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Biomedical subjects

C Lindsay

Publications and source records attributed to C Lindsay.

At least 19 recordsLinked to original sources
PubMed2001

Autologous plasma activates Akt/protein kinase B and enhances basal survival and resistance to DNA damage-induced apoptosis in B-chronic lymphocytic leukaemia cells.

We have studied the actions of autologous plasma on both basal and DNA damage-induced apoptosis in B-chronic lymphocytic leukaemia (B-CLL) cells. Apoptosis was quantified using morphological criteria and Western blot analysis for the apoptosis-specific p85 fragment of poly(ADP ribose) polymerase. Cell viability was estimated using the methyl thiazol tetrazolium bromide dye reduction assay. Plasma cultures showed lower rates of basal apoptosis as well as a decreased cytotoxic response to chlorambucil and gamma-radiation compared with cultures in fetal calf serum. Experiments using neutralizing antibodies suggested that the protective actions of plasma could not be accounted for by interleukin 4, the interferons alpha or gamma or stromal cell-derived factor 1, each of which have been shown to protect B-CLL cells from apoptosis in vitro. Plasma addition to B-CLL cells resulted in rapid activation of the Akt protein kinase, a key signalling enzyme that has been implicated in anti-apoptotic signalling. LY294002, an inhibitor of phosphatidylinositol 3'-kinase, blocked Akt activation by plasma. To the best of our knowledge, this is the first report to show that factors present in plasma promote basal survival of B-CLL cells and resistance to cytotoxic drugs via stimulation of the Akt cytoprotective-signalling pathway. Pharmacological blockade of this pathway may have potential in the development of novel therapeutic strategies for B-CLL treatment.

Antineoplastic Agents, Alkylating↗
PubMed2001

Just the croup.

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Child, Preschool↗
PubMed1999

Stereolithographic modelling as an aid to orbital brachytherapy.

PURPOSE: This paper describes the technique of stereolithographic biomodelling and its application to a patient who was treated using orbital brachytherapy. METHODS AND MATERIALS: The process uses a moving laser beam, directed by a computer, to draw cross-sections of the model onto the surface of photo-curable liquid plastic. Using a stereolithographic apparatus (SLA), solid or surface data is sliced by software into very thin cross-sections. A helium cadmium (HeCd) laser then generates a small intense spot of ultraviolet (UV) light that is moved across the top of a vat of liquid photo monomer by a computerised optical scanning system. The laser polymerises the liquid into a solid where it touches, precisely printing each cross-section. A vertical elevator lowers the newly formed layer, and a recoating and levelling system establishes the next layer's thickness. Successive cross-sections (0.25 mm thick), each one adhering to the one below, are built one on top of the other, to form the part from the bottom up. The biomodel allowed the implant to be planned in detail prior to the surgery. The accurate placement of brachytherapy catheters was assured, and the dosimetry could be determined and optimised prior to the definitive procedure. CONCLUSIONS: Stereolithography is a useful technique in the area of orbital brachytherapy. It allows the implant to to be carried out with greater accuracy and confidence. For the patient, it minimises the risk to the eye and provides them with a greater understanding of the procedure.

Adult↗
PubMed1999

Improved cyclosporine bioavailability in black pediatric liver transplant recipients after administration of the microemulsion formulation.

Black transplant recipients are associated with low cyclosporine bioavailability, which may contribute to the poorer clinical outcomes observed with these patients. In this analysis, we compared cyclosporine exposure in black (n = 9) and nonblack (n = 18) pediatric maintenance liver transplant recipients by using steady-state pharmacokinetic profiles obtained after administration of the original and microemulsion formulations of cyclosporine. Treatment with the original cyclosporine formulation resulted in lower mean dose-normalized, area under the concentration-versus-time curve values for black compared with nonblack pediatric liver transplant recipients. On conversion to the microemulsion formulation of cyclosporine, black and nonblack patients experienced increases in cyclosporine bioavailability of 102% and 39%, respectively (P =.009 and P =.001). Because the increase in mean bioavailability was substantially greater for blacks, area under the concentration-versus-time curve values for this pediatric subpopulation became similar to those levels obtained for nonblacks receiving the microemulsion formulation for cyclosporine. When patients were further stratified by age, ethnic differences in bioavailability with the original formulation of cyclosporine were most apparent in the 1- to 5-year age group. Conversion to the microemulsion formulation resulted in a 164% increase (P =.05) in bioavailability for black patients within this age group such that, again, these levels became similar to area under the concentration-versus-time curve values obtained for young nonblacks receiving cyclosporine for microemulsion. Improvements in cyclosporine bioavailability after administration of the microemulsion formulation of cyclosporine may translate to improved long-term graft and patient outcomes for black pediatric liver transplant recipients.

Adolescent↗
PubMed1999

Lessons from Sissy.

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Catheterization, Central Venous↗
PubMed1999

Variability in the size of the nucleus in spermatozoa from Houbara bustards, Chlamydotis undulata undulata.

Semen collected from 3-year-old male Houbara bustards contained large proportions (6-40%) of spermatozoa with large nuclei. In these spermatozoa, the length of the nucleus was up to twice the mean length of the nucleus in normal spermatozoa. The lengths of the acrosome, midpiece and flagella were all normally distributed, but the length of the nucleus formed a bimodal distribution. The proportion of spermatozoa with large nuclei varied among males, but not among different semen samples collected from the same male throughout the breeding season. The proportion of motile spermatozoa with large nuclei was half that of normal spermatozoa, but their velocity was significantly greater. After insemination into females, spermatozoa with large nuclei were observed in the outer perivitelline layer of eggs laid, indicating that they were stored and transported within the oviduct and reached the egg at about the time of fertilization. Furthermore, there was no difference in the ability to produce viable progeny in females that were mated with males producing greater proportions of spermatozoa with large nuclei compared with those producing 'normal' spermatozoa. Thus, the abnormal spermatozoa did not appear to impede fertility. There were no signs of triploidy in the males that produced spermatozoa with large nuclei, or in their progeny, as demonstrated by the size of erythrocytes. Therefore, it appears that the spermatozoa with large nuclei were the result of aberrant spermatogenesis.

Analysis of Variance↗
PubMed1998

Effects of smoking cessation on maternal airway function and birth weight.

OBJECTIVE: To evaluate the effects of smoking cessation before or early in pregnancy on maternal airway function and birth weight. METHODS: Measurements of forced expiratory spirometry including forced vital capacity, forced expiratory volume in 1 second, forced expiratory flow rates between 0.2 and 1.2 L, 25% and 75%, and 75% and 85%, and instantaneous flows at lung volumes of 25%, 50%, and 75% were carried out by a wedge bellow spirometer in 40 pregnant exsmokers and were compared with those of 175 nonsmoking and 97 currently smoking pregnant women. Spirometric testing was conducted at a mean (+/- SD) gestational age of 21.5 +/- 7.0 weeks. In exsmokers, the average lifetime cigarette consumption was 17.1 +/- 8.1/day for a mean duration of 9.7 +/- 3.9 years, similar to that observed in current smokers. The median duration of smoking abstinence was 20 weeks before study spirometry. RESULTS: All spirometric measurements in exsmokers were similar to those of nonsmokers and were significantly higher than those of current smokers. Spirometric measurements for nonsmokers, current smokers, and exsmokers were respectively: forced expiratory volume in 1 second (3.36 +/- 0.39, 3.09 +/- 0.45, and 3.35 +/- 0.32 L); forced expiratory flow rate between 25% and 75% (ie, mid-expiratory phase) (3.85 +/- 0.69, 3.21 +/- 0.76, and 3.86 +/- 0.66 L/sec); forced expiratory flow rate between 75% and 85% (ie end-expiratory phase) (1.39 +/- 0.35, 1.03 +/- 0.35, and 1.41 +/- 0.39 L/sec); instantaneous flow at lung volume of 50% (4.35 +/- 0.82, 3.76 +/- 0.89 and 4.36 +/- 0.68 L/sec); and instantaneous flow at lung volume of 25% (1.91 +/- 0.47, 1.47 +/- 0.49, and 1.92 +/- 0.46 L/sec). Mean gestational age at delivery was similar among the three groups (277 +/- 11,274 +/- 12, and 274 +/- 11 days for nonsmokers, current smokers, and exsmokers, respectively). The mean birth weight of babies born to exsmokers (3408 +/- 511 g) was similar to that of babies born to nonsmokers (3469 +/- 461 g), but was significantly greater than that of babies born to smoking pregnant women (3189 +/- 485 g; P < .001). CONCLUSION: Smoking cessation either before or at an early stage of pregnancy is associated with early, reversible increments of maternal airway function and mean birth weights that are higher than among women who continue smoking.

Adult↗
PubMed1998

Evaluation of semen from individual male domestic fowl by assessment of sperm: perivitelline interaction in vitro and in vivo.

1. Spermatozoa in semen samples from 8 individual male domestic fowls were shown to have a differential and characteristic ability to hydrolyse holes in the inner perivitelline layer from laid eggs in an in vitro assay. 2. The number of holes produced by samples of spermatozoa per unit area of inner perivitelline layer in vitro was linearly correlated with sperm ATP content (r = 0.85) and motility (r = 0.76). 3. The number of holes formed in the inner perivitelline layer in vitro was also linearly correlated with the numbers of holes formed in the inner perivitelline layer of eggs fertilised in vivo, in inseminated hens (r = 0.90); and was correlated logarithmically with the proportion of fertile eggs laid by these hens.

Animals↗
PubMed1997

Pharmacokinetics of an oral solution of the microemulsion formulation of cyclosporine in maintenance pediatric liver transplant recipients.

BACKGROUND: A comparison of the oral bioavailability of cyclosporine from the original formulation (CsA) and from the new formulation, cyclosporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 years; group 2, ages 6-17 years) in an open-label, multicenter, randomized crossover trial. All patients were at least 6 months past transplantation and were receiving CsA maintenance therapy. METHODS: In study period 1 (days 1 through 14), patients were administered either CsA or CsA-ME at the same b.i.d. dosage as their maintenance therapy. Upon entry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio. On day 29, all patients returned to the CsA treatment administered at study entry, with follow-up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2. RESULTS: Both the mean area under the concentration-versus-time curve and the mean maximum blood concentration of cyclosporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with those receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creatinine and blood pressure did not differ significantly between treatment groups. CONCLUSIONS: This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.

Absorption↗
PubMed1997

Do prostacyclin and thromboxane contribute to the "protective effect" of pregnancies with chronic hypertension? A preliminary prospective longitudinal study.

OBJECTIVE: The aim of this study was to assess prospectively the urinary excretion of renal and systemic metabolites of thromboxane and prostacyclin in normotensive and chronic hypertensive pregnancies. STUDY DESIGN: Pregnant hospital employees were invited to collect 24-hour urine samples weekly from the seventh week until delivery. Concentrations of renal metabolites (thromboxane B2, 6-keto-prostaglandin F1alpha) were measured by radioimmunoassay after extraction. Systemic metabolites (2,3-dinor-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1alpha) were assessed by enzyme immunoassay after extraction and high-pressure liquid chromatographic separation. RESULTS: Thromboxane B2 excretion was similar in normotensive and hypertensive pregnancies, whereas a twofold increase of 6-keto-prostaglandin F1alpha was observed in hypertensive compared with normotensive pregnancies (7537 +/- 349 vs 3857 +/- 202 pg/mg creatinine, p < 0.001). During pregnancy in both conditions measurements displayed uniform excretion of thromboxane B2 with progressively increased levels of 6-keto-prostaglandin F1alpha in chronic hypertension (R2 = 0.60, p < 0.005). Mean excretion of 2,3-dinor-thromboxane B2 averaged 1208 +/- 65 and 898 +/- 48 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mainly due to significant decreased concentrations in hypertension in the first half of pregnancy. Conversely, 2,3-dinor-6-keto-prostaglandin F1alpha levels were 845 +/- 39 and 1226 +/- 67 pg/mg creatinine in normotensive and hypertensive pregnancies (p < 0.001), mostly because of significantly increased production in hypertension from 22 weeks onward. Ratios of both renal and systemic metabolites favored increased prostacyclin production in chronic hypertension. CONCLUSION: In contrast to preeclampsia, uncomplicated mild to moderate chronic hypertensive pregnancies are characterized by an excess production of prostacyclin with unaltered or even lower thromboxane concentrations, which may contribute to the general favorable outcome of this hypertensive condition.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled, interventional study.

STUDY OBJECTIVE: To determine the hemodynamic effects of i.v. milrinone lactate in pediatric patients with nonhyperdynamic septic shock. Specifically we tested the hypothesis that i.v. milrinone would increase cardiac index by 20% and decrease systemic vascular resistance index by 20% during a 2-h study period. DESIGN: Prospective, double-blinded, randomized, placebo-controlled, descriptive, interventional study. SETTING: Twenty-six-bed pediatric ICU at Children's Medical Center of Dallas and a 10-bed pediatric trauma ICU at Parkland Memorial Hospital. PATIENTS/PARTICIPANTS: Twelve patients (age range, 9 months to 15 years) with nonhyperdynamic septic shock despite administration of catecholamines (cardiac index [CI] normal [3.5 to 5.5 L/min/m2] or low [< or =3.5 L/min/m2]; systemic vascular resistance index [SVRI] normal [800 to 1,600 dyne.s.cm5/m2] or high [> or =1,600 dyne.s.cm5/m2]; and pulmonary capillary wedge pressure [PCWP] normal [8 to 12 mm Hg] or higher) with clinical signs of poor perfusion were enrolled, randomized, and treated in a blinded fashion with i.v. milrinone and placebo. INTERVENTIONS: Patients were randomized into two groups. Group A received a loading dose of 50 micrograms/kg i.v. of milrinone followed by a continuous i.v. infusion of 0.5 microgram/kg/min while group B received an equal volume loading dose and continuous infusion of placebo. After 2 h, group A received an equal-volume loading dose followed by a continuous infusion of placebo while the milrinone infusion continued, while group B received a 50 micrograms/kg loading dose of milrinone followed by a continuous infusion of 0.5 microgram/kg/min while the placebo infusion remained. Outcome variable were measured at baseline, 0.5, 1.0, 2.0, 2.5, 3.0, and 4.0 h. Echocardiographic measurements were taken at baseline, hour 2, and hour 4 in all subjects. No changes in other inotropic or mechanical ventilatory support were allowed during the study period. MEASUREMENTS AND MAIN RESULTS: Milrinone significantly increased CI, stroke volume index (SVI), right and left ventricular stroke work index, and oxygen delivery (Do2) at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05) while significantly decreasing SVRI, pulmonary vascular resistance index, and mean pulmonary arterial pressure at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05). No clinically or statistically significant changes in heart rate, systolic and diastolic BP, mean systemic arterial pressure, or PCWP were observed during milrinone treatment compared to placebo. CONCLUSIONS: CI, SVI, and Do2 significantly increased while SVRI significantly decreased when compared to placebo after i.v. administration of milrinone to pediatric patients with nonhyperdynamic septic shock. No adverse effects were observed. In a volume-resuscitated pediatric patient with septic shock, when administered in addition to catecholamines, milrinone will improve cardiovascular function.

Adolescent↗
PubMed1995

Development of an enzyme-linked immunosorbent assay for 2,3-dinor-6-keto-prostaglandin F1 alpha in urine using a monoclonal antibody.

OBJECTIVES: To develop and validate an enzyme-linked immunosorbent assay (ELISA) for measurement of urinary 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3D6KPGF1 alpha) using a monoclonal antibody and a horseradish peroxidase-linked antigen. DESIGN AND METHODS: Assay validation included optimization of the standard curve, antibody cross-reactivity, accuracy and imprecision studies together with preliminary measurement of clinical samples. RESULTS: Optimal conditions of the standard curve (0.078-10.0 micrograms/L) used 2 mg/L of antibody and 3 micrograms/L of peroxidase conjugate in each well, at pH 7.2. The coefficient of variation of various concentrations of the standard curve averaged 6.8%. Antibody cross-reactivity was < 0.01% for related prostanoids. Recovery of known amounts (0.1-5.0 micrograms/L) of 2,3D6KPGF1 alpha added to an urinary sample was 101.2 +/- 6.3%. Imprecision studies with non-pregnant (0.24 microgram/L) and pregnant (2.5 micrograms/L) samples displayed an intraassay variability of 8.9 and 9.9%, and an interassay variability of 9.6 and 10.0%, respectively. Urinary measurements in the non-pregnant and pregnant states were similar to those previously reported. An apparent decreased concentration was observed early in pregnancy in future preeclampsia. CONCLUSION: With similar precision and validity, our assay method is time- and cost-saving. Preliminary urinary measurements show that this analyte may be of interest as an early marker for preeclampsia.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Programmed instruction booklet for cardiac rehabilitation teaching.

Programmed instruction is an underused approach for educating hospitalized patients. This educational technique is based on the work of Skinner, who developed the linear programmed instruction technique. To test the effectiveness of this technique as a patient education tool, a programmed instruction booklet was developed for patients who were hospitalized after myocardial infarction. The booklet included basic information on cardiac anatomy and pathology, risk factors, diet, exercise, and medications. A quasi-experimental study design was implemented in which 59 hospitalized patients who had had a myocardial infarction underwent pretesting and posttesting. Patients were alternately assigned to a control group or an experimental group. The control group (n = 30) participated in the hospital's existing cardiac rehabilitation program, and the experimental group (n = 29) used the programmed instruction booklet. A one-way analysis of variance revealed a statistically significant improvement (p less than 0.05) in the posttest scores of the experimental group. The results of this study support the use of the programmed instruction method as one means of teaching cardiac rehabilitation information to hospitalized patients after myocardial infarction.

Adult↗
PubMed1976

Method of preparation and application of small quantities of semi-solid topicals.

Quantifying with accuracy small amounts of semi-solid viscus materials is critical in some situations. A sample dish and loading device for a micropipette is described which permits efficient and accurate loading and dispensing of microliter quantities. This is especially valuable for dealing with small quantities of radiolabelled viscus materials.

Administration, Topical↗