缺血性卒中或短暂性脑缺血发作患者的卒中预防指南

这份新声明旨在为缺血性卒中或短暂性脑缺血发作存活者的缺血性卒中预防提供全面和及时的循证推荐，循证推荐包括对危险因素的控制，动脉粥样硬化性疾病的干预措施，心源性栓塞的抗栓治疗以及非心源性卒中抗血小板药的应用。另外，还为其他多种特殊情况下复发性卒中的预防提供了推荐、包括动脉夹层分离、卵圆孔未闭、高同型半胱氨酸血症、高凝状态、镰状细胞病、脑静脉窦血栓形成、女性卒中（特别是与妊娠和绝经后激素替代治疗相关卒中），脑出血后肮凝药的应用，以及该指南在高危人群中执行和应用的特殊措施。     

Fluorimetric Studies of the Formation of Riboflavin-β-Cyclodextrin Inclusion Complex: Determination of the Stability Constant by use of a Non-linear Least-squares Model

The non-linear least-squares model for calculation of the stability constant (K_st) of a drug-cyclodextrin complex has been used in fluorimetry studies. Complexation of riboflavin with β-cyclodextrin (β-CyD) was monitored fluorimetrically by measuring changes in the fluorescence intensity of the vitamin in the presence of various amounts of β-CyD. Formation of an inclusion complex was confirmed in the solid state by differential scanning calorimetry (DSC) and in aqueous solution by proton nuclear magnetic resonance spectroscopy (¹H NMR). The experimental K_st value (2112 M^?1) derived from the fluorimetry studies appeared to fit well to a 1:1 drug-to-cyclodextrin molar ratio according to the non-linear mathematical model. The model is particularly suitable for fluorescent compounds of which fluorescence intensity is influenced by the presence of cyclodextrins.     

Aetiology of Acute Pharyngitis and Clinical Response to Empirical Therapy with Erythromycin Versus Amoxicillin

Guthrie R M, Ruoff G E, Rofman BA, Ginsberg D, Karp R R, BrownS M and Schulz GA. Aetiology of acute pharyngitis and clinicalresponse to empirical therapy with erythromycin versus amoxicillin.Family Practice 1988; 5: 29–35. One hundred and eighty-nine adults with acute pharyngitis hadculture and serological evaluation for groupA beta haemolyticstreptococci (GABHS), Mycoplasma pneumoniae, and Branhamellacatarrhalis. Sixteen patients had evidence for infection withGABHS, none for M. pneumoniae, and one for B. catarrhalis. Forthose with GABHS, there was no significant difference betweenempirical treatment by erythromycin or amoxicillin. For thosewithout GABHS, empirical treatment with erythromycin appearedto result in a statistically significant reduction in coughand a noticeable but less than significant reduction of othersymptoms when compared to empirical treatment with amoxicillin.The new formula tion of erythromycin utilized in this study(PCE) may be associated with a reduction in gastrointestinalintolerance from that reported with other erythromycin products.     

Subchronic Toxicity of Cupric Sulfate Administered in Drinking Water and Feed to Rats and Mice

Subchronic Toxicity of Cupric Sulfate Administered in DrinkingWater and Feed to Rats and Mice. HÉBERT, C. D., ELWELL,M. R., TRAVLOS, G. S., FITZ, C. J., AND BUCHER, J. R. (1993).Fundam. Appl. Toxicol. 21, 461–475. The effects of acute poisoning by cupric sulfate in a numberof species are well known; however, the effects of chronic low-levelingestion of cupric sulfate are less well characterized. Becauseexposure of humans to cupric sulfate may occur through drinkingwater, food, soil, or ambient air, subchronic toxicity studieswere conducted in male and female F344/N rats and B6C3F₁ miceby the drinking water (2-week exposure) and dosed feed (2-and13-week exposure) routes. Animals were evaluated for histopathology,clinical pathology, reproductive toxicity, and tissue metalaccumulation, and target organs were examined by a variety ofspecial stains and by electron microscopy to characterize theobserved lesions. In drinking water, cupric sulfate concentrationsof 300 to 100 ppm produced no ill effects, whereas concentrationsof 3000 to 30,000 ppm were lethal to rats and mice within 2weeks. In feed, cupric sulfate concentrations of 4000 to 16,000ppm caused significant reductions in body weight gain in bothspecies in the 2- and 13-week studies. Hyperplasia and hyperkeratosisof the limiting ridge of the forestomach were present in bothspecies in the 2- and 13-week studies. Rats in the dosed feedstudies had a dose-related increase in inflammation in the liverand changes in clinical chemistry parameters which were indicativeof hepatocellular damage and cholestasis. Histologic changesin the kidneys of rats consisted of a dose-related increasein the number and size of eosinophilic protein droplets in theepithelial cytoplasm and the lumina of the proximal convolutedtubules. Droplets were larger and more numerous in males thanin females. Urinalysis results were suggestive of renal tubularepithelial damage. Iron staining of spleens from treated animalsindicated a marked depletion of iron stores in both male andfemale rats, but not in mice, while hematologic and clinicalchemistry alterations in rats in the 13-week study, along withhistologic changes in bone in the 2-week dosed feed study, wereindicative of a microcytic anemia. Cupric sulfate produced noadverse effects on any of the reproductive parameters measuredin rats or mice of either sex. These results indicate that cupricsulfate at high exposure levels is a hepatic and renal toxicant,as well as an inducer of anemia in rodents, with rats more sensitivethan mice following subchronic exposure.     

Conformational features responsible for the binding of cyclic analogues of enkephalin to opioid receptors

Models of μ- and δ-receptor-bound backbone conformations of enkephalin cyclic analogues containing Phe⁴ were determined by comparing geometrical similarity among the previously found low-energy, backbone structures of -enkephalinamide, -enkephalinamide, -enkephalin and -enkephalin. The present μ-receptor-bound conformation resembles a β-I bend in the peptide backbone centred on the Gly³-Phe⁴ region. Two slightly different models were found for the δ-receptor-bound conformation; both of them are more extended than the μ-receptor-bound conformation and include a γ-turn (or a γ-like turn) on the Gly³ residue. Energetically favourable rotamers of Tyr and Phc side chains were also determined for the μ- and δ-conformations. The present models of μ- and δ-conformations share geometrical similarity with the low-energy structures of Leu-enkephalin and the analogue.     

In vitro oxyhaemoglobin saturation measurements in haemoglobin solutions using fibreoptic pulmonary artery catheters

We compared in vitro oxyhaemoglobin saturations using two pulmonaryartery catheters (catheter So₂) with oxyhaemoglobin saturations(So₂) measured by the IL282 co-oximeter and derived partialoxyhaemoglobin saturations (partial So₂) at different oxygentensions (Po₂) in six solutions: whole blood, 50:50 mixtureof whole blood and Plasmalyte A (haemodiluted blood), 50:50mixture of whole blood and 8% pyridoxylated haemoglobin-polyoxyethylene(PHP) conjugate (WB-PHP), 75:25 mixture of 8% PHP and PlasmalyteA solution (PHP66), 50:50 mixture of 8% PHP and Plasmalyte Asolution (PHP44) and stroma-free haemoglobin solution (SFH).Calculated P₅₀ values (Po₂, vs So₂) were 3.79, 3.58, 3.49, 3.15,3.04 and 2.07 kPa, respectively. However, if partial So₂ wasused the curves were shifted to the left, reducing P₅₀. CatheterSo₂ correlated well with So in whole blood (r² > 0.99 forboth catheters), haemodiluted blood (r² > 0.98 for both catheters)and WB-PHP solution (r² = 0.94 for both catheters). In PH P44(r² = 0.64 and r² = 0.57), PHP P66 (r² = 0.40 for the Oximetrixand r² = 0.25 for the Edwards catheter) and SFH solutions (r²= 0.33 for the Oximetrix and r² = 0.22 for the Edwards catheter)both catheters performed poorly. We conclude that mixed venousoxyhaemoglobin saturations measured by oximetric pulmonary arterycatheters are inaccurate in the presence of haemoglobin solutions.For accuracy a multi-wavelength co-oximeter should be used ifblood containing PHP or SFH is to be analysed. Present address: Department of Anaesthetics, Bristol Royal Infirmary,Bristol, UK     

Health impact of head and neck cancer

A multidimensional Head and Neck Quality of Life (HNQOL) instrument and a general health status measure were administered to 397 patients with head and neck cancer. Scores for the 4 domains of the HNQOL (communication, eating, pain, and emotional well-being) were calculated. Patient demographics, comorbidities, clinical characteristics, treatment data, disability status, and a global "overall bother" score were assessed. When compared with the US population aged 55 to 64 years, the group had significantly worse scores in the 8 health domains of the SF-36. Patients' overall bother scores from the head and neck cancer treatment correlated best with the HNQOL emotion domain (r = 0.71) and the HNQOL pain domain (r = 0.63), and least with the patients' perception of their response to treatment (r = 0.39). Pain, eating, emotion, physical component summary score, age, and an interaction term between eating and emotion were significant predictors for overall bother. Of the 217 patients who were working before the diagnosis of cancer, 74 (34. 1%) reported that they had become disabled. Patients who had more than 1 type of treatment were 5.9 times more likely to report themselves as disabled (odds ratio [OR] = 5.94, P < 0.01), even after adjusting for age, emotion score, and physical component summary score, which were other factors that predicted disability.