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SlideShare utilise les cookies pour ameliorer les fonctionnalites et les performances, et egalement pour vous montrer des publicites pertinentes. This report provides comprehensive information on the therapeutic development for Acute Sensorineural Hearing Loss, complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. Other mutations in the same gene have been found in dystonia-12 and alternating hemiplegia of childhood.
Demos MK, van Karnebeek CD, Ross CJ, Adam S, Shen Y, Zhan SH, Shyr C, Horvath G, Suri M, Fryer A, Jones SJ, Friedman JM; FORGE Canada Consortium.
Keywords: Neonatal hyperbilirubinaemia, Sensorineural hearing loss, Kernicterus, Exchange transfusion.
Incidence of hyperbilirubinaemia varies with ethnicity and geography, with incidence being high in East Asians, native Americans and Greek islanders, and low in African Americans. The major risk factors associated with pathological jaundice are worth taking a look at (Table-1).Of all these risk factors, prematurity appears to be the most significant. There are two major complications of hyperbilirubinaemia: acute bilirubin encephalopathy, and kernicterus.
We report two similar cases of infants with bilirubin levels that approached thresholds for exchange transfusion and subsequently developed sensorineural hearing loss as a consequence of neonatal hyperbilirubinaemia. The two cases being presented relate to the Aga Khan University Hospital (AKUH), Karachi, were they came separately between July 2012 and July 2013. Our first patient was a girlborn pre-term at 34 weeks of gestation after an uneventful pregnancy.
Neonatal hyperbilirubinaemia, a condition characterised by an excessive concentration of bilirubin in blood, remains the most common health issue in neonatal age group.
Some spontaneous improvement in auditory dysfunction as a complication of hyperbilirubinaemia in infants has been reported. Our patients developed unconjugated neonatal hyperbilirubinaemia that required exchange transfusion and subsequently developed early-onset sensorineural hearing loss as evidenced by the results of BAER. These cases emphasise the value of awareness among physicians regarding this condition that can help in timely detection of risk factors and prompt clinical monitoring and follow-up.
Although a final conclusion cannot be drawn from a Case Report, but from our two cases it seems re-assuring that the hearing loss may be transient, if developed after severe hyperbilirubinaemia. Neonatal hyperbilirubinaemia may be complicated by sensorineural hearing loss as auditory pathway is one of the most sensitive parts of the nervous system to this toxic agent, but if all possible risk factors are managed promptly with a vigilant follow-up, then these hazardous complications can be avoided. We are grateful to the patients and their families for giving their consent for publishing this report. This journal is a member of and subscribes to the principles of the Committee on Publication Ethics. OTOLARYNGOLOGY free pdf ebook was written by Enrica Aguilera on November 02, 1999 consist of 52 page(s). You're reading the first 10 out of 52 pages of this docs, please download or login to readmore. Severe acute respiratory syndrome, better known by its acronym SARS, is an atypical form of pneumonia. After the People's Republic of China suppressed news of the outbreak both internally and abroad, the disease spread rapidly, reaching neighbouring Hong Kong and Vietnam in late February 2003, and then to other countries via international travellers.
In May 2005, the New York Times reported that "not a single case of severe acute respiratory syndrome has been reported this year or in late 2004. The virus appears to have originated in Guangdong province in November 2002, and despite taking some action to control the epidemic, the People's Republic of China did not inform the World Health Organisation (WHO) of the outbreak until February 2003, restricting coverage of the epidemic in order to preserve face and public confidence. In early April, there appeared to be a change in official policy when SARS began to receive a much greater prominence in the official media. In late April, revelations occurred as the PRC government admitted to underreporting the number of cases due to the problems inherent in the healthcare system.
The epidemic reached public spotlight in February 2003, when an American businessman travelling from China came down with pneumonia-like symptoms while on a flight to Singapore. Study objectives: To characterize the long-term pulmonary function and health status in a prospectively identified cohort of patients who survived the severe acute respiratory syndrome (SARS).
Patients: Ninety-four patients who recovered from SARS were assessed at a uniform time point of 1 year after hospital discharge. Measurements: The study included the measurement of static and dynamic lung volumes, the determination of the diffusing capacity of the lung for carbon monoxide (DLCO), and a health status evaluation using the St. Conclusions: One year after recovery from SARS, persistent pulmonary function impairment was found in about one third of patients. The severe acute respiratory syndrome (SARS) is a recently described condition caused by infection with a coronavirus (CoV) (1) and is characterized by both an atypical pneumonia and efficient nosocomial transmission. First recognized in March 2003, SARS spread across the globe, caused many major outbreaks, and had an overall mortality rate of 11% (2) but was successfully contained in < 4 months. The purpose of this study was to characterize the long-term pulmonary function and health status in a prospectively identified cohort of patients who survived SARS in Singapore.
There were 206 cases of SARS in Singapore reported to the World Health Organization as of June 26, 2003. Pulmonary function tests at 1 year after hospital discharge included spirometry, and measurements of total lung capacity and diffusing capacity of the lung for carbon monoxide (DLCO).
Comparisons between groups were done with the Student t test for normally distributed continuous variables and with Mann-Whitney U tests for nonnormally distributed continuous variables. The baseline characteristics of the enrolled patients during their hospital admission for SARS are shown in Table 1. Comparing the SARS survivors who were enrolled in this study with those who were not included, there was no significant difference with regard to age, gender, steroid exposure, or severity of the acute illness as indicated by the length of hospitalization, the requirement for intensive care or mechanical ventilation, and the highest recorded serum lactate dehydrogenase (LDH) level (Table 2). At 1 year after hospital discharge, with regard to respiratory symptoms that were present at least a few days a month over the preceding year, 28 patients (30%) had cough, 19 (9.0%) had increased sputum production, 28 (30%) had shortness of breath, and 7 (7%) had occasional wheezing. Table 5 shows the serial pulmonary function data of 17 patients in the present study who were detected to have abnormalities from among a group of patients who had been evaluated at 3 months after hospital discharge in an earlier study. Impaired pulmonary function is present in about one third of patients 1 year after their recovery from SARS. To date, reported studies on the functional outcomes of patients during the recovery stage of SARS are limited, (3-6,9) and none has evaluated the outcomes at a uniform 1-year time point. The finding of higher prevalence of dynamic lung volume abnormalities than DLCO impairment in the present study, together with the significant improvement in DLCO but not dynamic lung volumes in serial lung function testing of a subset of our patients, suggest that DLCO abnormalities can improve with time.


The exact pathologic cause(s) of the pulmonary dysfunction in recovered SARS patients is not known. In contrast to the results of the earlier study (5) among patients averaging 28 days in the posthospital discharge period, significantly worse scores were not found in the symptoms domain of the SGRQ among our SAILS survivors at 1 year. In summary, 1 year after recovery from SARS, persistent pulmonary function impairment was found in about one third of patients.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjourual. Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS): a new syndrome.
Acute bilirubin encephalopathy and kernicterus are known to be the two major complications associated with it, resulting in neurotoxic effects, including sensorineural hearing loss, hypotonia, delayed motor skills and intellectual deficits. To the best of our knowledge, these are the first reported cases from Pakistan that showed some spontaneous improvement over time in sensorineural hearing loss acquired as a complication of neonatal hyperbilirubinaemia. Written consent was obtained from the parents of the patients for sharing our experience with the two babies.
No complications were noted during pregnancy or delivery with Activity-Pulse-Grimace-Appearance-Respiration (APGAR) score being 8 at 1 minute and 9 at 5 minutes. A retrospective study found spontaneous improvement in hearing loss in about 50% of infants within 15 months of diagnosis. Prompt management with phototherapy and exchange transfusion and regular follow-up of the cases revealed spontaneous improvement in hearing loss. Large-scale studies are required to confirm our findings and to determine the appropriate course of action which should ensure that timely intervention does take place, but dramatic interventions like cochlear implantation should only be opted for after a thorough follow-up and evidence of a stable condition without spontaneous improvement.
Follow-up of all infants and of appropriate family counselling regarding all possible outcomes, including remission, is necessary. It first appeared in November 2002 in Guangdong Province of the People's Republic of China. This lack of openness caused the PRC to take the blame for delaying the international effort against the epidemic. However, it was also in early April that accusations emerged regarding the undercounting of cases in Beijing military hospitals. The health status of SARS survivors was also significantly worse compared with the healthy population.
Although it has been > 1 year since the illness was successfully contained, published data on the condition of those who survived the illness are limited. The protocol and equipment used for pulmonary function testing in this study were similar to those used in an earlier study (9) that we conducted among recovered SARS patients. The linear regression model was used to study the association between known prognostic indicators of SARS and the 1-year pulmonary function outcomes, as well as the association between mechanical ventilation parameters during the acute illness and 1-year pulmonary function outcomes.
Of the seven enrolled patients who had required mechanical ventilation, the mean duration of mechanical ventilation was 1.5 days compared with 11 days for the five patients who required mechanical ventilation among the 80 survivors who were not included in this study.
The group means of forced expiratory volumes, static lung volumes, and diffusion capacity were all within normal limits (ie, > 80% predicted). In assessing long-term outcomes after acute lung injury, it is important to attempt the consecutive enrollment of survivors with defined time points for study, because there is a possibility of bias toward the selection of sicker patients with abnormal pulmonary function test results if studies enrolled any patient who returned for a follow-up evaluation.
Adverse long-term pulmonary sequelae of the ARDS include lung fibrosis, but untreated bronchiolitis obliterans-organizing pneumonia and bronchiolitis obliterans may 'also contribute to the physical morbidity in ARDS survivors.
First, the heterogeneity of acute lung disease encompassed by the case definition of SARS may account for the observed variation in pulmonary and extrapulmonary sequelae among our patients.
The health status of SARS survivors was also significantly worse compared with that of the healthy population. Consultez notre Politique de confidentialite et nos Conditions d’utilisation pour en savoir plus. We report two similar cases of neonatal jaundice requiring exchange transfusion that subsequently developed sensorineural hearing loss.
Maternal and neonatal risk factors present in the two cases were noted separately (Tables-2 and 3). No neonatal problems or trauma during normal vaginal delivery resulting in cephalohematoma or ecchymoses was reported. Urgent clinical need for accurate and precisebilirubin measurement the United States to prevent kernicterus. Incidence of neonatal hyperbilirubinemia: a population-based prospective study in Pakistan. Risk factors associated with hearing loss in term neonates with hyperbilirubinemia.J Trop Pediatr. Risk factors for neonatal jaundice inbabies presenting at the University of Benin Teaching Hospital, Benin City.
Follow-up studies of patients with neonatal icterus using acoustic evoked potential audiometry. After intense pressure, PRC officials allowed international officials to investigate the situation there.
Several of the doctors and nurses who had attempted to treat him soon came down with the same disease despite basic hospital procedures. Several studies (3-9) have reported persistent symptoms, as well as radiologic and functional abnormalities during follow-up several weeks or months after hospital discharge, but the prevalence and severity of the longterm sequelae of SARS remain largely unknown.
Survivors at 1 year after hospital discharge were eligible for enrollment in the study if they were [greater than or equal to] 21 years of age. The difference in the mean duration of mechanical ventilation between these two subsets of patients was not statistically significant (p = 0.443). As measured by the SGRQ, SARS survivors had significant worsening in health status compared with the healthy population.
This appears to be in contrast to information from several reviews (22,23) on survivors of the ARDS documenting the persistence of a mild reduction in DLCO as the most common abnormality found in pulmonary function testing, and that DLCO remained low in long-term follow-ups. In studies among survivors of ARDS, it is known that nearly all of the patients are symptomatic at hospital discharge, but there is significant improvement over the first year after ARDS in most patients.
Second, the proportion of patients who declined evaluation may have led to a bias toward the selection of sicker patients with abnormal pulmonary function. Chong in the preparation of the manuscript, as well as that of the staff of the Respiratory Function Laboratory, Tan Toek Seng Hospital.


This has revealed problems plaguing the aging mainland Chinese healthcare system, including increasing decentralization, red tape, and inadequate communication.
He reported that there were more SARS patients in his hospital alone than were being reported in all of China. Because lung function is known to improve for up to 1 year after discharge from the hospital in survivors of other causes of acute lung injury, (10,11) it is imperative that long-term studies of SARS survivors be conducted in order to determine the persistence of abnormalities in pulmonary function, and whether these abnormalities contribute to permanent impairment and disability.
Patients were excluded from the study if they had been immobile before being admitted to hospital for SARS, had a history of pulmonary resection, or had a documented neurologic or psychiatric disease. SGRQ scores were calculated using score calculation algorithms and missing data imputation recommended by its developer. The conventional level of statistical significance of 0.05 was used for all of the analyses.
Overall, pulmonary function defects were detected in half of the recovered SARS patients at 3 months after hospital discharge. Interestingly, all of the articles on ARDS survivors reporting normal lung volumes or very low rates of either obstruction or restriction were published earlier when cohorts were likely more heterogeneous, and lung injuries in the surviving population were most likely less severe. This is likely, because most of the patients who declined participation in the study offered a lack of symptoms and inconvenience as the main reasons for doing so. This report aims at increasing awareness of this condition among physicians to allow early detection of risk factors and prompt management and follow-up. A number of PRC officials were fired from their posts, including the health minister and mayor of Beijing, and systems were set up to improve reporting and control in the SARS crisis. The virulence of the symptoms and the infection of hospital staff alarmed global health authorities fearful of another emergent pneumonia epidemic.
As the majority of patients with SARS survive the illness (2) and medical personnel, physicians, nurses, and hospital workers are among those commonly infected in most countries, (2) an additional requisite for the identification and quantification of morbidity among survivors may be for the consideration of awarding compensation.
The diagnosis of SARS was confirmed by a positive serology result for SARS-CoV in all except 1 of the 94 patients enrolled in this study. For each subscale and for the overall questionnaire, scores range from 0 (no impairment) to 100 (maximum impairment). Domain scores other than the symptoms domain of the SGRQ were significantly higher (ie, worse) than the population norms (Table 6). The finding in the present study of persistent pulmonary function abnormalities in a significant proportion of SARS patients 1 year after hospital discharge is notable, not only for the long-term follow-up and management of these patients but also as a highlight of the permanent respiratory impairment that can result from the acute infection.
The presence of fibrosis was associated with significantly lower pulmonary function variables. Third, evaluations of arterial blood gas levels and exercise testing were not performed in this study. Since then, the PRC has taken a much more active and transparent role in combatting the SARS epidemic. On March 12, 2003, the WHO issued a global alert, followed by a health alert by the United States Centers for Disease Control and Prevention (CDC).
Total lung capacity and its subdivisions were measured by the nitrogen washout method with the spirometer, the testing adhered to standard criteria.
Because there were cases of patients with impairment in more than one of the four variables, the number of patients with mild and moderate impairment according to the ATS recommendations was 30 (32%) and 5 (5%), respectively.
Viral pneumonia usually resolves without any clinical or radiologic sequelae, whereas SARS-related radiologic sequelae appear to be quite common among survivors, as observed by several studies. It would be interesting to compare structural and functional changes in survivors of SARS during late recovery to see whether a similar correlation persists and whether these changes are different from those observed in ARDS survivors whose condition is not related to SARS. However, we did not anticipate that there was significant hypoxemia in these patients, because none of them was found to have hypoxemia or was assessed as requiring oxygen supplementation during routine follow-up. Table 4 shows the pulmonary function data of these 35 patients who had respiratory impairment. In an earlier study (9) evaluating pulmonary function and exercise capacity among patients from the same cohort, we found no evidence of exercise limitation solely because of ventilatory constraints, and there were very few patients with significant oxygen desaturation during exercise. Cardiopulmonary responses to exercise in SARS survivors had been evaluated in an earlier study (9) at 3 months after hospital discharge, but we do not have any longer term data on this.
Brainstem audiometry-evoked potential (BAER) was done on 13th day of life that showed severe bilateral peripheral auditory pathway dysfunction. Glucose-6-phosphate dehydrogenase deficiency (G6PD) level was 5.0 thus showing the neonate to be G6PD-deficient. She was regularly followed up and improvement in hearing was first noted at 8 months of life when she started responding to verbal commands. BAER done on 16th dayof life showed severe bilateral peripheral auditory pathway dysfunction. The four most common preexisting illnesses were hypertension (six patients), bronchial asthma (five patients), treated pulmonary tuberculosis (three patients), and diabetes mellitus (two patients). Corticosteroid myopathy may be a contributory factor, although only a small percentage of our patients had received treatment with steroids during their acute illness.
A generic health status measure, such as the Medical Outcomes Study 36-item short-form health survey, would have provided a more global assessment of the patients, especially with regard to their role limitations as a result of emotional problems, mental health, bodily pain, and general health perceptions. At a follow-up visit at 1 year 3 months of age, she was able to hear fine and at 2 years, her speech was normal for age. Magnetic resonance imaging (MRI) done on 16th day of life showed changes of hyperbilirubinaemia encephalopathy. The interaction of the data obtained from generic and disease-specific measures of health status may also have helped to determine the contributions of pulmonary and nonpulmonary factors to the longterm health status of SARS survivors. Spontaneous improvement in hearing was first noted at the age of 1 year when he started speaking words and responding to verbal commands. The preexisting medical conditions that may affect pulmonary function in the patients with pulmonary function abnormalities are as shown in Table 4.




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