Genetic testing has the potential to impact hearing preservation following cochlear implantation

Abstract

Background: Recent advances in less-invasive surgery and electrode design allow for a high degree of hearing preservation (HP) after cochlear implantation (CI), although residual hearing still deteriorates in some patients. To date, the factors predictive of preserving residual hearing remain a controversial topic.

Objective: The aim of this study was to investigate the predictive factors, including the etiology of hearing loss (HL) as a patient-related factor, influencing residual HP after CI.

Methods: Forty-four patients (50 ears, 41 families) with residual acoustic hearing who underwent CI were included. Auditory thresholds before and at 6 months after initial activation were measured. Genetic testing was performed to identify the responsible genes for HL.

Results: We identified the cause of HL in 21 families (51.2%). HP was marginally correlated with age at implantation, while it was independent of pre-operative low-frequency hearing thresholds, cochlear duct length, and electrode length. We found that patients who had pathogenic variants in the CDH23, MYO7A, or MYO15A gene showed statistically better HP scores compared with patients with HL due to other causes (p?=?.002).

Conclusions: Identification of the etiology of HL using genetic testing is likely to facilitate the prediction of HP after implant surgery.     

Hematoma Size in Deep Intracerebral Hemorrhage and its Correlation with Dot-Like Hemosiderin Spots on Gradient Echo T2*-Weighted MRI

BACKGROUND AND PURPOSE: Dot-like low intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large-sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size. METHODS: To investigate how dotHSs are related to the size (maximal diameter) of primary deep ICH, we analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for a maximal diameter of deep ICH < or =2 cm was estimated, using the number of dotHSs and risk factors for stroke. RESULTS: The number of dotHSs associated with the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR, 3.7; 95% confidence interval [CI], 1.4-10.1; P= .009). CONCLUSION: Though small sample size limited the power of our analyses, these findings suggest that the number of dotHSs may be associated with a small diameter of deep ICH.     

Carnitine palmitoyltransferase deficiency in a patient with severe psychomotor retardation

A 13-year-old girl who had severe brain damage due to unknown prenatal cause presented rhabdomyolysis triggered by a mild viral infection. Her muscle biopsy revealed mild variation in fiber size and type 2 fiber atrophy without excess lipid storage. Biochemical analysis of the biopsied material showed decreased carnitine palmitoyltransferase (CPT) activity (15% of the control). Serum and urinary carnitine levels were normal. Skeletal muscle CT scanning showed multiple low density spots. The patient was diagnosed as having CPT deficiency. She recovered from rhabdomyolysis without renal failure after a month with conservative therapy. CPT deficiency is usually found in young healthy persons. This is the first case report of CPT deficiency which presented severe psychomotor retardation since neonatal period.     

Organ specific ESR features in mouse main organs and ESR application to the model of pancreatic disorders

Nine main organs in the mouse were studied by ESR spectroscopy at 77K. Manganese ions were readily detected in the pancreas, small intestine, stomach and kidney. In particular, the pancreas gave strong ESR signals for the transition metal, suggesting that Mn(II) plays an important role in pancreatic function. All organs reveal different ESR spectra indicating organ specificity. C-centered radical, R-OO radical and C0Q10 or ascorbate radical are stable in the tissue. In the brain, heart and pancreas, N-centered radical heme-NO adduct was detected at 6 and 24 h after excision since common process is involved in tissue degeneration and ESR is sensitive to proteolysis and necrosis of tissues. In endotoxemia and/or CDE-diet-induced pancreatic lesions, R-OO radical and Mn(II) ion were detected in the signal at 77K. By the spin-trapping method (DMPO) at 25 degrees C, DMPO-OH adduct and 3-Line and 6-Line were detected in CDE diet-induced acute pancreatitis. These results suggest that damaged pancreatic tissues are in a highly oxidative environment that probably contains oxygen radicals, and that free radicals are considered to play an important role in the development of pancreatic lesions.     

Sex differences of human trabecular bone microstructure in aging are site-dependent.

In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.     

A case of lymphocytic adenohypophysitis associated with sarcoidosis of the lung and eye

Lymphocytic adenohypophysitis is considered to be an inflammatory disease of the adenohypophysis that is commonly present with visual disturbance and hypopituitarism. Its etiology remains unclear but it is often related to an autoimmune disorder involving other organs, such as the thyroid, parathyroid, or adrenal glands. We encountered a rare case of lymphocytic adenohypophysitis associated with sarcoidosis of the lung and eye during the follow-up period. A 23-year-old woman was hospitalized in July 1986, with a one-month history of headache and visual disturbances which began three days after her second normal delivery. On admission, she showed slight visual impairment and had a left temporal superior quadrantanopia. Endocrinological evaluation revealed thyroid and adrenal hypofunction, and low response of human growth hormone to the loading test. A skull X-ray showed normal shaped sella with some erosion of the dorsum. CT scan showed a rounded contrast-enhanced intrasellar mass extending into the suprasellar cistern. MRI (SR: 500/30) showed a homogeneous low intensity mass which contained a small high intensity area on the relative T2-weighted image (2000/50). A biopsy was performed via right frontotemporal craniotomy. The consistency of the resected tissue was firmer than that of pituitary adenoma. Histologically, the tissue showed diffuse lymphocytic infiltration with some normal adenohypophysis. Her postoperative course was uneventful and the visual impairment improved two months later after the operation. Six months after the operation, she was readmitted with complaints of general fatigue and breathlessness. Chest X-ray showed diffuse infiltration throughout both lung fields, but there was no bilateral hilar lymphadenopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of KW-3635, a novel dibenzoxepin derivative of a selective thromboxane A2 antagonist, on human, guinea pig and rat platelets.

We examined the binding of [3H]U-46619, a thromboxane A2 agonist, to human and guinea pig platelets and the binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to human, rat and guinea pig platelets. KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1- benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-c arboxylate monohydrate) concentration-dependently inhibited the [3H]U-46619 binding to human and guinea pig platelets with inhibition constants of 1.2 nM and 2.7 nM, respectively. KW-3635 also potently inhibited the [3H]SQ 29,548 binding to human and guinea pig platelets with inhibition constants of 1.9 nM and 3.2 nM, respectively. In contrast, KW-3635 was less active against thromboxane A2/prostaglandin H2 receptors in rat platelets with an inhibition constant of 97 nM. KW-3635 at 10(-5) M did not antagonize various receptors including prostaglandin E2, prostaglandin I2 and neurotransmitters. In addition, 10(-5) M KW-3635 did not alter the prostaglandin D2-induced cAMP accumulation in EBTr cells. KW-3635 was inactive towards thromboxane synthase, cyclooxygenase and prostaglandin I2 synthase up to 10(-5) M. KW-3635 slightly inhibited 5-lipoxygenase with an IC50 value of 71 microM. These data indicate that KW-3635 is a potent and selective non-prostanoic thromboxane A2 antagonist, and it can recognize the species differences in thromboxane A2/prostaglandin H2 receptors.     

Isolation of a renal function-facilitating constituent from the Oriental drug, salviae miltiorrhizae radix

An attempt was made to isolate the active component which exhibits an improving effect on renal function from Salviae Miltiorrhazae Radix (Chinese crude drug). Systematic isolation from aqueous extract of Salviae Miltiorrhizae Radix was carried out, and Compound 1 was found to be more effective than any of the other constituents in improving renal functional parameters; that is, a marked reduction of glomerular filtration rate following adenine ingestion was improved by administration of this substance. The renal plasma flow and renal blood flow were also increased in renal failure rats. On the basis of chemical and spectroscopic data, Compound 1 was shown to be identical with magnesium lithospermate B.     

Pulmonary nodules 10 mm or less in diameter with ground-glass opacity component detected by high-resolution computed tomography have a high possibility of malignancy

OBJECTIVES: For the histological diagnosis of small lung cancers of 10 mm or less in diameter (< or =10), resection by video-assisted thoracic surgery (VATS) with computed tomography (CT)-guided marking is feasible. One problem is that a small number of these pulmonary nodules are malignant. We retrospectively analyzed CT images of pulmonary nodules to find better criteria to select candidates for resection among patients with small pulmonary nodules. METHODS: Ninety-four patients with indeterminate peripheral pulmonary nodules underwent wedge resection by VATS. High-resolution CT using a 1.25 mm slice included the area of lesions. Nodules were classified by size (< or =10, 11 to 20, >20 mm) and whether they had a ground-glass opacity (GGO) component. RESULTS: The histology of all 94 nodules showed 52 primary lung cancers, 6 metastatic tumors, 5 benign tumors, 8 intrapulmonary lymph nodes, and 23 inflammatory nodules. Ninety-three percent of nodules larger than 20 mm, 75% of nodules 10 to 20 mm, and 43% of nodules < or =10 mm were malignant. Introducing a classification according to GGO component to nodules, malignancy was detected in 88% of nodules with a GGO component and in 30% of nodules without a GGO component among nodules < or =10 mm. Nodules < or =10 mm with a GGO component showed a statistically significant (p < 0.01) correlation with malignancy. CONCLUSIONS: Pulmonary nodules < or =10 mm with GGO should be considered to have a high possibility of malignancy and to be candidates for resection by VATS.