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PubMed2006

Addition of cyclopropyl alkynes to a Brook silene: definitive evidence for a biradical intermediate.

The addition of three newly developed mechanistic probes, (trans-2-phenylcyclopropyl)ethyne, (trans,trans-2-methoxy-3-phenylcyclopropyl)ethyne, and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne, 1a-c, to a Brook silene, 2-tert-butyl-2-trimethylsiloxy-1,1-bis(trimethylsilyl)-1-silene, 10, was examined. When alkyne 1a was added to silene 10 products derived from a formal ene reaction were obtained. When alkynes 1b-c were added to silene 10, in addition to the typical silacyclobutenes, a variety of silacycloheptenes were obtained in which the cyclopropyl ring had clearly opened. Formal ene-addition products were also produced from the addition of 1b to 10. Based on the relative positions of the phenyl and methoxy substituents within the seven-membered ring of the silacycloheptenes and the known behavior of the alkyne probes under both radical and ionic conditions, it was concluded that a biradical intermediate was formed during the addition of alkynes 1b-c to silene 10. In the addition of alkynes 1a-b to silene 10, the ene products are most likely formed by a competitive pericyclic reaction. We also present a straightforward method for the unambiguous determination of the regiochemistry of silacyclobutenes derived from the cycloaddition of terminal alkynes to silenes.

Journal Article↗
PubMed2006

Dark-field oxidative addition-based chemosensing: new bis-cyclometalated PtII complexes and phosphorescent detection of cyanogen halides.

Heavy metal complexes that are phosphorescent at room temperature are becoming increasingly important in materials chemistry, principally due to their use in phosphorescent organic light-emitting devices (OLEDs). Their use in optical sensory schemes, however, has not been heavily explored. Homoleptic bis-cyclometalated Pt(II) complexes are known to undergo oxidative addition with appropriate electrophiles (principally alkyl halides) by either thermal or photochemical activation. We have applied this general reaction scheme to the development of a phosphorescence-based sensing system for cyanogen halides. To carry out structure-property relationship studies, a series of previously unreported Pt(II) complexes was prepared. Most of the complexes (excluding those that incorporated substituents on the ligands that forced steric crowding in the square plane) were strongly orange-red phosphorescent (Phi = 0.2-0.3) in a room-temperature oxygen-free solution. These sterically demanding ligands also accelerated the addition of cyanogen bromide to these complexes but slowed the addition of methyl iodide, indicating that the oxidative addition mechanisms for these two electrophiles is different. The lack of solvent-polarity effect on the addition of BrCN suggests a radical mechanism. Oxidative addition of BrCN to the metal complexes in solution or dispersed in poly(methyl methacrylate) gave blue-shifted emissive Pt(IV) complexes. The blue-shifted products give a dark-field sensing scheme that is in sharp contrast to energy transfer-based sensing schemes, which have limited signal-to-noise because of the presence of lower-energy vibronic bands of the energy donor that can overlap with the emission of the acceptor.

Crystallography, X-Ray↗
PubMed2004

Stereoselective addition of dimethyl thiophosphite to imines.

Dimethyl thiophosphite (DMTP) was synthesized from dimethyl phosphite, and the diastereoselective addition of DMTP to benzaldimines bearing chiral auxiliary groups was examined. Yields of the product alpha-aminophosphonothionates ranged from 17% to 75% after chromatography. The addition of DMTP to the benzaldimine derived from (S)-phenylglycinol afforded the highest diastereoselectivity (83:17), whereas addition of DMTP to the benzaldimine derived from threonine methyl ester and alanine methyl ester were far less diastereoselective, affording 38:62 and 61:39 ratios, respectively. Addition of DMTP to the benzaldimine derived from (R)-alpha-methylbenzylamine (78:22) and (S)-serine methyl ester (73:27) were intermediate in selectivity. DMTP addition to the imines formed between serine methyl ester and acetaldehyde and isobutyraldehyde gave 55:45 and 70:30 ratios, respectively, with the diastereoselectivity corresponding roughly to the size of the alpha-alkyl group. The stereochemistry of the newly formed alpha-stereocenters resulting from the addition of DMTP to (S)- and (R)-phenylglycinol benzaldimines was confirmed by conversion of the product alpha-aminophosphonothionates to the known enantiomers of phosphonophenylglycine.

Catalysis↗
PubMed2005

Diastereoselective intermolecular radical addition to nitrones.

The intermolecular radical addition to chiral nitrones 2, 4, 5, and 16 was studied. The isopropyl radical addition to Oppolzer's camphorsultam derivative 2 of glyoxylic nitrone proceeded with excellent diastereoselectivity to give the desired isopropylated product 3a accompanied by the diisopropylated product 3b. A high degree of stereocontrol in the reaction of cyclic nitrone 4 was achieved. The ethyl radical addition to nitrone 4 with triethylborane afforded the desired ethylated product 9a accompanied by the diethylated product 10a and the ethylated nitrone 11a. To evaluate the utility of cyclic nitrone 4, several alkyl radicals were employed in the addition reaction, which afforded the alkylated products 9b-d with excellent diastereoselectivities. In the presence of Mg(ClO(4))(2), the ethyl radical addition to BIGN 16 afforded selectively syn isomers. In contrast, the alkyl radical addition to 16 took place even in the absence of Lewis acid to give anti isomers.

Free Radicals↗
PubMed2000

Asymmetric synthesis of alpha-amino acids based on carbon radical addition to glyoxylic oxime ether

The first asymmetric synthesis of alpha-amino acids based on diastereoselective carbon radical addition to glyoxylic imine derivatives is reported. The addition of an isopropyl radical, generated from i-PrI, Bu(3)SnH, and Et(3)B in CH(2)Cl(2) at 25 degrees C, to achiral glyoxylic oxime ether 1 proceeded regioselectively at the imino carbon atom of the oxime ether group to give an excellent yield of the C-isopropylated product 2. The competitive reaction using glyoxylic oxime ether 1 and aldoxime ether 4 showed that the reactivity of the glyoxylic oxime ether toward nucleophilic carbon radicals was enhanced by the presence of a neighboring electron-withdrawing substituent. Thus, the alkyl radical addition to glyoxylic oxime ether 1 proceeded smoothly even at -78 degrees C, in contrast to the unactivated aldoxime ether 4. A high degree of stereocontrol in the carbon radical addition to the glyoxylic oxime ether was achieved by using Oppolzer's camphorsultam as a chiral auxiliary. The stannyl radical-mediated reaction of the camphorsultam derivative 6 with an isopropyl radical at -78 degrees C afforded a 96:4 diastereomeric mixture, 7a, of the C-isopropylated product. The reductive removal of the benzyloxy group of the major diastereomer (R)-7a, by treatment with Mo(CO)(6) and the subsequent removal of the sultam auxiliary by standard hydrolysis, afforded the enantiomerically pure D-valine (R)-12 without any loss of stereochemical purity. To evaluate the new methodology, a variety of alkyl radicals were employed in the addition reaction which gave the alkylated products 7 with excellent diastereoselectivity, allowing access to a wide range of enantiomerically pure natural and unnatural alpha-amino acids. Even in the absence of Bu(3)SnH, treatment of 6 with alkyl iodide and Et(3)B at 20 degrees C gave the C-alkylated products 7 with moderate diastereoselectivities. The use of Et(2)Zn as a radical initiator, instead of Et(3)B, was also effective for the radical reaction. The enantioselective isopropyl radical addition to 1 using (R)-(+)-2, 2'-isopropylidenebis(4-phenyl-2-oxazoline) and MgBr(2) gave excellent chemical yield of the valine derivative 2 in 52% ee.

Journal Article↗
PubMed2007

Enantioselectivity reversal by achiral additives in the Soai reaction: a kinetic understanding.

Numerical kinetic simulations have been employed to understand the origin of enantioselectivity reversal of chiral beta-amino alcohol catalysts occurring in the presence of their achiral analogs in the autocatalytic addition of diisopropylzinc to pyrimidine carbaldehydes (Soai reaction). In a preceding work (Rivera Islas, J.; Lavabre, D.; Grevy, J. M.; HernAndez Lamoneda, R.; Rojas Cabrera, H.; Micheau, J. C.; Buhse, T. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 13743-13748), we provided a possible explanation for the phenomenon of spontaneous mirror-symmetry breaking observed in this reaction. The effect of enantioselectivity reversal, giving rise to steep and abrupt transitions between opposed optically active states, has been identified by our current approach as another manifestation of such mirror-symmetry breaking capability. In the present case, we considered the involvement of the chiral catalyst and its achiral analog in the reaction network. Our modeling indicates that the enantioselectivity reversal can be either caused (i) by an interaction between the chiral and achiral additives or (ii) by an interaction of the customary products of the Soai reaction with the additives. The second option, which stands for the reversible inhibition of the chirally selective autocatalysts by the additives, could also explain a number of further additive effects in the Soai reaction reflecting the extraordinary sensitivity of this system toward the initial addition of almost any, even catalytically inactive, chiral substance.

Catalysis↗
PubMed2002

Quantifying the benefits of additional channels of multifocal VEP recording.

For some individuals and for some locations, multifocal visual evoked potentials (mfVEP) may be too small or appear 'too noisy' to be reliably measured. By adding electrodes, especially electrodes placed lateral to the midline, and by recording with multiple channels, the amplitude of the signal can be increased in some field locations. However, the addition of electrodes involves certain costs; the set-up time is longer and the data analysis more time consuming and complex. The objective of this study was to assess the benefits of adding electrodes by quantifying these benefits using a signal-to-noise measure. In addition to the typical midline placement of electrodes, two electrodes were placed 1 cm above and 4 cm lateral to the inion on each side. This allowed for 3 channels of recording and 3 additional, derived channels. The mfVEPs were recorded with a 60 sector, pattern-reversing display presented to one eye. Two 7 min records were obtained from 14 individuals with no known visual problems. The two records were averaged and a signal-to-noise (SNR) measure was obtained for every response from all 6 channels. For each sector of the display and each subject, the benefits of additional electrodes were quantified by comparing the SNR from the traditional midline channel to the best SNR from amongst the 6 channels. The number of responses exceeding any given criterion SNR value was increased with the additional channels. For example, 79% of the responses for the typical midline channel exceeded a SNR of 0.6 (a false positive rate of about 2.5%) and this increased to 93% when the best SNR value was used. As expected, summing the mfVEP responses from contiguous sectors also increased the SNR values. Additional electrodes and multiple channels of recording substantially improve the quality of the mfVEP records and the SNR measure provides a useful metric for assessing these benefits.

Adult↗
PubMed2004

Effect of fluoride addition on the properties of dental alginate impression materials.

Fluoride-containing dental alginate impression materials can exert a considerable reduction in enamel solubility. The objective was to evaluate the effects of fluoride addition in the alginate impression materials on the properties and subsequent release of fluoride. Four experimental alginate impression materials were studied. Materials were mixed with distilled water (control) or 100-ppm fluoride solution. One or two percent NaF, or 1% SnF2 was added to the materials, which were mixed with distilled water. Fluoride release, flexibility, recovery from deformation, setting time, compressive strength and elastic modulus were determined in accordance with the ISO 1563 and ANSI/ADA Spec. 18. Fluoride release increased after addition of fluoride, and the released amount was 0.762-14.761 ppm. Addition of NaF or SnF2 resulted in higher fluoride release than the control group (p < 0.05). After fluoride addition, flexibility was 15.45-20.27%, and the recovery from deformation did not change except one material. Compressive strength after fluoride addition was 0.36-1.12 MPa. Addition of NaF or SnF2 in an alginate impression material may result in effective release of fluoride without deteriorating the properties of material itself.

Alginates↗
PubMed2003

Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML.

t(8;21)(q22;q22) is the most frequently observed karyotypic abnormality associated with acute myeloid leukemia (AML), especially in FAB M2. Clinically, this type of AML often shows eosinophilia and has a high complete remission rate with conventional chemotherapy. t(8;21) AML is also frequently associated with additional karyotypic aberrations, such as a loss of the sex chromosome; however, it is unclear whether these aberrations change the biological and clinical characteristics of t(8;21) AML. To investigate this issue, 94 patients with t(8;21) AML were categorized according to their additional karyotypic aberrations, which were detected in more than three cases, and then morphologic features, phenotypes, expression of cytokine receptors, and clinical features were compared to t(8;21) AML without other additional aberrant karyotypes. t(8;21) AML with loss of the sex chromosome and abnormality of chromosome 9 were found in 27 cases (29.3%) and 10 cases (10.6%), respectively; however, no differences were observed from the t(8;21) AML without other additional karyotypes in terms of morphological and phenotypic features. There was also no significant difference in the clinical outcome among these three groups. On the other hand, trisomy 4 was found in three cases (3.2%) and these cells showed low expressions of CD19 (P=0.06) and IL-7 receptor (P=0.05), and high expressions of CD33 (P=0.13), CD18 (P=0.03), and CD56 (P=0.03) when compared to t(8;21) AML without additional karyotypes. Moreover, all three t(8;21) AML cases with trisomy 4 did not show eosinophilia in their bone marrow and died within 2.4 years. These observations suggest that additional karyotypic aberration, t(8;21) with trisomy 4 is rare, but it may constitute a distinctive subtype of t(8;21) AML.

Adolescent↗
PubMed2006

Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome.

Clinical heterogeneity within t(12;21) or TEL/AML1-positive ALL (25% of childhood common/preB ALL) indicates that additional genetic changes might contribute to outcome. We studied the relation between additional genetic changes in TEL(ETV6) and AML1(RUNX1) (FISH), drug sensitivity (MTT assay) and clinical outcome in 143 DCOG and COALL-treated t(12;21)-positive ALL patients. Additional genetic changes in TEL and AML1 were present in 83% of the patients, and consisted of (partial) deletion of the second TEL gene (70%), an extra AML1 gene (23%) or an extra der(21)t(12;21) (10%). More than one additional change was observed in 20%. Disease-free survival (pDFS) of DCOG patients without additional genetic changes (4 years pDFS +/- s.e. 53 +/- 17%) and of those with an extra der(21)t(12;21) (60 +/- 22%) is poorer than that of compared to patients with other additional genetic changes in TEL or AML1 (79 +/- 6%; P-trend = 0.02). This was mainly due to the occurrence of early relapses within 2.5 years after the first diagnosis. Similar observations were found in the COALL cohort, albeit not significant owing to limited follow-up. Multivariate analysis including age, WBC and genetic abnormalities in TEL and/or AML1 showed that especially, in vitro resistance to prednisolone (hazard ratio 5.78, 95% CI 1.45-23.0; P=0.01) is an independent prognostic factor in DCOG- and COALL-treated t(12;21)-positive ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Cyclic beta-amino acid derivatives: synthesis via lithium amide promoted tandem asymmetric conjugate addition-cyclisation reactions.

The product distribution upon conjugate addition of homochiral lithium N-benzyl-N-alpha-methylbenzylamide to dimethyl-(E,E)-nona-2,7-dienedioate can be controlled to give either the cyclic 1,2-anti-1,6-anti-beta-amino ester (derived from conjugate addition and intramolecular enolate cyclisation) or the acyclic bis-beta-amino ester derivative (derived from double conjugate addition) in high de. The introduction of a protected nitrogen functionality into the diester skeleton facilitates, after conjugate addition and intramolecular enolate cyclisation, the asymmetric construction of piperidines in high de; variation in the N-protecting group indicates that the highest stereoselectivity is observed with alpha-branched N-substituents. Tandem conjugate addition-aldol reactions can also be achieved stereoselectively, with lithium amide conjugate addition to epsilon- and zeta-oxo-alpha,beta-unsaturated esters giving the corresponding five and six membered cyclic beta-amino esters in high de. N-deprotection by hydrogenolysis of the products arising from these reactions furnishes a range of polyfunctionalised transpentacin and transhexacin derivatives in high de and ee.

Amides↗
PubMed1991

The effect of time of addition of glutamine or nucleosides on proliferation of rat cervical lymph-node T-lymphocytes after stimulation by concanavalin A.

1. Addition of concanavalin A to T-cell lymphocytes from rat cervical lymph nodes increases the activity of glutaminase within 1 h and those of carbamoyl-phosphate synthase II and aspartate transcarbamoylase within 3 h. There was a similar time course for the effects of concanavalin A on rates of glutamine utilization, which was increased within 1 h, and on pyrimidine nucleotide synthesis, which was increased by 40% at 2 h and by 100% at 3 h. 2. A delay in the addition of glutamine to the culture medium after addition of concanavalin A caused a decrease in [3H]thymidine incorporation only after 4-6 h. In the absence of glutamine, delay in addition of guanosine or inosine caused a decrease in [3H]thymidine incorporation only after 6-8 h after the addition of concanavalin A. 3. In contrast, a delay in addition of adenosine or uridine to the culture medium had an immediate effect (i.e. within 2 h) on the rate of incorporation of [3H]thymidine. It is suggested that adenosine and uridine have specific effects on proliferation via specific receptors for these nucleosides in the membrane.

Animals↗
PubMed2004

Additional reverse transcription-polymerase chain reaction of peripheral slices is not superior to analysis of the central slice in sentinel lymph nodes from melanoma patients.

BACKGROUND: The status of the sentinel lymph node (SLN) is an important prognostic factor in patients with cutaneous melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) has been used as a sensitive means of detecting tumour cells in SLNs. OBJECTIVES: To determine whether RT-PCR analysis of the SLN using both the central and the peripheral slices is more sensitive than molecular analysis of the central slice only. METHODS: Eighty-three SLNs from 59 patients with primary cutaneous melanoma were identified by SLN mapping. All SLNs were bisected along their longitudinal axis to produce two equal halves. One half was used for histology and immunohistochemistry, and the other was analysed by RT-PCR for tyrosinase and MelanA. Parallel to the longitudinal axis, one central slice (approximately 2 mm in thickness) was cut manually. This central slice was used for our standard RT-PCR protocol. In the current study, up to eight additional peripheral slices (each approximately 2 mm in thickness) were cut parallel to the existing cut surface. These peripheral slices were analysed by additional RT-PCR. RESULTS: Standard RT-PCR of the central slice yielded positive results in 34 of 59 patients (57%). Additional RT-PCR of peripheral slices demonstrated positive findings in six additional patients (10%) who were initially negative by standard RT-PCR of the central slice. In detail, seven of those 34 patients positive by standard RT-PCR of the central slice had positive histological findings. In each of these seven patients, RT-PCR was positive both in the central slice as well as in the peripheral slices. The remaining 27 patients with positive RT-PCR results of the central slice showed negative histological findings. Only nine (33%) of these 27 patients had a positive RT-PCR also in the peripheral slices. Finally, all 25 patients with negative RT-PCR results in the central slice showed negative histological findings. Six of these patients (24%) revealed positive RT-PCR results on the analysis of peripheral slices. However, three of these patients expressed only MelanA but not tyrosinase. Thirty lymph nodes from 24 nonmelanoma patients served as negative controls for RT-PCR. In three of these 24 patients (13%) expression of MelanA but not tyrosinase was detected by RT-PCR. CONCLUSIONS: Molecular analysis of peripheral slices yielded six additional patients (10%) positive by RT-PCR who were initially negative by standard RT-PCR of the central slice. However, three of these six patients were found to express only MelanA but not tyrosinase. As MelanA expression was also found in 13% of control lymph nodes, positive MelanA expression alone in SLNs of melanoma patients requires cautious interpretation in order to avoid false-positive findings. Thus, additional molecular processing of peripheral slices did not significantly increase the number of patients with RT-PCR-positive SLNs.

Adult↗
PubMed2003

The effect of the addition of poly (methyl methacrylate) fibres on the transverse strength of repaired heat-cured acrylic resin.

The aim of the present study was to investigate the effect of addition of an experimental poly (methyl methacrylate) (PMMA) fibre in linear form, 0.75 mm in diameter on the transverse strength of repaired heat-cured poly (methyl methacrylate) denture base material. Specimens of heat-cured PMMA were repaired with an autopolymerizing acrylic resin and an autopolymerizing acrylic resin together with the addition of untreated and surface-treated PMMA fibres in different arrangements. The transverse bend test was carried out using a LIoyd's Instrument Material Testing Machine. From the results, it can be concluded that the box incorporated into the repair joint produced a significant decrease in the moduli of elasticity and rupture which may be due to stress concentration effects. The addition of one layer of untreated PMMA fibres significantly decreased the modulus of rupture. The addition of two layers of untreated fibres produced a slight but statistically non-significant increase in the modulus of rupture. The addition of surface-treated (with butadiene styrene latex emulsion) fibres into the repair complex gave no improvement compared with the addition of untreated fibres in terms of transverse strength. There was an insignificant decrease in the modulus of rupture compared with the untreated fibres.

Acrylic Resins↗
PubMed2000

Glycosyl-phosphatidylinositol-anchor addition signals are processed in Nicotiana tabacum.

Recent studies have demonstrated the existence of glycosyl-phosphatidylinositol (GPI)-anchored proteins in higher plants. In this study we tested whether GPI-addition signals from diverse evolutionary sources would function to link a GPI-anchor to a reporter protein in plant cells. Tobacco protoplasts were transiently transfected with a truncated form of the Clostridium thermocellum endoglucanase E reporter gene (celE') fused with a tobacco secretion signal (PR-1a) at the N-terminus and either a yeast (GAS1), mammalian (Thy-1) or putative plant (LeAGP-1) GPI-anchor addition signal at the C-terminus. The yeast and plant C-terminal signals were found to be capable of directing the addition of a GPI-anchor to the endoglucanase protein (EGE') as shown by the sensitivity of the lipid component of GPI to phosphatidylinositol-specific phospholipase C (PI-PLC) digestion. In contrast, the mammalian signal was poorly processed for anchor addition. When EGE' was fused to a truncated form of the LeAGP-1 signal (missing three amino acids predicted to be critical to signal cleavage and anchor addition), a GPI-anchor was not linked to the EGE' protein indicating the necessity for the missing amino acids. Our results show the conservation of the properties of GPI-signals in plant cells and that there may be some similar preferences in GPI-addition signal sequences for yeast and plant cells.

Amino Acid Sequence↗
PubMed2005

Genetic association studies in complex disease: disentangling additional predisposing loci from associated neutral loci using a constrained - permutation approach.

In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi-allelic loci only. We wanted to develop a method that is more suited for multi-allelic loci, such as microsatellite markers. We propose the Additional Disease Loci Test (ADLT): the alleles at an additional locus are permuted within the subsample of haplotypes that have identical alleles at the predisposing locus. The hypothesis being tested is, whether the predisposing locus is the sole factor predisposing to the trait that is in LD with the additional locus under study. We applied ADLT to simulated datasets and a published dataset on Type 1 Diabetes, genotyped for microsatellite markers in the HLA-region. The method showed the expected number of false-positive results in the absence of additional loci, but proved to be more powerful than existing methods in the presence of additional disease loci. ADLT was especially superior in datasets with less LD or with multiple predisposing alleles. We conclude that the ADLT can be useful in identifying additional disease loci.

Diabetes Mellitus, Type 1↗
PubMed1998

Safety and utility of atropine addition during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction.

OBJECTIVE: To assess the feasibility safety and side effects of the addition of atropine to dobutamine stress echocardiography for the detection of viable myocardium in patients with left ventricular dysfunction (ejection fraction < or = 35%) prior to coronary revascularization. BACKGROUND: The assessment of viable and/or ischaemic myocardium has high prognostic value as regards improvement of function and survival after coronary revascularization. The addition of atropine to dobutamine during echocardiographic testing for the presence of viable myocardium is not common practice. Consequently, no data exist on the safety and additional diagnostic value of this practice. METHODS: Two hundred patients with left ventricular ejection fraction < or = 35% were studied. RESULTS: Test end-points were: target heart rate in 164 (82%) of the patients, severe angina in 18 (9%), maximum dobutamine-atropine dose in six (3%), severe ST segment changes in five (2%), cardiac arrhythmias in four (2%), and hypotension in three (1%). Viability could be assessed echocardiogaphically in 105/200 (53%) from a biphasic response (improvement of wall motion with low dose dobutamine and worsening with high dose), in 93 from ischaemia and in 12 from sustained or late improvements. In 36/105 (34%) patients, ischaemic myocardium could only be assessed after the addition of atropine. Cardiac arrhythmias occurred in 11/200 (6%) and hypotension (decrease of systolic blood pressure >30 mmHg) in 21/200 (11%). Neither the use of atropine nor the induction of ischaemia were associated with an increased incidence of cardiac arrhythmias or hypotension. CONCLUSIONS: In a large group of patients with severe left ventricular dysfunction, dobutamine stress echocardiography is feasible and safe in 186/200 (93%); the addition of atropine was necessary in 34% to assess myocardial viability. Hypotension and cardiac arrhythmias were the most frequent side effects, but were not related to the induction of ischaemia or addition of atropine.

Adult↗
PubMed2002

Addition of an extra dose of salmeterol Diskus to conventional dose of salmeterol Diskus in patients with COPD.

Patients experiencing dyspnoea can request an additional dose of salmeterol during the dose interval for the control of their symptoms, although under treatment with salmeterol. In this study we have explored the effects on respiratory function of an additive dose of salmeterol Diskus in 15 chronic obstructive pulmonary disease (COPD) patients in regular treatment with a conventional dose of 50 microg salmeterol. On two different days, patients inhaled 50 microg Diskus. After 240 min, they inhaled additional 50 microg salmeterol Diskus (salmeterol arm) or placebo Diskus (placebo arm). Lung function was controlled before first drug administration and 0.5, 1, 2, 3, 4, 4.5, 6, 8, 10, and 12 h thereafter. The mean (95% CI) peak increase in FEV1 from baseline was reached after 4 h in the salmeterol arm (0.174 L; 0.144-0204) and after 5 h (0.141 L; 0.115-0.168) inthe placebo arm; after 12 h, the mean (95% Cl) increase in FEV1 from basal values was still 0.149 L (0.119-0.179) in salmeterol arm, but only 0.041 L (0.017-0.064) in placebo arm. The mean (95% CI) FEV1 AUC0-12h for all patients were 2.01 (1.72-2.30) L when salmeterol was added and 1.30 (1.03-1.58) L when placebo was inhaled. The difference (mean; 95% CI) between the FEV1 AUC0-12h of the two arms (0.71 L; 0.47-0.95) was statistically significant (P<0.0001), although the difference (mean; 95% CI) between the FEV1 AUC0-4h of the two treatments (0.08 L; -0.02-0.18) was notstatistically significant (P=0.126). The addition of an extra dose of salmeterol did not significantly increase the heart rate or decrease the SpO2. This study suggests that the addition of an extra dose of salmeterol does not give room for further increase in peak FEV1, but the effect of adding salmeterol to salmeterol is largely additive when considering the duration of action and safe.

Albuterol↗