IgG subclass responses to proinflammatory fraction of Brugia malayi in human filariasis.

Background & objectives: Earlier we demonstrated that immunization with F6, a proinflammatory molecular fraction isolated from the human filarial parasite Brugia malayi, protected the host and eliminated the infection in Mastomys coucha by a Th1/Th2 response including IgG2a antibody response. Whether F6 molecules become accessible to human host during natural course of infection and elicit similar response is not known. The present study was undertaken to determine the profile of IgG subclasses specifically reactive to F6 in different categories of bancroftian filariasis cases to infer any relationship between the levels of a particular F6-specific IgG subclass and the infection or disease status. Methods: Serum samples of normal individuals from filariasis non-endemic regions of India like Jammu & Kashmir, Uttarakhand, and Chandigarh [(NEN-W; n=10), healthy subjects from USA (NEN-U; n=10) and three categories of bancroftian filariasis cases from endemic areas: endemic normals (EN; n=10) with no symptoms and no microfilariae, asymptomatic microfilaremics (ASM; n=10) and chronic symptomatic amicrofilaremics (CL; n=10) were assayed for F6-specific IgG1, IgG2, IgG3 and IgG4 by ELISA using SDS-PAGE-isolated F6 fraction of B. malayi adult worms. Results: Significantly high levels of F6-specific IgG1, IgG2 and IgG3 were found in CL (P<0.001) and EN (P<0.01-0.001) bancroftian filariasis cases compared to NEN-U. Significant levels of F6-specific IgG1 (P<0.01) and IgG2 (P<0.01) but not IgG3 were found in ASM cases compared to NEN-U. The most abundant was IgG2 which when compared to NEN-U, was significantly high in CL (P<0.001) and EN cases (P<0.001), followed by ASM (P<0.01). F6-specific IgG4 response in EN, ASM and CL subjects was not significantly different from the levels of NEN-U. Among the non-endemic normals, the NEN-W subjects showed significant reactivity with IgG2 (P<0.001) but not with IgG1, IgG3 and IgG4 as compared to NEN-U subjects. IgG subclass levels were different in different categories. Interpretation & conclusions: The high levels of F6 reactive IgG1, IgG2 and IgG3 in endemic normals and chronic symptomatic bancroftian patients, and IgG1 and IgG2 in asymptomatic microfilaraemics, suggest that F6 molecules of parasite are accessible in these subjects for IgG subclass-specific immune response and IgG2 may be related to pathogenesis. Studies using individual F6 molecules will be done to identify the molecule(s) involved in infection and protective immunity.

Detection of prodromal symptoms of relapse in mania & unipolar depression by relatives & patients.

Background & objectives: Detection of prodromal symptoms among patients with mania by their immediate relatives has been seldom examined. We carried out this study to examine the ability to detect and report prodromol symptoms of manic relapses by patients themselves and their relatives. Methods: The ability of patients and their relatives to detect prodromal symptoms was examined among 60 remitted patients, 30 each with DSM-IV diagnoses of bipolar disorder and recurrent depressive disorder, with recent manic/depressive relapses, and their 60 immediate relatives, using an instrument composed of items from common symptom-scales, as well as by unstructured interview. Results: Seventy per cent of patients with mania reported prodromes prior to relapse. This was significantly (P<0.01) less than the proportion of their relatives (97%), as well as the proportion of patients with unipolar depression (93%), reporting prodromal symptoms (P<0.05) among patients. Mean duration of the prodromal period reported by patients with mania was about 20 days (median-10 days); relatives reported durations which were longer by about 5 days. Prodromes of unipolar depression (mean 42.7 days; median- 21 days), were significantly longer than of mania, when reported by patients, but not by their relatives. Differences in reporting of prodromes, between relatives and patients seen in mania, were not observed in unipolar depression. The number and type of prodromal symptoms of mania reported was similar among patients and relatives. Interpretation & conclusions: Our findings showed that relatives of patients with mania were better at detecting prodromes of relapse; thus, input from relatives can improve the early detection of prodromal symptoms to prevent relapses of bipolar disorder.

Antifilarial activity of Caesalpinia bonducella against experimental filarial infections.

BACKGROUND & OBJECTIVE: Lymphatic filariasis is a disabling disease that continues to cripple population in tropical countries. Currently available antifilarial drugs are not able to control the disease. Therefore, a better antifilarial is urgently required for proper management of the disease. We undertook this study to assess the antifilarial activity of Caesalpinia bonducella-seed kernel against rodent filarial parasite in experimental model. METHODS: Microfilaraemic cotton rats and Mastomys coucha harbouring Litomosoides sigmodontis and Brugia malayi respectively, were treated with crude extract or fractions of the seed kernel C. bonducella through oral route for 5 consecutive days. Microfilaricidal, macrofilaricidal and female worm sterilizing efficacy was assessed. RESULTS: Crude extract showed gradual fall in microfilariae (mf) count in L. sigmodontis-cotton rat model from day 8 post-treatment attaining more than 95 per cent fall by the end of observation period. It also exhibited 96 per cent macrofilaricidal and 100 per cent female sterilizing efficacy. The butanol fraction F018 caused 73.7 per cent reduction in mf count and 82.5 per cent mortality in adult worms with 100 per cent female sterilization. The aqueous fraction F019 exerted more than 90 per cent microfilaricidal activity and 100 per cent worm sterilization. Two chromatographic fractions, F024 and F025 of hexane soluble fraction exhibited 64 and 95 per cent macrofilaricidal activity, respectively. Both the fractions caused gradual fall in microfilaraemia and 100 per cent worm sterilization. In B. malayi-M. coucha model F025 showed gradual reduction in microfilaraemia and caused 80 per cent sterilization of female parasites INTERPRETATION & CONCLUSION: In conclusion, C. bonducella- seed kernel extract and fractions showed microfilaricidal, macrofilaricidal and female-sterilizing efficacy against L. sigmodontis and microfilaricidal and female-sterilizing efficacy against B. malayi in animal models, indicating the potential of this plant in providing a lead for new antifilarial drug development.

Serous fluid leakage following modified Blalock-Taussig operation using PTFE grafts.

BACKGROUND: Serous fluid leakage is an unusual but often devastating complication following the placement of a modified Blalock-Taussig shunt using a polytetrafluoroethylene graft. METHOD AND RESULTS: Between September 1994 and September 1999, out of 268 patients undergoing a modified Blalock-Taussig shunt using polytetrafluoroethylene grafts, 10 developed massive pleural effusion or seroma due to a leak from the surface of the shunt. The age of the patients ranged from 9 days to 7 years. There were 7 males and 3 females. Nine patients presented with respiratory distress between 2 and 12 weeks of shunt surgery and one presented with sudden cardiac arrest. The shunt was patent in all the patients. Initial management was conservative. i.e. by pharmacological means and tube thoracostomy. Reoperation was undertaken in 9 patients when conservative treatment failed. All patients survived except one who had a cardiac arrest before any intervention could be carried out. CONCLUSIONS: Patients with serous effusion have significant morbidity and mortality and often require reoperation. The initial management remains conservative but, if unsuccessful, re-exploration can be undertaken as it proved to be uniformly successful in our experience.

Fine needle aspiration cytology, histology and MIB-1 proliferative index in a case of dyshormonogenetic goitre.

The fine needle aspiration (FNA) cytologic findings along with histology and MIB-1 proliferative index in a case of dyshormonogenetic goitre is presented. A 12-year old female child from non-endemic zone presented with a isotopically cold solitary thyroid nodule with a history of goitre being present since birth. Past history of any neck irradiation or maternal ingestion of any goitrogen during the antenatal period and family history of goitre were negative. FNA cytology revealed an extremely cellular preparation with predominantly microfollicular pattern without colloid. Nuclei were round to oval, slightly enlarged with evenly distributed chromatin and inconspicuous nucleoli. Larger tissue fragments also showed foci of solid cell groups with nuclear crowding, overlapping and loss of polarity in addition to the prevalent microfollicular pattern. Occasional tissue fragments showed solid groups of trapped follicular epithelial cells in the matrix of fibrocollagenous tissue. Histology showed an intensely hyperplastic follicular cells with nodule formation, irregular fibrosis, pseudo capsular or vascular wall invasion mimicking malignancy. Immunohistochemistry for calcitonin was negative but thyroglobulin was positive. MIB-1 (Ki-67) proliferation index varied from 0.05 to 0.26 (mean 0.13) in the hyperplastic nodules versus 0.9 to 2.1 (mean 1.34) in the hyperplastic solid microfoci scattered amidst the grossly normal appearing thyroid tissue. The possible cytologic diagnostic pitfalls in favor of follicular neoplasm is discussed.

Role of radionuclide perfusion study in cold solitary thyroid nodule for diagnosis of malignancy: a complimentary diagnostic modality to fine needle aspiration cytology.

One hundred and forty eight subjects with euthyroid solitary thyroid nodules (STN) were taken up for radionuclide perfusion study. They were found to have a cold STN on 99mTc thyroid static scan. All had fine needle aspiration cytology (FNAC), and except for subjects with chronic lymphocytic thyroiditis, were subjected to surgery for tissue diagnosis by histopathology. The diagnostic findings in these patients of solitary thyroid nodules were correlated with the histopathology. Radionuclide perfusion study is considered useful to differentiate benign from malignant cold thyroid solitary nodules with high degree of sensitivity (95%) and specificity (87.9%).

Hyalinizing trabecular adenoma--a case report with FNAC histologic, MIB-1 proliferative index and immunohistochemical findings.

Hyalinizing trabecular adenoma is a recently described benign thyroid tumor, almost exclusively occurring in females. The morphological features of this entity overlap with both papillary and medullary carcinoma to varying extent. This, in turn, creates a situation of serious diagnostic pitfall particularly for a false positive diagnosis of papillary carcinoma in fine needle aspiration (FNA) cytology. False consideration of medullary carcinoma is also possible by the unwary especially if staining for Congo red and/or immunostaining for calcitonin is not resorted to. At histologic level, the distinctive architectural pattern is however of great help and thus poses a much lesser danger of misdiagnosis. We relate here our experience in a recently encountered case of hyalinizing trabecular adenoma and describe detailed FNA cytologic and histologic findings along with immunohistochemical profile using a panel of eight monoclonal antibodies. The tumor proliferative potential has also been assessed using MIB-1 (Ki-67) immunostaining. The various pros and cons of diagnostic pitfalls are discussed.