Reduced natriuresis during weightlessness

Summary The kidney response to weightlessness was measured in one volunteer during a 1-week space mission. Shortly after entering microgravity and later during the mission, consecutive urine sampling periods were monitored, covering in total about 50% of the inflight time. Preflight references were a sequence of ground-based experiments, which evaluated body fluid metabolism with different degrees of standardization. Additional variables, such as circadian rhythms and cortisol-associated stress, were also monitored. In contrast to current hypotheses, the volunteer showed a pronounced reduction in natriuresis and diuresis during the entire space flight, despite a considerable weight loss. For the first time, the urinary excretion of the renal natriuretic peptide urodilatin was also measured. Both, during the preflight experiments and during weightlessness, close correlations between urodilatin excretion and sodium excretion were observed. However, the correlation between natriuresis and urodilatin excretion was considerably altered during weightlessness. We conclude that the loss of body weight during space flight is not related to an increased renal fluid loss and that urodilatin might counteract the decrease in renal excretion observed in weightlessness.     

Effect of lysine vasopressin in depressed patients on mood and 24-hour rhythm of growth hormone, cortisol, melatonin and prolactin

Lysine-8-vasopressin (LVP) for 10 days and in doses up to 13.5 LVP units did not significantly alter the Hamilton Depression Rating Scale scores of 12 severely depressed, treatment-resistant patients who were evaluated in a double-blind crossover study. The 24-h rhythms of melatonin, cortisol, growth hormone and prolactin appeared remarkably stable over the course of repeated measurement. LVP administration did not affect these 24-h rhythms.     

Recovery after propofol infusion anaesthesia in children: comparision with propofol, thiopentone or halothane induction followed by halothane maintenance

We have compared the recovery profiles of 163 healthy Chinesechildren after general anaesthesia for minor surgical procedures.Patients were allocated randomly to receive one of four anaesthetictechniques: propofol infusion for induction and maintenanceusing a pharmacokinetic model-controlled syringe pump set initiallyat a target concentration of 8 µg ml^–1 and thenadjusted according to clinical requirements; propofol 2.5–3.5mg kg^–1, thiopentone 4–5 mg kg^–1 or 2–3%halothane for induction of anaesthesia followed by 1–2% halothane for maintenance of anaesthesia. All oatients breatheda mixture of 70% nitrous oxide in oxygen through a laryngealmask airway and received an appropriate regional anaestheticblock. Recovery was assessed using the time to achieve fullSteward score, open eyes on command, orientation and the timerequired to complete a simple ouzzle. Recovery was slowest withthe propofol infusion (mean 39.8 (SO 12.9) min when eyes openedon command). The recovery times were significantly shorter withthe three other techniques (propofol bolus 21.9 (9.9) min, thiopentone23.4 (11.3) min, halothane 20.1 (8.9) min), and the choice amongthese three methods had no significant influence on the recoveryprofile. (Br. J. Anaesth. 1994; 72: 554–558) ^*Present address: Department of Anaesthesia,Addenbrooke's Hospital,HillsRoad,Cambridge.     

Effect of age on pharmacokinetics of and blood pressure responses to prazosin and terazosin

Prazosin and terazosin are two alpha 1-adrenoceptor blocking agents, their principal difference being the longer half-life of terazosin. The present study was carried out to determine if elderly subjects are different from the young in their pharmacokinetic handling of these two drugs and if age influences the blood pressure response to each drug. Ten young healthy subjects (aged 19-30 years) and five older healthy subjects (aged 54-62 years) received 1 or 2 mg terazosin, 1 or 2 mg prazosin, or placebo 1 week apart according to a 5 X 5 Latin square design. Concentrations of prazosin and terazosin were measured using a high-performance liquid chromatographic procedure with a detection limit of approximately 0.25 ng/ml. Pharmacokinetic parameters of prazosin were virtually the same in both groups, whereas mean terazosin plasma concentrations were higher in the older group and pharmacokinetic analysis revealed higher peak plasma concentrations and a longer terminal elimination half-life. There was no evidence of increased sensitivity to the hypotensive action of the drug, as peak upright blood pressure falls were similar in the two groups. Symptoms of dizziness in the upright position were also less common. In view of their lack of sedative effects and minimal metabolic disturbances, further studies should be conducted to assess the suitability of these drugs as monotherapy for hypertension in elderly patients.     

Parathyroid variants: US evaluation

High-resolution (10-MHz) ultrasonography was performed in 181 patients with primary or secondary hyperparathyroidism during a 4-year period and evaluated retrospectively. Thirty-seven unusual-appearing parathyroid tumors were found among 235 parathyroid glands identified as abnormal. There was pathologic correlation in 36. The typical appearance of parathyroid adenoma was that of an oval hypoechoic or anechoic lesion in the neck, aligned in a craniocaudal direction and often posterior to the thyroid. Morphologic variations from the norm included giant size (n = 11) (4.6%), cystic changes in a solid tumor (n = 9) (3.8%), calcified glands (n = 6[in three patients]) (2.5%), a multilobulated configuration (n = 5) (2.1%), an inhomogeneous pattern (n = 5) (2.1%), and a parathyroid cyst (n = 1) (0.4%). Recognizing the abnormal parathyroid variants can increase the diagnostic accuracy of sonographic examination.     

GAS CHROMATOGRAPHIC MEASUREMENT OF PLASMA LEVELS OF SODIUM VALPROATE: TENTATIVE THERAPEUTIC RANGE OF A NEW ANTICONVULSANT IN THE TREATMENT OF REFRACTORY EPILEPTICS

1. A precise and rapid gas chromatographic method for the measurement of plasma sodium valproate concentrations is presented. 2. The extraction is a single step procedure, and is reproducible and linear throughout the concentration range encountered. 3. Clinical evaluation of the drug is presented in eighteen epileptics on the basis of the percentage of days on which subjects had seizures before and after sodium valproate therapy. 4. A tentative therapeutic range for sodium valproate is presented on the basis of plasma levels and therapeutic effect.     

Deaths involving MDMA and the concomitant use of pharmaceutical drugs

The increasing use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and tendency of users to combine MDMA with pharmaceutical agents (especially serotonergic medication) warrants a thorough understanding of MDMA's toxicity profile and potential for drug interactions. This study examined the involvement of MDMA and concurrently administered pharmaceutical drugs in cases reported to the Victorian State Coroner. The National Coroners Information System was used to conduct a comprehensive search and examination of all closed cases between 2002 and 2008 where MDMA was detected. Pathology, toxicology, and Coroners' findings were considered in all cases. In all, 106 fatalities were identified, of which 43 (41%) cases involved the concomitant use of MDMA with other drugs, including pharmaceuticals that were likely to result in an adverse drug reaction or varying risks (4 high-risk cases involved moclobemide and MDMA, in addition to 10 moderate-risk cases, and 5 minor-risk cases). These findings highlight the importance of recognizing and publicizing potential drug interactions between MDMA and pharmaceutical preparations that may result in lethal toxicity, in particular serotonin toxicity.