Hearing acuity in post spinal analgesia period

100 cases of either sex 96 males and 4 females in their mean age group of 45 year ± 14.51 standard deviation were selected for this study to analyse the Hearing Acuity in the post spinal analgesia period during a period of eight months in the E.N.T department of the J.N. Medical College A.M.U. Aligarh. The size of the needle used for spinal analgesia was 22G and the equipment for Audiometry was the pure tone Audiometer. Pure tone Audiometry was done pre-operatively and then on the 1st, 3rd, 5th and 12th subsequent post-operative days and then after six months. It was found that 12% of the patients showed incidence of mild hearing loss. However, the loss was transient, reversible, within low frequency range (250, 500, 1000 Hz), and no patient suffered from any permanent hearing loss.     

Prophylaxis in RSV infection (Palivizumab)--is it worthwhile?

Respiratory syncytial virus (RSV) is a recognised cause of lower respiratory tract infection in infants and young children. It causes severe respiratory disease in preterm infants with or without chronic lung disease. This study, conducted at Waterford Regional Hospital, evaluates the incidence of RSV infection in hospitalised children, its seasonal variation, and effectiveness of its prevention. Thirty eight percent of admitted children with bronchiolitis were RSV positive in the year 1999 November to March is the peak season for this infection. A highly selected group of 7 preterm children with or without chronic lung disease received Palivizumab prophylaxis. Not one of them acquired RSV infection. The high cost of Palivizumab was the main factor for its restricted use. Palivizumab was found to be effective in preventing RSV infection in our study. Since we had a small number of patients, further studies are needed for its economic and judicious use. Respiratory syncytial virus (RSV) is virulent easily transmissible and the most common cause of lower respiratory tract disease in children of less than 2 years of age. Up to 98% of children attending day care will be infected in single RSV season. Between 0.5% and 3.2% of children with RSV infection require Hospitalisation. Approximately 90,000 hospital admissions and 4500 deaths per year were reported in United States. In Ireland 2807 patients were admitted with Bronchiolitis in 1998. Major risk factors for hospitalisation due to RSV are Prematurity, chronic lung disease, congenital heart disease, compromised immunity and age younger then 6 weeks in otherwise healthy children. No effective treatment of RSV positive bronchiolitis beside supportive care in the form of adequate nutrition and oxygen therapy is available. Antiviral therapies such as Ribavirin has not been proved to be effective in RSV infection. Bronchodilators show variable results. Corticosteroids were not found effective. There is no effective vaccine available as yet. There is no proven method for active immunity. Various immunoglobulins are available for acquiring passive immunity against RSV infection. PREVENT study group in Jan. 1997 showed intravenous immunoglobulin (RSV- IGIV) use in reducing 41% to 63% hospitalisation in RSV patients. But RSV-IGIV was not licensed outside the United States because of risk of transmission of blood borne products, difficulty in administration ie. intravenous access, large fluid volume (15 ml/kg), high protein load (750 mg/kg), shortage of supply and need to postpone live vaccine (eg. MMR, varicella). monoclonal antibody Palivizumab was developed for prophylaxis against RSV infection. Clinical safety and efficacy of Palivizumab were demonstrated in IMpact trial published in Sept. 1998. Reduction in hospitalisation up to 55% was noted in this study. It was a pivotal randomised, double blind, placebo controlled phase 3 study conducted in 139 centres throughout Canada, United States and United Kingdom. We looked at our experience in patients admitted with bronchiolitis in Waterford Regional Hospital. We described the outcome of carefully selected Seven children of high risk group for Palivizumab prophylaxis. Its clinical Implications and cost effectiveness was evaluated in this study.     

PSTPIP1‐associated myeloid‐related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia

Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline‐serine‐threonine phosphatase‐interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1‐associated myeloid‐related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.     

The Achilles’ heel of cancer survivors: fundamentals of accelerated cellular senescence

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment–induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment–related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.

Cancer survival times have increased annually owing to advances in early detection and treatment that prolong patient survival. However, increasing survivorship has underscored the observation that cancer survivors develop age-related diseases prematurely, which cause significant morbidity, health expenditures, and mortality. Many cancer survivors have been exposed to chemotherapy, radiotherapy, or both; despite eradicating cancer cells, these therapies also damage normal cells to accelerate biologic aging, such that a discrepancy exists between their biologic and chronologic age (1). Considerable data exist regarding the phenotypes of accelerated aging. However, mechanical and molecular uncertainties have limited the study of these manifestations in a clinical context. Our Review discusses accelerated aging phenotypes in cancer survivors and the cellular mechanisms underpinning these phenomena. We then discuss the translational evidence on how accelerated aging phenotypes, mainly related to senescence, are being targeted while highlighting areas of uncertainty for future research to address.     

Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF) and possible role of oxidative stress

Hormesis, a biphasic dose–response phenomenon, which is characterized by stimulation of an end point at a low‐dose and inhibition at a high‐dose. In the present study we used human lungs fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) in hormetic effects of non coplanar PCB 101. Results from 3‐(4,5‐dime‐thylthiazol‐2‐yl)‐2,5‐diphenyltetrazo‐lium bromide (MTT) assay indicated that PCB101 at lower concentrations (10^?5 to 10^?1 μg mL^?1) stimulated HELF cell proliferation and inhibited at high concentrations (1, 5, 10, and 20 μg mL^?1) in a dose‐ and time‐dependent manner. Reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) (except 48 h) showed a significant increase at higher concentrations of PCB 101 than those at the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase (GSH‐Px) exhibited decreasing trends in dose and time dependent manner. Lipid peroxidation assay resulted in a significant increase (P < 0.05) of MDA level in PCB 101‐treated HELF cells compared with controls, suggesting that OS plays a key role in PCB 101‐induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB 101 exposure compared to lower concentrations. Overall, we found that HELF cell proliferation was higher at low ROS level and vice versa, which revealed activation of cell signaling‐mediated hormetic mechanisms. The results suggested that PCB 101 has hormetic effects to HELF cells and these were associated with oxidative stress. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1385–1392, 2015.     

Analysis of misoprostol and chlorhexidine policy gains in Pakistan: the advocacy experience of Mercy Corps Pakistan

While Pakistan has made progress toward achieving Millennium Development Goal 5 for maternal health, it is unlikely to achieve the target; further, it is also not on track for Millennium Development Goal 4 regarding child health. Two low-cost, temperature stable and life-saving drugs, misoprostol and chlorhexidine, can respectively avert maternal and newborn deaths, and are particularly pertinent for poor and marginalized areas which bear the brunt of maternal and newborn deaths in Pakistan. In response, Mercy Corps led focused advocacy efforts to promote changes in policies, protocols, and regulatory environments for misoprostol (2012–2014) and for chlorhexidine (2014). These short-duration advocacy projects facilitated significant policy gains, such as inclusion of misoprostol and chlorhexidine into province-specific essential drug lists, development and endorsement of clinical protocols for the two drugs by provincial health departments, inclusion of misoprostol into pre-service training curriculum for several health cadres, and application for registration of chlorhexidine (at the concentration required for newborn care) by two pharmaceutical companies. These results were achieved by a consultative and evidence-based process which generated feedback from community members, program implementers, and policymakers, and ultimately put the government in the driver’s seat to facilitate change. Community Action Dialogue forums were linked with provincial-level Technical Working Groups and Provincial Steering Committees, who passed on endorsed recommendations to the Health Secretary. The key factors which facilitated change were the identification of champions within the provincial health departments, prioritization of relationship building and follow-up, focus on concrete advocacy aims rather than broad objectives, and the use of multi-stakeholder forums to secure an enabling environment for the policy changes to take root. While these advocacy initiatives resulted in significant policy changes in Pakistan’s devolved health system, to ensure these policy changes have an impact on health outcomes, Pakistan should focus on the scale-up of appropriate use of chlorhexidine and misoprostol. Further, future policy initiatives in Pakistan should make use of similar multi-stakeholder policy forums, while ensuring a third party to facilitate the process so that civil society and community voices are not lost in the policy development discussion.     

Identification of hemoglobin Q India (α 1–64 Asp–His) through ARMS-PCR. First report from Pakistan

Various hemoglobinopathies have been reported from Pakistan excepting the rare ones like hemoglobin Q India. Our purpose of study was to identify the mutation (α 1 64 aspartate to histidine) through amplification restriction mutation system-polymerase chain reaction (ARMS-PCR) in patients where hemoglobin Q has been detected via high performance liquid chromatography (HPLC) and also to evaluate the cost effectiveness of the two technologies. All patients irrespective of age and gender who underwent HPLC for identification of their hemoglobin variant during January 1, 2006 to January 30, 2007 were studied. The blood samples with unknown peak at a retention time of 4.7 min were evaluated at the molecular level. Analysis of HPLC tracings of 11,008 subjects over a thirteen-month period identified ten individuals with hemoglobin Q. Male to female ratio was 1:1.5 and their age was variable ranging from 1 to 49 (mean 22.8) years. The mean hemoglobin level was 11.3 g/dl while MCV (fl) and MCH (pg) were 73.0 and 20.8 respectively. HPLC showed an unknown peak of 17.7% which was detected as Hb Q. ARMS based PCR showed Hb Q specific product of 370 bp and also an amplified product of 766 bp as the control fragment in these samples. This is the first ever report that documents the presence of Hb Q India (α 64 Asp to His) in Pakistani population. We recommend that HPLC be used as a useful screening tool especially in developing countries where PCR facilities may not be accessible.