Thrombocytopenia as a Prognostic Marker in Patients with Acute Encephalitis at a Tertiary Care Centre in Northern India.

Encephalitis is challenging to manage given the diversity of clinical and epidemiologic features. Various predictors of outcome have been studied so far including thrombocytopenia, cerebral edema, hypoglycaemia, development of status epilepticus and need for endotracheal intubation. Thrombocytopenia represents one of the potentially modifiable risk factors for poor prognosis in encephalitis. A better understanding of the epidemiology of this devastating disease and identification of predictors of outcome and management of reversible factors will pave the way for better management of the disease. MATERIAL: A total of 98 Hospitalised patients of Acute Encephalitis were enrolled in the study. Diagnoses were confirmed by CSF and Neuroimaging studies. Platelet count <150,000/cumm was considered as thrombocytopenia. Mild, moderate and severe thrombocytopenia was categorized at platelet count 100,000-150,000, 50,000-100,000 and <50,000/ cumm, respectively. Outcome at discharge was assessed using the Modified Ranking Score, categorized into 3 groups - good (0-2), fair (3-4), and poor (5-6). Chi-square, ANOVA and Independent samples 't'-tests were used to compare the data. OBSERVATION: Mean age of patients was 34.06±18.76 (range 14-85) years. Majority of patients were males (54.1). Mean GCS at admission was 9.41±1.90. Acute viral encephalitis(unclassified) (n=33; 33.7%), Scrub typhus (n=24; 24.5%) and Japanese encephalitis virus (n=12; 12.2%) were the most common underlying etiologies. A total of 74 (75.5%) patients had thrombocytopenia. Mild, moderate and severe thrombocytopenia was seen in 34 (34.7%), 30 (30.6%) and 10 (10.2%) cases. Thrombocytopenia was significantly higher in Dengue and Scrub as compared to other etiologies. Thrombocytopenia and its severity showed a significant association with lower GCS and higher mRS scores indicating a poor outcome. CONCLUSION: Thrombocytopenia is associated with a poor clinical status and adverse outcomes in patients with encephalitis of all causes.

Mutation Analysis in Chronic Myeloid Leukemia Patient in Chronic Phase on Imatinib Having Delayed Achievement of Milestones or Loss of Response.

Tyrosine kinase inhibitors (TKI's) are currently the drug of choice for management of chronic myeloid leukemia. Imatinib is the most commonly used first line TKI in India. Mutations leading to resistance to imatinib are the most common cause for imatinib failure. We studied pattern of kinase domain mutations in 40 patients of CML who either lost their response or did not achieve it in defined timepoints. Loss of molecular response was the most common indication for asking mutation analysis. Sixteen patients were found to have detectable mutations. M351T was the most common tyrosine kinase mutation followed by Y253H and H396R. Two patients had 2 mutations simultaneously. M351T is the most common mutation in our patient population.

A randomized study of very low-dose factor VIII prophylaxis in severe haemophilia - A success story from a resource limited country.

INTRODUCTION: Current factor prophylaxis strategy practised in developed countries is not feasible in resource constraint developing countries like India. AIM: The aim of this study was to investigate the efficacy and safety of very low-dose factor prophylaxis in India. METHODS: Children of 1-10 years of age with severe haemophilia were randomized to Prophylaxis group and Episodic (On demand) group. Children in prophylaxis group received very low-dose factor VIII (FVIII) concentrate, i.e. 10 units kg(-1) body weights on 2 days a week. Episodic group received factor concentrate in standard recommended doses. The study period was 11.5 months. RESULTS: In total 21 children were enrolled in this study, 11 assigned to prophylaxis and 10 to episodic group. Children on prophylaxis had 11 joint bleeds in comparison to 57 joint bleeds in episodic group. Mean number of haemarthrosis per patient per month were 0.08 (0.08 ± 0.13) in prophylaxis group compared to 0.48 (0.48 ± 0.34) in episodic group (P < 0.05). Total FVIII consumption was 87.51 and 56.32 units kg(-1) month(-1) in prophylaxis and episodic group respectively (P = ns). Overall median hospital emergency visits were 1 day in prophylaxis group and 9 days in episodic group (P ≤ 0.05). Median days of absenteeism from school were 25 days in episodic group and 3 days in prophylaxis group (P < 0.05). No significant complications were noted in prophylaxis group and compliance was 98%. CONCLUSION: To conclude, low-dose FVIII prophylaxis is cost effective, efficacious and a safe method of preventing joint bleeds and consequent joint damages.

Haemostatic Profile in Patients of Myeloproliferative Neoplasms-A Tertiary Care Centre Experience.

INTRODUCTION: Patients of MPN commonly present with abnormalities in laboratory coagulation tests that are consistent with hypercoagulable state. Some individuals with MPN exhibit a pattern of exclusive bleeding or thrombotic events; many others have both bleeding and thrombosis during the course of the disease. AIM: This study was undertaken to assess the haemostatic defects and platelet functions in patients of MPN. MATERIALS AND METHODS: One year prospective study was conducted at a tertiary care centre in North India in Department of Pathology in collaboration with Department of Clinical Haematology. All recently diagnosed cases of MPN along with 30 age and sex matched controls were included. Patients on antiplatelet drugs, antimyeloproliferative treatment, vitamin K agonists or antagonists, OCPs, Platelet count <1,00,000/µl, high grade fever, liver disease, pregnancy were excluded from this study. All the patients underwent screening investigations like CBC, peripheral smear evaluation, BT, PT, aPTT, Protein C and S measurement (clot based assay) and aggregation studies with ADP (5µM) (Optical Aggregometry with AGGRO/LINK 8 software and CHRONOLOG 700 aggregometer). RESULTS: In present study, 50 cases were included. There was an occult prothrombotic state, suggested by significantly (p<0.001) reduced levels of Protein C and Protein S, but no patient presented with frank thrombosis while 8 out of 50 patients had haemorrhagic manifestations ranging from subdural haematoma to pin point petechial haemorrhages. Patients of CML-CP, ET, PV, PMF, MPN-NOS showed significantly reduced maximal aggregation with ADP (5µM) when compared to control (p<0.001). MPV also showed a statistically significant increase in these patients. CONCLUSION: Thrombohaemorrhagic complications significantly affect the morbidity and mortality of MPN patients. This can be assessed by the use of platelet aggregation studies, Protein C and S activities and other coagulation studies. Timely diagnosis of these prothrombotic/haemorrhagic states can decrease the morbidity in these patients.

A rare case of adult acute lymphoblastic leukemia presenting with paraparesis and multiple osteolytic lesions.

Acute lymphoblastic leukemia presenting with bone involvement and multiple osteolytic lesions has been commonly reported in pediatric population. Various myeloid and lymphoid malignancies can rarely present with bony lesions. We are reporting an adult female patient with acute lymphoblastic leukemia who presented with paraparesis and multiple osteolytic lesions in skull initially giving false impression of multiple myeloma.

A case of pediatric acute lymphoblastic leukemia with invasive candidiasis: short review.

Mortality rate associated with invasive fungal infections is very high. Early suspicion for fungal infections is important during intensive chemotherapy for acute leukemia. Empirical treatment with antifungals amphotericin B or caspofungin should be started if patient is not responding to broad spectrum antibiotics and if expected duration of neutropenia is prolonged. We are reporting a 3 years old girl child with diagnosis of pre-B acute lymphoblastic leukemia who developed invasive candidiasis with typical clinical and radiological findings during induction chemotherapy. Candida non-albicans was isolated and she was treated with amphotericin B followed by caspofungin. Patient deteriorated after initial response and succumbed to death. Species identification and sensitivity pattern of fungus can help in selecting appropriate antifungal drug.

Rational Use of Recombinant Factor VIIa in Clinical Practice.

In the United States, the FDA-approved indications for recombinant factor VIIa is for bypassing inhibitors to factors VIII and IX in patients with hemophilia A and B respectively and for treatment of congenital factor VII deficiency. In European countries, rFVIIa is licensed for the above indications as well as for Glanzmann's thrombasthenia. In absence of high-quality data favoring off-label use of this agent and laboratory test to predict response to this agent, and in view of high cost of rFVIIa, off-label use of recombinant factor VIIa should be restricted to only when hemorrhage has not responded to transfusion or other conventional therapy. It appears, two such conditions where recombinant factor VIIa may be beneficial are traumatic and postpartum hemorrhages.

Can Metabolic Factors be Used Prognostically for Short-Term Mortality in HIV-Infected Patients?

Background: Metabolic abnormalities are common throughout the course of human immunodeficiency virus (HIV) infection and may occur either due to HIV infection or as a result of side effects of antiretroviral therapy. It has been established that dyslipidemia and dysglycemia associated with HIV disease reduce the long-term survival of the patients; but their role for predicting prognosis of short-term mortality in HIV patients is unknown. Aim: To study dyslipidemia and dysglycemia as a prognostic indicator for short-term mortality (3 months) in HIV patients. Subjects and Methods: An observational; prospective study was conducted at a tertiary care center over a period of 6 months. Consecutive HIV-positive patients hospitalized (both; HIV status known prior to hospitalization and the diagnosis made for the first time at admission) in medical wards from March to May 2010 were studied. All patients had their random blood sugars; fasting blood sugars (if possible); fasting lipid profile; and cluster of differentiation 4 (CD4) counts tested at the time of enrollment. The patients were followed for a period of 3 months; at the end of which they were categorized as survivors and non-survivors; and the demographic; clinical; and investigational parameters were compared between the above groups. Data was analyzed by applying Mann-Whitney U test; two sample t-test; Fisher-Exact test; and stepwise logistic regression analysis of significance; using the computer-based program; Stata; version 11.1. Results: A total of 82 patients were enrolled for the study of which 64 (78.05) were males and 18 (21.95) were females; with a mean (SD) age of 34.00 (7.0) years. The mean CD4 count was 206.23 (129.5) cells/mm 3 . The overall mortality within 3 months was 20.7 (17/82). Mycobacterium tuberculosis as opportunistic infection was found in 42 patients; out of which 13 expired (P

Can Metabolic Factors be Used Prognostically for Short-term Mortality in HIV-infected Patients?

Metabolic abnormalities are common throughout the course of human immunodeficiency virus (HIV) infection and may occur either due to HIV infection or as a result of side effects of antiretroviral therapy. It has been established that dyslipidemia and dysglycemia associated with HIV disease reduce the long-term survival of the patients; but their role for predicting prognosis of short-term mortality in HIV patients is unknown. Aim: To study dyslipidemia and dysglycemia as a prognostic indicator for short-term mortality (3 months) in HIV patients. Subjects and Methods: An observational; prospective study was conducted at a tertiary care center over a period of 6 months. Consecutive HIV-positive patients hospitalized (both; HIV status known prior to hospitalization and the diagnosis made for the first time at admission) in medical wards from March to May 2010 were studied. All patients had their random blood sugars; fasting blood sugars (if possible); fasting lipid profile; and cluster of differentiation 4 (CD4) counts tested at the time of enrollment. The patients were followed for a period of 3 months; at the end of which they were categorized as survivors and non-survivors; and the demographic; clinical; and investigational parameters were compared between the above groups. Data was analyzed by applying Mann-Whitney U test; two sample t-test; Fisher-Exact test; and stepwise logistic regression analysis of significance; using the computer-based program; Stata; version 11.1. Results: A total of 82 patients were enrolled for the study of which 64 (78.05) were males and 18 (21.95) were females; with a mean (SD) age of 34.00 (7.0) years. The mean CD4 count was 206.23 (129.5) cells/mm 3 . The overall mortality within 3 months was 20.7(17/82). Mycobacterium tuberculosis as opportunistic infection was found in 42 patients; out of which 13 expired (P

Abdominal angina: an unusual presentation of Takayasu's arteritis.

Takayasu's arteritis (TA) is an idiopathic large vessel vasculitis of young adults that affects the aorta and its major branches. The authors hereby present a case of TA that presented with abdominal aorta thrombosis. She was put on low-molecular weight heparin, antiplatelets, corticosteroids, cyclophosphamide along with haematinics and was referred to Department of Cardiothoracic and Vascular Surgery for further management.

An atypical case of dengue haemorrhagic fever presenting as quadriparesis due to compressive myelopathy.

Dengue haemorrhagic fever is a serious presentation of dengue viral infection. Case reports of cerebral haemorrhage due to dengue are rare. The authors report a rare case of dengue haemorrhagic fever presenting with fever and acute onset progressive quadriparesis of the upper motor neuron type. Rare cases of quadriparesis in dengue fever have been reported in the literature due to myositis, Guillain-Barre syndrome, myelitis and hypokalaemia. This case on investigations was found to have extramedullary compression due to haematoma in the cervical region as the cause of quadriparesis.

Synthesis, anticonvulsant and toxicity screening of newer pyrimidine semicarbazone derivatives.

A number of N-(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones (4a-t) were synthesized and tested for their anticonvulsant activity against the two seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out.

Acute psychosis: a presentation of cyanocobalamin deficiency megaloblastic anemia.

Cyanocobalamin deficiency is not rare in India. Patients present with megaloblastic anemia, pancytopenia and sometimes neuropsychiatric manifestations. Subacute combined degeneration of the cord, peripheral neuropathy, dementia, psychotic depression and paranoid schizophrenia are well reported. We are reporting a case of cyanocobalamine deficiency anemia who presented with acute psychosis which readily reversed on cyanocobalamin replacement.

HIV: a raft-targeting approach for prevention and therapy using plant-derived compounds (review).

It has been widely accepted that HIV-1 enters into and buds out from microdomains known as lipid rafts/caveolae of plasma membranes of infected cells. Since lipid rafts are recognized sites for budding and entry of HIV-1, and since lipids in rafts (including composition/dynamic structure) play a crucial role in modulating the functions of raft-associated signaling proteins and receptors, it has been consistently shown that modulating the composition/structure of lipid rafts have influenced the life cycle of HIV-1 inhibiting its replication. Since anti-retroviral multi-drugs treatment has severe side effects, one of the strategies could be to block the HIV-1 entry and its replication using natural compounds that can target lipid rafts. Dietary and plant-derived compounds have advantage over synthetic drugs exhibiting minimum side effects and are available in cost effective manner. Studies exploring the effects of dietary and plant-derived compounds targeting lipid rafts could be an evolving strategy to control the progression of AIDS. This article is intended to review: (i) composition/structure and conditions for the formation of lipid rafts in plasma membranes, (ii) interaction of HIV-1 with lipid rafts and (iii) to introduce a novel concept that dietary and plant-derived compounds, which can target lipid rafts, could have potential preventive/therapeutic values against the progression of AIDS. More emphasis has been given to the roles of omega-3 fatty acids and plant-derived various triterpenes, especially euphane-types of triterpenes extracted from Neem tree, targeting lipid rafts and its major component cholesterol.

Separation and quantification of lanthanides in synthetic standards by capillary electrophoresis: a new experimental evidence of the systematic "odd-even" pattern observed in sensitivities and detection limits.

The systematic zigzag pattern of sensitivities and detection limits (LODs) of lanthanides, previously observed in mass spectrometric and chromatographic measurements, was once more investigated through the indirect photometric detection with capillary electrophoresis. Well-designed chemometric experiments were performed for the electrophoretic separation and detection of lanthanides using standards with similar concentrations. A fused silica capillary 355 mm x 75 microm was used. Complete separation for all 14 lanthanides was achieved in approximately 3 min at a capillary temperature of 15 degrees C. Indirect photometric detection at 214 nm using a voltage of +25 kV and a hydrostatic injection (100 mm for 20 s) were used. The background electrolyte used consisted of an optimum mixture of 0.004 M HIBA (as complexing agent) and 0.010 M UVCat-1 (as a UV-absorbing co-ion) with a pH 4.4. A good reproducibility in migration times (<2.7% RSD), peak areas (<3.8% RSD) and peak heights (2.7% RSD) were systematically obtained. Calibration curves based on both peak areas and peak heights (from seven replicates) were prepared using weighted least-squares regressions, which were employed for the correct estimation of individual sensitivities and LODs. For a better estimation of LODs, the lowest concentration standard was injected 30 times. A new experimental evidence of the systematic "odd-even" pattern was again observed in the lanthanide sensitivities (and therefore in LODs). The calculated sensitivities were greater for lanthanides with an odd-atomic number than for their corresponding neighboring element with an even-atomic number (i.e., (57)La-(58)Ce, (59)Pr-(60)Nd; (63)Eu-(64)Gd, etc.). Concerning the LODs, a systematic zigzag pattern was observed where the odd atomic number elements have lower LODs than the even atomic number neighbor elements (i.e., (57)La-(58)Ce; (59)Pr-(60)Nd; (63)Eu-(64)Gd, etc.). The possible origin of this "odd-even" effect is briefly discussed. Accuracy errors were less than 5% for lanthanide concentrations of three synthetic standard solutions, which were considered as "unknown" samples.

Brain stem auditory evoked responses and visual evoked responses in children with tubercular meningitis.

Thirty two patients between 6 months and 14 years of age with tubercular meningitis were evaluated for brain stem auditory evoked response (BAER) and Visual evoked responses (VER), within 7 days of admission. Absolute latencies and interpeak latencies were compared with values obtained from normal children. BAER abnormality was found in 56.25% and VER in 28%children, respectively. BAER abnormality correlated with Glasgow Coma Scale at admission and discharge, stage of meningitis, raised intracranial pressure, seizure activity, and poor outcome. VER abnormality correlated with abnormal fundus findings only.

Suppressed ion chromatography for monitoring chemical impurities in steam for geothermal power plants.

A suppressed ion chromatography (IC) technique has been evaluated as a chemical monitoring tool for detecting major anions (F-, Cl-, NO3- and SO4(2-)) of condensed steam in geothermal power plants. It is shown that the suppressed IC technique provides a suitable means for preventing possible damage to generating equipment in the geothermal industry. An electrical conductivity detector (0.1 microS sensitivity) with an anion-exchange column (IonPac AS4A-SC), a micro-membrane suppressor (AMMS II), and an isocratic high-pressure pump system were successfully used for detecting low concentrations of inorganic anions. Method detection limits for the anions of interest were <0.184 mg/L. Details of the IC methodology as well as some experimental results obtained during its application for the chemical monitoring of geothermal steam pipes are also described.