The effect of angiotensin II on haemodynamic and plasma noradrenaline responses to tyramine infusion in man

Summary Six normal volunteers were studied on four separate occasions. On each occasion they received two concomitant infusions which were either placebo/placebo, placebo/tyramine, angiotensin II/placebo or angiotensin II/tyramine. Angiotensin II infusion was given at a constant rate of 2ng/kg/min whereas the tyramine infusion consisted of 10 min increments at 1.25, 2.5, 3.75, 5, 7.5 and 10 g·kg^–1·min^–1.Tyramine infusion caused a dose dependent increase in systolic blood pressure with increases in diastolic blood pressure and plasma noradrenaline only at the highest doses. These changes were not affected by concomitant angiotensin infusion.We have therefore found no evidence to support the enhancement of haemodynamic or plasma noradrenaline responses to tyramine infusion by low dose infusion of angiotensin II in man.     

Crisnatol mesylate: Phase I dose escalation by extending infusion duration

Summary Crisnatol mesylate is a rationally designed cytotoxic arylmethylamino-propanediol with broad spectrum cytotoxic activity. A phase I study with an unconventional escalation scheme was developed using a constant drug infusion rate (mg/m²/hr) and prolonging the infusion duration from 6 to 96 hours. Sixty-five patients received crisnatol at doses from 18 mg/m² in 6 hrs to 3400 mg/m² in 72 hours. The dose-limiting toxicity in two of five patients at 2700 mg/m² and two of three patients at 3400 mg/m² was neurologic and consisted of a syndrome of confusion, agitation, and disorientation. Phlebitis mandated the use of a central line. The mean terminal phase half-life (T_1/2 ) was 3.3 hours with a total body clearance (CL) of 22.8 L/hr/m² and a volume of distribution (Vd_ss) of 53 L/m². The median steady-state peak plasma concentration (C_ss) at 2700 mg/m²/72 hours was 2.7 g/ml and at 3400 mg/m²/72 hours was 3.8 g/ml. No responses were seen. The maximum tolerated dose (MTD) on this schedule is 2700 mg/m²/72 hours in patients with no liver disease and good performance status.     

Long-term observation of chronic subsutaneous administration of lisuride in the treatment of motor fluctuations in parkinson's disease

Summary Twenty-nine patients with advanced Parkinson's disease were treated with subcutaneous lisuride infusion in addition to a basic therapy consisting of levodopa + PDI in all, and deprenyl in some patients. At the time of the report, 13 patients are still receiving lisuride infusion after 5–36 months, while 16 have dropped out after 0.5–30 months one because of psychosis, three because of insufficient efficacy, three due to death unrelated to treatment, three because of difficulties in handling the pump as outpatients, and six for other reasons. Off-periods and parkinsonian disability in off and in on were reduced significantly. These improvements remained constant throughout the observation period. Once the optimal dose regimen is established, only minor adjustments of the doses of lisuride and levodopa are required in the individual case.     

Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3–5 days later by 100–150 g of indium-111 streptavidin, at the specific activity of 280–370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1–8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1–30:1) and 45:1 (range 12:1–120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1–30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01–0.3) for recurrences and 0.05 for primary tumour (range 0.005–0.2). Over 24–48 h 14% i.d. (range 8–18% i.d.) was found in the urine, 14% i.d. (range 629% i.d.) in the blood and 63% i.d. (range 56–70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer. Offprint requests to: G. Paganelli     

Devices for the treatment of diabetes: today

Although single or multiple daily subcutaneous injections of insulin with syringes are the mainstay of insulin delivery techniques for the treatment of diabetes mellitus, several other methods are now available. The present paper will review the main problems occurring with the classical subcutaneous insulin therapy and the possible solutions given by the use of new devices, including more particularly insulin jet injectors, pens, and portable pumps. This review has to be considered as an introduction to the presentations of this symposium devoted to implantable pumps, glucose sensors, and artificial pancreas, respectively.     

Differentiation of normal pressure hydrocephalus and cerebral atrophy by computed tomography and spinal infusion test

Summary The diagnostic value of computed tomography (CT) and spinal infusion test (SIT) was investigated in 27 patients with normal pressure hydrocephalus (NPH) and 35 patients with cerebral atrophy. The most consistent CT finding of NPH was dilatation of the temporal horns, that of cerebral atrophy widening of the convexity sulci. However, 43% of patients with cerebral atrophy demonstrated no cortical atrophy. The SIT showed an excellent relation with isotope cisternography and continuous intracranial pressure recording. NPH and cerebral atrophy were correctly differentiated in 71% by CT and SIT. A normal SIT and a CT scan without the typical features of NPH exclude impairment of cerebrospinal fluid absorption. An abnormal SIT and a CT scan showing ventricular enlargement without dilatation of convexity sulci, require isotope cisternography and possibly intracranial pressure recording to determine the degree of the absorption deficit.

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Zusammenfassung Der diagnostische Wert von Computertomographie (CT) und Spinalen Infusions-Test (SIT) wurde bei 27 Patienten mit Normal Pressure Hydrocephalus (NPH) und 35 Patienten mit zerebraler Atrophie untersucht. Der häufigste CT-Befund des NPH war Erweiterung der Temporalhörner und bei zerebraler Atrophie eine Erweiterung der Konvexitätssulci. Aber 43% der Patienten mit zerebraler Atrophie zeigte keine Rindenatrophie. Der SIT zeigte eine sehr gute Korrelation mit Isotopenzisternographie und kontinuierlicher intrakraniellen Druckmessung. NPH und zerebrale Atrophie wurden korrekt differenziert in 71% mittels CT und SIT. Ein normaler SIT und ein CT-Scan ohne die typischen Merkmale von NPH schließen Liquorrückresorptionsstörungen aus. Ein abnormer SIT und ein CT-Scan, der einen Hydrozephalus ohne Erweiterung der Konvexitätssulci zeigt, erfordern eine Isotopenzisternographie und eventuell intrakranielle Druckmessung zur Ermittlung des Grades der Liquorrückresorptionsstörung.

     

康莱特联合化学药物动脉灌注治疗转移性肝癌的临床研究

目的：观察康莱特联合化学药物动脉灌注治疗转移性肝癌的疗效。方法：152例转移性肝癌患者随机分为治疗组(康莱特联合化学药物动脉灌注)79例、对照组(化学药物动脉灌注)73例。结果：治疗组的稳定率为87．3％，1年生存率为73．4％，2年生存率为50．6％，均明显高于对照组；并可减低血液高凝状态，提高患者的细胞免疫功能，缓解化疗药物的毒副反应，改善患者的生活质量。结论：康莱特联合化学药物动脉灌注治疗转移性肝癌有较好的疗效。     

两种过滤方法对输液中微粒的影响

目的 :比较超滤法和常规三级过滤法对输液中微粒的影响。方法 :用光阻法检查两种不同的过滤方法滤过的输液中微粒数。结果 :常规三级过滤法滤过的 4 7批次的输液平均微粒数为 6 .5 6个 /ml(>10 μm)和 0 .71个 /ml(>2 5 μm) ,超滤法滤过的 6 3批次的输液平均微粒数为 2 .2 9个 /ml(>10 μm)和 0 .2 8个 /ml(>2 5 μm) ,两种方法有显著性差异 (P <0 .0 0 1)。结论 :超滤法明显优于常规三级过滤法。     

静脉输注地尔硫治疗冠状动脉搭桥术前不稳定性心绞痛

目的 :评价静脉输注地尔硫治疗冠状动脉搭桥 (CABG)术前不稳定性心绞痛的疗效和安全性。方法 :68例CABG术前不稳定性心绞痛病人停服肾上腺素 β受体阻滞剂、钙通道阻滞剂及抗血小板药物 ,静脉给予地尔硫 ,以 33～ 167μg·min- 1,持续微泵注入 72h以上。观察心绞痛症状、心电图、血压、心率及不良反应。结果 :65例 (96% )病人有效。与用药前相比 ,心绞痛发作平均次数减少 (5 .4±s 1.8)次·d- 1(P <0 .0 1) ,发作持续时间缩短 (7.6± 2 .5 )min(P <0 .0 1)。心肌耗氧指数降低。心电图异常者ST T明显改善 ,4 9例病人在病情稳定后 1wk内接受CABG。无严重不良反应。结论 :静脉输注地尔硫为CABG术前不稳定性心绞痛提供了一种较为安全有效的药物治疗手段     

Calcium-Induced Natriuresis: Physiologic and Clinical Implications

Assessment of the tubular reabsorption of calcium (Ca) by infusion is complicated by suppression of parathyroid hormone (PTH) secretion, and by activation of the serpentine Ca sensing receptor in the renal tubule, which inhibits Ca and sodium reabsorption, but little is known about the magnitude of the natriuretic effect of Ca in human subjects. Accordingly, we reanalyzed the relationship between serum Ca and urine Ca and sodium excretion expressed per unit of creatinine clearance (CaE and NaE), and per unit of time (UCa and UNa), during a standard Ca infusion, in 14 healthy volunteers and in 8 primary hyperparathyroid patients. In healthy subjects we observed a large effect of Ca infusion on NaE, which rose as high as 8 mmol/liter GFR. In patients with primary hyperparathyroidism both CaE and NaE during Ca infusion were significantly lower overall than in healthy subjects for comparable values of serum Ca (P < 0.05 by covariance analysis), due mainly to a decline or reversal of the slopes at the highest serum Ca levels. In both controls and primary hyperparathyroid subjects the variance of CaE as dependent variable was explained by both serum Ca and by NaE as independent variables (P < 0.001). We conclude that (1) The natriuretic effect of hypercalcemia was unexpected large and if maintained would lead to substantial depletion of extracellular fluid. (2) Patients with chronic hypercalcemia, including primary hyperparathyroidism, probably have mild sodium depletion, and are more susceptible to volume depletion. (3) Calcium reabsorption during Ca infusion is reduced by suppression of PTH secretion and increased by volume contraction due to sodium depletion. Discrimination between different basal levels of parathyroid function is successful because these effects usually cancel out. (4) The increase in tubular reabsorption of Ca due to volume contraction can initiate a vicious circle, of importance to the pathogenesis and treatment of severe hypercalcemia. Received: 11 May 1999 / Accepted: 13 January 2000