Differential time course of the vasodilator action of various calcium antagonists

Summary— It is rather the rate of the vasodilator effect than its magnitude which determines the triggering of reflex tachycardia associated with dihydropyridine calcium antagonists (DHP-CA). We therefore compared the rate of the vasodilator effects of a series of CA (both DHP and non-DHP) in rat isolated mesenteric artery preparations (size 256 ± 3 μm, length 2 mm) from male Wistar rats (weighing 300–350 g) in an isolated wire myograph according to Mulvany and Halpern [12]. The mean force of the KCl-induced contraction amounted to 2.3 ± 0.1 mN/mm. Potency (given as IC₅₀-values), differential time course of action and recovery of the contractile response of the vessels after wash-out were established. These three parameters adhere to the following sequences; (1. potency) S,S-barnidipine > (S)-lercanidipine > barnidipine HCl > amlodipine > nifedipine, lacidipine > (R)-lercanidipine > verapamil, mibefradil; (2. differential time course) lacidipine, amlodipine > (S)- and (R)-lercanidipine. S,S-barnidipine, barnidipine HCl > mibefradil, verapamil, nifedipine; (3. recovery) nifedipine > verapamil, S,S-barnidipine, amlodipine > barnidipine, lacidipine > mibefradil, (R)-lercanidipine > (S)-lercanidipine. In conclusion, S,S-barnidipine proved to be the most potent vasodilator agent; interestingly, barnidipine was 20 times less potent when applied as a racemic mixture. A slow onset of action in DHP is a very important mechanism in preventing reflex tachycardia. For non-DHP (verapamil, mibefradil) reflex tachycardia probably is prevented by a direct effect on the conductive tissue in the myocardium.     

马拉松赛对中老年人心脏结构、功能和血清酶的影响

为了了解中老年人马拉松赛后心脏结构、功能和血清磷酸肌酸激酶及同功酶变化的特点,对参加加拿大国家马拉松赛的10名50—73岁的马拉松运动员进行观察并与10名50岁以下的马拉松运动员作了比较,发现50岁以上有训练的马拉松运动员有较好的血管调节功能和良好的心脏代偿能力。血清磷酸肌酸激酶同功酶的变化,反映了马拉松跑对老年人心脏的影响。     

Prevalence of and risk factors for Helicobacter pylori infection in a multi-racial dyspeptic Malaysian population undergoing endoscopy

The aim of the present study was to determine the risk factors for Helicobacter pylori in a dyspeptic Malaysian population. A cross-sectional survey of 1060 consecutive patients presenting with dyspepsia at the Endoscopic Unit, University Hospital, Kuala Lumpur, Malaysia from January 1994 to July 1995 was undertaken. All patients answered a detailed questionnaire and underwent endoscopy, with two antral biopsies taken for diagnosis of H. pylori using a rapid urease test. An overall H. pylori prevalence of 49.0% was recorded. Helicobacter pylori prevalence in relation to the major endoscopic diagnoses were as follows: non-ulcer dyspepsia (NUD) 31.2%; duodenal ulcer (DU) 91.4%; and gastric ulcer (GU) 74.1%. The prevalence among the races were as follows: Malay 16.4%; Chinese 48.5%; and Indians 61.8%. Multiple logistic regression analysis identified the following as independent risk factors: > 45 years old 1.5 (1.1,2.0); male gender 1.6 (1.2,2.1); ethnic group: Chinese 2.5 (1.7,3.7); Indians 4.9 (3.2,7.5); level of education: low 2.3 (1.5,3.5); middle 1.7 (1.1,2.6); and smoking 1.6 (1.2,2.3). Analysis was also performed on DU, GU and non-UD patients separately; in both DU and GU patients, H. pylori prevalence was high regardless of age, sex, race or level of education. However, in DU patients, Indian race had an independent risk factor (Odds ratio = 7.8 (1.2,48.4)). The findings in the NUD group reflected the findings in the ‘all patients’ group; > 45 years old, male gender, Indian and Chinese race, and low level of education were also significant, independent risk factors. The overall differences in H. pylori prevalence between the different subgroups were mainly due to differences in the NUD group. The increased risk of H. pylori infection in Chinese and Indians points to either an inherent ethnic genetic predisposition or to socio-cultural practices peculiar to the particular race which may be responsible for transmission of the infection.     

What is a large breast? Measuring and categorizing breast size for tangential breast radiation therapy

Despite consensus in published studies that larger‐breasted patients who undergo radiation therapy tend to suffer from more severe acute skin reactions and a more adverse cosmetic outcome, there appears to be no consensus on the definition of a ‘large breast’. This paper describes an analysis of breast size that was undertaken on 50 patients and compares this data with other published studies. The desired outcome for the study was to formulate a definition of ‘large breast size’ that would be appropriate for Australian patients and that could be determined simply and quickly in busy radiation oncology clinics. Analysis suggests that cup and brassiere size may be used to separate breast size into two categories. On the basis of published data and results from this study, it is recommended that patients with a cup size ≥D or a bra size ≥18 could be categorized as having large breasts, with all other patients considered average in size.     

THE EFFECT OF RANITIDINE ON SYMPTOM RELIEF AND QUALITY OF LIFE OF PATIENTS WITH GASTRO-OESOPHAGEAL REFLUX DISEASE

SUMMARY A 4-week study involving 354 patients with the symptoms of gastro-oesophageal reflux disease was conducted to assess the effect of ranitidine (as effervescent tablets) on their relief and quality of life. All patients received 150 mg bd for 2 weeks, with those responding to treatment continuing on the same dosage for a further 2-week period and 'non-responders' having the dosage increased to 150 mg qds for a further 2 weeks. Quality of life and symptom assessments were carried out at 0, 2 and 4 weeks. Two weeks' treatment with ranitidine 150 mg bd was effective at controlling the GORD symptoms in 78% of patients. A 4-week treatment with either 150 mg bd or qds controlled the symptoms in 85% of patients. All patients had significant improvements in all dimensions of their quality of life over the study period.     

Pharmacodynamic behaviour of isolated resistance vessels obtained from hypertensive-diabetic rats

Summary— The influence of various vasodilator and constrictor drugs was studied in isolated mesenteric arteries obtained from obese and lean Zucker rats. The obese Zucker rats were moderately hypertensive and their isolated small arteries were not hypertrophied. All vasoconstrictor agents studied (noradrenaline, methoxamine, serotonin, calcium chloride, potassium chloride) caused the same effects in isolated arteries taken from obese and lean (control) Zucker rats, respectively. In vessels from obese Zucker rats, the vasodilator responses to sodium nitroprusside, methacholine, the K+-channel opener cromakalim and nifedipine were the same as in control preparations. In conclusion, isolated mesenteric arteries from obese Zucker rats do not show relevant structural changes, and the pharmacodynamic behaviour of such vessels appears to be the same as that of control preparations. Neither the diabetic hyperinsulinaemic state nor the hyperlipoproteinaemia in the obese Zucker rats appear to cause serious vascular damage.     

Inhibition of WY-14,643 induced hepatic lesion growth in mice by rotenone

The effect of rotenone treatment on [4-chloro-6-(2,3-xylidino)-2- pyrimidinylthio] acetic acid (WY-14,643) hepatic lesion growth in male B6C3F1 mice was investigated. Following induction of hepatic focal lesions by diethylnitrosamine (DEN) 35 mg/kg twice a week for 8 weeks, mice were placed into one of the four treatment groups: group I, control NIH-07 diet (control diet), group II, rotenone (600 mg/kg diet), group III NIH-07 diet containing WY-14,643 (1000 mg/kg diet), and group IV, NIH-07 diet containing WY-14,643 (1000 mg/kg diet) and rotenone (600 mg/ kg diet). Mice were killed after 30 and 60 days of dietary treatment. The effect of treatment with WY-14,643 and rotenone on hepatic lesion growth was examined by estimating the number of focal lesions per liver and the relative volume of focal lesions. WY-14,643 (group III) increased both the number and the volume of focal lesions. In particular, an increase in number and volume of basophilic lesions was seen. Co-treatment with WY-14,643 and rotenone (group IV) decreased both the number and the volume of the total number of focal lesions and basophilic foci compared with WY-14,643 treatment alone (group II). Alterations in the growth of hepatic focal lesions was further investigated by examining DNA synthesis and apoptosis within individual lesions. WY-14,643 (group III) treatment increased the DNA synthetic labeling index in all foci. Co-treatment of rotenone and WY-14,643 (group IV) decreased focal DNA synthesis and mitosis and increased the incidence of apoptotic hepatocytes. These data suggest that rotenone's ability to inhibit WY-14,643-induced hepatic focal lesion growth was mediated through a decrease in hepatic focal proliferation and an increase in focal apoptosis.