Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (^99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of ⁹⁹mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of ^99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P<0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P< 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P<0.01). Differences in kinetics of clearance of ^99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.     

Estimated daily energy expenditure and blood lipids in adolescents: the Québec Family Study.

PURPOSE: To examine the association between estimated daily energy expenditure and blood lipids in a sample of adolescents. METHODS: The sample consisted of 415 males and 356 females aged 10-19 years, mainly French Canadian, recruited from the greater Quebec City area through the media as part of Phase I of the Quebec Family Study. Estimates of daily energy expenditure (DEE) were obtained with a 3-day physical activity record. Blood lipids were measured by standard procedures. The sample was stratified into three activity groups (least active, less than 25th percentile of DEE; moderately active, 25-74th percentile of DEE; and most active, 75th percentile or greater of DEE), and also by clinical cutpoints for blood lipids. Analysis of covariance, controlling for age and fatness, was conducted to compare blood lipids within gender across activity groups. Logistic regression analysis, controlling for age and fatness, was used to estimate the relative risk of being classified with an undesirable level of a blood lipid parameter on the basis of the DEE. RESULTS: Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were not significantly different across activity groups in males or females. High-density lipoprotein cholesterol (HDL-C) was significantly different across activity groups in males (p <.05) and females (p <.05), but the pattern of variation was different between genders. In males, the TC/HDL-C and LDL-C/HDL-C ratios decreased between the moderately active and most active groups (p <.05). Significant differences remained when subcutaneous fatness was considered as a covariate. The results from logistic regression analysis indicated that the odds ratios for low HDL-C levels was significant only in low DEE girls (odds ratio 2.83) compared with high DEE girls. CONCLUSIONS: The results suggest that increased energy expenditure and physical activity are associated with higher levels of HDL-C in adolescents of both sexes.     

Transurethral collagen injection for treatment of stress urinary incontinence

Summary Minimally invasive treatment of urinary incontinence has become a subject of major interest in recent years. We examined the use of transurethral collagen injection for incontinence treatment. A total of 48 patients were selectet for this procedure from April 1993 to February 1997 – 26 male patients (19 post-RPX incontinence and 7 post-TUR incontinence) and 22 female patients (all after previous incontinence surgery) were treated by injection of collagen into the continence region. The whole group underwent an average of 1.8 sessions, and a mean collagen injection volume of 14.5 ml was delivered per session. Mean follow-up was 9.2 months. Of the female population, 68.2 % were cured or greatly improved. In the male population only 47.3 % of the post-RPX patients and 6/7 of the post-TUR patients benefited from the procedure. In males, treatment outcome depends on the degree of pretreatment incontinence, because all grade III incontinence patients did worse. Therefore we conclude: transurethral collagen injection is an interesting method in the treatment of urinary incontinence if proper patient selection is assured.      

Extraction of an artery in rectal biopsy]

A biopsy of a rectal carcinoma has led to the extraction of a 2.5 cm arterial specimen, followed by an arterial bleeding. The cause of this exceptional complication was the presence of atypical vessels reaching the rectal lumen due to tumor ulceration.     

Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level

High altitude residence is known to modify body biochemistry and hormone status. However, the effects of such a sojourn on these status observed at sea level both immediately and later after return are not as well established as are the effects of an intermittent acclimation. The aim of this study was therefore to investigate these changes. To achieve our objectives, nine subjects received intermittent acclimation at low pressure in a barometric chamber (8?h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Hormonal and biochemical changes were studied using samples of venous blood taken at sea level before and after acclimation, after return from the expedition and 1 and 2 months after descent. Concentrations of thyroid hormones, adrenaline, noradrenaline (NA), hormones of hydromineral metabolism (aldosterone, renin, arginine vasopressin, atrial natriuretic peptide) as well as prolactin, cortisol, insulin and endothelin 1 were measured. Biochemical measurements made were plasma osmolality, and concentrations of glucose, total cholesterol, total proteins, pre-albumin, transferrin, complement 3C, apolipoproteins A₁ and B and serum iron. Acclimation induced no alteration in hormone (except for NA with increases of about 1.5, fold P<0.05) and biochemistry data. After the expedition, hormone responses were characterized by a higher total triidothyronine concentration (+18%, P<0.05) while other hormones did not vary. A linear relationship was found between thyroid-stimulating-hormone and body mass changes after the expedition (r=0.67, P<0.05). The observed increased concentrations of plasma proteins and total cholesterol (P<0.05) could be related to the restoration of lean body mass. At 1 and 2 months after return, no changes in hormones were observed but a significant decrease in transferrin concentration was noticed. The higher serum iron concentration reported after 1 month (P<0.05) could have been the result of a physiological haemolysis. It was concluded that both acclimation and the expedition in the Himalayas affected hormone status and body biochemistry status even though the observed changes were slight and rapidly reversed.     

Fentanyl is more effective than remifentanil at preventing increases in cerebral blood flow velocity during intubation in children

PURPOSE: Controlling the cerebral and systemic hemodynamic responses to laryngoscopy and tracheal intubation may play a role in determining clinical outcome in pediatric neurosurgical patients. This study compared the effects of remifentanil and fentanyl on cerebral blood flow velocity (CBFV) and hemodynamic profile during laryngoscopy and tracheal intubation in children under sevoflurane anesthesia. METHODS: Sixty healthy children aged two to six years undergoing dental surgery under general anesthesia were enrolled. Each child was randomly assigned to receive a remifentanil or fentanyl infusion, at a rate of 0.75, 1.0, or 1.5 microg x kg(-1) x min(-1) after induction of anesthesia with 2% sevoflurane. Middle cerebral artery blood flow velocity was measured by transcranial Doppler (TCD) sonography. Once a baseline set of hemodynamic variables and TCD measurements were recorded, the opioid infusion was started. Measurements were taken at two-minute intervals, starting four minutes prior to laryngoscopy until four minutes following naso-tracheal intubation. RESULTS: Remifentanil caused a more significant decrease in mean arterial pressure and CBFV prior to tracheal intubation than did fentanyl (P < 0.001). During laryngoscopy and for two minutes following tracheal intubation, CBFV increased in all remifentanil groups (P < 0.05), whereas it remained stable in all fentanyl groups. CONCLUSION: This study suggests that fentanyl was more effective than remifentanil at preventing increases in CBFV during and immediately following laryngoscopy and tracheal intubation in children undergoing sevoflurane anesthesia. Fentanyl also seemed to provide a more stable hemodynamic profile prior to laryngoscopy and tracheal intubation when compared to remifentanil.     

Pharmacokinetics of intravenously administered 125I-labelled human alpha 1-acid glycoprotein

The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body.     

Effects on Behaviour and EEG of Single Chain Phospholipases A2 from Snake and Bee Venoms Injected into Rat Brain: Search for a Functional Antagonism

Abstract: Three phospholipase A₂ (PLA₂s), OS₁ and OS₁ purified from the taipan snake venom Oxyuranus scutellatus scutellatus and bee venom PLA₂ were injected to rats by the intracerebroventricular route. OS₁ showed no sign of neurotoxicity at doses at which OS₂ and bee venom PLA₂ produced multiform dose-dependent behavioural effects including motor disturbances (stereotyped movements), compulsive scratching, convulsions and breathing difficulties. EEG recordings showed at the very time when the animal was motionless the induction of several episodes of a low frequency hippocampal theta rhythm, index of long-term changes in synaptic neuroplasticity. Spike-wave discharges were also produced but the occurrence was not systematic. These seizures were often accompanied with behavioural convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic transmission could not abolish the neurotoxic effects of PLA₂s except for diazepam (10 mg/kg intraperitoneally) that prevented only OS₂-induced disturbances. Blockers of L-type Ca²⁺ channels and K⁺ channel openers were also without effect. The toxicity of OS₂ and bee venom PLA₂ is probably due to their initial specific binding to their neuronal receptor sites.     

Six months before ICH2: An overview on the harmonisation of the guidelines in toxicology

The aim of this paper is to emphasize the necessity of an international harmonisation of the guidelines in toxicology for the safety evaluation of pharmaceutical products, and the role of the International Conference on Harmonization (ICH). The organisation of the working-groups and the choice of the topics are descibed, and an overview of the achievement and on the difficulties encountered for this purpose is presented, some months before the ICH2 meeting in Orlando (USA). Originally presented at ECCP 93.