Serum TNF alpha levels: a prognostic marker for assessment of severity of malaria.

Complicated Plasmodium falciparum infection is associated with a 6.4% mortality rate in India, yet its prognostication is incompletely understood. The conventional prognostic markers of falciparum malaria include clinical, haematological and biochemical parameters. However these factors are non-specific. Hence there is a need of an accurate inexpensive objective marker for prognosticating falciparum malaria infection outcomes. Angiopoietins, angiogenic factors, eotaxins, adhesion molecules and inflammatory cytokines have been studied for prognostication of this common disease. Determination of the first four is technically difficult and requires a high level of expertise and equipment. Intermediary cytokines have the most promising role. This study was conducted with the aim to evaluate the serum level of TNF-α in patients with P. falciparum malaria and carry out statistical analysis of levels of serum TNF-α with parasite index, age, severity of anaemia, hypoglycaemia, hepatic and renal dysfunction. In our study the average TNF alpha level in 91healthy controls was 46.42 pg/ml whereas that in mild falciparum malaria was 100.45 pg/ml, in severe malaria - 278.63 pg/ml and in cerebral malaria it was 532.6 pg/ml. The mean TNF alpha level was significantly different in severe malaria and cerebral malaria compared to that in healthy controls (p < 0.02). The difference in levels of TNF alpha was significantly higher in falciparum malaria patients with anaemia, altered liver functions, hyperparasitemia, leucocytosis, hepatosplenomegaly and hypoglycaemia. The TNF levels did not correlate well with haemolysis markers and patients with altered renal function. Hence a raised TNF alpha can predict the likelihood of oncoming anaemia, hypoglycaemia, altered hepatic function and leucocytosis but not the grades of malaria. The duration of stay in hospital and change in parasite index between the 5(th) day and the 1(st) day of admission was used a clinical outcome marker in this study. The analysis showed that serum TNF alpha was raised significantly (p= 0.001) in patients with longer duration stay in hospital. The cytokine was significantly raised in patients having disorientation /cognitive disorder /coma and ARDS (p= 0.001, 0.0023 respectively). The study concluded that serum TNF alpha if done at time of admission and on day 3 can indicate the severity of disease and its complications.

Study of p53 and bcl-2 Oncoproteins in Ulcerative Colitis with Dysplasia.

BACKGROUND: Dysplasia in ulcerative colitis has been graded on haematoxylin and eosin stain using Riddle's criteria. This system was formed to nullify the inter-observer variation. Few cases of early dysplasia were missed when purely screened on morphology. This study was carried out to detect early dysplasia using p53 and bcl-2 oncoproteins. METHODS: A retrospective study was carried out on paraffin blocks of 100 histologically diagnosed cases of ulcerative colitis at a large service hospital. Haematoxylin and Eosin stained (H &E) slides of these cases were re-examined as per standard techniques. RESULTS: On correlating histological grades with p53 immunoscore it was found that 90.76% of cases graded as negative for dysplasia on H & E, got an immunoscore of 0 and other 9.24% cases which were graded as negative for dysplasia got a score 1+. This shows that the immunohistochemistry was able to pick up 6 cases, which were missed by routine histology. Nine out of 11 cases in which the pathologists could not rule out a dysplasia and graded them as indefinite (probably negative for dysplasia) got a score of 0. In these cases possibly the histological features may be construed as an acute inflammation or repair induced dysplasia which were suspicious for neoplastic dysplasia on routine histology sections. On analyzing our findings on bcl-2 immunohistochemistry it was seen that there was no significant concordance (p>0.05) of immunoscore with the grades of dysplasia estimated morphologically. CONCLUSION: Our study recommends that p53 should be used as regular immunohistochemical marker while grading the dysplasia of ulcerative colitis, especially in indefinite cases as it brings objectivity in grading. Our study also came to a conclusion that use of bcl-2 for grading dysplasia of ulcerative colitis is not of any significant help.