Biomedical subjects

A Suri

Publications and source records attributed to A Suri.

At least 37 records · Page 2Linked to original sources

PubMed2002

Subarachnoid hemorrhage and intracereebral hematoma following lumboperitoneal shunt for pseudotumor cerebri: a rare complication.

Placement of lumboperitoneal (LP) shunt as a surgical treatment for benign intracranial hypertension (BIH) is generally a safe procedure, with complications like mechanical failure, overdrainage and infections. Subarachnoid hemorrhage and intracerebral hematoma were seen after lumboperitoneal shunt in a patient having BIH. These complications were the cause of the patient's deterioration. After removal of the hematoma and performing a decompressive procedure, patient's neurological condition improved. The clinical features, investigations and clinical course are described and the literature reviewed.

Adult↗

PubMed2000

Posterior fossa tension pneumocephalus.

Posterior fossa tension pneumocephalus (PFTP) is a very rare clinical entity--OFF few case reports available prove how rare. Five patients with PFTP are presented. All were operated on for posterior fossa lesions. One was operated on in the lateral position and the rest in a sitting position. All the patients had postoperative (early) neurological deterioration, and computed tomography (CT) scans revealed PFTP in the left cerebellopontine angle in one case and in the IV ventricle in the rest. Air was aspirated from the posterior fossa in one case. All the cases were electively ventilated for 48-72 h. All the patients had an immediate onset of progressive neurological recovery after early intervention and elective ventilation. One patient died 10 days later because of a recurrence of empyema and the development of meningitis. PFTP is a rare but important complication of posterior fossa surgery. Early intervention and elective ventilation can produce a good recovery.

Adolescent↗

PubMed2000

Global myocardial revascularization without cardiopulmonary bypass using innovative techniques for myocardial stabilization and perfusion.

BACKGROUND: In off-pump coronary bypass grafting (CABG), invasiveness is reduced but technically perfect anastomosis is jeopardized by cardiac motion and the need to hurry to reduce the time of ischemia. Also, a major cause of postoperative morbidity and mortality is ungrafted circumflex coronary artery disease. We have devised a means of overcoming these shortcomings and performing multivessel CABG. The objective of this study was to assess the safety and efficacy of our technique. METHODS: One hundred patients with severe triple-vessel disease underwent multivessel off-pump CABG. For cardiac stabilization, a combination of local pericardial stabilization sutures and lifting and rotating the heart by means of posterior pericardial sutures were used. For myocardial perfusion, a technique of retrograde coronary sinus perfusion by arterial blood from the ascending aorta was used. RESULTS: Each patient received an average of 3.8 grafts (range 3 to 5). Complications included conversion to cardiopulmonary bypass (CPB) in 1 patient and a perioperative myocardial infarction in the same patient. In all other patients we were able to perform a satisfactory grafting in all territories with no operative mortality. Rapid recovery allowed 95% of our patients to resume normal activity within 1 month. A predischarge graft angiogram in 35 patients showed 97.8% patency. CONCLUSIONS: These results suggest that off-pump CABG with our techniques is effective and safe. Early clinical outcome and excellent patency rates suggest its more widespread use in selected cases.

Adult↗

PubMed2000

Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.

We have determined the crystal structure of I-Ag7, an integral component in murine type I diabetes development. Several features distinguish I-Ag7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-Ag7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-Ag7 epitope HEL(11-25) support a comprehensive structure-based I-Ag7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-Ag7 in autoimmunity.

Amino Acid Sequence↗

PubMed1999

Effect of craniopharyngioma fluid on femoral vessels of rat.

Craniopharyngioma fluid spillage during surgery is reported to cause aseptic meningitis, but effects of the spillage on vessels have not yet been studied. Therefore we experimentally studied the effect of external contact on femoral vessels of the rat to assess its possible role in the cerebral vascular complications. The major direct effect of the craniopharyngioma fluid on the femoral vessels was vasospasm, appearing on the fourth day after instillation. The vasospasm was observed in 83% of femoral vessels studied between 4-15 days and one of the vessels showed intra-luminal thrombus. The difference in the vessel diameter after instillation (4-15 days) was compared with the controls and was statistically significant (p < 0.01). These findings correspond well with the observed deterioration on post-operative days 5-7, due to vascular complications. No histopathologic (light-microscopic) changes of inflammation or necrosis were found in the femoral vessels. Our study shows that contact of craniopharyngioma fluid to arteries leads to vasospasm, and spillage during surgical excision may contribute to vascular complications encountered in the post-operative period. Prevention of spillage of this fluid and the routine use of cerebral vasodilators to prevent ischemic complications after craniopharyngioma surgery needs further evaluation.

Animals↗

PubMed1999

Dissecting the role of CD4+ T cells in autoimmune diabetes through the use of TCR transgenic mice.

Insulin-dependent diabetes mellitus (IDDM) is an immunological disorder wherein autoimmune-mediated destruction of islet cells in the pancreas results in persistent hyperglycemia. The non-obese diabetic mouse model of IDDM has revealed the importance of multiple factors that impact upon the disease process; however, understanding of primary immune mechanisms leading to IDDM remains elusive. The emergence of transgenic mouse models for IDDM has made important contributions towards clarifying many of these factors, including the cell types, the various effector molecules and the genetic elements involved in the pathogenesis of IDDM. In this review, we will focus on the primary mechanism and mediators of islet beta-cell death, the impact of T-helper lymphocytes on disease progression and the potential role of major histocompatibility complex class II molecules in conferring susceptibility to IDDM.

Animals↗

PubMed1999

Inhibition of CYP2D6 by quinidine and its effects on the metabolism of cilostazol.

OBJECTIVE: In vitro results are inconclusive as to whether cilostazol is metabolised by cytochrome P450 isoenzyme 2D6 (CYP2D6). The goals of this study were (1) to assure the dose of quinidine and timing relative to cilostazol used in this study were adequate to cause inhibition of CYP2D6, (2) to evaluate carryover effects of quinidine administration, and (3) to evaluate the effect of CYP2D6 deficiency and administration of quinidine (a CYP2D6 inhibitor) on the pharmacokinetics of a single 100 mg oral dose of cilostazol. DESIGN: This study was conducted as a single-centre, open-label, randomised sequence, 2-period, crossover pharmacokinetic trial. Water alone (treatment without quinidine) or two 200 mg oral doses of quinidine sulfate with water were administered 25 hours and 1 hour prior to a single 100 mg dose of cilostazol in period 1. Study participants were crossed over to opposite treatment in period 2. Metoprolol 25 mg, used as a positive control, was administered 1 hour after quinidine sulfate with water or using water alone to assess the magnitude of CYP2D6 inhibition by quinidine. STUDY PARTICIPANTS: 22 healthy nonsmoking Caucasian (14 male and 8 female) volunteers participated in the study. MAIN OUTCOME MEASURES: Serial blood and urine samples were collected at predose and after cilostazol administration to characterise cilostazol and its metabolite pharmacokinetics. Additional plasma samples were taken to assess the pharmacokinetics of quinidine. Urine samples were collected to measure metoprolol and hydroxymetoprolol. RESULTS: Administration of metoprolol with quinidine caused a significant (p < 0.001) decrease in the urinary 4-hydroxymetoprolol/metoprolol ratio compared with administration of metoprolol alone (42-fold decrease, 0.065 vs 2.707). Hence, quinidine effectively converted extensive metabolisers of CYP2D6 to poor metabolisers of CYP2D6. The 21-day washout period was adequate to have complete recovery from quinidine inhibition of CYP2D6. The analysis of variance demonstrated that the mean maximum plasma concentration (Cmax) for cilostazol, both adjusted and unadjusted for the free fraction, was higher in the control group than in the quinidine group (p = 0.023). However, the time to Cmax (p = 0.669), the area under the plasma concentration-time curve from time zero to infinity (AUC infinity; p = 0.133), and the apparent oral clearance (p = 0.135) were unchanged. The geometric mean ratios (90% confidence interval) comparing with quinidine (test) and without quinidine (reference) coadministration for Cmax and AUC infinity are 0.86 (0.77, 0.95) and 0.92 (0.84, 1.00), respectively. Similar patterns were observed for OPC-13015 and OPC-13213 with regard to Cmax, area under the plasma concentration-time curve from time zero to the last measurable concentration at time t, and AUC infinity (where determinable). The slight decrease in the systemic availability of cilostazol and its metabolites was thought to be a result of the increased gastrointestinal motility secondary to quinidine. CONCLUSIONS: Administration of quinidine sulfate 200 mg profoundly inhibited CYP2D6-mediated metabolism. The effects of quinidine inhibition of CYP2D6 metabolism were completely reversible during the 21-day washout period. Coadministration of quinidine with cilostazol had no substantial effect on cilostazol or its metabolites (OPC-13015 and OPC-13213). Hence, CYP2D6 does not have a significant contribution in the metabolic elimination of cilostazol.

Administration, Oral↗

PubMed1999

Effect of omeprazole on the metabolism of cilostazol.

OBJECTIVE: In vitro results suggest that cilostazol is metabolised by cytochrome P450 (CYP) isoforms 1A2, 2D6, 3A4 and 2C19. This study was designed to evaluate the effect of concomitant administration of omeprazole (a CYP2C19 inhibitor) on the pharmacokinetics of a single 100 mg oral dose of cilostazol. DESIGN: This study was conducted as a single-centre, open-label, nonrandomised, 2-period, crossover pharmacokinetic trial. A single 100 mg dose of cilostazol was administered orally on days 0 and 14. Oral omeprazole (40 mg every day) was administered on days 7 to 18. STUDY PARTICIPANTS: 20 healthy nonsmoking male and female volunteers. MAIN OUTCOME MEASURES: Serial blood samples were collected before and after cilostazol administration to characterise the pharmacokinetics of cilostazol and its metabolites. RESULTS: Following omeprazole coadministration, the increases in cilostazol maximum plasma concentration (Cmax) and area under the plasma concentration-time curve at time t (AUCt) were 18% (p = 0.062) and 26% (p < 0.001), respectively. For the 2 major circulating metabolites, OPC-13015 and OPC-13213, the OPC-13015 Cmax and AUCt increased by 29 and 69%, respectively (p < 0.001). However, for OPC-13213, the Cmax and AUCt decreased by 22 and 31%, respectively (p < 0.001). The plasma protein binding of cilostazol was unaffected by coadministration of omeprazole. CONCLUSIONS: Coadministration of cilostazol with omeprazole resulted in an increase in the systemic exposure of cilostazol and its active metabolite, OPC-13015, by 26 and 69%, respectively. For the other active metabolite, OPC-13213, systemic exposure decreased by 31% because of inhibition of cilostazol metabolism to this metabolite. These changes in systemic exposure were well tolerated. A dose of 50 mg cilostazol twice a day should be considered during coadministration of inhibitors of CYP2C19, such as omeprazole.

Administration, Oral↗

PubMed1999

Effects of CYP3A inhibition on the metabolism of cilostazol.

OBJECTIVE: In vitro results suggest that cilostazol is metabolised by cytochrome P450 (CYP) isoforms 1A2, 2D6, 3A and 2C19. This study investigated the role of CYP3A inhibition on the metabolism of cilostazol. DESIGN: The study was conducted as a single-centre, open-label, nonrandomised, 2-period, crossover pharmacokinetic trial. A single dose of cilostazol 100 mg was administered orally on days 1 and 15. Erythromycin (150 mg orally 3 times daily) was administered on days 8 to 20. 14C-erythromycin (3 microns Ci) was administered intravenously on days 1 and 15 one hour before cilostazol administration to determine baseline and the inhibitory effect of erythromycin treatment on CYP3A activity. STUDY PARTICIPANTS: 16 healthy nonsmoking male volunteers. MAIN OUTCOME MEASURES: Serial blood and pooled urine samples were collected before and after cilostazol administration to quantitate cilostazol and its metabolites. Serial exhalation samples were collected after intravenous 14C-erythromycin administration and radioactivity was quantitated by scintillation counting. Pharmacokinetics were determined by noncompartmental methods and compared before and after erythromycin administration. Tolerability assessments included adverse events, laboratory tests, vital signs and electrocardiographs. RESULTS: Following erythromycin coadministration, cilostazol maximum plasma concentration (Cmax), area under the plasma concentration-time curve at time t (AUCt), and area under the curve from zero to infinity (AUC infinity) increased significantly by 47, 87, and 73%, respectively, and an approximately 50% reduction in unbound clearance was observed for the major circulating metabolite of cilostazol, OPC-13015. Cmax decreased significantly (p < 0.001) by 24%, while AUCt increased by 8%; this increase was not significant. For the second major metabolite, OPC-13213, the Cmax and AUCt increased by 29 and 141%, respectively (p < 0.001). CONCLUSIONS: In vivo results are in agreement with previous in vitro human microsome studies, indicating that cilostazol is metabolised to OPC-13015 via CYP3A. In addition, OPC-13213 concentrations increased after inhibition of CYP3A because of inhibition of sequential metabolism of OPC-13213 via CYP3A. A starting dose for cilostazol of 50 mg twice daily should be considered during coadministration of inhibitors of CYP3A.

Administration, Oral↗

PubMed1998

DNA strand biases and the mutational resilience of genes.

This paper quantifies the resilience of a gene to each class of base substitution. The resilience of a gene is defined as the set of probabilities of synonymous base substitution (one for each type of base substitution on each DNA strand), and is derived from the fraction of all possible substitutions which result in no change of encoded amino acids. We discuss the resilience of the common mutational target genes, lacI and hypoxanthine-guanine phosphoribosyltransferase (hprt), and the p53 tumour suppressor gene. There are inherent strand biases to mutation in terms of the resilience differences between the non-template and template DNA strands. The ability to quantify resilience differences between the two DNA strands contributes to our understanding of strand bias to mutation.

Bacterial Proteins↗

PubMed1998

Molecular cloning of human testis mRNA specifically expressed in haploid germ cells, having structural homology with the A-kinase anchoring proteins.

We have cloned a human testis specific gene (hi), which encodes for a protein having regional homologies to the domain of A-kinase anchoring proteins. Open reading frame encodes a protein of 860 amino acids. The predicted protein has a molecular weight 95.8 kD and contains 32 cysteine residues and 34 potential phosphorylation sites. The deduced protein analysis revealed an eukaryotic secretory signal with a potential cleavage site. Northern blot analysis detected a single transcript of approximately 3.0 kb in testis and not in any other somatic tissues. Expression of hi transcript was observed only in round spermatids indicating post meiotic haploid gene expression.

Amino Acid Sequence↗

PubMed1998

Cloning of a novel human testis mRNA specifically expressed in testicular haploid germ cells, having unique palindromic sequences and encoding a leucine zipper dimerization motif.

A novel gene coding for a human sperm surface protein (HSS) has been cloned from a human testis cDNA library. The 2.5 kb cDNA (hss) contains five direct repeats, three mirror repeats, three possible stem loop structures and three unique palindromic motifs located at functionally relevant positions. Open reading frame encodes a protein of 766 amino acids. The deduced protein analysis revealed a NH2 terminus extracellular domain having a leucine zipper (LZ) motif, a transmembrane helical domain and a cytoplasmic domain at the COOH terminus. Tissue specific expression studies demonstrated the presence of hss transcript only in testis. Cell type expression of hss mRNA was observed only on the round spermatids suggesting haploid germ cell expression.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Pharmacokinetics of multiple-dose oral cilostazol in middle-age and elderly men and women.

Cilostazol is being developed for the treatment of intermittent claudication due to peripheral arterial disease (PAD). This study was conducted to investigate the effects of age and gender on the pharmacokinetics of cilostazol after multiple-dose administration. It was an open label, multiple-dose study of cilostazol administered to male and female subjects 50 years of age and older at a dose of 100 mg (oral tablet) twice daily for 7 days. Equal numbers of healthy male and female (7 per group), nonsmoking subjects stratified into age groups of 50 to 59 years, 60 to 69 years, and 70 years or older were enrolled. Serial plasma samples were obtained. Data were analyzed by model-independent methods. Cilostazol was absorbed at a moderate rate, with peak plasma concentrations occurring at an overall mean of 2.4 hours after administration. Cilostazol is extensively bound (95%), primarily to albumin. A trend toward increasing cilostazol free fraction with age was observed in the male subjects, which was explained by a decrease in plasma albumin concentration with age. Differences in plasma protein binding between age and gender groups (less than 15%) are not expected to have any clinical significance. Plasma cilostazol concentrations reached steady state by day 4. The pharmacokinetic characteristics of cilostazol were not affected by age or gender.

Administration, Oral↗

PubMed1998

Influence of plasma expansion on plasma protein binding of ketorolac.

STUDY OBJECTIVE: To determine the effect of dilution with intravascular volume expanders commonly used by anesthesiologists on clinically relevant levels of free serum ketorolac. DESIGN: In vitro study. SETTING: Pharmaceutics laboratory of a medical college. INTERVENTIONS: The effect of 6% hydroxyethylstarch, 5% albumin, 6% dextran 60, and lactated Ringer's solution on in vitro plasma protein binding of ketorolac was investigated by ultrafiltration. The binding was studied at three different drug concentrations: low therapeutic (0.3 microgram/ml), high therapeutic (3 micrograms/ml), and toxic (10 micrograms/ml), and at two or more volume expander dilutions. MEASUREMENTS AND MAIN RESULTS: The effect of plasma dilution on free ketorolac was consistent across all volume expanders tested and for each ketorolac concentration studied. As the plasma dilution with albumin, hydroxyethylstarch, dextran 60, or lactated Ringer's solution increased, the unbound ketorolac also increased from 3.2% to 3.3% in undiluted plasma to 5.0% to 8.7% in 50% dilution of the plasma with the investigated expanders. Dilution of plasma by only 10% resulted in a significant, but relatively minor, increase of unbound ketorolac to 3.2% to 3.8%. CONCLUSION: Because of the pharmacokinetic properties of ketorolac, this pharmacokinetic interaction can be expected to have only minor effects on unbound ketorolac concentrations when ketorolac is administered after the plasma expander. When ketorolac administration is followed by rapid plasma expander infusion, a transient increase of unbound ketorolac in plasma can be expected.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Seizures following posterior fossa surgery.

A retrospective analysis of seizure incidence in 511 patients who underwent posterior possa operations via a suboccipital craniectomy with prophylactic anticonvulsant agents, was performed. Thirty patients (5.9%) experienced seizures within 2 weeks postoperatively. Their mean age was 15 years. Twenty patients had seizures within 3 h of operation; 24 patients had generalized tonic clonic seizures. Focal motor seizures with secondary generalization and simple focal motor seizures were recorded in three patients each. The incidence of postoperative seizures was highest in patients with acoustic schwanommas (9.09%) followed by those with medulloblastomas (8.54%) and astrocytomas (8.33%). The sitting position, associated with venous air embolism (VAE) and or pneumocephalus, was related to the occurrence (p = 0.001) of postoperative seizures. Seizures occurred in 24 patients out of 250 cases operated on in the sitting position compared with 3/170 and 3/91 in the prone and lateral positions, respectively. Intraoperatively significant VAE occurred in 10 out of 30 patients and postoperative computed tomography revealed pneunocephalus in 20 out of 30 patients. A higher percentage was found in patients with a preoperative ventriculoperitoneal shunt or intraoperative ventriculostomy (6.5%) than in those without (5.1%), but the difference was not statistically significant. In conclusion, seizures after posterior fossa surgery are a significant problem which is not reflected in the published literature. Our study highlights the significance of the sitting position in the causation of seizures after posterior fossa surgery.

Adolescent↗

PubMed1997

The recovery of a B2 insertion in the lacI gene of a rat cell line containing a lambda/LIZ shuttle vector.

The bacterial lacI gene is in use as a reporter gene for mutation in transgenic mice, rats and in cell lines. During a mutagenesis study in which we used such a rat cell line, we recovered a mutant which features an insertion of a rat B2 repeated sequence element. This sequence element was inserted between positions 77 and 78 in the lacI gene. When the inserted sequence was compared to the published rat B2 sequences, two short deletions, possibly mediated by short repeat sequences, were revealed. This is the first demonstration of the recovery of a repeated sequence element into the lacI gene used in transgenic animals and cell lines, and confirms previous findings that such sequences indeed move around the genome.

Animals↗

PubMed1997

An HPLC assay utilizing solid-phase extraction for CI-1010, an alkylating radiosensitizer, in rat plasma.

CI-1010, a 2-nitroimidazole, is a chiral prodrug for the active moiety PD 146923 and is under development as an alkylating radiosensitizer to be used as an adjuvant to radiotherapy. Because CI-1010 has an estimated half-life < or = 2 min under physiological conditions its metabolites/degradation products PD 146415, an inactive moiety, and PD 146923 were assayed to support rat toxicology studies. The method involves the processing of plasma samples through phenyl solid-phase extraction cartridges followed by chromatography on CN columns with UV detection at 325 nm. The assay appears linear over the range 0.050-100 micrograms ml-1 for both PD 146415 and PD 146923. Interrun accuracy and precision estimates for PD 146415 and PD 146923 were within +/- 6.50 and < or = 3.27%, respectively, and +/- 12.8 and < or = 4.06%, respectively, for quality controls containing nominal concentrations of 0.400, 4.00 and 40.0 micrograms ml-1. The absolute recovery of CI-1010, PD 146415 and internal standard, PD 126675, were approximately 40, 96 and 95%, respectively. The recovery of PD 146923 appeared concentration dependent and ranged from 68 to 92%. PD 146415 and PD 146923 were both stable in rat plasma at 4 degrees C and -77 degrees C for at least 7 h and 154 days, respectively. CI-1010 was not stable in rat plasma at 4 degrees C. CI-1010, PD 146415 and PD 126675 were stable for at least 63 days in 10 mM phosphate buffer at pH 3.0 and 4 degrees C. Under identical conditions PD 146923 was stable for only 8 days. The applicability of this method to determine concentrations of PD 146415 and PD 146923 in rat plasma is reported in this paper.

Alkylating Agents↗

PubMed1997

Pharmacokinetics and pharmacodynamics of enantiomers of ibuprofen and flurbiprofen after oral administration.

The main objective of this study was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model for the analgesic effect of ibuprofen and flurbiprofen using subjective as well as objective parameters. Serum concentrations of the individual enantiomers after oral administration of racemic ibuprofen (400 mg) and flurbiprofen (100 mg) were monitored using reversed phase HPLC. The pharmacokinetic data of the S-enantiomer was linked to the effect data using a hypothetical effect compartment. The effect data were fitted to Emax model. PK/PD analysis were performed using both objective (evoked potentials) and subjective (pain intensity scale) parameters. Concentrations of S-ibuprofen were found to be consistently larger than of R-ibuprofen and differed in various pharmacokinetic parameters after oral administration of racemic ibuprofen. Pharmacokinetic parameters of the enantiomers of flurbiprofen, such as volume of administration and clearance, also differed. Comparison of cumulative effects calculated as the area under the effect-time curve (AUCE) showed a statistically significant difference from placebo for both ibuprofen and flurbiprofen using evoked potential values. However, using pain rating values ibuprofen AUCE did not differ statistically significant from placebo whereas flurbiprofen AUCE did. PK/PD modeling of both evoked potentials and pain rating data than in evoked potential data. Hence, EP monitoring may allow to evaluate analgesic activity with a smaller number of subjects than pain rating.

Administration, Oral↗