FEVER OF UNKNOWN ORIGIN

Forty six patients of fever of unknown origin in Service Hospitals who met the standard criteria were studied between 1989 and 1997. Infectious diseases contributed 21 patients (45.65%) of which 13 (28.26%) were diagnosed to have tuberculosis. Eight patients each (17.39%) of malignancies and collagen vascular diseases were seen, solid tumours were found in 5 patients. One (2.17%) patient had intrabdominal abscess. No diagnosis was made in 4 (8.69%) patients. The pattern and height of fever bore no correlation to aetiology. Serially repeated radiograph of chest was the most contributory investigation giving diagnostic information in 41.3%. Tissue/body fluid biopsy and cytology, serology, ultrasonography, computerised tomography and laparotomy were other useful investigations.KEY WORDS: Fever of unknown origin, Pyrexia     

Evidence for systemic oxidative stress in tobacco chewers

Objective. To evaluate erythrocyte malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione reductase (GR) in tobacco chewers, in view of possible oxidative stress in oral smokeless tobacco. Material and methods. Sixty healthy male tobacco chewers, aged 30.6±4.7 years with a 3 to 10‐year (7.37±2.1) history of tobacco chewing, were included in the study. Thirty‐two healthy male volunteers, aged 26.5±4.8 years, served as controls. All the participants were from the same community and of similar dietary habits. Results. The erythrocyte MDA level and activities of erythrocyte SOD and GR were estimated. There was a significant duration‐ (tobacco chewing) dependent increase in erythrocyte MDA levels along with a significant duration‐ (tobacco chewing) dependent decrease in erythrocyte SOD and GR activity. Conclusion. Oral smokeless tobacco causes a duration‐dependent increase in oxidative stress.     

Extraluminal colonic arteriovenous haemangioma: an unusual cause of chronic lower gastrointestinal bleeding

Lower gastrointestinal bleeding is a common general surgical presentation in acute and chronic settings. Vascular anomalies account for 2% of such cases and can therefore be missed. We discuss a rare vascular anomaly in one of our patients where the diagnosis was not established for a ten-year period. We describe the subsequent management and a brief review of the literature of this uncommon condition.     

Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response

We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine candidate may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine candidate (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen.     

Sleep Deprivation Predisposes Gujarati Indian Adolescents to Obesity

Background and Aim:

Recent studies on various populations indicate that lack of sleep is one of the potential risk factors predisposing the youth to obesity. Since there is a significant rise in obesity among Indian youth and because research indicating the role of sleep in development of obesity among Indian population is scant, the current study was undertaken to assess the effect of sleep duration on adiposity among Gujarati Indian adolescents.

Materials and Methods:

A randomized cross-sectional study was done on 489 voluntarily participating Indian adolescents in the age group of 16-19 years. Participants were grouped into two categories 1). Adequate Sleep Duration at Night (more than seven hours, ASDN) and 2) Inadequate Sleep Duration at Night (less than seven hours, IASDN) as reported by the participants. The participants were later assessed for adiposity in terms of BMI, BF %, FM, FMI and waist circumference, meal frequency per day and physical activity status.

Results:

In both boys as well as girls, the BMI, BF%, FM and FMI were significantly lower in the ASDN group than the IASDN group. However, there was an insignificant difference in the meal frequency and physical activity status between the ASDN and IASDN group.

Conclusion:

Inadequate sleep duration increases adiposity among Gujarati Indian adolescents but further studies are required to find out the mechanisms through which sleep affects adiposity in this population.     

Design,Synthesis, Structural Characterization by IR, 1H, 13C, 15N, 2D‐NMR,X‐Ray Diffraction and Evaluation of a New Class of Phenylaminoacetic Acid Benzylidene Hydrazines as pfENR Inhibitors

Recent studies have revealed that plasmodial enoyl‐ACP reductase (pfENR, FabI), one of the crucial enzymes in the plasmodial type II fatty acid synthesis II (FAS II) pathway, is a promising target for liver stage malaria infections. Hence, pfENR inhibitors have the potential to be used as causal malarial prophylactic agents. In this study, we report the design, synthesis, structural characterization and evaluation of a new class of pfENR inhibitors. The search for inhibitors began with a virtual screen of the iResearch database by molecular docking. Hits obtained from the virtual screen were ranked according to their Glide score. One hit was selected as a lead and modified to improve its binding to pfENR; from this, a series of phenylamino acetic acid benzylidene hydrazides were designed and synthesized. These molecules were thoroughly characterized by IR, ¹H, ¹³C, ¹⁵N, 2D‐NMR (COSY, NOESY, ¹H‐¹³C, ¹H‐¹⁵N HSQC and HMBC), and X‐ray diffraction. NMR studies revealed the existence of conformational/configurational isomers around the amide and imine functionalities. The major species in DMSO solution is the E, E form, which is in dynamic equilibrium with the Z, E isomer. In the solid state, the molecule has a completely extended conformation and forms helical structures that are stabilized by strong hydrogen bond interactions, forming a helical structure stabilized by N‐H…O interactions, a feature unique to this class of compounds. Furthermore, detailed investigation of the NMR spectra indicated the presence of a minor impurity in most compounds. The structure of this impurity was deduced as an imidazoline‐4‐one derivative based on ¹H‐¹³C and ¹H‐¹⁵H HMBC spectra and was confirmed from the NOESY spectra. The molecules were screened for in vitro activity against recombinant pfENR enzyme by a spectrophotometric assay. Four molecules, viz. 17, 7, 10, and 12 were found to be active at 7, 8, 10, and 12 μm concentration, respectively, showing promising pfENR inhibitory potential. A classification model was derived based on a binary QSAR approach termed recursive partitioning (RP) to highlight structural characteristics that could be tuned to improve activity.     

A recombinant Newcastle disease virus (NDV) expressing infectious laryngotracheitis virus (ILTV) surface glycoprotein D protects against highly virulent ILTV and NDV challenges in chickens

Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). Currently, modified live ILTV vaccines are used to control ILT infections. However, the live ILTV vaccines can revert to virulence after bird-to-bird passage and are capable of establishing latent infections, suggesting the need to develop safer vaccines against ILT. We have evaluated the role of three major ILTV surface glycoproteins, namely, gB, gC, and gD in protection and immunity against ILTV infection in chickens. Using reverse genetics approach, three recombinant Newcastle disease viruses (rNDVs) designated rNDV gB, rNDV gC, and rNDV gD were generated, each expressing gB, gC, and gD, respectively, of ILTV. Chickens received two immunizations with rNDVs alone (gB, gC, and gD) or in combination (gB + gC, gB + gD, gC + gD, and gB + gC + gD). Immunization with rNDV gD induced detectable levels of neutralizing antibodies with the magnitude of response greater than the rest of the experimental groups including those vaccinated with commercially available vaccines. The birds immunized with rNDV gD showed complete protection against virulent ILTV challenge. The birds immunized with rNDV gC alone or multivalent vaccines consisting of combination of rNDVs displayed partial protection with minimal disease and reduced replication of challenge virus in trachea. Immunization with rNDV gB neither reduced the severity of the disease nor the replication of challenge virus in trachea. The superior protective efficacy of rNDV gD vaccine compared to rNDV gB or rNDV gC vaccine was attributed to the higher levels of envelope incorporation and infected cell surface expression of gD than gB or gC. Our results suggest that rNDV expressing gD is a safe and effective bivalent vaccine against NDV and ILTV.