Determination of DNA antibodies in normal and pathological sera by a new counterimmunoelectrophoresis method.

A quantitative counter-immunoelectrophoresis technique has been applied to the evaluation of antibodies against native and single-stranded DNA. Anti-DNA antibodies have been found at high dilutions in patients with systematic lupus erythematosus, without correlation with the existence of renal lesions or with the degree of DNA binding assessed by Farr assay. Significant precipitates were also observed at significantly lower dilutions in other pathological situations and in normal subjects, posing the problem of the nature of the precipitates in these cases.

Intratracheal E. coli lipopolysaccharide induces platelet-dependent bronchial hyperreactivity.

Bronchial hyperresponsiveness (BHR) characterizes asthma and accompanies respiratory infections. Because endotoxin [lipopolysaccharide (LPS)] induces either hyper- or hyporesponsiveness of the guinea pig airways and protects against bronchopulmonary anaphylaxis in sensitized guinea pigs, we compared the effects of the intratracheal administration of Escherichia coli LPS on bronchopulmonary responsiveness to intravenous serotonin or acetylcholine in sensitized and nonsensitized guinea pigs. LPS (1 mg) induced BHR within 1-2 h, with a threefold increase in the bronchial response after serotonin challenge in both groups (n = 6; P < 0.005) and a marked influx of neutrophils into the perivascular and peribronchial connective tissue and the bronchoalveolar lavage fluid. This BHR was not leukocyte dependent, since it was still observed in animals depleted of circulating leukocytes with vinblastine and was not modified by antineutrophil serum, unless platelet counts were < 100,000/mm3. This suggested that LPS-induced BHR involves platelets, and indeed antiplatelet serum, which depleted platelets, or prostacyclin, which inhibited platelets, was effective in suppressing BHR. Neither aspirin, mepyramine, nor the platelet-activating factor antagonist WEB 2170, administered before LPS instillation, prevented BHR, whereas the association of methysergide, mepyramine, and aspirin was effective, without modifying platelet and leukocyte counts. This association has been shown to prevent the release of ATP by ex vivo platelets. Our results suggest that platelets or a platelet-derived product mediates LPS-induced BHR.

Comparative pharmacokinetics of intravenous propranolol in obese and normal volunteers.

Plasma pharmacokinetics of a single IV dl-propranolol dose (8 mg) were investigated in 12 obese subjects (mean +/- SD: 110.3 +/- 20.4 kg; 198.7 +/- 32.5% of ideal body weight) and compared with those of 12 healthy subjects (66.7 +/- 6.8 kg; 94.5 +/- 7.8% of ideal body weight). In obese subjects plasma alpha-1 glycoprotein acid concentrations and propranolol protein binding capacity did not differ significantly from control subjects. When compared with controls, obese subjects showed a significant increase (P less than .01) in AUC (161.0 +/- 67.0 vs 109.6 +/- 23.1 hr.micrograms/L), and significant decreases (P less than .01) in Vss (208.9 +/- 71.9 vs 318.6 +/- 91.8 L), V beta (234.3 +/- 70.4 vs 340.7 +/- 89.1 L), and total clearance (57.5 +/- 18.3 vs 75.9 +/- 15.4 L/hr). Elimination half-life was similar for the two populations (3.5 +/- 0.9 hr in obese subjects vs 3.1 +/- 0.9 hr in controls). Therefore, neither lipophilicity of propranolol nor drug plasma protein binding can explain these data. Altered hepatic function and tissue blood flow in obese subjects are proposed as an explanation for the decrease in total clearance and volume of distribution.

Two identical active X chromosomes in human mammary carcinoma cells.

Chromosome G-banding analysis of two human mammary carcinoma cell lines, Elco and MCF-7, showed the existence of two X chromosomes in both cell lines. To determine the state of activity of the X chromosomes, a methylation-sensitive restriction endonuclease, HpaII, was used to distinguish the active X from the hypermethylated, inactive X chromosome with a probe for the phosphogalactokinase locus by Southern blot hybridization. DNA digested with the restriction enzymes PstI and BstXI showed a band at either 1.05 or 0.9 kilobases. After HpaII digestion, a 50% reduction in intensity was observed in the female controls, whereas total reduction of the band was observed for the tumor cell lines and the male control. This indicates the absence of an inactive X and the presence of only active X chromosomes in the mammary carcinoma cell lines and the male control. To investigate the mechanisms involved in the alteration of the X chromosome composition and activity, restriction fragment length polymorphism analyses of seven additional X chromosome markers (L1.28, DX13, p52A, pX65H7, L782, pA13.RI, and pXG-12) were performed on the DNA isolated from the tumor cells and controls. Heterozygosity for at least one of the seven markers was detected in the six female controls whereas only homozygosity was detected for each marker in the tumor cell lines and the male control. These results indicate that the two active X chromosomes identified in each of the two tumor cell lines are identical, resulting from duplication or nondisjunction of the active X and loss of the inactive X chromosome.

Transposition of the oncogene ets-1 in t(11;19) translocation in acute leukemia.

The specific chromosomal rearrangement t(11;19)(q23;p13) has been identified as a nonrandom chromosomal rearrangement in acute leukemia. The breakpoint, 11q23, coincides with the ets-1 oncogene locus. However, only very few studies have been done to verify the genomic alteration and transposition of ets-1 in the t(11;19) chromosomal rearrangement. In the present study, we identified the t(11;19)(q23;p13) translocation in two acute leukemic cases. One of the cases, biphenotypic leukemia, has been followed thoroughly. An abnormal karyotype was identified in the patient's blood and marrow samples at diagnosis and at relapse, while only normal karyotypes were identified at remission. In situ hybridization of chromosomal preparations with the ets-1 probe pHE5.4 resulted in silver grains nonrandomly localized to 19p13 in the metaphase spreads prepared from the blood sample taken at relapse, while no detectable grains were found on chromosome 19p13 in a sample taken at remission. To determine if genomic alterations of ets-1 are associated with this translocation, Southern blot hybridizations with the pHE5.4 probe were performed on deoxyribonucleic acid (DNA) isolated from blood or marrow samples of the patient at remission and relapse as well as on DNA from a disease-free normal control. Any DNA digested with AvaII, SstI, XbaI, and Bam HI, followed by hybridization with pHE5.4, demonstrated no genomic alterations or amplification of the ets-1 oncogene. Our study indicates that the ets-1 oncogene is transposed in the t(11;19) translocation without detectable alteration at the DNA level. The absence of ets-1 amplification in t(11;19) and its presence in the t(4,11) and t(9;11) translocations demonstrated by others suggests the possible existence of different molecular mechanisms involving the ets-1 oncogene in the pathogenesis of these leukemias.

A comparison of flunisolide inhaler and beclomethasone dipropionate inhaler in bronchial asthma.

Ninety-nine patients, who had never previously taken inhaled steroids were enrolled in a randomized, single-blind, parallel study, the aim of which was to compare the efficacy and safety of flunisolide inhalation, 500 mcg twice daily, with beclomethasone dipropionate inhaler 100 mcg four times daily for the treatment of chronic asthma. The treatment period was for 6 weeks. The patients were examined clinically at entry, week 3 and week 6 and both treatment groups showed a marked improvement in almost all parameters during the course of the study. Flunisolide was statistically significantly superior to beclomethasone dipropionate for wheezing at week 6, coughing at week 6 and chest tightness at weeks 3 and 6. The number of asthma attacks per day decreased significantly more with flunisolide treatment than with beclomethasone dipropionate. The over-all evaluation of efficacy by both doctors and patients also showed flunisolide to be superior to beclomethasone dipropionate. In several other parameters there was a trend shown favouring flunisolide, and beclomethasone dipropionate did not show a superiority over flunisolide in any efficacy parameter. Both drugs were well-tolerated, with unpleasant taste being the most frequent complaint in the flunisolide group. No patient in either group withdrew from the study because of adverse events. In this study, flunisolide inhaler was more effective than beclomethasone dipropionate inhaler for the treatment of chronic asthma exhibited by patients who had never been treated with inhaled steroids.

[Beta-blockers and migraine. Efficacy of time-release propranolol versus placebo]. / Bêta-bloquants et migraine. Efficacité, contre placebo, du propranolol à libération prolongée.

The efficacy and safety of long-acting propranolol (LA.P) 160 mg once-daily in the prophylactic treatment of migraine were tested against placebo in a multicentric, double-blind, randomized study comparing the two groups in a parallel manner over a treatment period of 12 weeks, and following a 4 week-placebo run-in period. Fifty-five out of the 74 patients who entered the trial included at the end of the run-in period. Forty-one patients completed the study. Out of the 14 patients who withdrew from the study, none discontinued because of side-effects. The statistical analysis was done according to the "intention to treat" principle. LA.P was significantly more efficient than placebo in reducing the frequency of migraine attacks (p = 0.01 by variance analysis). LA.P reduced the average number of monthly crises by 48% on day 84. There was a slight but significant reduction of the systolic blood pressure and heart rate in the erect position. There was no significant difference between LA.P and placebo regarding either the number of complaints or the number of side-effects elicited out of an 17 item questionnaire. None of the observed side effects led to a withdrawal of treatment.

[Dermatopolymyositis during desensitization with candidin]. / Dermatopolymyosite au cours d'une désensibilisation à la candidine.

A dermatopolymyositis observation is reported. An urticaria has preceded the dermatopolymyositis and has been treated by a desensitivity procedure. The possible connection between this treatment and the dermatopolymyositis occurring is debated. This observation gives the opportunity to point out the importance of a thorough knowledge of the phenomena involved by such a treatment.

[Histamine-release and migraine]. / Histaminolibération et migraine.

Some studies suggested a role for histamine in the pathogenesis of the migraine. So we decided to investigate the histamine-release in two groups of patients: 8 common migraine patients, 8 healthy subjects. Plasma from either controls or migraineurs were mixed with the same control whole blood and histamine release was measured using a radio-enzymatic assay. Migraine plasma induced an histamine release significantly more important than control plasma (p less than 0.01). The nature of an "histamine releasing factor" in the plasma of migraine patient is discussed. This work is an argument for a possible immuno-allergic process in migraine.

[Reproducibility of intradermal tests after anaphylaxis caused by muscle relaxants]. / Reproductibilité des tests cutanés intradermiques après anaphylaxie aux myorelaxants.

Intradermal tests with 5 muscle relaxants were performed on two occasions in 56 patients who had experienced an adverse event during general anaesthesia: anaphylactoid reaction with at least one positive test 19.5 +/- 13.5 months previously in 50 cases; adverse reaction unrelated to muscle relaxants and with negative tests 21 +/- 6.4 months previously in 6 cases. Sixteen healthy subjects who had never been tested served as controls; their tests were all negative. The reproducibility of 244 assessable tests in the 56 patients reached 88.1%. Twenty-three (9.4%) of the tests previously positive had become negative and six (2.5%) of the tests previously negative had become positive. Tests performed with pancuronium or vecuronium had more often become negative (47% and 40% respectively) than those performed with the other 3 muscle relaxants tested (P less than 0.001). These results suggest that skin tests should be repeated prior to general anaesthesia in all patients who previously developed an anaphylactoid reaction to muscle relaxants.

[Predictive value of intradermal tests using muscle-relaxing drugs]. / Valeur prédictive des tests intradermiques aux curarisants.

A retrospective postal inquiry was carried out to find out a possible relation between the results of intradermal tests carried out for a previous anaesthetic and the course of a second anaesthetic performed afterwards. This study included 350 patients who have had an intradermal test to vecuronium, alcuronium, suxamethonium, gallamine, pancuronium, thiopentone, fentanyl and droperidol between March 1984 and November 1986. Eighty-nine did not reply (25.4%), 183 (52.3%) did not undergo new general anaesthetic since the skin tests, whilst 78 (22.3%) did. The inquiry was then sent to the 73 anaesthetists corresponding to the last group of patients. The 51 complete answers included 62 anaesthetics. Twenty-four patients had negative intradermal tests before the new anaesthetic, the other 27 having had a test positive to at least one muscle relaxant. Of these latter, 16 were given a muscle relaxant during their general anaesthetic, selected among those resulting in a negative intradermal test. Thirteen had undergone skin testing because of an anaphylactic reaction during induction. No new anaphylactic reaction was observed. Three anaesthetists only were not aware of the results of the intradermal tests at the time of the new anaesthetic. These data tend to demonstrate that a muscle relaxant could be injected in a patient who has had a previous anaphylactic reaction with positive intradermal tests, provided that the drug chosen for the new anaesthetic does not give a positive intradermal reaction.

[Skin tests and chymopapain-specific immunoglobulins E after chemonucleolysis]. / Tests cutanés et immunoglobulines E spécifiques à la chymopapaïne après chimionucléolyse.

Skin tests (prick tests) with chymopapain were performed on 3 groups of patients: 75 patients awaiting chemonucleolysis with chymopapain (group I), 42 of these 75 patients 2-3 weeks after chemonucleolysis (group II), and 60 atopic patients suffering from asthma and/or rhinitis with positive skin tests to at least one of the airborne allergens (group III). A positive skin test was found in one patient of group I (1.33%), one patient of group III (1.7%) and 11 patients of group II (26.2%). Thus, sensitization to chymopapain is not more frequent among atopic patients, and chemonucleolysis has a highly significant (P less than 0.001) sensitizing effect. Chymopapain-specific IgE's were found in one out of 75 patients (1.33%) before, and in 14 out of 45 patients (31%) after chemonucleolysis; the difference was significant (P less than 0.001). Concordance between skin tests and specific IgE's reached the 74% level. Our results are consistent with those of the literature. They show that prick tests with a 10 mg/ml solution of chymopapain constitute, for the time being, a simple, reliable and cheap method for detecting subjects at risk.

[Role of platelet serotonin in common migraine. Concentrations and uptake]. / Rôle de la sérotonine plaquettaire dans la migraine commune. Taux et captation.

Concentrations and uptake of platelet conjugated and unconjugated serotonin were measured in 15 healthy subjects and in 19 patients with common migraine. Venous blood was taken between migrainous attacks in all patients and during attacks in 8 of them. A significant decrease in unconjugated serotonin concentrations was observed during the attacks, whereas conjugated serotonin concentrations were the same as in controls. In addition, migrainous attacks were accompanied by a significant decrease in serotonin uptake by the platelets, with fall in Km, Vmax and -y. This abnormality was corrected when platelets removed from patients during attacks were incubated in plasma from controls, but it persisted when platelets from controls were incubated in plasma taken from patients during attacks. These findings suggest that one or several factors present in plasma are responsible for the decrease in serotonin uptake observed during migrainous attacks. Finally a study of correlations between these changes and the time elapsed since the last migrainous attacks demonstrated cyclic variations in abnormalities between attacks.

[Plasma releasing factors in common migraine]. / Facteurs plasmatiques de libération au cours de la migraine commune.

Many platelet abnormalities have been described in migraine, but they are now regarded as secondary phenomena rather than primary causative factors. In this study, we attempted to assess the presence of bioamine-releasing factors in the plasma of patients with common, non-dietary migraine. Blood samples were collected from 17 such patients, either during attacks (n = 9) or during attack-free periods (n = 8). Ten healthy volunteers served as controls. Release experiments were performed by adding 1 volume as controls. Release experiments were performed by adding 1 volume of migraineur's platelet-poor plasma to 1 volume of either control's whole blood (histamine release) or isolated platelets (catecholamines or serotonin release). Endogenous unconjugated bioamines were measured in whole blood and in isolated platelets from migraineurs' blood collected during and between attacks. We also measured plasma levels of histamine and of unconjugated and conjugated serotonin and catecholamines, as well as the inhibition of serotonin uptake and labelled serotonin release from controls' platelets in the presence of migraineurs' plasma collected during or between attacks. The results obtained suggest the presence of two plasma bioamine-releasing factors: a histamine-releasing factor present in migraineurs' blood during and between attacks, and a catecholamine and serotonin releasing factor present only during attacks in migraineurs' platelet-poor plasma. The latter factor is thermolabile and dialysable, with an apparent molecular weight lower than 16 kd. Gel-filtered fractions of semi-purified catecholamine-serotonin releasing factor induced the same events as the migraineurs' platelet-poor plasma from which they were obtained.

[Common migraine. Changes in conjugated and unconjugated catecholamines]. / Migraine commune. Variations des catécholamines conjuguées et non conjuguées.

Plasma levels of conjugated and unconjugated catecholamines were measured in 27 migraineurs between attacks, in 9 migraineurs 1 to 2 hours after the onset of an attack, and in 30 controls. There were no significant changes in conjugated catecholamines; in contrast, a significant rise (p less than 0.01; KS test) in unconjugated dopamine, noradrenaline and adrenaline levels was observed during attacks. These results confirm that migrainous attacks are associated with platelet activation and with overactivity of the sympathetic system.

[Platelet release of dopamine in the common migraine attack]. / Libération plaquettaire de dopamine lors de la crise de migraine commune.

Several arguments suggest that dopamine (DA) plays a role in the physiopathology of migraine. Conjugated and unconjugated plasma and platelet DA, as well as platelet phenolsulfotransferase M activity (responsible for DA sulfatation) were measured in 30 control subjects, 27 common migraine patients between attacks and 9 migraineurs during an attack. No modification of any of the parameters tested was detected in attack-free periods. During the attack no change of conjugated DA was observed; in contrast, a significant decrease of unconjugated platelet DA and a significant and correlated increase of plasma unconjugated DA were demonstrated. This corresponds to a release of unconjugated DA by the very dense bodies in platelets of migraine patients during the attack.

[Immediate hypersensitivity to latex: a new problem. Future perspectives]. / L'allergie immédiate au latex: un problème nouveau. Perspectives d'avenir.

From a series of 30 cases of immediate allergy to the latex of Hevea Brasiliensis, the authors recall the principal clinical aspects of these allergies, specially contact urticaria (during the use of surgical or cleaning gloves) and systemic anaphylactic accidents, essentially the anaphylactic shock during surgical procedures. They mention the diagnostic procedures; skin tests and measurement of specific IgE (RAST). They show the interest of biological research, yielding to the identification of the allergens of the latex in order to obtain non allergenic latex. Such a result would be of interest to limit the number of the accidents in a period where the use of rubber protective material is much larger/gloves and condoms).

Blocking antibodies to inhalant allergens and asthma.

The mechanisms of specific immunotherapy are not still established. Among the lot of immunological changes, induced by immunotherapy, the increase of specific IgG 1, and then of IgG 4 antibodies, during the first months is well demonstrated. The skin-tests, the histamine-release and the human basophil degranulation are significantly decreased after incubation of allergen with the serum of desensitized patients. This antigen neutralizing capacity (blocking antibodies) disappeared when IgG 4 were suppressed from the serum by the mean of activated columns linked either with allergen, or protein A or antihuman IgG4 antibodies. Conversely, the total amount of serum blocking activity was found using pure IgG 4. However, the role of IgG 4 antibodies remains a subject of controversy. Since a clear correlation has yet to be established with symptom scores.

[Clinical effectiveness and tolerance of loratadine versus cetirizine in the treatment of seasonal allergic rhinitis]. / Efficacité clinique et tolérance de la Loratadine versus Cétirizine dans le traitement de la rhinite allergique saissonnière.

A double blind multicentre study of seasonal rhinitis (108 patients) has compared Loratadine and Cetirizine. The results of clinical scores are significantly good for both products. Only tolerance is different and in favour of Loratadine, since sleepiness was found in 9.5% of patients treated with Cetirizine, and 3.6% with Loratadine.