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Biomedical subjects

J Lever

Publications and source records attributed to J Lever.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of stress induced by manual restraint and immobilisation in the estuarine crocodile, Crocodylus porosus.

This study compared the stress induced in captive estuarine crocodiles, Crocodylus porosus, by two different handling methods: manual restraint (noosing with ropes) and immobilization by electro-stunning. To stun, a short charge (approx. 6 s) at 110 V was delivered to the back of the necks of C. porosus using a custom-built device, which immobilized the animals for 5-10 min. Immobilized and restrained animals were measured and sexed, and the condition of the skin assessed. Blood samples were taken from some animals immediately after restraint or immobilization. Other animals were returned to their pens to recover for periods of 30 min, 1, 4, 12, 24 or 48 hours after which they were stunned and blood samples taken. Individual animals (mean body length 1.96 m, N=99) were bled only once. Haematocrit and haemoglobin concentrations were measured and plasma samples were analysed for corticosterone, glucose and lactate levels. Following restraint, there were significant increases in haematocrit, haemoglobin, glucose, lactate and corticosterone concentrations in C. porosus. For restrained animals, recovery to baseline levels occurred after approximately 8 hours. The stress response of stunned animals was significantly reduced compared to manually captured and restrained crocodiles. Both groups showed a significant increase in haematocrit, haemoglobin concentration and lactate levels, however the magnitude of change was significantly reduced, and recovery was faster in stunned animals. No increase in either glucose or corticosterone levels occurred with immobilisation. The results imply that immobilization by electro-stunning is much less stressful.

Alligators and Crocodiles↗
PubMed2001

Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus.

The pharmacokinetics of mycophenolic acid (MPA) was studied after oral administration of mycophenolate mofetil (MMF) in 8 liver transplant patients. The mean (+/- SD) maximum MPA plasma concentration of 10.6 (+/- 7.5) mg/ml was achieved within 0.5 to 5 hours. The mean (+/- SD) steady-state area under the plasma concentration versus time curve (AUC(0-12)) was 40 (+/- 30.9) mg/ml/h. The mean (+/- SD) half-life was 5.8 (+/- 3.8) hours. There was poor correlation between trough blood concentrations of tacrolimus (r = -0.004) or serum creatinine (r = 0.689) with MPA AUC, while the serum bilirubin concentrations correlated (r = 0.743) well with MPA AUC, suggesting impairment in MPA conjugation in patients with liver dysfunction. The mean (+/- SD) ratio of the AUC of mycophenolic acid glucuronide (MPAG) to MPA was 64 (+/- 84), which correlated significantly with serum creatinine (r = 0.72) but not with serum bilirubin concentrations (r = 0.309), indicating accumulation of MPAG in patients with renal dysfunction. In 7 primary liver transplant patients on the same dose of MMF, the trough plasma concentrations of MPA during the first week of therapy ranged from < 0.3 to 1.5 microg/ml. The MPA concentrations increased by several folds during the next few weeks, which correlates well with increases in serum albumin concentrations. Changes in albumin appear to partially contribute to the variations in the pharmacokinetics of MPA in liver transplant patients.

Adult↗
PubMed2000

Receipt of preventive health care services by lesbians.

BACKGROUND: We measured receipt of age-appropriate preventive health services by lesbians and assessed whether provider and individual characteristics, including disclosure of sexual orientation, are independently associated with receipt of these services. METHODS: A questionnaire was printed in a national biweekly gay, lesbian, and bisexual news magazine, and self-identified lesbians living in all U. S. states (N =6935) responded to the survey. Main outcome variables were receipt of a Pap smear within the preceding 1 and 2 years and, for women aged > or= 50, receipt of a mammogram within the past 1 and 2 years. RESULTS: Fifty-four percent had Pap smears within 1 year and 71% within 2 years, with increasing rates among older and more educated respondents. Seventy percent of respondents aged > or = 50 had a mammogram in the past year, and 83% within 2 years; rates did not vary significantly controlling for education. Sixty percent had disclosed their sexual orientation to their regular health care provider. Controlling for patient and provider characteristics, disclosure was independently associated with receipt of Pap smears, but not mammograms. CONCLUSIONS: It is important for providers to identify their lesbian patients' unmet needs for preventive health care. Additionally, it is important for providers to provide complete and appropriate preventive health care for their lesbian patients. Further research is needed to determine why lesbians are not receiving Pap smears at the recommended rate and whether this disparity is reflective of aspects of cervical cancer screening or indicates a more general problem with access to health care including receipt of preventive services.

Adolescent↗
PubMed2000

Opposite clear corneal incisions to correct pre-existing astigmatism in cataract surgery.

In cataract surgery, the clear corneal incision (CCI) has a small flattening effect on corneal curvature, which can be used to reduce pre-existing astigmatism (PEA). Adding an identical, penetrating CCI opposite the first one can enhance the flattening effect. The paired opposite CCIs (OCCIs) are placed on the steepest meridian axis to flatten it. One CCI is used to perform cataract surgery, and the opposite CCI is made to enhance the flattening effect on the cornea to modulate PEA. During the past 12 months, we have used 2.8 to 3.5 mm OCCIs in 33 eyes with PEA greater than 2.00 diopters (D) having cataract surgery. The mean astigmatism correction achieved with this technique was 2.06 D. This technique is simple and effective and yields stable results that rival those of arcuate keratotomy. The OCCI technique has a potential application for the correction of astigmatism in general refractive surgery. Opposite clear corneal incision nomograms with variables such as width, length, and distance from the limbus will be needed for future applications.

Astigmatism↗
PubMed1998

Comparison of tacrolimus absorption in transplant patients receiving continuous versus interrupted enteral nutritional feeding.

OBJECTIVE: To determine the effect of enteral nutritional feeding on the absorption of tacrolimus administered through a nasoduodenal tube to organ transplant patients. METHODS: A nonrandomized, prospective study of tacrolimus absorption was performed in 10 liver or lung transplant patients who received Osmolite enteral nutrition through a nasoduodenal feeding tube. Multiple blood samples were collected just prior to and at 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 12 hours after nasoduodenal administration of tacrolimus on 2 consecutive days, once when tacrolimus was administered along with the continuous enteral feeding and the other time when the enteral feeding was withheld 1 hour prior to and 8 hours after tacrolimus administration, to assess tacrolimus absorption. The whole blood tacrolimus concentrations were measured by the microparticulate enzyme immunoassay method. Pharmacokinetic parameters between the two time periods were compared by using a paired t-test at a significance level of a p value of 0.05 or less. RESULTS: The time to reach peak blood concentrations (p = 0.055), dose-normalized trough concentrations (p = 0.617), maximum blood concentrations (p = 0.197), and dose-normalized AUC (p = 0.755) were not significantly different between two study periods. CONCLUSIONS: This study demonstrated that simultaneous administration of Osmolite enteral feedings with tacrolimus did not interfere with tacrolimus absorption in transplant patients.

Absorption↗
PubMed1997

Pregnancy after liver transplantation under tacrolimus.

BACKGROUND: The maternal and fetal risk of pregnancy after organ transplantation under tacrolimus has not been reported. This was prospectively studied in 27 pregnancies by 21 female liver recipients who were treated with tacrolimus before and throughout gestation. METHOD: Twenty-seven babies were born between October 1990 and April 1996. In 15 cases, samples were obtained at or after delivery and stored (-40 degrees C) for comparison of tacrolimus concentration in the maternal blood with different combinations of cord and infant venous blood, breast milk, or a section of the placenta. RESULTS: The 21 mothers had surprisingly few serious complications of pregnancy and no mortality. Two infants with 23 and 24 weeks gestation died shortly after birth. The mean birth weight of the other 25 was 2638+/-781 g after a gestational period of 36.6+/-3.3 weeks. Mean birth weight percentile for gestational age was 50.2+/-26.2 (median 40). On the day of delivery, the mean tacrolimus concentrations (ng/ml) were 4.3 in placenta versus 1.5, 0.7, and 0.5 in maternal, cord, and child plasma, and 0.6 in the first breast milk specimens. The infants had a 36% incidence of transient perinatal hyperkalemia (K+>7.0 meq/L) and a mild reversible renal impairment, which were thought to reflect in part maternal homeostasis. One newborn had unilateral polycystic renal disease (the only anomaly). All 25 babies have had satisfactory postnatal growth and development with a current mean weight percentile of 62+/-37 (median 80). CONCLUSIONS: Pregnancy by postliver transplant mothers under tacrolimus was possible with a surprisingly low incidence of the hypertension, preeclampsia, and other maternal complications historically associated with such gestations. As in previous experience with other immunosuppressive regimens, preterm deliveries were common. However, prenatal growth for gestational age and postnatal infant growth for postpartum age were normal.

Adult↗
PubMed1996

Functional outcome of thoracolumbar burst fractures without neurological deficit.

Thoracolumbar burst fractures are a major cause of disability; however, there are few studies on the functional outcome of patients with this injury. The purpose of this study is to evaluate the functional outcome of patients with thoracolumbar burst fractures using a generic and a condition-specific health status survey. The SF-36 survey (generic) and the Roland scale (condition-specific) were administered to 24 patients who had a minimum of 2 years follow-up after a thoracolumbar burst fracture without neurologic deficit. The average SF-36 score was 65% (compared to 45% for dialysis and 66% for diabetes) and the Roland score was 65% (compared to 58% for low back pain). Of the patients, 33% were able to return to their previous employment, but only 8% were able to return to their pre-injury level of sports. There was a strong correlation (r = 0.71) between the Roland scale and the SF-36 pain scale. There were poor correlations between the Roland scale and residual kyphosis (r = 0.003), and between the SF-36 pain scale and residual kyphosis (r = 0.10). There was no significant difference in the functional outcome of those patients treated operatively versus nonoperatively.

Adult↗
PubMed1995

Capillary blood versus arterial or venous blood for tacrolimus monitoring in liver transplantation.

Tacrolimus has been found to be useful in clinical solid organ transplantation. A very careful monitoring of the tacrolimus levels and dose adjustments are essential, at least in the immediate post-liver transplantation, situation. However, quite often after liver transplantation, patients have limited venous access for daily monitoring of tacrolimus levels. When the blood is sampled from a multilumen central venous catheter, used also for intravenous administration of tacrolimus, falsely elevated concentrations of tacrolimus have been observed. The present study examines the concentration of tacrolimus in capillary blood samples obtained from finger stick and compares its concentrations in simultaneously drawn samples from arterial line, peripheral venous puncture, and multilumen centrally placed venous catheter from the port used for tacrolimus infusion and the port not used for tacrolimus infusion. Ten adult post-liver transplantation recipients were studied. Whole blood concentration of tacrolimus in capillary blood was comparable to that of arterial blood, as well as to that of peripheral venous blood samples (r2 = 0.99; P = 0.72). Concentrations of tacrolimus in venous blood drawn from the port of the multilumen catheter used for intravenous tacrolimus infusion were 3-23 times higher (P = 0.0015), while the concentrations of venous blood drawn from the port not used for tacrolimus infusion were 1.7-4.5 times higher (P = 0.016), as compared with arterial, capillary, or peripheral venous whole blood concentrations.

Adult↗
PubMed1995

Tacrolimus analysis: a comparison of different methods and matrices.

We determined the through blood and plasma concentrations of tacrolimus from the day of transplantation through 30 days posttransplantation in four liver and four kidney transplant patients by three different methods. The first method involved a solid phase extraction of the blood or plasma using Sep-Pak columns (SPs) followed by quantitation of tacrolimus using an enzyme-linked immunosorbent assay (ELISA); the second method involved a liquid-liquid extraction using methylene chloride (MC) followed by quantitation of tacrolimus using the ELISA, and the third method involved a high-performance liquid chromatography (HPLC) fractionation of the extract obtained from the solid-phase extraction and quantitation of tacrolimus in the fractions by ELISA. The trough plasma tacrolimus concentrations ranged from 0.1 to 5.2 ng/ml. While the trough plasma concentrations of tacrolimus were similar and independent of the method of analysis in kidney transplant patients and in liver transplant patients with normal biochemical profile, in patients with liver dysfunction, tacrolimus plasma concentrations were higher when measured by SP-ELISA and MC-ELISA methods as compared to the HPLC-ELISA method. In plasma samples obtained from liver transplant patients with liver dysfunction, the presence of some metabolites that cross-reacted with the antibody used in the ELISA could be documented in the HPLC fraction corresponding to the metabolites. This indicates that while tacrolimus metabolites that cross-react significantly with the antibody used in the ELISA do not accumulate in kidney transplant patients, they can appear in the plasma of patients, they can appear in the plasma of patients with liver dysfunction. The trough blood tacrolimus concentrations in patients were significantly higher than the corresponding plasma concentrations and ranged from 1.4 to 107 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1995

Clinical pharmacokinetics of tacrolimus.

Tacrolimus, a novel macrocyclic lactone with potent immunosuppressive properties, is currently available as an intravenous formulation and as a capsule for oral use, although other formulations are under investigation. Tacrolimus concentrations in biological fluids have been measured using a number of methods, which are reviewed and compared in the present article. The development of a simple, specific and sensitive assay method for measuring concentrations of tacrolimus is limited by the low absorptivity of the drug, low plasma and blood concentrations, and the presence of metabolites and other drugs which may interfere with the determination of tacrolimus concentrations. Currently, most of the pharmacokinetic data available for tacrolimus are based on an enzyme-linked immunosorbent assay method, which does not distinguish tacrolimus from its metabolites. The rate of absorption of tacrolimus is variable with peak blood or plasma concentrations being reached in 0.5 to 6 hours; approximately 25% of the oral dose is bioavailable. Tacrolimus is extensively bound to red blood cells, with a mean blood to plasma ratio of about 15; albumin and alpha 1-acid glycoprotein appear to primarily bind tacrolimus in plasma. Tacrolimus is completely metabolised prior to elimination. The mean disposition half-life is 12 hours and the total body clearance based on blood concentration is approximately 0.06 L/h/kg. The elimination of tacrolimus is decreased in the presence of liver impairment and in the presence of several drugs. Various factors that contribute to the large inter- and interindividual variability in the pharmacokinetics of tacrolimus are reviewed here. Because of this variability, the narrow therapeutic index of tacrolimus, and the potential for several drug interactions, monitoring of tacrolimus blood concentrations is useful for optimisation of therapy and dosage regimen design.

Drug Interactions↗
PubMed1995

Selective labeling of the dopamine transporter by the high affinity ligand 3 beta-(4-[125I]iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester.

The iodine-125 analog of the dopaminergically selective cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester (RT1-121) was evaluated as a probe for the dopamine transporter in rat striatum. Saturation and kinetic studies indicated that [125I]RTI-121 binds to both high and low affinity components. The Kd of the high affinity component was 0.14 +/- 0.01 nM (mean +/- standard error), whereas the low affinity component demonstrated an affinity of 1.59 +/- 0.09 nM. The corresponding numbers of striatal binding sites labeled by [125I]RTI-121 were 295 +/- 6 and 472 +/- 59 pmol/g of tissue (original wet weight), respectively. Intrastriatal injections of 6-hydroxydopamine eliminated > 90% of specific [125I]RTI-121 binding in the striatum. The pharmacological profile of specific [125I]RTI-121 binding in the rat striatum was consistent with that of the dopamine transporter. There was a strong (r = 0.98, p < 0.0001) correlation between the potencies of drugs that displaced specific [125I]RTI-121 binding and the potencies of these drugs to inhibit the uptake of [3H]dopamine. In contrast, no correlation was found for the potencies of drugs to inhibit the uptake of either [3H]norepinephrine or [3H]serotonin. Autoradiographs produced using [125I]RTI-121 demonstrated a distribution of label consistent with the distribution of dopaminergic neurons in rat brain. Because of its high affinity and high selectivity for the dopamine transporter, [125I]RTI-121 may be an extremely useful ligand for the dopamine transporter.

Animals↗
PubMed1993

FK506 measurement: comparison of different analytical methods.

In this study, we used solid-phase extraction with Sep-Pak and a liquid-liquid extraction with methylene chloride as two primary methods of extracting FK506 from plasma. The extracts were either analyzed directly by enzyme-linked immunosorbent assay (ELISA) or subjected to high-performance liquid chromatography (HPLC) separation and different fractions were analyzed by ELISA. Serial blood samples were obtained from four kidney transplant patients and four patients who underwent liver transplantation, from day 1 until day 30-35 posttransplantation. There was no significant difference in the FK506 plasma concentration as measured by all four methods in normal transplant patients. However, in liver transplant patients, the solid-phase extraction method gave higher FK506 concentrations than the methylene chloride extraction during the early postoperative period. The concentrations measured after methylene chloride extraction were higher than that after HPLC-ELISA. This higher FK506 concentration measured by direct ELISA could be attributed to possible cross-reacting metabolites that were present in the plasma of patients with abnormal liver functions. Once liver function returns to normal, all four methods give identical plasma concentrations for FK506.

Chemistry Techniques, Analytical↗
PubMed1992

A cocaine analog and a GBR analog label the same protein in rat striatal membranes.

Because some evidence suggests that cocaine and GBR12935 bind to different sites, we utilized photoaffinity probes from both classes of compounds to see if they label the same protein. [125I]RTI-82 a cocaine analog, and [125I]DEEP, a GBR analog, labeled protein(s) showing the same molecular weight, a similar pharmacological profile and a similar sensitivity to neuraminidase.

Animals↗