[Graves' dermopathy on the big toe]. / Dermopathie basedowienne localisée aux hallux.

BACKGROUND: Localized myxoedema is a rare dermopathy in patients with Graves' disease. The pretibial area is the most commonly affected region but herein we present a case of myxoedema of the big toe. PATIENTS AND METHODS: A 44-year-old male with Graves' disease ongoing for seven years presented bilateral ophthalmopathy and myxoedema of the big toes. The myxoedema was treated successfully with intralesional steroids. DISCUSSION: The physiopathology of myxoedema involves fibroblast activation and glycosaminoglycan production. This activation could result from stimulation of TSH receptors at their surface by TSH receptor antibodies (TRAK) or from an inflammatory process. The pretibial topography may be related to the high frequency in this area of microtrauma, with modulation of the cytokine microenvironment. CONCLUSION: The atypical localization seems to correlate with a Koebner phenomenon. Treatment of Graves' disease is generally insufficient to resolve the cutaneous problems. Topical corticosteroid therapy generally results in rapid improvement of recent lesions.

[Effects of flunitrazepam on the baroreflex control of heart rate and on adrenergic activity]. / Effets du flunitrazépam sur le contrôle baroréflexe de la fréquence cardiaque et sur l'activité adrénergique.

The effects of intravenous flunitrazepam (25 micrograms . kg-1) on the baroreflex control of heart rate and plasma catecholamine levels were determined in ten ASA 1 unpremedicated patients. Plasma concentrations of flunitrazepam were also measured. The data was obtained before and 5, 10 and 15 min after flunitrazepam administration. The baroreflex gain was significantly decreased at 5 min, the time of the highest flunitrazepam plasma concentration. Catecholamine plasma levels were decreased at each study time. It was concluded that flunitrazepam induced a transient depression in baroreflex function and a sustained decrease in adrenergic activity.

[Is automatic oscillometric measurement of blood pressure reliable in hypotension?]. / La mesure oscillométrique automatique de la pression artérielle reste-t-elle fiable en cas d'hypotension?

The reliability of an automatic oscillometric device for measurement of blood pressure (BP) was assessed in a large range of BP values during intraoperative normotension and induced hypotension. Direct BP measurements were carried out with a radial catheter. Data were compared with those obtained with the oscillometric device placed on the opposite arm. Nine patients were studied, undergoing 234 measurements of BP ranging from 55 to 208 mmHg (7.3 to 27.7 kPa) for systolic blood pressure (Pasys), from 32 to 130 mmHg (4.3 to 17.3 kPa) for diastolic blood pressure (Padia) and from 36 to 154 mmHg (4.8 to 20.5 kPa) for mean blood pressure (Pa). Good correlation between the two techniques was found for Pasys measurements recorded during both normotension and hypotension (r = 0.93; p less than 0.01). 92% of the values recorded with the oscillometric device were lower than those measured invasively. In the other cases (8% of the data), the mean difference between the two techniques was 5.5 mmHg (0.7 kPa). When BP values lower than 90 mmHg (12 kPa) for Pasys, 60 mmHg (8 kPa) for Padia and 70 mmHg (9,3 kPa) for Pa were considered individually, the correlation coefficients were 0.83, 0.73 and 0.77 respectively. These findings suggested that the oscillometric method can be considered as relatively suitable for monitoring moderate hypotension induced by vasodilators. The invasive technique must however remain the method of choice during profound hypotension.

[Hemodynamic and adrenergic effects of flumazenil after general anesthesia with flunitrazepam]. / Effets hémodynamiques et adrénergiques du flumazénil après anesthésie générale comportant du flunitrazépam.

Reversal of benzodiazepine-induced sedation by flumazenil has been reported to produce no or minor hemodynamic alterations although some adverse responses have been observed. To better delineate circulatory and adrenergic modifications induced by flumazenil, 20 consenting patients scheduled for short orthopedic procedures were included in a double blind controlled study. Anesthesia consisted in flunitrazepam (30 to 40 micrograms.kg-1) plus halothane (0.5 vol. % in N2O-O2, 60-40 vol. %) and alfentanil. At the end of surgery, patients received 15 minutes after discontinuation of halothane and N2O, either flumazenil (1 mg) or placebo according th randomization. Heart rate and blood pressure were obtained before reversal and repeatedly for 30 minutes following flumazenil or placebo. Level of consciousness was also assessed and blood samples were withdrawn for subsequent determination of plasma levels of norepinephrine. Flumazenil administration induced in all cases an immediate and total reversion of sedation while recovery was slow in the placebo group. No significant changes in heart rate and blood pressure values were found in both groups. By contrast, plasma levels of norepinephrine were significantly increased in all patients. It is concluded that reversal of benzodiazepine-induced sedation or anesthesia is not associated with significant variations of usual hemodynamic or adrenergic responses.

Comparative studies of protein biosynthesis: the main experimental parameters in pulse and pulse-chase experiments must be standardized.

The influence of experimental conditions was investigated in pulse and pulse-chase experiments involving L-[35s]methionine incorporation by isolated rat hepatocytes. The incorporation of the labelled amino acid must be linear as a function of dose and time, and similar hepatocyte densities should be used to compare radioactive uptake. High hepatocyte densities give greater precision. In pulse-chase experiments, it was shown that a pool of free radioactivity moves progressively during the chase phase from the intracellular compartment. Protein-associated radioactivity must therefore be expressed as a function of both total radioactive uptake and total labelled protein.

Purification and characterization of reverse gyrase from Sulfolobus shibatae. Its proteolytic product appears as an ATP-independent topoisomerase.

Sulfolobus shibatae B12 is a thermophilic archaebacterium that contains an inducible virus named SSV1. The viral DNA has been shown to be positively supercoiled before encapsidation. We have previously purified an archaebacterial DNA topoisomerase from Sulfolobus acidocaldarius DSM 639, reverse gyrase, likely responsible for this positive supercoiling reaction. In order to study an homogeneous system containing both reverse gyrase and one of its preferential substrate, SSV1 DNA, we have purified this enzyme from S. shibatae. During the course of the purification, we have detected another topoisomerase activity. In order to separate and purify these two topoisomerases, we have devised a new purification procedure. Purified S. shibatae reverse gyrase is a 124-kDa monomer, with a Stokes radius of 43 A and a sedimentation coefficient of 6.2 S. It is able to perform a DNA reverse gyration per se at 10 mM NaCl in a Mg- and ATP-dependent manner. The other topoisomerase is a monomer of about 40 kDa, with a Stokes radius of 25 A and a sedimentation coefficient of 4 S. This additional topoisomerase activity is Mg-dependent and ATP-independent and catalyzes only a relaxation reaction of negatively supercoiled DNA at 150 mM NaCl. This new ATP-independent topoisomerase activity seems to be a proteolysis product of reverse gyrase.

Effect of streptozotocin-diabetes on rat liver asialoglycoprotein receptor turnover: in vivo degradation and in vitro biosynthesis.

The metabolic turnover of the Hepatic Binding Protein (HBP) was investigated in streptozotocin-diabetic rats. We have already shown that diabetes induced a decreased ligand binding capacity while the immunoreactive HBP was normal. To explore the eventual modifications due to diabetic state upon the turnover of HBP, we followed the in vivo degradation of HBP and its biosynthesis in vitro. After in vivo labelling with L-[3H] leucine and purification of HBP from rat livers, we found a 20% decrease in diabetic HBP half-life. By in vitro incubations of freshly isolated hepatocytes and a 2 h-pulse in the presence of L-[35S] methionine, we showed that diabetes provokes an increased uptake of L-[35S] methionine in hepatocytes allowing an augmented synthesis of HBP although the L-[35S] methionine incorporation into total proteins was less efficient.

Hemodynamic responses to low doses of naloxone after narcotic-nitrous oxide anesthesia.

Hemodynamic responses to reversal of phenoperidine-nitrous oxide anesthesia were studied in 14 adult patients before and after naloxone administration (1.5 +/- 0.25 microgram/kg), and, at comparable intervals, in 11 control patients who were permitted to resume respiration spontaneously. Naloxone reversal resulted in significant increases in heart rate (31%), cardiac index (50%), left ventricular stroke work index (53%), and systemic blood pressure (21%), compared with initial values. The heart rate-systolic arterial pressure product, an indirect index of myocardial oxygen consumption, increased significantly (77%). However, changes of similar magnitude occurred after spontaneous recovery in control patients, in whom the only significant treatment-related difference was a longer recovery time. Whether naloxone is used or not, the observed hemodynamic changes may be harmful to patients who have diminished cardiac reserve.

Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis.

Fentanyl kinetics were studied in patients with cirrhosis and in patients with normal hepatic and renal function undergoing surgery under general anaesthesia, the latter group served as the controls. Plasma fentanyl concentrations declined bi-exponentially in the controls with an average elimination half-life (T1/2 beta) of 263 min; total plasma clearance (Cl) as 10.8 ml min-1 kg-1, and total apparent volume of distribution (V beta) 3.81 litre kg-1. No significant change was observed in patients with cirrhosis: T1/2 beta was 304 min, Cl 11.3 ml min-1 kg-1 and V beta 4.41 litre kg-1. These data suggest that the elimination half-life of fentanyl is not primarily influenced by the rate at which it is metabolized in the liver.

Thiopentone pharmacokinetics in patients with chronic alcoholism.

The pharmacokinetics of thiopentone were compared in nine control patients and 10 patients with chronic alcoholism (without signs of cirrhosis or hepatitis) undergoing orthopaedic or abdominal surgery under general anaesthesia. The mean (+/- SD) alcohol intake was 92 +/- 14 litre of ethanol per year in the alcoholic patients and less than 10 litre yr-1 in the controls. Thiopentone plasma concentrations were measured by high pressure liquid chromatography after the administration of a single bolus dose (5-9 mg kg-1). The plasma clearance of thiopentone was significantly increased from 3.7 +/- 0.9 ml min-1 kg-1 in the controls to 5.4 +/- 2.2 ml min-1 kg-1 in the patients with chronic alcoholism. The volume of the central compartment and the total apparent volume of distribution were similar in both groups. The terminal elimination half-life was of 684 +/- 168 min in the alcoholics and did not differ significantly from the value found in the controls (750 +/- 212 min).

Effects of droperidol on sympathetic activity and baroreflex control of heart rate in humans.

The effects of intravenous droperidol, 0.2 mg . kg-1, on baroreflex control of heart rate and on plasma catecholamine levels were determined in 10 ASA physical status I unpremedicated patients. Baroreflex control of heart rate was assessed by a pressor test using phenylephrine. Plasma concentrations of norepinephrine and epinephrine were determined by high pressure liquid chromatography, and plasma droperidol concentrations were measured by radioimmunoassay, from blood samples withdrawn before baroreflex evaluation. All data were obtained before and 5, 10, and 15 min following droperidol administration. Baroreflex response was significantly decreased after droperidol at each time of the study with the maximal decrease (-47% from control) observed at 5 min. No resetting of baroreflex was present since the pulse interval at the reference pressure was unchanged. Plasma norepinephrine concentrations were moderately but significantly increased only at 5 min, while no significant change in epinephrine concentrations was observed. It is concluded that droperidol induces a moderate but sustained alteration of baroreflex function and a transient increase in plasma norepinephrine concentrations.

[Anesthesia in patient with the ventricular pre-excitation syndrome]. / L'anesthésie chez les sujets atteints de syndrome de pré-excitation ventriculaire.

The Wolff-Parkinson-White syndrome or its variant, the pre-excitation syndrome, are described in about 1.2 per 1000 of the population, so the anaesthetic management of patients with this syndrome is important. Our experience is reported in 15 elective operations on seven patients with pre-excitation syndrome. The most significant feature is the occurrence of variation of the morphology of QRS complexes. Rhythm disturbance most commonly encountered is supraventricular tachycardia, but different cardiac arrhythmias may occur and sometimes these are fatal. In our study, major complications or cardiac arrhythmias did not occur. With regard to the anaesthetic technique, care should be taken not to produce tachycardia. Atropine is not absolutely contraindicated for premedication. Preoperative use of propranolol or of quinidine is questionable.

Comparison of sufentanil and fentanyl to supplement N2O-halothane anesthesia for total hip arthroplasty in elderly patients.

Sufentanil was compared with fentanyl as a supplement to nitrous oxide-halothane anesthesia in a double-blind study of 30 elderly patients undergoing total hip arthroplasty. Comparisons were made with respect to (a) hemodynamic (heart rate and blood pressure) and adrenergic (plasma norepinephrine and epinephrine levels) responses during surgery and recovery; (b) time to extubation after the end of surgery; and (c) postoperative analgesia. No difference was observed between the two groups with respect to demographic data, blood gas tensions, or hemodynamic and adrenergic responses to surgery and recovery. Total doses of opioids used were 0.7 +/- 0.3 micrograms/kg of sufentanil and 6 +/- 2.6 micrograms/kg of fentanyl. Times between end of surgery and extubation were not different (60 +/- 54 min in the fentanyl group and 58 +/- 52 min in the sufentanil group). The number of patients needing postoperative analgesia did not differ between the two groups, but use of analgesia was significantly delayed in the sufentanil group (168 +/- 25 vs 127 +/- 29, P less than 0.05). This study suggests that in elderly patients sufentanil confers a greater residual analgesia than fentanyl in the immediate postoperative period.

Comparative effects of induced hypotension and normovolaemic haemodilution on blood loss in total hip arthroplasty.

The effects of deliberate hypotension and normovolaemic haemodilution on operative blood loss were studied in patients undergoing hip arthroplasty. Thirty patients were anaesthetized with halothane-nitrous oxide, and assigned to one of three groups. In group I, mean arterial pressure was decreased to 55 mm Hg by sodium nitroprusside. In group II, 23 +/- 2 ml/kg of blood was withdrawn just before the surgical procedure and replaced by twice volume with 4% albumin and Ringer lactate solution. The shed blood was reinfused at the end of the surgical procedure. In group III, the blood replacement was equal to blood loss and this group served as control. Intraoperative blood losses were 1050 +/- 185 ml and 900 +/- 130 ml in the autotransfused and control groups, respectively, and 320 +/- ml in the hypotensive group. However, the total red cell loss was significantly less in the hypotensive and autotransfused groups than in the control group. No complications occurred any of the three groups. Deliberate hypotension was the most effective means of reducing intraoperative bleeding and the time for this procedure was shorter than for normovolaemic haemodilution combined with autotransfusion.

Effects of diazepam and midazolam on baroreflex control of heart rate and on sympathetic activity in humans.

The effects of induction of anesthesia with diazepam and midazolam on baroreflex control of heart rate and on plasma levels of catecholamines were investigated in this study. Group 1 subjects (n = 10) received diazepam, 0.4 mg/kg. Group 2 subjects (n = 10) received midazolam, 0.3 mg/kg. Baroreflex function was assessed using a pressor test (phenylephrine). In addition, samples for subsequent determination of plasma norepinephrine and epinephrine levels and plasma diazepam or midazolam concentrations were collected before and 5, 10, and 15 min after intravenous drug administration. The pressor baroreflex slope declined significantly after diazepam or midazolam administration with the maximal changes (-45 and -43%, respectively) observed when plasma diazepam or midazolam concentrations were the highest. Norepinephrine plasma concentrations decreased at each measurement with both drugs. In contrast, epinephrine concentration decreased only after midazolam. The authors conclude that diazepam or midazolam used for induction of anesthesia results in a transient depression of baroreflex function and a sustained decrease of sympathetic tone. This study also indicates that the depression of arterial baroreflex heart rate responses under diazepam or midazolam anesthesia are less pronounced than the depression of baroreflex responses reported by other investigators with potent inhalational anesthetics. However, this disruptive effect of diazepam and midazolam on sympathetic control of circulation might induce a limited ability to compensate for hemodynamic alterations related to hypovolemia.

Effects of propofol on baroreflex control of heart rate and on plasma noradrenaline levels.

The effects of propofol induction (2.5 mg kg-1) and of two continuous infusion rates of propofol (100 and 200 micrograms kg-1 min-1) on baroreflex control of heart rate and on plasma noradrenaline concentration were investigated in 11 unpremedicated patients. Baroreflex function was assessed using a pressor test (phenylephrine) and a depressor test (sodium nitroprusside). In addition, samples for subsequent determination of plasma noradrenaline levels and blood propofol levels were collected before each test. Baroreflex sensitivity and plasma noradrenaline concentrations were not significantly changed at any time of the study. By contrast, a significant and sustained resetting of baroreflex set point was observed, allowing unchanged heart rate at lower arterial pressure. It is concluded that the effects of propofol on baroreflex function and noradrenaline concentration are moderate.

Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement.

BACKGROUND: The goal of this study was to evaluate the effectiveness on postoperative pain, and cognitive impact, of patient-controlled analgesia (PCA) compared with subcutaneous (s.c.) injections of morphine in elderly patients undergoing total hip replacement (THR). METHODS: Forty patients older than 70 yr were randomly assigned to two different postoperative analgesic techniques for 48 h: i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCA group) or regular s.c. morphine injections (SC group). Postoperative pain was assessed at rest and when moving, using a visual analogue scale (VAS) every 4 h. A Mini Mental Status (MMS) examination was used to assess cognitive functions before surgery, at 2 h, 24 h and 48 h after surgery, and at hospital discharge. Side-effects were also recorded systematically during the first 48 h after surgery. RESULTS: The PCA group showed significantly lower pain scores than the SC group both at rest and during mobilization. However, the clinical significance of pain scores was weak. There was no intergroup difference in postoperative MMS scores. The incidence of side-effects was similar in both groups. CONCLUSIONS: We conclude that in healthy elderly subjects undergoing THR, the flexibility of the analgesic regimen is more important than the route of administration with regard to efficacy, adverse effects and recovery of cognitive function.