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Biomedical subjects

S Sundar

Publications and source records attributed to S Sundar.

At least 37 records · Page 2Linked to original sources
PubMed2005

Immunostimulatory cellular responses of cured Leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovani.

Development of an effective immunoprophylactic agent for visceral leishmaniasis (VL) has become imperative due to the increasing number of cases of drug resistance and relapse. Live and killed whole parasites as well as fractionated and recombinant preparations have been evaluated for vaccine potential. However, a successful vaccine against the disease has been elusive. Because protective immunity in human and experimental leishmaniasis is predominantly of the Th1 type, immunogens with Th1 stimulatory potential would make good vaccine candidates. In the present study, the integral membrane proteins (IMPs) and non-membranous soluble proteins (NSPs), purified from promastigotes of a recent field isolate, Leishmania donovani stain 2001, were evaluated for their ability to induce cellular responses in cured patients (n = 9), endemic controls (n = 5) of visceral leishmaniasis (VL) and treated hamsters (n = 10). IMPs and NSPs induced significant proliferative responses (SI 6.3 +/- 4.1 and 5.6 +/- 2.3, respectively; P < 0.01) and IFN-gamma production (356.3 +/- 213.4 and 294.29 +/- 107.6 pg/ml, respectively) in lymphocytes isolated from cured VL patients. Significant lymphoproliferative responses against IMPs and NSPs were also noticed in cured Leishmania animals (SI 7.2 +/- 4.7 & 6.4 +/- 4.1, respectively; P < 0.01). In addition, significant NO production in response both IMPs and NSPs was also noticed in macrophages of hamsters and different cell lines (J774A-1 and THP1). These results suggest that protective, immunostimulatory molecules are present in the IMP and NSP fractions, which may be exploited for development of a subunit vaccine for VL.

Adolescent↗
PubMed2005

Evaluation of PCR for diagnosis of Indian kala-azar and assessment of cure.

This study was done to evaluate PCR with Ld1 primers for the diagnosis of Indian visceral leishmaniasis (VL) and to assess its role in prediction of the disease outcome. The PCR assay was performed with DNA isolated from the peripheral blood of parasitologically confirmed cases of VL before the initiation of treatment, just after the end of treatment, and at 3 and 6 months of follow-up. The pretreatment PCR result was positive for 100 of 101 patients (sensitivity, 99%; confidence interval [CI], 94 to 100%). None of the 150 negative controls tested were PCR positive (specificity, 100%; CI, 96.8 to 100%). Of 60 patients who were treated at our center, 51 (85%; CI, 73 to 93%) became negative immediately after treatment and continued to be negative at 3 and 6 months of follow-up. At the 3-month follow-up, two of the remaining nine patients were PCR positive, making 58 (96.7%; CI, 87 to 100%) patients PCR negative. At the 6-month follow-up, all patients became PCR negative. One patient who was PCR negative immediately after the end of treatment relapsed 11 months later. This limited prospective study with VL patients suggests that the PCR assay is a highly sensitive and specific (99% and 100%, respectively) tool for the diagnosis of VL. In the majority of patients, it can identify a successful disease outcome; however, its translation into the field setting remains a major challenge.

Animals↗
PubMed2005

Evaluation of the status of tuberculosis as part of the clinical case definition of AIDS in India.

AIM: To assess HIV associated tuberculosis in a high tuberculosis prevalence setting and its status in the clinical case definition of AIDS. METHODS: All HIV patients attending the infectious disease clinic, Varanasi, India between January 2001 and December 2003 were included in the study. They were stratified into three distinct immunological categories depending on their CD4 levels in accordance to Centers for Disease Control (CDC) classification. Tuberculosis of different organs was defined as detailed below. RESULTS: Tuberculosis was the commonest opportunistic disease, seen in 163 patients. Of these, 68 had exclusively pulmonary tuberculosis, 55 extrapulmonary disease, and 40 the disseminated form. Pulmonary and extrapulmonary tuberculosis had low positive predictive value (PPV) (51% and 42%) for CD4 levels of <200 when compared with the disseminated form (specificity 87% and PPV 75%). Among 86 patients with radiological evidence of tuberculosis, typical radiological features of post-primary tuberculosis were present in 60 cases (70%). Other features such as effusion (14 patients, 16%) and miliary shadows (12 patients, 14%) were comparatively rare. CONCLUSION: Keeping pulmonary and extrapulmonary forms of tuberculosis in AIDS defining illness should be reconsidered. In a similar way tuberculosis in HIV patients from areas endemic with tuberculosis occurs in patients with a wide range of immune status and has a better prognosis than other AIDS defining illnesses. Therefore the inclusion of tuberculosis in clinical case definition of AIDS is not justified.

AIDS-Related Opportunistic Infections↗
PubMed2005

Management of visceral leishmaniasis: Indian perspective.

Diagnosis and treatment of Indian visceral leishmaniasis (VL) is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternative drugs. Amphotericin B is the most effective, though toxic, drug for patients with refractory VL. Lipid formulations of amphotericin B, though safe and effective, are too expensive to be useful for poor patients of this region. These hold advantage as large quantity of the drug can safely be given over a short period of time, thus leading to a decrease in the hospital stay to a few days instead of several weeks. Oral miltefosine, an alkyl phospholipid, has recently been approved and marketed in India for the treatment of VL. Miltefosine cures 94% patients with VL if given in a daily dose of 50-100 mg for 28 days. Most common adverse events are mild vomiting and diarrhea. Paromomycin, an amino glycoside, is undergoing a pivotal phase-III clinical trial, and is likely to be approved and available to patients with VL at an affordable cost. To protect the already scarce inventory of antileishmanial drugs, it is time that combination chemotherapy is introduced for the treatment of VL in India.

Antiprotozoal Agents↗
PubMed2004

Synthesis and surface properties of aqueous dispersions of poly(ester-imide) prepared from anhydride terminated polyester prepolymer and diisocyanate.

Aqueous dispersions of poly(ester-imide)s [P(E-I)s] have been prepared by dispersing the P(E-I)s in water without any external solubilizing agents. P(E-I)s were prepared from anhydride-terminated polyester prepolymer and diisocyanate. The -COOH groups in the polymer were then neutralized using triethylamine and the P(E-I)s were subsequently dispersed in water. The influence of the degree of ionization of polymers on the particle size and viscosity of the dispersion has been studied. The dispersions were crosslinked using polyaziridine. The crosslinked dispersion cast films were characterized for dynamic mechanical properties. As the ionic content increased the particle size decreased and the viscosity increased. When the amount of crosslinker added was varied, for a fixed percentage of ionization, the glass transition temperature Tg shifted to higher values. Critical surface tension (CST) measurements indicated reorganization of hydrophobic groups on the surface after crosslinking.

Cyanates↗
PubMed2004

Information needs of Asian and White British cancer patients and their families in Leicestershire: a cross-sectional survey.

The aim of this questionnaire survey was to find the information needs of British Asian cancer patients. An additional objective was to find the extent of family involvement when the patient was given the cancer diagnosis and the patients' views about information disclosure. We interviewed 82 Asian patients and 220 random white control patients. More white British patients gave positive answers to the statement 'I want as much information as possible' than Asian patients (93.1 vs 77.5%, P<or=0.001). However, 92.6% of Asian patients wanted to know if they had cancer. Many more Asians (66.2 vs 5.1%, P<0.001) indicated the general practitioner (GP) as the preferred source of information. This may be because 56% of English-speaking Asian patients would prefer to discuss their illness in their mother tongue. In Leicester, many Asian patients have Asian GPs. The vast majority of both Asian and British patients agreed that family or friends should be present when patients are given the cancer diagnosis. However, Asians were more likely to be alone (24 vs 15%, P=0.008) when told they have had cancer. The majority of patients (both white British and Asian) want to control the disclosure of information to relatives and friends and would like to be present at doctor/family meetings.

Adolescent↗
PubMed2004

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy.

OBJECTIVE: To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. METHODS: Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 > or = 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m(2)) was given on day 1, and 5-Fluorouracil (370 mg/m(2)) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. RESULTS: Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. CONCLUSION: Oxaliplatin and 5-Fluorouracil/Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer.

Adult↗
PubMed2004

Platinum-based chemotherapy in metastatic breast cancer: current status.

Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently approximately 60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer.

Adult↗
PubMed2003

Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: a multicenter study.

Widespread antimony resistance renders conventional amphotericin B the only option for the treatment of visceral leishmaniasis (VL) in North Bihar, India. Because of its excellent safety profile, a large dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) was given to each of 203 patients with VL at 4 treatment centers, and the patients were discharged the next day. At initial clinical and parasitological follow-up, performed on day 30 after treatment, evidence of a cure was seen in 195 (96%) of 203 patients (95% CI, 92-98); 4 patients experienced treatment failure. Two patients were lost to follow-up, 2 died (one due to progressive disease and another, 5 months after treatment, due to an unrelated illness), and 12 experienced relapses during follow-up. Thus, 183 patients (90%; 95% CI, 85-94) had obtained final cure 6 months after treatment. Very few adverse events (fever with rigor, in 9.8% of patients) were seen. Single-dose L-AmB (7.5 mg/kg) treatment is safe and effective, and it may be used for the mass treatment of VL in India.

Adolescent↗
PubMed2003

Cholestatic jaundice and pseudomembranous colitis following combination therapy with doxorubicin and docetaxel.

We report a case of cholestatic jaundice and pseudomembranous colitis (PMC) following combination therapy with docetaxel and doxorubicin. This clinical syndrome has not been previously reported with this combination. In particular, this is the first report of non-Clostridium difficile-associated PMC with docetaxel-based chemotherapy. Docetaxel is principally metabolized by the hepatic cytochrome p450 mixed-function oxidases, in particular by the isoform CYP3A. This patient was on long-term erythromycin prophylaxis following splenectomy. Erythromycin is a known inhibitor of CYP3A. We postulate that erythromycin probably contributed to the observed clinical syndrome. Clinicians should be aware of potential drug interactions, when unusual toxicities occur with novel combinations of chemotherapeutic agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

The in vivo susceptibility of Leishmania donovani to sodium stibogluconate is drug specific and can be reversed by inhibiting glutathione biosynthesis.

Resistance to pentavalent antimonial (Sb(v)) agents such as sodium stibogluconate (SSG) is creating a major problem in the treatment of visceral leishmaniasis. In the present study the in vivo susceptibilities of Leishmania donovani strains, typed as SSG resistant (strain 200011) or SSG sensitive (strain 200016) on the basis of their responses to a single SSG dose of 300 mg of Sb(v)/kg of body weight, to other antileishmanial drugs were determined. In addition, the role of glutathione in SSG resistance was investigated by determining the influence on SSG treatment of concomitant treatment with a nonionic surfactant vesicle formulation of buthionine sulfoximine (BSO), a specific inhibitor of the enzyme gamma-glutamylcysteine synthetase which is involved in glutathione biosynthesis, and SSG, on the efficacy of SSG treatment. L. donovani strains that were SSG resistant (strain 200011) and SSG sensitive (strain 200016) were equally susceptible to in vivo treatment with miltefosine, paromomycin and amphotericin B (Fungizone and AmBisome) formulations. Combined treatment with SSG and vesicular BSO significantly increased the in vivo efficacy of SSG against both the 200011 and the 200016 L. donovani strains. However, joint treatment that included high SSG doses was unexpectedly associated with toxicity. Measurement of glutathione levels in the spleens and livers of treated mice showed that the ability of the combined therapy to inhibit glutathione levels was also dependent on the SSG dose used and that the combined treatment exhibited organ-dependent effects. The SSG resistance exhibited by the L. donovani strains was not associated with cross-resistance to other classes of compounds and could be reversed by treatment with an inhibitor of glutathione biosynthesis, indicating that clinical resistance to antimonial drugs should not affect the antileishmanial efficacies of alternative drugs. In addition, it should be possible to identify a treatment regimen that could reverse antimony resistance.

Amphotericin B↗
PubMed2002

Noninvasive management of Indian visceral leishmaniasis: clinical application of diagnosis by K39 antigen strip testing at a kala-azar referral unit.

Firm diagnosis of visceral leishmaniasis (kala-azar) requires organ aspiration and microscopic examination of tissue specimens. To determine the usefulness of noninvasive diagnosis by strip test detection of anti-K39 immunoglobulin (Ig) G antibody in blood specimens obtained by fingerstick, 143 Indian patients with suspected kala-azar (fever, splenomegaly, anemia) were studied. Of 120 strip test-positive subjects (subjects with presumed kala-azar [group A]), amphotericin B treatment induced clinical cure in 119. Of 23 strip test-negative subjects (subjects presumed to have other diseases [group B]), 16 had other disorders diagnosed at entry, 4 responded to empiric antimalarial therapy, 2 were proven to have kala-azar, and 1 died elsewhere after undergoing splenic aspiration. Six months after treatment ended, all 120 patients in group A and the 18 assessable patients in group B were healthy. In a region in India where visceral infection is prevalent, strip test detection of anti-K39 IgG is a clinically promising diagnostic guide in persons with suspected kala-azar.

Adolescent↗
PubMed2002

Alteration of Fas and Fas ligand expression during human visceral leishmaniasis.

Several studies in murine systems have suggested a role of apoptosis in the pathogenesis of leishmaniasis. However, the role of apoptosis in visceral leishmaniasis in man has not been explored. In this study, we show that patients with visceral leishmaniasis demonstrate significant dysregulation of Fas and Fas ligand. Levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) were elevated in plasma of patients with active visceral leishmaniasis (VL) and individuals co-infected with VL-HIV-1 compared to healthy controls. The levels of sFas and sFasL were normalized 6 months after successful treatment. In VL patients, the expression of membrane bound Fas, and to a lower extent FasL, were up-regulated on Leishmania donovani-infected spleen cells, the site of parasite multiplication. Expression of Fas and FasL on peripheral blood mononuclear cells was within normal range, probably reflecting that the blood is not a normal site of L. donovani infection. Furthermore, this is suggested by the finding that in vitro infection of macrophages with L. donovani up-regulated Fas expression on the surface of infected cells and enhanced the levels of sFasL in supernatants from infected cultures. How this dysregulation may affect the pathogenesis of human visceral leishmaniasis is discussed.

Animals↗