Spindle Cell Carcinoma: A Confirmatory Diagnostic Analysis by Immunohistochemical Studies

Introduction: WHO defines it as a ‘‘carcinoma within which there are some elements resembling a squamous cell carcinoma that are admixed with a spindle cell component. Spindle cell carcinoma is an uncommon poorly differentiated type of SCC com- prising up to 3% of SCC and it is also known as sarcomatoid carcinoma which is a rare biphasic malignant neoplasm. . Case Report: A 20 year old female patient complains of pain and growth in lower front teeth region since 3 months and gave a history of growth 2yrs back in the front teeth region for which she has been operated but it has recurred again. Discussion: The histological features mimicked other connective tissue sarcomas & spindle cell malignancies at light micro- scopic level. Hence, after undergoing immunohistochemistryA careful study based on clinical, radiological and histopathologi- cal and immunohistochemical examination was done and a final diagnosis of spindle cell carcinoma was given.

Study of parenting styles, family functioning and its relation to coping strategies in children of specific learning disorder

Background: Families of children with disabilities otherwise experience higher stress; and relation between parenting styles and coping of children is well known. Parental factors and family functioning may play a role in shaping the child, especially having issues like SLD. The objective is to study was coping strategies of children with SLD, parenting styles of their parents, their family functioning and relation of these with each other.Methods: It is a cross-sectional study undertaken after Institutional Ethics Committee approval, parent's consent and child's assent. Participants were 100 consecutive children, diagnosed with SLD, 9-13 years of age. Tools used were: Semi-structured proforma, Parenting Practices Questionnaire, Family Assessment Device and Children's Coping Strategies Checklist Revision 1.Results: Authoritarian parenting style was significantly was associated with less use of 'active' and 'support seeking'; and increased use of 'distraction' and 'avoidance' strategies. High scores on Authoritative style was associated with 'active' and 'support seeking' strategies. Avoidance coping strategy was associated with poor (high scores) and active coping strategies with higher (low scores) on problem solving, communication, and general family functioning.Conclusions: Parenting practices and family functioning can be pivotal in determining child's attitude and coping. Assessment of this can be routinely included in child evaluation.

The Study of Phenomenology, Family Factors, Functioning and Quality of Life in Childhood and Adolescent Depression

Background and Objectives: Depression is a common psychiatric illness. The illness can present as asimple sadness to a major depressive disorder or even bipolar disorder. It is also found to affect childrenand adolescents. The aims and objectives of our study were, to assess the phenomenology, family factors,quality of life and functional status of children and adolescents with depression.Methodology: Subjects diagnosed with depression, before 18 years of age, were recruited in the study.Parents and children were interviewed. Demographic details were taken. Scales i.e. Children DepressionInventory, Family Assessment Device, The PedsQL core generic scale and Children's Global Assessmentscale were applied.Results: Females had slightly higher scores on CDI. On using Pearson’s correlation test significantcorrelations were found between the Family Assessment Device and PedsQL scale and CDI scale.Conclusion: In the population under study, the family functioning was found to be unhealthy in familiesof girls with depression, versus families in which boys had depression. Overall depressive features were lessin families with better affective responsiveness and affective involvement. In families who did not useproblem solving as coping, somatic complaints were more. Better expression of emotions and behavioralcontrol, was found in families having clear role definition

INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for Primary Care Physician: Development and Validation.

Objectives: To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings. Study design: Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study. Setting: Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India. Participants: 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI). Intervention: All study subjects were first administered INDTNMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard). Results: According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and ‘Normal’ group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDTNMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as ‘indeterminate’, 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs. Conclusion: Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.

INCLEN Diagnostic Tool for Epilepsy (INDT-EPI) for Primary Care Physicians: Development and Validation.

Objective: To evaluate the diagnostic accuracy of a new diagnostic instrument for epilepsy – INCLEN Diagnostic Tool for Epilepsy (INDT-EPI) – with evaluation by expert pediatric neurologists. Study design: Evaluation of diagnostic test. Setting: Tertiary care pediatric referral centers in India. Methods: Children aged 2-9 years, enrolled by systematic random sampling at pediatric neurology out-patient clinics of three tertiary care centers were independently evaluated in a blinded manner by primary care physicians trained to administer the test, and by teams of two pediatric neurologists. Outcomes: A 13-item questionnaire administered by trained primary care physicians (candidate test) and comprehensive subject evaluation by pediatric neurologists (gold standard). Results: There were 240 children with epilepsy and 274 without epilepsy. The candidate test for epilepsy had sensitivity and specificity of 85.8% and 95.3%; positive and negative predictive values of 94.0% and 88.5%; and positive and negative likelihood ratios of 18.25 and 0.15, respectively. Conclusion: The INDT-EPI has high validity to identify children with epilepsy when used by primary care physicians.

INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD): Development and Validation.

Objective: To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD). Design: Diagnostic test evaluation by cross sectional design. Setting: Tertiary care pediatric centers. Participants: 156 children aged 65-117 months. Methods: After randomization, INDT-ADHD and Connor’s 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. Main outcome measures: Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. Results: INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner’s Parents Rating Scale was moderate (r =0.73, P= 0.001). Conclusions: INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD): Development and Validation.

Objective: To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD). Design: Diagnostic test evaluation by cross sectional design Setting: Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India. Methods: Children aged 2-9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard). Main outcome measures: Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. Results: 154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P<0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for ‘ASD group’ was 82.52% [Cohen’s κ=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = -0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance. Conclusion: INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder.

Effect of Progressive Resistance Exercise Training on Hepatic Fat in Asian Indians with Non-Alcoholic Fatty Liver Disease.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance and lifestyle measures form the cornerstone of therapy. Objective: To study the effect of progressive resistance training (PRT) on hepatic fat content, body composition and insulin sensitivity in patients with NAFLD. Methods: This study included 24 adult patients with NAFLD diagnosed on ultrasonography. Subjects with alcohol intake >140 gm/week and any secondary cause of fatty liver were excluded. Patients underwent thrice weekly sessions (40 minutes each) of resistance exercises including flexion at biceps, triceps, and hip flexion, knee extension and heel rise for 12 weeks. Pre- and post-intervention evaluation included anthropometry, BIA analysis, short insulin tolerance test (SITT), lipid profile and hepatic fat quantification by MRI. Results: Twenty four patients (17 males, 7 females, mean age 39.8±10.5 yrs) completed the study protocol with 78.7% compliance to PRT protocol. There was significant decrease in waist, hip and mid-thigh circumferences and skinfold thicknesses at biceps, triceps, subscapular and suprailiac regions (p<0.05), with no significant change in BMI and WHR. Insulin sensitivity improved significantly at 12 weeks as indicated by increase in k-value (rate of change of glucose) on SITT (0.84 vs 1.3, p=0.002). A decrease in total cholesterol and LDL-c with increase in HDL-c was noted after 12 weeks (p<0.05). Hepatic fat content also decreased at 12 weeks (22.3±3.9 vs 21.4±4.0 %, p=0.01). Conclusion: Moderate intensity PRT is associated with significant improvement in hepatic fat, truncal subcutaneous fat and insulin sensitivity in patients with NAFLD.

Synthesis of multiple biologically active 1, 2-dihydro-pyrimido [1, 2-A]-benzimidazole-3- carbonitrile.

A variety of 1,2-dihydropyrimido-[1,2-a]-benzimidazole-3-carbonitrile derivatives were synthesized under microwave irradiation using water and acetonitril as solvent system. All the compounds were tested in vitro for α-glucosidase inhibitory and DPPH free radical scavenging activity. 4-Amino-2-(4-flourophenyl)-1,2-dihydropyrimido [1,2-a]-benzimidazole-3-carbonitrile (4c) was found to be a potent intestinal α- glucosidase inhibi tory activity (IC50; 91μM) along with moderate DPPH scavenging property. This compound was further evaluated for cytotoxicity activity against HT-29 colon cancer cell line. The IC50 value for its cytotoxicity activity was found to be 662 μM.

Cyanide-induced changes in the levels of neurotransmitters in discrete brain regions of rats and their response to oral treatment with a-ketoglutarate.

Cyanide is a potential suicidal, homicidal and chemical warfare agent. It produces histotoxic hypoxia following inhibition of cytochrome c oxidase, a terminal respiratory chain enzyme. The profound metabolic changes lead to neurotoxicity including alterations in the levels of neurotransmitters. The present study addressed the effect of acute exposure of lethal and sub-lethal doses of potassium cyanide (KCN; 0.75 or 2.0 LD50; po) on the levels of neurotransmitters in discrete brain regions of rats and its response to treatment with a-ketoglutarate (-KG; 0.5 g/kg; po; -10 min) alone or with sodium thiosulphate (STS; 1.0 g/kg; ip; -15 min). KCN significantly decreased norepinephrine, dopamine and 5-hydroxytryptamine levels in different brain regions which were resolved by a-KG and/or STS. Corpus striatum and hippocampus were more sensitive as compared to cerebral cortex and hypothalamus. -KG, a potential cyanide antidote alone or with STS showed neuroprotective effects against cyanide.

Nephrogenic fibrosing dermopathy.

An adult female patient on hemodialysis for chronic renal failure presented with large, brownish, and indurated plaques with bound-down skin on both lower limbs and abdomen along with difficulty in movement of the legs. Histopathological features revealed thick collagen bundles admixed with mucin and intercalating spindle-like cells characteristic of nephrogenic fibrosing dermopathy (NFD). Immunohistochemical study showed prominent CD68 positivity and weak CD34 positivity suggesting that the plaques were more than 20-weeks old. NFD in patients with chronic renal failure of unknown cause is a poor prognostic indicator. Early detection before the development of contracture and prompt treatment of NFD and underlying renal failure may reverse this disabling condition.

Nucleus management in manual small incision cataract surgery by phacosection.

Nucleus management is critical in manual small incision cataract surgery (MSICS), as the integrity of the tunnel, endothelium and posterior capsule needs to be respected. Several techniques of nucleus management are in vogue, depending upon the specific technique of MSICS. Nucleus can be removed in toto or bisected or trisected into smaller segments. The pressure in the eye can be maintained at the desired level with the use of an anterior chamber maintainer or kept at atmospheric levels. In MSICS, unlike phacoemulsification, there is no need to limit the size of the tunnel or restrain the size of capsulorrhexis. Large well-structured tunnels and larger capsulorrhexis provide better control on the surgical maneuvers. Safety and simplicity of MSICS has made it extremely popular. The purpose of this article is to describe nucleus management by phacosection in MSICS.

Secretory factors of human neuroblastoma (IMR-32) and human glioblastoma (U87MG) cell lines induce neurite outgrowths in PC12 cells.

Neurite outgrowth is essential for the communication of the nervous system. The rat Pheochromocytoma (PC12) cells are commonly used in the neuronal cell study. It is well known that exogenous stimuli such as Nerve Growth Factor (NGF) induce neurite outgrowth. In the present study it has been investigated whether or not the conditioned medium from human neuroblastoma cell line (IMR-32) and human glioblastoma cell line (U87MG) may augment neurite outgrowth in PC12 cells. PC12 were cultured with and without conditioned media of IMR-32 and U87MG. The result showed that both the conditioned media induce neurite outgrowth within 48 hr and stops further proliferation of PC12 cells. However no outgrowth was noted in PC12 cells incubated without conditioned medium. In conclusion, it is shown that both the conditioned media (IMR-32 and U87MG) have the potential to induce the neurite outgrowth in the PC12 cells.

Association of DNA pattern of metastatic lymph node with disease free survival in patients with intraoral squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: Intraoral squamous cell carcinoma (OSCC) is one of the common tobacco related cancers affecting Indian population. These tumours are slow growing, endophytic and are mostly well differentiated. Cervical lymph node is the common site of metastasis of these tumours. In most of the patients cervical lymph node metastasis rather than the primary tumour, affects prognosis. However, no reports are available on the DNA pattern of the metastatic lymph nodes in patients with intraoral squamous cell carcinoma. Therefore, the present study was undertaken to observe DNA pattern of primary tumours and their corresponding metastatic lymph nodes and its association with the clinicopathological parameters and prognosis. METHODS: DNA flow cytometry was successfully carried out on 68 paraffin embedded specimens of the primary tumours and their 22 corresponding metastatic cervical lymph nodes. The findings were evaluated for their possible association with clinicopathological features of the tumour and disease free survival of patients with intraoral carcinoma. RESULTS: Analysis of nuclear DNA patterns revealed 32 (47.0%) diploidy and 36 (52.9%) aneuploidy in primary tumours whereas metastatic lymph nodes showed 7 (31.8%) diploidy and 15 (68.1%) aneuploidy. The aneuploidy group in metastatic lymph node had significantly higher S phase fraction (SPF) (P<0.01) and poor histological grade (P<0.002) as compared to their counterparts with diploidy. DNA pattern of metastatic lymph node further showed a significant association with disease free survival in the log rank test. Aneuploidy and high SPF in metastatic lymph node was found to be associated with early recurrence while DNA pattern of the primary tumour did not show significant association with the disease free survival. INTERPRETATION AND CONCLUSION: It may be concluded that aneuploidy and high SPF in metastatic lymph node might be considered as an important discriminatory risk factor in patients with similarly staged intraoral squamous cell carcinoma.

A prospective randomized double masked controlled clinical trial to determine the efficacy of multiple drop centbucridine as an ocular surface anaesthetic.

In this study, the ocular surface anaesthetic and analgesic efficacies of 0.5% and 1% centbucridine both in saline were compared with 4% lignocaine drops in distilled water in normal healthy volunteers divided into three equal groups. In 99 healthy eyes, keeping one eye as an unanaesthetized control, one drop of any of the above three coded drugs was instilled in the contralateral eye, followed by one more drop of the same drug in the same eye after 3 minutes. The oneset of anaesthesia, achievement and duration of peak activity, total duration of action, the depth of analgesia, and period of burning sensation were all noted in this double-masked randomized controlled trial with the various drug solutions. Total peak duration of anaesthetic as well as analgesic effects in the 99 healthy normal eyes were found to be the highest with centbucridine 1%, followed by 4% lignocaine and 0.5% centbucridine respectively.

In-vivo slit scanning confocal microscopy of normal corneas in Indian eyes.

OBJECTIVE: To study the cellular populations of healthy corneas of Indian eyes using confocal microscopy and to evaluate the correlation with age, gender and laterality. METHODS: The central corneas of 100 eyes of 50 healthy subjects were examined using an in-vivo slit scanning confocal microscope (Confoscan 2). Images were analysed for cell densities of the epithelium, stroma and endothelium. RESULTS: Good quality images enabling analysis of all cell layer populations were obtained in 74 eyes of 43 healthy subjects (22 males and 21 females) with a mean age of 31.89 +/- 13.47 (range 19-71 years). The basal epithelial cell density was 3601.38 +/- 408.19 cells/mm2 (range 3017.3-4231.1 cells/mm2). The mean keratocyte nuclei density in the anterior stroma was 1005.02 +/- 396.86 cells/mm2 (range 571.6-1249.6 cells/mm2) and in the posterior stroma was 654.32 +/- 147.09 cells/mm2 (range 402.6-1049.1 cells/mm2). Posterior keratocyte nuclei density was 30.76% less than the anterior stromal keratocyte nuclei density. The difference in keratocyte nuclei density was statistically significant (P=0.001). The mean endothelial cell density was 2818.1 +/- 361.03 cells/mm2 (range 2118.9-4434 cells/mm2) and the mean endothelial cell area was found to be 385.44 +/- 42.66 mm2 (range 268.9-489.2 mm2). Hexagonal cells formed 22.5-69.4% of the endothelial cell populations (mean 42.04 +/- 11.81%). Mean coefficient of cell size variation was 32.29 +/- 3.06 (range 27.2-39.2). No statistically significant differences were found in cell densities of any corneal layer either between female and male patients or between right and left eyes. Basal epithelial cell density, anterior stromal keratocyte nuclei and posterior stromal keratocyte nuclei density were unaffected by age (r=0.12, 0.07, -0.12 respectively) (P=0.001). There was a statistically significant negative correlation between mean endothelial cell density and increase in age (r=-0.42, P=0.001). Coefficient of cell size variation and age were positively correlated (r=0.73, P=0.001). CONCLUSION: In-vivo slit scanning confocal microscopy is useful for the study of corneal cell populations. Our study provides normative data of these cell populations.

Risk factors for mortality within first 24 hours of head injury.

OBJECTIVE: Immediate or instantaneous death following cranial trauma occurs due to unpreventable primary brain insults. However, death occurring within 24 hours of head injury can be averted by timely institution of the therapeutic measures that could prevent secondary brain insults. From the management point of view, this is the most important subset of all head injured patients. Therefore, it is important to study risk factors associated with such deaths. METHODS: In a retrospective study undertaken at Trauma Center, Safdarjang Hospital, New Delhi, the demographic characteristics, neurological and radiological findings were studied for 100 head injured children admitted in the pediatric surgical ward, who later died after surviving the initial neurosurgical resuscitation. Death occurring within first 24 hours of head injury was defined as "early" death; and "late death", if it occurred thereafter. RESULTS: Bivariate analysis revealed the severity of head injury GCS<=8 (OR: 3.09; 95% CI: 1.22-7.8), a finding of diffuse brain edema, (OR: 3.73; 95% CI: 0.95-14.74), midline shift (OR: 4.8; 95% CI: 1.03-22.37) on cranial CT scans were found to be statistically associated with early deaths. Child's age or gender, the mode of injury and the presence of extracerebral injuries were not found to be significantly associated. When these variables were simultaneously considered in a multivariate logistic regression model, the diffuse brain edema on head CT scan was found to be both clinically and statistically significant of early death (Adj. OR: 527; 95% CI: 1.23-22.6). However, absence of hemorrhagic contusion was clinically important predictor of an early death (Adj. OR: 6.45; 95% CI: 0.68.-62.5) though not statistically significant

Outdoor air pollution and emergency room visits at a hospital in Delhi.

Several reports from large metropolitan cities have indicated significant association between acute morbidity and mortality from cardio-respiratory disorders and daily levels of major pollutants in the ambient air. Despite the wide-spread public concern about the adverse health effects of air pollution, there is substantial uncertainty regarding the effects of these pollutants at a concentration typical of Delhi, which is one of the ten most polluted cities in the world and the most polluted city in India. This study was undertaken to correlate the daily levels of various pollutants with the number of patients visiting the All India Institute of Medical Sciences (AIIMS, New Delhi) casualty for aggravation of certain defined cardiorespiratory disorders. Daily counts of patients visiting the emergency room of the AIIMS for acute asthma, acute exacerbation of chronic obstructive airway disease (COAD) and acute coronary event was obtained in prospective manner from January 1997 to December 1998. Daily mean levels of ambient CO, NOx and SO2 were monitored along with temperature and humidity. Data was analysed using one day time lag for events of interest. Time series analysis was undertaken using Poisson regression and population averaged general estimation equation, correcting for auto-correlation, days of the weak and season. The ambient levels of pollutants exceeded the national air quality standards on most of the days, over the two year period. Further, emergency room visits for asthma, COAD and acute coronary events increased by 21.30%, 24.90% and 24.30% respectively on account of higher than acceptable levels of pollutants. It is concluded that there is considerable burden of cardiorespiratory diseases in Delhi due to high levels of ambient air pollution.