Leucoéncephalopathie multifocale progressive

Summary A young woman presented a mixed congenital and familial immunodeficiency syndrome consisting in an absence of IgA and lowered levels of IgG and IgM, with a defect in cellular immunity. She had a mild malabsorption syndrome with slight alterations of the jejunal mucosa. Non-caseating tuberculoid granulomata were found in skin lesions, in lymph nodes and in the spleen. At age 27 the patient died of a neurological disease of 4 months duration. Autopsy revealed a very widespread demyelinating process involving mainly the right cerebellar hemisphere but also most of the pons and left cerebellum, with the typical morphologic characters of PML. In the hemispheres lesions were limited to microscopical microglial nodules with discrete demyelination. A review of 86 published cases of PML revealed 9 other cases in which lesions showed a strong predilection for the subtentorial territories. This sampling allows for the assumption that some 11% of the cases of PML have this particular lesion distribution. Other pertinent features of this case are briefly discussed.

     

Analgesic efficacy and safety of a caudal bupivacaine-fentanyl mixture in children

The analgesic efficacy and safety of a single caudal injection of a bupivacaine-fentanyl mixture was investigated in this prospective, controlled, triple-blinded study of 34 children, aged 1-11 yr and of ASA physical status I-II undergoing urological surgery. After induction of anaesthesia and before surgery, the children were randomly assigned to receive a caudal injection of 1.0 ml.kg-1 bupivacaine 0.125% with epinephrine 1:400,000 and either fentanyl 1.0 microgram.kg-1 in 1.0 ml of normal saline or 1.0 ml of normal saline. After completion of surgery, patients were assessed in the recovery room for six hours from the time of the caudal injection and for a further 18 hr on the ward. While in the recovery room arterial oxygen saturation and respiratory rate were monitored continuously and recorded hourly together with end-tidal carbon dioxide, pain and sedation scores. Other complications were also recorded. While on the ward, pain and sedation scores, respiratory rate and side effects were recorded every two hours. Postoperative analgesia was provided by intravenous morphine. Analgesic requirements were recorded for the 24-hr study period. Pain and sedation scores did not differ between groups. Respiratory depression or hypoxia did not occur. The incidences of other side effects did not differ. There were no differences in the numbers of patients requiring morphine within eight hours, the time to first morphine administration or the total morphine requirements. We conclude that a single caudal injection of a bupivacaine-fentanyl mixture with epinephrine administered prior to surgery, while safe, offers no advantage over an injection of bupivacaine 0.125% with epinephrine for paediatric urological surgery.     

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy,duration, and absorption of a paediatric oral liquid preparation of ranitidine hydrochloride

The objectives of this study were to assess the clinical efficacy of a new oral ranitidine liquid preparation in reducing gastric acidity and volume, to determine the degree of absorption of the drug, and to determine the duration of drug effect. Eighty preoperative children between the ages of one and six years were enrolled in each of three centres. Each subject was allocated to one of the following groups: Group A - apple juice, 5 ml.kg-1 plus placebo liquid; Group B - apple juice, 5 ml.kg-1 plus ranitidine hydrochloride 2 mg.kg-1; Group C - water, 5 ml and placebo liquid; or Group D - water, 5 ml and ranitidine liquid 2 mg.kg-1. All study agents were administered at least two hours before surgery along with a dye marker, sulfobromophthalein 1 ml (50 mg.ml-1). Following induction of anaesthesia, gastric fluid was aspirated, and analyzed for pH, volume, and sulfobromophthalein content (as an index of the ingested fluids). A serum sample was also drawn and analyzed for ranitidine content by high performance liquid chromatography. Groups B and D had fewer subjects with pH below 2.5 and gastric volume > 0.4 ml.kg-1. The duration of reduced volume and acidity was shown to be greatest from two to four hours after drug administration. Thirty-three percent of subjects receiving oral ranitidine, 2 mg.kg-1 hydrochloride as a single dose demonstrated no measurable effect on gastric pH and volume; 28 of those subjects had adequate ranitidine serum levels.     

Systolic arterial pressure determination by a new pulse monitor technique

The Doppler ultrasound (DUS) technique is a widely accepted non-invasive technique to estimate systolic blood pressure (SBP) accurately in paediatric patients. The DUS has a number of limitations. A new pulse monitor, Mr Pulse (MP), operating on the principle of a finger plethysmograph, was developed to offer an alternative technique to estimate SBP. From 104 paired SBP measurements taken in 16 paediatric patients undergoing general anaesthesia, SBP determined by the MP technique correlated closely with that by the standard DUS technique (r2 = 0.98). Analysis of degree of agreement performed indicated that there was good agreement between SBP obtained by the MP and the DUS techniques. The mean +/- standard deviation of differences in paired SBP values between the two measurement techniques was 0.55 +/- 3.59 mmHg. Mr Pulse is as accurate as the DUS technique in estimating SBP and has the advantage of less critical sensor positioning as it is not subject to electrical interference. It has no electrical hazard.     

Effects of cell surface receptor-altering agents on the binding and biological activity of 12-O-tetradecanoylphorbol-13-acetate in isolated epidermal cells

Isolated epidermal cells were incubated with a variety of compoundsknown to interfere with or alter the ultrastructure of cellsurface receptors, and the ability of 12-O-tetradecanoyl-phorbol-13-acetate(TPA) to bind to these cells and induce epidermal ornithinedecarboxylase (ODC) activity was investigated. The - and ß-adrenergicantagonists, phentolamine and propranolol, and the cholinergicantagonist, atropine, which competed effectively for the bindingreceptors of [³H]dihydro--ergocryptine, [³H]dihydroalprenolol,and [¹⁴C]acetylcholine, did not inhibit the induction of ODCactivity by TPA or the specific binding of [³H]TPA to the cells.Neuraminidase treatments caused a time- and dose- related releaseof sialic acid from the cells and enhanced the stimulatory effectof cholera toxin on basal and TPA-induced ODC activities asmuch as the monosialoganglioside GM₁. Neuraminidase and theother membrane-altering agents, fucosidase, galactosidase, galactoseoxidase, phospholipases A2 and C, and NaIO₄, were used aloneand/or in various combinations in our studies. All treatmentstested inhibited the specific binding of several ¹²⁵I-labeledhormones and epidermal growth factor to the cells. In contrast,none of these treatments was able, in the same cell system,to affect either the binding or the biological activity of TPA.Therefore, these results suggest that the primary interactionof TPA at the plasma membrane level as well as its biologicaleffect in the intact cell do not proceed through adrenergicor cholinergic receptors and do not require the integrity ofthe cell surface glycoconjugates and phospholipids. In addition,the inhibitory effect of retinoic acid on TPA-induced ODC activityremained unaffected by some of the above treatments, suggestingthat retinoic add is unlikely to interfere with TPA interactionsat the plasma membrane level.     

The effects of antiinflammatory steroids on the response of the guinea-pig isolated ileum to acetylcholine,histamine, nicotine, 5-hydroxytryptamine and electrical stimulation

Summary High concentrations of antiinflammatory steroids (2.5–40 g/ml) reversibly inhibited the electrically induced contractions of the guinea-pig isolated ileum. At 40 g/ml they also reversibly inhibited contractions clicited by acetylcholine, histamine, nicotine and 5-hydroxytryptamine. PGE₁ (2.5 ng/ml), PGE₂ (2.5 ng/ml) and PGF₂ (25 ng/ml) antagonized these effects.The inhibition of contractions elicited by direct agonists were less pronounced than those elicited by indirect or partly indirect agonists. The inhibitory effect of steroids may be related to non-specific actions on biological membranes. An overall sensitization of the smooth muscle by PG's may explain their antagonism to inhibition by steroids.     

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

PURPOSE: The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. PATIENTS AND METHODS: Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. RESULTS: The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. CONCLUSION: Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.