Paracetamol treatment for patent ductus arteriosus: practice and attitudes in Australia and New Zealand.

Aim: To describe the current clinical practices and attitudes of neonatologists towards paracetamol treatment of PDA in Australia (AU) and New Zealand (NZ). Method: A web-based survey of all neonatologists registered under the 2017 Australia New Zealand Neonatal Network (ANZNN) was conducted. Results: The response rate for the survey was 67%, (141/210). Of those respondents, 37% stated their unit had a written policy outlining how to treat patent ductus arteriosus (PDA). Of the written policies, 53% mentioned paracetamol treatment. The majority of the respondents (70%) have prescribed paracetamol for PDA closure. When comparing between countries, 79% of AU respondents had compared with 44% of NZ respondents. Successful ductal closure in the infants who received paracetamol was anecdotally reported by 61% of respondents. The main reasons for clinicians not prescribing paracetamol were due to preferential NSAID use (61%) and lack of evidence to indicate efficacy (49%). Conclusion: Many neonatologists in AU and NZ have prescribed paracetamol for PDA closure. However, considerable practice variations exist. The results from this study suggest there may be a role for paracetamol in the treatment of PDA, however, further research is required to clarify the optimal use and provide evidence of efficacy.

Comparative safety and efficacy of two high dose regimens of oral paracetamol in healthy adults undergoing third molar surgery under local anaesthesia.

This study compared the efficacy and safety of single oral doses of 60 mg/kg and 90 mg/kg paracetamol in fit young adult patients undergoing third molar extractions. The study was a randomised, blinded, crossover design on 20 young, fit adults. Paracetamol was administered 30 minutes prior to the surgical extraction of the teeth, which was done under intravenous sedation and local anaesthesia. There were no clinically or statistically significant differences in the pain scores between 60 mg/kg or 90 mg/kg doses until the intake of rescue analgesics. There was a reduction in factor VII activity with 90 mg/kg dose compared to 60 mg/kg dose. It may be concluded that the 90 mg/kg dose, though safe, does not offer any advantages over 60 mg/kg dose of paracetamol in young fit adults undergoing third molar surgery.

Adsorption of bovine serum albumin (BSA) onto lecithin studied by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy.

The adsorption of bovine serum albumin (BSA) to lecithin was investigated by ATR-FTIR spectroscopy. Lecithin films were prepared by casting aliquots of 3.2 microg lecithin in methanol onto ZnSe ATR prisms. Surface morphology and the thickness of the films were investigated by laser scanning confocal electron microscopy and scanning electron microscopy and the thickness of the films used for adsorption studies was estimated to be 40 A. The dependency of the CO peak area on the lecithin mass in the calibration curve confirms that the thickness of the film is below the penetration depth of the infrared evanescent wave. Size exclusion HPLC and fluorescence spectroscopy show that BSA conformation in up to 1M NaCl and CaCl(2) solutions is similar to that in water with no aggregation or changes in protein conformation seen over 4h. The kinetics of BSA adsorption on the lecithin film from water, NaCl and CaCl(2) solutions demonstrates that ions promote the protein adsorption. BSA bound more in the presence of NaCl compared to CaCl(2) at equivalent concentrations. The adsorption appeared greatest at a 0.1M concentration for both NaCl and CaCl(2). The results are explained in terms of absorptive reactivity of BSA and lecithin surfaces upon salt addition.

Analysis of lecithin-cholesterol mixtures using Raman spectroscopy.

FT-Raman spectroscopy has been used to investigate interactions between lecithin and cholesterol. Raman spectra of lecithin show multiple peaks which can be classified into three regions: hydrophobic chain, interfacial, and headgroup regions. Binary lipid mixtures (1:1, w/w, lecithin:cholesterol) were prepared by physical mixing, granulation, coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). Regardless of the preparation method, no changes in the spectra were observed in the hydrophobic region. A shift in the wavenumber of the choline methyl asymmetric stretching mode was observed when the samples were prepared by coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). This may indicate a modification of phospholipids in the headgroup region in these samples. The difference in degrees of frequency shift (physical mixing approximately granulation

Local delivery of chlorhexidine using a tooth-bonded delivery system.

Films containing 20% w/w chlorhexidine base (particle size 63-125 microm) in poly(epsilon-caprolactone), MW 35,000-45,000, were prepared by solvent evaporation and sections attached to the mesio-lingual and mesio-buccal surfaces of the lower first molar in healthy volunteers. Saliva (<1.5 microl) was collected on Periopaper and chlorhexidine concentrations measured by HPLC were typically higher in the area immediately adjacent to the tooth-bonded film sections and lower at more distant sites. Analysis of variance of chlorhexidine concentrations, adjacent to the film sections, showed concentrations were significantly different on the buccal and lingual sides of the tooth and depended on the time of sampling (n=5, P<0.05).

Comparison of the effects of potential parenteral vehicles for poorly water soluble anticancer drugs (organic cosolvents and cyclodextrin solutions) on cultured endothelial cells (HUV-EC).

The effect of dilution of parenteral vehicles (organic cosolvent and 0.1 M cyclodextrin solutions) on cultured endothelial cells (HUV-EC) were compared in vitro. Cell morphology was observed by phase contrast light microscopy and cell viability by measuring 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction or intracellular lactate dehydrogenase (LDH) activity and total protein. Disruption of the HUV-EC monolayer was observed at dilutions of 1 in 20 for the melphalan and PEP cosolvents, 1 in 100 for an investigational drug cosolvent, and 1 in 10 for 0.1 M dimethyl-beta-cyclodextrin. In comparison, 0.1 M SBE7M- and HP-beta-cyclodextrin caused only minor disruption at a 1 in 5 dilution. MTT reduction, intracellular LDH, and total protein were decreased following exposure to 1 in 10 dilution of the melphalan cosolvent. For other test solutions, intracellular LDH activity and total protein were measured, and reductions were observed following exposure to 1 in 10, 20, and 50 dilutions of the investigational drug cosolvent and 1 in 5 dilution of DM-beta-cyclodextrin (0.1 M). At a dilution of 1 in 10, no delayed toxicity was observed for cosolvents or cyclodextrin solutions. Hence, 0.1 M SBE7M- or HP-beta-cyclodextrin formulations may be less damaging to the venous endothelium at the site of injection than organic cosolvent formulations.

Determination of small sample volumes in the analysis of drugs at specific sites in the oral cavity.

Two methods for the determination of sample volumes between 0.2 and 0.6 microliters were compared by preparing standard curves for volumes over this range. The first method used a Periotron and the second the sample mass. A linear model was fitted and 95% confidence limits for volumes estimated by each method were calculated. This showed that use of either the maximum Periotron reading or the sample mass allowed estimation of volumes to within +/- 0.056 microliter and +/- 0.047 microliter respectively. It is proposed that measurement of sample mass provides a simple and accurate method to determine sample volume when analysing drug concentrations at specific sites in the oral cavity.