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Diels-Alder heterocycloaddition reactions of 2,5,8-quinolinetriones and 1-azadienes afford 1,8-diaza-2,9,10-anthracenetriones, which are simple analogues of the antitumoral antibiotic diazaquinomicin A. Cytotoxicity in this series and antitumor activity of the lead compound, 6-methyl-1,8-diaza-2,9,10-anthracenetrione, are reported.

From September 1989 to September 1990, a total of 25 newborn infants with severe RDS (on mechanical ventilation and with a FiO2 above 0.6) were treated with porcine surfactant (Curosurf), since its efficacy has been demonstrated in a prior clinical trial (Pediatrics 1988; 82: 683-91). The mean birth weight and gestational age were 1,327 +/- 566 g and 29.5 +/- 3.8 weeks, respectively. Twenty-four percent of the babies had an arterial pH below 7.1. At a mean postnatal age of 9.1 +/- 10.7 hours, a dose of 200 mg/Kg of Curosurf was given by the tracheal route. Mean paO2 rose from 47 +/- 14 mm Hg to 166 +/- 64 mm Hg (p less than 0.001). The paO2 increased in 24 of the 25 cases and in 20 (80%) the post-treatment paO2 was a least two times higher than the pre-treatment value. An hour after surfactant treatment, the paCO2 decreased from 58 +/- 21 mm Hg to 45 +/- 16 mm Hg (p less than 0.01) and the pH increased from 7.19 +/- 0.15 to 7.28 less than 0.11 (p less than 0.001). The following complications were observed: pulmonary interstitial emphysema (16%), pneumothorax (8%), patent ductus arteriosus (36%), intraventricular hemorrhage (28%) and bronchopulmonary dysplasia (24%). The neonatal survival rate and the survival rate after discharge from the hospital were 76% and 64%, respectively. The combined survival and absence of DBP was 32%. Nonsurvivors had lower birth weights and gestation ages, as well as lower paO2 5 min after treatment and higher FiO2 24 hours after surfactant treatment than did the survivors.

Pulmonary function was measured by computerized pneumotacography in 26 preterm-newborn infants without respiratory problems. Mean (+/- SD) for birth weight, gestation and postnatal age were 2,034 +/- 412 g, 34.1 +/- 1.7 weeks, and 2.2 +/- 1.6 days, respectively. An esophageal balloon, a differential transducer and nasal prongs were used to measure pressure and flow. The following parameters were measured in each respiration by the mean squares method: Dynamic compliance (Cdyn), total respiratory resistance (RRt) and work (WRt), respiratory time constant (KTt), rate (f) and maximal inspiratory and expiratory flows (PIF, PEF). Replication of the method was found to be good, as the differences between two determinations were not significant (p less than 0.05). The mean differences were less than 6.26%. The mean (+/- SD) and the 3rd and 97th percentiles for each parameter were the following: f: 52 +/- 7 (39-66) r.p.m., Tv: 6.6 +/- 1.1 (4.5-8.7) ml/kg, Vmin: 342 +/- 82 (128-502) ml/min, Cdin: 3.7 +/- 1.1 (1.5-6) ml/cm, RRt: 83 +/- 47 (37-204) cm/L/sec, TRt: 27 +/- 15 (2-57.1) g/cm/kg, PIF: 2.2 +/- 0.5 (1.1-3.2) L/min and PEF: 1.9 +/- 0.6 (0.7-3) L/min.

After the design and use of a computerized system for the prescription of parenteral nutrition, the authors drew up clinical choice tables, as well as others of a pharmaceutical elaboration, based on the same algorithm of the computer program. The conclusion reached was that the nutrition selection process based on these tables is simpler, saves more time, is based on a logical plan of decision making and does not need a computer support.

Some N-substituted bicyclo[3.2.1]octane-3-spiro-3'-pyrrolidine hydrochlorides (IX-XII) prepared from bicyclo[3.2.1]octan-3-one (I), were assayed in vitro against influenza A viruses. All materials showed activity similar to 1-adamantanamine hydrochloride. A 1H-NMR study revealed only one isomer at the spiro carbon atom.

This work describes an immunoenzymatic method for the detection of total IgE in human sera. The assay is performed using specially formulated microtiter plates as solid phase (Dynatech microElisa). This facilitates the dispensing of the reagents, the washing steps and the reading of the results. The whole assay is done using commercially available reagents. This guarantees the high specificity and reliability of the test as well as the low interassay variation. The method uses 10 micro liters of human serum and is performed in two work days. IgE levels ranging between 10 and 1000 I.U./ml can be accurately assayed without modifications of the test volumes. The microplate test, when compared with other methods, has an additional advantage: the absorbance values of the wells can be processed by a microcomputer. The method has been compared with a commercial kit (EnzygnostTM) and the correlation found in 150 cases was excellent (r = 0.983). Using this method, we have assayed more than one thousand sera with very satisfactory results. In addition, the cost of each test has been reduced by 75%.

Allergic reactions to food colors have been known since 1958. Reactions to tartrazine, our example, include generalized pruritus, urticaria, angioedema, paresthesias, vomiting, migraine, rhinorrhea and nasal obstruction, coughing, asthma attacks and purpura. Many patients who are allergic to antiinflammatory drugs such as acetyl-salicylic acid and indomethacin show cross-reaction to tartrazine. Doses producing these reactions range from minimal amounts up to 750 mg. Symptoms appear after periods of time ranging from minutes to 6 to 14 hours. In view of these facts (some of which represent a threat to the patient's life), additives, colouring matter, etc, do not usually appear in product labels or specifications, or in handbooks or catalogues used in practice. We drew up a list of drugs which may contain food dyes and coloring matter, yellow No. 5. A letter was written to 233 laboratories of which 159 (68%) replied. 72 (45%) in the affirmative and 87 (55%) in the negative, 74 (32%) did not reply.

In the daily practice of allergology, one of our commonest problems concerns the prescription of nonsteroidal anti-inflammatory drugs for our patients who are intolerant of acetylsalicylic acid, whose basic clinical expression of this intolerance is primary bronchial asthma. Our problem is the high frequency with which the syndrome appears after the administration of other analgesics chemically unrelated to acetylsalicylic acid. Most authors accept that derivatives of pyrazolones and indoles, and of phenylisopropionic and anthranilic acids must be avoided. This avoidance is based on collected clinical experience and the currently accepted hypothesis concerning the pathogenesis of the syndrome (pyrazolones, indoles, etc. are inhibitors of the byosynthesis of the E series of prostaglandins, particularly PG synthetase). On the other hand there is no agreement concerning what type of analgesics, anti-inflammatory drugs and antipyretics we should prescribe for these patients. The conclusions of the protocol which we carried out are as follows. Dextropropoxyphene chlorhydrate, diviminol, tilidine chlorhydrate, salicylamide, benzidamine, pentazocine, isonixine, hyoscine bromide and ergotamine tartrate can be prescribed safely for these patients in the usual therapeutic dosage. To the list of prohibitions should be added the derivatives of glaphenine and phenylacetic acid. As regards paracetamol, our opinion is that its use should be restricted to those cases in which the previously listed drugs cannot be substituted for it, and always after administration under medical supervision in a hospital setting.

Peripheral blood mononuclear cells from patients with hypersensitivity to L. perenne and D. pteronyssinus were incubated with specific antigen. They were then cultured for 7 days in the absence of antigen and the IgE contained in the supernatants was determined using an enzyme immunoassay (ELISA). Pre-incubation of the cells with antigen produced an inhibitory effect on the spontaneous IgE synthesis in most of the cases (101 of the 134 individual studied). This inhibition was more pronounced and more frequent in those cultures with an elevated spontaneous production of IgE (3,000-10,000 pg/ml). This effect depended on the dose of antigen and the duration of cell exposure. Both spontaneous IgE production kinetics and antigen-mediated inhibition were studied. A study of the IgE content of the cell pellets indicated that the antigen did not induce inhibition of the IgE release. We therefore believe that the inhibition observed must be due to some kind of IgE synthesis suppression.

CFY strain rats (both sexes, 180-210 g) were fasted for 24 hr. Several anticholinergic agents atropine, oxyphencyclimine, propantheline, trantheline, hexocyclium) were administered (i.p.) in equimolar doses (28.78 nM X kg-1), and to compared to the cyto-protective effect of atropine sulfate (0.01 mg X kg-1). Their effects were studied in (1) one hour pylorus-ligated rats, being given when the surgical procedure had just finished: volume and acid output were measured; (2) the gastric mucosal lesions induced by 0.6 M HCl. Drugs were applied 30 min before the administration of HCl (1 ml, i.g.). Rats were killed 1 hr later and the number and severity of lesions were calculated. We found that (1) atropine, oxyphencyclimine, and propantheline did not significantly decrease acid secretion, while trantheline and hexocyclium inhibited acid output; (2) all drugs provided significant protection against the gastric damage induced by HCl; (3) no significant difference was found in the extent of protection produced by the different drugs in the HCl-model. We conclude that atropine, oxyphencyclimine, and propantheline are gastric cytoprotective agents.

Contradictory data have been found on cimetidine-induced gastric cytoprotection. In our paper the effect of cimetidine administered intraperitoneally in doses of 2.5, 10 and 50 mg X kg-1, on: 1. The gastric acid secretory responses in 1 and 4 hr pylorus-ligated rats, and 2. The rat gastric mucosal lesions induced by intragastric administration of 0.6 M HCl, 0.2 M NaOH, 96% ethanol and 25% NaCl is discussed. It was found that: 1. Cimetidine dose-dependently inhibited the gastric acid secretion in 1 and 4 hr pylorus-ligated rats, but a dose of 2.5 mg X kg-1 did not exert any significant inhibition; 2. All doses of cimetidine significantly prevented the gastric lesion development induced by different necrotizing agents (0.6 M HCl, 0.2 M NaOH, 96% ethanol, and 25% NaCl); 3. The cytoprotecting dose of cimetidine was of 2.5 mg X kg-1; and 4. The duration of cimetidine-induced cytoprotection was 1 hr long before the administration of the necrotizing agent. These results suggest a real cimetidine-induced gastric cytoprotection.

We carried out a double-blind clinical trial in 30 patients who were sensitized to Bermuda grass pollen. Before and after immunotherapy we performed in vivo tests (skin tests and standardized tests of specific and nonspecific bronchial hyperreactivity), in vitro tests (histamine release), and specific IgE and IgG antibodies to BGP. We found a significant decrease (P less than .001) in specific bronchial hyperreactivity and skin sensitivity to BGP in the group of patients treated with immunotherapy, a decrease in the delayed responses (P less than .05) in histamine release (P less than .01), and an increase (P less than .001) in specific IgE and IgG antibodies to BGP. The placebo group showed no changes in these parameters.

The isomeric 3-aminobicyclo[3.2.1]octane-3-carboxylic acids were synthesized and compared with the widely used (1R,2S,4S)-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid as to specificity to the Na+-independent membrane transport system L of the Ehrlich ascites tumor cell and of the rat hepatoma cell line HTC. The presence of an additional methylene group in the ring system leads to an optically symmetrical amino acid, with the advantages that the product is devoid of isomeric contamination. Hence, optical resolution is not necessary to secure a homogeneous test substrate for discrimination of amino acid transport systems. Through its inhibitory action on the cellular uptake of known system-specific amino acids, the bicyclo[3.2.1]octane amino acid proved more reactive than the bicycloheptane analogue with the Na+-independent amino acid transport system of the test cells and not perceptibly reactive with the accompanying Na+-dependent systems. Recent evidence of the presence of a second component of Na+-independent amino acid transport, beyond system L, increases the importance of securing a variety of possibly discriminatory model substrates.

Forty-two adult patients had been evaluated with a history of Urticaria and Angioedema (U-AE) associated with ingestion of non-steroidal anti-inflammatory drugs (NSAID). None developed attacks of bronchospasm. None had chronic urticaria. The same reaction was repeated in 36 individuals on at least two different occasions following administration of these drugs. Based on patients'history we distinguished three groups: Group A: twenty-three patients who had presented U-AE with the administration of pyrazolone drugs. Thereafter, sixteen of them had taken aspirin without adverse reactions. Group B: Nine patients in whom aspirin caused U-AE, after three of them had taken pyrazolone drugs without intolerance. The remaining six had not taken analgesic drugs since the last reaction. Group C: Ten patients who had developed U-AE with aspirin as well as with pyrazolone drugs. The objective of our study was the following: 1) to observe tolerance level of these patients to other NSAID different from those which had produced the first reactions. 2) To test to see if the patients who had suffered U-AE by noramidopyrine and aminophenazone tolerated other pyrazolone drugs like sulfinpyrazone and phenylbutazone. 3) To see if reactions are produced with tartrazine in patients who had presented U-AE with pyrazolone drugs, given that this colouring (tartrazine) is a pyrazolone derivative. Skin test (prick and intracutaneous test) with noramidopyrine, phenylbutazone and noramidopyrine metasulphonate MG, were carried out on the patients in group A, group C and 30 normal controls. In all the groups oral challenge tests were performed with progressive doses of naproxen, indomethacin, paracetamol, ciclofenac, mefenamic acid, piroxicam and phenylbutazone. Oral challenge tests were accomplished with aspirin in group A and with propiphenazone in group B. Oral challenge tests with sulfinpyrazone and tartrazine were also performed on various patients in group A and group C. The interval between the administration of progressive doses of a drug was 3 and as half hours and were allowed to pass at least 24 hours before testing other different analgesics. The test was considered positive if cutaneous rash, wheals, AE or hypotension were produced. In this case, the test was halted and 7 days were allowed to pass before continuing the study with a new drug. Based on the oral challenge tests performed, three types of patients could be distinguished: 1) individuals sensitive only to the pyrazolone drugs and who can take with impunity other NSAID.(ABSTRACT TRUNCATED AT 400 WORDS)