Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers,major metabolites of phenytoin,on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study

The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 g·ml^–1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.     

硝酸甘油与美托洛尔预防气管插管所致循环副作用的比较

①目的　比较硝酸甘油与美托洛尔在麻醉诱导中对心率、血压和左室射血功能的影响。②方法　２４例病人随机分为３ 组,每组８ 例。麻醉诱导均选用芬太尼、硫喷妥钠和琥珀酰胆碱。于静脉诱导后分别静注美托洛尔、硝酸甘油和生理盐水,监测气管插管时平均动脉压（ Ｍ Ａ Ｐ）、心率（ Ｈ Ｒ）和每搏量（ Ｓ Ｖ）变化。③结果　插管后美托洛尔组 Ｍ Ａ Ｐ低于对照组, Ｈ Ｒ 低于对照组及硝酸甘油组, Ｓ Ｖ 高于硝酸甘油组,差异均有显著性（ Ｆ＝ ４．０７～５．９６,ｑ＝ ３．４４～４．４９, Ｐ 均＜ ０．０５）。④结论　美托洛尔与硝酸甘油皆可预防气管插管所致的循环副作用,但美托洛尔作用优于硝酸甘油。     

Developing rational protocols for paediatric psychopharmacological prescribing.

The number of child psychiatrists, paediatricians and general practitioners prescribing psychotropic medication for children in the UK is increasing. Medication is being used not just to treat children of normal intelligence with hyperkinetic disorder or depression, but also to modify behavioural problems in children with developmental disorders and severe learning difficulties. Literature reviews highlight the lack of robust randomized controlled drug trials on which to base clinical practice and the authors have found no appropriate existing protocols to help develop a systematized approach. Against such a background the authors have developed a comprehensive set of protocols covering prescribing details for individual drugs, and also addressing issues such as informed consent, long-term monitoring and school liaison. All children referred to the authors' clinics go through a standardized decision-making process. This article describes both the protocols themselves and the philosophies that guided their development. The authors describe how such a system benefits the children, their families, general practitioners and schools, whilst also facilitating audit and research.     

妇科癌症病人化疗期间呕吐的心理疗法

目的呕吐是癌症患化疗期间常见的症状之一,频繁的呕吐不仅给患带来痛苦,而且影响生活质量,甚至迫使患中止化疗;方法对100例妇科癌症病人采取有效的。理疗法或。理疗法加药物疗法;结果呕吐的发生率与单纯应用止吐药物患相比P<0．05,差异有显性;结论妇科癌症病人化疗期间呕吐的B理疗法或B理疗法结合药物疗法明显强于单纯药物疗法。     

Statins and peripheral neuropathy

Within the past 3 years seven cases of reversible peripheral neuropathy apparently caused by statins have been reported. Here we report seven additional cases associated with long-term statin therapy, in which other causes of neuropathy were thoroughly excluded. The neuropathy was in all cases axonal and with affection of both thick and thin nerve fibers. The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to 1 year in four cases after statin treatment had been withdrawn. We suggest that long-term statin treatment may be associated with chronic peripheral neuropathy. Received: 6 July 1998 / Accepted in revised form: 1 October 1998     

Compliance and adverse drug reactions: a prospective study with ethinylestradiol using continuous compliance monitoring

Summary This study examined the relationship between adverse reactions and patient compliance with ethinylestradiol at 40 g twice daily versus 20 g four times daily. In a randomized study 61 female patients with primary- infertility were prescribed the drug twice daily (n = 31) or four times daily (n = 30). Ethinylestradiol was administered for 7 days before the sperm cervical mucus penetration-test was performed for hormonal standardization of the cervical mucus quality. Drug compliance was measured by continuous monitoring using the Medication Event Monitoring System. Two parameters were evaluated: percentage of prescribed doses taken (administration compliance) and adherence to the prescribed dose schedule (regimen compliance, number of days with two or four dosing events recorded). Adverse drug reactions were assessed using a standardized questionnaire. Fourty-four women experienced side effects, of which 81% were rated by patients as being mild. Patient compliance was higher with the twice daily than with the four times daily regimen: 85% versus 65% prescribed doses taken (P<0.05). There was no significant difference in compliance comparing patients with and without adverse reactions (82% versus 72%, respectively), but compliance was lower and more irregular with at least 3 versus one or two adverse reactions reported: 54% versus 84% in administration compliance and 31% versus 58% in regimen compliance (P<0.05). Compliance was also lower in patients with nausea and vomiting than in those without these symptoms, 59% versus 91% and 34% versus 66% (P<0.005), respectively, and lower with moderate or severe compared to mild side effects; 48% versus 85% and 25% versus 59% (P<0.005). Thus the mere occurrence of side effects was not associated with low compliance. However, the number and nature of symptoms and their intensity as perceived by patients may have considerably influenced drug use behavior.Abbreviations ADR adverse drug reactions - SCMPT sperm cervical mucus penetration-test Prof. Dr. E. Weber died 7 December 1992     

A comparison of iopamidol and ioxaglate in CT enhancement

We evaluated the adverse reactions (AR) rate produced in patients to see if any difference related to the diferent chemotoxicities of two low-osmolality contrast media (CM), could be detected. We compared the AR rate intravenous administration for brain or body computed tomography (CT) enhancement of either the ionic CM ioxaglate 320 mgI/ml or the non-ionic iopamidol 300 mgI/ml at a dose of 0.8 gI/kg. Three hundred and thirty patients (164 ioxaglate, 166 iopamidol) were studied according to a randomized double-blind design. AR reported by the patients (subjective) and/or observed by the radiologist (objective) were recorded by the radiologist on the patients record card. Laboratory test were performed prior to and 24 h after contrast administration.Fifty-nine mild to moderate AR occurred in 30 patients (18.3%) receiving ioxaglate, 4 mild to moderate AR occurred in 2 patients (1.2%) receiving iopamidol (P < 0.05). No severe AR occurred in either group.The results of our study are comparative to the available evidence from 16 comparative randomized trials of iopamidol versus ioxaglate both after intraarterial and intravenous administration that gave an overall odds ratio of 3.9 [confidence interval (CI) 95% = 3.1–4.9].The diagnostic efficacy of the two CM was comparable. This study showed that the non-ionic CM iopamidol was better tolerated than the ionic ioxaglate after intravenous administration. We conclude that the chemotoxicity of the molecule influences the AR when CM with comparable osmolality are administered. Correspondence to: Carlo Del Favero     

Effect of occupational mercury exposure on plasma lysosomal hydrolases

Summary The activities of three plasma lysosomal hydrolases, -galactosidase, -glucuronidase and -N-acetylglucosaminidase, were studied in 20 workers exposed to metallic mercury vapor in a chlorine alkali plant and in 10 nonexposed referents. The urinary excretion and blood levels of mercury were determined on the day of study, and the history of mercury exposure was reviewed from the records of mercury concentrations in urine and blood over periods of up to 133 months. The average levels of -N-acetylglucosaminidase and -glucuronidase were higher in the plasma of exposed workers, but the difference was not significant. No significant positive correlation was seen between lyosomal enzyme activities and cumulative long-term exposure to mercury. It is concluded that measurement of plasma lysosomal hydrolase-activities is not of great value in the biological monitoring of workers exposed to low concentrations of metallic mercury vapor.In line with published data, the concentration of mercury showed a clearcut diurnal variation in nonexposed persons, persons currently exposed and persons with a history of past exposure. The excretion rate of mercury remained constant throughout the day.     

Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers

Summary O-(-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period.There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (90 arbitrary units i.e. 48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (–1.1, –5.9, and –7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group.