Effects of intracerebroventricular administration of aminophylline on hyperbaric-induced increase in carotid blood flow

Carotid blood flow was measured in rats by implanted transit-time ultrasonic flowprobes during hyperbaric experiments at up to 70 bar (7 MPa) using an helium-oxygen hyperoxic (partial pressure of O₂ = 400 mbar) mixture. Before the hyperbaric experiment, an intracerebroventricular injection of phosphate saline buffered solution (PBS) or aminophylline, an adenosine receptor blocker, in PBS was given. Throughout the hyperbaric experiment carotid blood flow increased with ambient pressure in both PBS, i.e. control, and aminophylline treated rats. The increase in carotid blood flow was significantly attenuated in aminophylline treated rats. Additional experiments showed that the increased carotid blood flow was independent of hyperoxia as well as of temperature. The hypothesis that the hyperbaric dependent increase in carotid blood flow was mediated by brain adenosine receptors and its implication regarding a cerebral vasodilatation are discussed.     

FURTHER INVESTIGATIONS ON THE α1-ADRENOCEPTOR BLOCKING PROPERTIES OF AR-C 239 IN RATS

AR-C 239, a new alpha-adrenoceptor blocking drug, appears to act selectively on alpha 1 sites in rats. At peripheral sites, this drug did not change the tachycardia induced by spinal sympathetic outflow stimulation in pithed rats, and did not antagonize the inhibitory effects of clonidine on this preparation. In addition, AR-C 239 showed predominant alpha 1-adrenoceptor blocking properties in the bisected rat vas deferens preparation. AR-C 239 did not prevent or reverse the centrally mediated hypotensive and bradycardic actions induced by clonidine, in intact animals. In conclusion, AR-C 239 seems to be a very useful tool for the characterization of peripheral and central alpha 1-adrenoceptors, in this animal species.     

The diagnostic value of the measurement of the ankle-brachial systolic pressure index in primary health care

We investigated the value of the ankle-brachial systolic pressure index (ABPI) as a test for the diagnosis of peripheral arterial occlusive disease (PAOD) in general practice. ABPI measurements on 231 legs of 117 subjects performed in three general practice centers (GPC) were compared with the diagnostic conclusions of a Vascular Laboratory. The optimum cutoff value for the ABPI, its accuracy and diagnostic value were estimated. In a subpopulation of 51 subjects for whom repeated measurements were available, we checked whether taking the mean of three consecutive ABPIs for test outcome would enhance diagnostic performance.

Receiver Operating Characteristic analysis showed that overall performance of the GPC ABPI was good (area under the curve ≈ 0.9). Performing repeated ABPI measurements was superior to performing a single measurement. The optimum cutoff value for the ABPI was 0.97, associated with a diagnostic odds ratio (OR) of 17 and an accuracy of 81%. In a somewhat more selected subpopulation, the optimum cutoff value was 0.92 (OR 70, accuracy 90%).

On the basis of our results, we suggest the following rule of thumb: if the ABPI < 0.8 or if the mean of three ABPIs < 0.9, it is highly probable that PAOD is present (PV+ ≥ 95%); if the ABPI > 1.1 or if the mean of three ABPIs > 1.0, PAOD can be ruled out (PV− ≥ 99%).

In conclusion, in primary health care, the ABPI measurement can be a useful supplementary test in ambiguous diagnostic situations with regard to PAOD.     

Linear non-conjugated dienes from biomass as termonomers in EPDM synthesis, 2. Comparison with 5-ethylidene-2-norbornene termonomer

A comparative study of 5-ethylidene-2-norbornene (ENB) or 5,7-dimethylocta-1,6-diene (5,7-DMO) as diene termonomer in ethylene-propylene-diene (EPDM) terpolymer synthesis is presented. The reactivities of the cyclic and linear non-conjugated dienes are first compared in homopolymerization in the presence of two conventional Ziegler-Natta catalytic systems: TiCl₃, 1/3AlCl₃, 14MgCl₂ associated to AlEt₃, and VOCl₃ (or VCl₄) associated to AlEt₂Cl. ENB polymerization yields a branched poly(ENB) in agreement with a predominant cationic reaction, whereas polymerization of 5,7-DMO proceeds exclusively by a Ziegler-Natta mechanism. In terpolymerization, ENB is much more reactive than 5,7-DMO and is incorporated more easily in the terpolymer. However, the high sensitivity of ENB toward acidic species also results in cationic side reactions and therefore limits the utilization of ENB to a low concentration range. We have shown that the productivity of vanadium catalysts, which are mainly used in industrial EPDM synthesis, is drastically reduced in the presence of ENB an 5,7-DMO, due to the rapid reduction of vanadium involving the diene.     

Clinical toxicity of interleukin-2.

Interleukin-2 (IL-2) is increasingly used to treat patients with cancers refractory to conventional treatment. Flu-like syndromes are extremely frequent but usually mild. A variety of skin complications (mostly erythema and mucositis) have been reported. Life-threatening skin reactions have also been described. Acute reactivation of psoriasis can also occur. Immediate hypersensitivity reactions have so far not been described, but IL-2 treatment has been shown to predispose to acute hypersensitivity reactions to iodine-containing contrast media. Hypothyroidism is the major endocrine complication and antithyroid antibodies have been detected in approximately 50% of patients. Neurological and psychiatric disturbances with moderate or severe mental status changes are common and sometimes treatment-limiting. The occurrence of peritumoural oedema in patients with brain metastases can also be a major practical problem. Musculoskeletal disorders are transient and resolve spontaneously. The vascular leak syndrome is the most frequent and severe complication of IL-2 of which weight gain, generalised oedema, hypotension and impaired renal function are the main features. Even though a damaging effect on vascular endothelium cells by various cytokines released by activated lymphoid cells or mediated by non-lymphocyte-dependent factors has been proposed to be involved, the mechanism remains unclear. Other cardiovascular injuries, possibly life-threatening, including myocarditis, angina pectoris and myocardial infarction, can occur during the first days of treatment. Supraventricular arrhythmias are the most common rhythmic disorder. Decreases in myocardial contractility and haemodynamic pattern similar to those of septic shock have been encountered in most cases. Acute renal dysfunction is common but resolves with symptomatic management. Intrahepatic cholestasis with hyperbilirubinaemia is observed in most patients but permanent liver damage has not been described. Several cases of pancreatitis have been reported. Anaemia, thrombocytopenia, lymphocytopenia and eosinophilia are frequent and occur in most if not all patients. Some data suggest a high incidence of infectious complications, particularly in patients with surgically tunnelled catheters, but marked flu-like syndromes may be confounding. Finally, death directly related to IL-2 treatment has been noted in less than 1% of all patients. Investigations are under way to minimise IL-2 toxicity with varying dose regimens and combined treatments.     

Polysomnographic study of the autonomic nervous system in potential victims of sudden infant death syndrome

To determine the influence of sleep stages and night-time distribution on cardiac autonomic activity, the polysomnographic recordings of 18 victims of sudden infant death syndrome (SIDS) and of 36 control infants were studied. Autoregressive spectral analyses of heart rate (HR), using both short-term and whole-night methods, were evaluated as a function of sleep stages. The two main peaks of normalized LF and HF were computed during the night and the sympathovagal balance (LF/HF) was determined.In both NREM and REM sleep, SIDS infants were characterized by significantly lower normalized HF powers and higher LF/HF ratios. This finding was observed in both short-term and whole-night HR spectral analyses. In addition, SIDS victims were characterized by the presence of a high desynchronized peak of sympathetic tonus in the late hours of the night, a finding not seen in the control subjects.This report adds further indirect evidence for a possible sleep-related impairment of autonomic controls in some infants who died of SIDS.     

Dose of desferrioxamine and evolution of HIV-1 infection in thalassaemic patients

To study the relationship between the dose of desferrioxamine (DFX) and the progression of the HIV-1 disease in thalassaemia major patients (TMP), 64 seropositive TMP patients were studied. Cumulative incidence of CDC stage IV was calculated using a non-parametric life-table method. The association with the mean daily dose of DFX was tested with a Cox proportional hazards model which was also used to adjust for confounding variables. The median of the mean daily dose of DFX over the seropositive period was 40mg/kg (range 0-65mg/kg). Age at seroconversion (P < 0.02) and splenectomy (P < 0.03) were found to be associated with the mean daily dose of DFX. 6.5 years after seroconversion, 11% of those who had been prescribed more than 40mg/kg of DFX daily had entered stage IV versus 35% of those who had been prescribed a lower dose (P < 0.01). When the dose was taken as a continuous variable it was found that the rate of progression was significantly smaller in TMP receiving a higher dose (P < 0.002). even after adjusting for age and splenectomy (P < 0.02). Although it should be noted that these results were obtained in an observational study, possibly biased by a non-random allocation of the DFX dose, we believe that they are striking enough to support the claim that the role of DFX in the progression of HIV disease should be further evaluated.