Analytical Qbd Approach For Development And Validation Of Rp-High Performance Liquid Chromatography Method For Determination Of Tofisopam In Pure Form And Tablets

A novel, simple, optimized reversed-phase chromatography method for assay of Tofisopam in pure and tablet form is developed. The experimental trial was by Box Behnken design using the Design Expert® software 10 version. The attributes selected were peak symmetry, number of theoretical, and peak purity. The predicted data satisfied with actual experimental data. The optimized chromatographic conditions required a quaternary pump with a mobile phase of Water: Acetonitrile 25:75 v/v at 1 mL/min, oven temperature at 25oC at 310 nm using C18(250 × 4.6 mm Id, 5μm) column and PDA detector with a run time of 5 min. The method was validated for linearity, precision, accuracy, and specificity. The method produced a linear response over a concentration range of 4–24 ppm with an overall average accuracy of 99.98%. The method was robust, reproducible, and specific with respect to the retention time of tofisopam.

A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome TM ) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India.

Background: In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. Materials and Methods: A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. Results: The average body weight of patients was 26.4±14.8 (n=22), 32.9±19.4 (n=23) and 37.9±20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2±13.4, 16.0±10.9 and 22.7±16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17±9.8, 16.2±8.3, and 14.7±10.7 days, respectively. The time to resolve fever was 13.3±10.2, 10.9±7.1, 10.1±6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4±9.6, 10.6±7.6 and 7.3±3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. Conclusions: This small randomized study showed that the indigenous liposomal formulation Fungisome TM appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

Assessment of use of complementary alternative medicine and its impact on quality of life in the patients attending rheumatology clinic, in a tertiary care centre in India.

Purpose: Complementary and alternative medicine (CAM) has witnessed an increase in use in recent times in rheumatological conditions and is expected to have impact on the quality of life (QOL). We had planned to conduct this study to investigate the extent of use of CAM and its effect on QOL of patients at a tertiary care center. Materials and Methods: Ethics committee approval was obtained. Sixty patients suffering from osteoarthritis (OA) and rheumatoid arthritis (RA) were enrolled as per the selection criteria, after obtaining their informed consent. Each patient was interviewed for CAM use/non-use, and Western Ontario and McMaster Universities (WOMAC) (modified) index for QOL was recorded by the study personnel. Statistical Analysis: The normality was checked by using Kolmogorov-Smirnov test. Descriptive statistics was performed and Mann-Whitney U-test was used to compare the QOL of CAM users and non-users. Results: Of the 60 patients enrolled with OA (10) and RA (50), 58% (35/60) used CAM. Ayurveda and massage therapy were the commonest [80% (28/35)], followed by yoga asana [34% (12/35)] and homoeopathy [20% (7/35)]. It was observed that combinations of therapies were used too. Nearly half [49% (17/35)] of the CAM users were on self-prescribed medication and 71% (25/35) of them did not inform the physician of CAM use. The QOL of CAM users (WOMAC score: 56.31 ± 6.82) was better than that of CAM non-users (WOMAC score: 60.16 ± 4.02) (P value 0.01). Conclusion:Patients with RA frequently used CAM and QOL improvised with CAM use. We observed that self-administration of CAM was common and this was not informed to the treating physician.

Disseminated histoplamosis.

A case of disseminated histoplasmosis in a 45-year-old male patient with acquired immunodeficiency syndrome (AIDS) from Pune is reported. The patient presented with high-grade fever and pain in hypochondrium. Clinical signs were pallor and hepatosplenomegaly. Bone marrow and splenic aspirate revealed numerous intracellular oval shaped yeast forms. Histoplasma capsulatum was isolated from the bone marrow and splenic aspirate. H. capsulatum infection is an opportunistic infection usually reported from patient with AIDS in areas endemic for H. capsulatum. The present case highlights the fact that histoplasmosis could be an emerging opportunistic infection in India.

Tissue concentration, systemic distribution and toxicity of clofazimine--an autopsy study.

There are very few autopsy studies available on systemic distribution of clofazimine, a drug with anti-mycobacterial activity, used in multidrug therapy (MDT) regimen of leprosy and in erythema nodosum leprosum (ENL). An autopsy study was done on a 45 year old female of lepromatous leprosy (LL) on MDT and long term high dosage of clofazimine. Patient succumbed to intractable abdominal pain, diarrhoea, hypokalemia following clofazimine treatment. Autopsy study revealed yellowish brown discoloration of skin, viscera and body fluids. Chemical extraction of the drug revealed the highest concentration of the drug in jejunum (1.5mg/gm),followed by spleen (1.2mg/gm), pancreas (0.4mg/gm), adrenal (0.25mg/gm), liver (0.21mg/gm), and less than 0.2mg/gm in lung, fat, large intestine and stomach. It can be inferred from the present study that the drug is absorbed from the jejunum and gets deposited in fat, reticulo-endothelial cells (R-E cells) and hepatocytes. The drug is best demonstrated in cryostat sections and is lost partly during tissue processing and staining. The drug toxicity can be fatal as seen in the present case.

A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy.

76 skin biopsies that included material from 7 controls, 65 granulomatous skin lesions and 2 each of granulation tissue and chronic non-specific inflammation, were subjected to histopathological evaluation on haematoxylin and eosin and pertinent special stains. Mast cell study was done on slides stained by toluidine blue method, with special reference to their location, and morphology and cell count were done with the help of occculomicrometre. In normal skin, mast cell density was 11.43/mm2 with a range of 6-22/mm2 and an S.D. of 5.94. Highest value in the whole series was seen in TVC (66/mm2), followed by lupus vulgaris (50/mm2). Mast cell counts were normal in indeterminate and TT leprosy and showed a rise over the immunological spectrum BT to LL, with values in LL being 32.86/mm2 (28-40/mm2).

Pathology of Toxoplasma myocarditis in acquired immunodeficiency syndrome.

Involvement of the myocardium by Toxoplasma gondii is seen in patients of acquired immunodeficiency syndrome (AIDS), mostly in association with toxoplasma encephalitis. Only few patients die as a direct result of cardiac dysfunction. Clinico-pathological findings of three cases of toxoplasma myocarditis are reported, one of which presented and died due to massive pericardial effusion. All cases showed diffuse myocarditis with parasites on histopathological examination. Incidence of toxoplasma myocarditis in patients dying with AIDS was 8.3% (3 out of 36 cases).

Dedifferentiated chordoma--a case report.

A case of a recurrent sacro-coccygeal chordoma is reported which histologically showed an admixture of a conventional chordoma and a pleomorphic sarcoma. These tumours are called dedifferentiated chordomas and carry an ominous prognosis.

Autopsy study of pediatric deaths.

OBJECTIVE: Childhood autopsies occurring during January 1997 to December 1999 were reviewed. METHOD: Of the total 1,445 deaths autopsied, 441 (30.5%) were of pediatric patients. RESULT: Of these deaths, 70.3% occurred during neonatal period, 8.6% in infancy, and 21.1% in childhood. Birth asphyxia (57.7%) was the most frequent mode of death in the neonatal period. Infections (67.2%) predominantly accounted for infant and childhood mortality, those of respiratory tract (46.1%) being most frequent in infancy, early and mid childhood, and enteric fever in late childhood (33.3%). Discrepancy between ante-mortem and post-mortem diagnosis occurred in 29 cases (6.6%). CONCLUSION: Autopsy is an important clinical tool providing useful information to the physician. Few published reports are available on pediatric autopsies. This study aims to help in a better understanding of causes of deaths in neonates, infants and children.

Protein profile in leprosy.

Serum proteins and plasma fibrinogen were estimated in 103 patients in various groups of leprosy and 52 patients of reactional leprosy. Total proteins, serum globulin and fibrinogen showed significant rise while serum albumin showed fall over the immunological spectrum from TT to LL. Type II reactional leprosy similarly revealed significant rise in globulin and fibrinogen. The comparison of these parameters between most of the comparable groups of leprosy was statistically significant. ENL patients after complete subsidence of reaction and after steroid treatment showed significant decrease in these protein fractions, thus conferring some prognostic implication on these tests.

Blood transfusion associated fatalities.

16 post transfusion deaths were studied by reviewing clinical and blood bank records and by postmortem examination whenever possible. 13 of these cases belonged to regional blood bank, 2 were transfused in other hospitals and referred for management of transfusion reactions and one case be longed to other blood bank in the city. 3 deaths could not be attributed to transfusion reaction. Post transfusion endotoxaemia (7 cases) was the most frequent mode of transfusion associated fatality followed by cardiac overload (5 cases) and septicaemia (3 cases). In two cases endotoxaemia coexisted with cardiac overload. The pretransfusion compromised clinical course unfavourably thereby contributing significantly in death. The 3 clinically stable patients succumbed to posttransfusion endotoxaemia. The incidence of transfusion associated fatality in the present institute was 0.028% amongst total transfusions.

Study of systemic fungal infections in autopsy material.

A retrospective study of 2526 autopsy cases was done in order to find out the pattern of systemic fungal infections. The autopsy records were reviewed for case histories, gross and histological findings. The histological sections from cases showing evidence of fungalo infections were reviewed. The fungal infections were found in 28 cases. Of these 11 (93.29 percent) were aspergillosis, 8 (28.27 percent) were mucormyosis, 6 (21.43 percent) were monilial infections and 3 (10.71 percent) were monilial infections and 3 (10.71 percent) were cryptococcosis. The incidence of systemic fungal infection was 1.11 percent. The most common type of fungal infection was aspergillosis. The maximum number of fungal infection was seen in the respiratory system. The fungal infections presented as opportunistic infections in all but one case. The metabolic disturbance was the most frequent predisposing condition for systemic fungal infections.

Fibrinolytic phenomenon in leprosy.

Fibrinolytic activity in eighty-one patients with different types of leprosy and thirty-two normal healthy controls was studied by Euglobulin Lysis Time Method, Fibrinolytic activity was markedly decreased in patients with lepromatous leprosy and those with ENL reaction. Decline in fibrinolytic activity during ENL was independent of frequency of attacks. Fibrinolytic activity was partly restored after subsidence of ENL reaction, though it failed to attain normal levels. Cutaneous vasculitis seems to be most probable cause of fall in fibrinolytic activity in lepromatous leprosy and ENL reaction.