Parathyroid adenoma screening efficacies of different imaging tools and factors affecting the success rates

PurposeWe aimed to compare the efficacy of three different parathyroid adenoma screening tools—high-resolution ultrasonography (USG), technetium Tc 99m-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy, and magnetic resonance imaging (MRI)—and we evaluated the factors affecting the detection success rates.MethodsParathyroid imaging was evaluated by USG, double-phase 99mTc-MIBI parathyroid scintigraphy, and cervical MRI in patients with hyperparathyroidism (n=39).ResultsAmong the 39 patients, USG, parathyroid scintigraphy, and MRI correctly identified 35 adenomas (89.7%), 28 adenomas (71.8%), and 26 adenomas (66.7%), respectively. Positive predictive values for USG (34/35), scintigraphy (27/28), and cervical MR (26/26) imaging were 97.1%, 96%, and 100%, respectively. Parathyroid adenomas were detected with 92.3% (36/39) certainty when both USG and scintigraphy modalities were applied together. Minimally invasive parathyroidectomy under local anesthesia with unilateral incision was successfully performed in 24 (61.5%) patients.ConclusionsMinimally invasive surgery for parathyroid adenomas has been developed and has equal success with traditional surgery. However, accurate localization of adenomas should be obtained prior to surgery. In this study, ultrasound was found to be effective in localizing adenomas for successful surgery. Adding other imaging modalities does not improve localizing the parathyroid adenomas.     

Spontaneous dislocation of posterior chamber intraocular lenses (PC IOLs) in patients with retinitis pigmentosa – Case series

PurposeTo report the outcomes of intraocular lens (IOL) dislocation management in 6 cases with Retinitis Pigmentosa (RP).SettingPrivate practice, Los Angeles, USA.DesignRetrospective interventional case series.MethodsThe medical reports of six eyes of four RP patients with capsule bag fixated posterior chamber IOL dislocation were retrospectively reviewed. Pre-operative data included demographics, systemic or ocular disorders, history of trauma, previous intraocular surgery and pre-operative visual acuity. Outcome measures included the type of surgery, surgical complications, elevation of intraocular pressure (IOP), ocular inflammation, cystoid macular edema (CME) and IOL dislocation at 3 months or greater post-operatively.ResultsThe medical records of six eyes of four patients operated on between December 2009 and May 2011 were evaluated. In four cases, dislocated PC IOL implants were sutured to the sclera. In two eyes of one patient anterior chamber IOLs (AC IOLs) were implanted after PC IOLs were explanted. One eye developed CME during the follow-up period. Despite modest tilt in one case and modest decentration in another, stability and centration of the IOLs was excellent during the follow-up period. No eyes had intraocular inflammation requiring long term medical treatment, new onset glaucoma or retinal detachment. Mean follow-up time was 6.9 months (range 3-20).ConclusionsCataract surgeons should be aware of the increased risk for decentration and malposition of PC IOLs in patients with RP. Satisfactory results can be achieved by fixation of the PC IOL or AC IOL implantation.     

Homocysteine Metabolism in Children with Idiopathic Nephrotic Syndrome

Background

Homocysteine metabolism is altered in children with idiopathic nephrotic syndrome. Hyperhomocysteinemia is a risk factor of early atherosclerosis and glomerulosclerosis and may occur at time of first occurrence of idiopathic nephrotic syndrome.

Methods

Thirty children with first episode of idiopathic nephrotic syndrome (FENS) aged 1–16 years along with 30 age‐ and sex‐matched healthy controls were enrolled in this study. Homocysteine and cysteine were measured with HPLC; vitamin B₁₂ and folic acid were measured with electro‐chemilumiscence immunoassay. Primary outcome measure was plasma homocysteine level in children with FENS and in controls. Secondary outcome measures were (1) plasma and urine homocysteine and cysteine levels in children with FENS at 12 weeks and 1 year (remission) and (2) plasma and urine levels of vitamin B₁₂ and folic acid in children with FENS, at 12 weeks and 1 year (remission).

Results

Plasma homocysteine and cysteine levels were comparable to controls in children with FENS, at 12 weeks and 1‐year remission. Plasma levels of vitamin B12 and folic acid were significantly decreased compared to controls in FENS due to increased urinary excretion, which normalize during remission at 12 weeks and 1 year. Urinary homocysteine and cysteine levels were significantly raised in FENS compared to controls and continued to be raised even at 12‐week and 1‐year remission.

Conclusion

Homocysteine metabolism is deranged in children with FENS. Renal effects of long‐term raised urinary homocysteine levels need to be studied.     

Evaluation of genotoxicity after application of Listerine(R) on human lymphocytes by micronucleus and single cell gel electrophoresis assays

Listerine (LN) is one of the most commonly used mouth rinses worldwide although very limited information is available concerning its genotoxicity. In another view, the biological safety profile of oral care products is frequently assumed on the basis of simplistic test models. Therefore, the present study was undertaken to investigate the in vitro genotoxic potential of LN using micronucleus and single cell gel electrophoresis tests as genetic endpoints. Different concentrations of LN (0-100% of ml/culture, v/v) were applied to whole human blood cultures (n = 5). The result of the present study showed that there were no statistically significant differences (p > 0.05) between the control group and the groups treated with LN alone in both analysed endpoints. In conclusion, our result first demonstrated the absence of genotoxicity of LN on human lymphocytes.     

ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice

Hair cells of the inner ear, the mechanosensory receptors, convert sound waves into neural signals that are passed to the brain via the auditory nerve. Little is known about the molecular mechanisms that govern the development of hair cell–neuronal connections. We ascertained a family with autosomal recessive deafness associated with a common cavity inner ear malformation and auditory neuropathy. Via whole-exome sequencing, we identified a variant (c.2207G>C, p.R736T) in ROR1 (receptor tyrosine kinase-like orphan receptor 1), cosegregating with deafness in the family and absent in ethnicity-matched controls. ROR1 is a tyrosine kinase-like receptor localized at the plasma membrane. At the cellular level, the mutation prevents the protein from reaching the cellular membrane. In the presence of WNT5A, a known ROR1 ligand, the mutated ROR1 fails to activate NF-κB. Ror1 is expressed in the inner ear during development at embryonic and postnatal stages. We demonstrate that Ror1 mutant mice are severely deaf, with preserved otoacoustic emissions. Anatomically, mutant mice display malformed cochleae. Axons of spiral ganglion neurons show fasciculation defects. Type I neurons show impaired synapses with inner hair cells, and type II neurons display aberrant projections through the cochlear sensory epithelium. We conclude that Ror1 is crucial for spiral ganglion neurons to innervate auditory hair cells. Impairment of ROR1 function largely affects development of the inner ear and hearing in humans and mice.Sensorineural hearing loss (SNHL) is diagnosed in approximately 1 per 500 newborns (1). A genetic etiology is present in more than half of the cases. Inner ear anomalies (IEAs), demonstrated with computerized tomography or magnetic resonance imaging, are associated with SNHL in about one-third of individuals (2). Although IEAs can be diagnosed in patients with other clinical manifestations, such as those seen in Waardenburg [Mendelian Inheritance in Man (MIM) 193500], Pendred (MIM 274600), or BOR (MIM 113650) syndromes, the majority of cases fall into the category of nonsyndromic deafness. Despite recent progress in identifying genes that determine many forms of hearing loss (hereditaryhearingloss.org/), the genetic basis of IEAs in humans remains largely unknown.The inner ear is a complex organ that is built from a simple structure, referred to as the otocyst, through a series of morphogenetic events. Roughly, it consists of a dorsal vestibular and a ventral auditory component (3). Studies in model organisms have identified a number of genes that play roles in proper development of the inner ear. Mouse models have been particularly relevant because the anatomy and physiology of the murine auditory system are similar to those of humans. Mutations in human orthologs of many of these genes have been reported to cause deafness in humans as well (4).Next-generation sequencing technologies have allowed rapid identification of novel human deafness genes. Approximately 85% of disease-causing mutations in Mendelian disorders have been found in the protein-coding regions, despite the fact that this portion accounts for less than 2% of the entire human genome (5). Accordingly, whole exome sequencing (WES) has been frequently used because it allows for a targeted enrichment and resequencing of nearly all exons of protein-coding genes.In this study, via WES, we detected a mutation in ROR1 (receptor tyrosine kinase-like orphan receptor 1; MIM 602336), encoding receptor tyrosine kinase-like orphan receptor 1, that associates with an IEA and nonsyndromic deafness in a family. Further characterization of Ror1 mutant mice revealed that Ror1 deficiency results in defective hair cell innervation and abnormal cochlear development.     

Sequence typing of human adenoviruses isolated from Polish patients subjected to allogeneic hematopoietic stem cell transplantation – a single center experience

ABSTRACT

Purpose: Human adenoviruses (HAdV) from species A, B and C are commonly recognized as pathogens causing severe morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The purpose of the present study was to determine HAdV types responsible for viremia in HSCT recipients at a large tertiary hospital in Poland.

Methods: Analysis of partial nucleotide sequences of HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40 HSCT recipients.

Results: We identified six different HAdV serotypes belonging to species B, C and E. We demonstrated high variability in sequences of detected HAdV types, and patients infected with the same HAdV types were not hospitalized at the same time, which suggests the low possibility of cross-infection. In almost all patients, anti-HAdV antibodies in IgG class were detected, which indicates a history of HAdV infection in the past. Clinical symptoms accompanying HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen detected. There were no cases with high-level HAdV viremia and severe systemic or organ infections. Graft-versus-host disease (GvHD) was present in patients infected with species B and C, but grade II of GvHD was observed only in patients infected with HAdV-B.

Conclusions: The predominance of HAdV-C and common presence of anti-HAdV antibodies in IgG class may strongly suggest that most infections in the present study were reactivations of HAdV persisting into the patient’s mucosa-associated lymphoid tissues. Variability of HAdV sequences suggests that cross-infections between patients were very rare.

ABBREVIATIONS: GvHD: graft-versus-host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell transplantation     

Human papilloma virus persistence and neopterin,folate and homocysteine levels in cervical dysplasias

Objective  

To investigate the relationship between human papilloma virus (HPV) infection persistence and serum folate, vitamin B12, homocysteine, neopterin levels in cervical dysplasia.