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.

Prevalence of Human metapneumovirus infection among patients with influenza-like illness: Report from a Tertiary Care Centre, Southern India.

BACKGROUND: Human metapneumovirus (HMPV), discovered in the 21st century, has emerged as an important cause of influenza-like illness in children and adults causing mild upper respiratory tract infection to severe bronchiolitis and community-associated pneumonia. The aim of this study was to determine the prevalence of HMPV in the Union Territory of Puducherry, India, as part of National Influenza Surveillance Programme. MATERIALS AND METHODS: From November 2011 to December 2013, a total of 447 nasopharyngeal samples were collected from patients with acute respiratory infections and tested for HMPV RNA by real-time polymerase chain reaction. RESULTS: HMPV was identified in 23/447 (5%) samples with 11/23 in the age group of 14-30 years. Most of the HMPV infections were mild with no fatalities. Two patients were co-infected with the respiratory syncytial virus and one with influenza B virus. The seasonal distribution showed increasing HMPV infection cases in rainy months except for a peak in summer of 2012. Phylogenetic analysis based on the sequences of the nucleoprotein gene of one HMPV strain showed a high degree of sequence identity with Indian strains obtained during 2006 and 2011. CONCLUSION: This study shows that HMPV infection is more common in adults than in children. Sequence homology suggests the circulation of closely related HMPV strains within the country.

Preparation, characterization, and photocatalytic activity of sulfate-modified titania for degradation of methyl orange under visible light.

Hydrated titania was prepared by a sol-gel method, taking tetraisopropyl orthotitanate as starting material, and then promoted with different weight percentages of sulfate by an incipient wetness impregnation method. The materials were characterized by various advanced techniques such as PXRD, BET surface area, N(2) adsorption-desorption measurements, FTIR, and SEM. Analytical results demonstrated that TiO(2) is mesoporous in nature, and sulfate modification could inhibit the phase transformation and enhance the thermal stability of TiO(2). It was also found that sulfate modification could reduce the crystallite size and increase the specific surface area of the catalysts. The degradation of methyl orange under solar radiation was investigated to evaluate the photocatalytic activity of these materials. Effects of different parameters such as pH of the solution, amount of catalyst, additives, and kinetics were investigated. At 2.5 wt% sulfate loading, the average percentage of degradation of methyl orange was nearly two times than that of neat TiO(2). The photocatalytic degradation followed first-order kinetics.

Evaluation of lactophenol cotton blue stain for detection of eggs of Enterobius vermicularis in perianal surface samples.

A lacto-phenol cotton blue (LPCB) stain for detecting eggs of Enterobius vermicularis in perianal surface samples was evaluated prospectively. Two hundred children treated in the paediatrics ward and outpatients department of Jipmer Hospital in Pondicherry were studied. From each child two anal surface samples were collected by Scotch cellophane tape method. One cellophane tape containing anal surface samples was pressed against surface of the glass slide containing a drop of LPCB while another cellophane tape was placed on a clean glass slide without adding any LPCB. Both the specimens from each child were examined by microscopy for presence of the eggs of the parasite. The anal samples collected from 50 children were positive for the eggs of E. vermicularis--48 were detected by cellophane tape using LPCB and 36 by cellophane tape method without using any LPCB. Using LPCB stain, naturally transparent and colourless eggs of the parasites were stained deep blue which facilitated their easy detection and accurate identification in routine microscopy. We therefore recommend Scotch cellophane tape using LPCB as a simple, rapid, inexpensive and overall more sensitive method for detecting E. vermicularis eggs in anal surface samples for diagnosis of enterobiasis in children.

Acute pulmonary edema as a complication of anti-snake venom therapy.

Polyvalent Anti-snake Venom (ASV) is a life-saving antivenin for severe envenomation due to snake bite in India. ASV infusion is occasionally associated with severe allergic reactions, i.e. anaphylaxis and death. We report a rare instance of non-cardiogenic pulmonary edema due to ASV infusion in an eleven years old boy.

Perinephric abscess due to Aspergillus fumigatus.

Invasive aspergillosis is rare in healthy children. Severe systemic complications due to aspergillosis may be seen in AIDS patients with severe neutropenia and macrophage dysfunction.

Hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition in children associated with immunodeficiency, life threatening infections and malignancy. Infection associated hemophagocytosis responds well to appropriate antimicrobioal therapy and rarely to steroids when the infective agent is suspected to be of viral origin.

Congenital indifference to pain.

Congenital analgesia can vary from simple analgesia without any systemic dysfunction to more serious conditions associated with peripheral neuropathy, self-mutilation, and mental retardation. Prevention of injury is important for normal growth of the child.

Enteric fever: a changing perspective.

All the cases of enteric fever admitted between 1988-1992 were studied. There was a gradual rise in the number of admitted cases. Central nervous system (CNS) complications like encephalopathy (14.9%), meningitis (8.8%), seizures (8.5%) and cerebellitis (3.4%) were noted more during 1991 and 1992. Other complications like myocarditis (4.6%), hepatitis (9.5%) and gastrointestinal bleeding were noted in increasing numbers during 1991-1992. Multidrug resistant (MDRT) cases were 46.3% in 1991 and 33.5% in 1992. There was a significant difference in the time taken for defervescence (a gradual rise) between the years but between the individual drugs there was no such significant difference. Deaths were noted only in 1991 and 1992 in cases of MDRT with complications. There has been an increase in resistance of S. typhi to commonly used drugs like ampicillin, chloramphenicol and cotrimoxazole. S. typhi resistant to ciprofloxacin was cultured in 2 cases each from 1990-1992. Further, the time taken for defervescence with ciprofloxacin also showed a gradual rise from 3.5 days in 1990 to 6.2 days in 1992. Nevertheless, ciprofloxacin is still the drug of choice for treatment of complicated cases of MDRT.

Undergraduate training in neonatal resuscitation -- a modified approach.

PIP: On one day in January 1993, in Pondicherry, India, prior to rounds in the labor room, professors trained 50 final year, undergraduate medical students at the Jawaharlal Institute of Postgraduate Medical Education and Research in neonatal resuscitation using a modified program of the neonatal advanced life support course. They compared their results with those from students in the March-April 1992 multiday course, which occurred after some students had finished their labor room rounds. In 1992, the pretest was administered after the theory lectures, while, in 1993, it was administered before the course, including the theory lectures, began. The 1992 students scored significantly higher on the pretest than did the 1993 students (e.g., score of 11-20, 73.3% vs. 0%; p .001). There was essentially no difference in posttest scores between the 2 groups, however. All the 1993 students did the resuscitation procedure on the mannequin on their own. 92% rated the content of the program and use of audiovisual aids to be optimum. The same percentage wanted the neonatal advanced life support program to last one day. About 33% wanted a short respite between lectures. The students identified the following messages to be important: early identification of the high risk neonate, correct resuscitation techniques, and use and misuse of drugs during resuscitation. They all considered the training to be adequate, informative, and applicable to real life during their labor room rounds and later as a basic physician. These findings indicated that the modified neonatal advanced life support course was effective and that professors should conduct it for all final year medical students before the student begin labor room rounds, ideally in one day.^ieng

In vitro multidrug resistance of P388 murine leukemia selected for resistance to diaziquone.

P388 leukemia sublines were isolated from leukemia-cell-bearing CD2F1 mice that had been treated in vivo with increasing amounts of diaziquone (AZQ). The sublines isolated for in vitro studies were AZQ19 and AZQ30 which corresponded to the 19th and 30th in vivo passages, respectively. The AZQ19 subline displayed a very low degree of resistance to AZQ (1.5-fold), whereas the AZQ30 subline was sensitive. Both sublines, however, had much higher degrees of resistance to Adriamycin than to AZQ (24-fold for AZQ30 cells and 10-fold for AZQ19 cells). Both cell lines were also more resistant to actinomycin D, colchicine, and vincristine than to AZQ. The AZQ19 line was resistant to the alkylator thio-TEPA to the same degree that it was to AZQ, but the AZQ30 line was sensitive to thio-TEPA. On the other hand, AZQ30 cells were resistant to hydrogen peroxide with a very low degree of resistance (1.27-fold, P less than 0.05), whereas the AZQ19 line was sensitive. Drug accumulation experiments indicated that AZQ-resistant cells differed from the parental line in that they did not accumulate Adriamycin or vinblastine. In the case of AZQ, however, resistant and parental lines accumulated the same amounts of exchangeable AZQ. Using the immunoblotting technique, no P-glycoprotein was found in resistant cells. The resistant lines consumed oxygen at greater rates than the parental line. Oxygen consumption (Mean +/- SD) in sensitive cells was 2.0 +/- 0.4% O2 consumed/min, whereas in resistant cells it was nearly 3.1 +/- 0.6% O2 consumed/min. The increase in oxygen consumption with drug resistance was statistically significant (P less than 0.01). The kinetics of production of hydroxyl free radicals and of AZQ free radicals were faster in the resistant lines reflecting, in essence, their increased oxygen consumption. It appears that the two sublines analyzed here show resistance mechanisms that may have been elicited by the two distinct chemical constituents of AZQ. Therefore, in the AZQ19-resistant line, the alkylating aspect of AZQ was emphasized, whereas in the AZQ30 line, the quinone and, thus, free radical aspect was emphasized. This is consistent with AZQ30 cells being sensitive to the alkylator thio-TEPA and resistant to hydrogen peroxide, and the AZQ19 line being resistant to thio-TEPA and sensitive to hydrogen peroxide. In addition, the AZQ30 cell line was relatively more resistant than the AZQ19 line to Adriamycin.

Regulation of viral and cellular genes in a human neuroblastoma cell line latently infected with herpes simplex virus type 2.

A latent state of the herpes simplex virus type 2 genome was established in a human neuroblastoma cell line (SMS-KCNR) to initiate studies on the mechanism by which host cells interact and regulate latent viral genes. To establish viral latency, it was necessary to prevent virus replication by briefly exposing the infected cells to antiherpetic acycloguanosine (20 microM) and human interferon (120 U/ml). Subsequently however, these cells could be propagated without any antiherpetic agents and almost 60% of the cell population contained viral genome. While these cells did not produce any infectious virus, immunoblot analysis revealed two intracellular polypeptides with molecular weights of 87.5 kDa and 67 kDa, respectively, that interacted with hyperimmune anti-HSV2 rabbit serum. Two cellular enzymes, acetylcholinesterase and choline acetyltransferase, involved in metabolism of neurotransmitters were expressed at a higher level in the latently infected cells than in the mock-infected control cells. Infectious HSV-2 could be reactivated from these cells only after the cells had undergone massive morphological differentiation and maturation to flat cell types by extensive treatment with 20 micron bromodeoxyuridine.

Reductive activation of diaziquone and possible involvement of free radicals and the hydroquinone dianion.

To analyze the mode of action of diaziquone [AZQ] on DNA, we examined the activity of two AZQ analogues and N,N',N"-triethylenethiophosphoramide on three forms [supercoiled (Form I), open circular (Form II), and linear (Form III)] of PM-2 DNA. The AZQ analogues contained chlorine atoms which substituted either the carbethoxyamino groups or the aziridine groups of the parent compound. N,N',N"-triethylenethiophosphoramide is a triaziridine compound containing pentavalent phosphorus instead of a quinone group. We found that only when reduced with sodium borohydride did AZQ change the topology of the three forms of PM-2 DNA by introducing mainly single strand breaks. The AZQ analogue containing only aziridines (RQ2) was active in both its oxidized and its reduced forms, while the analogue containing only the carbethoxyamino groups (RQ14) or N,N',N"-triethylenethiophosphoramide were not active in either form. Under similar experimental conditions, Adriamycin alone altered the electrophoretic mobility of PM-2 DNA, while borohydride reduced Adriamycin did not. By using electron spin resonance spectroscopy, we showed that dihydrodiaziquone (AZQH2) oxidizes to the semiquinone in the presence of oxygen. Although AZQH2 was active against DNA, it was not active against cellular DNA synthesis as measured by [3H]thymidine incorporation into exponentially growing HEp-2 cells. However, AZQ alone prevented [3H]thymidine incorporation into HEp-2 cells. We found that HEp-2 cells have the ability to reduce AZQ to its free radical anion, but AZQH2 does not autoxidize to the free radical in the presence of cells. The reductive ability of HEp-2 cells may be responsible in part for preventing the oxidation of AZQH2 to the free radical. We found that under our conditions (1-h incubations) the aziridines are essential for the activity of aziridinyl quinones against PM-2 DNA and that in the case of AZQ the hydroquinone is also required.