Rapid production of cadmium infinite coordination polymer nanofiber via solvent induced precipitation method.

The precipitation synthesis of cadmium infinite coordination polymer (Cd-ICP) nanofibers with a high degree of uniformity is reported. The elemental analyses (CHN and ICP-OES), energy-dispersive X-ray spectroscopy (EDX) and thermogravimetric analysis (TGA) show that thermally robust monodisperse solid consists of bi-carboxylic acid linker and cadmium ion. The coordination between the Cd2+ ion and bi-carboxylic acid linker was investigated by Fourier transform infrared (FT-IR) spectroscopy. The photoluminescence (PL) properties of the Cd-ICP were studied in comparison with those of the bi-carboxylic acid linker. It was shown that the emission intensity of the Cd-ICP is much stronger than linker due to the structural rigidity after the coordination of linker to Cd ions. The field emission scanning electron microscopy (FE-SEM) results show that after calcination of the Cd-ICP the morphology changed from fiber to hexagonal-like disc. Furthermore, the results of UV-Vis spectroscopy show larger band gap for obtained CdO relative to the bulk counterpart.

Effect of smoking on retrobulbar blood flow in thyroid eye disease.

PurposeTo evaluate the effect of smoking on retrobulbar blood flow parameters by color Doppler imaging in patients with thyroid eye disease.Patients and methodsIn this observational case series, blood flow parameters in the ophthalmic artery, superior ophthalmic vein, central retinal artery, and vein were determined by color Doppler imaging in patients with thyroid eye disease. Patients were grouped as smokers and non-smokers. Never smokers and those who had stopped smoking for at least 1 year before onset of ophthalmopathy were considered as non-smokers. A thorough ophthalmic examination including Hertel exophthalmometry was performed. Orbital CT scan was also carried out in all patients.ResultsFifty-one orbits from 30 patients between 21 and 62 years old (mean±SD: 40.8±12.0) were enrolled in this study. Smokers had greater proptosis and more active and sever disease. (P<0.05) Muscle involvement based on CT scan did not vary in smokers and non-smokers. Maximum velocity (3.78±1.74 vs 5.27±2.14, P<0.001; t-test) and minimum velocity (1.74±0.78 vs 3.26±1.36, P =0.014; t-test) in superior ophthalmic vein were significantly lower in smokers than non-smokers. Even after adjusting for age, sex, and clinical activity score and severity, smokers had a lower minimum velocity in superior ophthalmic vein (P =0.01; ANCOVA analysis).ConclusionCigarette smoking may correlate with increase in orbital venous congestion in thyroid eye disease.

Transcutaneous chemical collection of caffeine in normal subjects: relationship to area under the plasma concentration-time curve and sweat production.

A novel transcutaneous chemical collection device (TCD) has been developed to study the phenomenon of outward transcutaneous chemical migration. The TCD is a Bandaid-like device containing an immobilized aqueous media and binding reservoir material to prevent back-transfer into the skin. This device, when placed against the skin, allows collection and quantitation of chemicals that diffuse directly through the skin from within the body. The relationship of the amount of drug collected in the TCD to the amount in the body available for collection (as represented by the area under the plasma-concentration time curve, AUC) and the effects of sweating, a potential confounding factor, on collection of drug in a TCD were studied, using caffeine as a model compound. TCD were placed on the skin of normal male volunteers. Twenty-four hours later subjects took caffeine by mouth. Blood samples were collected and TCD were removed at various times after drug intake and analyzed by HPLC for caffeine. Studies of the sweating effect were carried out in a similar manner, except that one arm of each subject was maintained at 40 degrees C to induce local sweating, the other arm acted as a non-sweating control. The amount of caffeine collected was linearly related to the AUC. Sweating seemed to have a large (40%) contribution to transdermal collection in the early period (5.5 h) of the study, but this difference was much less (14%) at longer collection times (10 h).

Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin.

Terfenadine is a nonsedating H1-antagonist that when overdosed, used with hepatic compromise, or when given with ketoconazole results in accumulation of parent terfenadine, prolongation of the QT interval, and torsades de pointes in susceptible patients. Nine subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral erythromycin (500 mg every 8 hours). All subjects increased metabolite concentrations after the addition of erythromycin for 1 week. The maximum concentration of metabolite increased by a mean of 107% and the mean metabolite area under the concentration-time curve increased by 170%. Three subjects accumulated unmetabolized terfenadine after administration of erythromycin for 1 week. Electrocardiographic data revealed changes in QT intervals and ST-U complexes in a subset of subjects who accumulated terfenadine. We conclude that erythromycin alters the metabolism of terfenadine, leading to accumulation of terfenadine in certain individuals that is associated with altered cardiac repolarization.

Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram.

OBJECTIVES: To establish whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by concomitant administration of grapefruit juice and to determine whether any effect of grapefruit juice is dependent on the timing of administration in relation to the dose of terfenadine. METHODS: Twelve healthy volunteers were studied in a prospective randomized trial. The primary end points were QT prolongation on the surface electrocardiogram and the pharmacokinetic parameters: area under the concentration-time curve (AUC), maximum concentration, and time to maximum concentration of terfenadine and its acid metabolite terfenadine carboxylate. All subjects received 60 mg terfenadine twice a day with 240 ml water for 7 days. They were then randomized to drink 240 ml of double-strength grapefruit juice simultaneously with terfenadine (simultaneous group) for an additional 7 days or to drink the same dose of grapefruit juice 2 hours after terfenadine for 7 days (delayed group). Twelve timed electrocardiograms and plasma terfenadine and metabolite levels were measured on days 7 and 14. RESULTS: None of the 12 subjects had quantifiable levels of terfenadine when the drug was administered with water. All six subjects who took terfenadine and drank grapefruit juice simultaneously had quantifiable terfenadine levels. Only two of six who drank grapefruit juice 2 hours after terfenadine had quantifiable levels. The AUC of the acid metabolite increased 55% (p < 0.05) in the simultaneous group and 22% (p = NS) in the delayed group. The mean QT interval increased from 420 to 434 msec (p < 0.05) in the simultaneous group and decreased from 408 to 407 msec (p = NS) in the delayed group. CONCLUSIONS: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in systemic terfenadine bioavailability and result in increases in QT interval. The clinical significance of an increase in QT interval of this magnitude is unclear.

Transcutaneous theophylline collection in preterm infants.

Transcutaneous collection of theophylline and its metabolite, caffeine, was undertaken in 33 preterm infants (2 to 89 days old) who were receiving routine theophylline therapy. Collection was done by means of a novel adhesive transcutaneous collection system. The transcutaneous collection system accumulated substances that migrated from the blood to the skin surface by trapping them in an activated charcoal-gel matrix. On one to three occasions, four transdermal collection systems were applied to the back or abdomen of each infant for 4 to 12 hours. During that time, blood samples were obtained for routine monitoring of plasma theophylline levels. Amounts of theophylline (95 +/- 198 ng) and caffeine (83 +/- 77 ng) in the transcutaneous collection system were significantly correlated with the respective average plasma drug concentration and postconceptional age (p less than 0.01). Skin reactions were limited to mild erythema. We concluded that theophylline and caffeine can be collected on the surface of the skin of preterm infants with a novel transcutaneous collection system. Amounts collected by means of the transcutaneous collection system correlated with plasma concentrations consistent with a diffusion process, but they were poor predictors of individual concentrations.

The effect of fluconazole on the steady-state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans.

Terfenadine is rapidly and nearly completely biotransformed during a first pass to an active acid metabolite. Accumulation of unmetabolized terfenadine has been associated with altered cardiac repolarization. Drug-drug interactions resulting in the accumulation of terfenadine have been reported for ketoconazole and erythromycin. Six subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral fluconazole (200 mg once daily). The mean metabolite area under the concentration-time curve increased by 34% and the time to maximum concentration of the metabolite was delayed from 2.3 to 4 hours by concurrent fluconazole. Unmetabolized terfenadine was not present in any subject, and cardiac repolarization was not significantly changed from baseline during any phase of the study. We conclude that a pharmacokinetic interaction between terfenadine and fluconazole exists; however, the absence of accumulation of parent terfenadine in plasma suggests that a clinically significant interaction is unlikely.

Relation between aortic dicrotic notch pressure and mean aortic pressure in adults.

It has recently been suggested that mean arterial pressure provides a reliable estimate of dicrotic notch pressure in infants and children. The aim of the present study was twofold: (1) to investigate the relation existing between aortic dicrotic notch pressure and both the steady and pulsed component of aortic pressure in adults (i.e., mean and pulse aortic pressures, respectively); and (2) to evaluate mean aortic pressure as an estimate of aortic dicrotic notch pressure. High-fidelity pressure recordings were obtained at the aortic root level in 17 men (52 +/- 13 years). Pressure data were analyzed at rest over 10 consecutive beats in each patient, and, in 6 patients, during the Valsalva maneuver (over 22 to 50 consecutive beats). At rest, dicrotic notch pressure was greater than mean pressure (109.0 +/- 17.9 vs 99.6 +/- 12.5 mm Hg, p = 0.0001). Dicrotic notch pressure was positively related to mean pressure (r = 0.93) and to pulse pressure (r' = 0.77), but not to patient's heart rate, cardiac output, or total estimated arterial compliance. There was a spontaneous beat-to-beat relation between dicrotic notch and mean pressures (1) at rest in 16 of 17 patients (mean r = 0.85), and (2) in all patients undergoing the Valsalva maneuver (mean r = 0.97). During the maneuver, intravascular mean pressure ranged from 59 to 171 mm Hg. Dicrotic notch pressure was positively related to mean pressure (r = 0.98) and to pulse pressure (r' = 0.44). Both at rest and during the Valsalva maneuver, mean pressure underestimated dicrotic notch pressure, and the higher the dicrotic notch pressure, the more negative the percent error (each p = 0.0001). In conclusion, aortic dicrotic notch pressure was mainly related to the steady component of aortic pressure. The mean aortic pressure slightly but significantly underestimated aortic dicrotic notch pressure, and thus should be used with greater caution in adults than in young patients as an estimate of end-systolic pressure.

A comparison between systolic aortic root pressure and finger blood pressure.

BACKGROUND: Digital photoplethysmography is used to assess hemodynamic variability and baroreflex sensitivity. Numerous studies have critically evaluated the accuracy of the photoplethysmographic device against peripheral pressure. The aim of our study was to compare finger blood and aortic root pressure. METHODS: We prospectively compared simultaneous recordings of systolic pressure at the aortic root and finger level over three consecutive respiratory cycles in 15 patients (56+/-11 years) undergoing routine cardiac catheterization. Data were obtained at baseline, during deep breathing maneuver (0.1 Hz), and after left ventricular cineangiography. RESULTS: At baseline, systolic finger pressure overestimated systolic aortic pressure (145.2+/-22.5 vs 115.0+/-20.1 mm Hg; p<0.001). The pressure difference (30.2+/-17.0 mm Hg) was not influenced by systolic aortic pressure. There was no relationship between pressure difference and the main determinants of the pulse wave amplification phenomenon. There was a beat-to-beat relationship between finger and aortic pressure in 14 of 15 subjects (slope ranging from 0.37 to 1.70; ordinate: from -56 to +98 mm Hg). During the deep breathing maneuver and after left ventricular cineangiography, finger pressure still overestimated aortic pressure by 32.3+/-15.0 mm Hg and 38.3 13.9 mm Hg, respectively (each p<0.001). There was a beat-to-beat relationship between systolic aortic root pressure (IAoBP) and systolic finger (FBP) in 13 of 15 patients, with major scattering of both slopes and ordinates. Throughout the study, there was no predictable relationship between the level of IAoBP and pressure bias. CONCLUSIONS: As expected, FBP was almost always higher than IAoBP. Importantly, the differences in systolic pressure did not correlate with known determinants of the pulse wave amplification phenomenon. The device must be used cautiously if one wants to noninvasively track spontaneous or induced changes in IAoBP.

Agroterrorism. Agricultural infrastructure vulnerability.

The intentional contamination of animal feed to reduce the availability of animal-derived human food or to infect human populations is seldom mentioned, but animal feed could be an easy target for bioterrorists. The period of delay between the contamination of the animal feed and adulteration of the human food product provides an additional degree of uncertainty about the source of the contamination and minimizes the possibility of apprehending the terrorist. The less obvious and more natural the source of biological contamination, the greater the likelihood that the animal feed contamination will be mistaken as a natural phenomenon. However, the problems related to managing natural food contamination and intentional food contamination remain the same. Rapid testing and separation of contaminated feed are important steps, followed by the more specific identification of the contaminant to determine the source of adulteration and/or the possibility of decontamination. At this time identification of the bioagents is dependent on the availability of antibody-specific test systems. The rapid development of specific antibodies for the development of sensitive and specific test kits is the key to identifying contamination and dealing effectively with the disposal or decontamination of the animal feed and, ultimately, preventing the contamination of animal-derived human food products.

Pulse pressure response to the strain of the valsalva maneuver in humans with preserved systolic function.

Arterial pulse pressure response during the strain phase of the Valsalva maneuver has been proposed as a clinical tool for the diagnosis of left heart failure, whereas responses of subjects with preserved systolic function have been poorly documented. We studied the relationship between the aortic pulse amplitude ratio (i.e., minimum/maximum pulse pressure) during the strain phase of the Valsalva maneuver and cardiac hemodynamics at baseline in 20 adults (42 +/- 14 yr) undergoing routine right and left heart catheterization. They were normal subjects (n = 5) and patients with various forms of cardiac diseases (n = 15), and all had a left ventricular ejection fraction >/=40%. High-fidelity pressures were recorded in the right atrium and the left ventricle at baseline and at the aortic root throughout the Valsalva maneuver. Aortic pulse amplitude ratio 1) did not correlate with baseline left ventricular end-diastolic pressure, cardiac index (thermodilution), or left ventricular ejection fraction (cineangiography) and 2) was positively related to total arterial compliance (area method) (r = 0.59) and to basal mean right atrial pressure (r = 0.57) (each P < 0.01). Aortic pulse pressure responses to the strain were not related to heart rate responses during the maneuver. In subjects with preserved systolic function, the aortic pulse amplitude ratio during the strain phase of the Valsalva maneuver relates to baseline total arterial compliance and right heart filling pressures but not to left ventricular function.

Itraconazole affects single-dose terfenadine pharmacokinetics and cardiac repolarization pharmacodynamics.

The object of this study was to examine prospectively the effects of itraconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (QTc intervals) of single-dose terfenadine in six healthy volunteers. It was designed as a prospective cohort study with each subject serving as his own control, set in an outpatient cardiology clinic. The participants were six healthy volunteers (two men, four women; ages 24-35) not taking any prescription or over-the-counter medications. Single-dose terfenadine administration (120 mg) was accompanied by pharmacokinetic profiles and serial determination of the QTc interval for 12 hours. The subjects then began daily oral itraconazole (200 mg each morning) for 7 days. Repeat pharmacokinetic and pharmacodynamic determinations were made after administration of a second dose (120 mg) of terfenadine while receiving itraconazole. The main outcome measures were terfenadine and acid metabolite serum concentrations; corrected QT intervals as determined by 12-lead electrocardiogram (ECG); and presence or absence of late potentials as determined by signal-averaged ECGs over 150 cardiac cycles. There were significant changes in the pharmacokinetic parameters of acid metabolite after treatment with itraconazole. All subjects had detectable levels of unmetabolized terfenadine after addition of itraconazole, which was associated with QT prolongation. There was no evidence of late depolarization as manifested by an increase in QRS duration found using signal-averaged electrocardiography. Itraconazole influences the metabolism of terfenadine in normal volunteers and results in the accumulation of unmetabolized parent drug associated with altered cardiac repolarization. This drug combination should be avoided.

Use of reflectance spectrophotometry in the human corticosteroid skin blanching assay.

A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a human rater to measure blanching response in the skin. This study evaluated an instrumental alternative to the human rater and used this method to measure the differences between a number of brand name and generic topical corticosteroid products (six creams and six ointments). Products were applied to the forearms of normal volunteers and the blanching responses were assessed after 6 and 16 hours in both occluded and non-occluded skin sites. Only the fluocinolone acetonide generic and brand name preparations were different from each other. The spectrophotometric method proved to be equivalent but not superior to the standard human observer method.

Population variability in the pharmacokinetics of terfenadine: the case for a pseudo-polymorphism with clinical implications.

Terfenadine is nearly completely first pass biotransformed. Unmetabolized terfenadine plasma concentrations have been associated with altered cardiac repolarization. During previous drug interaction studies, 2 subjects were found to have quantifiable concentrations of unmetabolized terfenadine with accompanying electrocardiographic repolarization changes while on terfenadine alone. To determine whether these subjects were representative of the population, 150 healthy volunteers (109 males, 41 females, ages 19-49) were screened for their ability to metabolize terfenadine after achieving steady-state. Blood was obtained at known times of maximum terfenadine concentration after dosing. Eleven subjects had quantifiable concentrations of terfenadine demonstrating wide intersubject variability in terfenadine metabolism. Further studies to determine whether such subjects are more susceptible to untoward terfenadine-associated events are underway.

[Coronary spasm and diffuse coronary vasoconstriction responsible for transient left ventricular insufficiency]. / Spasmes coronaires et vasoconstriction coronaire diffuse responsables d'une insuffisance ventriculaire gauche transitoire.

A 52 year old patient presenting with spontaneous anginal chest pain for 4 days was admitted to hospital for a more intense and prolonged chest pain associated with signs of left ventricular failure (gallop, pulmonary crepitations, hypoxemia). Coronary angiography showed marked septal hypokinesia and spontaneous localised spasm of the left anterior descending and marginal arteries with a variable degree of luminal narrowing of the other segments of these two arteries and of the right coronary artery. These changes regressed after intracoronary injection of molsidomine. The signs of left ventricular failure disappeared in 48 hours. The wall motion abnormality, monitored by 2D echocardiography, regressed slowly over 3 days. On the other hand, the electrocardiogram, which showed anterior wall subendocardial ischaemia with prolongation of the QTc interval during the spasm, remained abnormal for a long time. Therefore, in the absence of organic heart disease, coronary spasms associated with vasoconstriction can induce a sufficiently severe and durable alteration of left ventricular function to create clinical signs of cardiac failure and profound and prolonged ST-T wave changes on the electrocardiogram.

[Relationship between end-systolic aortic pressure and mean aortic pressure in adults]. / Relation entre la pression aortique télésystolique et la pression aortique moyenne chez l'adulte.

The mean blood pressure is an accurate estimate of the end-systolic aortic pressure in children. The aim of this study was: 1) to assess the relationship between the pressure at the incisura (PIAo) and the mean (MAoP) and pulse (PAoP) pressures of the supravalvular aorta in adults: and 2) to evaluate MAoP as an estimate of PIAo in adults. High fidelity pressure recordings were carried out in the supravalvular aorta in 17 men. The pressures were measured at rest in 10 consecutive beats and. In 6 subjects, during a Valsalva manoeuvre. At rest, PIAo was greater than the MAoP (109 +/- 17.9 versus 99.6 +/- 12.5 mmHg, p = 0.0001). There was a positive linear correlation between PIAo and MAoP (r = 0.93) and between PIAo and PAoP (r' = 0.77) whereas no correlation was observed between PIAo and heart rate, cardiac output or estimated total systemic arterial compliance. A beat-to-beat relationship was observed between PIAo and MAOP: 1) at rest in 16 of the 17 subjects and 2) in each subject who performed a Valsalva manoeuvre. Both at rest and during Valsalva, MAOP underestimated PIAo significantly, especially when PIAo was increased (p = 0.0001). The authors conclude that end-systolic supraaortic pressure is mainly related to the mean component of aortic pressure. MAOP slightly but constantly underestimated PIAo and this should lead to caution in assimilating MAOP to end-systolic aortic pressure in adults, especially in subjects with very high aortic pressures.

Resolution of terfenadine enantiomers by beta-cyclodextrin chiral stationary phase high-performance liquid chromatography.

Enantiomers of terfenadine were resolved by high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) column packed with beta-cyclodextrin (beta-CD) covalently bound to silica. Separation was achieved in both the reverse phase and normal phase modes. Resolution of enantiomers was confirmed by ultraviolet-visible absorption, circular dichroism, and mass spectral analysis.

Enantiomeric analysis of terfenadine in rat plasma by HPLC.

Enantiomeric pairs of the antihistaminic drug terfenadine and its carboxylic acid derivative were directly separated by HPLC using an ovomucoid protein column. Absolute configurations of terfenadine enantiomers were assigned by comparing their circular dichroism spectra with those of 1-phenyl-1-butanol enantiomers of known absolute stereochemistry. Terfenadine and its major carboxylic acid metabolite extracted from blood plasma following an oral administration of a racemic terfenadine to rats were found to be enriched in the (S)- and (R)-enantiomers, respectively. The results indicated that the (R)-enantiomer of an orally administered racemic terfenadine was preferentially oxidized in rats to form a carboxylic acid metabolite enriched in the (R)-enantiomer.

Matching dicrotic notch and mean pulmonary artery pressures: implications for effective arterial elastance.

It has been suggested that pulmonary artery pressure at the end of ejection is close to mean pulmonary artery pressure, thus contributing to the optimization of external power from the right ventricle. We tested the hypothesis that dicrotic notch and mean pulmonary artery pressures could be of similar magnitude in 15 men (50 +/- 12 yr) referred to our laboratory for diagnostic right and left heart catheterization. Beat-to-beat relationships between dicrotic notch and mean pulmonary artery pressures were studied 1) at rest over 10 consecutive beats and 2) in 5 patients during the Valsalva maneuver (178 beats studied). At rest, there was no difference between dicrotic notch and mean pulmonary artery pressures (21.8 +/- 12.0 vs. 21.9 +/- 11.1 mmHg). There was a strong linear relationship between dicrotic notch and mean pressures 1) over the 10 consecutive beats studied in each patient (mean r = 0.93), 2) over the 150 resting beats (r = 0.99), and 3) during the Valsalva maneuver in each patient (r = 0.98-0.99) and in the overall beats (r = 0.99). The difference between dicrotic notch and mean pressures was -0.1 +/- 1.7 mmHg at rest and -1.5 +/- 2.3 mmHg during the Valsalva maneuver. Substitution of the mean pulmonary artery pressure by the dicrotic notch pressure in the standard formula of the pulmonary vascular resistance (PVR) resulted in an equation relating linearly end-systolic pressure and stroke volume. The slope of this relation had the dimension of a volume elastance (in mmHg/ml), a simple estimate of volume elastance being obtained as 1.06(PVR/T), where T is duration of the cardiac cycle. In conclusion, dicrotic notch pressure was of similar magnitude as mean pulmonary artery pressure. These results confirmed our primary hypothesis and indicated that human pulmonary artery can be treated as if it is an elastic chamber with a volume elastance of 1.06(PVR/T).