同步放化疗治疗中晚期食管癌60例

目的 观察对中晚期食管癌患者同步放化疗,疗效及毒副作用.方法 中晚期食管癌120例,随机分放化疗组60例(简称放化组)和单纯放疗组60例(简称单放组).放疗采用常规分割,DT40 Gy后缩小照射野,避开脊髓斜野照射,加量DT20～30 Gy,6～7周完成.放化组放疗1、4周后应用顺铂(DDP)20 mg/d、亚叶酸钙(CF)0.1 g/d,CF静脉滴注1/2量时5-氟尿嘧啶(5-Fu)500 mg/d静脉滴注,连续5 d为1个周期,化疗当天进行放疗.结果 放化组与单放组1、2、3年生存率分别为67%、46%、34%和52%、38%、24%;放射性肺炎分别为14例和12例;外周血细胞下降分别为26例和17例;胃肠道反应分别为25例和9例;死亡分别为38例和48例.两组治疗效果比较差异有统计学意义(P＜0.05).结论 放疗同步PLF方案化疗治疗中晚期食管癌生存率高,毒副作用及不良反应低.     

Selective coating of cylindrical matrices with a central hole. I. An interpretation of the swelling process

Cylindrical matrices were prepared by compression either of polyvinyl alcohol 100000 or mixtures of the excipient and a drug (sodium salicylate or theophylline). To modify the cylindrical shape, a hole was bored in the centre of the flat surface through both sides of the matrices. Different swellable systems were obtained applying an impermeable coating to one, two or three surfaces of the perforated matrices. The swelling of the perforated matrices was modified according to the number and the position of the coated surfaces (selective coating) and the loaded drug. Pseudo-zero order kinetics were obtained when the interior hole was the only uncoated surface.     

Drug Education: Supporting Parents to Support Children

Such research evidence as exists on effective drug strategies in prevention and education draws attention to the importance of involving parents along with other community agencies and school governors. Much depends nevertheless on the way in which 'involvement' is interpreted and the assumptions that are made about parents' knowledge of drugs and drug education as well as their attitudes to drug issues. As the age of initial experimentation and contact with drugs continues to fall, the importance of enskilling parents to support drug education programmes for 5 year olds and upwards continues to rise. This paper reports the first wide ranging survey of parents' knowledge of drugs and drug issues across an entire English county embracing younger as well as older children. The need for more coordinated, informed and systematic guidance to parents is established.     

The Problem of Intractability: The Continuing Need for New Medical Therapies in Epilepsy

Summary: Treatment of epilepsy, one of the most common neurologic disorders, has evolved from "institutional" poly-therapy to "dogmatic" monotherapy, and, most recently, to "rational" polypharmacy. The introduction of bromides for the treatment of epilepsy was followed first by phenobarbital and then by phenytoin as therapeutic options. Although attempts to combine medications were legion, none was supported by studies that demonstrated the benefit of such combinations. The issue of adverse effects became a principal argument in favor of monotherapy. Monotherapy, using newly developed drugs, avoided problems due to drug interactions but was ineffective in 20–30% of patients. A greater understanding of basic disease mechanisms and developments in molecular biology have led to an increased number of effective drugs for the estimated 6–12% of patients with epilepsy whose condition is intractable. Clinical research continues to build on the work of basic scientists in attempting to develop treatments based on a desire to move beyond the palliative and to affect the causative mechanisms of the disease. Novel medical approaches now under exploration include the use of drugs with complementary mechanisms of action, stimulation of various components of the nervous system, biochemical manipulations, focal intracerebral drug perfusion, and gene therapy.     

Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey

 The behavioral effects of GBR 12909, a selective dopamine uptake inhibitor, were determined in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of stimulus termination and a second-order schedule of IV drug self-administration. Intermediate doses of GBR 12909 increased FI response rate markedly, and the highest dose decreased response rate below control values. The 5HT uptake inhibitors, alaproclate and fluoxetine, and the 5HT agonist, quipazine, attenuated the behavioral-stimulant effects of GBR 12909, whereas the 5HT_2A/2C antagonist, ritanserin, enhanced the behavioral-stimulant effects of the lowest dose. GBR 12909 reliably maintained self-administration, and ritanserin increased response rate maintained by the highest dose. The dopamine agonist, quinpirole, increased FI response rate in only one of three subjects, and ritanserin enhanced the behavioral-stimulant effects of quinpirole in that subject. The dopamine agonist, apomorphine, only decreased FI response rate, and ritanserin did not alter its behavioral effects. The pharmacological profile of GBR 12909 administered alone and in combination with selective 5HT drugs in the present study was similar to that obtained previously with cocaine, further demonstrating that 5HT can reliably modulate the behavioral effects of psychomotor stimulants with prominent dopaminergic actions. Received: 9 July 1996 / Final version: 22 November 1996     

IgA antiendomysium antibodies in human umbilical cord sections as a screening test in relatives of patients with celiac disease

We performed the serum IgA antiendomysium antibody (EmA) assay by indirect immunofluorescence on human umbilical cord sections in 86 subjects with celiac disease, in 187 first-degree relatives of such patients, and in a control group of 68 unrelated subjects, to investigate the suitability of the method in the screening of populations at risk of gluten sensitivity. Conventional EmA assay using monkey esophagus sections was performed in parallel experiments. The results obtained showed a perfpect correlation between the two methods. All the celiac patients and none of the controls were positive for EmA. EmA positivity was also observed in 11 apparently healthy relatives: intestinal biopsy performed in five of them invariably showed villous atrophy and increase of mucosal lymphocytes. Taking into account the low cost of EmA assay on human umbilical cord, especially when compared to monkey esophagus sections, the method is probably suitable and effective in identifying latent, asymptomatic gluten sensitivity in at-risk populations.     

Neuropharmacology and Drug Interactions in Clinical Practice

Summary: Absorption, distribution, and clearance are key pharmacokinetic principles. These parameters can be highly variable among patients and among compounds, and are factors that must be considered in the wide variability in response to medications. Current antiepileptic drugs (AEDs) present many challenges in their administration. However, understanding and utilizing pharmacokinetic principles can assist the clinician in the appropriate optimization of AEds.     

Drug related hospital admissions

Summary As part of a high-intensity monitoring study of drug events as the cause of admission to departments of internal medicine, the effect of an educational intervention programme was studied. Two departments were included, one specialising in geriatrics and one that received patients by non-selected referral. The series consisted of 607 consecutive admissions studied before and 703 after the intervention. The drug events considered were adverse drug reactions and dose-related therapeutic failures, mainly due to non-compliance.A modest, statistically non-significant decrease in drug related hospital admissions (DRH) was seen, from 14% before to 13% after the intervention period. However, DRHs classified as definitely avoidable showed the significant decrease of 83%.There was no apparent relationship between the topics selected for the intervention programme and changes in the pattern of DRHs. No relationship between alterations in sales data and hospital admissions caused by a given drug could be demonstrated. A blinded external evaluation of case abstracts did not disclose any significant shift in the investigators' assessments.The intervention may have had an non-specific effect on avoidable DRHs.     

Two genes for chloramphenicol resistance common to Staphylococci and streptococci

Southern blot hybridization and pneumococcal transformation were used to study the epidemiology at a molecular level of the genes for chloramphenicol resistance (cat) in streptococci and staphylococci. The cat gene of staphylococcal plasmid pC194 showed homology to the cat genes of the chromosomal elements of 5 different strains of Streptococcus pneumoniae and of Streptococcus agalactiae B109. DNA sequence homology was also detected between the cat gene of staphylococcal plasmid pC221 and the cat gene of broad host range conjugative plasmid pIP501, originally isolated from S. agalactiae. Two different cat genes appear to be present in clinical isolates of both streptococci and staphylococci.     

Differences in bioavailability between cocaine and cocaethylene and their implications for drug-reward studies

Cocaethylene, a psychoactive metabolite resulting from combined ethanol/cocaine consumption, is of interest because its psychostimulant properties may partially underlie combined cocaine/ethanol use, and because it has the potential for use as a probe of drug reward mechanisms due to its enhanced selectivity at monoamine uptake sites compared to cocaine. To determine the relative systemic bioavailabilities of cocaine and cocaethylene, sequential plasma samples were obtained from awake rats following drug administration. Following intravenous administration of 3 µmol/kg (molar equivalent of 1 mg/kg cocaine-HCl), both drugs achieved similar time courses and areas under the plasma concentration versus time curve. In contrast, intraperitoneal administration of 44 µmol/kg (molar equivalent of 15 mg/kg cocaine HCl) showed peak plasma levels, and the area under the plasma concentration vs time curve for cocaine to be approximately twice that for cocaethylene. Comparison of dose corrected areas under the curve of the two routes of administration for each drug indicated that relative systemic bioavailability of cocaethylene following intraperitoneal administration is only 58% that of cocaine. In addition, the elimination of both cocaine and cocaethylene was found to be slower following intraperitoneal administration compared to the intravenous route. The implications of these results are discussed with respect to the relative potency of these two compounds, as inferred from behavioral, drug reward, and lethality studies. Also, the differences noted will need to be taken into account when making mechanistic interpretations from comparative drug reward studies.