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R Pillai

Publications and source records attributed to R Pillai.

At least 37 records · Page 2Linked to original sources
PubMed1999

Paclitaxel vs cyclophosphamide in peripheral blood stem cell mobilization: comparative studies in a murine model.

Paclitaxel is a promising drug for the treatment of breast and ovarian cancer. It also may play a role in mobilization of peripheral blood stem cells (PBSC), as an alternative to cyclophosphamide (Cy). We investigated the PBSC-mobilizing potential of paclitaxel compared to Cy in a murine model. C57B1/6 mice were primed with intraperitoneal injections of Cy (200 mg/kg) or paclitaxel (60 mg/kg) and were sacrificed 4, 6, 8, or 10 days later. Spleens were harvested and processed to obtain low-density mononuclear cells that were used as PBSC. The number of hematopoietic progenitors (CFU-C) on day 4 was significantly higher in the paclitaxel group when compared to mice receiving Cy (72.0 +/- 1.8 vs 9.8 +/- 2.8, p < 0.001). By day 6, CFU-C became significantly higher in the Cy-treated group compared to the paclitaxel-treated group (195.6 +/- 31.9 vs 95.8 +/- 20.7, p < 0.05) and this trend was maintained. However, the total number of CFU-C recovered per spleen was greater in the paclitaxel-treated group (1.27 x 10(5) +/- 0.53 x 10(5) vs 1.06 x 10(5) +/- 0.36 x 10(5), NS). In contrast to paclitaxel, mobilization with Cy was associated with marked perturbation in the proportion of lymphoid cell subsets in the PBSC population along with functional impairment of lymphocytes. After 24 hours of in vitro IL-2 activation, the cytotoxic effector cell function of the Cy-mobilized PBSC population was lower than that of paclitaxel-mobilized cells when tested against three tumor cell lines (B16, melanoma; C1498, AML; and Yak-1, lymphoma). These results indicate that paclitaxel is an efficient mobilizer of PBSC, leading to early (day 4 to 6) mobilization of PBSC when compared to Cy (day 6 to 8). In addition, paclitaxel was associated with less perturbation of phenotypic and functional characteristics of cells contained within the mobilized PBSC population.

Animals↗
PubMed1999

Experience with the atypical antipsychotics--risperidone and olanzapine in the elderly.

There is paucity of published data regarding controlled trials with risperidone and olanzapine in elderly psychotic patients. Medical records of 151 hospitalized geropsychiatric patients (risperidone patients n = 114 and olanzapine patients n = 37) were analyzed for demographic data, target symptoms, doses, effects, side effects, comorbid medical conditions and concurrent medications. The mean age of the patients was 71 years. The male: female ratio was essentially the same for both groups. The mean daily dose was 3 mg for risperidone and 10 mg for olanzapine. 78% of the risperidone group and 75% of the olanzapine group appear to have responded to treatment. The discontinuation rates of medication was the same in both groups (22%). Adverse events were reported in 16-17% in both groups. It appears from this study that both risperidone and olanzapine are relatively safe and effective in geropsychiatric patients with comorbid medical illnesses. Controlled studies and head-to-head comparison studies are recommended.

Aged↗
PubMed1998

Fifth-year hemodynamic performance of the prima stentless aortic valve.

BACKGROUND: The medium-term hemodynamic performance of stentless valves has not been widely reported, particularly in comparison with in vitro studies. Therefore, we have assessed prospectively the hemodynamics of the Edwards Prima valve in its fifth year after implantation in the aortic position, and compared the results with those at 1 month after implantation and also with in vitro data. METHODS: Thirty-five patients (age, 77 +/- 6 years; 19 men) were prospectively studied by Doppler echocardiography at 1 month and 52 +/- 8 months after implantation of a Prima stentless valve. Valve hemodynamics were assessed by measuring the mean pressure gradient, mean valve resistance, and effective orifice area. Left ventricular systolic function was quantified by ejection fraction, the degree of hypertrophy by ventricular mass index, and the ratio of ventricular wall thickness to cavity radius as a measure of ventricular geometry. RESULTS: With a mean valve size of 24.6 +/- 2.2 mm in the fifth year after implantation, the mean pressure gradient was 6.2 +/- 3.5 mm Hg, the mean valve resistance, 29 +/- 16 dyne x s(-1) x cm(-5)), and the effective orifice area was 2.05 +/- 0.50 cm2. Compared with 1 month after operation, there was a 47% decrease in mean valve resistance (p = 0.002) and a 39% increase in effective orifice area (p = 0.001). Furthermore, both effective orifice area and mean valve resistance in the fifth year did not differ from their in vitro counterparts, whereas the left ventricular ejection fraction (0.64 +/- 0.14), the left ventricular mass index (119 +/- 49 g/m2), and the ratio of ventricular wall thickness to cavity radius (0.44 +/- 0.13) were within the normal range. CONCLUSIONS: This study suggests that the Prima valve is a reliable stentless aortic bioprosthesis. This is supported by a favorable medium-term clinical outcome, durable hemodynamic performance, and normal mean values of left ventricular ejection fraction and mass index in the fifth year after implantation.

Aged↗
PubMed1998

Target specific optimization of cationic lipid-based systems for pulmonary gene therapy.

PURPOSE: Cationic lipids are capable of transferring foreign genes to the pulmonary epithelium in vivo. It is becoming increasingly clear that factors other than lipid molecular structure also influence efficiency of delivery using cationic lipid systems. This study is aimed at evaluating the effect of formulation variables such as cationic lipid structure, cationic lipid/DNA ratio, particle size, co-lipid content and plasmid topology on transgene expression in the lung. METHODS: The effect of varying the surface and colloidal properties of cationic lipid-based gene delivery systems was assessed by intratracheal instillation into rats. An expression plasmid encoding chloramphenicol acetyl transferase (CAT) was used to measure transgene expression. RESULTS: Cationic lipid structure, cationic lipid/DNA ratio, particle size, co-lipid content and topology of the plasmid, were found to significantly affect transgene expression. Complexation with lipids was found to have a protective effect on DNA integrity in bronchoalveolar lavage fluid (BALF). DNA complexed with lipid showed enhanced persistence in rat lungs as measured by quantitative polymerase chain reaction. CONCLUSIONS: Fluorescence microscopy analysis indicated that the instilled formulation reaches the lower airways and alveolar region. Data also suggests cationic lipid-mediated gene expression is primarily localized in the lung parenchyma and not infiltrating cells isolated from the BALF.

Animals↗
PubMed1998

Ultrasonic nebulization of cationic lipid-based gene delivery systems for airway administration.

PURPOSE: This study relates to the development of gene therapies for the treatment of lung diseases. It describes for the first time the use of ultrasonic nebulization for administration of plasmid/lipid complexes to the lungs to transfect lung epithelial cells. METHODS: Plasmid complexed to cationic liposomes at a specific stoichiometric ratio was nebulized using an ultrasonic nebulizer. We assessed: (i) the stability of plasmid and plasmid/lipid complexes to ultrasonic nebulization, (ii) the in vitro activity of plasmid in previously nebulized plasmid/lipid complex, (iii) the in vivo transgene expression in lungs following intratracheal instillation of nebulized plasmid/lipid formulations compared to un-nebulized complexes, (iv) the emitted dose from an ultrasonic nebulizer using plasmid/lipid complexes of different size, and (v) the transgene expression in lungs following oral inhalation of aerosolized plasmid/lipid complex generated using an ultrasonic nebulizer. RESULTS: Integrity of plasmid formulated with cationic lipids, and colloidal stability of the plasmid/lipid complex were maintained during nebulization. In contrast, plasmid alone formulated in 10% lactose was fragmented during nebulization. The efficiency of transfection of the complex before and after nebulization was comparable. Nebulization produced respirable aerosol particles. Oral exposure of rodents for 10 minutes to aerosol produced from the ultrasonic nebulizer resulted in transgene expression in lungs in vivo. CONCLUSIONS: The performance characteristics of the ultrasonic nebulizer with our optimized plasmid/lipid formulations suggests that this device can potentially be used for administering gene medicines to the airways in clinical settings for the treatment of respiratory disorders.

Aerosols↗
PubMed1998

Recognition and management of hypercholesterolaemia in patients awaiting elective coronary artery bypass grafting.

The recently published Scandinavian Simvastatin Survival Study showed that long-term treatment with simvastatin, in patients with ischaemic heart disease and serum cholesterol levels between 5.5 and 8.0 mmol/l, improved survival. The present study was conducted in order to evaluate whether patients with ischaemic heart disease awaiting coronary revascularisation are aware of their serum cholesterol levels and whether raised levels are being treated adequately. One hundred consecutive patients admitted from our waiting list for elective coronary artery bypass grafting, with or without valve replacement, were included in the study. The patients were asked whether they had a history of raised serum cholesterol and, if so, how this was being treated. Fasting serum cholesterol levels were subsequently taken in the morning before surgery. Forty-six patients gave a positive history of raised blood cholesterol levels; 25 of these were on cholesterol-lowering medication at the time of admission, 15 were on a lipid-lowering diet and six were not being treated. Thirty-one (67%) of these 46 patients had a serum cholesterol of more than 5.5 mmol/l, compared with 30 (56%) of the 54 patients without a positive history of hypercholesterolaemia, and 61% of the total 100 patients. These data suggest that an inadequate number of patients awaiting coronary artery bypass grafting are aware of their cholesterol status. The management of hypercholesterolaemia among these patients could be improved.

Adult↗
PubMed1997

Comparison of serum S-100 beta levels during CABG and intracardiac operations.

BACKGROUND: The risk of overt and subtle cerebral injury may be higher in intracardiac operation (ICO) rather than coronary artery bypass grafting (CABG). S-100 protein is a specific astroglial protein whose serum level increases after cerebral injury. Elevated serum levels of S-100 have been detected after adult cardiac operations and correlated with neurologic injury. METHODS: The level of S-100 protein was measured serially over 24 hours in 40 patients (27 undergoing aortic valve replacement, 9 mitral valve replacement, 4 closure of atrial septal defect) undergoing ICO and 20 patients undergoing CABG. RESULTS: The groups were similar with respect to age and cardiopulmonary bypass times. The S-100 level was not elevated before operation in any patient. Peak S-100 levels were reached at skin closure, when 35 of the ICO patients (88%) and 13 of the CABG patients (65%) had elevated S-100 levels. At skin closure peak S-100 levels were significantly greater in the ICO group (median [interquartile range], 0.76 [0.44-1.16] versus 0.3 [0-0.55] microgram/L; p < 0.01). At 5 hours S-100 levels were still elevated in 22 patients in the ICO group compared with 1 patient in the CABG group (p < 0.01), and at 24 hours 17 ICO patients had persistently elevated S-100 levels in comparison with 2 in the CABG group (p < 0.01). One valve patient had a stroke 24 hours after operation accompanied by a secondary increase in the S-100 level. There was no significant difference in postoperative S-100 levels between 5 patients in the ICO group with a prior history of stroke and those without. The peak S-100 level correlated with patient age (r = 0.59; p < 0.001) but not with the duration of cardiopulmonary bypass or core temperature during the operation. CONCLUSIONS: Intracardiac operation results in a significantly greater elevation in S-100 levels than CABG. Elevated S-100 levels correlate with increasing patient age but not with the duration of cardiopulmonary bypass or intraoperative core temperature. These findings raise the possibility that ICO patients may be more vulnerable to even subtle levels of cerebral injury than CABG patients.

Adult↗
PubMed1997

Rupture of the atrial septum and tricuspid valve after blunt chest trauma.

A previously fit 19-year-old male driver was involved in an unrestrained, head-on collision. Transesophageal echocardiography revealed rupture of the chordae subtending both leaflets of the tricuspid valve with severe tricuspid regurgitation and disruption of the interatrial septum. When cardiac injury is suspected after blunt chest trauma, transesophageal echocardiography facilitates appropriate management as it provides safe, rapid, and accurate diagnostic images.

Adult↗
PubMed1997

Serum S-100 protein concentration after cardiac surgery: a randomized trial of arterial line filtration.

INTRODUCTION: Embolization of gaseous and particulate matter is incriminated in the neuropsychological morbidity of CPB and can be reduced by membrane oxygenators and arterial line filtration. It is not known if the use of arterial line filtration in conjunction with membrane oxygenators might have an additive effect in reducing cerebral injury. METHODS: Forty patients undergoing elective coronary artery surgery were prospectively randomized to a 43 microns heparin coated arterial line filter (Cobe Sentry) or to no filtration (control group). All operations were performed by one surgeon (DPT) using intermittent ischaemia with nonpulsatile CPB, a COBE CML membrane oxygenator and alpha-stat paCO2 management. Flow rates were maintained between 2.0 and 2.4 l-1 m2 per min with a perfusion pressure of 50-80 mmHg and a systemic temperature of 34 degrees C. Cerebral injury was defined by careful neurological examination and serial measurement of the serum concentration of S-100 protein (a highly specific astroglial cell derivative, elevated serum levels of which correlate with proven cerebral injury). RESULTS: There was no difference [mean (S.D.)] in the control and filter groups with respect to age [61(9) vs. 62(9) years], ejection fraction, number of grafts [2.8(0.6) vs. 2.6(0.7)] or CPB times [55(19) vs. 57(18) min]. Preoperatively, no patient had detectable S-100. In the postoperative period 23 of 40 patients (58%) showed elevated S-100 levels. At 1, 5 and 24 h the respective number of patients in the control and filter groups with elevated S-100 was (14 vs. 9), (4 vs. 0), (4 vs. 0)) (P < 0.05). No patient had overt cerebral injury. CONCLUSIONS: This study suggests that (i) subclinical cerebral injury is common (58% of patients in this study) even after apparently uncomplicated surgery with short CPB times; (ii) serum S-100 protein is a valuable marker for investigating potentially cerebral protective innovations during CPB; and (iii) arterial line filtration significantly reduces but does not eliminate cerebral injury.

Aged↗
PubMed1997

Extrusion of Teflon aortic pledgets from a sternal wound six years after cardiac surgery.

We present a case of a cardiac surgery patient with a persistent low-grade discharge from his sternal wound for over six years. It finally healed when some suture material and Teflon felt pledgets were extruded. These had been used intraoperatively to close the aortic cannulation site. The extrusion of prosthetic material from this site after this length of time has never been described.

Coronary Artery Bypass↗
PubMed1997

Left ventricular remodelling and improvement in Freestyle stentless valve haemodynamics.

OBJECTIVE: To assess how left ventricular (LV) hypertrophy, geometry and function change after stentless aortic valve replacement for aortic stenosis, and to elucidate the physiological mechanism of the improvement in stentless valve haemodynamics. METHODS: 81 patients with aortic stenosis (age 75 +/- 6 years, 47 male) underwent aortic valve replacement (plus CABG in 33 patients) with a Freestyle stentless porcine valve (mean size 23 +/- 2 mm). They were prospectively investigated by Doppler echocardiography at 2 weeks, 3-6, 12, and 24 months after operation. Two hundred and forty-six echocardiograms were obtained and analysed. Aortic valve performance was assessed from its effective orifice area (EOA), the transvalvular increase in mean flow velocity (delta mV), the deceleration time of aortic flow velocity, and mean pressure drop (mPG). LV hypertrophy was assessed from LV mass index; LV geometry, from the ratio of wall thickness to the radius (T/R ratio) and LV function, from stroke volume index (LVSVI) and myocardial stroke work (SW). RESULTS: By 2 years after operation, LV mass index had fallen from 162 +/- 64 to 109 +/- 36, g/m2, and T/R ratio from 0.61 +/- 0.25 to 0.43 +/- 0.10. LVSVI increased from 29.4 +/- 10 to 42 +/- 17, ml/m2, and myocardial SW from 3.1 +/- 1.6 to 5.2 +/- 2.2, mJ/cm3 (all P < 0.001 by ANOVA), while LV outflow tract diameter remained unchanged. At the same time, stentless valve EOA increased from 1.59 +/- 0.75 to 2.2 +/- 0.72, cm2, and delta mV (from 82 +/- 31 to 49 +/- 24, cm/s) and mPG (from 9.7 +/- 5.0 to 5.2 +/- 3.7 mmHg) both fell significantly (all P < 0.001 by ANOVA): as the deceleration time of aortic flow velocity increased from 153.6 +/- 64.1 to 202.7 +/- 37.6 ms (P < 0.001 by ANOVA). CONCLUSION: After stentless aortic valve replacement, LV mass index and wall thickness both fall towards normal, and myocardial stroke work increases. These ventricular remodelling processes are accompanied by a more physiological flow jet at valve cusp level, which permits a greater stroke volume to be ejected with a smaller transvavular velocity increase, so that effective orifice area increases.

Aged↗
PubMed1997

Large airway obstruction by a chronic dissecting aortic aneurysm in the Marfan syndrome.

We describe a patient with the Marfan syndrome who presented with an acute aortic dissection. She underwent composite graft replacement of the aortic root. She returned two years later with dyspnoea and stridor due to tracheal compression by a large chronic dissection of the thoracic aorta. Marfan patients are at risk of chronic dissection involving the remaining distal aorta and require regular noninvasive assessment following surgery.

Adult↗
PubMed1996

Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass.

BACKGROUND: There is no simple method to determine the incidence or severity of brain injury after a cardiac operation. A serum marker equivalent to cardiac enzymes is required. S100 protein leaks from the cerebrospinal fluid to blood after cerebral injury. We sought to determine the pattern of release after extracorporeal circulation (ECC). METHODS: Thirty-four patients without neurologic problems underwent coronary bypass using ECC. Four had carotid stenoses. Nine others underwent coronary bypass without ECC. Serum S100 levels were measured before, during, and after the operation. RESULTS: S100 was not detected before sternotomy. Postoperative levels of S100 were related to duration of perfusion (r = 0.89, p < 0.001). Patients who did not have ECC had undetectable or fractionally raised levels except in 1 who suffered a stroke. No patient in whom ECC was used suffered an event, but those with carotid stenosis had greater S100 levels. CONCLUSIONS: S100 protein leaks into blood during ECC and may reflect both cerebral injury and increased permeability of the blood brain barrier. S100 is a promising marker for cerebral injury in cardiac surgery if elevated levels can be linked with clinical outcome.

Aged↗
PubMed1996

Lipid and fatty acid composition of muga silkworm, Antheraea assama, host plants in relation to silkworm growth.

The lipid and fatty acid composition of the leaves (tender, medium and mature) of muga host plants, Machilus bombycina, Litsaea monopetala (primary food plants) and L. cubeba and L. salicifolia (family: Lauraceae) (secondary food plants) was investigated by standard procedures, gas chromatography after saponification and esterification. The total lipid content of M. bombycina and L. monopetala leaves was recorded to be higher (16 and 18 g%), respectively, than that of L. cubeba (10 g%) and L. salicifolia (12 g%). GC analysis identified the presence of eight fatty acids (C14 to C22) and the concentration varied from 0.0297 to 8.1572 g% dry leaf powder. Among the fatty acids, (C14 to C22), polyunsaturated fatty acids were recorded to be highest in concentration in mature leaves of the primary host plants. The concentrations of saturated and polyunsatuated fatty acids were found to be at a minimum level in all the types of leaves of secondary muga host plants.

Animals↗
PubMed1996

Valve replacement with the ATS open pivot bileaflet prosthesis.

OBJECTIVE: We sought to evaluate the ATS open pivot bileaflet valve with respect to haemodynamics and thromboembolism. METHODS: We prospectively studied 200 consecutive patients aged 13-80 years. One hundred and nineteen aortic, 103 mitral and 11 tricuspid valves were replaced in 172 single, 23 double and 5 triple valve procedures. Thirty-eight were re-operations and 51 underwent coronary bypass. Transvalvular gradients were determined by transoesophageal and transthoracic echocardiography. Patients were followed for 12 months to 3 years. RESULTS: There were four hospital (2%) and three late deaths, each non-valve related. Two patients were reoperated for partial valve dehiscence. One aortic reoperation patient suffered a potential transient thromboembolic event. One tricuspid prosthesis thrombosed after anticoagulation was discontinued but thrombolysis resolved this problem. There were no other thromboembolic events. Valve gradients were equivalent or better than those for other bileaflet valves. CONCLUSIONS: The ATS valve has excellent haemodynamic characteristics and a very low thromboembolic rate, probably related to the convex self-washing hinge mechanism. Consequently, we have reduced anticoagulant levels to INR (international normalised ratio) 1.5 to 2.0 for aortic valve patients in sinus rhythm. Early experience suggests that the ATS valve functions well in the tricuspid position.

Adolescent↗
PubMed1996

Hemodynamic performance of the PRIMA Edwards stentless aortic xenograft: early results of a multicenter clinical trial.

Between June 1991 and July 1993, 200 PRIMA Edwards stentless aortic bioprostheses were implanted in 4 European centres. Mean age of the group was 68.5 years (S.D. 8.0). The subcoronary implantation technique was used in 161 patients, the inclusion cylinder technique in 39 patients. Valve diameters ranged from 19 mm to 29 mm. Transthoracic Doppler echocardiographic studies were performed at discharge, and after 6 months and 12 months; a complete one-year follow-up was obtained. At 12 months peak systolic gradients ranged from 35.2 mmHg (19 mm valve) to 10.9 mmHg (29 mm valve) and effective orifice area ranged from 0.8 cm2 (19 mm valve) to 2.8 cm2 (29 mm valve). 30-day mortality was 3%, 12-month mortality was 5%. Complications were thrombo-embolism in six patients (3%), haemorrhage in three patients (1.5%), endocarditis in two patients (1%), and total AV-block requiring an endocavitary pacemaker in 14 patients (7%). At one year aortic regurgitation was evident in 27% patients but only one patient showed grade III. The stentless xenograft still offers good hemodynamics at one year. Morbidity and mortality are acceptable. Evaluation of the long-term performance of this new type of xenograft will be an important issue in future.

Adult↗