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Biomedical subjects

A Meunier

Publications and source records attributed to A Meunier.

106 records · Page 6Linked to original sources

[Translumbar intra-aortography. Hemodynamic consequences (author's transl)].

The hemodynamic consequences of the translumbar intra-aortic injection of 80 ml of contrast media were studied in 28 patients, in whom cardiac output was determined using thermodilution. These measurements revealed that the vasoplegia produced by the intra-aortic injection of contrast media is of smaller amplitude and longer duration than that evidenced during regional flow determinations. Moreover, the decrease in vascular peripheral resistances and the increase in cardiac output, accompanied by bradycardia, persist for several minutes. These phenomenons are related to an increase in ventricular filling, resulting from the expansion of the intravascular compartment secondary to plasma hyperosmolality.

Aortography↗

Preparation of well-defined protein conjugates using enzyme-assisted reverse proteolysis.

A two-step approach to the production of well-defined protein conjugates is described. In the first step, a linker group, carbohydrazide, having unique reactivity (a hydrazide group) is attached specifically to the carboxyl terminus by using enzyme-catalyzed reverse proteolysis. Since the hydrazide group exists nowhere else on the protein, specificity is assured in a subsequent chemical reaction (formation of a hydrazone bond) of the modified protein with a molecule (chelator, drug, or polypeptide) carrying an aldehyde or keto group. The product is sufficiently stable at neutral pH, no reduction of the hydrazone bond being necessary for the hydrazones described. Protein modification is thus restricted to the carboxyl terminus and a homogeneous product results. With insulin as a model, conditions are described for producing such well-defined conjugates in good yields. The use of other linker groups besides carbohydrazide, and applications of these techniques to antibody fragments, are discussed.

Chemistry, Organic↗

Protein conjugates of defined structure: synthesis and use of a new carrier molecule.

A new carrier molecule, NH2OCH2CO-(Gly)3-[Lys(H-Ser-)]5-Gly-OH, has been synthesized to facilitate the preparation of protein conjugates of defined structure. Special features are as follows: (i) (aminooxy)-acetyl as a terminal group, which reacts specifically to form an oxime bond under very mild conditions with an aldehyde group placed on a protein in a prior step; (ii) a spacer group of three Gly residues; and (iii) a set of five Lys residues, each of which is acylated with a Ser residue. A second form of the carrier molecule, HCO-m-C6H4CH = NOCH2CO-(Gly)3-[Lys(H-Ser)]5-Gly-OH, was also prepared. This form possesses a terminal aldehyde group which permits site-specific attachment by formation of a hydrazone bond to the carboxyl termini of polypeptide chains which have been modified enzymatically with carbohydrazide in a prior step. Once the carrier is linked to protein in one of the above ways, i.e. through formation of either an oxime or hydrazone bond, the Ser residues of the carrier (but not of the protein) may be oxidized by very mild periodate treatment to generate aldehyde groups. Drugs possessing a hydrazide group (e.g. methotrexate gamma-hydrazide or desacetylvincaleukoblastine hydrazide) may then be conjugated via hydrazone formation to the aldehyde groups of the carrier. A cluster of five drug molecules may thus be attached to a single site on a protein, giving a relatively homogeneous product in spite of the high drug conjugation ratio. Synthesis of the carrier, formation of a pentadrug-protein conjugate, and wider implications of the chemistry are presented.

Amino Acid Sequence↗

[Evaluation of blood pressure self-monitoring of the residual efficacy of telmisartan compared to perindopril. The EVERESTE study].

UNLABELLED: The aim of this multicentre, prospective, randomised, open study was to compare the trough effect of telmisartan (T) and perindopril (P) on diastolic blood pressure (DBP) after a 12-week treatment, using self blood pressure measurement (SBPM). METHODS: To enter the study, patients had to be 18 years of age or older and were required to suffer from mild to moderate hypertension (90 < or = PAD < 110 mmHg and/or PAS < 180 mmHg). At the end of a 3-week run-in placebo period, patients were allocated to receive either T (40 mg) or P (4 mg) once daily for a period of 12 weeks. Patients whose clinic DBP remained higher than or equal to 90 mmHg at the end of the sixth week, were given a double dose regimen. SBPM was performed over 7 consecutive days at 3 different times: at the end of the washout period (W0), at week 6 (W6) and week 12 (W12). A clinic determination of blood pressure (BP) was also performed at each visit, using the same automatic device as that used for SBPM. RESULTS: 671 patients were selected and 441 were randomised (age: 55 +/- 12 years: 240 men and 201 women). Study populations were the following: the safety population (n = 441, T = 220; P = 221), the intent-to-treat (ITT) population (n = 435, T = 217 and P = 218), and the per protocol population (n = 368, T = 188; P = 180). ITT analysis showed a greater diminution of trough DBP from W0 to W12 with T than with P (T: -6.6 +/- 6.7 mmHg and P: -5.1 +/- 7.0 mmHg; p = 0.018 according to ANOVA for repeated measures). Regarding clinic BP, the same results were observed. Likewise, the per-protocol analysis provided similar findings. Doubling dose was significantly less frequent with T (41%; n = 85) than with P (55%; n = 115; p = 0.005). The overall frequency of adverse events was similar in both treatment groups: T = 34% (n = 74) vs p = 32% (n = 70). Most of them were of mild to moderate intensity and transient. As expected, the occurrence of cough was more frequent with P [5% (n = 12), T < 1% (n = 2), p = 0.007]. CONCLUSION: The trough effect on DBP was statistically higher with T (40 mg) than with P (4 mg), using SBPM as well as automatic clinic BP measurement.

Adult↗

[Compared efficacies of somes antispasmodic drugs on the digestive tract and the bladder of the anesthetized dog (author's transl)].

The antispasmodic activity of tiemonium, mebeverine, pitofenone + fenpiverinium association and N-butyl scopolammonium was compared in the anesthetized dog. Strain gauges were fixed on the gastric antro-fundic border, on the pylorus, on the descending duodenum and on the terminal colon. Pressure transducers were connected with water filled small balloons inserted into the gall bladder and the bladder. Five minutes after the intra-venous injection of the drugs, contraction of the smooth musculature was induced by 3 intra-venous injections of BaCl2 (1 mg.kg(-1)) at 3 minutes intervals. The results were expressed as ED50 values (mg.kg(-1)). 2. Tiemonium was the most potent of the 4 antispasmodic drugs. Its ED50 values were very similar for the different organs, ranging from 0.13 +/- 0.022 for the duodenum to 0.31 +/- 0.03 for the bladder. Mebeverine and pitofenone + fenpiverinium association were equipotent but for colon contraction, where mebeverine was more active (ED50 = 0.68 +/- 0.06). Other ED50 relatives to these 2 compounds were ranging from 0.40 +/- 0.02 (duodenum) to 1.32 +/- 0.14 (gall bladder). N-butyl scopolammonium was found to be the weakest antispasmodic drug on this model. Its activity was very weak on colon (ED50 = 5.21 +/- 0.037), gall bladder (ED50 = 5.40 +/- 0.074) and bladder (ED50 = 5.02 +/- 0.059). 3. The strong antispasmodic activity demonstrated on this model with tiemonium seems to be due to its potent inhibition of membrane Ca++ ions, added to its moderate anticholinergic activity.

Anesthesia↗