Reliability of the Brazilian version of the Functional Assessment of Cancer Therapy-Lung (FACT-L) and the FACT-Lung Symptom Index (FLSI)

OBJECTIVES:

The purpose of this study was to assess the reliability of the Brazilian version of the Functional Assessment of Cancer Therapy‐Lung (FACT‐L) with the FACT‐Lung Symptom Index (FLSI) questionnaire.

INTRODUCTION:

The assessment of quality of life in patients with lung cancer has become an important evaluative endpoint in current clinical trials. For lung cancer patients, one of the most common quality of life tools available is the FACT‐L. Despite the amount of data available regarding this questionnaire, there are no data on its performance in Brazilian lung cancer patients.

METHODS:

The FACT‐L with the FLSI questionnaire was prospectively administered to 30 consecutive, stable, lung cancer outpatients at baseline and at 2 weeks.

RESULTS:

The intraclass correlation coefficient between test and retest for the FACT‐L ranged from 0.79 to 0.96 and for the FLSI was 0.87. There was no correlation between these questionnaire dimensions and clinical or functional parameters.

CONCLUSIONS:

The Brazilian version of the FACT‐L with FLSI questionnaire is reliable and is quick and simple to apply. This instrument can now be used to properly evaluate the quality of life of Brazilian lung cancer patients.     

Frequency of the mdr-1 C>T gene polymorphism in patients with COPD

BACKGROUND AND AIM:

The multi‐drug resistant‐1 (MDR‐1) gene is located on human chromosome 7 and encodes a glycosylated membrane protein that is a member of the ATP‐binding cassette transporters superfamily. The aim of the study was to reveal the role of the C3435T MDR‐1 gene polymorphism in chronic obstructive pulmonary disease.

METHOD:

DNA samples from 41 patients with chronic obstructive pulmonary disease and 50 healthy control participants were used to compare MDR‐1 gene profiles. Genotyping assays were performed using the StripAssay technique that is based on reverse‐hybridization.

RESULTS:

The T allele polymorphism in the MDR‐1 gene located at position 3435 in exon 26 was shown to correlate with chronic obstructive pulmonary disease.

CONCLUSION:

These preliminary results suggest that the T allele polymorphism of the MDR‐1 gene is associated with chronic obstructive pulmonary disease.     

Desaturation - distance ratio: a new concept for a functional assessment of interstitial lung diseases

INTRODUCTION:

The functional evaluation has become increasingly important in the understanding and management of patients with interstitial lung diseases. The cardiopulmonary exercise test and the six‐minute walk test (6MWT), through their isolated variables, have been used to do this evaluation, with some limitations.

OBJECTIVES:

We proposed a new composite index (desaturation distance ratio using continuous peripheral oxygen saturation (SpO₂) and the distance walked as a more reliable tool for doing a functional evaluation of these patients.

METHODS:

6MWT was performed by interstitial lung diseases patients and controls. Analyzed parameters were walked distance and desaturation area (DAO₂), obtained by taking the difference between maximal SpO₂ possible (100%) and patient''s SpO₂ every 2 seconds. desaturation distance ratio was calculated using the ratio between DAO₂ and distance walked.

RESULTS:

Forty‐nine interstitial lung diseases patients and 11 control subjects completed the protocol. The mean (SD) age was 60 (12) years and 65 (9) years, respectively (p:NS). Data obtained from 6MWT showed a significant statistical difference between interstitial lung diseases patients and controls: mean walked distance (430 and 602 meters, respectively); SpO₂ minimal maintained at least 10 seconds ‐ SpO₂ min (85% and 94%, respectively), and median desaturation distance ratio (10 and 2.5, respectively). A correlation analysis, considering interstitial lung diseases patients, revealed the best correlation between desaturation distance ratio and DLco (r =  ‐ 0.72; p<0.001), being the correlation between SpO₂ min and DLco of 0.61 (p<0.001) and among walked distance and DLco of 0.58 (p<0.05).

CONCLUSION:

Desaturation distance ratio is a promising concept and a more reliable physiologic tool to assess pulmonary diseases characterized by involvement of the alveolar‐capillary membrane, such as interstitial lung diseases.     

Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

INTRODUCTION:

Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown.

OBJECTIVES:

The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure.

METHOD:

Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression.

RESULTS:

Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis.

CONCLUSIONS:

Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.     

Phase Contrast Microradiography of Mouse Lung Using Synchrotron X-ray: Correlation with Optical Microscopy

Purpose

The purpose of this study is to evaluate the feasibility of phase contrast X-ray microtomography and microradiography, using a polychromatic synchrotron X-ray, for analysis of the mouse lung microstructure.

Materials and Methods

Normal mice were used for experiments. Some of the mouse lungs were prepared by the lung fixation-inflation method. The resulting sponge-like inflated lung samples were used for microtomography. The remaining mouse lungs were cut into 10 um sections and were used for microradiography and optical microscopic correlation. The experiments on mouse lung samples were performed at the 7B2 beamline of the Pohang Light Source in Korea.

Results

Phase contrast X-ray microtomography of inflated lung samples showed individual alveolar structure on 3-D reconstruction. Phase contrast microradiographs of thin lung samples showed microstructure of lung, such as alveoli and bronchioles, and were well correlated with optical microscopic images.

Conclusions

The results indicate that the phase contrast X-ray microtomography and microradiography using polychromatic synchrotron X-ray is feasible for evaluation of microstructure of the lung.     

KGFR promotes Na+ channel expression in a rat acute lung injury model

Background

Binding of keratinocyte growth factor (KGF) to the KGF receptor (KGFR) plays an important role in the recovery of alveolar epithelial cells from acute lung injury (ALI).

Objectives

To evaluate the effect of gene therapy via adenovirus gene transfer of KGFR on the treatment of ALI.

Methods

Sprague-Dawley rats were divided into four groups: normal controls, injury controls, normal adenovirus transduced group and injury adenovirus transduced group. The ALI model was induced by lipopolysaccharide (LPS) injection. Recombinant adenovirus (AdEasy-KGFR) was injected via the tail vein. Expression of the sodium (Na⁺) channel in rat alveolar type II (ATII) epithelial cells was determined by PCR, immunohistochemistry and immunoelectron microscopy of rat lung tissues.

Results

Gene expression of the Na⁺ channel and KGFR in ATII cells was higher in the normal adenovirus transduced group than the three other groups; expression of these two genes in the injury adenovirus transduced group was higher than the injury control group. Na⁺ channel protein expression was lower in the injury adenovirus transduced group but higher than the injury control group.

Conclusions

KGFR over-expression induced Na channel expression could potentially be beneficial for ALI therapy.     

Fallopian tube origin of supposed ovarian high-grade serous carcinomas

INTRODUCTION:

Serous carcinomas are the most frequent histologic type of ovarian and peritoneal cancers, and can also be detected in the endometrium and fallopian tubes. Serous carcinomas are usually high‐grade neoplasms when diagnosed, yet the identification of an associated precursor lesion remains challenging. Pathological examination of specimens obtained from prophylactic bilateral salpingo‐oophorectomies that were performed for patients harboring BRCA1/2 mutations suggests that high‐grade serous carcinomas may arise in the fallopian tubes rather than in the ovaries.

OBJECTIVE:

To investigate the presence and extent of fallopian tube involvement in cases of serous pelvic carcinomas.

METHODS:

Thirty‐four cases of serous pelvic carcinoma with clinical presentations suggesting an ovarian origin were analyzed retrospectively. Histologic samples of fallopian tube tissues were available for these cases and were analyzed. Probable primary site, type of tubal involvement, tissues involved in the neoplasia and vascular involvement were evaluated.

RESULTS:

Fallopian tube involvement was observed in 24/34 (70.6%) cases. In 4 (11.8%) of these cases, an intraepithelial neoplasia was present, and therefore these cases were hypothesized to be primary from fallopian tubes. For an additional 7/34 (20.6%) cases, a fallopian tube origin was considered a possible primary.

CONCLUSIONS:

Fallopian tubes can be the primary site for a subset of pelvic high‐grade serous carcinomas.     

Comparison between proximal row carpectomy and four-corner fusion for treating osteoarthrosis following carpal trauma: a prospective randomized study

OBJECTIVE:

To compare the functional results of carpectomy and four‐corner fusion surgical procedures for treating osteoarthrosis following carpal trauma.

METHODS:

In this prospective randomized study, 20 patients underwent proximal row carpectomy or four‐corner fusion to treat wrist arthritis and their functional results were compared. The midcarpal joint was free of lesions in all patients.

RESULTS:

Both proximal row carpectomy and four‐corner fusion reduced the pain. All patients had a decreased range of motion after surgery. The differences between groups were not statistically significant.

CONCLUSIONS:

Functional results of the two procedures were similar as both reduced pain in patients with scapholunate advanced collapse/scaphoid non‐union advanced collapse (SLAC/SNAC) wrist without degenerative changes in the midcarpal joint.     

Lung Morphometry,Collagen and Elastin Content: Changes after Hyperoxic Exposure in Preterm Rabbits

INTRODUCTION

Elastic and collagen fiber deposition increases throughout normal lung development, and this fiber network significantly changes when development of the lung is disturbed. In preterm rats and lambs, prolonged hyperoxic exposure is associated with impaired alveolization and causes significant changes in the deposition and structure of elastic fibers.

OBJECTIVES

To evaluate the effects of hyperoxic exposure on elastic and collagen fiber deposition in the lung interstitial matrix and in alveolarization in preterm rabbits.

METHODS

After c-section, 28-day preterm New-Zealand-White rabbits were randomized into 2 study groups, according to the oxygen exposure, namely: Room air (oxygen = 21%) or Oxygen (oxygen ≥ 95%). The animals were killed on day 11 and their lungs were analyzed for the alveolar size (Lm), the internal surface area (ISA), the alveoli number, and the density and distribution of collagen and elastic fibers.

RESULTS

An increase in the Lm and a decrease in the alveoli number were observed among rabbits that were exposed to hyperoxia with no differences regarding the ISA. No difference in the density of elastic fibers was observed after oxygen exposure, however there were fewer collagen fibers and an evident disorganization of fiber deposition.

DISCUSSION

This model reproduces anatomo-pathological injuries representing the arrest of normal alveolar development and lung architecture disorganization by just a prolonged exposition to oxygen.

CONCLUSIONS

In the preterm rabbit, prolonged oxygen exposure impaired alveolization and also lowered the proportion of collagen fibers, with an evident fiber network disorganization.     

Endoscopic ultrasound guided fine needle aspiration of non-pancreatic lesions: an institutional experience

Background

Endoscopic ultrasound guided fine needle aspiration biopsy (EUS‐FNA) has proven to be an effective diagnostic modality for the detection and staging of pancreatic malignancies. In recent years EUS‐FNA has also been used to diagnose lesions of non‐pancreatic sites such as structures in close proximity to the gut wall within the mediastinum, abdomen, pelvis and retro‐peritoneum.

Aims

To evaluate experience with EUS‐FNA of non‐pancreatic sites at a large university medical centre.

Methods

The study cohort included 234 patients who underwent EUS‐FNA of 246 lesions in non‐pancreatic sites (122 peri‐pancreatic and coeliac lymph nodes; 9 peri‐pancreatic masses; other sites: mediastinum 12, gastric 25, liver 27, oesophagus 17, duodenum/colon/rectum 15, retro‐peritoneum 8, lung 7, miscellaneous 4).

Results

The cytology diagnoses were classified as non‐neoplastic/reactive in 82 (33%), atypical/suspicious for malignancy in 25 (10%), malignant in 86 (35%) and non‐diagnostic in 53 (22%) cases. Surgical pathology follow‐up was available in 75 (31%) cases. Excluding the non‐diagnostic cases there were 7 false negative and 3 false positive cases. The sensitivity, specificity and positive predictive value of EUS‐FNA in the diagnosis of lesions of non‐pancreatic sites was 92%, 98% and 97%, respectively.

Conclusions

EUS‐FNA can be effectively used as a diagnostic modality in the diagnosis of lesions from non‐pancreatic sites.     

Follow-up after acute respiratory distress syndrome caused by influenza a (H1N1) virus infection

BACKGROUND:

There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome.

METHODS:

Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit.

RESULTS:

Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months.

CONCLUSIONS:

Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.     

Genetic association analysis of inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) variants with essential hypertension

Background

Inositol polyphosphate phosphatase‐like 1 (INPPL1, SHIP2) is a negative regulator of insulin signalling and has previously been found to be associated with hypertension, obesity and type 2 diabetes in a cohort of families with diabetes in the UK presenting features of metabolic syndrome. In particular, a haplotype of three genetic polymorphisms (rs2276047, rs9886 and an insertion/deletion polymorphism in intron 1) was found to be strongly associated with increased susceptibility to hypertension.

Objective and methods

To assess if INPPL1 variants play a direct role in the development of essential hypertension, we genotyped the three previously associated INPPL1 polymorphisms in a cohort of 712 families with severe hypertension from the BRIGHT study transmission disequilibrium test cohort.

Results

We found no evidence of significant association between hypertension and any of the three INPPL1 polymorphisms or haplotypes (p>0.1).

Conclusion

These results suggest that INPPL1 variants may be involved in mechanisms causing hypertension in metabolic syndrome patients specifically.     

Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

OBJECTIVE:

Blood neurotrophins, such as the brain‐derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain‐derived neurotrophic factor were evaluated in healthy individuals.

METHODS:

The concentric strengths of knee (large) and elbow (small) flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise.

RESULTS:

The levels of brain‐derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain‐derived neurotrophic factor in the arms and legs.

CONCLUSION:

The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain‐derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain‐derived neurotrophic factor.     

Impact of MELD allocation policy on survival outcomes after liver transplantation: a single-center study in northeast Brazil

OBJECTIVE:

To analyze the impact of model for end‐stage liver disease (MELD) allocation policy on survival outcomes after liver transplantation (LT).

INTRODUCTION:

Considering that an ideal system of grafts allocation should also ensure improved survival after transplantation, changes in allocation policies need to be evaluated in different contexts as an evolutionary process.

METHODS:

A retrospective cohort study was carried out among patients who underwent LT at the University of Pernambuco. Two groups of patients transplanted before and after the MELD allocation policy implementation were identified and compared using early postoperative mortality and post‐LT survival as end‐points.

RESULTS:

Overall, early postoperative mortality did not significantly differ between cohorts (16.43% vs. 8.14%; p = 0.112). Although at 6 and 36‐months the difference between pre‐ vs. post‐MELD survival was only marginally significant (p = 0.066 and p = 0.063; respectively), better short, medium and long‐term post‐LT survival were observed in the post‐MELD period. Subgroups analysis showed special benefits to patients categorized as non‐hepatocellular carcinoma (non‐HCC) and moderate risk, as determined by MELD score (15‐20).

DISCUSSION:

This study ensured a more robust estimate of how the MELD policy affected post‐LT survival outcomes in Brazil and was the first to show significantly better survival after this new policy was implemented. Additionally, we explored some potential reasons for our divergent survival outcomes.

CONCLUSION:

Better survival outcomes were observed in this study after implementation of the MELD criterion, particularly amongst patients categorized as non‐HCC and moderate risk by MELD scoring. Governmental involvement in organ transplantation was possibly the main reason for improved survival.     

Does minor histocompatibility antigen HA-1 disparity affect the occurrence of graft-versus-host disease in tunisian recipients of hematopoietic stem cells?

INTRODUCTION:

Minor histocompatibility antigen HA‐1 (MiHAg‐HA‐1) disparity between a patient and his or her human leukocyte antigen (HLA) genoidentical donor has been widely associated with an increased risk of graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation.

OBJECTIVE:

To examine the effect of HA‐1 disparity on the incidence of both acute and chronic graft‐versus‐host disease in Tunisian recipients of hematopoietic stem cells.

METHODS:

A total of 60 patients and their 60 respective sibling hematopoietic stem cell donors were enrolled in this study. All patients prophylactically received cyclosporine A and/or methotrexate for graft‐versus‐host disease. An HA‐1 genotyping assay was performed with the SSP‐PCR method, and HLA‐A*0201‐ and/or HLA‐A*0206‐positive samples were identified using the Luminex HLA typing method.

RESULTS:

The Luminex HLA typing assay showed that 54 patients were positive for either the HLA‐A*0201 or HLA‐A*0206 alleles. Among these cases, six pairs were mismatched for MiHAg‐HA‐1. Both acute and chronic graft‐versus‐host disease occurred in four mismatched patients (Fisher''s p‐values were 0.044 and 0.170, respectively). A univariate logistic regression model analysis showed that only acute graft‐versus‐host disease may be affected by recipient MiHAg‐HA‐1 disparity (p: 0.041, OR: 6.727), while chronic graft‐versus‐host disease correlates with both age and recipient/donor sex mismatch (p: 0.014, OR: 8.556 and p: 0.033, OR: 8.664, respectively).

CONCLUSION:

Our findings support previously reported data suggesting a significant association between HA‐1 disparity and the risk of acute graft‐versus‐host disease following hematopoietic stem cell transplantation.     

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure: demographics, etiologic and pulmonary histologic analysis

OBJECTIVES:

Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life.

METHODS:

This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression.

RESULTS:

In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema.

CONCLUSIONS:

For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.     

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

BACKGROUND:

Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients.

OBJECTIVE:

The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy.

METHODS:

Sixty‐five patients, treated in two tertiary‐care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor‐Node‐ Metastasis; Age‐Metastasis‐Extracapsular‐Size; distant Metastasis‐Age‐Completeness of primary tumor resection‐local Invasion‐Size and American‐Thyroid‐Association classification

RESULTS:

Patients ages ranged from 4 to 20 years (median 14). The mean follow‐up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease‐free status in follow‐up). Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014). The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy.

CONCLUSIONS:

Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.     

Speech and non-speech processing in children with phonological disorders: an electrophysiological study

OBJECTIVE:

To determine whether neurophysiological auditory brainstem responses to clicks and repeated speech stimuli differ between typically developing children and children with phonological disorders.

INTRODUCTION:

Phonological disorders are language impairments resulting from inadequate use of adult phonological language rules and are among the most common speech and language disorders in children (prevalence: 8 ‐ 9%). Our hypothesis is that children with phonological disorders have basic differences in the way that their brains encode acoustic signals at brainstem level when compared to normal counterparts.

METHODS:

We recorded click and speech evoked auditory brainstem responses in 18 typically developing children (control group) and in 18 children who were clinically diagnosed with phonological disorders (research group). The age range of the children was from 7‐11 years.

RESULTS:

The research group exhibited significantly longer latency responses to click stimuli (waves I, III and V) and speech stimuli (waves V and A) when compared to the control group.

DISCUSSION:

These results suggest that the abnormal encoding of speech sounds may be a biological marker of phonological disorders. However, these results cannot define the biological origins of phonological problems. We also observed that speech‐evoked auditory brainstem responses had a higher specificity/sensitivity for identifying phonological disorders than click‐evoked auditory brainstem responses.

CONCLUSIONS:

Early stages of the auditory pathway processing of an acoustic stimulus are not similar in typically developing children and those with phonological disorders. These findings suggest that there are brainstem auditory pathway abnormalities in children with phonological disorders.     

The novel IFNGR1 mutation 774del4 produces a truncated form of interferon-gamma receptor 1 and has a dominant-negative effect on interferon-gamma signal transduction

Background

Patients with interferon‐γ receptor 1 (IFNγR1) deficiency show selective susceptibility to intracellular pathogens such as mycobacteria. IFNγR1 deficiency is an inherited immunodeficiency disorder, which can be either recessive or dominant. Dominant forms of IFNγR1 deficiency are known to be associated with mutations that introduce a premature stop codon in the intracellular domain of IFNγR1. One such mutation, 818del4, is believed to be the most common type. Although these mutations are presumed to exert a dominant‐negative effect on IFNγ signal transduction, the underlying molecular mechanism is unresolved.

Objective

We characterised the 774del4 mutant of IFNγR1 using a gene‐expression system to examine the effects of this mutation on IFNγ signal transduction.

Results

We identified a novel dominant mutation in IFNGR1, designated 774del4, which produced a truncated form of IFNγR1 in a patient with recurrent mycobacterial infections. IFNγR1 was overexpressed on the surfaces of CD14‐positive cells from the peripheral blood of this patient, and STAT1 phosphorylation in response to high doses of IFNγ was partially deficient. We expressed two truncated forms of IFNγR1, 774del4 and 818del4, in HEK 293 cells using transient transfection and found that these mutants overexpressed IFNγR1 on the cell surface because of impaired receptor stability, which resulted in a dominant‐negative effect on IFNγ signal transduction.

Conclusion

Like the 818del4 mutation, 774del4 produces a truncated form of IFNγR1, which has a dominant‐negative effect on IFNγ signal transduction through altered receptor stability.     

Sensitivity and specificity of auditory steady-state response testing

INTRODUCTION:

The ASSR test is an electrophysiological test that evaluates, among other aspects, neural synchrony, based on the frequency or amplitude modulation of tones.

OBJECTIVE:

The aim of this study was to determine the sensitivity and specificity of auditory steady‐state response testing in detecting lesions and dysfunctions of the central auditory nervous system.

METHODS:

Seventy volunteers were divided into three groups: those with normal hearing; those with mesial temporal sclerosis; and those with central auditory processing disorder. All subjects underwent auditory steady‐state response testing of both ears at 500 Hz and 2000 Hz (frequency modulation, 46 Hz). The difference between auditory steady‐state response‐estimated thresholds and behavioral thresholds (audiometric evaluation) was calculated.

RESULTS:

Estimated thresholds were significantly higher in the mesial temporal sclerosis group than in the normal and central auditory processing disorder groups. In addition, the difference between auditory steady‐state response‐estimated and behavioral thresholds was greatest in the mesial temporal sclerosis group when compared to the normal group than in the central auditory processing disorder group compared to the normal group.

DISCUSSION:

Research focusing on central auditory nervous system (CANS) lesions has shown that individuals with CANS lesions present a greater difference between ASSR‐estimated thresholds and actual behavioral thresholds; ASSR‐estimated thresholds being significantly worse than behavioral thresholds in subjects with CANS insults. This is most likely because the disorder prevents the transmission of the sound stimulus from being in phase with the received stimulus, resulting in asynchronous transmitter release. Another possible cause of the greater difference between the ASSR‐estimated thresholds and the behavioral thresholds is impaired temporal resolution.

CONCLUSIONS:

The overall sensitivity of auditory steady‐state response testing was lower than its overall specificity. Although the overall specificity was high, it was lower in the central auditory processing disorder group than in the mesial temporal sclerosis group. Overall sensitivity was also lower in the central auditory processing disorder group than in the mesial temporal sclerosis group.