SEARCH · PubMed Health

Results for “Extended”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed2001

Prostaglandin F2alpha added to extended boar semen at processing elicits in vitro myometrial contractility after 72 hours of storage.

Improved fertility will maximize productivity of the swine industry. Myometrial contractility is an essential component in the fertilization process because it is the mechanism by which spermatozoa are transported to the site of fertilization. In the present study, we evaluated the potential use of PGF2alpha supplementation to the extended pig semen in regard to inducing myometrial contractility of sows. Extended boar semen (80 mL) was supplemented with PGF2alpha (5 mg) for 72 h at 17 +/- 1 degrees C. Cumulative doses of 0.1, 1, 10 and 100 microL of the mixture were tested on uterine strips obtained from diestrus sows. An increase in myometrial contractility was recorded with PGF2alpha supplementation when compared to extended semen or extender treatment alone after 72 h of incubation. Addition of PGF2alpha to the extended boar semen at the time of the experiment did not differ from the 72 h treated group. The results from this study support that PGF2alpha preparations can be added to extended doses of boar semen at processing to enhance myometrial contractility at the time of insemination for up to 72 h.

Animals↗

PubMed1999

Conventional and extended-release etodolac for postsurgical dental pain.

This double-masked, parallel-group, randomized study compared the analgesic efficacy and tolerability of a single investigational 1200-mg dose of extended-release etodolac with those of a single 400-mg dose of extended-release etodolac and twice-daily doses of conventional etodolac 200 and 400 mg and placebo given 8 hours apart in 237 patients with moderate or severe postoperative pain following surgical removal of > or = 2 impacted third molars. Both doses of conventional etodolac and the 1200-mg dose of extended-release etodolac were significantly more effective on all summary analgesic measures than placebo (P < 0.05). Conventional etodolac had an onset of analgesic activity within 45 (400 mg) to 60 (200 mg) minutes and an analgesic duration of 5 to 6 hours. Extended-release etodolac 1200 mg had an onset of action within 60 minutes and an analgesic duration of 12 to 24 hours. At hours 2 and 3, conventional etodolac 400 mg was significantly more effective than the other treatments; from hours 6 through 12, extended-release etodolac 1200 mg was significantly more effective than the other treatments (both, P < 0.05). No serious adverse events were observed in this study, with an incidence of side effects in the active etodolac groups no different than that with placebo. Extended-release etodolac 1200 mg has a prolonged analgesic duration and an acceptable side-effect profile in the oral surgery pain model.

Adult↗

PubMed2001

Bed nucleus of the stria terminalis and extended amygdala inputs to dopamine subpopulations in primates.

The 'extended amygdala', a forebrain continuum implicated in complex motivational responses, is comprised of the bed nucleus of the stria terminalis and its sublenticular extension into the centromedial amygdala. Dopamine is also involved in motivated behavior, and is increased in several brain regions by emotionally relevant stimuli. To examine how the extended amygdala influences the dopamine cells, we determined the organization of inputs from subdivisions of the bed nucleus of the stria terminalis and sublenticular extended amygdala to the dopamine subpopulations in monkeys. Inputs from the bed nucleus of the stria terminalis and corresponding regions of the sublenticular extended amygdala are differentially organized. The medial bed nucleus of the stria terminalis and its medial sublenticular extension have a mediolateral organization with the densest inputs to the medial substantia nigra, pars compacta, and relatively few inputs to the central and lateral substantia nigra. In contrast, the lateral bed nucleus of the stria terminalis (and its continuation into the sublenticular extended amygdala) projects across the mediolateral extent of the substantia nigra. The subnuclei of the lateral bed nucleus of the stria terminalis also have differential projections to the dopamine cells. While the central core of the lateral bed nucleus of the stria terminalis has restricted inputs, the surrounding dorsolateral, capsular and juxtacapsular subdivisions project strongly to the dorsal tier dopamine neurons. The posterior subdivision of the lateral bed nucleus of the stria terminalis and its continuation into the central sublenticular extended amygdala project more broadly to both the dorsal tier and densocellular region of the ventral tier. From these results we suggest that specific subdivisions of the bed nucleus of the stria terminalis have differential influences on the dopamine subpopulations, influencing dopamine responses in diverse brain regions.

Amygdala↗

PubMed2000

Viability and fertility of rabbit spermatozoa diluted in Tris-buffer extenders and stored at 15 degrees C.

Artificial insemination (AI) in rabbits is not extensive in the breeding programs of the rabbit meat industry. A limiting factor is related to the semen preservation. In order to improve the use of AI, two experiments have been conducted to evaluate sperm viability and fertility of rabbit semen chilled and stored at 15 degrees C after dilution in Tris-based extenders. In Experiment 1, pooled semen samples were diluted 1:10 (semen/extender) in four different Tris-based extenders (Tris-citric-glucose (TCG), TES-Tris-glucose (TTG), Tris-citric-fructose (TCF) and TES-Tris-fructose (TTF)) and stored at 15 degrees C. Sperm viability was evaluated at 0, 24, 48, 72 and 96 h following dilution for total sperm motility (TSM), forward progressive motility (FPM), plasma membrane integrity (PMI) and acrosome integrity (NAR). Viability of spermatozoa declined with time of storage (P<0.05), irrespective of the extender used. There were interactions between extender and time of storage (P<0.05) in all viability parameters evaluated. After 96 h of storage, TCG provided the highest sperm viability (P<0.05) and TTG the lowest (P>0.05). In Experiment 2, a field trial was conducted at a commercial farm to evaluate the conception and farrowing rates of rabbit spermatozoa extended in TCG. After synchronization of oestrous and induction of ovulation, 3713 does with different physiological conditions (nulliparous, primiparous, lactating and re-breeding) were inseminated one time (15x10(6) sperm per doses) with semen stored at 0 (n: 1275), 24 (n: 1503) and 48 h (n: 935) at 15 degrees C. Overall conception and farrowing rates were 77.1+/-0.7 and 70.4+/-0.7, respectively, and the mean litter size was 7.6+/-0.1. Fertility results were unaffected by the time of semen storage (P>0.05). Regardless of time of semen storage, fertility results were affected by the physiological conditions of does (P<0.05). Nulliparous and lactating does showed the highest fertility and primiparous the lowest. In summary, these results indicate that Tris-buffer extenders are effective for preserving viability and fertilizing capability of rabbit spermatozoa stored at 15 degrees C.

Acrosome Reaction↗

PubMed2001

Extended field-of-view ultrasound.

When ultrasound became a clinical reality in the 1970s, extended field of view was the only form of imaging available because all ultrasound images were created with articulated arm scanners that encompassed the area of interest in its entirety. With the advent of high-quality real-time imaging in the 1980s, the extended field of view was lost, and with it went an important diagnostic component as well as an important means of communicating diagnostic findings to referring clinicians. Through the magic of computer technology, extended field of view imaging is back! Extended field of view images can now be created very easily and conveniently, in real time. The convenience and accuracy of real-time imaging is maintained while important anatomical perspectives are added. This article reviews the status of real-time extended field of view sonography. The technical details as well as the clinical relevance of this method are summarized. The day-to-day clinical utility of extended field of view imaging is liberally illustrated.

Computer Systems↗

PubMed1999

Differential induction of Fos-like-immunoreactivity in the extended amygdala after haloperidol and clozapine.

The extended amygdala is composed of the central and medial amygdaloid nucleus which through the sublenticular extended amygdala (SLEA) and the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) merge into the bed nucleus of stria terminals (BST). Based on anatomical connections with limbic areas, the extended amygdala has been proposed to play an important role in cognitive and affective processes. This study examines the effect of the atypical antipsychotic clozapine and the classical antipsychotic haloperidol on Fos-like-immunoreactivity (FLI) induction in areas belonging to the extended amygdala. Acute administration of clozapine (10-20 mg/kg) induced FLI in the central amygdaloid nucleus, IPAC, SLEA, and BST lateral division and, as previously described, in areas connected to the extended amygdala, such as the prefrontal cortex and nucleus accumbens shell. In contrast, acute administration of haloperidol (0.1-1 mg/kg) failed to induce FLI in the BST lateral division and SLEA but increased FLI in the IPAC. A small increase in FLI was observed in the central amygdaloid nucleus after 0.1 but not after 1 mg/kg of haloperidol. The present results, showing a preferential influence of clozapine, as compared to haloperidol, in the extended amygdala propose a new brain structure involved in the pharmacological effects of atypical antipsychotics.

Amygdala↗

PubMed2001

Weekly quizzes in extended-matching format as a means of monitoring students' progress in gross anatomy.

We compared weekly quizzes in extended-matching format with multiple-choice questions and oral examinations as means of monitoring students' progress in gross anatomy. Students' performance on 19 weekly oral examinations or 10-question quizzes based on extended-matching or multiple-choice formats were correlated with their success on 3 interim examinations and the final comprehensive examination. The Kuder-Richardson formula 20, an estimate of precision of the test, was 0.64 for extended-matching quizzes. Students' performance on interim examinations did not differ significantly. There was a significant correlation between students' mean scores on weekly quizzes and mean scores on interim examinations in both the extended-matching (r = 0.516) and multiple-choice group (r = 0.823). The mean grades (ranging from 2 to 5) on the final exam, based on understanding of anatomical concepts and their application in clinical practice, were significantly higher in extended-matching group (4.8) than in the multiple-choice (4.1) and orally examined groups (3.9) (p < 0.05). We conclude that extended-matching quizzes were at least as effective as multiple-choice quizzes and oral examinations and may be better for acquiring synthetic understanding of anatomical concepts especially in combination with other means of knowledge assessment. We recommend them as a reliable and objective means of monitoring students' performance during a gross anatomy course.

Anatomy↗

PubMed2002

Glycine-extended gastrin-17 stimulates acid secretion only via CCK-2 receptor-induced histamine release in the totally isolated vascularly perfused rat stomach.

The effects of gastrin precursors have been discussed during recent years. However, the mechanism for their action, whether through a novel receptor on the parietal cell or a cholecystokinin-2 (CCK-2) receptor on the enterochromaffin like (ECL) cells, is still not settled. This study examines the effect of glycine-extended gastrin-17 (Gly-G-17), the main non-amidated gastrin precursor, on gastric acid secretion and histamine release in the totally isolated vascularly perfused rat stomach. Glycine-extended gastrin-17 at the concentrations from 0.52 to 520 nmol L(-1) was administered to the totally isolated vascularly perfused rat stomach. Glycine-extended gastrin-17 at 52 or 520 nmol L(-1), and gastrin-17 at 0.52 nmol L(-1)were co-administered to examine whether glycine-extended gastrin augmented maximal gastrin stimulated acid secretion and histamine release. Both Gly-G-17 at 52 nmol L(-1) and gastrin-17 (G-17) at 0.52 nmol L(-1) were administered together with the histamine-2 receptor antagonist ranitidine at 10 micromol L(-1). Gastric acid and venous histamine output were measured. Glycine-extended gastrin-17 at lower concentrations from 0.52 to 5.2 nmol L(-1) did not stimulate gastric acid output or histamine release, whereas higher concentrations from 52 to 520 nmol L(-1) elicited a concentration-dependent increase in acid secretion and histamine release. The outputs of acid and histamine at 520 nmol L(-1) Gly-G-17 were at the same level as those found for G-17 at its maximally effective concentration of 0.52 nmol L(-1). Glycine-extended gastrin-17 at maximally effective concentration of 520 nmol L(-1) did not augment maximal gastrin stimulated acid secretion or histamine release. Ranitidine inhibited G-17 and Gly-G-17 stimulated acid secretion to a similar degree. This study confirms that the stimulatory effect of Gly-G-17 on gastric acid secretion is via a CCK-2 receptor on the ECL cell.

Animals↗

PubMed1998

The A and the extended V N-terminal regions of streptococcal protein I/IIf mediate the production of tumour necrosis factor alpha in the monocyte cell line THP-1.

The induction of tumour necrosis factor (TNF)-alpha from the monocytic cell line THP-1 by the streptococcal antigen I/II from Streptococcus mutans serotype f (protein I/IIf) was studied by use of recombinant polypeptides containing the discrete domains of the protein. The derivatives carrying the N-terminal alanine-rich region (A region) and the adjacent variable region (extended V region) of the protein bound to THP-1 cell extracts in a saturable fashion, and one derivative lacking both the A and the extended V regions was not able to bind monocyte cell extracts, suggesting that the domains responsible for the binding of protein I/IIf to monocytes were the A and the extended V regions. Sodium metaperiodate pretreatment of THP-1 cell extracts, tunicamycin pretreatment of monocyte cells or competition with N-acetyl neuraminic acid (NANA) and fucose resulted in a 45-70% reduction in binding activity of the derivatives carrying the extended V region, demonstrating the lectin-like mode of recognition of the monocytic receptor by the extended V region and the role of NANA and fucose in this recognition process. Besides, the stimulation of monocytes to release TNF-alpha by the derivatives containing the A region and the extended V region was effective and was not affected by the addition of polymyxin B or vitamin D3, suggesting that CD14 does not play the role of receptor in stimulation of monocytes by protein I/IIf to release TNF-alpha.

Bacterial Proteins↗

PubMed2004

Efficacy and cardiovascular tolerability of extended dialysis in critically ill patients: a randomized controlled study.

BACKGROUND: Extended dialysis is an increasingly used modality of renal replacement therapy that theoretically offers advantages of both intermittent and continuous therapies in the intensive care unit (ICU). METHODS: We randomly treated 39 ventilated critically ill patients with oliguric acute renal failure with either continuous venovenous hemofiltration (CVVH; n = 19; age, 50.1 +/- 3.2 years; Acute Physiology and Chronic Health Assessment II [APACHE II] score, 32.3 +/- 1.2; 79% sepsis) and a substitution fluid rate of at least 30 mL/kg/h for 24 hours or with extended dialysis for 12 hours (n = 20; age, 50.8 +/- 3.6 years; APACHE II score, 33.6 +/- 1.0; 85% sepsis). The latter was performed using an easy-to-handle, single-pass, batch dialysis system. All hemodynamic parameters were monitored invasively by means of an indwelling arterial catheter. RESULTS: Average mean arterial blood pressure, heart rate, cardiac output, systemic vascular resistance, and catecholamine dose were not significantly different in both therapies. Urea reduction rate was similar with extended dialysis compared with CVVH therapy (53% +/- 2% versus 52% +/- 3%; P = not significant) despite an average rate of substitution fluid with the latter of 3.2 +/- 0.1 L/h. This was corroborated by the finding of similar amounts of urea eliminated in the collected spent total hemofiltration and dialysis fluid. Correction of acidosis was accomplished faster with extended dialysis than CVVH, and the amount of heparin used was significantly lower with extended dialysis (P < 0.01). CONCLUSION: Extended dialysis combines excellent detoxification with cardiovascular tolerability, even in severely ill patients in the ICU. The technically simple dialysis system used offers flexibility of treatment time.

APACHE↗

PubMed2002

[Patients with non-advanced pancreatic cancer benefit from extended lymphadenectomy].

BACKGROUND: Despite improvements in surgical technique and adjuvant therapy models, the overall outcome for patients with pancreatic cancer has not significantly improved over the recent decades. The aim of the study was to assess the value of extended lymphadenectomy for pancreatic cancer. STUDY DESIGN: We performed a retrospective analysis of 136 patients with pancreatic cancer who underwent pancreatectomy and standard or extended lymph node dissection, to compare the rate of perioperative complications and 5-year survival. RESULTS: Of 136 patients treated, 43 (32 %) underwent standard (group I) and 93 (68 %) extended (group II) lymphadenectomy. Both groups were comparable with regard to various clinicopathological factors including patients' age, gender, tumour location, advancement and radicality of performed resection. The mean operative time in the extended group was longer (385 +/- 78 min) than in the standard group (359 +/- 62 min) but observed difference was insignificant. Similarly, there were no significant differences with respect to transfused blood and plasma units. The mean number of resected lymph nodes was significantly (p < 0.001) higher in group II (29.0 +/- 17.7) compared to I (13.0 +/- 7.4). The overall morbidity and mortality rates were 43 % and 6 %, respectively, without significant differences between both groups. The overall 5-year survival was 16.7 % and was similar regardless the type of performed lymphadenectomy. However, patients with node-negative pancreatic cancer following extended lymphadenectomy had significantly higher (p < 0.01) 5-year survival (48 %) compared to the standard resection (22 %). CONCLUSION: Extended pancreatoduodenectomy can be performed with similar morbidity and mortality rates as the standard procedure. However, only patients with non-advanced pancreatic cancer are likely to benefit of 5-year survival.

Adult↗

PubMed2001

Involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinases in glycine-extended gastrin-induced dissociation and migration of gastric epithelial cells.

The various molecular forms of gastrin can act as promoters of proliferation and differentiation in different regions of the gastrointestinal tract. We report a novel stimulatory effect of glycine-extended gastrin(17) only on cell/cell dissociation and cell migration in a non-tumorigenic mouse gastric epithelial cell line (IMGE-5). In contrast, both amidated and glycine-extended gastrin(17) stimulated proliferation of IMGE-5 cells via distinct receptors. Glycine-extended gastrin(17)-induced dissociation preceded migration and was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) but did not require mitogen-activated protein (MAP) kinase activation. Furthermore, glycine-extended gastrin(17) induced a PI3-kinase-mediated tyrosine phosphorylation of the adherens junction protein beta-catenin, partial dissociation of the complex between beta-catenin and the transmembrane protein E-cadherin, and delocalization of beta-catenin into the cytoplasm. Long lasting activation of MAP kinases by glycine-extended gastrin(17) was specifically required for the migratory response, in contrast to the involvement of a rapid and transient MAP kinase activation in the proliferative response to both amidated and glycine-extended gastrin(17). Therefore, the time course of MAP kinase activation appears to be a critical determinant of the biological effects mediated by this pathway. Together with the involvement of PI3-kinase in the dissociation of adherens junctions, long term activation of MAP kinases seems responsible for the selectivity of this novel effect of G(17)-Gly on the adhesion and migration of gastric epithelial cells.

Cell Membrane↗

PubMed2003

Extended core 1 and core 2 branched O-glycans differentially modulate sialyl Lewis X-type L-selectin ligand activity.

It has been established that sialyl Lewis x in core 2 branched O-glycans serves as an E- and P-selectin ligand. Recently, it was discovered that 6-sulfosialyl Lewis x in extended core 1 O-glycans, NeuNAcalpha2-->3Galbeta1-->4(Fucalpha1-->3(sulfo-->6))GlcNAcbeta1--> 3Galbeta1-->3GalNAcalpha1-->Ser/Thr, functions as an L-selectin ligand in high endothelial venules. Extended core 1 O-glycans can be synthesized when a core 1 extension enzyme is present. In this study, we first show that beta1,3-N-acetylglucosaminyltransferase-3 (beta3GlcNAcT-3) is almost exclusively responsible for core 1 extension among seven different beta3GlcNAcTs and thus acts on core 1 O-glycans attached to PSGL-1. We found that transcripts encoding beta3GlcNAcT-3 were expressed in human neutrophils and lymphocytes but that their levels were lower than those of transcripts encoding core 2 beta1,6-N-acetylglucosaminyltransferase I (Core2GlcNAcT-I). Neutrophils also expressed transcripts encoding fucosyltransferase VII (FucT-VII) and Core2GlcNAcT-I, whereas lymphocytes expressed only small amounts of transcripts encoding FucT-VII. To determine the roles of sialyl Lewis x in extended core 1 O-glycans, Chinese hamster ovary (CHO) cells were stably transfected to express PSGL-1, FucT-VII, and either beta3GlcNAcT-3 or Core2GlcNAcT-I. Glycan structural analyses disclosed that PSGL-1 expressed in these transfected cells carried comparable amounts of sialyl Lewis x in extended core 1 and core 2 branched O-glycans. In a rolling assay, CHO cells expressing sialyl Lewis x in extended core 1 O-glycans supported a significant degree of shear-dependent tethering and rolling of neutrophils and lymphocytes, although less than CHO cells expressing sialyl Lewis x in core 2 branched O-glycans. These results indicate that sialyl Lewis x in extended core 1 O-glycans can function as an L-selectin ligand and is potentially involved in neutrophil adhesion on neutrophils bound to activated endothelial cells.

Animals↗

PubMed2003

On the role of the Escherichia coli RNA polymerase sigma 70 region 4.2 and alpha-subunit C-terminal domains in promoter complex formation on the extended -10 galP1 promoter.

Bacterial promoters of the extended -10 class contain a single consensus element, and the DNA sequence upstream of this element is not critical for promoter activity. Open promoter complexes can be formed on an extended -10 Escherichia coli galP1 promoter at temperatures as low as 6 degrees C, when complexes on most promoters are closed. Here, we studied the contribution of upstream contacts to promoter complex formation using galP1 and its derivatives lacking the extended -10 motif and/or containing the -35 promoter consensus element. A panel of E. coli RNA polymerase holoenzymes containing two, one, or no alpha-subunit C-terminal domains (alpha CTD) and either wild-type sigma 70 subunit or sigma 70 lacking region 4.2 was assembled and tested for promoter complex formation. At 37 degrees C, alpha CTD and sigma 70 region 4.2 were individually dispensable for promoter complex formation on galP1 derivatives with extended -10 motif. However, no promoter complexes formed when both alpha CTD and sigma 70 region 4.2 were absent. Thus, in the context of an extended -10 promoter, alpha CTD and sigma 70 region 4.2 interactions with upstream DNA can functionally substitute for each other. In contrast, at low temperature, alpha CTD and sigma 70 region 4.2 interactions with upstream DNA were found to be functionally distinct, for sigma 70 region 4.2 but not alpha CTD was required for open promoter complex formation on galP1 derivatives with extended -10 motif. We propose a model involving sigma 70 region 4.2 interaction with the beta flap domain that explains these observations.

Amino Acid Motifs↗

PubMed2002

Does extended lymphadenectomy improve survival of pancreatic cancer patients?

PURPOSE: Aim of the study was to assess the value of extended lymphadenectomy for pancreatic cancer. MATERIALS AND METHODS: A retrospective analysis of 201 patients with pancreatic and ampullary cancer who underwent pancreatectomy with standard or extended lymph node dissection were analysed in order to compare the rate of perioperative complications and 5-year survival. RESULTS: Of 201 patients treated, 65 (32%) underwent standard (group I) and 136 (68%) extended (group II) lymphadenectomy. These two groups were similar with regard to age, gender, tumour location, advancement and radicality of performed resection. The mean operating time in the extended lymphadenectomy group was longer (383 +/- 81 min) compared to the standard group (357 +/- 64 min) but observed difference was insignificant. Similarly, there were no significant differences with respect to transfused blood and plasma units. The mean number of resected lymph nodes was significantly (p < 0.001) higher in group II (29.0 +/- 17.7) compared to group I (13.0 +/- 7.4). The overall morbidity and mortality rates were 43% and 6.9%, respectively without significant differences between both groups. The overall 5-year survival for pancreatic and ampullary cancer was 16.7% and 67.6% respectively, and was similar regardless the type of performed lymphadenectomy. Patients with node-negative pancreatic cancer following extended lymphadenectomy had significantly higher (p < 0.01) 5-year survival (48%) compared to the standard resection (22%). CONCLUSIONS: Extended lymphadenectomy can be performed with similar morbidity and mortality rates compared to the standard resection. Benefits of 5-year survival can be achieved only in a limited group of patients with non-advanced pancreatic cancer.

Adult↗

PubMed1993

Use of the extended ADL scale with stroke patients.

The Extended ADL scale is a postal measure of Instrumental ADL ability, comprising sub-scales for mobility, household ability and leisure activity. Its validity was examined in 303 stroke patients who had participated in a rehabilitation study. Adequate Guttman scales were found in the mobility scale, an adjusted household scale and, in women, the leisure scale. Extended ADL scores at 6 months after discharge from hospital were independently predicted by the Barthel ADL score at discharge from hospital, the age of the patient, previous mobility, time spent in hospital for the stroke, the abbreviated mental test score at discharge and whether the patient was living alone or not. Extended ADL scores discriminated between patients in institutions and at home. In patients at home, the Extended ADL scores were lower in those who received social and nursing services than in those who did not. Death or institutionalization over the 6 months was uncommon in patients with high Extended ADL scores. These data support the validity of the Extended ADL scale and confirm it to be a useful measure of outcome in stroke research.

Activities of Daily Living↗

PubMed2004

Predicted serum valproic acid concentrations in patients missing and replacing a dose of extended-release divalproex sodium.

PURPOSE: Computer simulations were used to analyze changes in steady-state total plasma valproic acid concentrations when a patient misses a dose of once-daily extended-release divalproex sodium, replaces it at a later time, and resumes scheduled therapy. METHODS: Valproic acid concentration-time profiles were simulated for 1000 hypothetical patients for each of two missed-dose scenarios using a one-compartment (assumes rapid distribution) population kinetic model with nonlinear protein binding. For each scenario, a lognormal distribution of clearance of unbound valproic acid, volume of distribution of unbound valproic acid, protein-binding values, and albumin concentration was generated. All simulations incorporated 20% interpatient variability and 10% residual error. RESULTS: Our pharmacokinetic simulations predicted that the chance for high plasma valproic acid concentrations resulting in clinical toxicity is low when extended-release divalproex doses are replaced within 12 hours followed by resumption of scheduled administration, perhaps due to the controlled, near zero-order absorption characteristics of the extended-release formulation. If a patient misses a dose of extended-release divalproex, it should be replaced as soon as the patient remembers. The next dose should be taken at the regularly scheduled time. A missed dose of extended-release divalproex may be replaced up to 12 hours later without any clinically significant change in plasma valproic acid concentrations in a majority of the patients. CONCLUSION: Simulation of two scenarios suggested that a missed dose of extended-release divalproex sodium may be replaced up to 12 hours later without any clinically significant perturbation in plasma valproic acid concentrations in the majority of adolescent and adult patients with epilepsy.

Anticonvulsants↗

PubMed2005

Extended epoetin alfa dosing in chronic kidney disease patients: a retrospective review.

BACKGROUND: The effectiveness of extended dosing of epoetin alfa beyond once-weekly (QW) has not been well explored in patients being treated for anaemia of chronic kidney disease (CKD). The current study was undertaken to assess the effectiveness of extended dosing in maintaining haemoglobin (Hb) levels in this population. METHODS: A retrospective chart review was conducted to assess the efficacy of extended epoetin alfa dosing in patients being treated for CKD-related anaemia. Eligible patients were to have received epoetin alfa once every 2 weeks (Q2W), 3 weeks (Q3W), 4 weeks (Q4W), or >Q4W administered subcutaneously for at least 3 months to maintain Hb > or = 11.0 g/dl. Patients were > or =18 years with serum creatinine 1.5 to 6.0 mg/dl for females and 2.0 to 6.0 mg/dl for males, and were not receiving renal replacement therapy. Epoetin alfa dose and dosing frequency were adjusted during treatment at the clinician's discretion. For analysis, patients were stratified into dosing groups based on their most dominant dosing regimen. RESULTS: 243 patients (mean age, 71.5 years; 79% white, 54% female) who received extended epoetin alfa dosing for a mean of 10.3 months were eligible for analysis. Mean baseline estimated glomerular filtration rate and mean serum creatinine were 21.2 ml/min/1.73 m(2) and 3.1 mg/dl, respectively. Primary causes of CKD included hypertension (36%) and diabetes (28%). Most patients (82%) receiving an extended epoetin alfa regimen maintained Hb > or =11.0 g/dl. The most common dosing regimen was Q2W (51%). Mean Hb for each dosing group was maintained between 11.6 g/dl and 12.4 g/dl during the study, and glomerular filtration rate remained stable. Epoetin alfa was well tolerated across all groups. CONCLUSIONS: Data from private community nephrology practices showed that extended epoetin alfa dosing effectively maintained Hb > or =11.0 g/dl in 82% of these selected patients being treated for anaemia of CKD.

Aged↗