Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume

Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)ldt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [ · LV(0)], where is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while a is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min^–1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/1 [r = 0.82,n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the^99mTcDTPA study. They also correlated significantly with the plasma cyclosporin trough level in 14 patients with dermatomyositis on the 30 occasions when this measurement was made within 1 week of the renogram (r = –0.38,P < 0.05 for GFR/PV andr = –0.77,P < 0.001 for GFR/ECV). The ratio of GFR/PV to GFR/ECV is the ratio of extracellular fluid volume to plasma volume, and this was 4.0 (SD 0.99). We conclude that both GFR/PV and GFR/ECV can be easily measured with^99mTc-DTPA and are physiologically valid expressions of GFR. Although GFR/PV and GFR/ECV correlate with each other, the question is raised as to which of the two fluid volumes is the most appropriate for normalising GFR. Correspondence to: A.M. Peters     

Postnatal development of vascular β-adrenoceptor-mediated responses and the increase in the adrenaline content of the adrenal gland have a parallel time course

The present study was undertaken to analyse the relationship between postnatal development of vascular ₂-adrenoceptor-mediated responses and the content of adrenaline in the adrenal gland and its concentration in plasma. Dog saphenous vein tissue from newborn, two-weeks old and adult animals were either preloaded with ³H-noradrenaline (or ³H-adrenaline) to study prejunctional -adrenoceptor-mediated effects or mounted in organ baths to determine isoprenaline-induced relaxation of preparations contracted by phenylephrine to about 65010 of the maximum. The adrenal glands and samples of blood from the same animals were taken for estimation of adrenaline and noradrenaline.At birth, there were no -adrenoceptor-mediated effects pre- or postjunctionally. At two weeks, while the results at the prejunctional level were not significantly different from those obtained in newborns, at the postjunctional level there was a relaxant response to isoprenaline, which antagonised about 35010 of the previous contraction to 1.75 mol·l^–1 phenylephrine. In adults, isoprenaline (50 nmol·l^–1) increased by 24% tritium overflow evoked by electrical stimulation of tissues preloaded with ³H-noradrenaline but not that of tissues preloaded with ³H-adrenaline. On the other hand, propranolol (1 mol·l^–1) reduced by 21% the overflow of tritium evoked by electrical stimulation of tissues preloaded with ³H-adrenaline but not that of tissues preloaded with ³H-noradrenaline; postjunctionally, the maximal response to isoprenaline antagonised 70% of the previous contraction to 1.75 mol·l^–1 phenylephrine.At birth the catecholamine content of the adrenals was relatively low (2.9 ol·g^–1) and the adrenaline/noradrenaline ratio was 0.26; two weeks later, the catecholamine content was 14.5 mol·g-1and the adrenaline/noradrenaline ratio was 0.74; in adults, the catecholamine content was 24.5 mol·g^–1 and the adrenaline/noradrenaline ratio was 2.3. In plasma, the highest concentration of adrenaline was observed at birth (11.8 nmol·l^–1); two weeks later it was 5.5 nmol·l^–1 and in adulthood it fell to 3.1 nmol·l^–1.On the basis of these results, it is concluded that some link between the postnatal increase in adrenaline adrenal content and the development of ₂-adrenoceptor-mediated pre- and postjunctional effects may exist. Additionally it is suggested that circulating adrenaline may trigger the development of ₂-adrenoceptor-mediated responses as well as some hypertensive states occurring as a consequence of an overreactivity of the sympathoadrenal system. Correspondence to: S. Guimarães at the above address     

Relationship between plasma and bone concentrations of cefuroxime and flucloxacillin three different parenteral administrations compared in 30 arthroplasties

• (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin.
• (ii) Six groups of five patients participated in the study. The first three groups (A–C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D–F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously.
• (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients.
• (iv) Large inter-individual variation in bone concentration was observed.
• (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.

     

血液制品丙肝病毒与艾滋病毒检测

目的了解１９９３～１９９５年度临床使用的新鲜冰冻血浆（ＦＦＰ）和血液制品中艾滋病毒（ＨＩＶ）、丙肝病毒（ＨＣＶ）的感染情况。方法用ＥＬＩＳＡ、ＷＢ和ＰＣＲ对１１０批ＦＦＰ、人血丙种球蛋白、人血白蛋白检测了抗ＨＣＶ、ＨＣＶＲＮＡ、抗ＨＩＶ（１＋２）、ＨＩＶ－１ＲＮＡ。结果所有血制品抗ＨＣＶ的平均阳性率为１９．１％,ＨＣＶＲＮＡ为１７．３％;１９９３～１９９４年度ＦＦＰ的抗ＨＣＶＨＣＶＲＮＡ阳性率比１９９５年度高（３０％、２６％和０．５％）;人血丙球的抗ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于人血白蛋白（３０％、２０％和０．５％）;８９批抗ＨＣＶ阴性血制品ＨＣＶＲＮＡ的阳性率为５．６％,所有血制品的抗ＨＩＶ（１＋２）和ＨＩＶ－１ＲＮＡ均阴性。结论１９９３～１９９５年度临床上所使用的血制品,特别是１９９３～１９９４年度的ＦＦＰ,有传播ＨＣＶ的危险,这与当时没有对所有供血者进行抗ＨＣＶ筛检有关。     

High prevalence of type 2 diabetes in an urban settlement in Kerala, India

Background. Prevalence of type 2 or non insulin dependent diabetes mellitus is high among Indians living in India as well as abroad. Prevalence among persons of Indian origin in many countries is greater than that of people of other ethnic extraction. The Indian state of Kerala is distinguished by a high level of achievement in the health sector, characterised by both lower mortality rates and greater density of health care institutions that ensure access to most people. These attributes make the prevalence of diabetes and the pattern of its management in Kerala worth studying. Objective. To estimate the prevalence of diabetes among persons 20 years or older in an urban housing settlement in Trivandrum city, the capital of Kerala, as well as study the management of the disease in subjects affected. Design. Cross sectional survey for detecting diabetes and other chronic diseases in all willing residents of an urban housing settlement in Trivandrum, the capital city of Kerala, as part of a preventive campaign against lifestyle diseases. Fasting plasma glucose, serum triglycerides, cholesterol, height, weight and blood pressure were measured, and a detailed questionnaire administered to ascertain previous diabetic status and management. Results. Overall prevalence of type 2 diabetes is 16.3%. In the 30-64 age group, age standardised prevalence is 13.7%. Gender differences in prevalence are negligible. Greater prevalence is associated with advancing age, body mass index above 24.99, sedentary habits, serum total cholesterol > 239, serum triglycerides > 149, hypertension and smoking. Compared to non-diabetics, diabetics have greater mean and range of fasting plasma glucose values (8.87 + /-3.6 mM/l as against 4.34 + /-0.53 mM/l). 32 out of 38 diabetics among the subjects (82.4%) were already diagnosed even before the survey; of them, 89% were on medication. 3% of subjects had impaired fasting glucose, or FPG level between 110-125 mg/dl. Conclusion. Prevalence of type 2 diabetes among a group of urban residents in Trivandrum city in Kerala is very high. This is associated also with a high detection rate and compliance to treatment.     

普拉西坦在动物体内的药物代谢动力学

为研究普拉西坦在犬和大鼠体内药代动力学规律,给犬灌服普拉西坦后,抽取不同时间的血液,分离血浆,用ＨＰＬＣ测定血浆中药物浓度,采用３ｐ８７ 程序计算药代参数;应用ＨＰＬＣ测定大鼠灌服普拉西坦后各组织和胆汁、尿、粪中药物浓度。结果显示：血药浓度－时间曲线符合一室开放模型,其体内的Ｔ１／２为２．３～３．９ 小时;大鼠灌服普拉西坦后３ 小时各组织中有较高的浓度,以肾脏为最高,肝脏次之,依序为肠、肺、肌、心、生殖腺、脾、脂肪;脑组织也能测到一定的量。２４小时从胆汁排泄原形药物占给药量的０．７％ ,７２小时从尿和粪中排出原形药物量分别占给药量的２８．２６％ 和６．３５％ 。用平衡透析法测定普拉西坦的血浆蛋白结合率约为２０．１％ ～２２．２％ 。以上结果表明,普拉西坦吸收快,分布广,消除也快。     

Exercise induces a change in plasma fibrinogen concentration: fact or fiction?

This study examined the effect of exercise on plasma fibrinogen concentrations with simultaneous measurements of plasma volume changes. Eight moderately active males aged 26.6±3.6 years (mean±SD) completed maximal (VO₂max) and submaximal (75% VO₂max for 30 minutes) exercise trials separated by 7 days. Venous blood samples were obtained at rest, immediately postexercise, and following 30 minutes of recovery. Whole blood was analysed for haematocrit and haemoglobin, while citrated plasma was assayed for fibrinogen levels. Values of haematocrit and haemoglobin before and after exercise were utilised for the estimation of plasma volume changes. Plasma volume decreased (p<0.05) immediately following both maximal (−17.7±5.1%) and submaximal (−14.3±4.1%) exercise. Exercise resulted in decreased plasma fibrinogen levels (maximal exercise: from 266.3±14.5 to 222.2±23.9 mg·dL⁻¹; submaximal exercise: from 239.5±45.4 to 209.7±42.4 mg·dL⁻¹) only when postexercise raw data were corrected for the contraction of plasma volume. It is concluded therefore that changes in plasma volume in response to exercise should be taken into account when interpreting exercise effects on plasma fibrinogen concentration.     

Value of direct measurement of active renin concentrations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

In congenital adrenal hyperplasia (CAR) due to 21-hydroxylase deficiency, measurement of plasma renin activity (PRA) has been the method of choice in diagnosing salt loss and in monitoring adequacy of mineralocorticoid replacement therapy. Due to methodological problems in PRA determinations, direct immunoradiometric assays for the measurement of active renin concentration have been developed. We measured PRA and active renin concentrations simultaneously in 39 patients with CAH (30 salt-wasting, 9 simple virilizing) to evaluate the potential role of this new method in the management of this disease. PRA was determined with an enzymatic assay (sample volume: 2 × 1000 l plasma), active renin concentration with a direct immunoradiometric assay (sample volume: 2 × 200 l plasma or serum). We found a highly significant correlation between active renin and PRA in our patients (P < 0.001), as previously shown in healthy subjects. Active renin was as reliable as PRA to assess the quality of mineralocorticoid replacement.     

Role of tachykinins in airway narrowing induced by cigarette smoke in guinea pigs

To investigate the mechanism of the airway narrowing induced by cigarette smoke, anaesthetized guinea pigs were exposed to 200 puffs of smoke for 10 min. Airway narrowing was assessed by monitoring the total pulmonary resistance (R_L). Plasma extravasation was determined by measuring the amount of Evans blue dye extravasated into the trachea and main bronchi. Exposure to cigarette smoke caused a marked airway narrowing and plasma extravasation. Pretreatment with the dual NK₁ and NK₂ receptor antagonist, FK224, abolished such airway narrowing and significantly inhibited the extravasation. While the NK₁ receptor antagonist, FK888, inhibited the extravasation, it had no effect on airway narrowing. Atropine partially inhibited airway narrowing without affecting extravasation. Results suggest that the airway narrowing induced by cigarette smoke is caused by tachykinins, and that a cholinergic pathway is involved. Thickening of the airway walls induced by NK₁ receptor-mediated extravasation may not be involved in such airway narrowing.