Acute optic neuritis: a virological study in relation to multiple sclerosis.

Previous ultrastructural examination of peripheral blood lymphocytes revealed the presence of intranuclear filamentous structures in multiple sclerosis (MS) and in some optic neuritis (ON) patients. The present investigation was undertaken in the attempt to correlate the presence of such structures with the etiology of ON and MS and possibly to demonstrate the viral origin of the filaments. Suitable virological and serological techniques were used to detect and isolate infectious agents from peripheral blood samples and body excretions of 12 monosymptomatic ON patients at their first acute attack. Nevertheless, any efforts to demonstrate the presence of a virus in these patients have been unsuccessful: no evidence of active viral infection was obtained by serological studies of serum and cerebrospinal fluid samples, nor could viral antigens or inclusions be observed by immunofluorescence and cytochemical analysis. Negative results were also obtained from studies performed in parallel on MS patients and various controls. The significance of the failure to isolate infectious agents from either ON and MS patients is discussed.     

口服与注射长春瑞滨联合卡培他滨治疗蒽环类，紫杉类耐药性晚期乳腺癌的比较研究

目的 探讨口服长春瑞滨联合卡培他滨治疗葸环类、紫杉类耐药的转移性乳腺癌的疗效及不良反应。方法 80例确诊葸环类、紫杉类耐药的转移性乳腺癌患者随机分为两组。口服长春瑞滨联合希罗达组（试验组）：40例患者口服江苏豪森酒石酸长春瑞滨软胶囊45．50mg／（m^2-d），第1、8、15天服用，口服卡培他滨1650mg／（m^2·d），连服1—14d，每3周为1个周期，连用4个周期。注射长春瑞滨联合希罗达组（对照组）：40例患者，长春瑞滨（江苏豪森）25mg／（m^2·d）第1、8天静脉滴注，口服卡培他滨1650mg／（m^2·d），连服1-14d，每3周为1个周期，连用4个周期。治疗结束2周后评价疗效。结果 入组患者80例均可评价疗效，试验组有效率为42．5％，1年生存率为45．0％，中位进展时间4．7月，中位生存时间11．0月；对照组有效率为37．5％，1年生存率为42．5％，中位进展时间4．6月，中位生存时间10．6月；两组比较差异无统计学意义（P〉0．05）。在毒副反应方面，Ⅲ／IV便秘、局部静脉炎、HB下降、WBC下降、ANC下降、总Ⅲ／IV反应率两组比较。差异均有统计学意义（P〈0．05）。结论 口服长春瑞滨联合卡培他滨治疗葸环类、紫杉类耐药的转移性乳腺癌与静脉剂型疗效一致，并且在毒副反应上，口服长春瑞滨明显较静脉剂型轻，并且应用方便。     

Anbenshi的抗感染免疫作用

安本施(Anbenshi)是从清热解毒中药中华猕猴桃根中提取的多糖复合物制剂。本文观察了它的抗感染免疫作用。结果显示:该制剂有抑制细菌粘附的能力,抑制率与已知粘附抑制物ConA相近;它能诱生干扰素,效价及性质与聚肌胞类同;Anbenshi在体外无直接抑菌作用,但体内给药能明显增强小鼠对致病菌感染致死的保护作用,并能明显增强腹腔巨噬细胞的吞噬功能。Anbenshi的抗感染免疫作用,可能系通过抑制细菌在局部粘附作用和增强机体的免疫抗菌能力。     

The effect of cathartic agents on transmucosal electrical potential difference in the human rectum

Summary Active ion transport in the colon is generating a transmucosal electrical potential difference (PD) of about 40 mV. Cathartic agents inhibit electrolyte and water net-absorption or cause net-secretion which should be reflected in a change of PD.In 83 normal subjects the effect of an isotonic eletrolyte solution (control) and different cathartic agents on rectal PD was tested: Laxatives (bisacodyl, rhein), bile acids (cholic and deoxycholic acid), fatty acids (oleic and ricinoleic acid) and cardiac glycosides (meproscillarin, digitoxin, digoxin). Bisacodyl, deoxycholic acid in high concentration, meproscillarin and digitoxin significantly decreased PD, while the other substances did not.Cathartics act on different transport mechanisms which together with different absorption characteristics of the proximal and distal colon may explain the difference in effecting the PD. Rectal PD measurement provides an easy and convenient tool to document effects of cathartic agents on electrolyte transport, otherwise difficult to obtain, and is applicable for clinical use.To Prof. Dr. H.P. Wolff on the occasion of his 65th birthday     

Effects of selective α1 and α2 adrenoceptor active drugs on 86Rb+ efflux from pieces of rat parotid gland

Minute pieces of rat parotid gland were used in studies of adrenergic regulation of K+ efflux using ⁸⁶Rb+ as a probe for K+. Noradrenaline induced a concentration-dependent Rb+ efflux, whereas the β₁-selective agonist prenalterol was without effect. On the other hand, the β₂-selective drug, terbutaline, at high concentrations displayed a small enhancement of Rb+ -secretion. The selective α₁-adrenoceptor drug, phenylephrine, was as potent as noradrenaline, whereas the α₂-agonist clonidine had only a small effect. The noradrenaline-induced Rb+-efflux was effectively inhibited in the presence of prazosin, an α₁-blocker, whereas the α₂-antagonist, yohimbine, was roughly 50 times less potent. The results suggest that catecholamine-induced K+-secretion from the rat parotid gland is mediated via activation of post-synaptic α-adrenoceptors of the α₁-subtype.     

Effects of para-substituted beta-adrenoceptor blocking agents and methyl-substituted phenoxypropanolamine derivatives on maximum upstroke velocity of action potential in guinea-pig papillary muscles

Summary The effects of atenolol (2–5 mmol/l), sotalol (1–2 mmol/l) and pamatolol (0.1–1 mmol/l), together with N-tertiary butyl phenoxypropanolamines with o-methyl (D-2T: 50–100 mol/l) m-methyl (D-3T: 50–100 mol/l) and p-methyl (D-4T:100–200 mol/l) group as well as with o,p-methyl groups (D-24T) (50–100 mol/l) on action potentials (APs) were investigated in isolated guinea-pig papillary muscles. All the drugs in these concentrations produced a concentration-dependent reduction of the maximum upstroke velocity (V _max). The reduction ofV _max in premature APs induced by stimuli interpolated between the basic driving rate of 0.25, 0.1 or 0.027 Hz decayed exponentially during diastolic intervals. The time constants of these decay processes for atenolol, pamatolol and sotalol ranged between 260–541 ms, those for D-3T and D-4T between 655–1,166 ms, and D-2T and D-24T between 1,565–1,931 ms. A drug which provided larger values caused the reduction ofV _max in a wider range of the frequency. With respect to the aryloxypropanolamine derivatives so far studied (Sada and Ban 1980, 1981 a, b; Sada et al. 1983) fairly good correlations were found as follows: between logn-octanol/water partition coefficient (logP) and ED₂₀ at 0.25 Hz, ED₃₀ at 1 and 4 Hz for 11–14 compounds; between logP and resting block, between molecular weight and A _o ^c i.e. the value extrapolated to the time of APD₉₀ of the conditioning response relative to the predrugV _max value which may represent a fraction of channels blocked per AP for 100 mol/l of 20–22 compounds. With respect to 8 compounds with methyl substituents in the benzene ring or amine part the ortho methyl group makes a major contribution to increase the resting block and to increase log values.     

Cytostatic agents and contact allergy: the efferent limb

The effects upon the contact allergic reaction in the guinea pig of the 3 cytostatic agents most commonly used for their immunosuppressant properties, cyclophosphamide, methotrexate and azothioprine, have been investigated in an experimental model which allows comparison of the qualitative and quantitative aspects of the dermal inflammatory infiltrate and the macroscopic response. The 3 agents were given in single, relatively high doses and had effects on the dermal inflammatory infiltrate which varied in nature, degree and time course. Changes often showed a cyclical development with time, with "rebound" often following initial changes. Although cyclophosphamide had the most marked effect, all agents affected the mononuclear, basophil and eosinophil dermal infiltrates at some point in the experiment. Cyclophosphamide was the only agent found to affect the total white cell count of peripheral blood, but the leukopenia did not affect recruitment of mononuclear cells to the dermis. In the period immediately after administration of cyclophosphamide and methotrexate, the macroscopic score increased. Whilst the mechanism of this effect is unclear, it may be a manifestation of a basophil, perhaps IgE mediated reaction. Further manipulation of dose and dose interval may result in administration schedules relevant to the treatment of cell-mediated hypersensitivity in clinical practice.     

Splanchnic blood flow during halothane-relaxant anaesthesia in elderly patients

We have previously found that halothane-relaxant anaesthesia in elderly patients causes a change towards a hyperkinetic circulation, with a decrease in the arterial-mixed venous oxygen content difference. This could be attributed to vasodilation. In the present study the splanchnic contribution to these changes was investigated. Nine patients were studied during halothane-relaxant anaesthesia prior to surgery. During anaesthesia splanchnic blood flow was markedly reduced, while splanchnic oxygen uptake decreased only moderately compared with the awake level. This resulted in an increase in splanchnic oxygen extraction. It is concluded that the splanchnic vascular bed does not contribute to the "hyperkinetic" circulation during halothane anaesthesia.     

Animal models and treatment of prostate cancer

Model systems for prostate cancer in rats have been developed and used for investigations on tumor biology and therapy. The "Pollard tumors" provide a combination of in vitro and in vivo attributes by which investigations can be directed at local tumor development and spontaneous metastasis. The evolution and early applications of this model system are reviewed, and the therapeutic benefits of delayed release of cyclophosphamide are presented.     

Antimicrobial Resistance: Is Health Technology Assessment Part of the Solution or Part of the Problem?

Antimicrobial resistance is a serious challenge to the success and sustainability of our healthcare systems. There has been increasing policy attention given to antimicrobial resistance in the last few years, and increased amounts of funding have been channeled into funding for research and development of antimicrobial agents. Nevertheless, manufacturers doubt whether there will be a market for new antimicrobial technologies sufficient to enable them to recoup their investment. Health technology assessment (HTA) has a critical role in creating confidence that if valuable technologies can be developed they will be reimbursed at a level that captures their true value. We identify 3 deficiencies of current HTA processes for appraising antimicrobial agents: a methods-centric approach rather than problem-centric approach for dealing with new challenges, a lack of tools for thinking about changing patterns of infection, and the absence of an approach to epidemiological risks. We argue that, to play their role more effectively, HTA agencies need to broaden their methodological tool kit, design and communicate their analysis to a wider set of users, and incorporate long-term policy goals, such as containing resistance, as part of their evaluation criteria alongside immediate health gains.