Head to head comparison between neurology residents and a mobile medical application for diagnostic accuracy in cognitive neurology.

BACKGROUND: A novel Mobile Medical Application (App) App was created on iOS platform (Neurology Dx®) to deduce Differential Diagnoses (DDx) from a set of user selected Symptoms, Signs, Imaging data and Lab findings. The DDx generated by the App was compared for diagnostic accuracy with differentials reasoned by participating neurology residents when presented with same clinical vignettes. METHODS: Hundred neurology residents in seven leading Neurology centers across India participated in this study. A panel of experts created 60 clinical vignettes of varying levels of difficulty related to Cognitive neurology. Each neurology resident was instructed to formulate DDx from a set of 15 cognitive neurology vignettes. Experts in Cognitive Neurology made the gold standard DDx answers to all 60 clinical vignettes. The differentials generated by the App and neurology residents were then compared with the Gold standard. RESULTS: Sixty clinical vignettes were tested on 100 neurology residents (15 vignettes each) and also on the App (60 vignettes). The frequency of gold standard high likely answers accurately documented by the residents was 25% compared with 65% by the App (95% CI 33.1-46.3), P < 0.0001. Residents correctly identified the first high likely gold standard answer as their first high likely answer in 35% (95% CI 30.7-36.6) compared with 62% (95% CI 14.1-38.5), P < 0.0001. CONCLUSION: An App with adequate knowledge-base and appropriate algorithm can augment and complement human diagnostic reasoning in drawing a comprehensive list of DDx in the field of Cognitive Neurology (CTRI/2017/06/008838).

Status epilepticus: why, what, and how.

Status epilepticus (SE) is an important neurological emergency with high mortality and morbidity. The first official definition of SE was the product of 10 th Marseilles colloquium held in 1962 which was accepted by International League Against Epilepsy in 1964. There are as many types of SE as of seizures. SE is supposed to result from failure of normal mechanisms that terminate an isolated seizure. In half of the cases, there is no history of epilepsy and SE is precipitated by some intercurrent infection. In children, it is often infection, whereas in adults, the major causes are stroke, hypoxia, metabolic derangements, and alcohol intoxication or drug withdrawal. The treatment of SE aims at termination of SE, prevention of seizure recurrence, management of precipitating causes, and the management of complications. The extent of investigations done should be based on the clinical picture and cost benefit analysis. The first line antiepileptic drugs (AED) for SE include benzodiazepines, phenytoin, phosphenytoin, and sodium valproate. Mortality of SE ranges between 7 and 39% and depends on underlying cause and response to AEDs.

Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of aspirin in preventing stroke and mortality in tuberculous meningitis (TBM). METHODS: Patients with TBM diagnosed on the basis of clinical, MRI and cerebrospinal fluid (CSF) criteria were randomized into aspirin 150 mg daily or placebo. All the patients received four drug antitubercular treatment- RHZE (rifampicin, isoniazide, pyrazinamide and ethambutol) with or without corticosteroid. The primary endpoint was MRI proven stroke at 3 months and secondary end points were mortality and functional outcome assessed by Barthel Index score at 3 months. The adverse drug reactions were also analyzed. RESULTS: 118 TBM patients were randomized into aspirin and placebo groups. The baseline demographic, clinical (severity of meningitis, MRI and CSF changes) were not significantly different between the two groups. 19 (16.1%) patients lost from follow up. 21 (33.3%) patients developed stroke after randomization which was insignificantly lesser in aspirin (24.2%) compared to the placebo group (43.3%; OR 0.42, 95%CI 0.12-1.39). Aspirin resulted in absolute risk reduction of stroke in 19.1% and significant reduction in mortality compared to placebo (21.7% Vs 43.4%, P=0.02). On binary logistic regression analysis, the age (OR 1.09, CI 1.03-1.14, P=0.001) was the only independent risk factor of stroke and aspirin was significantly related to survival (OR 3.17, 95% CI 1.21-8.31). Aspirin was well tolerated and was not withdrawn in any patient because of side effects. INTERPRETATION: Aspirin resulted in insignificantly lesser strokes and significantly reduced 3 month mortality in patients with TBM.

Renal tubular acidosis presenting as respiratory paralysis: report of a case and review of literature.

Respiratory paralysis due to renal tubular acidosis (RTA) is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L) and hyperchloremic (110 meq/l) acidosis (pH 7.1). She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP) because acetazolamide used in FPP aggravates RTA and sodium bicarbonate used in RTA aggravates hypokalemic periodic paralysis.

A clinical, radiological and outcome study of status epilepticus from India.

The objective of this study is to evaluate the clinical and radiological characteristics and the outcome of status epilepticus (SE). 117 consecutive patients with SE were evaluated including their demographics, history of epilepsy, antiepileptic drug (AED) default, comorbidities, SE type and duration. The study included 22 children, 77 adults and 18 elderly patients with SE. Blood counts, serum chemistry, ECG, cranial MRI, cerebrospinal fluid and EEG were done. Patients were treated with IV phenytoin, valproate, lorazepam or diazepam as per a fixed protocol and responses to first and second drugs were noted. Death during hospital was recorded. The etiology of SE was infection in 53.8%, drug default in 7.9%, metabolic in 14.5%, stroke in 12.8% and miscellaneous in 11% of patients. 92.3% of patients had convulsive and 7.7% nonconvulsive SE. Cranial MRI was abnormal in 62%. Infection as an etiology was more common in children, drug default and metabolic causes in adults and stroke in adults and elderly. Following first AED, SE was controlled in 50%. 30% of patients remained refractory to second AED which was related to duration of SE and mortality. 29% patients died and death was higher in elderly (44%) compared to children (14%). Acute symptomatic SE is more common in developing countries. Refractory SE is associated with SE duration and mortality.

MRI pattern of infarcts in basal ganglia region in patients with tuberculous meningitis.

INTRODUCTION: This study aimed to evaluate the pattern of infarct in basal ganglia region in tuberculous meningitis (TBM) and ischemic strokes and its sensitivity and specificity in the diagnosis of these disorders. METHODS: Patients with TBM and ischemic strokes in basal ganglia region were retrospectively evaluated from our tuberculous meningitis and ischemic stroke registry. Magnetic resonance imaging findings were grouped into anterior (caudate, genu, anterior limb of internal capsule, anteromedial thalamus) and posterior (lentiform nuclei, posterior limb of internal capsule, posterolateral thalamus). The sensitivity and specificity of these patterns in diagnosing TBM and ischemic stroke were evaluated. RESULTS: There were 24 patients in each group. Infarct in TBM was purely anterior in eight patients and in ischemic stroke purely posterior in 18 patients. The frequency of caudate infarct was significantly higher in TBM compared to ischemic stroke (37.5% vs 8.3%). In TBM patients, purely posterior infarcts were present in seven patients; three had associated risk factors of ischemic stroke. The sensitivity of pure anterior infarct in the diagnosis of TBM was 33%, specificity 91.66%. For ischemic stroke, the sensitivity of posterior infarct was 75% and specificity 70.83%. CONCLUSION: TBM patients having infarcts in posterior region should be looked for associated risk factors of ischemic stroke.

Status epilepticus in encephalitis: a study of clinical findings, magnetic resonance imaging, and response to antiepileptic drugs.

This study evaluates clinical findings, magnetic resonance imaging (MRI), and response to antiepileptic drugs (AEDs) in encephalitis patients with status epilepticus (SE). Encephalitis patients with SE were included and they were grouped into herpes (HSE), Japanese (JE), dengue, and nonspecific encephalitis on the basis of virological studies. The demographic and clinical details, including SE type and duration, were noted. Cranial MRI and cerebrospinal fluid (CSF) were carried out. Response to first, second, and third AEDs were noted and the patients not responding to the second AED were considered refractory SE. The relationships of the mortality and the refractoriness of SE with various clinical findings, MRI, CSF, and the type of encephalitis were evaluated. Thirty SE patients with encephalitis aged 1 to 64 years were included. Nine patients had JE, 4 HSE, 1 dengue, and 16 nonspecific encephalitis. Generalized convulsive SE was present in 26 and nonconvulsive SE in 4 patients. The mean duration of SE was 21 (0.83 to 72) h. MRI was abnormal in 20 patients. A 46.7% of patients responded to the first AED and 36.7% remained refractory to the second AED. In 26.7% patients, the seizure continued even after the third AED. The response to AED was not related to the clinical, MRI, and laboratory variables. Nine patients died and the mortality was related to gender and Glasgow Coma Scale (GCS) score. In encephalitis with SE, 46.7% patients responded to the fist AED and 36.7% remained refractory to the second AED. One third of patients of died, which was related to the depth of coma.

Paroxysmal nocturnal haemoglobinuria presenting as cerebral venous sinus thrombosis.

Paroxysmal nocturnal haemoglobinuria (PNH) is associated with anaemia, intravascular haemolysis and venous thrombosis. Cerebral venous sinus thrombosis (CVST) is a late but serious complication of PNH. We for the first time report a young man who presented with CVST and was diagnosed to have PNH after 11 months. We highlight the reasons for delay in the diagnosis and discuss the special issues in the management.

Traditional journal club: a continuing problem.

OBJECTIVE: To evaluate the pattern, motivation and facilities for choosing journal club topics by residents in two medical institutions in India. METHOD: A self-appraisal questionnaire was used to compare motivation for choice of topics, availability of infrastructure, sites and type of articles accessed and formal training in computer based literature search in two medical institutions- a postgraduate institute (PGI) and medical college (MC) which provided mainly specialty and superspecialty training respectively. RESULTS: One hundred and fifty five out of two hundred and fifty five residents responded to the questionnaire. Super-specialty training was pursued by 58 and specialty training by 97 residents. The residents in PGI more frequently selected journal articles which they considered good and in MC, faculty guidance determined the choice of journal club topics. The super-specialty residents, however, more frequently selected patient management related topics compared to specialty residents. MEDLINE and MD Consult were more frequently accessed by PGI residents where infrastructure and training in literature search were superior to MC. CONCLUSION: In both the institutions surveyed, journal clubs were of traditional type. Better infrastructure and training at PGI were not reflected in quality of journal club. Successful journal club should focus on current, real patient's problem of most interest to the group.

Studies on the bioavailability of the provitamin A carotenoid, beta-carotene, using human exfoliated colonic epithelial cells.

The possibility of using exfoliated colonic epithelial cells for assessing the bioavailability of beta-carotene was examined. Analysis of exfoliated colonic epithelial cells showed the presence of beta-carotene and vitamin A. The beta-carotene content was significantly lower in cells from stool samples of subjects on a beta-carotene-poor diet than those receiving a single dose of a beta-carotene supplement. Colonic epithelial cells isolated from stool samples collected daily during a wash-out period while the subjects were on a beta-carotene-poor diet showed a steady decrease in beta-carotene content, reaching the lowest value on day 7. Kinetic analysis showed that a single dose of a beta-carotene supplement in the form of spirulina (Spirulina platensis) or agathi (Sesbania grandiflora) after the wash-out period caused an increase in the beta-carotene content after a lag period of 5-7 d, but the vitamin A levels during these periods were not significantly affected. Analysis of plasma beta-carotene concentration also showed similar changes, which correlated with those of exfoliated colonic cells. A relationship between the beta-carotene content of the diet and that of the colonic epithelial cells suggests that analysis of the beta-carotene content in exfoliated human colonic epithelial cells is a useful non-invasive method to assess the bioavailability of provitamin A beta-carotene.

Global outlook on nutrition and the environment: meeting the challenges of the next millennium.

As we enter the new millennium, nearly 800 million of the World's population will remain chronically malnourished. Nearly 200 million children are moderately to severely underweight, while 70 million are severely malnourished. And those who are yet to be born will be faced with the same set of circumstances that predispose them to malnutrition and its consequences. Eradication of nutritional deficiencies among women and children on a global scale are needed to ensure improved quality of life for the next generation of citizens. Primary deficiencies in vitamin A, iron, iodine, calcium, folic acid and trace elements such as zinc are compounded by pollutants caused by human activity. Environmental lead, arsenic, mercury, and other heavy metals that enter the food chain can seriously deplete body stores of iron, vitamin C and other essential nutrients leading to decreased immune defenses, intrauterine growth retardation, impaired psycho-social faculties and other disabilities associated with malnutrition. Increased susceptibilities to communicable diseases, and those provoked by water or insect borne vectors are additional risks encountered by malnourished individuals. Migration of populations from rural to urban centers and the expansion of major metropolitan areas have had a significant and adverse impact on the quality of life of these citizens. In the next 20 years most of the growth in urban populations will be in Asia and Latin America. Urbanization and the resultant burden on limited national resources is a major contributory factor to malnutrition. There are many other lifestyle-associated disabilities such as use of tobacco (cancer) and alcoholism that require active intervention. Within the family unit, socioeconomic factors and the status of women (literacy, economic independence) are major determinants of the quality of life. In the coming century, the World will have to meet these challenges by careful planning and international cooperation.

The induction of SOS function in Escherichia coli K-12/PQ37 by 4-nitroquinoline oxide (4-NQO) and fecapentaenes-12 and -14 is bile salt sensitive: implications for colon carcinogenesis.

The response of Escherichia coli to genotoxic agents involves the triggering of a complex system of genes known as the SOS response. In E. coli PQ37, a test organism used for the assessment of genotoxicity, lacZ, the beta-galactosidase gene is placed under the control of sfiA, one of the SOS genes through an operon fusion. The induction of beta-galactosidase activity, when the organism is exposed to genotoxic agents, is an indirect measure of the genotoxic activity of the test compound. Incubation of E. coli PQ37 with either 4-nitroquinoline oxide (4-NQO) or one of the fecal mutagens, fecapentaene-12 or -14 (F-12 or F-14) in the presence of sodium taurocholate or sodium deoxycholate resulted in a significant enhancement of induction of beta-galactosidase activity. The molecular mechanisms of 4-NQO-induced mutagenesis in E. coli are similar to those of the effects of UV light in which both replication-dependent and repair-dependent pathways of mutagenesis exist. Since E. coli PQ37 is excision-repair-deficient, alternate pathways are involved in this system. Bile salts by themselves do not trigger the SOS response, and hence their role in enhancing the SOS-inducing potency of mutagens may involve the potentiation of the cleavage-inactivation of lexA (repressor of SOS) by the protein product of the SOS-controlled gene, recA. The potentiating effect of bile salts on the fecal mutagens, F-12 and F-14, has implications in their suspected role in colon carcinogenesis associated with high-fat, low-fiber diets.

Rosai dorfman disease - an unusual presentation: A case report.

Rosai Dorfman Disease (Sinus Histiocytosis with massive lymphadenopathy) is a rare self-limiting histiocytic disorder of unknown etiology usually presenting with cervical lymphadenopathy and haematological abnormalities. Extra-nodal presentation is rare . This ease is such a rare presentation of Rosai Dorfman Disease.

Lectin binding to human colonocytes is predictive of colonic neoplasia.

OBJECTIVE: The aim of this study was to determine whether lectin binding to exfoliated human colonocytes could be used as a noninvasive test for colorectal polyps or cancer. METHODS: Colonocytes were harvested from 31 patients (10 controls, 10 with adenomatous polyps, and 11 with cancer), incubated with a panel of fluorescent-labeled lectins, and assayed by flow cytometry. RESULTS: The lectins jacalin (JAC) and wheat germ agglutinin (WGA) were useful in predicting the presence of a colorectal neoplasm (p = 0.0018 for JAC and p = 0.0099 for WGA). For JAC, sensitivity reached 81% with a specificity of 80%, and for WGA the sensitivity and specificity were both 75%. CONCLUSIONS: Lectin binding to human colonocytes can predict the presence of malignant and premalignant lesions of the colon, and has potential as a noninvasive screening tool for colorectal neoplasms.

Lupus vulgaris of nose - a case report.

Lupus vulgaris which is a mucocutaneous form of Tuberculosis is not an uncommon condi-tion. But the disease resulting in excessive destruction is rare today. We report a case of lupus vulgaris which almost completely destroyed the nose.

Peripheral ameloblastoma involving tongue-a rare case.

Peripheral ameloblastoma is a rare tumour of oral cavity. It presents as a mass without bony continuity. Here we report a unique case of peripheral ameloblastoma involving tongue, with review of relevant literature.

p53 tumor suppressor protein and tissue proliferative fraction in infiltrating duct carcinoma.

BACKGROUND AND OBJECTIVES: Breast cancer continues to frustrate oncologists worldwide. In India, it is the second most common neoplasm among women and is increasing in incidence. Several molecular markers have been associated with a poor prognosis in patients with breast cancer, and the presence of these markers is often thought to provide information on the biological behavior of the malignant breast tumor. Much attention has recently been focused on the tumor suppressor gene p53. Mutation or alteration in this gene leads to the loss of negative growth regulation and hence to rapid cell proliferation. The present study was designed to evaluate the connection between expression of the p53 protein and its relation to the tissue proliferative compartment as measured by expression of the proliferating cell nuclear antigen (PCNA). METHODS: Expression of p53 and PCNA were detected by immunocytochemistry in paraffin-embedded sections of infiltrating duct carcinoma and control breast tissue (normal tissue and adenoma). RESULTS: A significant correlation was observed between expression of p53 and PCNA. A significant correlation was also observed between expression of p53 and grade of tumor and stage of disease. CONCLUSIONS: Our results support the hypothesis that accumulation of p53 is associated with a high tumor proliferation rate an association that might be expected in view of the role of wild p53 as a negative regulator of cell proliferation.