Biomedical subjects

Pankaj Desai

Publications and source records attributed to Pankaj Desai.

10 recordsLinked to original sources

PubMed2006

Methylphenidate and cocaine: a placebo-controlled drug interaction study.

Up to thirty percent of cocaine addicted individuals may meet diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD). Methylphenidate (MPH) is a highly effective and commonly used treatment for ADHD but, like cocaine, is a cardiovascular and central nervous system stimulant with the potential to cause toxicity at high doses. The present study was undertaken to investigate the likelihood of a toxic reaction in individuals who use cocaine while concurrently taking MPH. Seven non-treatment seeking cocaine-dependent individuals completed this placebo-controlled, crossover study with two factors: Medication (placebo, 60 mg MPH, 90 mg MPH) and Infusion (saline, 20 mg cocaine, 40 mg cocaine). Physiological measures included vital signs, adverse events, and electrocardiogram. Subjective response was measured with visual analog scale (VAS) ratings of craving and drug effect. Cocaine pharmacokinetic parameters were calculated for each participant at each drug combination, using a non-compartmental model. MPH was well tolerated, did not have a clinically significant impact on cocaine's physiological effects, and decreased some of the positive subjective effects of cocaine. MPH did not significantly alter the pharmacokinetics of cocaine. The study results suggest that MPH at the doses studied can likely be used safely in an outpatient setting with active cocaine users.

Adult↗

PubMed2006

Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model.

BACKGROUND: Haemodialysis vascular access dysfunction is currently a huge clinical problem. In an attempt to reduce the morbidity associated with haemodialysis vascular access dysfunction, we have previously developed and validated a local perivascular paclitaxel release system that has been shown to release paclitaxel for at least 3 weeks. The aim of the current study was to evaluate the in vivo use of these perivascular wraps (for both safety and efficacy) at different time points in our pig model of arteriovenous graft stenosis. METHODS: Paclitaxel-loaded ethylene vinyl acetate wraps were placed around the graft-vein anastomosis on one side, with control polymers being placed on the contralateral side in our pig model of arteriovenous graft stenosis. Animals were sacrificed at early (10-11 days), middle (23-24 days) and late (32-38 days) time points. The entire graft-vein anastomosis was removed at the time of sacrifice and assessed for the extent of luminal stenosis using histomorphometric techniques. RESULT: Graft-vein anastomoses treated with the paclitaxel-loaded polymers had an almost complete absence of luminal stenosis at the middle (23-24 days) and late (32-38 days) time points (when one would expect the development of neointimal hyperplasia) as compared with the contralateral control graft-vein anastomoses (37.90% luminal stenosis in the controls vs 0.10% in the paclitaxel group). There were minimal local side effects from this procedure. CONCLUSIONS: Our results demonstrate the safety and efficacy of paclitaxel-loaded perivascular wraps in the setting of a pig model of arteriovenous graft stenosis. We believe that such a local approach which could be easily applied at the time of surgery is ideally suited for use in the clinical setting of haemodialysis vascular access dysfunction. It is likely that this novel approach could result in a significant reduction in the huge economic and health morbidity costs currently associated with this recalcitrant clinical problem.

Animals↗

PubMed2006

Development of a local perivascular paclitaxel delivery system for hemodialysis vascular access dysfunction: polymer preparation and in vitro activity.

Hemodialysis vascular access dysfunction (HVAD) is currently a huge clinical problem. The major cause of HVAD is venous stenosis (as a result of venous neointimal hyperplasia) which leads to thrombosis in polytetrafluoroethylene dialysis access grafts and fistulae. Despite the magnitude of the clinical problem there are currently no effective therapeutic interventions for this condition. In an attempt to reduce the morbidity associated with HVAD, we have developed and validated a local perivascular paclitaxel release system for use in a pig model of arteriovenous graft stenosis. Ethylene vinyl acetate polymers with 5% paclitaxel were formulated. The release profile of paclitaxel was then manipulated to maximize its biological impact in the in vivo situation. In vitro experiments were performed to confirm that the paclitaxel released from the polymer was biologically active against cell types that were similar to those present in the in vivo lesion of neointimal hyperplasia. Our results demonstrate that the paclitaxel polymer wraps which we have developed are mechanically stable with a burst release phase followed by a slower continuous release phase. The paclitaxel released from these polymeric wraps retains its physicochemical and biological properties and is able to inhibit the proliferation of smooth muscle cells, endothelial cells and fibroblasts in vitro. We believe that these paclitaxel-loaded polymeric wraps could be ideally suited for perivascular drug delivery in the context of dialysis access grafts and fistulae.

Arteriovenous Shunt, Surgical↗

PubMed2005

Vascular access in hemodialysis: issues, management, and emerging concepts.

This article (1) identifies the types of hemodialysis access, (2) summarizes the clinical standard of care for dialysis access grafts and fistulae, (3) describes the pathology and pathogenesis of venous stenosis in dialysis access grafts and fistulae, (4) tabulates avail-able therapies for hemodialysis vascular access dysfunction and speculates on the rea-sons for the lack of effective therapies, and (5) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. The possibility that dialysis access grafts and fistulae could be the ideal clinical model for testing novel local therapies to block neointimal hyperplasia is discussed.

Arteriovenous Anastomosis↗

PubMed2005

Labor epidural analgesia in pre-eclampsia: a prospective study.

AIM: To assess the safety of labor epidural analgesia in subjects with pre-eclampsia. METHODS: Nulliparous laboring women were included in the prospective study. One hundred pre-eclamptic nullipara who were given epidural analgesia (group I) were compared with 100 nullipara with pre-eclampsia who were not given epidural analgesia (group II). The outcome was further compared with 200 women who were not pre-eclamptic, but who were given epidural analgesia (group III), and also with 200 women who were normotensive and who were not given epidural analgesia (group IV). RESULTS: In group I, 58% of subjects delivered normally compared with 60% in group II. The operative vaginal delivery rate was 28% in group I compared with 24% in group II (P = 0.62), and the cesarean section rate was 14% and 16% in groups I and II, respectively, (P = 0.8). The difference was not statistically significant. The incidence of a prolonged second stage of labor was also not increased in pre-eclamptic women who received epidural analgesia. Five of the neonates in group I had a 5-min APGAR score <6 compared with seven neonates in group II. The necessity of neonatal resuscitation was also not significantly increased in group I (P = 1.0). The incidences of fetal distress (P = 0.71), non-progressive second stage of labor (P = 0.66) and cephalopelvic disproportion (P = 0.90) were not statistically different in the pre-eclampsia group compared with the non-pre-eclampsia group. Similar results were noted when these outcome measures were compared with the other two groups. With regard to hypotension and tachycardia in the pre-eclamptic subjects who were given epidural analgesia, no statistical difference (P = 0.72) was seen when compared with the normotensive subjects. CONCLUSION: In the absence of coagulopathy, epidural analgesia is a safe and effective method for labor pain relief, even for subjects with pre-eclampsia.

Adult↗

PubMed2005

Novel therapies for hemodialysis vascular access dysfunction: fact or fiction!

Hemodialysis vascular access dysfunction is a major cause of morbidity in the hemodialysis population and contributes significantly to the overall cost of end-stage renal disease programs. At a histological level, most hemodialysis vascular access dysfunction (in both native arteriovenous fistulae and PTFE dialysis access grafts) is due to venous stenosis and thrombosis, secondary to venous neointimal hyperplasia. However, despite a wealth of experimental and clinical data on the use of novel therapeutic interventions that target neointimal hyperplasia in the setting of coronary artery disease, there are unfortunately no effective therapeutic interventions for hemodialysis vascular access dysfunction at the present time. This is particularly unfortunate, since neointimal hyperplasia in the setting of hemodialysis vascular access fistulae and grafts could be the ideal clinical model to test novel therapeutic interventions for neointimal hyperplasia.

Arteriovenous Shunt, Surgical↗

PubMed2003

Ring expansive routes to quinolizidine alkaloids: formal synthesis of (-)-lasubine II.

The application of two nitrogen ring expansion reactions to lasubine alkaloid synthesis is reported. The approach involves a conjugate reduction/alkylation sequence carried out on triisopropylsilyl-protected (S)-4-(-)-hydroxycyclopentenone, the formation of the quinolizidone ring system through nitrogen ring expansion, and the addition of an arylmetallic species to the resulting lactam. This work resulted in the preparation of 2-epi-lasubine II and a formal synthesis of lasubine II. [reaction: see text]

Alkaloids↗

PubMed2003

Synthesis of the chlorofusin cyclic peptide: assignment of the asparagine stereochemistry.

An efficient synthesis of two diastereomers of the chlorofusin cyclic peptide bearing either the l-Asn3/d-Asn-4 or d-Asn3/l-Asn4 stereochemistry is detailed. Four key subunits were prepared, sequentially coupled, and cyclized to provide the two diastereomeric macrocycles. The absolute stereochemistry at the asparagine residues 3 and 4 was assigned as l and d, respectively, by correlating the NMR data of the two diastereomers with that reported for the natural product. [structure: see text]

Amino Acids↗

PubMed2003

Hemodialysis vascular access dysfunction: from pathophysiology to novel therapies.

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of over USD 1 billion per annum. Most hemodialysis grafts fail due to a venous stenosis (venous neointimal hyperplasia) which then results in thrombosis of the graft. Despite the magnitude of the clinical problem there are currently no effective therapies for this condition. The current review (a) describes the pathogenesis and pathology of venous stenosis in dialysis access grafts and (b) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. Special emphasis is laid on the fact that PTFE dialysis access grafts could be the ideal clinical model for testing out novel local therapies to block neointimal hyperplasia.

Animals↗

PubMed2002

Hemodialysis vascular access dysfunction from basic biology to clinical intervention.

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of over 1 billion dollars per annum. Venous stenosis and thrombosis as a result of venous neointimal hyperplasia are the major causes of hemodialysis vascular access dysfunction. Despite the magnitude of the clinical problem, there are currently no effective therapies for this condition. We believe that this could be because of an inadequate understanding of the pathogenesis of this condition. At a histological level, venous neointimal hyperplasia (both in human specimens and in a pig model) is characterized by the presence of smooth muscle cells/myofibroblasts, microvessel formation (angiogenesis), and the accumulation of extracellular matrix components, all of which could be potential targets for therapeutic intervention. In particular, polytetrafluoroethylene dialysis access grafts could be the ideal clinical model for testing out novel local therapies to block neointimal hyperplasia. The current review describes the lesion of venous neointimal hyperplasia in human samples and in a pig model and suggests possible future directions for the development of effective local therapies for this condition.

Arteriovenous Shunt, Surgical↗