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Biomedical subjects

Raman P Singh

Publications and source records attributed to Raman P Singh.

8 recordsLinked to original sources
PubMed2006

Structured treatment interruptions with tenofovir monotherapy for simian immunodeficiency virus-infected newborn macaques.

We demonstrated previously that prolonged tenofovir treatment of infant macaques, starting early during infection with virulent simian immunodeficiency virus (SIVmac251), can lead to persistently low or undetectable viremia even after the emergence of mutants with reduced in vitro susceptibility to tenofovir as a result of a K65R mutation in reverse transcriptase; this control of viremia was demonstrated to be mediated by the generation of effective antiviral immune responses. To determine whether structured treatment interruptions (STI) can induce similar immunologic control of viremia, eight newborn macaques were infected with highly virulent SIVmac251 and started on a tenofovir STI regimen 5 days later. Treatment was withdrawn permanently at 33 weeks of age. All animals receiving STI fared much better than 22 untreated SIVmac251-infected infant macaques. However, there was a high variability among animals in the viral RNA set point after complete drug withdrawal, and none of the animals was able to achieve long-term immunologic suppression of viremia to persistently low levels. Early immunologic and viral markers in blood (including the detection of the K65R mutation) were not predictive of the viral RNA set point after drug withdrawal. These results, which reflect the complex interactions between drug resistance mutations, viral virulence, and drug- and immune-mediated inhibition of virus replication, highlight the difficulties associated with trying to develop STI regimens with predictable efficacy for clinical practice.

Adenine↗
PubMed2005

Attenuated poxvirus-based simian immunodeficiency virus (SIV) vaccines given in infancy partially protect infant and juvenile macaques against repeated oral challenge with virulent SIV.

An infant macaque model was developed to test pediatric vaccine candidates aimed at reducing HIV transmission through breast-feeding. Infant macaques were given multiple immunizations during the first 3 weeks of life with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins Gag, Pol, and Env (ALVAC-SIV or modified vaccinia virus Ankara [MVA]-SIV). After repeated daily oral inoculations with virulent SIVmac251 at 4 weeks of age, significantly fewer ALVAC-SIV-immunized infants were infected compared with unimmunized infants. Monkeys not infected after oral challenge in infancy were rechallenged at 16 months of age or older by repeated weekly oral SIV exposure; unimmunized animals were infected after fewer SIV exposures than were animals vaccinated with ALVAC-SIV or MVA-SIV. When infected, ALVAC-SIV- and MVA-SIV-vaccinated animals also had reduced viremia compared with unimmunized animals. The results of these investigations suggest that immunization of human infants with poxvirus-based HIV vaccine candidates may offer protection against early and late HIV infection through breastfeeding.

Administration, Oral↗
PubMed2004

The clinical benefits of tenofovir for simian immunodeficiency virus-infected macaques are larger than predicted by its effects on standard viral and immunologic parameters.

Previous studies have demonstrated that tenofovir (9-[2-(phosphonomethoxy)propyl]adenine; PMPA) treatment is usually very effective in suppressing viremia in macaques infected with simian immunodeficiency virus (SIV). The present study focuses on a subset of infant macaques that were chronically infected with highly virulent SIVmac251, and for which prolonged tenofovir treatment failed to significantly suppress viral RNA levels in plasma despite the presence of tenofovirsusceptible virus at the onset of therapy. While untreated animals with similarly high viremia developed fatal immunodeficiency within 3-6 months, these tenofovir-treated animals had significantly improved survival (up to 3.5 years). This clinical benefit occurred even in animals for which tenofovir had little or no effect on CD4 and CD8 lymphocyte counts and antibody responses to SIV and test antigens. Thus, the clinical benefits of tenofovir were larger than predicted by plasma viral RNA levels and other routine laboratory parameters.

Adenine↗
PubMed2004

Performance evaluation of iterative tomography algorithms for incomplete projection data.

Projection data obtained through optical techniques for tomographic measurements, such as interferometry for refractive-index-based measurements, are often incomplete. This is due to limitations in the optical system, data storage, and alignment and vignette issues. Algebraic iterative reconstruction techniques are usually favored for such incomplete projections. A number of iterative algorithms, based on additive and multiplicative corrections, are used with a known simulated phantom and noise source to assess the reconstruction performance of incomplete data sets. In addition, we present reconstructions using experimental data obtained from a coherent gradient sensing interferometer for a steady temperature field in a fluid medium. We tested the algorithms using the simulated data set for incompleteness conditions similar to those found in the experimental data, and the best-performing algorithm is identified.

Journal Article↗
PubMed2004

CD8+-cell-mediated suppression of virulent simian immunodeficiency virus during tenofovir treatment.

The ability of tenofovir to suppress viremia in simian immunodeficiency virus (SIV)-infected macaques for years despite the presence of virulent viral mutants with reduced in vitro susceptibility is unprecedented in this animal model. In vivo cell depletion experiments demonstrate that tenofovir's ability to suppress viremia during acute and chronic infection is significantly dependent on the presence of CD8+ lymphocytes. Continuous tenofovir treatment was required to maintain low viremia. Although it is unclear whether this immune-mediated suppression of viremia is linked to tenofovir's direct antiviral efficacy or is due to independent immunomodulatory effects, these studies prove the concept that antiviral immune responses can play a crucial role in suppressing viremia during anti-human immunodeficiency virus drug therapy.

Adenine↗
PubMedDate not supplied

Retrograde coronary sinus perfusion for management of coexistent critical unstable carotid and coronary artery disease.

The case report describes a difficult and not uncommon situation of a patient suffering from an evolving myocardial infarction with hemodynamic instability along with a critical bilateral extracranial carotid artery stenosis. A technique of retrograde coronary sinus perfusion was used to temporarily stabilize the cardiac status while the carotid lesion was being tackled.

Aged↗
PubMedDate not supplied

Mitral valve replacement on a beating heart.

We report the case of a patient who needed mitral valve replacement but was at a high risk of myocardial injury with the conventional technique (cardioplegic arrest on cardiopulmonary bypass). Valve replacement was carried out on a beating heart on cardiopulmonary bypass by perfusing the heart continuously with oxygenated noncardioplegic normothermic blood via the coronary sinus.

Adolescent↗