Biomedical subjects

A Saxena

Publications and source records attributed to A Saxena.

At least 19 recordsLinked to original sources

PubMed2001

Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells.

Dendritic cells (DCs) that acquired antigen from apoptotic tumor cells are able to induce major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes and antitumor immunity. In the present study, we investigated the efficiency of antitumor immunity derived from DCs that had phagocytosed apoptotic/necrotic BL6-10 melanoma cells compared with that of DCs pulsed with the tumor mTRP2 peptide. Our data showed that phagocytosis of apoptotic/necrotic tumor cells resulted in maturation of DCs with up-regulated expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5. These mature DCs displayed enhanced migration toward the CC chemokine MIP-3beta in a chemotaxis assay in vitro and to the regional lymph nodes in an animal model in vivo. Our data also showed that vaccination with DCs that had phagocytosed apoptotic/necrotic BL6-10 cells was able to (i) more strongly stimulate allogeneic T-cell proliferation in vitro, (ii) induce an in vivo Th1-type immune response leading to more efficient tumor-specific cytotoxic CD8(+) T-cell-mediated immunity and (iii) eradicate lung metastases in all 6 vaccinated mice compared with mice vaccinated with DCs pulsed with the tumor mTRP2 peptide, in which lung metastases were reduced (mean number of 16 per mouse) but not completely eradicated. Therefore, DCs that had phagocytosed apoptotic/necrotic tumor cells appear to offer new strategies in DC cancer vaccines.

Animals↗

PubMed2001

Interaction between sine-Gordon breathers.

Using the exact breather lattice solution of the sine-Gordon equation, we obtain the asymptotic interaction between two breathers. We identify the exponential dependence of the interaction on the breather separation as well as its power-law dependence on the breather frequency. Numerical simulation of the breather lattice demonstrates its instability. However, stabilization of such structures is found to be feasible through ac driving and damping. Finally, other limits of the original periodic solution are traced, obtaining the leading-order terms in the interaction between "pseudosphere" solutions and kink-antikink pairs.

Journal Article↗

PubMed2001

Three-dimensional elastic compatibility and varieties of twins in martensites.

We model a cubic-to-tetragonal martensitic transition by a Ginzburg-Landau free energy in the symmetric strain tensor. We show in three dimensions (3D) that solving the St. Venant compatibility relations for strain, treated as independent field equations, generates three anisotropic long-range potentials between the two order parameter components. These potentials encode 3D discrete symmetries, express the energetics of lattice integrity, and determine 3D textures. Simulation predictions include twins with temperature-varying orientation, helical twins, competing metastable states, and compatibility-induced elastic frustration. Our approach also applies to improper ferroelastics.

Journal Article↗

PubMed2001

Novel and potent tacrine-related hetero- and homobivalent ligands for acetylcholinesterase and butyrylcholinesterase.

Based upon synthetic and biochemical results, a novel and potent tacrine analogue and heterobivalent analogues of tacrine, were designed. The role played by the amino groups of homo- and heterobivalent ligands in the interaction with the peripheral and catalytic sites of AChE and BuChE were investigated. The syntheses of these materials together with the results of AChE/BuChE inhibition assays are detailed.

Acetylcholinesterase↗

PubMed2001

Detection of coronary artery anomalies in tetralogy of Fallot using a specific angiographic protocol.

Patients with tetralogy of Fallot were studied with a prespecified angiographic protocol aimed to delineate the types and incidence of coronary artery anomalies and to look for any correlation with other abnormalities detected by simultaneous detailed angiography. The incidence of coronary anomalies was found to be 7.0%; no association was found with these anomalies with any of the other abnormalities detected.

Abnormalities, Multiple↗

PubMed2001

One and a half ventricle repair with pulsatile bidirectional Glenn: results and guidelines for patient selection.

BACKGROUND: The guidelines for performing a one and a half ventricle repair with pulsatile bidirectional Glenn remains controversial. This retrospective report summarizes the experience of a single institution, with an attempt at providing an answer. METHODS: Fifty consecutive patients, aged 4 months to 42 years, underwent intracardiac repair along with a superior cavopulmonary connection. Twenty-seven of the patients had had previous surgical palliation. Repair consisted of patch closure of the ventricular septal defect (n = 25), tricuspid valve repair (n = 26), reconstruction of the right ventricular outflow tract (n = 34), transpulmonary annular patch (n = 34), right ventricle to pulmonary artery homograft conduit (n = 4), and concomitant repair of atrioventricular canal (n = 9). Ten patients were left with a fenestration in the atrial septum. RESULTS: There were six hospital deaths (12%) and two late deaths (4.5%). Forty-two survivors were followed from 8 months to 116 months. Eighty-eight percent are in functional class I. Actuarial survival at 97 months was 74%. CONCLUSIONS: Moderate right heart hypoplasia constitutes a safe anatomic category for a pulsatile bidirectional Glenn. It is advisable not to proceed with a one and a half ventricle repair if postoperative residual pulmonary artery hypertension is anticipated. Patients requiring an intricate intracardiac repair and those with concomitant right heart hypoplasia may be better suited for a Fontan type of repair to reduce the complexity of the procedure.

Actuarial Analysis↗

PubMed2001

Factors influencing late course of residual valvular and infundibular gradients following pulmonary valve balloon dilatation.

BACKGROUND: Though acute and follow-up benefits of pulmonary valve balloon dilatation (PVBD) for pulmonic valve stenosis are well known, the late course of residual gradients at individual valvular and infundibular levels is not well described. Furthermore, the factors influencing this late course have not been studied. MATERIALS AND METHODS: We assessed the transpulmonary gradients by echo-Doppler in 96 patients (61 male, mean age 10.7 years) at a mean follow-up interval of 58.8+/-32.1 months (minimum 2 years) following PVBD. The patients were divided into three groups based on the residual gradients at valvular and infundibular levels immediately following PVBD as assessed by pull-back of an end-hole catheter across the right ventricular outflow tract: Group A with minor pressure gradients at both valvular and infundibular levels of less than 30 mmHg (n=60, 62.5%), Group B with predominantly infundibular gradients of more than 30 mmHg with a valvular gradient of less than 30 mmHg (n=27, 28.1%), and Group C with a residual valvular gradient of greater than 30 mmHg irrespective of the infundibular gradient (n=9, 9.4%). Demographic characteristics, hemodynamic parameters and procedural variables were correlated with the change in gradient at follow-up (late fall) and with long-term results. RESULTS: The mean follow-up trans-pulmonary gradient was 20+/-14 mmHg which was significantly lower than that immediately post-PVBD (43+/-32 mmHg), P<0.001. The late fall (mean 24+/-29, range -55 to 110 mmHg) varied widely depending upon the acute result group: patients in Groups A and B showed significant late fall of 9+/-12 mmHg (P<0.05 for follow-up gradient compared to that following PVBD) and 58+/-31 mmHg (P<0.0001), respectively, while patients in Group C showed an insignificant late fall of 14+/-37 mmHg (P=0.21). In particular, each one of the patients in Group B showed decrease in trans-pulmonary gradients. On multivariate analysis, the extent of infundibular gradient emerged as the most important predictor of late fall (coefficient of determination 75%, P<0.0001). Patients who underwent PVBD at less than 2 years of age had a significantly greater late fall (41+/-33 mmHg) as compared to older patients (22+/-25 mmHg), P<0.05. A sub-optimal long-term result (transpulmonary gradient >25 mmHg, n=24) was significantly related to older age (P<0.001), dysplastic valve morphology (P=0.002), greater baseline trans-pulmonary gradients (P<0.001) and higher post-PVBD gradients (P=0.04). CONCLUSIONS: The long-term course of patients following PVBD depends upon the site and magnitude of the residual gradients. Even high residual infundibular gradients show marked reduction at follow-up, especially in infancy.

Adolescent↗

PubMed2001

Analysis of the CD40/CD40L role in the sustenance of alloreactive antibody production.

CD40 ligand (CD40L) is important for T/B lymphocyte interaction. To understand the cellular basis of humoral allosensitization we, therefore: (1) measured CD40L protein and gene expression in sensitized and non-sensitized uremic unactivated peripheral CD4+ T lymphocytes; (2) studied the impact of blocking the CD40/CD40L pathway on alloreactive antibody (allo-Ab) production by engrafted sensitized PBLs into severe combined immunodeficient (SCID) mice after in vitro preactivation with IL2/LPs/HLA class II allopeptides and adjuvants as a potent stimulus to produce allo-Ab (Shoker et al. Transplantation 1999;68;1188); and (3) studied the modifying effect of CD40/CD40L blockade on T helper type I and II cytokine gene expression in the respective mice spleen. The CD40L protein was measured by flow cytometry and the gene expression was measured by quantitative RT-PCR. Alloreactive antibodies (alo-Abs) produced by sensitized PBLs engrafted into SCID mice with and without blockade of the CD40 receptor were measured by the PRA-STAT ELISA method. The modifying effects of CD40 blocking on allo-Ab production and cytokine gene expression by the engrafted cells measured by RT-PCR were then compared. There was no detectable CD40L protein expression in either the uremic or the control groups. The CD40L gene expression of 0.04 +/- 0.02 attomoles (aM) in the sensitized group was significantly higher than in the non-sensitized patients (0.009 +/- 0.007 aM, P < 0.0001) or the control CD4+ T cells (0.016 +/- 0.004 aM, P < 0.001). Blockade of the CD40 receptor abrogated the production of allo-Ab antibodies by the engrafted sensitized cells in 60% of the tested mice (n = 10); decreased the mean +/- S.D. optic density of allo-Ab to 0.1 +/- 0.13 and the mean +/- S.D. PRA to 12 + 16). In the presence of the control Ab, allo-Ab production in SCID sera was present in 100% of the 10 SCID mice tested; the mean +/- S.D. PRA was 75 +/- 20, and the mean + S.D. OD activity was 0.412 +/- 0.17. All cytokine genes were, otherwise, expressed in the presence or absence of CD40 blockade. The results suggest a potential role of an enhanced CD40/CD40L interaction in the sustenance of alloreactive antibody production without significant deviation to T helper-like I or II responses. Blocking the CD40/CD40L pathway may have a potential therapeutic benefit to treat sensitized uremic patients.

Adjuvants, Immunologic↗

PubMed2001

A modified technique of devascularization for surgical management of portal hypertension in children.

In developing countries surgery is indicated in patients with portal hypertension for a variety of reasons. This study prospectively evaluates a modified technique of devascularization for secondary prophylaxis of variceal bleeding in patients with portal hypertension of different aetiologies. Transabdominal extensive oesophagogastric devascularization combined with transmural ligation of oesophageal and gastric varices was performed in 16 paediatric patients (nine with extrahepatic portal venous obstruction, and seven with non-cirrhotic portal fibrosis) in an elective setting. The Sugiura devascularization procedure was modified to minimize the operating time and to avoid the problems associated with oesophageal transection and anastomosis. The operative mortality rate as well as the oesophageal leak rate was zero. One patient developed an oesophageal stricture. During a 12-month follow-up, patients were seen with residual varices (2), recurrent varices (3) and rebleeding (1). Porto-systemic encephalopathy was seen in one patient only. This technique is a simple, straightforward, safe and effective modification of the Sugiura procedure in controlling bleeding, providing good quality of life with minimal porto-systemic encephalopathy.

Child↗

PubMed2001

Tramadol for postoperative shivering: a double-blind comparison with pethidine.

In most operating and recovery rooms, shivering is controlled by the use of humidifiers, warming blankets, and inhalation of humidified heated oxygen. However, pharmacological control is an effective alternate treatment modality. This randomized, double-blind trial, conducted in 30 ASA Grade 1 or 2 patients, was designed to explore the efficacy of tramadol and pethidine in the treatment of post-anaesthetic shivering. Tramadol is an inhibitor of the re-uptake of serotonin (5-hydroxytryptamine) and norepinephrine in the spinal cord. This facilitates 5-hydroxytryptamine release, which influences thermoregulatory control. We compared the efficacy of tramadol with that of pethidine, presently a widely used drug for the control of shivering. Patients received either tramadol 1 mg/kg or pethidine 0.5 mg/kg intravenously and the grade of shivering, pulse rate, blood pressure and respiratory rate were observed every 10 minutes after injection for one hour Shivering was significantly more likely to have ceased in the tramadol group (12 of 15 versus 4 of 15 cases, P<0.05) at 10 minutes after drug administration and this control was better sustained. No patients receiving tramadol had a recurrence of shivering. It is concluded that intravenous tramadol 1 mg/kg is more effective for the treatment of postoperative shivering than pethidine 0.5 mg/kg.

Adult↗

PubMed2001

Proximal fourth metatarsal injuries in athletes: similarity to proximal fifth metatarsal injury.

Proximal fourth metatarsal injuries are rarely reported. We present five case histories in which athletic patients sustained injuries at the shaft-base junction of the fourth metatarsal. Similar to proximal fifth metatarsal injuries, adduction of the forefoot appears to be associated. Our patients returned to their activities in two to eight months. These patients injuries tended to take longer to heal than other lesser metatarsal fractures and stress fractures (which are typically more distal). Some patients were continually symptomatic, even after three months of rest and immobilization. This coincides with proximal fifth metatarsal injuries and stress fractures. For treatment of proximal fourth metatarsal injuries to be successful, ideal treatment appears to involve nonweightbearing below-knee cast/boot immobilization for three weeks. This is followed by an additional three or more weeks of weightbearing immobilization. Healing may still be prolonged.

Adolescent↗

PubMed2001

Goblet cell carcinoids of the appendix: immunophenotype and ultrastructural study.

BACKGROUND: Goblet cell carcinoids of the appendix are rare neoplasms with uncertain biological behavior. OBJECTIVE: The aims of our study were to evaluate the immunophenotype of this neoplasm with cell cycle/cell proliferation markers and to understand their histogenesis with ultrastructural analysis using conventional carcinoids as a frame of reference. METHODS: Clinical data and archival pathologic material of all goblet cell carcinoids of the appendix recorded by the Saskatchewan Cancer Registry between 1970 and 1998 were reviewed and evaluated by light microscopy, histochemistry, immunohistochemistry, and electron microscopy. RESULTS: Seven cases of goblet cell carcinoids were identified among 110 cases of conventional carcinoids of the appendix. Histopathology revealed widespread infiltration of the periappendiceal fat in all cases, with extensive perineural invasion. The cells stained strongly positive for mucicarmine, periodic acid-Schiff, periodic acid-Schiff diastase, Alcian blue, cytokeratin, and carcinoembryonic antigen. Most cases were positive for synaptophysin. Increased expression of cell proliferation markers and cell cycle markers was observed. Expression of p53 was strong in one case. Electron microscopy demonstrated the presence of mucinous vacuoles of varying sizes and occasional membrane-bound neuroendocrine granules. CONCLUSIONS: Goblet cell carcinoids of the appendix arise from a pluripotent cell with divergent neuroendocrine and mucinous differentiation. These neoplasms are widely invasive; they demonstrate a high cellular proliferation rate and dysregulation of the cell cycle with up-regulation of cyclin D1 and p21, and down-regulation of p16. Complete removal of the tumor is recommended because of the unpredictable biological behavior of this tumor, which includes delayed local recurrences and lung metastases.

Adult↗

PubMed2001

Mitral valve repair in a predominantly rheumatic population. Long-term results.

Valve repair in rheumatic patients poses special problems due to valve deformity and mixed lesions. We present our experience from January 1988 through June 1999, in this retrospective study of 818 patients (377 males). The mean age was 22.8 +/- 11.3 years (range, 2 to 70 years). The cause of mitral regurgitation was rheumatic in 718 (88%) patients, congenital in 51, myxomatous in 34, infective in 7, and ischemic in 8. Most patients (64%) were in New York Heart Association functional class III or IV. Congestive heart failure was present in 116 patients (14%). Reparative procedures included posterior collar annuloplasty (n=710), commissurotomy (n=482), cusp-level chordal shortening (n=237), cusp thinning (n=222), cleft suture (n= 166), and cusp excision/plication (n=42). Operative mortality was 4% (32 patients). Preoperative left ventricular dysfunction, presence of congestive heart failure, and advanced functional class were associated with greater mortality. Follow-up ranged from 1 to 144 months (mean, 44.9 +/- 33.2 months) and was 96% complete. Most survivors (70%) had no or trivial mitral regurgitation. Forty patients required reoperation for valve dysfunction. There were 23 (2.8%) late deaths. Actuarial, reoperation-free, and event-free survival at 11 years were 92.6% +/- 1.0%, 65.0% +/- 10%, and 38% +/- 6.0%, respectively Among the survivors, 85% were in New York Heart Association functional class I. We conclude that mitral valve repair in rheumatic patients, using current techniques, can effectively correct hemodynamic and functional abnormalities with satisfactory results.

Adolescent↗

PubMed2001

Pushing the envelope. Case studies on how fast you can and cannot return the elite athlete to running.

When treating an elite athlete, a physician always must keep in mind the status of the athlete in training, upcoming sports events, and the athlete's financial status. If the treatment requires the athlete to withdraw from regular training or sports events, a modified training program should be considered. This modified training must be balanced with returning the athlete back to full form and keeping him or her physically fit.

Adolescent↗

PubMed2000

Synthesis, chiral chromatographic separation, and biological activities of the enantiomers of 10,10-dimethylhuperzine A.

(+/-)-10,10-Dimethylhuperzine A (2, DMHA) has been synthesized, and its enantiomers have been separated using chiral HPLC. (-)-DMHA inhibits AChE with a Ki value approaching that of (-)-huperzine A, whereas (+)-DMHA shows no AChE inhibitory activity. On the other hand, both enantiomers are equally potent against glutamate-induced neurotoxicity when tested in neurons.

Acetylcholine↗

PubMed2000

Association between mutations of the follicle-stimulating-hormone receptor and repeated twinning.

Follicle-stimulating hormone (FSH) has a role in folliculogenesis and spontaneous twinning. Using the candidate gene approach, we searched for mutations in the gene encoding the FSH receptor in a woman who had given birth to two sets of dizygotic twins without fertility treatment. We identified two linked mutations (Thr307Ala and Asn680Ser) that were closely associated with this phenotype. We suggest that expression of both mutations increases the sensitivity of the receptor to FSH.

Adenine↗

PubMed2000

Anomalous colloidal stability of protein coated polystyrene latex beads studied by small angle light scattering.

Results of small angle laser light scattering experiments carried out on polystyrene latex beads coated with lysate of Plasmodium falciparum (Pf) antigen (Ag) and human seropositive sera (10:1 ratio) are reported for various NaCl concentrations (0-300 mM). The protein coated beads showed time-dependent coagulation. The normalised intensity of scattered light I(s)(t)/I(0) showed I(s)(t)/I(0)=1+(Gammat)(delta) behaviour with the coagulation rate, Gamma and exponent, delta showing anomalous dependence on NaCl concentration. The coagulation rate exhibited strong increase up to NaCl concentration of 50 mM, above this and up to 300 mM the coagulation rate was found to remain independent of NaCl concentration yielding non-DLVO behaviour. The same was true for delta which increased from 1.04+/-0.06 to 6.94+/-0.07 as NaCl concentration was raised from 0 to 50 mM. Above 50 mM it remained constant with delta=6.94+/-0.07. Results are discussed through Smoluchowski aggregation kinetics and theoretical construction of interparticle interaction potentials relevant to our problem.

Animals↗

PubMed2000

Molecular geometry fluctuation model for the mobility of conjugated polymers.

We present a model to describe electrical transport in dense films of conjugated polymers. The essential physical features of the model are as follows: (i) thermal fluctuations in the molecular geometry of the polymer modify the energy levels of localized electronic states in the material, and (ii) the primary restoring force for these fluctuations is steric, which leads to spatial correlation in the energies of the localized electronic states. The model describes the electric field dependence of the mobility and explains the carrier density dependences of mobility observed in polymer diodes and field effect transistors.

Journal Article↗