A matched case control study with propensity score balancing examining the protective effect of paracetamol against parentally reported apnoea in infants

Background

Central apnoea occurs in infants and if not detected leads to death. Central apnoea is a prostaglandin E₂ (PGE2) mediated effect that is susceptible to pharmacologic manipulation in animal models. Paracetamol and ibuprofen are centrally and peripherally acting PGE2 inhibitors, respectively.

Aim

To determine if infants who had received paracetamol or ibuprofen are relatively protected from apnoea.

Methods

We performed a matched case control study using propensity score balancing to adjust for non-random drug assignment. We included infants from prospective studies of central apnoea and bronchiolitis. We matched on age, prematurity and fever to adjust for the infants’ underlying risk of apnoea. The primary outcome measure was odds of exposure to paracetamol or ibuprofen by apneic infants compared to their controls.

Results

Forty-two apneic and 729 non-apneic infants were identified. Infants with apnoea were younger than those without, median age 6.5 versus 12.2 weeks and were more likely to be premature. These differences were balanced using matching. Differences between those who did and did not receive paracetamol were satisfactorily balanced using the propensity score. Ibuprofen was used too infrequently to analyse it further. In the unadjusted analysis fewer apneic infants had had prior paracetamol use 5/42 (12%) versus 211/729 (29%) or prior ibuprofen use 1/42 (2%) versus 51/729 (7%). In the adjusted analysis paracetamol was protective against apnoea; OR 0.30 (95% CI 0.11, 0.78).

Conclusions

Prior paracetamol use was protective against apnoea in infants. We could not demonstrate an effect for ibuprofen.     

Studies of sex pheromone production under neuroendocrine control by analytical and morphological means in the oriental armyworm, Pseudaletia separata, Walker (Lepidoptera: Noctuidae)

Most female moths produce species-specific sex pheromone blends in the modified epidermal pheromone gland (PG) cells generally located between the 8 and 9th abdominal segments. The biosynthesis is often regulated by pheromone biosynthesis activating neuropeptide (PBAN) either in or prior to de novo fatty acid synthesis or at the formation of oxygenated functional group. In Pseudaletia separata, information about life span, calling, PG morphology, daily fluctuation of pheromone production and its hormonal regulation is limited.We measured pheromone titer daily (16:8; L:D) at 2 h intervals in scotophase. Blend ratio stabilized during the 2nd day (till 4-5th) at 6th hour of scotophase, with the ratio of 27.5:12.8:44.4:15.3 for Z-11-16OH:16OH:Z-11-16Ac:16Ac, respectively. Females showed calling behavior from this time. We found with light and fluorescence microscopy that PG consisted of intersegmental membrane (A part), and dorso-lateral region of 9th abdominal segment (B part), encountering for ∼35% of total production revealed by gas chromatography. Ratios did not reveal difference. We did not find precursor (triacylglycerols) accumulation in form of lipid droplets, implying that PBAN stimulates de novo biosynthesis of 16:acyl precursors. In vivoHez-PBAN injections (1-3 × 5 pmol, 2 h intervals) into 3 days old 16-18 h decapitated females stimulated pheromone production, both in A and B parts. Blend analyses including ratios suggest stimulation of the initial phase of synthesis, but desaturation of fatty acyl intermediates do not follow proportionally. More saturated fatty acid is converted from the available pool to the final OH and Ac, compared to females kept intact in scotophase. In vitro studies (PGs incubated 4-6 h in the presence of 0.25 or 0.5 μM Hez-PBAN, especially with surplus 2 mM malonyl-CoA) revealed higher saturated component ratio than the unsaturated, compared to natural blend or in vivo injections.     

Metabolic health and vascular complications in type 1 diabetes

AimsOptimal glycaemic control benefits risk of microvascular and macrovascular complications in type 1 diabetes (T1DM) but the importance of other components of metabolic health is less certain, particularly in the context of routine clinical practice.MethodsData for this cross-sectional analysis derived from a database covering inner North West London adult diabetes clinics. People with T1DM and with complete information for height, weight, blood pressure and serum high and low-density lipoprotein cholesterol (HDL-c and LDL-c) and triglyceride concentration measurements were included.ResultsAmong the 920 participants, those with complications were older and had longer duration of diabetes but had similar HbA1c to people without complications. Systolic hypertension and low HDL-c were independently associated with complications. From having 0 risk factors, the prevalence of micro and macrovascular disease increased with increasing number of risk factors. Relative to those with ≥1 risk factor, those with 0 risk factors (n = 179) were at lower risk of retinopathy (OR 0.6 (0.4–0.9), p = 0.01) and nephropathy [OR 0.1 (0.04–0.3), p = 0.002], independent of individual characteristics.ConclusionsIn routine clinical management of T1DM, associations between lipid and blood pressure risk factors and prevalent micro and macrovascular disease remain, implying that more intensive risk factor management may be beneficial.     

Incidence and pattern of dry eye after cataract surgery

Purpose

The objectives of the study were to identify the incidence and pattern of dry eye after phacoemulsification and manual small incision cataract surgeries.

Value of Antibiotic Prophylaxis for Percutaneous Gastrostomy: A Double-Blind Randomized Trial

Purpose

To compare peristomal infection rates following percutaneous gastrostomy (PG) after a single dose of prophylactic antibiotics versus placebo and evaluate rates of peristomal infection in patients receiving concurrent antibiotics.

Neuronal involution during ageing. Ultrastructural study in the rat cerebellum.

Involutive phenomena have been investigated by electron microscopy in the Purkinje Pk neuron of the cerebellar cortex of the aging rat. The still limited number of specimens available to date, however, suggest an age-related progression of morphological and functional deteriorations involving particularly the intraneuronal "nucleus-ribosome system" (NRS). The impairments are characterized by changes in the nucleolar texture. These alterations are accompanied by modifications in the repartition and relative proportion of RNP components of the nucleolus. In addition, other nuclear elements such as interchromatin and perichromatin granules may vary in importance with age. Recognizable changes in the ribosomal constituents of the NRS are evidenced by modifications in the density and distribution of free ribosomes. An altered structure and organization of GER cisternae are also evident. Furthermore, "light" cytoplasmic areas, an increased evidence of neurotubules and the gradual congestion of the pericaryon by age pigments are other valuable ultrastructural features that may be regarded as part of the sequence of morphologic events occurring during neuonal ageing. The above ultrastructural data will subsequently form the basis of a model of ageing in the nerve cell, which will complete the previously proposed model of neuronal maturation. Therefore, this long-term study essentially purports the investigation of subcellular events taking place in the Pk neuron all along the normal life span in rats. This model will also be used to evaluate the changes in the sequence and the reinforcement of the processes of evolution versus involution as affected by certain xenobiotics, such as abused drugs(alcohol and narcotics). The intraneuronal modifications found in the nuclear and cytoplasmic structures of the NRS could possibly reflect the molecular dysfunction related to the production of various types of RNA and neuronal proteins. This hypothesis is supported by biochemical data obtained from analysis of the brain of aged animals. Ultrastructural and biochemical data appear to be in good agreement with the neurophysiologic interpretation of a slow-down and reduced efficiency of the CNS during the progressive development of senescence in human and animal subjects.     

Gastrin induces histamine release from human cutaneous mast cells

Physiologic concentrations of human gastrin I (G17) and a synthetic analog of the carboxy-terminal region of gastrin, pentagastrin, provoked a dose-related release of histamine from human cutaneous mast cells in vitro. The N-terminal tridecapeptide portion of gastrin (G1-13) neither stimulated histamine release nor blocked the action of G17. In vivo correlation studies demonstrated that low concentrations (10(-12)M to 10(-10)M) of G17 or pentagastrin administered intradermally provoked a modest but definite wheal-and-flare response in four out of six normal subjects and a more marked, dose-related response in a patient with mastocytosis. These results indicate that physiologic concentrations of gastrin can stimulate mediator release from human cutaneous mast cells. We propose that this response may be mediated through receptors recognizing the carboxy-terminal region of the gastrin molecule. The possible role of gastrin-induced human mast cell-mediator release should be considered in the assessment of allergic disorders and in experimental models investigating mast cell function.     

Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve, 45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated intravenous administration

The selection of a suitable vehicle for administration of NCEs in non-clinical studies is always a challenge for poorly soluble compounds. Challenge is increased if the dose formulation is intended for intravenous (i.v.) administration where isotonic, biologically compatible pH and solution form is an absolute requirement. Vehicle toxicity and tolerability data are not readily available for a number of combination vehicles therefore, an i.v. tolerability studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was administered via lateral tail vein and effects on clinical signs, body weights, feed consumption, clinical pathology and histopathology were evaluated. Clinical signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg during the course of the study. At 2 mL/kg, injection site injury without systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of 5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to 28 days without any discomfort or injury to rats.     

Study on the effects of mechanical pressure to the ultrastructure and secretion ability of mandibular condylar chondrocytes

During mandibular movement, condyle is subjected to repetitive compression and the mandibular condylar chondrocytes (MCCs) can detect and respond to this biomechanical environment by altering their metabolism. The present study was undertaken to investigate the effects of pressure to the ultrastructure, aggrecan synthesis, nitric oxide (NO) and prostaglandin F(1)alpha(PGF(1)alpha) secretion in MCCs. In vitro cultured rabbit MCCs were incubated and pressed under continuous pressure of 90kPa for 60min and 360min by hydraulic pressure controlled cellular strain unit. The ultrastructure, aggrecan mRNA expression, activity of nitric oxide synthase (NOS) and PGF(1)alpha secretion were investigated. Besides, nitric oxide inhibitor was used together with pressure to investigate the role of NO in mechanical effects. The appearance of MCC on TEM showed that after been pressed under 90kPa for 60min, the cellular processes became elongated and voluminous, together with aggrecan mRNA increasing. Under 90kPa for 360min, some of the cells showed distinct sign of apotosis and the aggrecan mRNA decreased. Pressure of 90kPa could cause increase of NOS activity and decrease of PGF(1)alpha composition. Inhibitor experiments indicated that pressure-induced upregulation of aggrecan mRNA and inhibition of PGF(1)alpha synthesis was partly mediated by NO. Continuous pressure could cause changes on the ultrastructure and function of MCC, as well as up-regulation of aggrecan synthesis, increase of NO secretion and decrease of PGF(1)alpha composition. NO was the upstream molecule, which mediated the response of aggrecan and PGF(1)alpha to mechanical pressure.