Selection criteria for resuscitation and survivability rates for neonates at the limit of viability.

AIM: To evaluate outcomes of a cohort of infants born at 23 weeks' gestational age after introducing a new selection score for resuscitation in the delivery room (DR). METHODS: This was a retrospective charts review study using data from the maternal and newborn registry funded by the Qatar National Research Fund. Parents were consulted prenatally and their wishes were honored. The plan of resuscitation was based on the new selection score. The seven components of the score were four antenatal and three immediate postnatal in the DR. Each component received a score of zero, one, or two according to its presence, uncertainty or absence, respectively. Only a score of≥7 would receive active resuscitation unless specified otherwise during prenatal consultation. RESULTS: The study reviewed 60 infants that were delivered over a two year period. The DR death rate was 23 of 60 (38%). Thirty-seven infants (61%) were admitted to the NICU. The score was applied only on 37 infants where all score criteria were reported in their files. Twenty infants had score <7; of them 13 (65%) died in the DR and 7 were admitted to NICU of whom two (29%) survived to discharge. Seventeen babies with scores≥7 admitted to NICU of whom nine (51%) survived to discharge. The survival rate to discharge was 13 of 37(35%). A satisfaction survey included 33 neonatal physicians; 32 neonatologists stated the score was easy to comprehend, 26 voted for easy to implement, and 30 voted for ethical relief and moral comfort. CONCLUSIONS: Using a resuscitation score of seven was associated with improved survival until the discharge of those infants resuscitated. NICU physicians described the score as functional and convenient.

Percutaneous absorption of coumarin, griseofulvin and propranolol across human scalp and abdominal skin.

The objective of this study was to investigate the role of the transfollicular pathway in the diffusion process of chemicals through excised human skin in vitro. Skin was obtained from 5 cadavers (3 males, 3 females) within 24 h of death. The age of the subjects varied between 18-77 years. Three radiolabelled drugs, namely 14C-coumarin, 3H-propranolol and 3H-griseofulvin, were studied. The permeation parameters such as flux, lag time, diffusion coefficient and permeability constant were determined across scalp and abdominal skin using the Thomas Diffusion Cell. For all tested substances the flux through scalp skin was higher than across abdominal skin and the lag time was decreased. The differences were statistically significant at p less than 0.05 for coumarin and propranolol. These data suggest that the transfollicular pathway in permeation might have a significant impact on the diffusion parameters for some drugs. Also, in the case of coumarin, permeability seems to be epidermis/dermis-controlled, whereas for griseofulvin and propranolol the Stratum corneum apparently is the permeability limiting barrier.

Percutaneous absorption of rosmarinic acid in the rat.

Rosmarinic acid (RA) is a nonsteroidal anti-inflammatory agent. The purpose of the study was to investigate the transdermal absorption of RA, its tissue distribution and absolute bioavailability. In ex vivo experiments, permeation of RA across excised rat skin was about 8 times higher from alcoholic solution than from water, indicating that ethanol may act as sorption promoter. The flux from water or alcoholic solution was 4.4 or 10 micrograms/cm2/h, and the tleg was 7.8 or 3.7 h, respectively. After I.V. administration, RA is best described by a 2-compartment open model; t1/2 = 1.8 h, t1/2 alpha = 0.07 h, V tau = 2.3 L/kg, V beta = 15.3 L/kg. Upon topical administration of RA in form of a W/O ointment (25 mg/kg, 50 cm2), the absolute bioavailability was 60%. 0.5 hours after I.V. administration, RA was detected and measured in brain, heart, liver, lung, muscle, spleen and bone tissue, showing the highest concentration in lung tissue (13 times the blood concentration), followed by spleen, heart and liver tissue. 4.5 hours (peak time) after topical administration of about 3 mg on the hind leg over 20 cm2, RA was measured in blood, skin, muscle and bone tissue. The percutaneous route of administration seems to be a promising one for the therapeutic use of RA as nonsteroidal anti-inflammatory agent.

Study on the peroral absorption of the endekapeptide cyclosporine A.

The beagle dog was found to be a suitable model for pharmacokinetic and bioavailability studies of cyclosporine A (CsA). All pharmacokinetic parameters studied were in the same order of magnitude as those found in man. Three CsA peroral formulations in the form of capsules were compared with a commercially available P.O. solution (to be diluted for administration) and a solution for intravenous administration. Of the three experimental capsule formulations, one based on a microemulsion resulted in an extent of absolute and relative bioavailability not different from that of the available P.O. solution. The advantage, however, is that it is a capsule preparation, ready to swallow, and does not need any manipulation by the patient to dilute the solution. The other two capsule preparations, based on a Gelucire gel with sorption promoters and a microemulsion containing Azone, resulted in a lesser bioavailability than the solution.

A source of error in the chromatographic study of 35S-sulfate labeled mucous glycoproteins secreted by the gill epithelium of Mytilus edulis.

HPLC combined with [35S]-sulfate/[3H]-glucosamine radiolabeling were employed to study the synthesis and secretion of mucous glycoproteins. The secreted radiolabeled glycoproteins were separated from the medium by precipitation with a mixture of trichloroacetic-phosphotungstic acids (TCA/PTA). The redissolved glycoproteins were chromatographed on an anion exchange protein column at varying pH of the mobile phase and fractions were collected for liquid scintillation counting. Varying the pH of the mobile phase from pH 3 to 7 resulted in a decrease of glycoprotein bound [35S] from 69.5 to 0.5% of the total recovered [35S]-sulfate with the remainder recovered as free [35S]-sulfate. The [3H]-labeled glycoprotein recovered under the uV peaks at this pH range was 99.5%. When high performance size exclusion chromatography was performed the change in mobile phase pH did not affect the 100% recovery of either [35S]-or [3H]-labels under the uV peaks. No free [35S]-sulfate was obtained when [35S]-labeled glycoproteins were separated from the medium using dialysis. These data suggest that the standard method of TCA/PTA precipitation of [35S]-labeled glycoproteins may cleave the [35S]-sulfate ester linkages to the oligosaccharide chains. The [35S]-sulfate may then rebind to the macromolecule by a relatively strong noncovalent bond. This may prove critical in anion exchange protein HPLC studies.