrinogen-coated surfaces over that observed with unstimulated platelets, but GPIIb and IIIa retention was EDTA sensitive. This correlated with the EDTA-reversible nature of Zn+2- activated platelet adhesion to fibrinogen-coated surfaces. The data (1) show that platelet adhesion to fibrinogen is accompanied by the induction of high-affinity interactions between GPIIb-IIIa and immobilized fibrinogen that are EDTA-resistant and enhanced by platelet activation with some but not all agonists, and (2) implicate these interactions in stabilizing platelet contacts with fibrinogen-coated surfaces.     

Induction of pulmonary inflammation by components of the pneumococcal cell surface

Using a rabbit model of experimental pneumonitis, the components on the surface of the pneumococcus that incite pulmonary inflammation were identified. Rabbits were challenged intratracheally with live pneumococci, capsular polysaccharide, purified cell walls, or cell wall subcomponents. Leukocytosis and elevation of protein concentration was quantitated in bronchial lavage fluid during the first 24 h after challenge. Of the pneumococcal surface components tested, cell wall preparations had the highest specific activity in inducing inflammation; abnormalities in bronchial lavage fluid cytochemistry appeared rapidly and in a dose-dependent manner. Cell wall building blocks and the products of penicillin-induced hydrolysis of the cell wall were also highly inflammatory, indicating that inflammation can be generated by disruption of the cell wall during lysis of bacteria by beta-lactam antibiotics. Administration of inhibitors of arachidonic acid metabolism suggested that inhibition of the lipoxygenase pathway reduced inflammation associated with cell walls. We propose that pulmonary inflammation during pneumococcal pneumonia arises in large part from the interaction of the bacterial cell wall with complement and noncomplement-mediated host defenses.     

Clinical isolates of Streptococcus pneumoniae that exhibit tolerance of vancomycin.

The ability of Streptococcus pneumoniae to escape lysis and killing by vancomycin, a property termed "tolerance," has recently been noted in a laboratory strain of the species. Vancomycin tolerance in clinical isolates represents a potential new health risk. We determined the prevalence of vancomycin and penicillin tolerance among 116 clinical isolates of pneumococci by monitoring lysis and viability after exposure to the respective antibiotic for 4 hours. Eight percent of the strains were tolerant to penicillin and 3% were tolerant to vancomycin. The 3 vancomycin-tolerant isolates also had a high ratio of minimum bactericidal concentration to minimum inhibitory concentration, in contrast to nontolerant strains. They were of serotype 9V and had reduced susceptibility to penicillin. Only 1 was also tolerant to penicillin. Growth rate and ability to divide were not affected in the 3 vancomycin-tolerant strains, and they all lysed with deoxycholate, which indicates autolysin production. Vancomycin tolerance among clinical isolates of pneumococci will necessitate tracking to determine the magnitude of the evolving health risk, since tolerance may contribute to treatment failure (in particular, cases of meningitis, in which bactericidal activity is critical for eradication) and since it may also be a favored background for acquisition of resistance of vancomycin.     

Virulence in mice of pneumococcal clonal types with known invasive disease potential in humans

Streptococcus pneumoniae isolates of serotypes 1, 4, 6B, 7F, 14, and 19F belonging to clonal types with known invasive disease potential in humans were used to infect C57BL/6 and BALB/c mice. Most isolates were able to colonize the nasopharynx for 7 days. One serotype 19F isolate of the clonal type ST162 had higher bacterial numbers than other isolates and clonal types of the same serotype. Serotype 4 clones caused the most-severe invasive disease, whereas serotype 1 clones caused low-level bacteremia without disease symptoms. BALB/c mice were more likely than C57BL/6 mice to develop meningitis. Disease kinetics varied significantly between clonal types. Although most induced a robust tumor necrosis factor response, some isolates of serotype 1 and 7F did not, suggesting that invasive disease caused by different clonal types may result in different degrees of host response. Capsular serotype, other clonal properties, and host factors are important for the development of pneumococcal disease.     

Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhibitors concurrently with the antibiotic.     

Preinfection systemic inflammatory markers and risk of hospitalization due to pneumonia

RATIONALE: Elevated proinflammatory cytokines are associated with severity of pneumonia, but the role of preinfection cytokine levels in the predisposition to pneumonia in humans is less clear. OBJECTIVE: To ascertain role of preinfection inflammatory markers on susceptibility to community-acquired pneumonia (CAP). METHODS: Longitudinal analysis over 6.5 yr of a cohort that consisted of 70- to 79-yr-old well-functioning elderly individuals. MEASUREMENTS: Association between preinfection tumor necrosis factor (TNF), interleukin 6 (IL-6), and C-reactive protein (CRP) levels and CAP requiring hospitalization. RESULTS: Of the 3,075 participants, 161 (5.2%) developed at least one episode of CAP requiring hospitalization over a median duration of 3.3 yr. The highest tertiles of TNF (> 3.7 pg/ml) and IL-6 (> 2.4 pg/ml) were associated with increased risk of CAP, and the adjusted odds ratios were 1.6 (95% confidence interval [CI], 1.02-2.7) and 1.7 (95% CI, 1.1-2.8), respectively. The adjusted risk of CAP with at least one of these markers in the highest tertile was 1.6 (95% CI, 1.1-2.3). TNF and IL-6 levels in the highest tertile had a synergistic effect (p = 0.01 for interaction), and risk of CAP for both markers in the highest tertile was 2.8 (95% CI, 1.8-4.3). An FEV(1) of 50% or less of predicted was associated with the highest risk of CAP (adjusted odds ratio, 3.6; 95% CI, 2.3-5.6). Furthermore, TNF and IL-6 levels modified risk of CAP in participants with coexisting medical conditions and history of smoking. CONCLUSION: In the well-functioning elderly subjects, preinfection systemic levels of TNF and IL-6 were associated with higher risk of CAP requiring hospitalization in smokers and those with coexisting medical conditions.     

16例脑结核瘤抗结核治疗系列观察

目的:报告16例颅内结核瘤患者的临床、影像学表现及抗结核治疗的结果.设计:本文共纳入苏丹Khartoun市全国神经系统疾病中心连续观察的16例脑结核瘤患者.诊断则依据其临床、头颅影像学特征及对抗结核治疗有效等方面.本组中共有7例具有脑组织或脑外组织的病理组织学资料.结果与结论:本组病例最常见的临床表现是头痛(100%)、全身性抽搐(68.7%)及偏瘫(56.2%).头颅横断面电子计算机体层摄影(CT)/核磁共振成像(MRI)显示单个或多个明显增强的病变及病灶周围水肿.经抗结核治疗后,多数存活患者(13/15)病变完全吸收.病变部分吸收与就诊延迟、颅内多个大病灶及晚期粟粒性结核病有关.我们主张对颅内结核瘤,即使是拟诊病例,应早期经验性试用抗结核治疗,尤其在结核病高发地区.     

Decreased accessibility of platelet-bound fibrinogen to antibody and enzyme probes

The binding of fibrinogen to platelets is a multiphasic process leading to apparently nonreversible associations between fibrinogen and stimulated platelets. To further investigate changes in platelet- fibrinogen interactions, the present study examined the accessibility of platelet-bound fibrinogen and its GPIIb-IIIa receptor to antibody and enzyme probes as a function of time after platelet stimulation with adenosine diphosphate (ADP). Whereas only minimal changes in fibrinogen and 10E5 binding were observed within 60 minutes after platelet stimulation and equilibrium fibrinogen binding, the binding of polyclonal antifibrinogen antibodies decreased significantly (75% +/- 13%, mean +/- SD, n = 9). Similar decreases were noted with rabbit antifibrinogen Fab and F(ab')2 fragments. In addition, plasmin (32 mU/mL) added to platelets five minutes compared with 60 minutes after equilibrium fibrinogen binding dissociated 52% +/- 12% compared with 33% +/- 7% of platelet-bound fibrinogen in five minutes, and 83% +/- 15% compared with 66% +/- 14% of bound fibrinogen in 15 minutes. No difference in plasmin cleavage products was observed, however, by sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE). Complete fibrinogen dissociation occurred 30 minutes after plasmin addition, confirming that fibrinogen was not internalized. In contrast, dissociation of platelet-bound fibrinogen by chymotrypsin was less affected by time after equilibrium fibrinogen binding, and minimal changes in antifibrinogen antibody recognition and plasmin-induced dissociation of fibrinogen bound to stimulated but glutaraldehyde-fixed platelets were observed. The data suggest that ADP-induced fibrinogen binding to fresh platelets is accompanied by progressive rearrangements of fibrinogen on the platelet surface.