Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study

OBJECTIVE: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. METHODS: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. MAIN OUTCOME MEASURES: Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). RESULTS: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. CONCLUSION: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.     

8—Br—cAMP对人视网膜母细胞瘤HXO—Rb44细胞癌基因的表达效应

目的 研究８－Ｂｒ－ｃＡＭＰ对培养的人视网膜母细胞瘤ＨＸＯ－Ｒｂ４４细胞癌基因表达的效应及其与该细胞生长的关系。方法 ｃ－ｆｏｓ ｍＲＮＡ,Ｎ－ｍｙｃ ｍＲＮＡ及ｐ２１ｒａｓ ｍＲＮＡ均以原位杂交ＲＮＡ斑点印迹技术检测,对繁殖细胞核抗原,ｖ－Ｆｏｓ,Ｎ－Ｍｙｃ和Ｐ＾２１ｒａｓ蛋白表达的免疫反应性则采用免疫组化及收白质斑点印迹技术检测。     

Compliance and medication knowledge among elderly Japanese home-care recipients

Objectives: To investigate the risk factors for noncompliance in elderly home-care recipients; and to evaluate to what extent regular home visits and drug counseling by a pharmacist contribute to compliance. Subjects: One hundred and sixty-three elderly home-care recipients aged 62 years and over took part in this study. All subjects were cognitively normal, and taking a regimen of one or more prescribed drugs. Medication use was observed by pharmacist-conducted interviews during home visits. Compliance was estimated by comparing prescribed regimens with medications actually being taken at home. Results: The mean age with (SD) of the subjects was 78.7 (8.3) years. Eighteen per cent were regularly counseled by a pharmacist about medication. Poor compliance with prescribed medications was associated with subjects aged 80 years and over, who were administering their own medication, consuming less than three meals a day, did not have one dose packages, and who were not receiving pharmacist counseling. In multiple logistic regression analyses, frequency of meals (OR 5.99; 95% CI 1.25–28.79), pharmacist counseling (OR 5.32; 95% CI 2.00–14.20), and age (OR 0.96; 95% CI 0.92–1.00) were independent predictors of good compliance for home-care recipients with physical disabilities. Compliance correlated inversely with knowledge of drug names, and drug purposes in the uncounseled group. Compliance, however, positively correlated with knowledge of drug purposes in the counseled group. Conclusion: In this study, compliance among elderly Japanese home-care recipients was found to be associated with receiving pharmacist counseling, frequency of meals, and age. Received: 22 June 1998 / Accepted in revised form: 2 December 1998     

Effect of novel environmental stimuli on rat behaviour and central noradrenaline function measured by in vivo microdialysis

Rationale: Although physically aversive stimuli induce functional changes in central noradrenergic neurones, little is known about the noradrenergic response to environmentally aversive stimuli. Objectives: The first aim was to characterise environmental features that are perceived as stressful by rats. The second was to investigate whether changes in the concentration of extracellular noradrenaline are induced by these environmental features. Methods: A light/dark shuttle-box was used to test rats’ behavioural response to a range of stimuli (novelty, bright light, and the presence of an unfamiliar rat), either before or after microdialysis probe implantation. Changes in the concentration of extracellular noradrenaline in the frontal cortex and hypothalamus in vivo were then evaluated on exposure to these same test conditions. Results: Naive rats spent less time in a brightly-lit test arena than a dark one. However, the behavioural response to the light arena was attenuated by the presence of an unfamiliar rat. Probe implantation intensified the response to the light arena but did not affect behaviour in the dark arena. In the microdialysis studies, there was no change in the concentration of extracellular noradrenaline on transfer of rats to the dark arena but there was an increase in both the frontal cortex (+45%) and hypothalamus (+75%) on exposure to the light arena. A similar increase was induced in both brain regions when the light arena contained an unfamiliar rat. Conclusions: Implantation of a microdialysis probe modifies the behavioural responses to certain environmental stimuli. Regardless of this, the extent to which rats perceive a novel environment as aversive is not the only determinant of the noradrenergic response to such stimuli. However, differences in stimulus controllability in the microdialysis and the behavioural experiments could influence the apparent intensity of the stress. Received: 29 October 1998 / Final version: 19 March 1999     

Practical approach to recurrent respiratory infections

Respiratory diseases are a major cause of morbidity and mortality in developing countries. Recurrent respiratory infections in children pose a great challenge to the pediatrician where he has to exercise his clinical acumen and methodical, approach, for correct diagnosis and treatment. It is a fact that children should suffer 7 to 8 upper respiratory infections per year until they are 5 years of age when their immune status reaches adult level. In this situation, it is essential to find out whether the frequencies are abnormal. Whenever a child has the following, problems, then only it needs to be investigated.—(a) repeated bacterial pneumonias; (b) a child less than 3 months old having repeated respiratory infections; (c) a child of 9 months old without a history of exposure infections; (d) infections, complicating into bronchiectasis and; (e) in a child where there is no history of allergy or asthma. Once the problem is established as a true recurrent respiratory infection, the clinician should pose questions—whether it is chronic, acute or recurrent, to find out the site of pathology, seriousness of the problem, response to previous medications, to establish the possible diagnosis which fall into six categories—congenital anamolies, aspiration syndrome, genital disorders, immunological, diseases, immune deficiency disorders and allergic diseases. The author discusses quoting some examples for various categories avoiding non pulmonary causes for recurrent respiratory infections in children.     

Fitness in the fit: does physical conditioning affect cardiovascular risk factors in middle-aged marathon runners?

OBJECTIVE: The study was designed to assess cardiovascular risk factorsin marathon runners with different degrees of fitness. DESIGN: A total of 30 male middle-aged marathon runners were dividedaccording to their marathon running time into fit (265 ±8 min), fitter (222 ± 5 min) and fittest (178 ±12 min). The three groups of 10 runners each were comparablein age, weight, and body surface area. Cardiovascular risk factorswere assessed by measuring arterial pressure before and duringexercise (150 watts) and determination of plasma lipoproteins,uric acid, glucose and white blood cell count before and aftera marathon run. RESULTS: All measured laboratory values such as high-density lipoproteincholesterol (P<0.05), low-density lipoprotein cholesterol(P <0.05), total cholesterol (non-significant), triglycerides(non-significant), blood sugar (non-significant), uric acid(P <0.05), and white blood cell count (P <0.05) indicateda lower cardiovascular risk in the fastest when compared withthe slowest runners. Resting blood pressure was similar in thethree groups but consistently lower at all levels of exercisein the fittest when compared with the less fit runners. Thefittest runners also showed greater increases in high-densitylipoprotein cholesterol after the marathon run (14% vs 8% inthe slowest runners, P<0.05). CONCLUSIONS: We conclude that even at the extreme end of a continuum suchas represented by well-conditioned, middle-aged marathon runners,cardiovascular risk factors are related to the degree of fitness,as measured by the marathon running time.     

Effect of low concentrations of K+ and Cl− on the Na+-dependent neuronal uptake of [3H] dopamine

The specific uptake of [³H] dopamine (DA) was studied using a crude synaptosomal fraction obtained from rat striatum. In a medium containing a 10 mM NaHC03/NaH2PO4 buffer and no added K⁺ ions, addition of NaCl elicited an increase in DA uptake for Na⁺ concentrations from 10 to 60 mM, and then a decrease of uptake for Na⁺ concentrations up to 130 mM. These data confirm that rather low NaCl concentrations produce a maximal DA uptake. This biphasic curve of uptake resulted from significant changes in the V _max of the DA uptake. Except for 10 mM Na⁺, this curve was not significantly modified when 9 mM NaHCO₃/NaH₂PO₄ were replaced by 9 mM NaCl. This result indicates that the Cl^– dependence of the DA uptake is mainly secondary to the Na⁺ dependence. Addition of KCl up to 3 mM did not modify the ascending part of the NaCl-dependent uptake curve. In contrast, the reduction in uptake produced by high Na⁺ concentrations was prevented in a concentration-dependent manner by KCl; this effect resulted from a decrease in the K_m and an increase in the V _max for the uptake.Measurements of membrane potential, with the help of the fluorescent probe 3,3-diethylthiadicarbocyanine iodide [DiSC₂(5)] and purified synaptosomes prepared from rat striatum and cerebral cortex, revealed that addition of 3 mM KCl to a medium containing a high Na⁺ concentration and no K⁺ ions produced a marked and stable decrease in the fluorescence level. This decrease which corresponds to an increase in membrane polarization was blocked by 0.1 mM ouabain. These data suggest that low K⁺ concentrations are likely to prevent the decrease in uptake elicited by high Na⁺ concentrations by restoration, via a Na⁺/K⁺ ATPase-mediated mechanism, of the membrane potential and/or a transmembrane electrochemical Na⁺ gradient more favourable to DA uptake.     

Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin. Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.     

Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck

In vitro models are currently being used to study head and neck squamous cell carcinoma (HNSCC). Several hundred HNSCC cell lines have been established by various investigators and used to study a broad spectrum of questions related to head and neck cancer. The head and neck model with respect to multistage carcinogenesis is now complete. Several techniques exist for the culture of normal epithelial cells from the upper aerodigestive tract (UADT). The biology of these UADT cells (oral cavity, oropharynx, hypopharynx and larynx) is being studied. Successful culture of premalignant lesions (dysplastic mucosa, leukoplakia, erythroplakia) has resulted in establishment of a limited number of premalignant cell lines and cell cultures. HPV infection of normal oral epithelial cells for immortalization ( premalignant cells) coupled with transformation with carcinogens (malignant cells) has established an experimental model for progression. Two in vivo models for oral carcinogenesis, the 7,12 dimethylbenz(a)anthracene-induced hamster cheek pouch model and the 4-nitroquinoline-N-oxide rat oral model, have been established in culture. Thus, multistage carcinogenesis models have been established from both human tissues and animal models and include cultures of normal, premalignant and malignant cells. Culture techniques for growing dissociated primary tumor cells for short term experimental analysis are being used. The culture of normal or tumor tissue as organ/explant cultures allows for the maintenance of normal cell-cell and cell-matrix interactions, but limits experimentation since these cultures cannot be propagated. Several three dimensional model systems are being used to obtain this histological complexity but allow for experimentation. The ability to culture normal, premalignant and malignant cells coupled with the use of a variety of culture techniques, should allow for the continued growth and experimentation in head and neck cancer research.