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Biomedical subjects

S A Leonard

Publications and source records attributed to S A Leonard.

At least 19 recordsLinked to original sources
PubMed2002

Addition of epinephrine to epidural ropivacaine during labour--effects on onset and duration of action, efficacy, and systemic absorption of ropivacaine.

Addition of epinephrine to epidural anaesthetic solutions may enhance efficacy and duration of analgesia. We postulated that addition of epinephrine 5 microg.mL(-1) to epidural ropivacaine would improve efficacy, decrease systemic absorption and reduce neonatal effects. Twenty-one multiparous women were studied. An initial dose of ropivacaine 30 mg followed by an infusion of ropivacaine 10 mg.h(-1) was given via a lumbar epidural catheter. According to random allocation, epinephrine 5 microg.mL(-1) was added to ropivacaine. Ropivacaine concentrations were measured in maternal venous plasma after one hour of infusion and in both umbilical venous and maternal plasma at delivery. Neonatal neurologic and adaptive capacity score (NACS) tests were performed at 2 and 24 h postpartum. All women delivered vaginally. The groups had similar ropivacaine dose requirements, epidural-delivery intervals and satisfaction scores. Bromage scores for motor block were greater in the epinephrine group (2; range: 1-3) than controls (1; range: 0-2). Mean plasma ropivacaine concentrations (+/-SD) were less in the epinephrine group (0.17 +/- 0.05 mg.L(-1), n = 10) than controls (0.31 +/- 0.14 mg.L(-1), n = 11; P < 0.05) after one h of infusion but not at delivery. UV ropivacaine concentrations and NACS scores were similar in the two groups. The addition of epinephrine to ropivacaine decreases maternal plasma concentrations after one h of epidural infusion but also increases motor block.

Clinical Trial↗
PubMed2001

Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.

The low molecular weight heparin, enoxaparin (by inhibition of factors Xa and IIa) and amide local anaesthetics (by altering platelet function) exert anti-clotting effects. Although these agents are often used in combination during the perioperative period, their potential interactive effect on clotting has not been defined. Blood from 10 ASA I-II patients who received enoxaparin 0.5 mg kg(-1) s.c. was studied using a Thrombelastograph (TEG) either alone or in combination with levobupivacaine (2.5 mg ml(-1) or 2.5 microg ml(-1)) or saline (50% dilution). In blood from patients who had received enoxaparin 0.5 mg kg(-1) s.c. 12 h previously, levobupivacaine 2.5 mg ml(-1) (but not 2.5 microg ml(-1)) produced significant changes in TEG clotting parameters (mean (SD) 15.7 (4.8) mm, 29.6 (25.6) mm, 34.4 (14.6) mm, 34.3 (12.2) degrees compared with control values of 6.1 (1.3) mm, 2.5 (0.5) mm, 63.5 (6.4) mm and 74.1 (2.9) degrees for r, K, MA, and alpha angle respectively).

Adult↗
PubMed2001

Absorption, distribution, metabolism, and excretion of a respirable antisense oligonucleotide for asthma.

EPI-2010 is a respirable antisense oligonucleotide (RASON), which selectively attenuates discordantly overexpressed adenosine A(1) receptors in allergic lung (Nature 1997;385:721). In the present study, aerosolized [(35)S]-labeled EPI-2010 (5 mg exposure; specific activity 0.055 Ci/mmol) was administered to normal rabbits by endotracheal tube to assess biodistribution, route of elimination, and potential cardiovascular toxicity. The animals were killed at 0, 6, 24, 48, and 72 h after inhalation of EPI-2010. Duplicate aliquots from different tissues and samples were solubilized and assessed for radioactivity. Approximately 1.4% of the total aerosolized EPI-2010 was deposited into the lung. The concentration of the drug in the lung at 0, 6, 24, 48, and 72 h was 64.0 +/- 1.5, 67.0 +/- 4.4, 32.0 +/- 3.7, 23.4 +/- 1.4, and 2.1 +/- 0.5 microg equivalents, respectively. Only a small amount of the radioactivity was detected in extrapulmonary tissues. By 72 h, 67.5% of the administered dose was excreted in the urine, which represented the major pathway of elimination. In postlabeling studies, intact full-length EPI-2010 could only be detected in the lung. Autoradiographic analysis after inhalation of [(35)S]-labeled EPI-2010 showed a relatively uniform deposition of drug throughout the lung. The aerosolized EPI-2010 did not have any significant systemic effects on the cardiovascular system as determined by Cardiomax-II analysis. This pattern of distribution and the lack of effect on cardiovascular function support the concept that RASONs offer the potential to safely address respiratory targets for which systemic distribution and systemic bioavailability may be contraindicated.

Administration, Inhalation↗
PubMed2001

RASONs: a novel antisense oligonucleotide therapeutic approach for asthma.

Inhalation based approaches enable the local delivery of antisense oligonucleotides (ASONs) to the respiratory tract and thus facilitate the ability of ASONs to target and modulate the activity of discordantly expressed respiratory disease genes. Studies involving EPI-2010, a respirable antisense oligonucleotide (RASON), targeting the adenosine A(1) receptor, a G-protein-coupled-receptor (GPCR) that plays an important role in the aetiology of asthma, demonstrate that ASON therapeutics can be delivered directly to the lung as an aerosol. EPI-2010 has been shown to inhibit adenosine A(1) receptor expression and significantly improve allergen-induced airway obstruction and bronchial hyper-responsiveness in animal models of human asthma. Absorption, tissue distribution, metabolism and excretion (ADME) and safety studies of aerosolised EPI-2010 suggest that phosphorothioate RASONs can be delivered to target respiratory tissues in low, safe, efficacious and long-acting doses. This supports the concept that RASONs offer the potential to address a variety of respiratory targets including those for which approaches employing systemic distribution and systemic bioavailability of the therapeutic agent may be undesirable. In addition, our studies with EPI-2010 indicate that the RASON approach may represent a technology that is uniquely positioned to address the challenges of the post-genome era in respiratory drug discovery, since it enables simultaneous in vivo target validation and antisense therapeutic discovery in an accelerated timeframe.

Adenosine↗
PubMed2000

Protein crystallization by design: chymotrypsinogen without precipitants.

Protein crystals are usually obtained by an empirical approach based on extensive screening to identify suitable crystallization conditions. In contrast, we have used a systematic predictive procedure to produce data-quality crystals of bovine chymotrypsinogen A and used them to obtain a refined X-ray structure to 3 A resolution. Measurements of the osmotic second virial coefficient of chymotrypsinogen solutions were used to identify suitable solvent conditions, following which crystals were grown for approximately 30 hours by ultracentrifugal crystallization, without the use of any precipitants. Existing structures of chymotrypsinogen were obtained in solutions including 10-30 % ethanol, whereas simple buffered NaCl solutions were used here. The protein crystallized in the tetragonal space group P4(1)2(1)2, with one molecule per asymmetric unit. The quality of the refined map was very high throughout, with the main-chain atoms of all but four residues clearly defined and with nearly all side-chains also defined. Although only minor differences are seen compared to the structures previously reported, they indicate the possibility of structural changes due to the crystallization conditions used in those studies. Our results show that more systematic crystallization of proteins is possible, and that the procedure can expand the range of conditions under which crystals can be grown successfully and can make new crystal forms available.

Animals↗
PubMed2000

Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using thromboelastography.

Amide local anaesthetics inhibit platelet function. We hypothesized that residual anaesthetic in the epidural space could decrease efficacy of an epidural blood patch in preventing postdural puncture headache. Levobupivacaine has recently been approved for epidural anaesthesia. Its effects on coagulation have not previously been studied. The aim of this study was to determine the effects of levobupivacaine on clotting using thromboelastography. Ten ASA Class I volunteers were studied. Venous blood samples were analysed using a Haemoscope 2000D TEG analyser. Whole blood, a 50% saline control and two levobupivacaine solutions (2.5 mg mL(-1) and 2.5 microg mL(-1) in blood) were compared. The former reproduces that produced in the epidural space by blood (20 mL for an epidural blood patch) and levobupivacaine 0.5% (20 mL). The latter approximates plasma concentrations following epidural injection of levobupivacaine 0.5% (20 mL). P < 0.05 was considered significant. Maximum amplitude (MA), a measure of clot strength, is decreased by levobupivacaine 2.5 mg mL(-1). Levobupivacaine 2.5 mg mL(-1) decreases clot strength and may reduce efficacy of a prophylactic epidural blood patch.

Adult↗
PubMed1993

Quantitation of 5-methylcytosine by one-dimensional high-performance thin-layer chromatography.

A method for the quantitative analysis of DNA 5-methylcytosine by one-dimensional high-performance thin-layer chromatography using alkylamino modified silica (HPTLC-NH2) plates is described. The preparative method is simple, involving enzymatic digestion of DNA with micrococcal nuclease and phosphodiesterase II to 3'-monophosphate nucleosides, conversion by T4 polynucleotide kinase to 32P-labeled 3',5'-bisphosphate nucleosides, and chromatographic separation of nuclease P1-cleaved 5'-monophosphate nucleosides. The weak, basic anion exchanger property of the HPTLC-NH2 plate enables separation of multiple samples in one dimension, whereas traditional polyethyleneimine cellulose plates require development of individual samples in two dimensions for analysis of 5'-methylcytosine.

5-Methylcytosine↗
PubMed1990

The role of exercise and posture in preventing low back injury.

Low back injury is a serious problem for U.S. industries, accounting for as much as one third of all workers' compensation payments. The number of low back injuries can be reduced effectively through the stressing of proper posture and the use of back care exercises. Body posture that maintains the spine's three natural curves decreases intradiscal stress. Back care exercises decrease the likelihood of low back injury by strengthening and adding flexibility to the spine's supportive structures.

Back Pain↗
PubMed1989

Occult pulmonary artery associated with failure to thrive and recurrent pneumonia--a case report.

Occult pulmonary artery is an uncommon cardiovascular defect. Associated symptoms include recurrent pulmonary infections and congestive heart failure. The authors describe a one-year-old boy initially diagnosed as having broncho-pulmonary dysplasia who developed severe failure to thrive, recurrent pneumonias, and pulmonary hypertension. The presence of an occult right pulmonary artery was suspected by lung perfusion scan and diagnosed by cardiac catheterization and angiography. After surgical repair, his clinical course improved and his growth and development were normal. This case demonstrates the importance of including occult pulmonary artery in the differential diagnosis of infants with failure to thrive associated with recurrent pulmonary infection.

Blood Vessel Prosthesis↗
PubMed1987

Toxic shock syndrome. A newly recognized complication of influenza and influenzalike illness.

Nine cases of severe hypotension or death compatible with toxic shock syndrome (TSS) as a complication of influenza and influenzalike illness were identified in Minnesota with onsets between Jan 2, 1986, and Feb 23, 1986, in which five of the patients died. During this time, an influenza outbreak was occurring in the state. Cultures of respiratory secretions were performed in eight patients; Staphylococcus aureus was isolated from all of them. Seven S aureus isolates were available for determination of exotoxin production; five isolates produced toxic shock syndrome toxin-1, one produced enterotoxin B, and one produced both. Acute influenza B infection was confirmed in three of four patients for whom throat cultures or acute and convalescent serum samples were available. Two patients fulfilled the Centers for Disease Control-confirmed case definition for TSS. Four additional patients fulfilled the CDC criteria for a probable case of TSS, and TSS was a likely diagnosis in the remaining three patients. The initial presentation was suggestive of nonsuppurative tracheitis or viral pneumonia in eight patients. In the remaining patient, the initial clinical presentation was compatible with staphylococcal pneumonia. This report demonstrates that TSS can occur as a complication of influenza and influenzalike illness.

Adolescent↗
PubMed1987

Diagnostic ultrasound in the urologist's office.

The clinical value of diagnostic ultrasound in the management of urologic patients is now firmly established. The use of real time diagnostic ultrasound equipment in the solo office practice of a urologist was evaluated by retrospective office record review covering a period of at least one year. The appropriate use of this equipment in daily office practice is shown to be clinically useful, cost-effective, and easily performed by a urologist. The routine use of diagnostic ultrasound by urologists is recommended.

Costs and Cost Analysis↗