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Free and cued selective reminding and selective reminding in the elderly.

Free and Cued Selective Reminding (FCSR) differs from Selective Reminding (SR) because of a study procedure which controls cognitive processing and a reminding procedure which allows for cued recall. Performance on FCSR and SR was compared in two studies to determine which test produces better recall and to identify the factors that account for the superior recall. When the tests were administered to very elderly normal subjects using the standard clinical protocol, twice as many words were retrieved from long-term memory in FCSR than SR. The second experiment, which manipulated study and reminding conditions in a younger sample of normal elderly, suggests that the improvement in free recall was due to the study procedure and the method of reminding.

Aged↗

The delta-selective opioid peptide dermenkephalin and the mu-selective hybrid peptide dermenkephalin-[1-4]-dermophin-[5-7] display strikingly different conformations despite identical tetrapeptide N-termini. A quantitative 2-D NMR and molecular modeling analysis.

The selective recognition of the aminoterminal binding pharmacophore Tyr-D-Xaa-Phe of the opioid heptapeptide dermorphin, Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 (DRM)1, and of dermenkephalin, Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 (DREK), by the mu-opioid receptor and delta-opioid receptor, respectively, depends upon the constitution / conformation of the C-terminal tripeptide. The hybrid peptide DREK-[1-4]-DRM-[5-7] is very potent at, and exquisitely selective for the mu-opioid receptor, and differs only from dermenkephalin by its C-terminal tripeptide. Comparison of the structural features of DREK-[1-4]-DRM-[5-7] and dermenkephalin by nmr analysis and molecular modeling revealed striking differences, as well in the trans (Tyr5 - Pro6) isomer (population 75%) than in the cis isomer.. Whereas the folded C-terminal tail of dermenkephalin influenced the tertiary structure of the N-terminal tetrapeptide and placed the Tyr1 and Phe3 aromatic rings in definite orientations that are best suited for the delta-receptor, there were only weak contacts, as shown by NOE data, between the aminoterminal and carboxyterminal parts of the hybrid peptide. This promoted increased flexibility of the whole backbone and relaxed orientations for the side-chains of Tyr1 and Phe3 that are compatible with the mu-receptor but unsuitable for the delta-receptor. The steric hindrance introduced by Pro6 in DREK-[1-4]-DRM-[5-7], plus the absence of large hydrophobic side-chains in positions 5 and 6 may prevent close contacts between the N-terminal and C-terminal domains and reorientation of the main pharmacophoric elements Tyr1 and Phe3.

Amino Acid Sequence↗

CD133+ cell selection is an alternative to CD34+ cell selection for ex vivo expansion of hematopoietic stem cells.

CD133 is a new stem cell antigen that may provide an alternative to CD34 for the selection and expansion of hematopoietic cells for transplantation. This study compared the expansion capacities of CD133(+) and CD34(+) cells isolated from the same cord blood (CB) samples. After 14 days culture in stroma-free, serum-free medium in the presence of stem cell factor (SCF), Flt3-1, megakaryocyte growth and development factor (MGDF), and granulocyte colony-stimulating factor (G-CSF), the CD133(+) and CD34(+) fractions displayed comparable expansion of the myeloid compartment (CFC, LTC-IC, and E-LTC-IC). The expansion of CD133(+) CB cells was up to 1262-fold for total cells, 99-fold for CD34(+) cells, 109-fold for CD34(+) CD133(+) cells, 133-fold for CFU-GM, 14.5-fold for LTC-IC, and 7.5-fold for E-LTC-IC. Moreover, the expanded population was able to generate lymphoid B (CD19(+)), NK (CD56(+)), and T (CD4(+) CD8(+)) cells in liquid or fetal thymic organ cultures, while expression of the homing antigen CXCR4 was similar on expanded and nonexpanded CD133(+) or CD34(+) cells. Thus, the CD133(+) subset could be expanded in the same manner as the CD34(+) subset and conserved its multilineage capacity, which would support the relevance of CD133 for clinical hematopoietic selection.

AC133 Antigen↗

Analysis of 1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection.

An analytical procedure was developed for the analysis of 1,3-butadiene, acrolein, isoprene, benzene and toluene in the gas phase of cigarette smoke and environmental tobacco smoke (ETS) utilizing cryogenic gas chromatography-mass selective detection (GC-MSD). The MSD was operated in the selective ion monitoring (SIM) mode. The compounds of interest eluted in less than 15 min. The gas phase of freshly generated mainstream smoke was introduced into the GC-MSD via a 10-port gas sampling valve on a puff-by-puff basis. This method minimizes the ageing of tobacco smoke. The levels of 1,3-butadiene in the mainstream smoke ranged from 16 to 75 micrograms/cigarette. The gas phase of sidestream smoke was trapped in methanol using three midget impingers at -78 degrees C. The amount of 1,3-butadiene in the sidestream smoke ranged from 205-361 micrograms/cigarette. The concentration of 1,3-butadiene in ETS in a smoke-filled bar amounted to 2.7-4.5 micrograms/m3.

Acrolein↗

Quantitative determination of selected compounds in a Kentucky 1R4F reference cigarette smoke by multidimensional gas chromatography and selected ion monitoring-mass spectrometry.

Eight compounds from a Kentucky 1R4F reference cigarette smoke condensate have been determined by selected ion monitoring-mass spectrometry (SIM-MS) to confirm the validity of multidimensional gas chromatography (MDGC) as a quantitative tool in complex mixture analyses. Four electrostatically precipitated smoke condensate samples of 100 cigarettes each are dissolved individually in 25 mL of 2-propanol. The 2-propanol contains two methyl esters (C8 and C14) and seven deuterium-labeled compounds used as internal standards (IS). Analysis of the compounds of interest, pyridine; acetamide; acrylamide; phenol; o-, m-, and p-cresol; and quinoline, is accomplished by using two heartcuts. Heartcut times of the MDGC analysis are selected such that at least one IS is transferred with each group of compounds being analyzed. This study shows that the MDGC technique previously developed and described can be used for quantitative analyses. A comparison is made between the two types of internal standards. The results obtained for both types of internal standards agree within 20% of each other, on the average, with higher standard deviations for approximately 60% of the compounds where methyl esters are used as internal standards.

Chromatography, Gas↗

Examination of the enantiomeric distribution of certain monoterpene hydrocarbons in selected essential oils by automated solid-phase microextraction-chiral gas chromatography-mass selective detection.

A viable approach for the determination of sources of essential oils based on automatic injection solid-phase microextraction-chiral-gas chromatography-mass selective detection is demonstrated. With no sample preparation, it is shown that the source of essential oils such as peppermint, spearmint, and rosemary can be easily distinguished. Short fiber exposure times of approximately 6 s to the headspace above submicroliter quantities of the selected oils are all that is required to obtain both the required sensitivity and resolution to afford analyses with excellent reproducibilities (relative standard deviation values consistently less than 5.0%).

Autoanalysis↗

Selective antimicrobial modulation of human microbial flora: infection prevention in patients with decreased host defense mechanisms by selective elimination of potentially pathogenic bacteria.

To reduce the frequency and severity of bacterial infection, selective antimicrobial modulation (SAM) was applied in 39 patients with severely decreased host defense mechanisms. The objective was to eliminate potentially pathogenic aerobic microorganisms with minimal disturbance of the normal anaerobic bacterial flora. Elimination of potentially pathogenic aerobic microorganisms was easily accomplished in patients not infected at hospitalization. The anaerobic flora seemed to be undisturbed, and selection of or overgrowth with resistant microorganisms did not occur. The microbiologic results of the SAM regimen correlated with the incidence of infection. Only three major infections occurred in 23 patients who were free of potentially pathogenic microorganisms; 10 major infections occurred in 16 patients who were not free of potential pathogens. Seven of these 10 infections were present at hospitalization. The incidence of major infections was 47% in the patients on the SAM regimen and 82% in a group of control patients with a similar risk of infection.

Adolescent↗

Non-repetitive single-chain Fv linkers selected by selectively infective phage (SIP) technology.

By using the selectively infective phage (SIP) technology, we selected non-repetitive linkers for a single-chain Fv fragment to have genes more robust against deletions in PCR-based gene assembly and directed evolution experiments than is the case for the classical (Gly4Ser)3 linker. We designed linkers encoding turns at both ends and random positions in the middle where glycines and polar and charged residues were allowed to occur. After only a single round of SIP, all clones obtained were fully functional. Properties such as antigen binding constants, urea denaturation curves and expression of soluble scFv fragments were identical with those of the parental fragment with the (Gly4Ser)3 linker. This demonstrates that SIP is a very fast and powerful technique to remove rapidly sequences of poor functionality, exclusively yielding sequences of the desired overall property in a single round.

Amino Acid Sequence↗

Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada.

OBJECTIVES: Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), potentially increasing treatment costs due to additional physician visits and wastage of medication. This study assessed drug switching and associated costs among elderly chronic NSAID users. METHODS: Data for patients who filled their first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the first day without NSAID exposure following the index filling date, or death. Patients could switch NSAIDs several times during follow-up. Person-days of exposure were categorized by the NSAID most recently dispensed: rofecoxib, celecoxib, Arthrotec(R) or non-Arthrotec (nA) nsNSAID. Cox regression models compared time to switch between groups, adjusting for patient baseline characteristics. Upon a switch, pills remaining from the previous prescription were considered wasted. The costs of wasted pills and switch-associated physician visits were estimated. RESULTS: Throughout follow-up, patients filled 38 267 prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388 for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38-0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib prescriptions, respectively. These costs were 34% higher for Arthrotec prescriptions than for nA-nsNSAIDs. CONCLUSIONS: Compared with recipients of nsNSAIDs, coxib recipients were less likely to switch medications and had approximately half the adjusted costs for switching-related wasted resources per prescription.

Aged↗

Improved results with selective distal splenorenal shunt in a highly selected patient population. A prospective study.

In a 5-year period 299 patients were admitted to the Heinz-Kalk Hospital with bleeding esophageal varices. Patients with acute bleeding were treated with endoscopic sclerotherapy. Sessions were performed as many times as needed for each individual case. One hundred seventy-eight patients in Child-Pugh class C were excluded from surgical treatment; the remaining 121 patients (Child AB) were selected using the following criteria: liver volume (ultrasound) between 1000 to 2500 ml, portal perfusion (sequential scintigraphy) more than 30%, no activity or progression of liver disease proved by biopsy, no stenosis of the hepatic arteries, and suitable anatomy to perform the Warren shunt. Only 32 patients fulfilled these criteria. In seven of these cases the shunt was technically impossible to perform. Operative mortality rate was 8% and the late mortality rate was 12%. No history of rebleeding, encephalopathy, and/or shunt thrombosis was recorded. Five-year survival rate, according to the method of Kaplan-Meier was 75%. We conclude that the Warren shunt is the treatment of choice for elective management of bleeding esophageal varices. The postoperative results can be improved with strict selection using the above criteria. The preoperative use of sclerotherapy has a positive influence. Prophylactic management to prevent encephalopathy is also recommended.

Adolescent↗

U1 snRNP can influence 3'-splice site selection as well as 5'-splice site selection.

To address the mechanisms that underlie splice site selection and splice site partner assignment, we analyzed the splicing of yeast (Saccharomyces cerevisiae) transcripts containing splice site region duplications. When the 5'-splice site region was duplicated, both sites were utilized to the same extent, indicating little or no influence of proximity on 5'-splice site choice. However, the effect of a 5'-mutant site was greatly enhanced by the presence of an adjacent wild-type site, and this effect was reversed by the restoration of base-pairing with U1 snRNA. 3'-Splice site choice was apparently influenced by proximity, as the site closest to the 5'-splice site was greatly preferred. Studies with strains carrying some U1 snRNA mutations showed an increase in the use of the distal 3'-splice site, indicating a role for U1 snRNP in 3'-splice site selection. The data are compared with those from mammalian splice site choice experiments and suggest mechanisms that influence differential splice site choice as well as exon skipping.

Base Sequence↗

Auditory selective attention in young and elderly adults: the selection of single versus conjoint features.

The effects of aging on the behavioral and neurophysiological correlates of auditory selective attention were investigated when selection was between either unidimensional or multidimensional stimuli. Attentional processes were studied by recording event-related brain potentials (ERPs) from 16 young (M = 22 years) and 16 elderly adults (M = 74 years) while they detected target tones based on a single location cue or a conjunction of location and pitch cues. Performance declined from the single- to the conjoint-cue task for both age groups but more so for the elderly. The ERP data showed that both age groups used a hierarchical processing strategy to perform the conjoint-cue task, but processing of the pitch dimension took longer for the elderly than for the young. The ERP data also showed that the scalp distribution of a late aspect of the waveform was more restricted in both anterior and posterior directions for the elderly. This suggests that frontal-lobe dependent attentional processes may be less efficacious with aging.

Acoustic Stimulation↗

An alternative to current thinking about positive selection, negative selection and activation of T cells.

Given that recognition by the T-cell receptor (TCR) of allele-specific determinants on major histocompatibility complex (MHC)-encoded restricting elements (Rs) is germline encoded, whereas recognition of peptide (P) is somatically encoded, two combining site repertoires, anti-R and anti-P, are implied. As a consequence, the three pathways of T cells, positive selection, negative selection and activation, must be signalled by qualitatively distinct interactions engaging the TCR. These are spelled out as they provide an alternative to the current thinking that these pathways depend on affinity-based quantitatively distinguishable interactions.

Cell Differentiation↗

A selective NK-2 antagonist blocks the increase of canine colonic tone and ileal contractions induced by the NK-2 selective receptor agonist, [beta Ala8] neurokinin A-(4-10).

BACKGROUND: The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non-peptide NK-2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK-2 receptor agonist [beta Ala8] neurokinin A-(4-10). METHODS: Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum. 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK-2 antagonist SR48968, 10, 100, 1000 micrograms/kg, followed after 30 min by 2 micrograms/kg of the agonist [beta Ala8] neurokinin A-(4-10). Experiments were replicated twice in each dog. RESULTS: The NK-2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose-dependent fashion (Spearman's rank, r = 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [beta Ala8] neurokinin A-(4-10) increased ileal contractions: pre-treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [beta Ala8] neurokinin A-(4-10) interrupted the motility front; this effect was not antagonized by SR48968. CONCLUSIONS: SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK-2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract.

Animals↗

The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a non-selective non-steroidal anti-inflammatory drug or a cyclo-oxygenase-2-selective inhibitor.

BACKGROUND: The effect of low-dose aspirin on endoscopic ulcer incidence in cyclo-oxygenase-2-selective inhibitor or non-selective non-steroidal anti-inflammatory drug users remains controversial. AIM: To compare prospectively the incidence of endoscopic ulcers in healthy subjects receiving low-dose aspirin plus celecoxib or naproxen. METHODS: In this double-blind, placebo-controlled, 1-week study, subjects (50-75 years) were randomized to receive aspirin 325 mg o.d. plus either celecoxib 200 mg o.d., naproxen 500 mg b.d., or placebo. Baseline and end of study endoscopies were performed. The primary end point was incidence of one or more gastric and duodenal ulcers. RESULTS: A lower incidence of gastric and duodenal ulcers was seen in celecoxib/aspirin-treated subjects (19%) vs. naproxen/aspirin (27%; RR: 0.63, 95% CI: 0.44-0.92). Both naproxen/aspirin and celecoxib/aspirin groups demonstrated a higher incidence of gastric and duodenal ulcers vs. placebo/aspirin (8%; RR: 3.7, 95% CI: 1.8-7.6 and RR: 2.6, 95% CI: 1.2-5.8, respectively). CONCLUSIONS: Fewer endoscopic ulcers were observed in patients treated with celecoxib/aspirin vs. naproxen/aspirin. However, celecoxib/aspirin was associated with a significantly higher incidence of gastric and duodenal ulcers than aspirin alone. Further studies are required to determine the generalizability of these findings in the aspirin users and to determine the appropriate strategy to minimize risk in susceptible patients.

Aged↗

Haemodynamic effects of cigarette smoking during chronic selective and non-selective beta-adrenoceptor blockade in patients with hypertension.

1 Haemodynamic effects of cigarette smoking before and during chronic treatment with propranolol and metoprolol were studied in 16 patients with essential hypertension. 2 Smoking of cigarettes induced an increase in blood pressure of the same degree in all experimental sessions. Heart rate increased by 16 beats/min during smoking alone, but increased significantly less, when a beta-adrenoceptor blocker was used. Forearm blood flow decreased during smoking in both medication periods. 3 Plasma adrenaline rose significantly during smoking from 0.37 nmol/l to 0.77 nmol/l; plasma noradrenaline did not change. 4 It is concluded that the blood pressure changes induced by smoking are not essentially altered during chronic treatment with selective or non-selective beta-adrenoceptor blockade. Only the increase in heart rate is significantly less pronounced during treatment with both drugs.

Adolescent↗

Continuous culture selection of bifidobacteria and lactobacilli from human faecal samples using fructooligosaccharide as selective substrate.

The human large intestine contains a large and diverse population of bacteria. Certain genera, namely Bifidobacterium and Lactobacillus, are thought to exert health-promoting effects. Prebiotics such as fructooligosaccharides (FOS) have been shown to stimulate the growth of endogenous bifidobacteria. In this study, changes of lactic acid producing bacteria in continuous culture fermentors (semi-defined, anaerobic medium containing 5 g 1(-1) FOS, dilution rate of 0.1 h-1, pH 5.5) were followed over a 21 d period after inoculation with blended human faeces from four healthy adults. Samples were also taken every 3 d for influent/effluent FOS, short chain fatty acid (SCFA), lactate and microbiological analyses. Results showed that SCFA concentrations decreased abruptly 1 d after inoculation while lactate concentrations increased. Classical methods of enumeration using selective media showed that the proportion of total culturable count represented by bifidobacteria and lactobacilli increased from 11.9% on day 1 to 98.1% on day 21. However, molecular methods using genus-specific 16S rRNA oligonucleotide probes indicated that the bifidobacterial population maintained a level between 10 and 20% of total 16S rRNA during the first 6 d and disappeared rapidly when the maximum concentration of lactate was reached. Lactobacilli, which were initially present in low numbers, increased until day 9 and remained at high levels (20-42% of total 16S rRNA) to day 21, with the exception of day 18. Although FOS has usually been regarded as a selective substrate for bifidobacteria, these observations suggest that: (1) lactobacilli are also able to use FOS, (2) lactobacilli can out-compete bifidobacteria in continuous culture at pH 5.2-5.4 when FOS is the primary carbon and energy source, and (3) bifidobacteria can grow faster on FOS than lactobacilli under controlled conditions.

Adult↗

Long term follow-up of patients following successful selective and non-selective portasystemic shunt surgery.

The long term morbidity and mortality of two consecutive groups of patients undergoing successful shunt surgery for bleeding oesophageal varices has been studied. Twenty-seven patients with a non-selective shunt in the form of a mesocaval Dacron 'H' graft and 21 patients with selective variceal decompression via a distal lienorenal shunt, all of whom had a patent shunt on discharge from hospital, were included in the study. Shunt associated encephalopathy was documented in 77% of the patients following mesocaval shunts and only 19% of patients following distal lienorenal surgery. Other postoperative morbidity was largely related to problems with the synthetic Dacron graft. Late shunt blockage, often resulting in recurrent variceal bleeding, was documented in 25% of these patients and shunt infection was responsible for complicating fatal disseminated sepsis in 18.5%. Long term survival, as assessed by life table analysis, following distal lienorenal shunt surgery was consistently better than that following mesocaval shunts. This was largely due to specific problems which could be directly related to the synthetic nature of the Dacron graft. It is concluded that the mesocaval Dacron interposition graft carries the potentially lethal long term complications of shunt blockage and infection rendering it unsuitable as a portasystemic shunt. Provided that successful surgery can be performed the distal lienorenal shunt may be a more appropriate alternative due to its reduced shunt related morbidity and, possibly, mortality.

Blood Vessel Prosthesis↗