鼠诱发性高眼压和细胞凋亡的实验研究

目的 探讨鼠实验性急慢性高眼压的视网膜组织损伤机制。方法 应用前房内连续灌注生理盐水的方法制成急性高眼压鼠模型。实验后第1、2、4、5、7和10d观察视网膜反应。巩膜表浅静脉烧灼法制成慢性高眼压模型，分别于实验后1和2个月观察视网膜损害情况。用TUNEL技术和半胱胺酸天冬胺酸酶免疫组化研究法以证实视网膜细胞的凋亡机制，NADPH辅酶反应识别一氧化氮诱导的细胞。结果 急性高眼压模型的免疫组化研究证实节细胞凋亡是早期的细胞死亡，而在对照组一氧化氮合成酶在视网膜组织并不表现明显的活性。慢性高眼压模型实验提示一氧化氮合成酶活性增加，表明一氧化氮具有神经保护作用而并非仅存有细胞毒性作用。TUNEL和半胱胺酸天冬胺酸酶研究表明，凋亡开始于慢性高眼压的不同阶段。结论 了解高眼压所致的视网膜损害的机制为研究在细胞变性过程中某些物质对凋亡、一氧化氮合成酶和突触传递的影响，尤其是对研究青光眼节细胞死亡的机制提供了基础。     

Adrenal function and high dose inhaled corticosteroids for asthma

OBJECTIVE: To investigate effects on adrenal function of fluticasone, a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate. METHODS: 34 children on high doses (400-909 micrograms/m2/d) of inhaled beclomethasone dipropionate or budesonide were recruited into a double blind, crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate, given using a standard spacer (Volumatic). The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline (after a two week run in), after six weeks treatment with an equal dose of beclomethasone, and after six weeks of treatment with half the dose of fluticasone, both given through a spacer device. RESULTS: The comparison of effects between fluticasone and beclomethasone during treatment periods, although favouring fluticasone in all measured variables, reached significance only after correction for urinary creatinine excretion (tetrahydrocortisol and 5 alpha-tetrahydrocortisol geometric means: 424 v 341 micrograms/m2/d). The baseline data showed adrenal suppression in the children taking beclomethasone (total cortisol geometric means: 975 v 1542 micrograms/d) and a dose related suppression in the children taking budesonide. Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods. CONCLUSIONS: Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses. The baseline data also support the claim that spacer devices should be used for the administration of high doses of inhaled topical steroids.     

Measured and predicted bone mineral content in healthy boys and girls aged 6–18 years: adjustment for body size and puberty

Dual-energy X-ray absorptiometry (DEXA) is a rapid and precise technique for the assessment of bone mineralization in children. Interpretation of the results in growing children is complex as results are influenced by age, body size (height and weight) and puberty. Conventionally, bone mineral data derived from DEXA have been presented as an areal density [BMD; bone mineral content (BMC, g)/projected bone area (BA, cm²)], yet this fails to account for changes in BMC that result from changes in age, body size or pubertal development. Measurement of BMC and BA of the whole body, lumbar spine and left hip were made in 58 healthy boys and girls using DEXA. The relationship between BMC and BA was curvilinear, with the best fit being that of a power model (BMD = BMC/BA^λ, where λ is the exponent to which BA is raised in order to remove its influence on BMC). The value of λ changed when measures of body size and puberty were taken into account (e.g. for lumbar spine from 1.66 to 1.49). Predictive formulae for BMC were produced using regression analysis and based on the variables of age, body size and pubertal development. This provides a method for interpreting the measured BMC which is independent of such variables and a constant reference range for children aged 6-18 y.     

Serum creatinine levels in the US population: third National Health and Nutrition Examination Survey

This report describes the distribution of serum creatinine levels by sex, age, and ethnic group in a representative sample of the US population. Serum creatinine level was evaluated in the third National Health and Nutrition Examination Survey (NHANES III) in 18,723 participants aged 12 years and older who were examined between 1988 and 1994. Differences in mean serum creatinine levels were compared for subgroups defined by sex, age, and ethnicity (non-Hispanic white, non-Hispanic black, and Mexican-American). The mean serum creatinine value was 0.96 mg/dL for women in the United States and 1.16 mg/dL for men. Overall mean creatinine levels were highest in non-Hispanic blacks (women, 1.01 mg/dL; men, 1.25 mg/dL), lower in non-Hispanic whites (women, 0.97 mg/dL; men, 1.16 mg/dL), and lowest in Mexican-Americans (women, 0.86 mg/dL; men, 1.07 mg/dL). Mean serum creatinine levels increased with age among both men and women in all three ethnic groups, with total US mean levels ranging from 0.88 to 1.10 mg/dL in women and 1.00 to 1.29 mg/dL in men. The highest mean creatinine level was seen in non-Hispanic black men aged 60+ years. In the total US population, creatinine levels of 1.5 mg/dL or greater were seen in 9.74% of men and 1.78% of women. Overall, among the US noninstitutionalized population, 10.9 million people are estimated to have creatinine values of 1.5 mg/dL or greater, 3.0 million have values of 1.7 mg/dL or greater, and 0.8 million have serum creatinine levels of 2.0 mg/dL or greater. Mean serum creatinine values are higher in men, non-Hispanic blacks, and older persons and are lower in Mexican-Americans. In the absence of information on glomerular filtration rate (GFR) or lean body mass, it is not clear to what extent the variability by sex, ethnicity, and age reflects normal physiological differences rather than the presence of kidney disease. Until this information is known, the use of a single cutpoint to define elevated serum creatinine values may be misleading.     

Intussusception associated with Yersinia pseudotuberculosis infection

Intussusception associated with Yersinia pseudotuberculosis infection was developed in three boys; two of them had a history of drinking untreated water. All intussusceptions were localized at the ileocolic region, and all patients completely recovered with Gastrografin^R enema and supportive treatment without complication and operation.     

Validation of a skills assessment scoring system for transesophageal echocardiographic monitoring of hemodynamics

Objective Transesophageal echocardiography (TEE) is increasingly used in hemodynamic monitoring in the intensive care unit. This paper describes and validates a scoring system for assessing competence in TEE performed by intensivists for this indication. Design Prospective study over an 18-month period. Settings Two medical intensive care units. Methods The scoring system is used to assess four aspects of TEE: quality of the views (score out of 14); semiquantitative evaluation of respiratory variations in the superior vena cava, valve regurgitation, size of the right ventricle (score out of 10); accuracy of measurement of velocity-time integrals for pulmonary and aortic flow, peak velocity of the E and A waves of mitral flow, left ventricular fractional area change (score out of 8); summary and proposed treatment (score out of 8). The scoring system was validated by using it to assess intensivists after 1 month (M1), 3 months (M3) and 6 months (M6) of training. TEE was done on a mechanically ventilated, hypotensive patient and scored by comparing the intensivist's examination with that of the expert examiner. The intensivists were divided into two groups of theoretical expertise at the start of training. Results Nineteen intensivists were evaluated. The scores at M1 for level 0 (no experience in echocardiography) and level 1 (previous experience) were, respectively, 18.5 ± 4 and 24.7 ± 5. The scores at M1, M3, and M6 were, respectively, 20.4 ± 5, 30.4 ± 5 and 35.7 ± 3. At M6, the intensivists had performed TEE 29 ± 10 times. Conclusion The scoring system was discriminatory and sensitive to change, and could be used as a tool to assess an intensivist's mastery of TEE. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Breathing During Sleep in Patients with Myotonic Dystrophy and Non-myotonic Respiratory Muscle Weakness

Sleep apnoea and hypopnoea have been reported in myotonic dystrophy,but it is unclear whether this is simply attributable to therespiratory muscle weakness which is common in this condition.We therefore investigated whether breathing and oxygenationduring sleep were more abnormal in patients with myotonic dystrophythan in patients with non-myotonic muscle weakness. Seven subjectswere studied in each of three groups: normal controls, myotonicdystrophy and non-myotonic weakness. Patients in the lattergroup were chosen to represent a similar range of severity ofrespiratory muscle weakness to those with myotonic dystrophy.Detailed polysoranography was performed; the severity of breathingdisorders during sleep was quantified in terms of the frequenciesof apnoea and hypopnoea and the degree of arterial desaturation.The myotonic patients showed more frequent apnoea and hypopnoeaand more severe desaturation than the other two groups; theresults in the non-myotonic patients were generally intermediate.The results suggest that abnormal breathing during sleep iscommon in myotonic dystrophy and is not due solely to the directeffects of respiratory muscle weakness. Somnolence, which isa well recognized symptom of myotonic dystrophy, was not clearlyattributable to the sleep apnoea/hypopnoea syndrome nor to abnormalsleep architecture in the myotonic patients.     

Human immunodeficiency virus type 1-infected blood donors: behavioral characteristics and reasons for donation. The HIV Blood Donor Study Group

Between May 1988 and September 1989, 829 human immunodeficiency virus type 1 (HIV-1)-seropositive donors were identified from 3,919,000 units of blood donated at 20 United States (US) blood centers. Of the 829,512 (62%) were interviewed to assess behavioral characteristics of the largest subgroup, men reporting sex with men, use of the confidential unit exclusion (CUE) and reasons for donation among all donors. Among 216 men reporting sex with men, 97 percent had male and 72 percent had female sexual contact since 1978. The majority identified themselves as bisexual (29%) or heterosexual (26%). Although 61 percent of 512 donors were aware of their risk behavior at donation, including 57 percent of those infected through heterosexual transmission, only 5 percent used the CUE. Reasons for donation included failure to read carefully (46%) or comprehend (15%) the deferral materials, pressure to donate (27%), a desire to be tested for HIV-1 (15%), and a reliance on screening to identify infected blood (10%). Reasons given for a perception of being at low risk included no recent risk behaviors, infrequent risk behaviors, or modification of risk behaviors. To reach high-risk donors, centers should assess whether referral materials provide necessary medical information and are clearly written for persons with diverse cultural and language backgrounds. Staff should be encouraged to avoid the use of culturally stigmatized terms and behaviors that may be perceived as high pressure.     

Identification of the blood component responsible for increased susceptibility to gut-derived infection

It has previously been reported that the transfusion of allogeneic whole blood increases sepsis-related mortality and decreases the ability of the host to kill bacteria that have translocated from the intestinal tract. To determine which blood component contributes to this adverse effect, the impact of the transfusion of white cells (WBCs), red cells (RBCs), and plasma on microbial translocation, bacteria killing, and mortality rate was studied. Blood from C3H/HeJ mice was separated into WBCs, RBCs, and plasma, and these fractions were transfused to Balb/c mice. Controls received sterile saline. Five days after transfusion, all Balb/c mice underwent a 20-percent burn and gavage with 1 × 10(10) Escherichia coli labeled with 14C-glucose. Mortality was observed for 10 days. Four additional groups, receiving the same treatment as above, were sacrificed 4 hours after the burn, and mesenteric lymph nodes, liver, kidney, and blood were harvested aseptically. For each tissue, quantitative colony counts, radionuclide counts, and percentage of translocated bacteria that remained alive were calculated. By radionuclide counts, no difference was observed in the degree of 14C E. coli translocation among the groups. In contrast, the percentage of viable bacteria and the mortality rate were significantly higher in the group receiving allogeneic WBCs than in all other groups (p < 0.05). It is concluded that WBCs are the component in transfused blood that has an adverse effect on host resistance to gut- derived infection.     

Antigen structural requirements for immunoglobulin isotype switching in mice

L-Tyrosine-p-azobenzene-p-arsonate (RAT) is immunogenic and serves as a carrier for anti-hapten antibody responses in guinea pigs, rats, and mice. However, the murine anti-N-2,4-dinitrophenyl (DNP) plaque-forming cell (PFC) response to the bifunctional antigen 2,4-dinitrophenyl-6-amino-caproyl-L- tyrosine-p-azobenzene-p-arsonate (DNP-SAC-RAT; or BI-1) is extremely weak (2,000-4,000 PFC/spleen) and exclusively IgM in both primary and secondary responses. The 6-amino-caproyl group serves as a spacer in this antigen between the DNP haptenic and RAT carrier epitopes. In view of recent evidence indicating that different T helper cells synergize for optimal antibody responses, a trifunctional antigen, N-2,4- dinitrophenyl-6-amino-caproyl-L-tyrosine-p-azobenze-p-arsonate-(proline)9-L- tyrosine-p-azobenzene-p-arsonate (DNP-SAC-RAT-PRO(9)-RAT; or TRI), was prepared to investigate the effect of adding a second RAT epitope to BI-1. The nonaproline spacer between the two RAT epitopes in TRI is assumed to be a rigid rod of approximately 28 A. TRI induced about twice as many PFC as BI-1 in primary responses of A/J mice, and induced both IgM and IgG PFC in secondary responses. Furthermore, TRI induced IgG PFC responses in mice primed with p-azobenzene-p-arsonate-keyhole limpet hemocyanin, BI-1, or RAT, whereas boosting with BI-1 failed to induce IgG PFC, even in mice primed with TRI. These findings indicate that the minimum antigen structural requirements for inducing IgG PFC in mice are two carrier epitopes and one haptenic epitope. In addition, priming with a mono-epitope carrier (RAT) is sufficient preparation for IgG responses to a trifunctional immunogen. Because TRI differs from BI-1 by the (proline)(9) spacer as well as the additional RAT epitope, two other compounds, N-2,4-dinitrophenyl-6-amino- caproyl-(proline)(9)-L-tyrosine-p-azobenzene-p-arsonate (DNP-SAC-PRO(9)-RAT; or BI-2) and N-2,4-dinitrophenyl-6-amino-caproyl-(proline)(9)-L-tyrosine-p- azobenzene-arsonate (DNP-SAC-RAT-PRO(10); or BI-3), were prepared to evaluate the possible role of the spacer in the observed responses. BI-2, but not BI-3, induced IgG as well as IgM PFC in TRI-primed mice. However, BI-2 failed to induce IgG responses in RAT-primed mice, indicating that TRI and BI-2 were not equivalent immunogens. Because anti-prolyl antibodies had been found in guinea pigs immunized with N-2,4-dinitrophenyl-(proline)10-L-tyrosine-p- azobenzene-p-arsonate (DNP-PRO(10)-RAT), it seemed possible that priming with TRI might induce anti-prolyl antibodies, which, in turn, could cross-link BI-2 molecules into aggregates containing at least two carrier epitopes. To help resolve this question, mice were immunized with acetyl-(proline)10-L- tyrosine-p-azobenzene-p-arsonate and boosted with BI-2. IgG PFC responses were detected, suggesting that anti-prolyl antibodies were indeed responsible, because priming with RAT and boosting with BI-2 did not induce IgG formation. Accordingly, the observations that IgG responses in RAT-primed mice were induced only by TRI and not by any of the bifunctional antigens indicate that two carrier epitopes per antigen molecule are indeed required for IgG induction. They also provide indirect evidence for synergistic help in the switching of immunoglobulin isotypes.