[Drug administration to paediatric inpatient]. / L'administration des médicaments à l'enfant hospitalisé.

OBJECTIVE: Available commercial drugs in France are often unsuitable for children. The aim of this study was, for every medicinal form orally or parenterally administered, to identify and to quantify difficulties met by the nurses administering drugs to paediatric inpatients and to propose solutions to main identified problems. MATERIAL AND METHOD: The study was realized in 14 hospitals by direct observation. The observer, provided with a questionnaire, followed during a time slot of at least 2 h for one or several nurses and raised all the oral or injectable administrations. RESULTS: One thousand and nine hundred forty-six observations were performed. The children were 12.6 +/- 17 months old, and weighed 8.5 +/- 9.4 kg. Injectable drugs: half of the observations showed a posology and a mode of dilution not corresponding to the summary of product characteristics. Eight percent of orally administered drugs were injectable drugs. In 35.5% of cases, administered amount was lower than the quarter of the present quantity in the therapeutic unity. The rest of the therapeutic unity was thrown (77.2% of cases). Liquid oral forms: liquid oral forms were ready for use regarding 83.8% of cases. The medicine was readministered to the same patient (23.5%), and/or administered to other patients (80.0%). Capsules: 66.9% of the administered capsules were prepared by the hospital pharmacies. The pharmacies organized with an unit dose drug dispensing system produced significantly more preparations than those working by global distribution (P < 0.0001). In 58.4% of cases, the administered capsule was an off-label drug. Tablets: 46% of drug administration concerned a tablet without pediatric indication. 46.7% of tablets were cut, 74% were crushed. Bags: in 35.2% of observations, the bag was not administered in its entirety. CONCLUSION: Our study confirms the unsuitability of drugs to paediatric inpatients, the necessity of recommendations of good practices in the administration of drugs to paediatric inpatients, and proposes corrective actions.

Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein.

The kidney and several other thyroid hormone-responsive tissues contain a NADP-regulated thyroid hormone (TH)-binding protein (THBP), with an apparent molecular mass of 36 kDa on SDS-PAGE, responsible for most of the intracellular high-affinity T3 and T4 binding. THBP was purified to homogeneity from human kidney cytosol and used to generate proteolytic peptides. Microsequencing of four peptides revealed identity to amino acid sequences deduced from a human cDNA homolog to a cDNA encoding kangaroo mu-crystallin. This protein is a major structural kangaroo lens protein with no known function in other species. A full-sized cDNA (TH5.9) was isolated by 5'- and 3'-rapid amplification of cDNA ends using a human brain cDNA library and gene-specific PCR primers, confirming identity to the previously cloned human cDNA. The TH5.9 cDNA encodes a 314-residue protein (theoretical mol wt = 33,775) with significant homologies (40 to 60%) with two bacterial enzymes: lysine cyclodeaminase and ornithine cyclodeaminase. The TH5.9 cDNA was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein. Purified GST fusion protein, but not GST, bound T3 specifically with high affinity [dissociation constant (Kd) = 0.5 nM] in the presence of NADPH, and was labeled by UV-driven cross-linking of underivatized [(125)I]T3. T3 binding and photoaffinity labeling of GST fusion protein were activated by NADPH [activation constant (K[act]) = 10(-8) M], but not by NADH. The expressed protein displays the appropriate binding properties, indicating that TH5.9 cDNA encodes the NADP-regulated THBP characterized in human tissues.

[Osteoarticular amyloidosis and dysglobulinemia: apropos of 2 cases]. / Amylose ostéoarticulaire et dysglobulinémie: à propos de deux cas.

We report two cases of bone and joint amyloidosis involvement related to plasma cell dyscrasia. The radiographic appearances mimic numerous benign or malignant diseases. MR imaging shows a diffuse low signal in T1 and an heterogeneous low or mild low signal in T2 weighted spin-echo sequence.

High affinity thyroid hormone-binding protein in human kidney: kinetic characterization and identification by photoaffinity labeling.

The binding of thyroid hormones and its regulation of NADPH and NADP+ were studied in human kidney cytosol, and a 38-kDa polypeptide (p38) was identified by photoaffinity labeling of cytosol with underivatized [125I]T3, SDS-PAGE, and autoradiography. The cytosolic thyroid hormone binding and p38 photolabeling were strongly activated by NADPH (maximum at 10(-7) M), whereas other nucleotides were less effective or ineffective. NADP+ did not activate T3 binding and p38 photolabeling, provided it was protected from conversion to NADPH by the addition of an exogenous oxidizing enzymatic system (oxidized glutathione plus glutathione reductase). Furthermore, NADP+ inhibited NADPH activation (half-maximum inhibitory effect at approximately 2 x 10(-5)M), and oxidation of NADPH to NADP+ induced dissociation of bound T3. The equilibrium dissociation constant (Kd) of the NADPH-activated cytosolic T3-binding sites was 0.3 nM, similar to the Kd of the nuclear T3 receptors. The kidney contained 200 times more cytosolic NADPH-activated thyroid hormone-binding sites than nuclear T3 receptors. Nonradioactive iodothyronines competed with [125I]T3 for both NADPH-activated binding and p38 photolabeling, with the following order of decreasing affinity: D-isomer of T3 > T3 > T4 > triiodothyroacetic acid > 3'-isopropyl-3,5-diiodothyronine > rT3. NADPH-activated T3 binding and photolabeled p38 were also detected in human heart and liver cytosols, but not in pancreas, cultured fibroblast and erythrocyte cytosols, or plasma. Rat kidney cytosol contained a 35-kDa photolabeled polypeptide homolog to human p38. The native molecular mass of the human photolabeled protein was 50 kDa, whereas that of the rat protein was 60 kDa, as determined by nondenaturing polyacrylamide gel electrophoresis. Two-dimensional PAGE of photolabeled p38 indicated an isoelectric point of 5.3. These findings describe the molecular properties of a NADPH/NADP+-regulated thyroid hormone-binding protein not previously identified in human and rat kidney cytosol.

Identification by photoaffinity labelling of a pyridine nucleotide-dependent tri-iodothyronine-binding protein in the cytosol of cultured astroglial cells.

High-affinity 3,3',5-tri-iodo-L-thyronine (T3) binding (Kd approximately 0.3 nM) to the cytosol of cultured rat astroglial cells was strongly activated in the presence of pyridine nucleotides. A 35 kDa pyridine nucleotide-dependent T3-binding polypeptide (35K-TBP) was photoaffinity labelled using underivatized [125I]T3 in the presence of pyridine nucleotides and the free-radical scavenger dithiothreitol. Maximum activations of T3 binding and 35K-TBP photolabelling were obtained at approx. 1 x 10(-7) M NADP+ or NADPH, or 1 x 10(-4) M NADH. NAD+ and other nucleotides were without effect. NADPH is the form which activates T3 binding and 35K-TBP photolabelling, since cytosol contains NADP(+)-reducing activity, and the activation of both processes in the presence of NADPH and NADP+ was prevented by an exogenous NADPH oxidation system. NADPH behaved as an allosteric activator of T3 binding. The NADPH oxidation system promoted the release of bound T3 in the absence of any change in the total concentration of the hormone. The 35K-TBP photolabelling and [125I]T3 binding were similarly inhibited by non-radioactive T3 (half-maximum effect at 0.5-1.0 nM T3). The concentrations of iodothyronine analogues that inhibited both processes were correlated (3,3',5-tri-iodo-D-thyronine > or = T3 > L-thyroxine > tri-iodothyroacetic acid > 3,3'5'-tri-iodo-L-thyronine). Molecular sieving and density-gradient centrifugation of cytosol identified a 65 kDa T3-binding entity, which included the 35K-TBP. These results indicate that 35K-TBP is the cytosolic entity involved in the pyridine nucleotide-dependent T3 binding, and suggest that the sequestration and release of intracellular thyroid hormones are regulated by the redox state of astroglial cell compartment(s).

[Pharmacovigilance of antibiotics. Evaluation by the Midi-Pyrénées Pharmacovigilance Center between 1989 and 1992]. / Pharmacovigilance des antibiotiques. Bilan du Centre Midi-Pyrénées de Pharmacovigilance de 1989 à 1992.

The present retrospective study investigates the antibiotic-induced side effects in a regional French Pharmacovigilance Center between 1989 and 1992. Five-hundred and seventy six side effects were reported, involving 611 drugs and accounting for 18% of the total activity of the pharmacovigilance center. Most of the side effects involved penicillins and systemic quinolones followed by sulfonamides, cephalosporines and glycopeptides. When expressed in number of adverse effects in Defined Daily Dose, the maximal frequency of side effects was observed with sulfonamides. In contrast, the frequency of penicillin-induced adverse events was low. The most frequently reported side effects were cutaneous and/or immunologic (54%) and digestive (24%) disturbances. Among serious side effects, 3 toxic epidermal necrolysis (2 with cotrimoxazole), 16 pseudomembranous colitis (11 with beta-lactam antibiotics, 4 with macrolides and lincomycines and 1 with vancomycin), 14 neuropsychiatric reactions (seizures, confusions and hallucinations with beta-lactam antibiotics and fluoroquinolones) were notified. Five antibiotic-induced side effects led to the death.

[Basal C peptide levels in response to intravenous tolbutamide in the detection of incorrect insulin therapy (or prolonged misuse)]. / Le dosage du peptide C basal et en réponse au tolbutamide intraveineux dans le dépistage des insulinothérapies abusives (ou abusivement prolongées).

Fifty nine insulin dependant diabetics were hospitalised for a trial withdrawal of insulin: 17 patients rapidly showed signs of lack of insulin, 18 did not develop cetoacidosis but could not be stabilised on diet and oral hypoglycemic agents, 24 were stabilised without insulin. A statistical study (multifactorial analysis of correlations, plotting of ROC graphs) validated the classification of these diabetics into 3 groups. It also showed that in patients with hypoglycemia, the values of C-protein, and after intravenous injection of tolbutamide, were good predictive factors for insulin-dependance: all patients with basal C-protein less than 1,9 ng/ml could not be stabilised without insulin; when the basal C-protein greater than or equal to 1,9 ng/ml and the amplitude of response at the 5th min was greater than or equal to 0,4 ng/ml, the diabetes could be stabilised by diet and oral hypoglycemic agents in 90 p. 100 of cases. This institutes an easy, reliable and economic method of detecting abusive insulin therapy.

Prolactin receptors in human breast cancer.

Prolactin receptors have been measured in 92 human breast carcinomas. Both free and total receptors (after desaturation by MgCl2) have been looked for. Free receptors have been found in 46% of the cases, total receptors in 72%. Specific binding ranges from 0.8 to 8.0%. No correlation could be found between prolactin receptors and age, weight, menopausal status and pathological features (differentiation, histoprognostic grading, cellular density). A highly significant correlation has been found between prolactin receptors on the one hand and estradiol and progesterone receptors on the other.