Case Report Open Tracheostomy after Aborted Percutaneous Approach due to Tracheoscopy Revealing Occult Tracheal Wall Ulcer

Tracheostomy is a common procedure for intensive care patients requiring prolonged mechanical ventilation. In this case report, we describe a 78-year-old female patient admitted for an aneurysm of the cerebral anterior communicating artery. Following immediate endovascular coiling, she remained ventilated and was transferred to the neurological intensive care unit. On postoperative day ten, a percutaneous tracheostomy (PCT) was requested; however, a large ulcer or possible tracheoesophageal fistula was identified on the posterior tracheal wall following bronchoscopic assessment of the trachea. Therefore, the requested PCT procedure was aborted. An open tracheostomy in the operating room was completed; however, due to the position and depth of the ulcer, a reinforced endotracheal tube (ETT) was placed via the tracheostomy. Four days later, the reinforced ETT was replaced with a Shiley distal extended tracheostomy tube to bypass the ulceration. Careful inspection and evaluation of the tracheostomy site before PCT prevented a potentially life-threatening issue in our patient

Rescue of Photoreceptor Degeneration by Curcumin in Transgenic Rats with P23H Rhodopsin Mutation

The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP). There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects

Haemoglobin diagnostic cut-offs for anaemia in Indian women of reproductive age

Background The persistent high prevalence of anaemia among Indian women of reproductive age (WRA) despite aggressive long-term iron supplementation could be related to over-diagnosis from an inappropriately high haemoglobin (Hb) diagnostic cut-off. To develop an appropriate cut-off for Indian WRA, we hypothesized that during iron-folic acid (IFA) supplementation to a mixed (anaemic/non-anaemic) WRA population, the positive slope of the Hb-plasma ferritin (PF) response in anaemic women would inflect into a plateau (zero-response) as a non-anaemic status is reached. The 2.5th percentile of the Hb distribution at this inflection point will be the diagnostic Hb cut-off for iron-responsive anaemia. Method A hierarchical mixed effects model, with a polynomial mean and variance model to account for intraclass correlation due to repeated measures, was used to estimate the response curve of Hb to PF, or body iron stores, in anaemic and non-anaemic WRA (without inflammation), who were receiving a 90-day IFA supplementation. Results The Hb response curve at low PF values showed a steep increase, which inflected into a plateau at a PF of 10.1 µg/L and attained a steady state at a PF of 20.6 µg/L. The Hb distribution at the inflection was a normal probability distribution, with a mean of 12.3 g/dL. The 2.5th percentile value of this distribution, or the putative diagnostic Hb cut-off for anaemia, was 10.8 g/dL (~11 g/dL). Conclusion The derived Hb cut-off is lower than the current adult values of 12 g/dL and could partly explain the persistently high prevalence of anaemia

Exome Analysis Identified a Novel Mutation in the RBP4 Gene in a Consanguineous Pedigree with Retinal Dystrophy and Developmental Abnormalities

<div><p>Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5^th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.</p> </div

Levels of serum retinol in siblings with the RBP4 c.111+1 G>A change.

<p>Levels of serum retinol in siblings with the RBP4 c.111+1 G>A change.</p

Serum RBP4 and transthyretin (TTR) levels in affected and unaffected family members.

<p>Serum RBP4 and TTR levels were examined by western blot analysis as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050205#s2" target="_blank">Methods</a>. A) The patients, IV-2 and IV-4 had undetectable levels of wild type RBP4 in contrast to their unaffected sibling and the control. A faint band was observed in the region of predicted mutant RBP4 in both patients and their unaffected sibling (Asterisk). B) TTR levels (TTR monomer (15 kDa) and dimer (30 kDa) were indistinguishable between affected and unaffected subjects.</p

Genetic analysis of a family with retinal degeneration.

<p>A. Pedigree of the family with retinal degeneration. Family members that were available for study were genotyped for the RBP4 c.111+1 G>A mutation. B. The reverse complement sequence of the heterozygous subject IV-3 (G/A) and the homozygous subject IV-2 (A/A) are shown. C. Protein encoding transcripts of <i>RBP4</i> reported by <i>Ensembl</i> (<a href="http://uswest.ensembl.org" target="_blank">http://uswest.ensembl.org</a>). Three protein coding transcripts are reported by <i>Ensembl</i>. Transcripts ENST00000371464 and ENST00000371467 encode the same protein (CCDS 31249). ENST00000371469 does not have a CCDS identifier. The <i>RBP4</i> c.111+1 mutation would affect all three of the predicted protein coding transcripts.</p

Electroretinogram responses from patient IV-4 with photopic single flash and 30 Hz flicker response stimuli.

<p>Both panels show responses at younger age 38 years on top and at 55 years on bottom. The single flash cone responses at age 38 was reduced approximately 80% from normal and was no longer detectable 17 years later (Panel A). The cone flicker response was similarly reduced at age 38 and further diminished by age 55 (Panel B).</p

Goldman Visual Field (GVF) of the patient IV-4 at age 38 and at age 55.

<p>GVF demonstrated progressive loss from retinal disease. At age 38, both eyes showed a central “tunnel” vision of 15 degrees and large peripheral temporal islands OU (panel A and B), but by age 55, these had constricted to less than 5 degrees, with a small temporal islands for both eyes (panel C and D).</p