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PubMed2004

Phosphate addition to hemodiafiltration solutions during continuous renal replacement therapy.

OBJECTIVE: Hypophosphatemia often occurs during continuous renal replacement therapy (CRRT). The addition of phosphate to dialysate and replacement solutions facilitates phosphate handling, but the risk of precipitation with calcium within these solutions has not been addressed. DESIGN AND SETTING: Experimental study with a retrospective observational study in a medico-surgical intensive care unit. METHODS AND PATIENTS: We tested the addition of phosphate to calcium-rich lactate- and bicarbonate-based solutions (Hemosol LG2 and Hemosol B0) used in CRRT to see whether precipitation occurs. Two milliliters of potassium phosphate added to 5-l bags gives a physiological phosphate concentration of 1.2 mmol/l. In addition, calcium and phosphate homeostasis was retrospectively evaluated in 20 consecutive CRRT patients where potassium phosphate had been added to these solutions. MEASUREMENTS AND RESULTS: Total and ionized calcium, phosphate, pH, PCO(2) and bicarbonate remained essentially unchanged 5 h after the addition of 2 ml of potassium phosphate to 5-l Hemosol solutions. Visual inspection did not reveal any precipitate. Of the 20 patients studied, 14 received more than 24 h of phosphate supplementation to dialysate and replacement solutions. Phosphate remained stable throughout CRRT despite phosphate intake from nutrition in 11 cases. No adverse event was noted on potassium, calcium, pH and bicarbonate homeostasis. CONCLUSIONS: The addition of phosphate to Hemosol solutions does not precipitate with the calcium within these solutions. This practical method effectively prevents hypophosphatemia in CRRT patients.

Aged↗

PubMed2002

An additive factor analysis of the effect of sub-anaesthetic doses of nitrous oxide on information processing: evidence for an impairment of the motor adjustment stage.

RATIONALE: Nitrous oxide (N(2)O) inhalation, at subanaesthetic concentrations, impairs choice reaction time (RT). However, the functional locus of this effect remains to be ascertained. In the present study, this issue was investigated by applying the additive factor logic to the RTs of rats performing a visuo-motor task. METHOD: The task consisted of either a left-side or a right-side body displacement to a visual stimulus displayed in either the left or right hemispace. The experimental design involved the manipulation of two task factors (stimulus luminance and foreperiod duration) the effects of which are additive on RT. Inhaled N(2)O (from 0% to 60%) was varied as the third factor of the design. RESULTS: N(2)O prolonged RT in a dose-dependent manner and this effect was additive with that of stimulus luminance, whilst it interacted with that of foreperiod duration. Moreover, at low concentrations (10-20%), N(2)O abolished the effect of foreperiod, possibly through a disturbance of time estimation processes, whereas at higher concentrations (30-40%) N(2)O enhanced the effect of foreperiod, probably by slowing down motor processes. Movement time (MT) was decreased by N(2)O at 20-40%. CONCLUSIONS: The present data provide evidence that N(2)O impairs information processing by altering at least the stage of motor adjustment. In addition, N(2)O spares the sensory processes implemented during the stimulus preprocessing stage. A subsidiary result is that at some concentrations, N(2)O displays opposite effects on reaction time and movement time. These results demonstrate that the additive factor method constitutes a powerful new tool for studying the pharmacology of information processing in animal models.

Anesthetics, Inhalation↗

PubMed2000

Additional hepatocellular carcinomas undetectable before surgery.

The presence of small additional hepatocellular carcinomas (HCCs) undetectable before hepatic resection is a crucial topic for hepatic surgeons. We assessed the incidence of pathologically diagnosed multiple HCCs in 267 patients who underwent hepatic resection for HCC. Ninety-five additional HCC nodules were detected in 72 of the patients (27%). The survival rate of these 72 patients was significant worse than for the 195 with single nodular HCC (p = 0.0013). Twenty-one (22%) were detected before surgery, 29 (31%) during surgery, and 45 (47%) on pathologic examination after surgery. The mean nodule diameters for each group were 2.1, 1.0, and 0.9 cm, respectively (p < 0.0001). None of the 21 nodules detected before surgery was well differentiated, whereas 30 of the 74 nodules in the other two groups were well-differentiated. Although the mean nodule diameter of the well-differentiated HCC group was the smallest, there was no significant difference among the three groups assigned according to tumor differentiation (p = 0.2355). Altogether, 9 of 16 patients with additional nodules detected before surgery (56%) and 49 of 59 with additional nodules detected during or after surgery (88%) had cirrhosis of the liver. The odds ratio for detecting a new HCC nodule during or after surgery in the presence of cirrhosis was 5.444 (p = 0.0087). Improvement in the detection of small additional HCC nodules before and during surgery and meticulous follow-up after surgery are necessary for patients with cirrhosis. For patients without cirrhosis, surgical treatment may be performed according to the results of preoperative imaging studies.

Analysis of Variance↗

PubMedDate not supplied

Magnetic resonance angiography of the peripheral vessels in patients with peripheral arterial occlusive disease: when is an additional conventional angiography required?

The purpose of this work was to find out how often the clinician asks for a conventional angiography (CA) in patients with peripheral arterial occlusive disease (PAOD) after a magnetic resonance angiography (MRA) has been performed and how often the CA reveals additional information for therapy planning. Quality criteria for the MRA were defined and tested to see whether they can predict the need for an additional CA. In this prospective study, 81 patients suffering from PAOD (Fontaine classification IIa, n = 13; IIb, n = 33; III, n = 10; IV, n = 25) were examined with a 1.5-T MR-scanner with dedicated coils using a step-by-step technique. The vascular surgeon decided whether he could plan the therapy on the basis of the MRA or if he needed an additional CA. The MRA was assessed in terms of the image quality of the MRA and regarding therapeutic management of the patient in a two-grade scale: sufficient and insufficient. In 27/81 (33%) patients, the clinician asked for a CA, which revealed new information in only 11 patients. The relative number of MRAs with insufficient image quality was significantly higher (p < 0.01) in the group with additional information on CA (8/11) compared to the group without additional information (0/16). The assessment of an MRA based on image quality and regarding therapeutic management of the patient might reduce the number of CAs for therapy planning in patients with PAOD.

Aged↗

PubMed2006

Additive antitumor effect of concurrent treatment of 4-hydroxy tamoxifen with 5-fluorouracil but not with doxorubicin in estrogen receptor-positive breast cancer cells.

PURPOSE: The sequential addition of tamoxifen (TAM) to chemotherapy seems superior to its concurrent addition in patients with breast cancer. This study was conducted to clarify the hypothesis that there are differential interactions among TAM and chemotherapeutic agents. METHODS: Estrogen receptor (ER)-alpha-positive or -negative breast cancer cells were treated with 4-hydroxy TAM (4OHT), 5-fluorouracil (FU) and/or doxorubicin (Dox). Changes in the expression levels of genes related to sensitivity and resistance to TAM, 5-FU or Dox were tested. RESULTS: Concurrent treatment of 4OHT with 5-FU but not with Dox additively inhibited the growth of ER-alpha-positive cells. 5-FU did not change the expression levels of any tested genes related to either sensitivity or resistance to TAM. Although Dox did not change the expression levels of any genes related to the sensitivity to TAM, Dox significantly increased the expression levels of some genes related to TAM resistance, Eph A-2, ER-beta, Fos and vascular endothelial growth factor. 4OHT significantly decreased thymidilate synthase (TS) activity. CONCLUSIONS: Although the antitumor effect of concurrent 4OHT and 5-FU was additive, that of concurrent 4OHT and Dox was less than additive in ER-alpha-positive cells. The increased expression of genes related to TAM resistance by Dox might be responsible for the interaction. Decreased TS activity by 4OHT might increase the antitumor activity of 5-FU. These findings may provide a preclinical rationale for concurrent use with 5-FU and TAM.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Time interval of measles vaccination in patients with Kawasaki disease treated with additional intravenous immune globulin.

UNLABELLED: A standard treatment with a dose of 2 g/kg of intravenous immune globulin (i.v.IG) is sometimes ineffective in some patients with Kawasaki disease (KD), who are commonly treated with additional i.v.IG. An interval of 6 to 7 months in Japan and 11 months in the United States is recommended before vaccination against measles after i.v.IG treatment for KD, but it is not known how long after treatment with additional i.v.IG. We studied the persistence of measles antibody titers in six episodes of KD in five patients without history of measles infection or vaccination, 4 to 28 months of age, after additional infusion of i.v.IG. The total dose was 4 g/kg in five episodes and 6 g/kg in one episode. Enzyme immunoassay antibody titers against measles were still positive (> or =400) in all patients tested 3 months after additional infusion of i.v.IG and positive in one patient and equivocal (> or =200 and <400) in three patients after 6 months, but negative (<200) in all after 9 months following infusion. Neutralization test antibody titers against measles were still positive (> or =1:4) in all patients 3 months after additional infusion of i.v.IG, but only one after 6 months, and negative (<1:4) in all after 9 months following infusion. CONCLUSION: We suggest that an appropriate interval between infusion of 4 g/kg of intravenous immune globulin and measles vaccination be 9 months. The 11-month interval recommended in the United States for 2 g/kg may be longer than necessary.

Antibodies↗

PubMed2005

Pulse additions of soil carbon and nitrogen affect soil nitrogen dynamics in an arid Colorado Plateau shrubland.

Biogeochemical cycles in arid and semi-arid ecosystems depend upon the ability of soil microbes to use pulses of resources. Brief periods of high activity generally occur after precipitation events that provide access to energy and nutrients (carbon and nitrogen) for soil organisms. To better understand pulse-driven dynamics of microbial soil nitrogen (N) cycling in an arid Colorado Plateau ecosystem, we simulated a pulsed addition of labile carbon (C) and N in the field under the canopies of the major plant species in plant interspaces. Soil microbial activity and N cycling responded positively to added C while NH (4) (+) -N additions resulted in an accumulation of soil NO (3) (-) . Increases in microbial activity were reflected in higher rates of respiration and N immobilization with C addition. When both C and N were added to soils, N losses via NH(3) volatilization decreased. There was no effect of soil C or N availability on microbial biomass N suggesting that the level of microbial activity (respiration) may be more important than population size (biomass) in controlling short-term dynamics of inorganic and labile organic N. The effects of C and N pulses on soil microbial function and pools of NH (4) (+) -N and labile organic N were observed to last only for the duration of the moisture pulse created by treatment addition, while the effect on the NO (3) (-) -N pool persisted after soils dried to pre-pulse moisture levels. We observed that increases in available C lead to greater ecosystem immobilization and retention of N in soil microbial biomass and also lowered rates of gaseous N loss. With the exception of trace gas N losses, the lack of interaction between available C and N on controlling N dynamics, and the subsequent reduction in plant available N with C addition has implications for the competitive relationships between plants species, plants and microbes, or both.

Bacterial Physiological Phenomena↗

PubMed2002

Gene discovery in the auditory system: characterization of additional cochlear-expressed sequences.

To identify genes involved in hearing, 8494 expressed sequence tags (ESTs) were generated from a human fetal cochlear cDNA library in two distinct sequencing projects. Analysis of the first set of 4304 ESTs revealed clones representing 517 known human genes, 41 mammalian genes not previously detected in human tissues, 487 ESTs from other human tissues, and 541 cochlear-specific ESTs (http://hearing.bwh.harvard.edu). We now report results of a DNA sequence similarity (BLAST) analysis of an additional 4190 cochlear ESTs and a comparison to the first set. Among the 4190 new cochlear ESTs, 959 known human genes were identified; 594 were found only among the new ESTs and 365 were found among ESTs from both sequencing projects. COL1A2 was the most abundant transcript among both sets of ESTs, followed in order by COL3A1, SPARC, EEFY1A1, and TPTI. An additional 22 human homologs of known nonhuman mammalian genes and 1595 clusters of ESTs, of which 333 are cochlear-specific, were identified among the new cochlear ESTs. Map positions were determined for 373 of the new cochlear ESTs and revealed 318 additional loci. Forty-nine of the mapped ESTs are located within the genetic interval of 23 deafness loci. Reanalysis of unassigned ESTs from the prior study revealed 338 additional known human genes. The total number of known human genes identified from 8494 cochlear ESTs is 1449 and is represented by 4040 ESTs. Among the known human genes are 14 deafness-associated genes, including GJB2 (connexin 26) and KVLQT1. The total number of nonhuman mammalian genes identified is 43 and is represented by 58 ESTs. The total number of ESTs without sequence similarity to known genes is 4055. Of these, 778 also do not have sequence similarity to any other ESTs, are categorized into 700 clusters, and may represent genes uniquely or preferentially expressed in the cochlea. Identification of additional known genes, ESTs, and cochlear-specific ESTs provides new candidate genes for both syndromic and nonsyndromic deafness disorders.

Auditory Pathways↗

PubMedDate not supplied

Comparison of the additive effects of nipradilol and carteolol to latanoprost in open-angle glaucoma.

PURPOSE: To compare the effects of nipradilol and carteolol on intraocular pressure (IOP) when added to latanoprost treatment for glaucoma patients. METHODS: Fifty patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two groups randomly. One group received nipradilol 0.25% twice daily (nipradilol preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily (carteolol preceding group; n = 25), for 3 months in addition to latanoprost. Then, nipradilol and carteolol were switched, and the subjects were treated for 3 more months. One eye was selected randomly for analysis. RESULTS: In the nipradilol preceding group, IOP was 21.4 +/- 2.3 mmHg (mean +/- SD) at baseline, and 16.8 +/- 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of nipradilol decreased IOP to 15.8 +/- 1.7 mmHg, and the change to carteolol, to 15.3 +/- 2.0 mmHg. In the carteolol preceding group, IOP was 21.2 +/- 2.0 mmHg at baseline, and 17.0 +/- 2.1 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 +/- 1.8 mmHg, and the change to nipradilol, to 16.3 +/- 1.9 mmHg. Additional IOP reduction was greater with carteolol than with nipradilol (cross-over analysis of variance; P = 0.0005). CONCLUSIONS: Both nipradilol and carteolol have additive effects when used in combination with latanoprost. Carteolol, however, may have a more potent effect than nipradilol.

Antihypertensive Agents↗

PubMed2005

Bayesian model selection and averaging in additive and proportional hazards models.

Although Cox proportional hazards regression is the default analysis for time to event data, there is typically uncertainty about whether the effects of a predictor are more appropriately characterized by a multiplicative or additive model. To accommodate this uncertainty, we place a model selection prior on the coefficients in an additive-multiplicative hazards model. This prior assigns positive probability, not only to the model that has both additive and multiplicative effects for each predictor, but also to sub-models corresponding to no association, to only additive effects, and to only proportional effects. The additive component of the model is constrained to ensure non-negative hazards, a condition often violated by current methods. After augmenting the data with Poisson latent variables, the prior is conditionally conjugate, and posterior computation can proceed via an efficient Gibbs sampling algorithm. Simulation study results are presented, and the methodology is illustrated using data from the Framingham heart study.

Age of Onset↗

PubMed1989

An additive factors analysis of the effect(s) of location cues associated with auditory stimuli on stages of information processing.

The additive factors method (AFM) was used as a tool for assessing the locus (or loci) of the detrimental effect of auditory location cues in the chain of (visual) information processing. In the first experiment the location variable was factorially combined with response specificity, which is assumed to affect the response adjustment stage. A second experiment was performed in which movement amplitude, assumed to affect the response programming stage, was manipulated in addition to the location variable and a different variety of response specificity. Finally, the location variable was combined with relative S-R frequency, which is also assumed to affect the response programming stage, in a third experiment. The results of these experiments showed additive effects of the location variable with motor variables. The remaining two experiments were designed to assess the effects of location cues on response selection. In these experiments the location variable was combined with the number of response alternatives. Response speed decreased with an increase in the number of response alternatives. However, the effects of the location variable and number of response alternatives were additive. According to the additive factor logic, then, the results of experiments 1, 2 and 3 seem to indicate that the locus of interference of the location cues is not in the later response stages of the reaction process. The results of the last two experiments were interpreted to suggest that the effects of location cues and the number of response alternatives affect either different processes within the response selection stage or affect different process stages. It was concluded that the latter alternative explains most of the data currently available and that the stimulus identification stage is the most likely candidate for the locus of the location effect.

Adolescent↗

PubMed1986

Volume changes upon addition of Ca2+ to calmodulin: Ca2+-calmodulin conformational states.

Measurement of the volume change by a rapid density method upon sequential addition of calcium ion to calmodulin showed relatively large, nonuniform increases for the first 4 moles Ca2+ per mole calmodulin. Substantially larger volume increases (approximately 15 ml/mol protein) were observed upon addition of the second and fourth moles Ca2+ relative to the first and third moles added per mole calmodulin. A total volume increase of approximately 170 ml/mol protein attended the addition of 4 moles Ca2+, as expected for multidentate carboxylate coordination to metal ion. Marginal changes in volume were observed upon further additions, the data showing a remarkably sharp transition after [Ca2+]/[calmodulin] = 4. The results are consistent with an ordered binding of Ca2+ in which pair-wise additions produce similar volume changes; the volume change behavior, however, does not indicate an absence of distinct conformational states for a Ca2+(1)-calmodulin and a Ca2+(3)-calmodulin complex as has been proposed on the basis of 1H-NMR evidences.

Animals↗

PubMed1986

Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function.

The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function.

Adjuvants, Immunologic↗

PubMed1996

Does additional lubrication reduce condom failure?

It has been suggested that using additional spermicide with condoms provides added contraceptive effect and protection from infection, and that water-based lubricants may lower condom breakage rates. This questionnaire-based study investigated the use of additional lubrication with condoms amongst 525 female students presenting for post-coital contraception, and the current and past experience of condom and additional lubrication use amongst 481 controls attending the same health centre. Of those requesting post-coital contraception, 83% claimed condom failure as the cause, with 66% of the control group having also experienced condom failure at some time. Use of additional water-based lubrication was significantly associated with lower condom failure rates (odds ratio 8.88, 95% C.I.: 3.79, 20.8). Gender, regularity of use of condoms and using oil-based lubricants were not associated with higher failure rates. Additional lubricant use was not significantly associated with increased condom slippage.

Condoms↗

PubMed1994

Multiple-buffer-additive strategies for enhanced capillary electrophoretic separation of peptides.

A dodeca-peptide from the beta-subunit of thyroid stimulating hormone (TSH) was used as a model system for developing "multiple-buffer-additive" strategies to effect the separation of structurally-similar peptides. A series of synthetic peptides included six peptides with identical amino acid composition and two with multiple alanine substitutions at selected positions. Those with identical amino acid composition included the native and reverse sequences of residues 101-112 of the beta-TSH and four "computer-shuffled" amino acid sequences. Buffer additives such as acetonitrile (ACN), hexane sulfonic acid (HSA), and hexamethonium bromide (HxMBr), were shown to alter selectivity dramatically. HSA, an ion-pairing agent, and ACN, known to alter the hydrophobic environment of the solute, and HxMBr, which is thought to negate solute-wall interactions, are shown to independently effect only partial resolution of the mixture. It is shown that only with the proper combination of HSA and ACN are all mixture components resolved. These results re-affirm that CE selectivity may be altered by changes in buffer ionic strength or with the addition of HSA, but also show that further changes in selectivity can be achieved through alteration of buffer hydrophobicity. The observed changes in selectivity accompanying the addition of HSA and ACN may be due to differing electrophoretic mobilities resulting from nearest-neighbor effects or subtle differences in peptide secondary structure or solvation. This emphasizes the importance of employing multiple-buffer-additive strategies for effecting the resolution of peptide mixtures that are difficult to separate.

Amino Acid Sequence↗

PubMed1992

Counting knowledge and skill in cognitive addition: a comparison of normal and mathematically disabled children.

The relationship between counting knowledge and computational skills (i.e., skill at counting to solve addition problems) was assessed for groups of first-grade normal and mathematically disabled (MD) children. Twenty-four normal and 13 MD children were administered a series of counting tasks and solved 40 computer-administered addition problems. For the addition task, problem-solving strategies were recorded on a trial-by-trial basis. Performance on the counting tasks suggested that the MD children were developmentally delayed in the understanding of essential and unessential features of counting and were relatively unskilled in the detection of certain forms of counting error. On the addition task, the MD children committed many more computational errors and tended to use developmentally immature counting procedures. The immature counting knowledge of the MD children, combined with their relatively poor skills at detecting counting errors, appeared to underlie their poor computational skills on the addition task. Suggestions for future research are presented.

Child↗

PubMed1989

Wettability of a hydrophilic addition silicone impression material.

Silicone impression materials, long noted for their poor wettability, have typically demonstrated contact angles with water greater than 90 degrees. This study compared the wettability of a new hydrophilic addition silicone with that of other impression materials. Specimens from various viscosities of polyether, polysulfide, hydrophobic addition silicone, and hydrophilic addition silicone were formed against a smooth surface. The advancing contact angle of a saturated aqueous solution of CaSO4 on the impression materials was measured after 1 minute. Mean contact angles were calculated and results were analyzed by ANOVA and a multiple comparison of means procedure. Differences between pairs of contact angle means were found to be statistically significant except for the polyether-hydrophilic addition silicone pair. The wettability of the hydrophilic addition silicone impression material was found to be not significantly different from that of a polyether impression material.

Calcium Sulfate↗

PubMed1995

Examination of the additivity assumption using the spiral and standard Salmonella assays to evaluate binary combinations of mutagens.

Binary combinations of pure chemicals and complex mixtures were evaluated for their ability to produce additive mutagenicity responses in the spiral and standard Salmonella mutagenicity assays. Single chemicals were selected that were representative of the primary chemical class responsible for much of the mutagenic activity of each complex mixture. The following agents were evaluated in the absence of S9: 1-nitropyrene, diesel exhaust extract, and the chlorinated drinking water mutagen 3-chloro-4-dichloromethyl-5-hydroxy-2-[5H]-furanone (MX). In the presence of S9, the following agents were evaluated: 4-aminobiphenyl, benzo[a]pyrene, and an organic extract from the particulate emissions resulting from the combustion of polyethylene in a rotary kiln incinerator. Binary combinations of the agents within each S9 group were tested. The results were analyzed for additivity by determining whether the difference between the expected response of the binary mixture was significantly different from the observed response. In general, the combinations of mutagens produced additive responses at low doses in both assays. However, at high doses, the results generally departed from additivity, especially for combinations of indirect-acting mutagens. A requirement for exogenous metabolic activation imposes conditions, such as different S9 optima for each mutagen, that complicate the application of the additivity assumption to binary combinations of indirect-acting mutagens. Although the two bioassays generally gave similar results for each binary combination of mutagens, the spiral assay permitted a gradient of mutagen and/or S9 concentrations to be evaluated, and it allowed the mutagens to be evaluated in the absence of solvents, eliminating any potential solvent-mutagen interactions. These features of the spiral assay may be advantageous when studying chemical interactions.

Drug Interactions↗