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At least 757 records · Page 42Linked to original sources

PubMed2006

Migration of glaucoma drainage device extender into anterior chamber after trauma.

PURPOSE: Glaucoma drainage devices, on rare occasions, need repositioned and the intraocular portion of the implant tube is found to be "too short" to do so. Previously, a technique was described for "extending" the tube with angiocatheter material (rather than replacing the entire apparatus), and had been performed successfully without complication for 7 years. This case describes the first known complication: trauma causing anterior chamber migration of the tube extension requiring retrieval and reconstruction of the tube extension apparatus. PATIENT AND METHODS: One eye of 1 patient (age 8) with a prior glaucoma drainage device and tube extension with angiocatheter material with elevated intraocular pressure after direct trauma to the eye from a pencil. Office examination revealed inferior corneal edema and no tube segment visible in the anterior chamber on limited examination due to age-related compliance. Gonioscopy under anesthesia revealed the tube extender in the inferior anterior chamber. The tube extender was retrieved from the anterior chamber. The glaucoma drainage device was surgically exposed and the tube extension was reconstructed, including securing the tube extension with a suture placed through the lumens of both the angiocatheter extender and the tube extension. RESULTS: The reconstructed tube extension maintained good draining function with the secured extension and no further migration of the tube extension into the anterior chamber was seen. CONCLUSIONS: Tube extension using angiocatheter material continues to be a viable, cost-effective option in difficult cases. Placing a securing suture in patients prone to eye trauma can be considered.

Anterior Chamber↗

PubMed2004

Extended vertical trapezius myocutaneous flap in head and neck reconstruction as a salvage procedure.

In surgical treatment of head and neck cancer, when local tumor recurrence or failure of the previous reconstruction method occurs, reoperation for reconstruction of complicated soft-tissue defects can become a challenge for the plastic surgeon. This article describes the authors' experience with the extended vertical trapezius myocutaneous flap for head and neck complicated soft-tissue defects in nine patients ranging in age from 17 to 72 years. The causes of the defects were squamous cell carcinoma of the external ear (n = 2), lip (n = 2), larynx (n = 1), and oral cavity floor (n = 1); congenital hemifacial atrophy-temporomandibular joint ankylosis (n = 1); synovial sarcoma at the mandibular ramus (n = 1); and malignant fibrous histiocytoma at the posterior cranial fossa (n = 1). Eight of the nine patients had previously been operated on using other flap procedures, including free flaps and/or distant pedicled flaps (pectoralis major and deltopectoral flaps). One patient had been operated on using a graft procedure. After failure of the previous flap procedures in four patients and tumor recurrence in five patients, the extended vertical trapezius myocutaneous pedicled flap was used as a salvage procedure. The mean flap size was 7 x 34 cm. The flap was based solely on the transverse cervical artery. Superior muscle fibers of the trapezius were preserved and the caudal end of the flap was extended from 10 to 13 cm beyond the caudal end of the trapezius muscle. Three weeks postoperatively, the pedicle was separated. No flap failure occurred. The donor sites were closed primarily. There were no disabilities with regard to shoulder motion. Tumor recurrence was observed in two patients. In conclusion, for complicated soft-tissue defects of the head and neck, the extended vertical trapezius flap can be preferred as a salvage procedure because it is a simple, reliable, large flap that is located far enough from the damaged area.

Adolescent↗

PubMed2006

A comparison of postoperative pain between DIEP and extended latissimus dorsi flaps in breast reconstruction.

BACKGROUND: The senior author (A.P.) has performed 70 consecutive breast reconstructions over 3 years using the free deep inferior epigastric perforator (DIEP) and pedicled extended latissimus dorsi flaps. This study set out to compare these two methods of reconstruction by looking at postoperative morphine requirements and lengths of stay in hospital. METHODS: Patient notes were retrospectively reviewed and the total morphine used by patient-controlled analgesia was measured. RESULTS: The mean morphine per kilogram required by patients who had DIEP flaps (0.21 mg/kg; n = 22) was significantly less than the amount required by patients who had extended latissimus dorsi flaps (0.47 mg/kg; n = 48; p < 0.001). An observed trend also revealed that DIEP flap patients remained in hospital for less time compared with extended latissimus dorsi flap patients, although the difference was not significant (p > 0.01). CONCLUSIONS: This study shows that DIEP flap patients require less postoperative morphine and therefore might experience less pain than extended latissimus dorsi flap patients. DIEP flap patients may also leave the hospital sooner.

Female↗

PubMed2005

Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils.

PURPOSE: To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents. MATERIALS AND METHODS: Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured. RESULTS: After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection. CONCLUSION: Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

Acrylic Resins↗

PubMed2006

Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up.

OBJECTIVE: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer. SUMMARY BACKGROUND DATA: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases. METHODS: This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the "ipsilateral approach" 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed. RESULTS: There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was >or=0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE. CONCLUSIONS: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Adult↗

PubMed2004

Designing for beam propagation in periodic and nonperiodic photonic nanostructures: extended Hamiltonian method.

We use Hamiltonian optics to design and analyze beam propagation in two-dimensional (2D) periodic structures with slowly varying nonuniformities. We extend a conventional Hamiltonian method, adding equations for calculating the width of a beam propagating in such structures, and quantify the range of validity of the extended Hamiltonian equations. For calculating the beam width, the equations are more than 10(3) times faster than finite difference time domain (FDTD) simulations. We perform FDTD simulations of beam propagation in large 2D periodic structures with slowly varying nonuniformities to validate our method. Beam path and beam width calculated using the extended Hamiltonian method show good agreement with FDTD simulations. By contrasting the method with ray tracing of the bundle of rays, we highlight and explain the limitations of the extended Hamiltonian method. Finally, we use a frequency demultiplexing device optimization example to demonstrate the potential applications of the method.

Journal Article↗

PubMed2006

Construction of an extended invariant for an arbitrary ordinary differential equation with its development in a numerical integration algorithm.

For an arbitrary ordinary differential equation (ODE), a scheme for constructing an extended ODE endowed with a time-invariant function is here proposed. This scheme enables us to examine the accuracy of the numerical integration of an ODE that may itself have had no invariant. These quantities are constructed by referring to the Nosé-Hoover molecular dynamics equation and its related conserved quantity. By applying this procedure to several molecular dynamics equations, the conventional conserved quantity individually defined in each dynamics can be reproduced in a uniform, generalized way; our concept allows a transparent outlook underlying these quantities and ideas. Developing the technique, for a certain class of ODEs we construct a numerical integrator that is not only explicit and symmetric, but preserves a unit Jacobian for a suitably defined extended ODE, which also provides an invariant. Our concept is thus to simply build a divergence-free extended ODE whose solution is just a lift-up of the original ODE, and to constitute an efficient integrator that preserves the phase-space volume on the extended system. We present precise discussions about the general mathematical properties of the integrator and provide specific conditions that should be incorporated for practical applications.

Journal Article↗

PubMed2001

Characterization of an extended-spectrum class C beta-lactamase of Citrobacter freundii.

Citrobacter freundii GC3 is a clinical isolate which showed moderate resistance to oxyimino beta-lactams such as ceftazidime and aztreonam. This drug resistance was due to an extended-spectrum class C beta-lactamase encoded by chromosomal gene(s). The GC3 beta-lactamase showed high amino acid sequence homology to a known C. freundii beta-lactamase, i.e., 346 of 361 amino acids were identical with those of C. freundii GN346 beta-lactamase (Tsukamoto, K. et al, Eur. J. Biochem. 188, 15-22, 1990). Asp198 was the only dissimilar amino acid found in the omega loop region, known as the hot spot for extended-spectrum resistance in class C beta-lactamases (Haruta, S. et al, Microbiol. Immunol. 42, 165-169, 1998). However, Asp198 was eliminated as a cause of the extended-spectrum resistance by the substitution of Asn for Asp198. Subsequent investigation suggested that the moderate resistance to oxyimino beta-lactams is attributable to the replacement of amino acids on the enzyme's surface area, far from the active-site. Some or all of the replacements are assumed to delicately modify the active-site configuration. The GC3 beta-lactamase is the first example of an extended-spectrum class C beta-lactamase in which mutations are independent of the omega loop.

Amino Acid Sequence↗

PubMed1998

HLA-Cw alleles associated with HLA extended haplotypes and C2 deficiency.

There are four MHC-linked complement genes, BF, C2, C4A and C4B, that are inherited as single DNA units, known as complotypes. Extended haplotypes were initially defined by studying the distribution of complotypes in relation to HLA-B and HLA-DR loci in Caucasian families. In order to analyze the distribution of HLA-Cw alleles in relation to extended haplotypes, we studied a large panel of MHC homozygous and heterozygous cell lines representing previously described Caucasian-derived extended haplotypes and 14 patients with complete C2 deficiency. HLA alleles were assigned using sequence-specific oligonucleotide probe hybridization (SSOP). Family analysis served to assign haplotypes for heterozygous samples. We found distinctive HLA-Cw alleles for each independent extended haplotype. Their association in each instance was statistically significant. All patients with C2 deficiency carrying the haplotype [HLA-B18, S042, DR2] were associated with HLA-Cw*1203. These conserved allelic combinations may become an important tool for the study of human evolution and may contribute to the expeditious selection of prospective donors in clinical transplantation.

Alleles↗

PubMed2006

Extended coagulation profiles of healthy baboons and of baboons rejecting GT-KO pig heart grafts.

INTRODUCTION: Derangements of coagulation, e.g. thrombotic microangiopathy (TM) and disseminated intravascular coagulation (DIC), limit the success of pig-to-baboon organ transplantation. Studies have investigated the coagulation profile in baboons post-xenotransplantation (XTx), but an extended coagulation profile of healthy baboons pre-XTx has not been reported. METHODS: Blood was drawn from nine healthy male baboons (approximate age 5 yr, mean weight 15 kg) that had not undergone any prior surgical or therapeutic procedures. An extended coagulation profile, consisting of markers of thrombin activation, fibrinolysis, endothelial activation, the protein C pathway, and overall reactive state, was investigated by a reference coagulation laboratory, using tests for human plasma. The mean value +/- SD was calculated for 18 parameters (analytes); values outside of the mean +/- 2 SD were excluded. Three baboons subsequently underwent transplantation with hearts from GT-KO pigs, and received either no therapy (B24603), CVF (B25003), or CVF + leflunomide (B24903), and their extended coagulation parameters were followed. RESULTS: For 14 of the 18 analytes, the human reference range reflected the coagulation status of healthy baboons. Exceptions included thrombin/antithrombin complex and fibrinopeptide A, which were elevated compared with the human reference range, while plasminogen activity was lower. The human assay failed to detect baboon plasminogen activator inhibitor-1. Immediately after GT-KO pig heart transplantation, the untreated B24603 demonstrated a coagulation profile consistent with its postoperative clinical status; DIC was not apparent, and the heart was electively excised within 2.5 h. In B25003 and B24903, that rejected their grafts on days 8 and 12, respectively, the coagulation profile showed evidence of DIC, particularly in B24903, which was clinically coagulopathic by this time. CONCLUSIONS: (i) The human reference range of extended coagulation parameters forms a basis for studies in baboons, with a few exceptions. (ii) Antibody-mediated rejection of GT-KO pig hearts in baboons can be associated with laboratory and clinical evidence of DIC.

Animals↗

PubMed1976

The kinetics of hydrolysis of some extended N-aminoacyl-l-lysine methyl esters.

1. The action of two active forms of bovine trypsin (alpha and beta-trypsin) on a series of specific methyl ester substrates of general formula: N-acetyl-(glycyl)n-L-lysine methyl ester (n = 0, 1, 2) and N2-benzoyl-L-arginine ethyl ester have been investigated. With the L-lysine methyl esters the catalytic rate constant for hydrolysis (kcat) was found to be significantly lower for alpha-trypsin than for beta-trypsin, whereas with N2-benzoyl-L-arginine ethyl ester there was no significant difference for the two enzymes. 2. By measurement of the kinetic constants (kcat and Km) in the presence of a nucleophile, which competes with water in the deacylation process, it has been shown that, in common with the specific ester substrates of trypsin, the rate-determining step for the extended L-lysine methyl esters is decaylation of the enzyme. 3. It has been found that by extending the aminoacyl group of N-acetyl-L-lysine methyl ester by one glycine residue (n = 1), a greatly enhanced deacylation rate constant is observed for both alpha and beta-trypsin. The higher rate constants were maintained at the higher levels by the addition of a further glycine residue (n = 2). These results have been interpreted in terms of the 'induced fit' hypothesis the substrates binding to an enzyme subsite adjacent to the active site. 4. The beta-trypsin-catalysed hydrolysis of the L-lysine substrates was investigated over a range of temperature (15--35 degrees C). The Arrhenius law was obeyed, within experimental error, by all three substrates allowing the estimation of the thermodynamic function of activation (delta S not equal to and deltaH note equal to) for the deacylation reactions. The significantly higher values of deltaS not equal to and deltaH not equal to obtained for the two extended substrates are interpreted in terms of additional hydrogen bonding between the longer aminoacyl chains and the enzyme molecule. The results are compared with those for non-extended specific substrates, which have a possible hydrophobic interaction with the enzyme surface.

Animals↗

PubMed2007

Fertility results of artificial inseminations performed with liquid boar semen stored in X-cell vs BTS extender.

The objective of the present field study was to compare the fertility results for boar semen diluted in X-cell stored up to 4-5 days before artificial insemination (AI) with semen diluted in Beltsville thawing solution (BTS) used for AI following 2-3 days of storage (where the first day being the collection day). A total number of 2601 double inseminations in Norwegian herds were included in this two-trial study. All the boars used in the study were mature cross-bred Norwegian Landrace x Duroc (LD), which were routinely used for AI in Norway. The inseminated gilts and sows were Norwegian Landrace x Yorkshire (LY). The AI doses contained 2.5 billion spermatozoa, and consisted of a mixture of semen from three, occasionally four, boars (i.e. heterospermic semen). Fertility was measured in terms of the likelihood of farrowing and subsequent litter size. The fertility of the semen in both of the extenders was satisfactory and no significant differences were found either in semen stored 4-5 days in X-cell compared with 2-3 days in BTS or in semen stored 2-3 days in X-cell compared with 2-3 days in BTS. The storage capability findings for the long-term extender X-cell could significantly simplify the practical issues of semen production and the distribution of AI doses containing 2.5 billion spermatozoa. However, in pig production systems where all semen is used within 2-3 days, the short-term extender BTS is as good as the more expensive extender X-cell.

Animals↗

PubMed2005

A prospective analysis of extended endoscopic mucosal resection for large rectal villous adenomas: an alternative technique to transanal endoscopic microsurgery.

INTRODUCTION: Endoscopic mucosal resection is a safe resection tool for selected flat, sessile and lateral spreading tumours of the colon. Transanal microsurgical resection of select rectal neoplastic lesions is another accepted modality. Recent data suggests transanal microsurgery may have high complication rates. We conducted a prospective clinicopathological evaluation of an extended endoscopic mucosal resection technique for highly selected lesions of the rectum and assessed outcome data over a maximal 24-month period. PATIENTS AND METHODS: Eighty-three patients with known rectal neoplastic lesions underwent chromoscopic colonoscopy and on-table staging using a high-frequency (12.5 MHz) mini-probe EUS by a single endoscopist. Patients with T2 or node positive disease were referred for surgery. Following extended endoscopic mucosal resection patients were followed-up at 3, 6, 12 and 24 months post 'index' resection with chromoscopic endoscopy and EUS. Procedural complications, recurrence rates and outcome data were collected. RESULTS: Sixty-two patients fulfilled inclusion criteria. Median procedure time was 48 mins (range 32-126). Lateral spreading tumours (median diameter 30 mm; range 18-42 mm) and sessile lesions (median diameter 38 mm; range 25-86 mm) accounted for 19% and 81% of lesions, respectively. Ninety-seven percent of patients undergoing EMR were discharged within 6-h of procedure. Thirty-day re-admission and death rate was 0%. Bleeding complications occurred in 5/62 (8%) of patients with all achieving complete haemostasis using endo clips. None required transfusion. There were no procedural related complications or perforations. Overall 'cure' rate at a median follow-up of 16 months was 98%. CONCLUSIONS: Extended endoscopic mucosal resection for rectal neoplastic lesions can achieve superior results to those of per-anal excision and trans-anal microsurgery with regard to complications and recurrence rates. Extended endoscopic mucosal resection may be an alternative therapeutic modality in selected patients.

Adenoma, Villous↗

PubMed2004

Does extended lymphadenectomy increase the morbidity of radical cystectomy?

OBJECTIVE: To report the events during and after radical cystectomy and urinary diversion for bladder cancer, in terms of major and minor complications, comparing a minimal with an extended lymphadenectomy, as more lymph nodes obtained during radical cystectomy may improve staging and thus the outcome. PATIENTS AND METHODS: We reviewed 92 consecutive patients who underwent radical cystectomy from March 1998 to February 2002; 46 had a minimal (group A) and 46 an extended lymphadenectomy (group B). Cases were selected according to the American Society of Anesthesiologists classification, only including those graded 2 or 3. We specifically evaluated the incidence and type of complications within 30 days after surgery. RESULTS: Because of extending the lymphadenectomy the operative duration was a median of 63 min longer in group B (P < 0.01). Complications requiring surgical interventions occurred in four (9%) patients in group A and five (11%) in group B (P = 0.28). Complications requiring no surgical intervention were also similar in both groups. Three patients died, two in group A and one in group B (P = 0.57). CONCLUSION: Extended lymphadenectomy in radical cystectomy does not increase the morbidity within 30 days of surgery.

Aged↗

PubMedDate not supplied

Changing children's intergroup attitudes toward refugees: testing different models of extended contact.

The present research evaluated an intervention, derived from the "extended contact hypothesis," which aimed to change children's intergroup attitudes toward refugees. The study (n=253) tested 3 models of extended contact among 5- to 11-year-old children: dual identity, common ingroup identity, and decategorization. Children read friendship stories based upon these models featuring in- and outgroup members. Outgroup attitudes were significantly more positive in the extended contact conditions, compared with the control, and this was mediated by "inclusion of other in self." The dual identity intervention was the most effective extended contact model at improving outgroup attitudes. The effect of condition on outgroup intended behavior was moderated by subgroup identity. Implications for theoretically based prejudice-reduction interventions among children are discussed.

Attitude↗

PubMed1997

Psychosocial characteristics of a group of males with ischemic heart disease and extended sick leave.

A number of studies have been published indicating that psychosocial distress provides a significant predictor for outcome and even mortality among post-myocardial infarction patients. In this study medical and psychosocial characteristics were examined in a group of males with ischemic heart disease (IHD) still on extended sick leave (23.4 months +/- 17.5) after a cardiac event compared with a matched control group with considerably shorter sick leave time (2.7 months +/- 0.8). Twelve men with IHD and extended sick leave were referred from the Regional Social Insurance Office and, after informed consent, were enrolled in the study. The matched controls were recruited from the Sahlgrenska University Hospitals out-patient Heart Clinic. The two groups underwent medical examination including estimation of ejection fraction and ergometer bicycle stress test. Blood samples were drawn for analysis of blood lipids. Psychosocial characteristics were studied by a self-administrative, reliable, valid and sensitive questionnaire. The two groups were comparable on matched variables. Significant differences were found between the groups concerning: memory, emotional control, sleeping habits, daily life, leisure time, sexual life, physical capacity and general health status. A factor analysis revealed an inferior functioning in the group with extended sick leave concerning the social, somatic, and control factor. It is concluded that differences in psychosocial characteristics are present in males with ischemic heart disease and with extended sick leave after a cardiac event, compared to a group with 'normal' sick leave time, suggestive of a need for further studies concerning these characteristics and an implementation of this knowledge in rehabilitation programmes.

Adaptation, Psychological↗

PubMed1995

Extended concentration-response curves used to reflect full agonist efficacies and receptor occupancy-response coupling ranges.

1. An approach is described for generating extended agonist concentration-response curves where the responses are unconstrained by the normal tissue maximum response. Functional antagonism is employed to hold the tissue state in the range where any change in stimulus can be translated into a measurable response. 2. The maximum response of these extended concentration-response curves provides an index of intrinsic activity reflecting the agonist efficacy and the receptor occupancy-response coupling range. 3. The use of this approach is illustrated with extended concentration-response curves for noradrenaline (NA), vasopressin, acetylcholine (ACh), and 5-methylfurmethide in the small mesenteric and tail arteries of the rat. Both NA and vasopressin can maximally activate the arteries, but the new protocol shows that NA can produce more cellular activation than vasopressin in the tail artery. Both ACh and 5-methylfurmethide are full agonists but ACh has a higher intrinsic activity than 5-methylfurmethide. The ACh muscarinic receptors in the mesenteric artery have a larger occupancy-response range than the ACh muscarinic-receptors in the tail artery, and the alpha-adrenoceptors in the tail artery appear to have a larger occupancy-response coupling range than those in the mesenteric artery. 4. This approach extends our ability to compare the efficacies of full agonists, and to compare the occupancy-response coupling ranges of receptors that can normally maximally activate the assay tissue. This is achieved without the use of an irreversible antagonist and should be applicable to many receptors and pharmacological assay systems where responses are stable and functional antagonists are available.

Acetylcholine↗

PubMed1998

Pharmacokinetic evaluation of twice-daily extended-release carbamazepine (CBZ) and four-times-daily immediate-release CBZ in patients with epilepsy.

PURPOSE: A new capsule dosage form of carbamazepine (CBZ) has been developed, consisting of three different types of beads (immediate-release, extended-release, and enteric-release) that may be taken sprinkled on food or swallowed for easy administration. We compared the pharmacokinetics of the extended-release dosage form of CBZ (Carbatrol capsules) twice daily with the conventional immediate-release formulation of CBZ four times daily. METHODS: The randomized, double-blind, two-way, cross-over study was conducted at two sites, with a planned sample size of 24 adult patients with epilepsy. Each treatment was administered for 2 weeks. At the end of the 2-week period, blood samples were obtained hourly for a 24-h period. RESULTS: The 90% confidence intervals (CI) of the ratio of the means of the extended-release formulation twice daily to the immediate-release formulation four times daily were within the range of 0.80-1.25 for each of the pharmacokinetic parameters for CBZ and for the summation of CBZ and CBZ-epoxide (CBZ-E). There was no difference in the frequency of seizures between treatment (p = 0.103). CONCLUSIONS: Our results demonstrate that extended-release CBZ twice daily was bioequivalent to immediate-release CBZ four times daily, with regard to CBZ levels and summation of CBZ and CBZ-E levels, based on the pharmacokinetic parameters evaluated. Substituting one formulation for the other did not cause patients to have a significant change in seizure frequency.

Adolescent↗