Head and neck blocks in infants, children, and adolescents

This review will discuss the use of peripheral nerve blocks of the head and neck and its application to the practice of pediatric anesthesia using simple, landmark based approaches.     

Fish scale collagen-a novel material for corneal tissue engineering

The ex vivo cultured limbal stem cells over a biocompatible scaffold are used in the management of limbal stem cell deficiency as an ideal replacement for human amniotic membrane (HAM). A novel source of collagen from fish scales (FSC) was used to fabricate the scaffold. In this study, we have evaluated the physicochemical, mechanical, and culture characteristics of FSC and compared with denuded HAM. The cultured corneal cells were characterized by real‐time polymerase chain reaction for putative stem cell markers. The swelling ratio, collagenase assay, and microbial resistance of FSC gave better results when compared to those of HAM. The mechanical and physical strengths of FSC were good enough to handle when compared to HAM. Under microscopic observation, epithelial migration was noted at the end of 48 h from limbal explants plated on FSC and on HAM at the end of 72 h. By the end of the 15th day, 90 to 100% confluent growth was seen resembling the morphological features of limbal epithelium. In conclusion, FSCs from a novel renewable biological source were optically clear with sufficient strength, and gave encouraging results in culture studies; the same may be tried as potential candidate for corneal transplantation after in vivo studies.     

Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia

Chromosome maintenance protein 1 (CRM1) is a nuclear export receptor involved in the active transport of tumor suppressors (eg, p53 and nucleophosmin) whose function is altered in cancer because of increased expression and overactive transport. Blocking CRM1-mediated nuclear export of such proteins is a novel therapeutic strategy to restore tumor suppressor function. Orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of this protein have been recently developed. Here we investigated the antileukemic activity of KPT-SINE (KPT-185 and KPT-276) in vitro and in vivo in acute myeloid leukemia (AML). KPT-185 displayed potent antiproliferative properties at submicromolar concentrations (IC(50) values; 100-500nM), induced apoptosis (average 5-fold increase), cell-cycle arrest, and myeloid differentiation in AML cell lines and patient blasts. A strong down-regulation of the oncogene FLT3 after KPT treatment in both FLT3-ITD and wild-type cell lines was observed. Finally, using the FLT3-ITD-positive MV4-11 xenograft murine model, we show that treatment of mice with oral KPT-276 (analog of KPT-185 for in vivo studies) significantly prolongs survival of leukemic mice (P < .01). In summary, KPT-SINE are highly potent in vitro and in vivo in AML. The preclinical results reported here support clinical trials of KPT-SINE in AML.     

Inferior alveolar nerve blocks for postoperative pain control after mandibular distraction with osteotomies in a neonate

We describe the use of inferior alveolar nerve blocks (IANBs) for postoperative pain control for a neonate undergoing mandibular distraction and osteotomies. In this case, bilateral IANBs were effective in keeping low pain scores as assessed on the neonatal infant pain scale (NIPS) and the amount of opioid and adjuvant analgesics used. The blocks were assessed to have lasted approximately 24 h making serial blocks for pain control logistically feasible. Additionally, pain control was improved throughout the period of distractor advancement (approximately 7 days). We propose the routine use of this regional technique for improved pain control after this procedure in neonates and suggest that improved pain control may facilitate earlier extubation in this challenging population.     

From the Cover: Melanopsin mediates light-dependent relaxation in blood vessels

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4^−/− mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430–460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.Photorelaxation, the reversible relaxation of blood vessels to cold light, was initially described by Furchgott et al. in 1955 (1). Subsequent studies have attempted to define the signal transduction mechanisms responsible for this phenomenon. The process seems to be cGMP-dependent but endothelial-independent. The role of nitric oxide (NO) in photorelaxation has been controversial (2–7), with some studies showing that NOS inhibition with l-NAME not only fails to inhibit the response (2) but in some cases enhances and prolongs it (3). Moreover, several published reports examining photorelaxation demonstrate an attenuation of the response with each subsequent light stimulation. A number of investigators have proposed that NO dependence results from the photo-release of NO stores from nitrosothiols and that the endothelium and NOS are important for the repriming of these stores (stores that become depleted with each photo-stimulation); however, the source of those nitrosothiols has not as yet been clearly identified (6). Importantly, photo-release of NO occurs in the UV-A spectrum at 366 nm (4–6), a wavelength at which intravascular nitrosospecies and nitrite have the potential to release substantial quantities of NO (7). However, this wavelength is very different from that at which others have observed vascular responses. Given the controversy surrounding the photorelaxation mechanism, we postulated an entirely new mechanism: that photorelaxation is mediated by transduction through photosensitive receptors in blood vessels. These photoreceptors are part of the family of non-image-forming (NIF) opsins. We now report a signaling cascade mediating photorelaxation via Opn4, cGMP, and phosphodiesterase 6 (PDE6) that is regulated by G protein-coupled receptor kinase 2 (GRK2).     

Secular trend in birthweight in an industrial hospital in India.

Measurement of birthweight is an indicator of community health. The mean birthweight (MBW) of babies born in 1963, 1983 and 1986 were measured in 2254, 3550 and 3368 babies, respectively. Mean (SD) birthweight was found to be 2652 (553) g in 1963, 2724 (502) g in 1983 and 2726 (478) g in 1986. There was a rise in MBW (72 g) between 1963 and 1983 and a reduction in the percentage incidence of low birthweight from 34.29% to 26.06%. A change in birthweight distribution (was also seen, except in extreme weight groups. The improvement in birthweight is statistically significant (p less than 0.001). A trend for increase has been noticed in birthweights, and the mean birthweight values are the same as the national average.