Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours

In 10 patients subjected to craniotomy for supratentorial cerebral tumours in neurolept anaesthesia, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice peroperatively by a modification of the Kety & Schmidt technique, using 133Xe. The relative CO2 reactivity was assessed indirectly as the % change of the arteriovenous oxygen difference (AVDO2) per mm change in PaCO2. The patients were premedicated with diazepam 10-15 mg perorally. For induction, thiopentone 4-6 mg/kg, droperidol 0.2 mg/kg and fentanyl 5 micrograms/kg were used, and for maintenance N2O 67% and fentanyl 4 micrograms/kg/h. During the first flow measurement the median and range of CBF was 30 ml/100 g/min (range 17-45), of AVDO2 8.0 vol % (range 4.1-9.5), and of CMRO2 2.28 ml O2/100 g/min (range 1.57-2.84). During the second CBF study, AVDO2 increased to 9.3 vol % (range 3.4-11) (P less than 0.05), and CMRO2 increased to 2.51 ml O2/100 g/min (range 1.88-3.00) P less than 0.05, while CBF was unchanged. The CO2 reactivity was present in all studies, median 1.8%/mmHg (range 0.5-15.1). The correlation coefficients between jugular venous oxygen tension/saturation, respectively, and CBF were high at tensions/saturations exceeding 4.0 kPa and 55%, indicating that hyperperfusion is easily unveiled by venous samples from the jugular vein during this anaesthesia.     

A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism

A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.     

Population toxicokinetics of tetrachloroethylene

 In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% confidence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% confidence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be verified by further experiments. Received: 20 April 1995/Accepted: 24 August 1995     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

α<Subscript>2β</Subscript> adrenoreceptor 301–303 deletion polymorphism in polycystic ovary syndrome

α_2β adrenoreceptor 301–303 deletion polymorphism does not influence basal metabolic rate, insulin resistance or weight gain in Greek women with polycystic ovary syndrome.     

2型糖尿病并脂肪肝与血脂紊乱的关系探讨

目的　探讨 2型糖尿病并脂肪肝患者与脂代谢紊乱之间的关系。方法　对 60例 2型糖尿病并脂肪肝和 5 2例 2型糖尿病不并有脂肪肝病例的血脂谱 ,空腹血糖 (FPG ) ,餐后 2小时血糖 ( 2hPG) ,空腹胰岛素 (FINS)进行测定 ,计算体重指数 (BMI)及胰岛素敏感指数 (ISI)。结果　 2型糖尿病并脂肪肝与不并脂肪肝相比 ,甘油三脂 (TG) ,低密度脂蛋白胆固醇 (LDL -C) ,FINS均升高 (P <0 .0 5 ,P <0 .0 1) ,而ISI明显降低 (P <0 .0 1)、脂蛋白a(Lp(a)降低(P <0 .0 5 )。结论　 2型糖尿病并脂肪肝比不并脂肪肝者存在明显脂代谢紊乱及胰岛素抵抗     

Thiamine deficiency in utero alters response to ethanol in adulthood

To determine whether prenatal thiamine deficiency, a frequent concomitant of alcoholism, reduces the response to ethanol during adulthood in the rat as does ethanol exposure in utero (Abel et al. 1981), pregnant Sprague-Dawley rats received either control or thiamine deficient diets together with daily injections of the thiamine antagonist pyrithiamine. At 7 months of age, male offspring were exposed to precisely regulated ethanol vapor concentrations in an inhalation chamber for 24 h and blood ethanol concentrations (BECs) and ethanol-induced intoxication were determined. Prenatally thiamine deficient rats and controls were indistinguishable in terms of appearance, body and liver weights, and the ratios of liver to body weight and brain to liver weight. However, total body water was significantly greater, and BECs and behavioral impairment were decreased, in the experimental rats. These findings indicate that prenatal thiamine deprivation is associated with reduced pharmacologic effect of ethanol as a result of increases in its volume of distribution and rate of metabolism.     

A comparison of the effects of a macrobiotic diet and a western diet on drug metabolism and plasma lipids in man

Summary We have compared the effects of two dietary regimens with different macronutrient compositions — a macrobiotic diet and a Western diet — on drug metabolism and plasma lipids in seven healthy volunteers.The macrobiotic diet, high in carbohydrate, low in protein and fat, and devoid of animal food sources, was eaten for a ten day control period, as was the Western diet, high in calories, fat, and protein, as well as animal food sources. We determined the influences of these diets on the clearance of orally administered antipyrine, oxazepam, and methadone, as well as on plasma lipids.There was a statistically significant change in antipyrine clearance as well as in plasma LDL-cholesterol and HDL-cholesterol after the dietary periods. This suggests that the influence of dietary changes may have some effect on the clearance of therapeutic drugs. However, this is not universal and is probably important when the drug is highly dependent on the mixed-function oxidase system.