Beneficial effects of Etanercept on experimental necrotizing enterocolitis

Purpose

Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats.

Methods

Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations.

Results

The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde were higher in the placebo group compared to the Etanercept group.

Conclusion

Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-α and interleukin-1β.     

The effect of mastoid surgery on atelectatic ears and retraction pockets

Summary Forty children and 53 adults with a total of 111 atelectatic ears were operated on and followed up. Eight-four ears underwent tympanoplasty, while 27 ears underwent both a tympanoplasty and a mastoid operation. There were no statistically significant differences between the two operation groups as far as their age groups and the extent of the disease present. After follow-up of over 4 years, aeration of the middle ear was found to be better in the tympanoplasty group alone when compared with ears with also had mastoid operations.     

The infant's eustachian tube lumen: the pharyngeal part

A study of Eustachian tube measurements in infants and children is presented. The study included 33 Eustachian tubes from normal temporal bones and 10 Eustachian tubes from temporal bones harbouring acute otitis media. The temporal bones underwent histologic serial sectioning. The lumen of the Eustachian tube's first portion, i.e. the pharyngeal part, was measured with the aid of a grid mounted on a microscope. These measurements show: A. The Eustachian tube lumen grows and enlarges to a small extent with age. B. Each age group presents a considerable variation in the range of area of the lumen comparable with the natural biological distribution. C. No statistical difference was found between the size of the pharyngeal portion of the lumen of the Eustachian tube from temporal bones which had acute otitis media and those coming from non-pathological ears. This comparison took into consideration age and physiological distribution. These findings are similar to our earlier findings regarding the isthmic region.     

Cholesteatoma in children

Of 325 previously untreated cholesteatomas, 109 were found to be in children 13 years old and younger--however, these 109 ears were not found to consist of one clinical entity. Sixty-three of the 109 ears presented a marginal perforation or a retraction pocket, at the level of Shrapnell's membrane or beyond the postero-superior quadrant. In this group the cholesteatoma was distributed mainly in the attic and mastoid and was associated with a non-cellular mastoid. A second group comprising 31 ears presented with cholesteatoma behind an intact drum and were considered to be primary cholesteatomas. These were distributed mostly in the tympanic cavity as cystic epidermoid formations--their mastoid was usually pneumatized. Eight cholesteatomas were related to a central perforation. These ears presented features very similar to the primary cholesteatomas i.e., a pneumatized mastoid and tympanic cavity distribution. The similar features of this group make us think that they may have also originated as primary cholesteatomas which eventually perforated and bring the percentage of primary cholesteatomas in children to 38.3%. Seven of the 109 ears with cholesteatoma were of an indeterminate character.     

Treatment of cholesteatoma

Clinicians view cholesteatoma as a middle ear condition in which stratified squamous epithelium produces non-self-cleansing amounts of keratin. This clinical definition includes retraction pockets as well as big, deep-seated epidermoids. The two may have different origins, and they often require different therapeutic approaches. Clearance and control of shallow retraction pockets may be achieved with suction cleaning. Larger or longstanding retraction pockets, if not too deep, may be excised, and the tympanic membrane grafted. Deep-seated cholesteatomas require more elaborate surgery, whether they involve advanced retraction pockets or big and deep-seated middle ear epidermoids. The intact wall technique, though elegant, has about a 50% failure rate, regardless of the surgeon's skill. The failures are due to either retraction pocket formation, with or without posterior wall atrophy or the reappearance of epidermoids (so-called residual disease). Reconstruction of the bony defect in the scutum does not prevent retraction pocket formation. It is obvious that an approach that envisages successful removal of the matrix as curing the disease is too simplified. The intact wall operation should be reserved for ears with extensive mastoid pneumatization and small cholesteatomas. Most ears with cholesteatoma (85%) are, however, poorly pneumatized and they fare best with a small radical conservative (modified) mastoidectomy. The procedure should aim at creating the smallest mastoid cavity possible. Small mastoid cavities, possessing a tympanic membrane, an adequate mastoplasty, and no recess behind the facial ridge, will be found to be dry in about 90% of cases. A technique for achieving a minimal mastoid cavity is described.     

Comparison of in vitro closure time (PFA-100) with whole blood electrical aggregometry and platelet surface antigen expression in healthy volunteers

It was the aim of this study to compare in vitro closure time (PFA-100), reflecting platelet-related primary hemostasis, to more platelet-specific tests like whole blood electrical aggregometry and platelet surface antigen expression in healthy volunteers. In vitro closure time was measured using a PFA-100. Platelet surface antigen expression (CD63, CD62-P, CD42b, CD36, CD31) was determined in accordance with the consensus protocol for flow-cytometric characterisation of platelet function. Platelet aggregometry was performed using a whole blood electrical aggregometer (ADP and arachidonic acid as agonists). Analysis of the obtained data revealed only a few significant correlations between the different platelet function tests used. This finding can be explained by the various aspects of platelet function being focused by these tests in different extents. Whenever platelet function is analysed, the investigator should be aware of the specific and limited evidence of the method used. For screening purposes, it may be useful to introduce a platelet function index, referring to basal platelet activity, platelet adhesion and platelet aggregation at low and high shear stress forces.     

The effect of combined therapy for treatment of monotherapy-resistant PDA in preterm infants

Objective: Hemodynamically significant PDA (hsPDA) is one of the most common problems in preterm infants. This study was conducted to investigate the effect of combined pharmacological (paracetamol?+?ibuprofen) therapy on monotherapy-resistant hsPDA in infants.

Subject and methods: The study included infants with persistent hsPDA, unresponsive to monotherapy. Combined treatment (paracetamol?+?ibuprofen) was started as paracetamol at a dose of 15?mg/kg every 6?hours for 5?days, and ibuprofen at an initial dose of 10?mg/kg followed by 5?mg/kg at 24 and 48?hours. Echocardiographic evaluation was performed at 2?days after the end of treatment. If hsPDA persisted after the combined treatment, a surgical PDA ligation was considered.

Results: A total of 12 infants were enrolled and 9 infants (75%) with monotherapy-resistant PDA were successfully treated with combined therapy. In three patients, no response was obtained to the combined treatment so surgical ligation was applied.

Conclusions: Combined therapy may be a useful treatment option for monotherapy-resistant hsPDA in preterm infants. Before surgical ligations, this combined therapy option should be considered.     

In vivo binding of benzomorphans to mu, delta and kappa opioid receptors: comparison with urine output in the rat

In vivo binding affinities of three benzomorphans, Win 44,441-3, bremazocine and MR 2266, were determined at the mu, delta and kappa types of opioid binding sites in rat brain, using an ex vivo labeling technique. The receptor occupancy of the benzomorphans and of previously tested diprenorphine were compared with their activities in increasing urine output (agonist ED50: bremazocine) or inhibiting bremazocine-induced diuresis (antagonist ID50: Win 44,441-3, MR 2266 and diprenorphine). The agonist, bremazocine, bound (in order of decreasing affinity) to the kappa approximately equal to mu greater than delta binding sites, and it's pharmacological effects appeared in the dosage range of kappa and mu binding. In order to positively identify which receptor type is responsible, the potency of the three antagonists to block the effects of bremazocine were compared to their ability to occupy the individual sites in vivo. A fractional occupancy of 0.5 would be expected at the ID50 if one assumes a linear relationship between receptor occupancy by the antagonist and the antagonistic effect. Such a linear relationship was observed for the three antagonists only at the kappa site, whereas variable occupancies were observed at the mu and delta sites. These results support the previously proposed hypothesis that kappa receptors mediate the effects of benzomorphan opioid drugs on urine flow.     

Clearance of middle ear effusions by the mucociliary system.

There are two extreme types of middle ear effusion leading to hearing loss (a) a rubber-like effusion seen in secretory otitis media and (b) a water-like effusion seen in serous otitis media. The possibility is considered that the degree of crosslinking in these two extreme cases is the basis of an altered mucus transport rate that leads to an accumulation of effusions and hence impaired hearing. It has been shown (King et al., 1974) that the requisite rheological property for transport activity is not unique to mucus structural macromolecules but is found with other polymeric systems that are loosely crosslinked e.g. guaran, polyacrylamide, gelatin and agarose. Studies on one of these systems guaran, indicate that the transport rate is dependent on the degree of crosslinking with a maximum rate found close to the gel point, i.e. in a region where there are very few crosslinks per macromolecule. The finding that mucus from different mucociliary epithelial sources involves a chemically similar structural glycoprotein suggests that differences observed in transport rate between various mucus samples are more likely due to differences observed in transport rate between various mucus samples are more likely due to differences in crosslinking than chemical variations of the glycoprotein units.