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Biomedical subjects

P Sidhu

Publications and source records attributed to P Sidhu.

At least 19 recordsLinked to original sources
PubMed2003

Tissue chamber model of acute inflammation in farm animal species.

A tissue chamber model of acute inflammation for use in comparative studies in calves, sheep, goats and pigs has been established and validated. Tissue chambers were prepared from silicon rubber tubing, of inner diameter 12.7 mm, length 115 mm and volume 15 ml, with 10 holes, each of 6mm diameter, at each end. In each animal two or four chambers were inserted at subcutaneous sites. Six weeks after implantation an acute inflammatory reaction in a single cage was generated by the intracaveal injection of 0.5 ml of 1% carrageenan solution. Serial samples of exudate (injected chamber), transudate (non-injected chamber) and blood were collected for measurement of exudate and transudate leucocyte count, prostaglandin (PG)E(2) concentration in exudate and serum thromboxane (Tx)B(2) concentration. In addition, skin temperature changes over exudate and transudate chambers were recorded. In all four species, carrageenan induced an acute inflammatory response, indicated by increases to peak values followed by return towards baseline in skin temperature, leucocyte count and PGE(2) concentration. For each of these variables in calves, sheep and goats the increases were significantly greater for exudate than for transudate. The degree of intra-species variation in each variable was acceptable. Marked inter-species differences were recorded: skin temperature rise was greatest in calves and least in sheep and goats; exudate PGE(2) concentration was increased in the order sheep>goat>pig>calf; serum TxB(2) concentration was increased in the order calf>goat>sheep>pig and exudate leucocyte count was increased to a greater extent in the pig than in the three ruminant species. The model has advantages over some previously described tissue chamber models of inflammation and will be suitable for use in comparative studies of inflammatory mechanisms and the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs.

Acute Disease↗
PubMed2001

Mechanical or bioprosthetic valves in the elderly: a 20-year comparison.

BACKGROUND: Our objective was to compare long-term results of mechanical and bioprosthetic valve replacement in patients older than 70 years. METHODS: Patients older than 70 years who had either a St. Jude Medical (SJM) mechanical prosthesis or any bioprosthesis (BP) implanted between January 1977 and December 1997 were identified. Alive patients were interviewed by telephone during a closing interval of 130 days. RESULTS: Complete follow-up was achieved with a total follow-up of 2,264 patient years. A total of 547 patients had 448 aortic valve replacements (199 SJM and 249 BP) and 99 had mitral valve replacements (76 SJM and 23 BP). A further 30 patients had double valve replacement. One hundred ninety of the 577 patients (33%) had coronary artery bypass grafting in addition to the valve replacement. Survival analysis showed no advantage for either mechanical or bioprosthetic valves. There was also no difference in thromboembolic rates, paravalvular leaks, structural dysfunction, and endocarditis rates. However, patients with mechanical valves had a significantly greater risk of major (p < 0.0001) and minor bleeding (p = 0.002) events. CONCLUSIONS: Bioprosthetic valves do not offer a survival advantage over mechanical valves among the elderly. However, anticoagulant-related mortality and morbidity is statistically higher for patients with mechanical valves.

Aged↗
PubMed2001

Self-managed anticoagulation: results from a two-year prospective randomized trial with heart valve patients.

BACKGROUND: This study was conducted to assess the ability of patients receiving heart valve replacements to practice self-managed anticoagulation using a portable coagulometer. METHODS: We carried out a prospective, randomized trial, comparing self-managed anticoagulation with conventional management. Patients practicing self-managed anticoagulation (51 patients) did so at home, measuring their international normalized ratio and then deciding on their dosage of warfarin, while conventionally controlled patients (n = 49) attended hospital clinics or were managed by their family physicians. RESULTS: We successfully trained 41 of 44 patients who agreed to self-manage their anticoagulant therapy; 34 of the 41 managed their own anticoagulation at home for 2 years. Their control, assessed by a number of tests in range (67.6% versus 58.0%) and time in therapeutic range (76.5% versus 63.8%), was significantly better than that for the group managed conventionally (p < 0.0001). There was no significant difference in mortality or morbidity between the two groups. CONCLUSIONS: Self-managed anticoagulation is a reliable, easily learned method of controlling anticoagulation, and it is suitable for approximately two thirds of patients, with excellent results.

Adult↗
PubMed2001

Behavior and neurotoxic consequences of lead on rat brain followed by recovery.

Long-term exposure to lead has been shown to produce behavioral disturbances in human and animal models. These disturbances are shown to be associated with alterations in cholinergic and dopaminergic neurotransmission in the central nervous system. The present experiment was designed to study the effect of lead exposure on neurotransmitters like dopamine, serotonin, norepinephrine, and activity of acetyl cholinesterase along with alterations seen in memory and locomotor functions. Lead was administrated orally in a dose of 50 mg/kg for 8 wks on alternate days and a study was done at the end of exposure and also after 8 wk of recovery. Lead exposure reduced the brain and body weight, which, however, did not improve even after recovery of 8 wk. The alterations seen in the various transmitters also remain unchanged at the end of recovery. Lead exposure for 8 wk affected the locomotor and cognitive functions as assessed by the rota rod treadmill and active avoidance test. However, following a recovery period, a significant improvement was seen in locomotor as well as cognitive behavior. The short-term memory as assessed by the passive avoidance test remains unchanged both following lead exposure as well as recovery.

Acetylcholinesterase↗
PubMed2000

Ocellar pigmentation and phototaxis in the nematode Mermis nigrescens: changes during development.

After 1 or 2 years of dormancy in the soil, Mermis nigrescens females emerge to lay eggs on vegetation where their grasshopper hosts are likely to feed. Females collected at this life stage exhibit a strong positive phototaxis and have a tubular region of pigmentation near the anterior tip consisting of concentrated oxyhaemoglobin. A previous investigation of the scanning motion of the 'head' and orientation of the 'neck' has implicated the shadowing of a photoreceptor inside the tube as the mechanism for identifying the direction of light during phototaxis. Here, we describe the development of the pigment in young adult females and investigate phototaxis in early developmental stages that lack the pigment. The orientation of the neck to a horizontal 420 nm stimulus (intensity 10(13 )photons s(-)(1 )cm(-)(2)) was measured for unpigmented fourth-stage larvae and immature adult females as well as mature females with pigmented ocelli. The orientation of the larvae and immature adults was weakly negative, whereas that of the mature adults was strongly positive. Head and neck movements were otherwise the same in the three stages. Thus, the pigmentation appears to be required for positive phototaxis, and the results provide further support for the shadowing role of ocellar haemoglobin.

Animals↗
PubMed1998

Conformation of kainic acid in solution from molecular modelling and NMR spectra.

Conformational behaviour of kainic acid in aqueous solution was elucidated by molecular mechanics and dynamics. The pucker of the five-membered ring in kainic acid was examined and compared with that of model compounds. In cyclopentane there is no barrier to pseudorotation, so that all puckered states coexist. In pyrrolidinium, the presence of a hetero-atom in the ring introduces a small barrier (about 0.6 kcal mol(-1)) to pseudorotation, separating two stable regions, A and B, which are equivalent by symmetry. In proline, the presence of the carboxylate group on C2 removes the symmetry but two stable conformational minima, A and B, remain. In kainic acid, the presence of side-chains on C3 and C4 introduces complications resulting in additional sub-minima in both regions, A and B. In solution, kainic acid is a complex mixture of conformers with comparable energies, because of the combination of several stable states of the pyrrolidinium ring with the torsional degrees of freedom arising from the two side-chains. The individual geometries, energies, and estimates of relative populations of these conformers were obtained from molecular dynamics simulations. The calculations were validated by a comparison of predicted inter-proton distances and vicinal proton coupling constants with the experimental quantities derived from NMR spectra.

Excitatory Amino Acid Agonists↗
PubMed1993

Atrial myxoma: national incidence, diagnosis and surgical management.

Despite being the most common benign intracardiac tumour with an excellent prognosis after surgical excision the incidence of atrial myxoma (except at autopsy) is unknown. We reviewed all patients admitted to the National Cardiac Surgery Unit (n = 26) with an atrial myxoma over a fifteen year period (1977-1991) to compile national incidence data and assess pre-operative diagnosis, management, surgical technique, and outcome. Preoperative symptoms were: congestive cardiac failure (12 patients), embolism (8 patients), constitutional (3 patients), asymptomatic (2 patients) and tachyarrhythmia (1 patient). The diagnosis was confirmed by 2D echocardiography alone in thirteen patients and by a combination of echocardiography and angiography in thirteen patients. At operation the site of the tumour was left atrial in 24 patients and bi-atrial in two patients. All cases were confirmed by histology. All patients made a good post-operative recovery, although one patient survived a pulmonary embolus and one patient developed a deep venous thrombosis. There has been one late death (five months after surgery) from a cerebrovascular accident. Serial echocardiography has revealed one recurrence to date (8 years after surgery). The surgical incidence of these tumours in the Republic of Ireland over the study period was 0.5 atrial myxomas/million population/year. Although rare atrial myxomas are the most important cardiac tumours to diagnose as the results from surgery are excellent.

Adolescent↗
PubMed1985

Reversed-phase high performance liquid chromatographic determination of nifedipine in human plasma.

A reversed-phase high performance liquid chromatographic method is presented by which the calcium channel blocker, nifedipine (NFP), may be measured in human serum using 17-alpha-ethinylestradiol as an internal standard. A mobile phase of phosphate buffer (0.01 M, pH 6.1)/methanol/acetonitrile (20:35:45) passed through a muBondapak C-18 column at 1.0 ml/min produced symmetrical bands for nifedipine and internal standard. A rapid and simple chloroform extraction of NFP from 1 ml serum samples proved to be efficient and reproducible. Recovery over a concentration range of 5-100 ng/ml was 92.3 +/- 5.1% (mean +/- SD, n = 6). Ultraviolet absorbance detection at 235 nm was sensitive to serum NFP concentrations of 5 ng/ml. Between-day coefficients of variation at 100 and 5 ng/ml were 4.0 and 11.4%, respectively (n = 10). Serum concentration data from NFP-treated subjects are presented.

Chromatography, High Pressure Liquid↗
PubMed1985

Effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of methotrexate in the rat.

The effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of intravenously-administered methotrexate have been studied in the Wistar-Furth rat. Eight test animals received total body irradiation (1000 rads) followed by intravenous administration of 3 X 10(8) bone marrow cells per kg body weight. Eight control animals were sham-irradiated and received an equal volume of blank suspension medium. One day after these treatments each rat received methotrexate (25 mg/kg) by rapid intravenous injection and serial blood samples were obtained over a 3 hour period. Serum methotrexate concentrations were measured by high performance liquid chromatography and pharmacokinetic parameters were calculated after NONLIN analysis of data. No significant differences were observed in total body clearances of test and control animals. As methotrexate in the rat is cleared predominantly by renal excretion of unchanged drug, these findings suggest that this process is not affected by radiation. Significantly larger volumes of distribution were observed in test animals. Increased extent of distribution in irradiated animals could be a result of a radiation-induced increase in membrane permeability and/or increased blood flow to irradiated areas. Future studies should assess the clinical significance of such findings.

Animals↗
PubMed1985

Cyclosporine disposition in the dog. Comparison of radioimmunoassay with high-performance liquid chromatographic assay and pharmacokinetics following intravenous administration.

Radioimmunoassay (RIA) and high performance liquid chromatography (HPLC) with ultraviolet absorbance detection have been compared as potential tools for cyclosporine pharmacokinetic studies in dogs. RIA clearly affords greater assay sensitivity, although crossreactivity with cyclosporine metabolites causes an over-estimation of parent drug concentrations with a subsequent reduction in the apparent values of clearance and volume of distribution. HPLC appears to be specific for parent cyclosporine. Thus, with the sacrifice of some sensitivity, HPLC-measured time-course data afford more reliable estimates of cyclosporine pharmacokinetic parameters. After the selection of a dosage regimen from preliminary studies, the pharmacokinetics of i.v.-administered cyclosporine were studied in six adult male mongrel dogs. Following administration of 20 mg/kg by constant-rate 30-min i.v. infusion the time courses of cyclosporine were studied in plasma and urine. Concentrations were measured by reversed-phase HPLC with ultraviolet absorbance detection. Data were fitted to triexponential equations using a digital computer with the CSTRIP and NONLIN programs, and pharmacokinetic parameters were calculated. Present findings suggest that cyclosporine is slowly yet extensively distributed into peripheral body regions that might serve as slowly releasing storage areas. Large volumes of distribution along with moderately slow clearances resulted in long half-lives for the disposition of cyclosporine. Less than 1% of the administered dose was recovered as parent cyclosporine in the urine, suggesting that renal clearance of cyclosporine was negligible. The potential relevance of present findings to cyclosporine therapy of transplant patients is discussed.

Absorption↗
PubMed1985

The plasma time course of orally-administered cyclosporine in the dog.

The plasma concentration time course of orally-administered cyclosporine has been studied in five adult male mongrel dogs. Cyclosporine concentrations were measured by high performance liquid chromatography with ultraviolet absorbance detection. Cyclosporine plasma concentrations were below assay sensitivity within 24 hours after administration. Peak plasma concentrations ranging from 411.8 to 1735.0 ng/ml were attained between post-administration times of 1 and 2.5 hours. Areas under plasma concentration time course curves (AUC = 4.63 +/- 5.60 micrograms/ml X hr, mean +/- SD) suggest that systemic availability is highly variable between animals. Present and previous findings discourage the oral route of cyclosporine administration for canine transplant research and suggest more extensive pharmacokinetic evaluation of cyclosporine following oral administration in humans.

Administration, Oral↗
PubMed1984

Pharmacokinetics of mitomycin C in non-oat cell carcinoma of the lung.

The disposition kinetics of the cancer chemotherapeutic agent mitomycin C have been studied in six male patients receiving mitomycin C in combination with cisplatin and vinblastine for non-oat cell carcinoma of the lung. Following rapid IV administration of mitomycin C (10 mg/m2), serum concentration-time course data were biexponential, with biologic half-lives of 46.2 +/- 12.1 min (mean +/- SD). Pharmacokinetic analysis of data by the CSTRIP and NONLIN digital computer programs generated parameters which suggested extensive distribution (V area = 656.8 +/- 169.8 ml X kg-1, mean +/- SD) and, as reported for other alkylating agents, rapid elimination (total body clearance = 10.3 +/- 3.2 ml X kg-1 X min-1, mean +/- SD). Interpatient variations in pharmacokinetic parameters were relatively small, suggesting that close monitoring of mitomycin C therapy might be unnecessary in patients with normal renal and hepatic function.

Antibiotics, Antineoplastic↗
PubMed1984

Reversed-phase high-performance liquid chromatographic determination of mitomycin C in human serum.

A reversed-phase high-performance liquid chromatographic method is presented by which the cancer chemotherapeutic agent, mitomycin C, may be measured in human serum. A mobile phase of methanol:water (35:65) passed through a mu-Bondapak C-18 column at a rate of 1.0 ml/min produced a sharp, symmetrical band for mitomycin C. An improved serum extraction procedure, using a reversed-phase sample preparation cartridge, proved to be efficient and reproducible. Recovery over a concentration range of 10-100 ng/ml was 81.6% with a between-day coefficient of variation of 4.6% (n = 5). The within-day coefficient of variation at 50 ng/ml was 5.6% (n = 10). Ultraviolet detection at a wavelength of 365 nm was sensitive to serum concentrations of 10 ng/ml. Serum concentration-time course data from lung cancer patients receiving mitomycin C by rapid intravenous injection are presented.

Chromatography, High Pressure Liquid↗
PubMed1984

Effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of mitomycin-C in the rat.

The effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of intravenously-administered mitomycin-C have been studied in the Wistar-Furth rat. Five test animals received total body irradiation (1000 rads) followed by intravenous administration of 3 X 10(8) bone marrow cells per kg body weight. Five control animals were sham-irradiated and received an equal volume of blank suspension medium. One day after these treatments, each rat received mitomycin-C (10 mg/kg) by rapid intravenous injection and serial blood samples were obtained. Serum mitomycin-C concentrations were measured by high performance liquid chromatography and pharmcokinetic parameters were calculated after NONLIN analysis of data. Smaller total body clearances in test animals were probably due to radiation-induced inhibition of microsomal enzyme activity. Reduced volumes of distribution were observed in test animals although the reason for this is unclear. Future studies should assess the clinical significance of these results.

Animals↗
PubMed1982

Reversed-phase high-pressure liquid chromatographic determination of serum methotrexate and 7-hydroxymethotrexate.

A reversed-phase high-pressure liquid chromatographic method for determining methotrexate and 7-hydroxymethotrexate in human serum is presented. A mobile phase of acetate buffer (0.2 M, pH 5.5 with 0.03 M ethylenediaminetetraacetate), methanol, and acetonitrile (85.3:8.4:6.3), passed through a mu Bondapak C18 column at 1.5 ml/min produced excellent resolution of sharp, symmetrical bands. An improved extraction process, using a sample preparation cartridge, resulted in analytical recoveries in excess of 90% for methotrexate and 70% for 7-hydroxymethotrexate, permitting the determination of serum concentrations of 2.20 and 2.13 x 10(-7) M, respectively, using only 200 microliter of serum. UV detection at 313 nm provided adequate sensitivity for each component. While the reproducibility for 7-hydroxymethotrexate was approximately equal to previous methods, that for methotrexate was greatly improved. Serum methotrexate data at selected time points following high dose methotrexate therapy are presented.

Chromatography, High Pressure Liquid↗
PubMed1980

Evaluation of enzyme immunoassay, radioassay, and radioimmunoassay of serum methotrexate, as compared with liquid chromatography.

We evaluated three commonly used clinical methods for measuring serum methotrexate: enzyme immunoassay (EMIT), radioassay, and radioimmunoassay. Because potentially interfering compounds can be resolved by liquid chromatography, this method was selected as the comparison method. Patients' serum samples, taken during 24 h after 6-h high-dose infusions, contained methotrexate in concentrations ranging from 10(-7) to 10(-4) mol/L. Chromatograms revealed substantial amounts of 7-hydroxymethotrexate in all samples, actually exceeding methotrexate by 12 and 24 h. Nevertheless, analysis of variance revealed no significant differences in results by any of the four methods, nor did results by the three test methods differ significantly after being adjusted by analysis of covariance with liquid chromatography as the covariate. Evidently any of the four techniques is suitable for monitoring serum methotrexate for 24 h after high-dose therapy.

Adolescent↗