Diagnostic radiology for radiotherapist: the case for structured training in cross-sectional imaging (CT and MRI).
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Biomedical subjects
Publications and source records attributed to S Sundar.
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Stored sera from 429 Indian subjects were assayed to extend the analysis of the accuracy of immunochromatographic strip-test detection of anti-K39 antibody in the non-invasive diagnosis of visceral leishmaniasis (VL). All 225 samples from patients with proven Leishmania infection tested positive [estimated sensitivity = 100%; 95% confidence interval (CI)=98%-100%]. Sera from 99 of the 100 symptomatic patients with other diseases were non-reactive (estimated specificity = 99%; CI = 94%-100%). However, samples from 13 of the 104 apparently healthy controls showed positive strip-test results (estimated specificity = 88%; CI = 79%-93%), yielding an overall specificity of 93% (190/204; CI = 88%-96%). If applied in a practical clinical setting (on symptomatic patients in whom active VL is suspected and other common infections have been excluded), strip testing of serum for anti-K39 antibody should be both sensitive and specific for diagnosing VL in India.
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In this randomized, double-blind, dose-ranging, multicenter trial, 84 patients with visceral leishmaniasis refractory to antimony therapy were administered liposomal amphotericin B (AmBisome) at cumulative doses of 3.75, 7.5, and 15.0 mg/kg for 5 consecutive days. Posttreatment apparent cure and definite cure were assessed at 2 weeks and 6 months after the end of therapy, respectively. Mild to moderate infusion-related fever and rigors were seen in 29 and 44% of patients, respectively. One patient each in the 3.75- and 7.5-mg groups had detectable parasites on splenic smear at posttreatment evaluation. At 6 months' follow-up, however, 2, 1, and 1 patients relapsed in the 3.75-, 7.5-, and 15.0-mg groups, resulting in definite cure rates of 89, 93, and 97%, respectively. There was no significant difference in the cure rates of the 3 groups. Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar.
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OBJECTIVE: To test short course, low dose liposomal amphotericin B as single or daily infusion treatment in Indian visceral leishmaniasis (kala-azar). DESIGN: Randomised, open label study. SETTING: Inpatient unit for leishmaniasis in Bihar, India. PARTICIPANTS: 91 adults and children with splenic aspirate positive for infection. INTERVENTIONS: Total dose of 5 mg/kg of liposomal amphotericin B given as a single infusion (n=46) or as once daily infusions of 1 mg/kg for five days (n=45). MAIN OUTCOME MEASURES: Clinical and parasitological cure assessed 14 days after treatment and long term definitive cure (healthy, no relapse) at six months. RESULTS: All but one person in each group had an initial apparent cure. During six months of follow up, three patients in the single dose group and two in the five dose group relapsed. Complete response (definitive cure) was therefore achieved in 84 of 91 subjects (92%): 42 of 46 patients in the single dose group (91%, 95% confidence interval 79% to 98%) and 42 of 45 in the five dose group (93%, 82% to 99%). Response rates in the two groups were not significantly different. CONCLUSION: Low dose liposomal amphotericin B (5 mg/kg), given either as a five day course or as a single infusion, seems to be effective for visceral leishmaniasis and warrants further testing.
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Growing antimony resistance in patients with visceral leishmaniasis (VL) over last two decades, especially in Indian subcontinent, renders this cheap and easily available drug useless for a vast majority of patients. Use of the second line drug pentamidine isethionate, a toxic drug with declining efficacy, has largely been abandoned. Thus, in these areas amphotericin B remains the only drug; although it cures > 97% patients, infusion-related adverse events are common and occasionally serious toxicity, such as myocarditis, or death can occur. In recent years India has been the center for clinical development of new anti-leishmanial drugs like lipid formulations of amphotericin B, new drugs like parenterally administered aminosidine and oral miltefosine. The alkyl phospholipid compound miltefosine is the first effective oral compound for VL and is likely to be marketed soon. In addition to the monotherapy, efforts in development of combination chemotherapy are needed if the menace of drug resistance is to be contained.
BACKGROUND: Current methods for diagnosis of post kala-azar dermal leishmaniasis (PKDL) do not offer adequate sensitivity and specificity. OBJECTIVES: To develop a simple and sensitive test for field diagnosis of PKDL. METHODS: Immunochromatographic nitrocellulose strips precoated with recombinant k39 antigen were evaluated for the detection of circulating antibodies to leishmanial k39 in PKDL sera. A drop of serum applied to the strip followed by buffer led to the development of two visible bands indicating the presence of anti-k39 IgG. RESULTS: The strip test was able to detect cases of PKDL with 91% sensitivity. The specificity of the test was evaluated using controls with other skin diseases, other common infections and healthy persons from endemic and non-endemic regions. Of 125 controls examined, all were negative on the strip test, indicating 100% specificity of the test. CONCLUSIONS: The immunochromatographic nitrocellulose strips provide a non-invasive, rapid and accurate method for diagnosing PKDL.
Reactive oxygen intermediates (ROI), nitrite and interferon-gamma (IFN-gamma) production were investigated at different times during treatment in 10 patients with visceral leishmaniasis (VL). Hydrogen peroxide (H2O2), superoxide (O2-) and IFN-gamma production by cultured monocytes from patients with active VL were significantly lower compared with the healthy controls. In contrast, nitrite levels in the supernatants from monocyte cultures of VL patients were comparable to healthy controls and increased significantly during antileishmanial therapy. On day 20 of treatment, a significant increase in the release of H2O2, O2- and IFN-gamma was observed. However, at follow-up, 4 months after the end of treatment, the production of H2O2, O2-, IFN-gamma and nitrite had declined significantly. Thus, the impairment in hydrogen peroxide and superoxide production suggests that down-regulation of these mediators may be involved in the reduced killing of parasites by monocytes of active VL patients. Furthermore, the monocytes regained respiratory burst activity as the antileishmanial therapy progressed, suggesting that an immune-based mechanism is involved in successful drug therapy.
Throughout the world, pentavalent antimonial compounds (Sb(v)) have been the mainstay of antileishmanial therapy for more than 50 years. Sb(v) has been highly effective in the treatment of Indian visceral leishmaniasis (VL: kala-azar) at a low dose (10 mg/kg) for short durations (6-10 days). But in the early 1980s reports of its ineffectiveness emerged, and the dose of Sb(v) was eventually raised to 20 mg/kg for 30-40 days. This regimen cures most patients with VL except in India, where the proportion of patients unresponsive to Sb(v) has steadily increased. In hyperendemic districts of north Bihar, 50-65% patients fail treatment with Sb(v). Important reasons are rampant use of subtherapeutic doses, incomplete duration of treatment and substandard drugs. In vitro experiments have established emergence of Sb(v) resistant strains of Leishmania donovani, as isolates from unresponsive patients require 3-5 times more Sb(v) to reach similarly effectiveness against the parasite as in Sb(v) responders. Anthroponotic transmission in India has been an important factor in rapid increase in the Sb(v) refractoriness. Pentamidine was the first drug to be used and cured 99% of these refractory patients, but over time even with double the amount of initial doses, it cures only 69-78% patients now and its use has largely been abandoned in India. Despite several disadvantages, amphotericin B is the only drug available for use in these areas and should be used as first-line drug instead of Sb(v). The new oral antileishmanial drug miltefosine is likely to be the first-line drug in future. Unfortunately, development of newer antileishmanial drugs is rare; two promising drugs, aminosidine and sitamaquine, may be developed for use in the treatment of VL. Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost.
In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain of Leishmania donovani (MHOM/ET/67:LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a >97% reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95% reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis.
The recombinant product (rK39) of the 39-amino-acid repeats encoded by a kinesin-like protein-encoding gene of Leishmania chagasi was evaluated by enzyme-linked immunosorbent assay (ELISA) for diagnostic potential and the ability to predict the response to therapy in Indian kala-azar or visceral leishmaniasis (VL); we also compared its performance with that of crude soluble antigen (CSA). At the diagnosis of VL, the anti-rK39 antibody titer was 59-fold higher than the anti-CSA antibody titer. With successful therapy, antibody titers declined steeply at the end of treatment and during follow-up. In contrast, patients who relapsed showed increased titers of antibodies to rK39. The extremely high levels of anti-rK39 antibodies in VL cases suggest the application of rK39 for sensitive and specific serodiagnosis, and rK39 ELISA is also valuable in monitoring drug therapy and detecting relapse of the disease.
Kala-azar in India is becoming increasingly difficult to treat, which may be due to the presence of species other than Leishmania donovani; Leishmania tropica was reported to cause the same clinical syndrome in the area. Over the past 3 years, we have collected samples from 241 patients with visceral leishmaniasis from across the region. Of the 189 isolates that grew on diphasic medium, 159 were successfully transferred to liquid medium for typing. Clinically, 80% of these were resistant to antimony. Lipophosphoglycan-specific monoclonal antibodies were used to distinguish the 2 species by agglutination of promastigotes; all 159 were shown to be L. donovani. Eighty-three isolates were confirmed to be L. donovani by isoenzyme analysis, by amplification of kinetoplast DNA, or both, in comparison with multiple reference strains; none were L. tropica. Thus, the rising incidence of clinical resistance to treatment is unlikely to be due to a different species causing kala-azar in north Bihar.
A simple and inexpensive cell dissociation sieve-tissue grinder apparatus consisting essentially of stainless steel sieve (the one popularly used for sieving tea leaves) and a glass syringe plunger acting as pestle, is described for making single cell suspension.
OBJECTIVE: The present study was conducted to evaluate the efficacy of low dose cyclosporine-A in the patients of severe aplastic anaemia, who cannot afford allogenic bone marrow transplantation and immunosuppressive therapy with antithymocyte globulin. METHODS: The diagnosis of severe aplastic anaemia was established by standard criteria. Twelve patients were given cyclosporine-A orally at a dose of 6 mg/kg body weight in divided doses in two daily equal proportions for six months. Eleven patients were put on oral stanozolol in the dosage of 1 mg/kg body weight/day in divided doses. All surviving patients were evaluated at three and six months. RESULTS: At the end of six months, 41.66% of twelve patients responded to cyclosporine-A. One patient had complete response and four patients had partial response. Only one out of 11 patients receiving stanozolol responded. CONCLUSIONS: i) Cyclosporine-A is a viable therapeutic option in the treatment of severe aplastic anaemia, ii) Low dose cyclosporine-A is able to slow down the stormy course of the severe aplastic anaemia, iii) Androgens have very little effect on the survival of patients of severe aplastic anaemia.
Pure red cell aplasia (PRCA) associated with non-Hodgkin's lymphoma, is an extremely rare condition, with few cases reported worldwide. More commonly PRCA is associated with thymoma or viral infections. Steroids and other immunosuppressive drugs are the preferred treatment of PRCA.
Synchronized chaotic systems have recently been applied to the area of secure communications in a variety of ways. At the same time, there have also been significant advances in deciphering messages masked by chaotic signals. It is important, therefore, to explore more secure approaches to using chaos in communication. We show that multiple chaotic systems can be synchronized through a scalar coupling which carries a stochastic signal generated by random multiplexing of the source systems. This approach, which is a variant of the active-passive decomposition method, promises enhanced security in chaos-based communication.