Innovative cost-effective method to repair lacrimal cannaliculi laceration - finding proximal end and stent.

Purpose: To explore a new technique to find out the proximal end of lacerated canaliculi and a new material for the stent. Methods: Surgery was performed on 9 eyes of 9 patients using a 5/0 prolene suture needle as a modified probe. Prolene suture was inserted as a stent and left in place for two months. All the data were analyzed. Results: The surgery was successful in all cases and the prolene were removed after two months. The mean follow-up time after the tube removal was 3.8 months (range 3-6 months). No other complications associated with the prolene sutures were noticed except for epiphora and corneal irritation in three cases. All the tubes were removed successfully without any difficulty. No iatrogenic injuries occurred during prolene removal. Conclusions: The reported surgical technique is a very cost-effective option for lacrimal canalicular laceration repair.

The role of biosimilars in value-based oncology care.

Biopharmaceuticals (biologics) represent one of the fastest growing sectors of cancer treatment. They are recommended for treating underlying cancer and as supportive care for management of treatment side effects. Given the high costs of cancer care and the need to balance health care provision and associated budgets, patient access and value are the subject of discussion and debate in the USA and globally. As the costs of biologics are high, biosimilars offer the potential of greater choice and value, increased patient access to treatment, and the potential for improved outcomes. Value-based care aims to improve the quality of care, while containing costs. The Centers for Medicare & Medicaid Services (CMS) has developed value-based care programs as alternatives to fee-for-service reimbursement, including in oncology, that reward health care providers with incentive payments for improving the quality of care they provide. It is anticipated that CMS payments in oncology care will be increasingly tied to measured performance. This review provides an overview of value-based care models in oncology with a focus on CMS programs and discusses the contribution of biosimilars to CMS value-based care objectives. Biosimilars may provide an important tool for providers participating in value-based care initiatives, resulting in cost savings and efficiencies in the delivery of high-value care through expanded use of biologic treatment and supportive care agents during episodes of cancer care.

Comparative study of visual outcome between open- and closed-globe injuries following surgical treatment of traumatic cataract in children.

OBJECTIVE: To compare final visual outcomes of surgically treated traumatic cataract between open-globe and closed-globe injuries in children, as classified by the Birmingham Eye Trauma Terminology system. METHODS: This is an observational cohort study with permission from Hospital Ethical Committee. We enrolled children meeting specific inclusion criteria, examined their eyes to review any co-morbidities due to trauma, performed surgery for traumatic cataracts, and implanted lenses. The patients were re-examined postoperatively. We classified the cases of traumatic cataract as either open-globe (Group 1) or closed-globe (Group 2) according to the Birmingham Eye Trauma Terminology system and compared visual acuity. RESULT: Our study cohort of 1076 eyes with traumatic cataracts included 405 eyes in Group 1 and 671 in Group 2. Postoperatively, the visual acuity was >20/60 in 223 (55.3%) and 377 (56.3%) operated eyes in Groups 1 and 2, respectively ( p < 0.001, analysis of variance). With further follow-up, >20/60 vision was significantly higher in Group 2 as compared to Group 1 (odds ratio = 1.61; 95% confidence interval = 0.85-3.02). Overall, 600 eyes (55.7%) regained final visual acuity >20/60. CONCLUSION: Closed-globe injury has more favourable prognosis for the satisfactory (>20/60) visual recovery after effective management of traumatic cataracts in children.

Regression analysis and categorical agreement of fluconazole disk zone diameters and minimum inhibitory concentration by broth microdilution of clinical isolates of Candida.

AIM AND OBJECTIVES: Rampant use of fluconazole in Candida infections has led to predominance of less susceptible non-albicans Candida over Candida albicans. The aim of the study was to determine if zone diameters around fluconazole disk can be used to estimate the minimum inhibitory concentration (MIC) for clinical isolates of Candida species and vice versa. Categorical agreement between the Clinical & Laboratory Standards Institute (CLSI) recommended disk diffusion and CLSI broth microdilution method was sought for. MATERIAL AND METHODS: Antifungal susceptibility testing by disk diffusion and Broth microdilution was done as per CLSI document M44-S3 and CLSI document M27-S4 for Candida isolates respectively. Regression analysis correlating zone diameters to MIC value was done. Pearson's correlation coefficient was calculated to determine correlation between disk zone diameters and MICs. RESULTS: Candida albicans (33.3%) was clearly outnumbered by other non-albicans species predominantly Candida tropicalis (42.5%) and Candida glabrata (18.4%). Ten percent of the strains were resistant to fluconazole by disk diffusion and 13% by broth microdilution. MIC range for Candida albicans and Candida tropicalis ranged from≤0.25-64µg/ml while that of Candida glabrata ranged from≤0.25-128µg/ml. Categorical agreement between disk diffusion and broth microdilution was 86.8%. Pearson's coefficient of correlation was -0.5975 indicating moderate negative correlation between the two variables. CONCLUSION: Zone sizes can be used to estimate the MIC values, although with limited accuracy. There should be a constant effort to upgrade the guidelines in view of new clinical data, and laboratories should make an active effort to incorporate them.

Successful repair of injury to the eyelid, lacrimal passage, and extraocular muscle.

INTRODUCTION: Injury is a known cause of monocular blindness. Ocular trauma may affect lacrimal canaliculi and the extraocular muscle. We report this case as it includes injury to lid, lacrimal canaliculi and inferior rectus. CASE DESCRIPTION: A 25-year-old male presented with an injury caused by a sharp object that resulted in a conjunctival tear, lid tear involving the lacrimal canal, and rupture of the inferior rectus muscle. All of the structures were repaired successfully during a single procedure. CONCLUSION: An extraocular injury involving the conjunctiva, lid, lacrimal passages, and extraocular muscles can be repaired successfully during a single procedure.

Significance of IFN-ɤ/IL-2 Ratio as a Circulating Diagnostic Biomarker in Extrapulmonary Tuberculosis.

Extrapulmonary tuberculosis (EPTB) remains a challenging diagnosis both for clinicians and microbiologists. We hypothesized that the profile of IFN-ɤ/IL-2 ratio in clinically diagnosed cases of EPTB would be distinct from that of age- and sex-matched healthy controls. Therefore, in our study, we have assessed the ratio of serum levels of IFN-ɤ and IL-2 in clinically diagnosed cases of EPTB to assess their potential role as diagnostic biomarkers. Sixty-nine (69) clinically confirmed EPTB cases and 69 age- and sex-matched healthy controls were included in the study. All the extrapulmonary specimens were subjected to Ziehl-Neelsen staining for acid-fast bacilli and culture on Lowenstein-Jensen (LJ) medium. Detection of serum levels of IFN-ɤ and IL-2 was carried out using commercially available ELISA kits following manufacturers' instructions. The ratio of serum levels of IFN-ɤ and IFN-ɤ/IL-2 was discriminative for the diagnosis of EPTB cases (p < 0.001), although the same was not observed with IL-2 (p > 0.05). Distribution of all biomarkers significantly differed between culture-positive and culture-negative cases (p < 0.05). Among the smear-positive and smear-negative ones, only IFN-ɤ and IFN-ɤ/IL-2 ratio could significantly differentiate (p < 0.05). Ratio of IFN-ɤ and IL-2 rather than the individual levels was the best discriminatory biomarker with the highest area under the ROC curve. Although IFN-ɤ and IFN-ɤ/ IL-2 ratio could aid in the diagnosis of EPTB, IL-2 has a limited utility in the diagnosis of EPTB. Further elaborate studies to validate these results are required.

Expression of Podoplanin in Different Grades of Oral Squamous Cell Carcinoma.

BACKGROUND: The expression of podoplanin is up-regulated in a number of different human cancers, including squamous cell carcinoma of the oral cavity and its relationship with tumor invasion raises the possibility that podoplanin expression could be used as a biomarker for diagnosis and prognosis. AIM: The aim of the present study is to evaluate the expression of podoplanin in different grades of squamous cell carcinoma (SCC) and to correlate the expression of podoplanin with relevant clinical features such as age, sex, site and associated habits. MATERIALS AND METHODS: Retrospective study was carried on formalin fixed, paraffin embedded blocks of oral SCC (OSCC) from the archives of Department of Oral and Maxillofacial Pathology, Vishnu Dental College, Bhimavaram. Thirty diagnosed cases were included, of which 10 were well-differentiated SCC (WDSCC) (n = 10), 10 moderately DSCC and 10 poorly DSCC. Demographics including age, sex, gender and associated habit history, were recorded. Immunohistochemical staining was done with podoplanin anti D2-40 antibody, for all the cases of OSCC and assessed qualitatively. The data obtained were tabulated and subjected to statistical analysis. RESULTS: In the present study, 27 cases of SCC showed podoplanin expression and remaining three cases showed no expression. The scoring criterion suggested by Yuan et al. was followed for semi-quantitative assessment. OSCC, seven cases presented weak expression (Immunoreactive score [IRS] 0-3), 15 presented moderate expression (IRS Score 4-7) and 5 presented high expression (IRS Score > 8). The assessment of podoplanin expression in the cytoplasm, the membrane and the cytoplasm and membrane (both) of tumor cells showed overall high positivity in the cytoplasmic followed by both and the membrane. CONCLUSION: Podoplanin could be a potent biomarker in assessing the cytoplasm/membrane staining of tumor cells. Furthermore, a high level of podoplanin expression is suggestive of high frequency of lymph node metastasis and immature status in the differentiation process of OSCC.

Recurrent paediatric pinworm infection of the vagina as a potential reservoir for Enterobius vermicularis.

Enterobius vermicularis infection remains one of the most common parasitic infections, particularly prevalent in children. Enterobiasis, although not usually dangerous, may cause significant morbidity. Elimination of the parasite from a family or an institution often poses problems, either because of an incomplete cure or re-infection. While there have been limited reports of ectopic enterobiasis throughout the world, ours is probably one of the rarest reports of recurrent vaginal E. vermicularis infection in the absence of any gastrointestinal symptoms despite complete treatment. A 4-year-old girl presented with recurrent episodes of vulval itching on 3-4 occasions over 2 years. There was no pruritis ani nor urinary/gastrointestinal complaints. The vulva was inflamed with 4-5 living worms, 6-7 mm in length, emerging from the anterior vaginal fornix, but with no vaginal discharge. Direct microscopic examination of vaginal swabs revealed adult worms of Enterobius but no eggs. Repeated stool samples from the patient, parents and a sibling were negative. The patient was treated orally with 100 mg of mebendazole for 3 days followed by two more courses at 3-week intervals over a period of 3 months. Recurrent vaginal enterobiasis despite complete treatment and in the absence of any gastrointestinal involvement suggests that the vagina is a potential reservoir for E. vermicularis, which supports the theory of rare ectopic enterobiasis through the ascending pathway of the female genital tract.

Current status of multidrug resistant tuberculosis in a tertiary care hospital of East Delhi.

BACKGROUND AND OBJECTIVE: Multidrug resistant tuberculosis (MDR-TB) is caused by infection due to Mycobacterium tuberculosis which is resistant to both isoniazid (INH) and rifampicin (RIF). It is caused by selection of resistant mutant strains due to inadequate treatment and poor compliance. MDR-TB is a major public health problem as the treatment is complicated, cure rates are well below those for drug susceptible tuberculosis and patient remains infectious for months despite receiving the best available therapy. The drug susceptibility pattern of M. tuberculosis is essential for proper control of MDR-TB in every health care setting, hence the study was initiated with the aim of studying the prevalence of MDR-TB in patients attending a tertiary care hospital in east Delhi. MATERIALS AND METHODS: Five hundred and forty-three pulmonary and extrapulmonary samples from suspected cases of tuberculosis received in the mycobacteriology laboratory from November 2009 through October 2010 were investigated for M. tuberculosis. All the samples were subjected to direct microscopic examination for demonstration of acid fast bacilli followed by culture on Lowenstein-Jensen (LJ) medium to isolate M. tuberculosis. Identification was done by conventional biochemical methods. Drug susceptibility of isolated M. tuberculosis strains was done by conventional 1% proportion method followed by sequencing of RIF resistant isolates to detect mutations to confirm resistance. RESULTS AND CONCLUSIONS: M. tuberculosis was isolated from 75 out of 543 suspected cases of pulmonary/extrapulmonary TB. Three of the total 75 M. tuberculosis isolates (4%) showed resistance to any one of the first line drugs. Prevalence of MDR-TB was 1.3%. The sequencing of single MDR strain showed mutations at codons 516, 517, and 518. Amplification of rpoB and sequential analysis of the amplicon is a better way of detection of mutation and the evidence of new mutation in this study indicate that mutations continue to arise, probably due to the ability of M. tuberculosis to adapt to drug exposure.

Blast lung: experience at CIMS.

Blast lung is a clinical condition which is characterised by respiratory difficulty and hypoxia without obvious external injury to the chest in bomb blast cases. Two patients of the bomb blast episode were brought at emergency department at Chhattisgarh Institute of Medical Sciences, Bilaspur in a state of shock. After proper wound care, resuscitation and investigation both the cases proved to be that of blast lung. In bomb blast cases although there might not be any external injury over chest wall, it will be sensible to rule out blast lung in all cases with the help of computerised tomography.

Awareness of changing trends in epidemiology of dengue fever is essential for epidemiological surveillance.

Dengue has become endemic in India with outbreaks occurring almost every year. The seroprevalence and serotypic data of the last 7 years in samples obtained from suspected dengue patients from a tertiary care hospital were analyzed. Out of 7846 serum samples received in the virology laboratory from suspected dengue cases during 2002 to 2008, 2366 (30.15%) were serologically confirmed. Serotyping was done using mRT-PCR. All the four serotypes were detected in 2003, while data in 2004, 2005 and 2006 revealed the the predominance of Den-3. In the year 2007 predominance of Den-2 was observed, whereas in 2008 Den-1 was the most common serotype isolated. Overall, Den-2 and Den-3 were the most predominant serotypes during 2003-2007 but Den-1 replaced these strains in the year 2008. Since the emergence of a new predominant strain can lead to the occurrence of an outbreak, presence of Den-1 in the year 2008 would pose an alarming situation before us. Well-targeted population-based epidemiological studies are urgently required to control dengue menace.

Mitochondrial electron transport chain functions in long-lived Ames dwarf mice.

The age-associated decline in tissue function has been attributed to ROS-mediated oxidative damage due to mitochondrial dysfunction. The long-lived Ames dwarf mouse exhibits resistance to oxidative stress, a physiological characteristic of longevity. It is not known, however, whether there are differences in the electron transport chain (ETC) functions in Ames tissues that are associated with their longevity. In these studies we analyzed enzyme activities of ETC complexes, CI-CV and the coupled CI-CII and CII-CIII activities of mitochondria from several tissues of young, middle aged and old Ames dwarf mice and their corresponding wild type controls to identify potential mitochondrial prolongevity functions. Our studies indicate that post-mitotic heart and skeletal muscle from Ames and wild-type mice show similar changes in ETC complex activities with aging, with the exception of complex IV. Furthermore, the kidney, a slowly proliferating tissue, shows dramatic differences in ETC functions unique to the Ames mice. Our data show that there are tissue specific mitochondrial functions that are characteristic of certain tissues of the long-lived Ames mouse. We propose that this may be a factor in the determination of extended lifespan of dwarf mice.

Profile of direct walk-in and referred clients attending Integrated Counselling and Testing Centre.

The HIV pandemic has had a profound impact on the health and economic conditions of individuals, and people living with HIV/AIDS are faced with the task of maintaining optimal health status despite an increasing insult to their immune status. The aim of the present study was to study the profile of direct walk-in and referred patients attending the Integrated Counselling and Testing Centre (ICTC) of a tertiary care hospital, which may provide important clues to understanding the epidemiology of the disease in a particular region. The study included all the attendees of the ICTC referred from the hospital or direct walk-in from January 2007 to December 2007. Three rapid HIV tests were used and the samples showing positive results in all the three tests were declared HIV positive. The results were analysed to correlate between HIV positivity, age, sex, route of transmission and direct walk-in/referred patients. A low proportion of ICTC attendees (27%) in our study were direct walk-ins. As regards HIV positivity, 312 (8.3%) out of 2440 males and 164 (4.3%) out of 1315 females were HIV positive. Among the referred HIV-positive patients 162 were males and 62 females, whereas among the direct walk-in HIV-positive patients, 150 were males and 102 females. Integrated counselling and testing is now seen as a key entry point for HIV prevention. In addition to scaling up ICTC services, it is also important to raise awareness by aggressive health education programmes and integration of ICTC into various community organizations.

Cytomegalovirus infection: an Indian perspective.

Human cytomegalovirus (CMV) poses an important public health problem as it may cause serious morbidity and mortality in congenitally infected newborns and immunocompromised patients, most notably transplant recipients and HIV-infected persons. It is probably one of the most common infections known to humans and is characterized by a self-limiting infection in healthy individuals. CMV infection is the single most frequent cause of infectious complications in the early period following kidney transplantation Post-transfusion cytomegalovirus infection is of concern in the immunocompetent as well as in certain categories of immunocompromised individuals such as neonates, pregnant women, recipients of bone marrow and other organ transplants and individuals with immunodeficiency disorders. The emergence of AIDS in India has necessitated the establishment of reliable tests for diagnosis of cytomegalovirus infection as a damaged immune system permits cytomegalovirus reactivation. The magnitude of this problem in India and the various diagnostic modalities used have not been adequately investigated and, hence, CMV infection is still a major health problem warranting strong preventive measures. The ultimate goal of the prevention program is to develop a vaccine that can be administered to seronegative women of childbearing age to prevent primary infection during pregnancy.

Age-related alterations in oxidatively damaged proteins of mouse skeletal muscle mitochondrial electron transport chain complexes.

Age-associated mitochondrial dysfunction is a major source of reactive oxygen species (ROS) and oxidative modification to proteins. Mitochondrial electron transport chain (ETC) complexes I and III are the sites of ROS production and we hypothesize that proteins of the ETC complexes are primary targets of ROS-mediated modification which impairs their structure and function. The pectoralis, primarily an aerobic red muscle, and quadriceps, primarily an anaerobic white muscle, have different rates of respiration and oxygen-carrying capacity, and hence, different rates of ROS production. This raises the question of whether these muscles exhibit different levels of oxidative protein modification. Our studies reveal that the pectoralis shows a dramatic age-related decline in almost all complex activities that correlates with increased oxidative modification. Similar complex proteins were modified in the quadriceps, at a significantly lower level with less change in enzyme and ETC coupling function. We postulate that mitochondrial ROS causes damage to specific ETC subunits which increases with age and leads to further mitochondrial dysfunction. We conclude that physiological characteristics of the pectoralis vs quadriceps may play a role in age-associated rate of mitochondrial dysfunction and in the decline in tissue function.

Onychomycosis--epidemiology, diagnosis and management.

Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts or nondermatophyte molds and represents about 30% of mycotic cutaneous infections. Increasingly onychomycosis is being viewed as more than a mere cosmetic problem. In spite of improved personal hygiene and living environment, onychomycosis continues to spread and persist. The prevalence rate of onychomycosis is determined by age, predisposing factor, social class, occupation, climate, living environment and frequency of travel. Onychomycosis in immunocompromised patients can pose a more serious health problem. Dermatophytes are the most frequently implicated causative agents in onychomycosis. Previously regarded as contaminants, yeasts are now increasingly recognised as pathogens in fingernail infections, as are some moulds. Clinical diagnosis of onychomycosis is based on the patients' history; a physical examination, microscopy and culture of nail specimens. The treatment of onychomycosis has been attempted throughout the ages, but only in the last two decades have safe, effective systemic treatments been available for this chronic superficial fungal disease. Oral Griseofulvin and Ketoconazole; once the agents of choice for the treatment of onychomycosis, have been superseded by newer systemic compounds that have a higher cure and lower relapse rates, cause fewer side effects and are suitable for short-term dosing.

Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes.

Mitochondrially generated ROS increase with age and are a major factor that damages proteins by oxidative modification. Accumulation of oxidatively damaged proteins has been implicated as a causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain (ETC) complexes I and III are the principle sites of ROS production, and oxidative modifications to their complex subunits inhibit their in vitro activity. We hypothesize that mitochondrial complex subunits may be primary targets for modification by ROS, which may impair normal complex activity. This study of heart mitochondria from young, middle-aged, and old mice reveals that there is an age-related decline in complex I and V activity that correlates with increased oxidative modification to their subunits. The data also show a specificity for modifications of the ETC complex subunits, i.e., several proteins have more than one type of adduct. We postulate that the electron leakage from ETC complexes causes specific damage to their subunits and increased ROS generation as oxidative damage accumulates, leading to further mitochondrial dysfunction, a cyclical process that underlies the progressive decline in physiologic function of the aged mouse heart.

Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers.

The endoplasmic reticulum (ER) is a target for endogenously generated reactive oxygen species (ROS) during aging. We have previously shown that the ER chaperones, protein disulfide isomerase (PDI) and immunoglobulin heavy chain binding protein (BiP), are oxidatively modified within the livers of aged mice. In this study we assess the functional consequences of the age-dependent oxidation of these two proteins. Specific activity measurements, performed on purified protein samples obtained from young and aged mouse livers, show definitive decreases in BiP ATPase activity and dramatic reductions in PDI enzymatic activity with age. Overall, these results suggest that protein folding and other activities mediated through PDI and BiP are diminished during aging. Furthermore, the relative loss of these chaperone-like activities could directly contribute to the age-dependent accumulation of misfolded proteins, a characteristic of the aging phenotype.

Age-related increases in oxidatively damaged proteins of mouse kidney mitochondrial electron transport chain complexes.

Mitochondrial dysfunction generates reactive oxygen species (ROS) which damage essential macromolecules. Oxidative modification of proteins, DNA, and lipids has been implicated as a major causal factor in the age-associated decline in tissue function. Mitochondrial electron transport chain complexes I and III are the principal sites of ROS production, and oxidative modifications to the complex subunits inhibit their in vitro activity. Therefore, we hypothesize that mitochondrial complex subunits may be primary targets for oxidative damage by ROS which may impair normal complex activity by altering their structure/function leading to mitochondrial dysfunction associated with aging. This study of kidney mitochondria from young, middle-aged, and old mice reveals that there are functional decreases in complexes I, II, IV, and V between aged compared to young kidney mitochondria and these functional declines directly correlate with increased oxidative modification to particular complex subunits. We postulate that the electron leakage from complexes causes specific damage to their subunits and increased ROS generation as oxidative damage accumulates, leading to further mitochondrial dysfunction, a cyclical process that underlies the progressive decline in physiologic function seen in aged mouse kidney. In conclusion, increasing mitochondrial dysfunction may play a key role in the age-associated decline in tissue function.

Lower levels of F2-isoprostanes in serum and livers of long-lived Ames dwarf mice.

F2-isoprostanes (IsoPs), lipid peroxidation products, are markers that quantitatively measure levels of oxidative stress. IsoP levels increase in tissues and serum of aging animals suggesting an increase in oxidative stress. This supports the Free Radical Theory of Aging, which proposes that elevated levels of reactive oxygen species (ROS) cause macromolecular damage, and is a factor in the age-associated decline in tissue function. Numerous studies have shown that the longevity of long-lived mutant mice correlates with their resistance to oxidative stress. However, although the Ames dwarf (DW) mice show resistance to oxidative stress, it has not been shown that these mice have inherently lower levels of ROS. Our results show that the serum and liver IsoP levels in DW mice are lower at all ages suggesting that the lower levels of endogenous ROS production in DW mice may be a factor in their resistance to oxidative stress and longevity.