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Biomedical subjects

T Cook

Publications and source records attributed to T Cook.

At least 127 records · Page 7Linked to original sources
PubMed1983

Comparative multiple dose kinetics of two formulations of indomethacin.

The kinetics of a controlled release (CR) formulation of indomethacin 75 mg (Indocid-Retard) given once daily was compared with a conventional 25 mg indomethacin capsule (Indocid) given 3 times daily for 7 days, to 14 healthy volunteers, using a randomized, cross-over, multiple-dose study design. The following differences in plasma indomethacin profiles after the 2 treatments were observed: average peak concentrations (Cmax) for the CR regimen were higher and the time to peak (Tmax) was significantly delayed. Trough (pre-morning dose) plasma concentrations (Cmin) on Days 2, 5, 6 and 7 were significantly lower after the CR-formulation. No statistically significant differences between preparations for area under the plasma concentration time curve (AUC0-24 h) or for renal clearance were observed. Average steady-state plasma concentrations (Cssp) on Day 7 of the multiple dose regimens averaged 0.477 and 0.427 microgram/ml for the 75 mg CR once daily and the conventional 25 mg t.i.d. treatments, respectively. These results show that the bioavailability of the CR and conventional indomethacin formulations under these multiple-dose conditions was not significantly different.

Adult↗
PubMed1981

Enhancement of uricosuric properties of indacrinone by manipulation of the enantiomer ratio.

Racemic indacrinone is a high-ceiling, relatively long-acting diuretic. Both enantiomers have uricosuric activity, but the diuretic activity resides predominantly in the (-) enantiomer. Usual therapeutic doses of racemic indacrinone have only transient uricosuric activity, so that, as with other diuretics, hyperuricemia occurs. Sixty-five healthy men participated in a multicenter, double-blind, randomized, balanced, incomplete-block study comparing the effects on plasma urate and urate clearance of indacrinone (-) enantiomer 10 mg given concomitantly with 0, 10, 20, 40, and 80 mg (+) enantiomer (10/0, 10/10, 10/20, 10/40, 10/80), as single daily doses for 7 days. Hydrochlorothiazide (HCTZ) 50 mg daily and ticrynafen (T) 250 mg daily were controls. Each subject received two of the seven treatments, so that there were 18 subjects per treatment. On days 7 to 8, morning (mean of 0-hr values on days 7 and 8), HCTZ, 10/0, 10/10, and 10/20 elevated plasma urate by 8% to 16%. 10/40 was approximately isouricemic, and 10/80 and T lowered plasma urate by 13% and 41%. There were corresponding changes in urate clearance.

Diuretics↗
PubMed1980

Dynamics and kinetics of ophthalmic timolol.

Timolol is a beta adrenergic antagonist in 0.25% or 0.5% eyedrop solution for glaucoma. In a double-blind crossover study in healthy males we measured systemic beta blockade, intraocular pressure, and timolol kinetics after the first and ninth 12-hourly dose of a 0.5% ophthalmic solution. Timolol ophthalmic and placebo were each given as 2 drops to each eye with precautions to prevent the normal loss of drug in tears and overflow (high dose) and as 1 drop to each eye with no special precautions (standard therapeutic dose). Exercise tachycardia, measured at 70 and 255 min after administration of drug, was lower at both levels. Postexercise 1-sec forced expiratory volume (FEV1) was not affected. Intraocular pressure measured at 3 and 8 hr after drug was lower at both dose levels. Timolol was consistently present in urine but was not detectable in most plasma samples. Dynamic effects were not greater after the ninth than after the first dose, and the urinary excretion data provided no evidence of drug cumulation.

Blood Pressure↗
PubMedDate not supplied

Therapeutic plasma concentrations of human factor IX in mice after gene delivery into the amniotic cavity: a model for the prenatal treatment of haemophilia B.

BACKGROUND: Several groups including our own have reported gene delivery to fetal organs by vector administration into the amniotic cavity. Based on these studies we hypothesised that the large surface of the fetal skin may be exploitable for high level production of systemically required gene products to be released into the fetal circulation. METHODS: We administered E1/E3-deleted adenoviral vectors carrying a bacterial beta-galactosidase gene or the human coagulation factor IX gene into the amniotic cavities of mid- to late-gestation mouse fetuses. The concentrations of human factor IX in the plasma of fetal or new-born mice were determined by ELISA. Reverse transcription PCR was used to identify sites of transgene expression. RESULTS: Application of 5 x 10(8) infectious units of the factor IX gene vector in utero resulted in plasma concentrations of human factor IX of up to 1.2 microg/ml without significant decrease in fetal survival. Transgenic protein was found to be produced in the fetal skin, mucosae and amniotic membranes and was shown to be present for several days after birth of healthy pups. CONCLUSION: As ultrasound-guided amniocentesis in humans is a well-established diagnostic procedure, delivery of the factor IX gene into the amniotic cavity appears to be a safe route for prenatal treatment of haemophilia B and may prevent haemorrhagic complications such as intracranial bleeding during delivery. Our study allowed for the first time a quantification of the expression of a potentially therapeutic transgene in rodents after prenatal gene delivery. It thus provides a model for the prenatal treatment of haemophilia B, but may also serve as a pathfinder to gene therapy of inheritable skin disorders such as epidermolysis bullosa.

Adenoviridae↗
PubMedDate not supplied

Some considerations in the analysis of rates of change in longitudinal studies.

This paper discusses and compares several estimators of mean rate of change in unbalanced longitudinal data based on a model with randomly distributed regression coefficients across individuals. The estimators are unweighted and weighted means of these coefficients. The paper also evaluates commonly used variance estimates corresponding to the estimators. Results show that in situations of very slight imbalance, the choice of method is not critical. When imbalance is substantial, however, one should weight the regression coefficients by their estimated precision. An example using data from a nutritional study on premature neonates illustrates some issues encountered in the analysis of longitudinal clinical data sets.

Humans↗
PubMedDate not supplied

Hypokalemia, hypophosphatemia, and compartment syndrome of the leg after downhill skiing on moguls.

Any process that increases intracompartmental pressure may precipitate compartment syndrome. We report the case of a patient with hypokalemia and hypophosphatemia who presented with compartment syndrome of the legs after a day of downhill skiing on moguls. The presentation is followed by a review of the pathophysiology, etiology, clinical presentation, and management of compartment syndrome, as well as the relationship between hypokalemia, hypophosphatemia, and the development of muscle injury.

Adult↗
PubMedDate not supplied

Prevalence and structure of ultrasound curricula in emergency medicine residencies.

Emergency medicine (EM) residency program directors were surveyed to determine the presence and structure of curricula for teaching ultrasound to EM residents. For those EM programs without an ultrasound curriculum (USC), information was requested on plans to implement one within the next 12 months. Ninety of 116 (78%) EM programs replied to the survey. One-half of EM residencies surveyed have USCs, and another 30% plan to implement one in the near future.

Curriculum↗
PubMedDate not supplied

Using ultrasound to determine external pacer capture.

Transcutaneous cardiac pacing is a temporary treatment of hemodynamically unstable bradycardias. However, the rhythmic skeletal muscle contractions that occur during external pacing can make it difficult to assess the hemodynamic status of the patient. We report a case of using bedside ultrasound to assess the effectiveness of transcutaneous pacer capture.

Adult↗
PubMedDate not supplied

Inducible nitric oxide synthase induction in Thy 1 glomerulonephritis is complement and reactive oxygen species dependent.

Thy 1 glomerulonephritis (GN) is a rat model of complement-dependent immune mesangial injury with induced glomerular nitric oxide (NO) synthesis. To examine mechanisms of inducible nitric oxide synthase (iNOS) induction, we studied the effects of treatment with the antioxidant N-acetyl-cysteine (NAC) and soluble complement receptor 1 (sCR1). Thy 1 GN was induced by intravenous anti-Thy 1 antibody. Glomeruli were isolated and kidney tissue taken from 30 min to 24 h after induction. Nitrite (NO-2) synthesis, luminol chemiluminescence for reactive oxygen species (ROS), and iNOS and cytokine mRNA were assayed in isolated glomeruli. Mesangial injury (mesangiolysis) and leucocyte infiltration were quantitated on tissue sections. NAC (i.p. 1,000 mg/kg, 1 h prior to anti-Thy 1) reduced glomerular NO-2 synthesis (3.5 +/- 0.66 vs. untreated 8.2 +/- 1.1, p = 0.02), and iNOS mRNA expression, and abolished enhanced chemiluminescence. In vitro incubation of nephritic glomeruli with 20 mM NAC also suppressed nitrite production (4.7 +/- 0.8 vs. untreated 12.2 +/- 0. 7 nmol NO-2/2,000 glomeruli/48 h, p = 0.003), and chemiluminescence. In NAC-treated animals, neutrophil infiltration (0.5 +/- 0 vs. untreated 9.6 +/- 1.6 glomerulus, p = 0.0005), and macrophage infiltration (1.7 +/- 0.4 vs. untreated 12.0 +/- 0.1, p = 0.006) were abolished, and mesangiolysis was significantly reduced (45.9 +/- 1.3 vs. untreated 34.4 +/- 2.1 cells/glomerulus, p = 0.009). NAC did not inhibit anti-Thy 1 antibody deposition. C1q was unaffected, but C3 was reduced. sCR1 treatment prevented iNOS mRNA induction, the enhanced chemiluminescence, and the neutrophil infiltration at 1 h. IL-1beta and TNFalpha mRNAs were not affected by either NAC or sCR1. These results show that NAC inhibits iNOS induction and NO synthesis in this model, and suppresses ROS synthesis and injury. They suggest that complement-dependent ROS generation is the critical initiating event that follows fixation of anti-Thy 1 antibody.

Acetylcysteine↗
PubMedDate not supplied

Percutaneous ultrasound-guided injection of the trachea in fetal sheep: a novel technique to target the fetal airways.

OBJECTIVE: To access the fetal airways percutaneously using ultrasound-guided injection of the fetal trachea in sheep. METHODS: Adenoviral gene therapy vectors and transduction-enhancing agents were delivered to the trachea via a needle inserted through the thorax or the neck of late-gestation (0.9 term, n = 3) or mid-gestation (0.5-0.8 term, n = 18) fetal sheep using ultrasound guidance. RESULTS: Injection of the trachea in the fetal thorax was successful in 16 out of 18 fetuses and achieved at the first attempt in 9 fetuses within 12 min [mean 7 min and 31 s +/- (SD) 3 min and 4 s]. Survival was 100%. Injecting the trachea in the neck was less successful. CONCLUSIONS: The fetal trachea of the sheep can be safely accessed by percutaneous ultrasound-guided injection to deliver vectors directly to the fetal airways for gene therapy. It may also enable tracheal occlusion for the antenatal treatment of congenital diaphragmatic hernia without the need for endoscopy or open surgery.

Adenoviridae↗
PubMedDate not supplied

Concept analysis of outcomes for advanced practice nursing.

The importance of accurately measuring health care outcomes is mentioned frequently in the literature. To do so, a common understanding of what constitutes a care delivery outcome is needed. In this article, a concept analysis of outcomes is provided, with identification of potential outcomes relevant to advanced practice.

Health Promotion↗