A study of acute febrile encephalopathy with special reference to viral etiology

Objective  To study the etiological profile of patients with acute febrile encephalopathy syndrome focusing chiefly on the viral etiology, and to correlate clinical and radiological features of patients with viral encephalitis. Methods  A prospective hospital based study conducted on the consecutive patients admitted in a pediatric unit during the period of 1^st February 2004 to 31st January 2005 based on the following inclusion criteria: (1) Age more than 1 month and less than 18 years and (2) A diagnoses of acute febrile encephalopathy, based on the following criteria: (i) fever (ii) acute depression of consciousness or mental deterioration for more than 12 hours with or without motor or sensory deficit and (iii) Total duration of illness at the time of admission 1 week or less. Results  The final study group comprised of 151 patients with mean age of 3.21 ± 2.9 (range of mth-13 years) and male: female ratio of 1.71: 1. A diagnosis other than viral encephalitis was reached in 94 patients (62.3 %). Pyogenic meningitis was the most frequent diagnosis 51(33.8 %) followed by tubercular meningitis 12 (7.9 %), and cerebral malaria 8 (5.2 %) in the patient group of non-viral causes. Fifty-seven cases (37.3%) were suspected as viral encephalitis and mean age of the cases suspected as viral encephalitis was 2.8 ± 2.9 (Range 1 mth-10 yrs) with male: female ratio of 1.28: 1. Etiological diagnosis was reached or considered probable in 41 (72%) cases out of the suspected patients. The most common etiological agent identified was enterovirus 71 in 20 patients (35.1 %). The other viruses identified were mumps in 6 (10.5%), Japanese encephalitis in 5 (8.7%), and measles in 4 (7%) cases. MRI brain was done in 39 patients and was abnormal in 14 patients. Out of 57 cases of suspected viral encephalitis 10 patients expired within 48 hours, 2 > 48 hours and 19 atients had significant neurological sequels at discharge. Conclusion  The etiology of acute febrile encephalopathy varies from infectious etiologies to noninfectious metabolic disorders. There are no distinguishing clinical or radiological features to differentiate the various causes of viral encephalitis. The clinical and the radiological findings in encephalitis should be interpreted in the geographical and other epidemiological background.     

Effect of Cuscuta reflexa Roxb on androgen-induced alopecia

Background  Alopecia is a psychologically distressing condition. Androgenetic alopecia, which affects millions of men and women, is an androgen-driven disorder. Here, Cuscuta reflexa Roxb is evaluated for hair growth activity in androgen-induced alopecia.
Methods  Petroleum ether extract of C. reflexa was studied for its hair growth–promoting activity. Alopecia was induced in albino mice by testosterone administration for 20 days. Its inhibition by simultaneous administration of extract was evaluated using follicular density, anagen/telogen ratio, and microscopic observation of skin sections. To investigate the mechanism of observed activity, in vitro experiments were performed to study the effect of extract and its major component on activity of 5α-reductase enzyme.
Results  Petroleum ether extract of C. reflexa exhibited promising hair growth–promoting activity as reflected from follicular density, anagen/telogen ratio, and skin sections. Inhibition of 5α-reductase activity by extract and isolate suggest that the extract reversed androgen-induced alopecia by inhibiting conversion of testosterone to dihydrotestosterone.
Conclusions  The petroleum ether extract of C. reflexa and its isolate is useful in treatment of androgen-induced alopecia by inhibiting the enzyme 5α-reductase.     

Scope of nanotechnology in ovarian cancer therapeutics

Background

Ovarian cancer is the most common cause of cancer related death from gynecologic tumors in the United States. The insidious nature of the disease precludes early diagnosis, therefore surgical debulking and chemotherapy are considered as standard treatment modalities for advanced stages. We investigated the effect of the LXR agonist, T0901317, on ovarian cancer cell proliferation and apoptosis as a potential therapeutic agent.

Results

T0901317 treatment resulted in a significant (P <0.001) inhibition of cell proliferation in a time- and dose-dependent manner in CaOV3, SKOV3 and A2780 cells. Western blot analysis demonstrated an induction of p21 and p27 with a concominant reduction in phospho-RB protein levels. Cell cycle analysis demonstrated a significant (P <0.001) arrest in the G1 cell cycle phase. Significant induction of Caspase-3 and BAX gene expression occurred with treatment. Induction of apoptosis was confirmed by significant (P < 0.001) elevation of caspase activity on FACS analysis, caspase-glo assay, BAX protein induction and decreased caspase 3 precursor protein expression on Western blot analysis. LXR α/β knockdown experiments did not reverse the anti-proliferative and cytotoxic effects of T0901317.

Conclusions

The LXR agonist, T0901317, significantly suppresses cell proliferation and induces programmed cell death in a dose- and time-dependent manner. Our results indicate that T0901317 induces its anti-proliferative and cytotoxic effects via an LXR-independent mechanism.     

Association of tuberculous endometritis with infertility and other gynecological complaints of women in India

Endometrial biopsy samples derived from 393 patients with assorted gynecological complaints were investigated for mycobacterial infection. By employment of four different techniques, mycobacterial pathogens were detected irrespective of the nature/type of clinical complaint. Mycobacterium tuberculosis was the predominant pathogen detected among the samples investigated.     

Plasmodium falciparum-free merozoites and infected RBCs distinctly affect soluble CD40 ligand-mediated maturation of immature monocyte-derived dendritic cells

Free plasmodium merozoites released from the parasitized hepatocytes and erythrocytes represent a transitory, extracellular stage in its mammalian host. In this study, we compared the effect of Plasmodium falciparum-free merozoites with infected RBCs (iRBCs) on the maturation of human monocyte-derived dendritic cells (DCs) in vitro. Phagocytosed-free merozoites prevented soluble CD40 ligand (sCD40L)-induced, phenotypic maturation of DCs and secretion of IL-12p70 but enhanced IL-10 production and primed, naive CD4+ cells to produce a high level of IL-10 compared with IFN-gamma. Free merozoites augmented sCD40L-induced ERK1/2 activation, and inhibition of ERK1/2 with its inhibitor PD98059 markedly abrogated IL-10 production and rescued IL-12 production. Therefore, the molecular mechanisms by which free merozoites antagonized sCD40L-induced DC maturation appeared to involve the activation of the ERK pathway. In contrast, phagocytosed iRBCs by itself induced DCs to semi-maturation, responded to CD40 signaling by maturing and secreting increased levels of TNF-alpha, IL-6, and also IL-12p70, and led to a pronounced, proinflammatory response by the allogenic CD4+ T cells. iRBCs regulate CD40-induced p38MAPK. Studies using inhibitors selective for p38MAPK (SB203580) showed that p38MAPK played an essential role in the maturation and function of DCs. Our results reveal the ability of free merozoites and iRBCs to distinctly alter the sCD40L-induced DC functioning by regulating the activation of the MAPK pathway that can inactivate or exacerbate immune responses to promote their survival and the development of parasite-specific pathologies.     

HN protein of Newcastle disease virus causes apoptosis in chicken embryo fibroblast cells

Newcastle disease virus (NDV), an avian paramyxovirus, induces apoptosis in chicken embryo fibroblast (CEF) cells. In the present investigation, the ability of haemagglutinin-neuraminidase (HN) protein of NDV to cause apoptosis in CEF cells was examined. The results revealed that cells expressing the HN protein demonstrated decreased DNA content, phosphatidylserine exposure and increased cytoplasmic vacuolation. Up-regulation of caspase-1, -9, -8, -3, loss of mitochondrial transmembrane potential and an increase in oxidative stress were also observed in cells expressing the HN protein. Based on the above results it can be concluded that HN protein of NDV causes apoptosis in CEF cells.     

Gemcitabine concurrent with radiation therapy for locally advanced head and neck carcinomas

Background

Management of advanced head and neck carcinoma is a challenging proposition. Presently concomitant chemo-irradiation has become the standard of care in such patients. Many chemotherapeutic drugs have shown radio-sensitising effects when used concomitantly along with radiation. The present study was carried out with the objective of assessing the feasibility and efficacy of low dose gemcitabine as radiosensitizer when used during radical radiotherapeutic management of patients with locally advanced head and neck carcinomas.

Patients and methods

From November 2000 to March 2003, Eighty histopathologically proven cases of squamous cell head and neck carcinoma were included in this trial, 40 patients were randomly assigned to receive radiotherapy alone and 40 patients to receive gemcitabine along with radiotherapy.

Results

All patients were assessable for toxicity and response. Severe mucositis (WHO level 5 reactions were observed in 67% patients in the CT/RT group vs 16% patients in the RT only group. No severe hematological toxicity was seen. The rates of complete and partial responses were 42.5% & 57.5% respectively for RT only and 62.5% &37.5%, respectively for CT/RT group. There was no significantdifference in the response rates at the end of treatment but disease free survival at three years was better in the CT/RT group (63.3% vs 20%). Nine of the 17 patients with complete response in the radiation only group developed relapse while no relapses were seen in CT/RT group.

Conclusion

In the present study the combination of gemcitabine and radiotherapy has not shown any statistical difference in locoregional control but survival advantage was seen as compared to radiotherapy alone. At the same time more mucosal and skin toxicity was encountered when Gemcitabine is given concurrently with radiation.     

Increase in endothelin B receptor expression in optic nerve astrocytes in endothelin-1 induced chronic experimental optic neuropathy

The purpose of this study was to determine whether endothelin B (ETB) receptor levels in the optic nerve are related to retinal ganglion cell (RGC) loss in a model of chronic endothelin-1 (ET-1) induced optic neuropathy. RGCs of adult Brown Norway rats were first retrogradely labeled with fluorochrome from the superior colliculi. An osmotic minipump was surgically implanted 7 days later to deliver 10⁻¹¹ M (n = 9), 10⁻⁹ M (n = 12) or 10⁻⁷ M (n = 9) ET-1 to the retrobulbar optic nerve for 28 days. RGC survival was expressed as the ratio of RGC counts in experimental versus control eyes in wholemounted retinas. Optic nerves were used for either ETB western blot analysis (n = 24) or immunohistochemistry (n = 6) for ETB and glial fibrillary acidic protein (GFAP) to localize astrocytes. ETB expression was higher in the experimental nerve compared to the fellow untreated control nerve in 19 (79%) of the 24 animals with a mean increase of 16.7 ± 4.5% in densitometric analyses of the immunoblots. Experimental nerves showed stronger labeling for both ETB and GFAP compared to control nerves. ETB-positive cells almost completely co-localized with GFAP-positive cells in both experimental and untreated control nerves, however, ETB expression was stronger in the astrocyte soma and proximal processes, while GFAP was expressed more strongly in the distal processes. There was a weak relationship between RGC loss and increase in ETB expression (r = −0.417, p = 0.076). There is an upregulation of ETB expression in optic nerve astrocytes in ET-1 induced chronic optic neuropathy causing RGC loss.     

Ocular morbidity prevalence among school children in Shimla, Himachal, North India

Background

Data on eye diseases among school children is not readily available. Considering the fact that one-third of India''s blind lose their eyesight before the age of 20 years and many of them are under five when they become blind, early detection and treatment of ocular morbidity among children is important.

Aim

To estimate the prevalence of ocular morbidity among school children of age 6-16 years.

Settings

Government and private coeducational schools in urban area of Shimla.

Design

Cross-sectional

Materials and Methods

Government and private coeducational schools selected by stratified random sampling. About 1561 school children, studying in elementary through secondary class in these schools were examined from August 2001 to January 2002 in Shimla. A doctor did visual acuity and detailed ophthalmic examination.

Statistical analysis

The Chi-square test was used to test differences in proportions. Differences were considered to be statistically significant at the 5% level.

Results

Prevalence of ocular morbidity was 31.6% (CI=29.9-32.1%), refractive errors 22% (CI=21.1-22.8%), squint 2.5% (CI=2.4-2.6%), color blindness 2.3% (CI=2.2-2.4%), vitamin A deficiency 1.8 % (CI=1.7-1.9%), conjunctivitis 0.8% (CI=0.79-0.81%). Overall prevalence of ocular morbidity in government and private schools did not show any statistical significant difference. Prevalence of conjunctivitis was significantly (P<0.5) more in government schools.

Conclusion

A high prevalence of ocular morbidity among high-school children was observed. Refractive errors were the most common ocular disorders.