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At least 613 records · Page 34Linked to original sources

PubMed2005

Effects of extended-access self-administration and deprivation on breakpoints maintained by cocaine in rats.

RATIONALE: Animal models that identify the effects of self-administration histories on subsequent patterns, levels of intake, and other aspects of reinforcement will help clarify the controlling variables of human drug use. OBJECTIVE: Identify the effects of extended-access to cocaine and 1 or 7 days of deprivation on cocaine-maintained breakpoints on a progressive ratio (PR) schedule of reinforcement. METHODS: Male, Sprague-Dawley rats were trained to self-administer intravenous cocaine (expt 1: 1.5 mg/kg per infusion; expt 2: 0.75 mg/kg per infusion), and then given various histories of self-administration and deprivation. Breakpoints, the number of infusions self-administered on a PR schedule, were assessed following the deprivation period. RESULTS: Rates of cocaine intake increased when access to cocaine was extended to 6 h/day. From day 1 to day 14, daily intake increased from 92 (+/-2.5) to 101 (+/-2.8) mg/kg in expt 1, and from 55 (+/-4) to 78 (+/-2.2) mg/kg in expt 2. Total intake across this 2-week period was approximately 1260 and 970 mg/kg in expts 1 and 2. Breakpoints were not different following this escalation period. The introduction of a 7-day deprivation period failed to alter breakpoints. CONCLUSIONS: There is dissociation between changes in rate of cocaine intake (or consumption) and breakpoints maintained on a PR schedule. Extended-access to cocaine produced increases in rate of intake without altering breakpoints. Depending on the experimental question, extended-access conditions may prove useful for studying changes in certain aspects of reinforcement, such as consumption, but not others, such as the strength of a drug as a reinforcer.

Animals↗

PubMed2003

The effects of pH and dissolved organic carbon on the toxicity of cadmium and copper to a freshwater bivalve: further support for the extended free ion activity model.

The extended free ion activity model (FIAM) was developed by integrating concepts from the original FIAM into biological receptor theory, to obtain a conceptual model that more precisely quantifies the interaction of chemical species at biological receptor sites. The extended FIAM was tested by determining the acute (48 h) valve movement behavior (VMB) (measured in terms of the duration of valve opening) of the Australian freshwater bivalve, Hyridella depressa, to increasing concentrations of total Cd or Cu, in a standard synthetic water under conditions of varying pH (6.5-7.5) and/or dissolved organic carbon (as model fulvic acid (FA)) concentrations (0-11.2 mg L(-1)). Valve movement behavior, measured using an automated data acquisition system, was shown to be a quantifiable and rapid, real-time endpoint for assessing the toxic effects of Cd and Cu exposures. The VMB of H. depressa to Cd was independent (p > 0.05) of pH and/or model FA concentration. In contrast, the VMB of H. depressa to Cu was highly dependent (p < 0.001) on pH and/or model FA concentration; individuals were more sensitive to Cu at low pH and model FA concentrations. The VMB of H. depressa was directly proportional to the activity of the free metal ion (Cd2+), for the linear region of the concentration-response curves. In contrast, the VMB of H. depressa was a weighted function of the activities of the free metal ion and the 1:1 metal hydroxide species (i.e. 2.02 x Cu2+ + CuOH+), whereby Cu2+ had a two-fold greater binding affinity than CuOH+ at the cell membrane surface. Moreover, the results for Cd and Cu are consistent with the extended FIAM, as opposed to the original FIAM, where the result for Cu would be regarded as an exception. The extended FIAM explained 98% of the variability in VMB, whereas the original FIAM explained only 63% (i.e. an improvement of 35%). The improved predictability of organism response to Cu is relevant to advancing water quality guidelines for protecting aquatic biota.

Animals↗

PubMed2006

Indications and techniques of extended resection for pancreatic cancer.

INTRODUCTION: The resectability rate and postoperative survival rate for pancreatic carcinoma are poor. Aggressive resection including vascular resection and extended lymphadenectomy represent one strategy for improving survival. This study was carried out to clarify the indications for extended resection, especially vascular resection, for pancreatic carcinoma. METHODS: From July 1981 to March 2005, we performed curative resection in 289 of 443 patients with pancreatic carcinoma in our department (65.2%). Vascular resection was performed in 201 (69.5%) patients and portal vein resection without arterial resection in 186 patients. Combined portal and arterial resection was performed in 14 patients and arterial resection without portal vein resection in 1. Extended lymphadenectomy including paraaortic lymph nodes was done. The postoperative survival rate was stratified according to operative and pathology findings. RESULTS: Operative mortality (any death within 30 days after surgery) occurred in 11 of the 289 curative resection patients (3.8%), including 1 of 88 patients without vascular resection (1.1%), 5 of 186 portal vein resection patients without arterial resection (2.7%), and 5 of 14 (35.7%) arterial resection patients undergoing portal vein arterial resection as well. Most patients who survived for 2 to 3 years had carcinoma-free surgical margins. CONCLUSIONS: The most important indication for vascular resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, vascular resection is contraindicated. Extended lymphadenectomy may be not of benefit.

Anastomosis, Surgical↗

PubMed1999

Value of extended resection and intraoperative radiotherapy for resectable pancreatic cancer.

Since 1984 intraoperative radiotherapy (IORT) combined with extended resection for pancreatic cancer has been performed in our clinic to prevent local recurrence. Following extended resection, a dose of 30 Gy of 9- to 12-MeV electrons is administered to the operative field, including the paraaortic area from the diaphragm above to the inferior mesenteric artery below. The 5-year survival rate was 15.3% in all 37 cases, 20.2% in patients who had macroscopic tumor clearance, and 16.9% in patients with stage IVa tumor according to the Japanese classification. In autopsies of 10 patients who underwent combined therapy, four had local recurrence enclosed by thick, firm connective tissue. There was no local control recurrence in two patients who underwent noncurative resection. Enhanced local control induced by the combined therapy, however, has only a limited impact on overall survival because of the systemic spread of disease, especially hepatic metastases. At present, as we have no effective treatment for hepatic metastases, it is important to perform an extended resection with IORT on carefully selected patients. The combined therapy may offer the best approach to control local recurrence when dealing with advanced, but not highly advanced, cancer as defined by the stage of tumor. Therefore a combination of IORT and extended resection can have an impact on the results of surgical treatment for pancreatic cancer when anticancer treatment of hepatic metastases is established.

Adult↗

PubMed1999

Extended left hepatectomy.

Extended left hepatectomy (resection of Couinaud segments II, III, IV, V, and VIII of the liver) has only slowly been appreciated as a viable resectional technique for large, strategically placed, left-sided and central hepatic lesions that extend to involve the right anterior sectoral portal pedicular structures. We report on the preoperative, intraoperative, and postoperative findings of 51 patients undergoing extended left hepatectomy at Memorial Sloan-Kettering from 1992 to 1998. Median age was 58 years (range 1-85), with 28 males and 23 females. Altogether 34 patients had metastatic hepatic malignancies, 14 had primary hepatic malignancies, and 3 had benign hepatic lesions. Median postoperative length of stay was 10 days (range 6-52). Postoperative morbidity and mortality were 53% and 8%, respectively. Multivariate analysis of multiple preoperative variables disclosed that only the largest hepatic lesion of >8 cm (p = 0.033) was an independent predictor of a positive microscopic margin or tumor within one high power field. No preoperative, intraoperative, or postoperative variables were independent predictors of postoperative morbidity or mortality. Utilization of extended left hepatectomy allows resection of critically positioned hepatic lesions previously thought unresectable. It can be performed relatively safely, although it is not without somewhat increased postoperative morbidity and mortality compared to lesser anatomic hepatic resections. Patient selection, as dictated by factors associated with adequate tumor clearance (tumor size and proximity to the right sectoral portal pedicular structures), may be important for determining appropriate candidates for this aggressive resectional technique.

Adolescent↗

PubMed1997

MRI of normal anterior cruciate ligament (ACL) and reconstructed ACL: comparison of when the knee is extended with when the knee is flexed.

The purpose of this study was to evaluate, using MRI, the morphology of normal anterior cruciate ligament (ACL) and ACL grafts when the knee was extended compared with when the knee was flexed. Eighteen normal controls and 22 ACL graft patients were studied. Spin-echo (SE) T1-weighted images (TR 330 ms/TE 15 ms, NEX 1) were obtained with a slice thickness of 3 mm. Oblique sagittal images parallel to the ACL were obtained at various flexed angles of the knee joint. In 12 of the 18 normal controls the ACL appeared convex toward the posterior side when the knee was extended and gradually became straight when the knee was flexed. In 15 of the 22 ACL graft patients the grafts appeared straight when the knee was extended and became convex toward the anterior side when the knee was flexed. It is concluded that the morphological changes seen on MR images of ACL grafts from when the knee is extended to when the knee is flexed are different from those in the normal ACL.

Adolescent↗

PubMed2005

Extended and standard supraglottic laryngectomies: a review of 110 patients.

The purpose of this study was to compare functional and oncological results of extended and standard supraglottic laryngectomies. One hundred ten patients with supraglottic carcinoma were treated. A standard supraglottic laryngectomy (SSL), a laterally extended supraglottic laryngectomy (LESL) and an anteriorly extended supraglottic laryngectomy (AESL) were performed on 32, 47 and 31 patients, respectively. Indications for postoperative radiotherapy included positive surgical margins (23% of patients) and/or node metastasis (63% of patients). Local recurrence occurred in 13% of SSL, 15% of LESL and 17% of AESL patients. Pulmonary complications due to aspiration were observed in 6% of SSL, 15% of LESL and 19% of AESL. The overall 5-year cure rates were 63% for SSL, 45% for LESL and 47% for the AESL procedures. Extended supraglottic laryngectomies provided as good a local tumor control as SSL. Extension to the hypopharynx (LESL) and to the vallecula (AESL) showed more frequent pulmonary complications and reduced cure rates.

Adult↗

PubMed2003

Debate: extended resection for pancreatic cancer; the affirmative case.

BACKGROUND/PURPOSE: A clinical study was carried out to clarify the indications for extended resection of pancreatic cancer. METHODS: From July 1981 to April 2000, 200 of 314 (63.7%) patients with pancreatic cancer underwent extended tumor resection. Portal vein resection was performed in 146 of the 200 (73%) resected cases. The postoperative survival rate was studied based on the operative and histopathological findings. RESULTS: Operative death (within 30 days postoperatively) occurred in 11 of the 200 (5.5%) resected patients. Most of the patients who survived for 2 or 3 years were in the group with carcinoma-free surgical margins. CONCLUSION: The most important indication for an extended operation combined with portal vein resection for pancreatic cancer is the likelihood of obtaining surgical cancer-free margins. There is no indication for an extended resection inpatients in whom the surgical margins will become cancer-positive if such a resection is employed.

Carcinoma, Pancreatic Ductal↗

PubMedDate not supplied

Extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization programs.

PURPOSE: To evaluate the effect of extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization (IVF) programs. METHODS: Thirty-six women undergoing IVF program had thin endometrium (<8 mm). Among them, 23 received fresh embryo transfer (control group), but 13 canceled embryo transfer and underwent frozen-thawed embryo transfer in the subsequent cycle after extended administration of exogenous estrogen (study group). RESULTS: In the study group, the mean endometrial thickness increased significantly from 6.7 mm in controlled ovarian hyperstimulation cycles to 8.6 mm after an extended estrogen therapy for 14 to 82 days (P=0.031). Their pregnancy rate was significantly higher than that in the control group (38.5% vs. 4.3%, P=0.016). Among 5 women achieving pregnancies in the study group, one was complicated with placenta accreta, and the other 4 had uneventful pregnancies. CONCLUSIONS: Extended estrogen administration followed by frozen-thawed IVF programs is beneficial for women with thin endometrium. However, the risk of abnormal placentation and peripartal complication should be kept in mind.

Drug Evaluation↗

PubMed2005

Comparison of dry mouth in women treated with extended-release formulations of oxybutynin or tolterodine for overactive bladder.

The incidence, severity and tolerability of dry mouth was compared in 790 women with overactive bladder who were treated with extended-release oxybutynin chloride 10 mg/day or extended-release tolterodine tartrate 4 mg/day for 12 weeks in a multicenter, double-blind, parallel-group study. Dry mouth was the most common adverse event associated with treatment, with an incidence rate of 28.1% in the oxybutynin group and 21.6% in the tolterodine group (P = 0.039). The majority of dry mouth events were mild in both treatment groups. Severe dry mouth occurred in 1.5% and 0.5% of patients in the oxybutynin and tolterodine groups, respectively (P = 0.173). Seven patients on extended-release oxybutynin and 4 patients on extended-release tolterodine discontinued treatment due to dry mouth (P = 0.380). The results of this analysis showed that dry mouth was common with both treatments, but most events were mild; there was no difference in the rate of severe dry mouth or in the rate of withdrawal due to dry mouth.

Adolescent↗

PubMed2005

Pharmacokinetic/pharmacodynamic (PK/PD) evaluation of a once-daily treatment using ciprofloxacin in an extended-release dosage form.

OBJECTIVE: To evaluate the suitability of a once-a-day dosing regimen of ciprofloxacin using a new extended-release dosage form based on PK/PD principles. METHODS: Ciprofloxacin's serum concentrations were measured after administration of 500 mg immediate-release twice-daily, and 1,000 mg extended-release once-daily to 19 healthy volunteers. Pharmacokinetic parameters were determined using non-compartmental and compartmental data analysis. Measured serum concentration profiles were linked to ciprofloxacin's effect against Escherichia coli (MIC 0.013 mg/l) from in vitro kill curve studies where the pharmacokinetics of ciprofloxacin were simulated and change in number of bacteria (CFU/ml) versus time was monitored. Resulting parameters were used to compare expected kill curves for the two dosing regimens based on measured ciprofloxacin concentrations. RESULTS: Fitting the data using an appropriate PK/PD model resulted in a set of mean pharmacodynamic parameters (bacterial growth rate constant, k0, maximum kill rate constant, Kmax, and EC50). The model included a novel term to account for a change in kill rate after approximately 4 h when Kmax decreased in concentration-dependent matter. The model allowed excellent curve fits of all ciprofloxacin concentrations investigated. Comparison of expected kill curves with the immediate-release versus extended-release treatments showed similar outcome. Both treatments resulted in a decrease in CFU/ml > 5 log units over 24 h. CONCLUSION: Results indicate that once-a-day dosing of equal total daily doses with the new and more compliance-friendly extended-release dosing form will be therapeutically equivalent to once-a-day dosing with traditional immediate-release dosage forms for treatment of infections with this microorganism.

Adult↗

PubMed1985

Loading doses and extended dosing intervals in topical gentamicin therapy.

Loading doses and extended dosing intervals were studied in a rabbit model using topically applied gentamicin in a concentration of 13.6 mg/ml. Loading doses consisting of one drop every minute for five minutes produced significantly higher gentamicin concentrations in the cornea during the early hours of treatment than regimens using one drop every hour and one drop every 30 minutes. Extended dosing intervals of two and four hours, when used in conjunction with an initial loading dose, produced peak gentamicin levels above 125 micrograms/g of cornea. However, trough levels with these extended dosing intervals were significantly lower than troughs during hourly gentamicin administration. An extended dosing interval regimen consisting of three drops every two hours maintained peak and trough levels equal to those produced by one drop an hour.

Administration, Topical↗

PubMed1992

Extended resection for locally advanced colorectal carcinoma.

We reviewed the medical records of 101 patients who underwent extended resection for locally advanced colorectal carcinoma between 1965 and 1989. Preoperative symptoms related to the genitourinary system were present in 46 patients. Malignant invasion of genitourinary structures by colorectal carcinoma was found in 43 of these 46 patients (93%). In contrast, 51% of the patients without such symptoms had malignant invasion of contiguous structures. Preoperative intravenous pyelography, computerized tomographic scans, and cystoscopy correctly predicted the presence or absence of malignant invasion in 89%, 83%, and 87% of patients, respectively. Tumor-positive resection margins had a negative impact on survival (mean survival: 11.4 months). The 5-year actuarial survival rate for the patients who underwent a curative extended resection (margins tumor negative) was 54%. A thorough preoperative evaluation can identify a significant number of patients with colorectal cancer extending into adjacent organs and structures. Such evaluation is vital for operative planning and patient preparation, since an appropriate extended resection can produce long-term local control and patient survival.

Adult↗

PubMed1994

Improved survival after extended bridge to cardiac transplantation.

In the past, left ventricular assist device (LVAD) support was frequently plagued by complications; thus, bridge to transplantation times were kept short. Increasing evidence suggests that extended bridging provides greater benefit due to improved end-organ perfusion and, thus, generally improved physical condition. To assess whether extended bridging translates into improved long-term survival after transplantation, we reviewed our experience with the HeartMate 1000 IP LVAD (Thermo Cardiosystems, Inc, Woburn, MA). Since January 1988, 19 patients (mean age, 45 +/- 9 years) have undergone extended bridging (mean time, 106 +/- 57 days). Their mean weight was 82 +/- 16 kg, and their mean body surface area was 2.0 +/- 0.2 m2. We define "extended" as the length of support necessary for systemic organ recovery after prolonged heart failure. During support, average pump flow indices ranged from 2.3 to 3.3 L.min-1.m-2, and all patients underwent physical rehabilitation. Between the time of LVAD implantation and explantation, the mean serum creatinine value decreased from 1.63 +/- 0.6 to 1.25 +/- 0.6 mg/dL (p = not significant), and the mean serum total bilirubin value decreased from 2.8 +/- 2.0 to 0.63 +/- 0.11 mg/dL (p < 0.05). All but 1 patient improved from New York Heart Association class IV to class I. Device-related complications were minimal. Twelve control patients ("de facto randomized") who did not receive the LVAD also were evaluated: actuarial survival at 1 year was 0% (p < 0.05); 3 (25%) underwent transplantation and died within 2 months; 9 (75%) died before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat.

The distribution of dopaminergic fibers in the principal components of the central extended amygdala (central amygdaloid nucleus (Ce), substantia innominata, and bed nucleus of the stria terminalis (BNST)), was studied using immunocytochemistry against tyrosine hydroxylase, dopamine beta-hydroxylase and dopamine. Dopamine fibers were found most densely distributed in the dorsolateral subdivision of the BNST and the lateral part of the Ce. Smaller numbers of dopaminergic fibers were found in the rest of the central extended amygdala. In contrast, dopamine beta-hydroxylase fibers were virtually absent from the dorsolateral bed nucleus of the stria terminalis and lateral part of the central amygdaloid nucleus, but were distributed in a moderate density in the medial part of Ce, dorsal substantia innominata and posterolateral BNST. Our results show that dopamine fibers are most concentration over those regions of the central extended amygdala with large numbers of GABAergic neurons whose projections remain within the central extended amygdala, while noradrenergic fibers are most heavily concentrated over those regions containing a large proportion of brainstem projection neurons. That dopamine fibers are concentrated over regions with GABAergic medium spiny neurons suggests that those regions might be organized as a striatal parallel.

Amygdala↗

PubMed1987

Progastrin and its glycine-extended posttranslational processing intermediates in human gastrointestinal tissues.

We examined the posttranslational modification of gastrin in human gastrointestinal and Zollinger-Ellison tumor tissues using antibodies specific for progastrin and its glycine-extended processing intermediates. Gel filtration of antral and duodenal extracts on Sephadex G-50 revealed multiple molecular forms of immunoreactive glycine-extended processing intermediates corresponding to known molecular forms of gastrin and cholecystokinin. Immunoaffinity chromatography studies of antral mucosal and gastrinoma extracts identified a molecular form of glycine-extended processing intermediates that was characterized by an amino terminus identical to that of gastrin heptadecapeptide. Large differences in the relative contents of precursors and products of gastrin synthesis were found in gastrinoma tissue as compared to gastrointestinal mucosal extracts. These studies suggest the potential importance of glycine-extended peptides as intermediates in the posttranslational processing of gastrin and cholecystokinin in humans and indicate that gastrin processing mechanisms may be altered in Zollinger-Ellison tumors.

Chromatography, Affinity↗

PubMed1989

HLA A1, B8, DR3 extended haplotypes in autoimmune chronic hepatitis.

Genetic determinants of the autoimmune type of chronic active hepatitis include the major histocompatibility complex alleles HLA-B8 and HLA-DR3, which are usually present as the haplotype A1, B8, DR3. In certain other autoimmune diseases, an extended haplotype including complement alleles confers a greater relative risk than does B8, DR3. Hence, extended haplotypes were ascertained in autoimmune chronic active hepatitis by typing for HLA, complement alleles C4A, C4B, and Bf, and glyoxalase type 1 or 2. Eight of the 10 B8, DR3 haplotypes were A1, B8, DR3. Of the 8, 7 had the extended haplotype A1, B8, C4AQ0, C4B1, BfS, DR3, but this haplotype occurred in four instances with glyoxalase 2 and in three with glyoxalase 1. Thus, we find that in autoimmune chronic active hepatitis there is a high frequency of null alleles for complement but an extended haplotype does not cause any greater risk for disease than B8, DR3 alone.

Alleles↗

PubMed1987

Use of a semen extender containing antibiotic to improve the fertility of a stallion with seminal vesiculitis due to Pseudomonas aeruginosa.

A breeding trial was conducted to determine if a semen extender containing polymixin-B sulfate would improve the fertility of a stallion with seminal vesiculitis due to Pseudomonas aeruginosa . Twenty-three mares were bred to the stallion by one of three methods: artificial insemination with raw semen (Group 1, n = 10), artificial insemination with semen mixed 1:1 with a nonfat dry skim milk/glucose extender containing 1000 units/ml polymixin-B sulfate (Group 2, n = 9), or natural service immediately following infusion of the uterus with 100 ml of the same extender (Group 3, n = 4). Artificial breedings contained a minimum insemination dose of 500 x 10(6) progressively motile spermatozoa. All mares were bred every other day while in estrus. Pregnancy status was determined by transrectal ultrasound examination 15 d after the last breeding. First-cycle pregnancy rate for Group 2 mares (78%) was greater (P < 0.01) than for Group 1 mares (10%). There was a tendency (P = 0.10) for the pregnancy rate of Group 3 mares (50%) to be greater than Group 1 mares. The use of a semen extender containing polymixin-B sulfate improved the fertility of this stallion.

Journal Article↗